Cardiology

On July 13, the Food and Drug Administration approved the first over-the-counter (OTC) norgestrel birth control pill (Opill). The daily oral contraceptive was approved for prescription use 5 decades ago, providing regulators with a half-century of data to show that the progestin-only drug can be used safely without a prescription. 

The drug is the latest in a series of medications that have made the switch from behind the pharmacy counter to retail shelves. 

Experts say several more classes of drugs to treat high cholesterol, asthma, and other common health problems could be next.
 

Why switch?

When a drug manufacturer submits a proposal for a switch to OTC, the key question that the FDA considers is patient safety. Some risks can be mitigated by approving OTC drugs at lower doses than what is available as the prescription version. 

“There is no drug that doesn’t have risks,” said Almut G. Winterstein, RPh, PhD, a distinguished professor in pharmaceutical outcomes and policy and director of the Center for Drug Evaluation and Safety at the University of Florida, Gainesville. “Risks are mitigated by putting specific constraints around access to those medications.”

Dr. Winterstein, a former chair of the FDA’s Drug Safety and Risk Management Advisory Committee, said that nonprescription drugs are unnecessary in a functional health care system. 

Many patients may struggle with accessing health clinicians, so making medications available OTC fills gaps left by not being able to get a prescription, according to Dr. Winterstein. 

A 2012 paper funded by the Consumer Healthcare Products Association (CHPA), the organization representing manufacturers and distributors of OTC medications, estimated that one quarter of people who bought OTC drugs would not otherwise seek treatment if these treatments were available only via prescription. The CHPA notes that the number of those who experience allergies who use nonprescription antihistamines and allergy-relief drugs increased by about 10% between 2009 and 2015. 
 

Cholesterol drugs

Approximately 80 million U.S. adults are eligible for cholesterol-lowering medications, particularly statins, but nearly half don’t take them, according to the Centers for Disease Control and Prevention. 

Fear of side effects is the most common reason people might avoid taking these drugs. But eliminating the need for a refill may encourage uptake of the statins. 

“It’s refill, refill, refill,” said Allen J. Taylor, MD, chairman of cardiology at MedStar Heart and Vascular Institute, in Washington. “We spend a ton of time refilling statins and it’s a headache for patients, too.” 

The need to secure regular prescriptions for the drug, “doesn’t put enough trust and faith in pharmacists and doesn’t put enough trust and faith in patients,” Dr. Taylor said. 

Moving statins to the front end of a pharmacy might not be the best move given the potential for drug interactions, but a nonprescription behind-the-counter approach could work, according to Dr. Taylor. 

“The concerns are modest at most, to where they can be monitored by a pharmacist,” he said. “There’s probably more people that would take a statin if they had that kind of access.” 

Many statin manufacturers have attempted to make the prescription-to-OTC switch. In 2005, an FDA advisory panel rejected Merck’s proposal for OTC sales of lovastatin after reviewing a study that found only 55% of OTC purchases would have been medically appropriate. 

In 2015, Pfizer pulled its application to make the cholesterol drug atorvastatin available to patients OTC because patients were not using the drug correctly. AstraZeneca is investigating an online platform that would allow patients to self-assess their eligibility for rosuvastatin. 
 

Asthma inhalers 

Inhalers are the main rescue therapy for asthma aside from a visit to the ED. 

The only inhaler available OTC is epinephrine sold under the brand name Primatene Mist, but this type of medicine device is not recommended as a first-line therapy for acute asthma symptoms, according to the American Medical Association. 

“It’s been around for a long time and has stayed over the counter even though newer, safer agents have come onto the market which aren’t available over the counter,” said William B. Feldman, MD, DPhil, MPH, a pulmonologist at Brigham and Women’s Hospital, Boston. 

Patients who have a hard time getting to a doctor or patients who lack insurance often face barriers accessing albuterol inhalers and beta agonist–corticosteroid combinations, according to Dr. Feldman. A switch to OTC distribution would widen access. 

“What we’re advocating is, if they’re going to have access to Primatene Mist, wouldn’t it be sensible to have access to a safer and more effective therapy?” Dr. Feldman said. 
 

Triptans

Migraines affect an estimated 39 million people in the United States, according to the American Migraine Foundation. Several drugs to treat migraine are available OTC, including nonsteroidal anti-inflammatory drugs, aspirin, and acetaminophen. Triptans, drugs used for the short-term treatment of acute symptoms, are prescription-only in the United States. 

But in the United Kingdom, triptans first became available in retail stores in 2006, leading to reduced costs for patients, employers, and the government. One study found that government health expenditures would be reduced by $84 million annually if the OTC switch were made in six European countries. 

However, overuse of the drug and potential contraindications have been cited as concerns with OTC access. 

For Dr. Winterstein, the decision to switch isn’t just about the freedom to buy a drug; it comes down to weighing potential risks and benefits. 

“Drugs are only as good as if they’re used in the context of how they should be used,” Dr. Winterstein said. “It’s not candy.”
 

A version of this article first appeared on Medscape.com.

On July 13, the Food and Drug Administration approved the first over-the-counter (OTC) norgestrel birth control pill (Opill). The daily oral contraceptive was approved for prescription use 5 decades ago, providing regulators with a half-century of data to show that the progestin-only drug can be used safely without a prescription. 

The drug is the latest in a series of medications that have made the switch from behind the pharmacy counter to retail shelves. 

Experts say several more classes of drugs to treat high cholesterol, asthma, and other common health problems could be next.
 

Why switch?

When a drug manufacturer submits a proposal for a switch to OTC, the key question that the FDA considers is patient safety. Some risks can be mitigated by approving OTC drugs at lower doses than what is available as the prescription version. 

“There is no drug that doesn’t have risks,” said Almut G. Winterstein, RPh, PhD, a distinguished professor in pharmaceutical outcomes and policy and director of the Center for Drug Evaluation and Safety at the University of Florida, Gainesville. “Risks are mitigated by putting specific constraints around access to those medications.”

Dr. Winterstein, a former chair of the FDA’s Drug Safety and Risk Management Advisory Committee, said that nonprescription drugs are unnecessary in a functional health care system. 

Many patients may struggle with accessing health clinicians, so making medications available OTC fills gaps left by not being able to get a prescription, according to Dr. Winterstein. 

A 2012 paper funded by the Consumer Healthcare Products Association (CHPA), the organization representing manufacturers and distributors of OTC medications, estimated that one quarter of people who bought OTC drugs would not otherwise seek treatment if these treatments were available only via prescription. The CHPA notes that the number of those who experience allergies who use nonprescription antihistamines and allergy-relief drugs increased by about 10% between 2009 and 2015. 
 

Cholesterol drugs

Approximately 80 million U.S. adults are eligible for cholesterol-lowering medications, particularly statins, but nearly half don’t take them, according to the Centers for Disease Control and Prevention. 

Fear of side effects is the most common reason people might avoid taking these drugs. But eliminating the need for a refill may encourage uptake of the statins. 

“It’s refill, refill, refill,” said Allen J. Taylor, MD, chairman of cardiology at MedStar Heart and Vascular Institute, in Washington. “We spend a ton of time refilling statins and it’s a headache for patients, too.” 

The need to secure regular prescriptions for the drug, “doesn’t put enough trust and faith in pharmacists and doesn’t put enough trust and faith in patients,” Dr. Taylor said. 

Moving statins to the front end of a pharmacy might not be the best move given the potential for drug interactions, but a nonprescription behind-the-counter approach could work, according to Dr. Taylor. 

“The concerns are modest at most, to where they can be monitored by a pharmacist,” he said. “There’s probably more people that would take a statin if they had that kind of access.” 

Many statin manufacturers have attempted to make the prescription-to-OTC switch. In 2005, an FDA advisory panel rejected Merck’s proposal for OTC sales of lovastatin after reviewing a study that found only 55% of OTC purchases would have been medically appropriate. 

In 2015, Pfizer pulled its application to make the cholesterol drug atorvastatin available to patients OTC because patients were not using the drug correctly. AstraZeneca is investigating an online platform that would allow patients to self-assess their eligibility for rosuvastatin. 
 

Asthma inhalers 

Inhalers are the main rescue therapy for asthma aside from a visit to the ED. 

The only inhaler available OTC is epinephrine sold under the brand name Primatene Mist, but this type of medicine device is not recommended as a first-line therapy for acute asthma symptoms, according to the American Medical Association. 

“It’s been around for a long time and has stayed over the counter even though newer, safer agents have come onto the market which aren’t available over the counter,” said William B. Feldman, MD, DPhil, MPH, a pulmonologist at Brigham and Women’s Hospital, Boston. 

Patients who have a hard time getting to a doctor or patients who lack insurance often face barriers accessing albuterol inhalers and beta agonist–corticosteroid combinations, according to Dr. Feldman. A switch to OTC distribution would widen access. 

“What we’re advocating is, if they’re going to have access to Primatene Mist, wouldn’t it be sensible to have access to a safer and more effective therapy?” Dr. Feldman said. 
 

Triptans

Migraines affect an estimated 39 million people in the United States, according to the American Migraine Foundation. Several drugs to treat migraine are available OTC, including nonsteroidal anti-inflammatory drugs, aspirin, and acetaminophen. Triptans, drugs used for the short-term treatment of acute symptoms, are prescription-only in the United States. 

But in the United Kingdom, triptans first became available in retail stores in 2006, leading to reduced costs for patients, employers, and the government. One study found that government health expenditures would be reduced by $84 million annually if the OTC switch were made in six European countries. 

However, overuse of the drug and potential contraindications have been cited as concerns with OTC access. 

For Dr. Winterstein, the decision to switch isn’t just about the freedom to buy a drug; it comes down to weighing potential risks and benefits. 

“Drugs are only as good as if they’re used in the context of how they should be used,” Dr. Winterstein said. “It’s not candy.”
 

A version of this article first appeared on Medscape.com.

On July 13, the Food and Drug Administration approved the first over-the-counter (OTC) norgestrel birth control pill (Opill). The daily oral contraceptive was approved for prescription use 5 decades ago, providing regulators with a half-century of data to show that the progestin-only drug can be used safely without a prescription. 

The drug is the latest in a series of medications that have made the switch from behind the pharmacy counter to retail shelves. 

Experts say several more classes of drugs to treat high cholesterol, asthma, and other common health problems could be next.
 

Why switch?

When a drug manufacturer submits a proposal for a switch to OTC, the key question that the FDA considers is patient safety. Some risks can be mitigated by approving OTC drugs at lower doses than what is available as the prescription version. 

“There is no drug that doesn’t have risks,” said Almut G. Winterstein, RPh, PhD, a distinguished professor in pharmaceutical outcomes and policy and director of the Center for Drug Evaluation and Safety at the University of Florida, Gainesville. “Risks are mitigated by putting specific constraints around access to those medications.”

Dr. Winterstein, a former chair of the FDA’s Drug Safety and Risk Management Advisory Committee, said that nonprescription drugs are unnecessary in a functional health care system. 

Many patients may struggle with accessing health clinicians, so making medications available OTC fills gaps left by not being able to get a prescription, according to Dr. Winterstein. 

A 2012 paper funded by the Consumer Healthcare Products Association (CHPA), the organization representing manufacturers and distributors of OTC medications, estimated that one quarter of people who bought OTC drugs would not otherwise seek treatment if these treatments were available only via prescription. The CHPA notes that the number of those who experience allergies who use nonprescription antihistamines and allergy-relief drugs increased by about 10% between 2009 and 2015. 
 

Cholesterol drugs

Approximately 80 million U.S. adults are eligible for cholesterol-lowering medications, particularly statins, but nearly half don’t take them, according to the Centers for Disease Control and Prevention. 

Fear of side effects is the most common reason people might avoid taking these drugs. But eliminating the need for a refill may encourage uptake of the statins. 

“It’s refill, refill, refill,” said Allen J. Taylor, MD, chairman of cardiology at MedStar Heart and Vascular Institute, in Washington. “We spend a ton of time refilling statins and it’s a headache for patients, too.” 

The need to secure regular prescriptions for the drug, “doesn’t put enough trust and faith in pharmacists and doesn’t put enough trust and faith in patients,” Dr. Taylor said. 

Moving statins to the front end of a pharmacy might not be the best move given the potential for drug interactions, but a nonprescription behind-the-counter approach could work, according to Dr. Taylor. 

“The concerns are modest at most, to where they can be monitored by a pharmacist,” he said. “There’s probably more people that would take a statin if they had that kind of access.” 

Many statin manufacturers have attempted to make the prescription-to-OTC switch. In 2005, an FDA advisory panel rejected Merck’s proposal for OTC sales of lovastatin after reviewing a study that found only 55% of OTC purchases would have been medically appropriate. 

In 2015, Pfizer pulled its application to make the cholesterol drug atorvastatin available to patients OTC because patients were not using the drug correctly. AstraZeneca is investigating an online platform that would allow patients to self-assess their eligibility for rosuvastatin. 
 

Asthma inhalers 

Inhalers are the main rescue therapy for asthma aside from a visit to the ED. 

The only inhaler available OTC is epinephrine sold under the brand name Primatene Mist, but this type of medicine device is not recommended as a first-line therapy for acute asthma symptoms, according to the American Medical Association. 

“It’s been around for a long time and has stayed over the counter even though newer, safer agents have come onto the market which aren’t available over the counter,” said William B. Feldman, MD, DPhil, MPH, a pulmonologist at Brigham and Women’s Hospital, Boston. 

Patients who have a hard time getting to a doctor or patients who lack insurance often face barriers accessing albuterol inhalers and beta agonist–corticosteroid combinations, according to Dr. Feldman. A switch to OTC distribution would widen access. 

“What we’re advocating is, if they’re going to have access to Primatene Mist, wouldn’t it be sensible to have access to a safer and more effective therapy?” Dr. Feldman said. 
 

Triptans

Migraines affect an estimated 39 million people in the United States, according to the American Migraine Foundation. Several drugs to treat migraine are available OTC, including nonsteroidal anti-inflammatory drugs, aspirin, and acetaminophen. Triptans, drugs used for the short-term treatment of acute symptoms, are prescription-only in the United States. 

But in the United Kingdom, triptans first became available in retail stores in 2006, leading to reduced costs for patients, employers, and the government. One study found that government health expenditures would be reduced by $84 million annually if the OTC switch were made in six European countries. 

However, overuse of the drug and potential contraindications have been cited as concerns with OTC access. 

For Dr. Winterstein, the decision to switch isn’t just about the freedom to buy a drug; it comes down to weighing potential risks and benefits. 

“Drugs are only as good as if they’re used in the context of how they should be used,” Dr. Winterstein said. “It’s not candy.”
 

A version of this article first appeared on Medscape.com.

THE CASE

A 30-year-old woman sought care at her rural family physician’s office for progressive dyspnea and peripheral edema, which she had been experiencing for several weeks. She was G1P0 and in her 35th week of gestation.

Her medical history was remarkable for mild preeclampsia, which was being managed observantly by her obstetrician in consultation with a maternal-fetal medicine specialist. She had been evaluated by her local hospital’s labor and delivery department and her maternal-fetal medicine specialist earlier in the week and seen the previous day by her obstetrician for these signs and symptoms. They all reassured her and told her these symptoms were normal during pregnancy. No diagnostic studies were performed. However, she remained concerned and decided to see her family physician for another opinion.

Upon presentation to her family physician, the patient was afebrile. Her blood pressure was 135/98 mm Hg; heart rate, 96 beats/min; and respiration, 20 breaths/min and slightly labored. Edema of 2 to 3+ was noted in her lower extremities, hands, and face. Bibasilar breath sounds were diminished, and her abdomen was nontender.

The family physician suspected left ventricular systolic dysfunction. He worked in a small office that lacked access to a laboratory or radiographic studies. However, he did have an ultrasound machine available, and although he was not skilled in echocardiography to assess cardiac function, he was able to obtain a bedside lung ultrasound.

THE DIAGNOSIS

While no B-lines were seen on the lung ultrasound, bilateral plural effusions were noted (FIGURE). This finding, paired with the patient’s signs and symptoms, prompted the family physician to suspect a diagnosis of acute ­decompensated heart failure with presumptive peripartum cardiomyopathy. The patient was immediately driven to the hospital by her family physician for emergency admission with stat obstetric and cardiology ­consultations.

An in-hospital echocardiogram revealed severe global hypokinesia with a left ventricular ejection fraction of 25% to 30%, which confirmed the family physician’s ­suspicions. Laboratory studies were significant for elevated N-terminal pro-brain natriuretic peptide (43,449 pg/mL; normal, < 125 pg/mL), troponin (1.12 ng/mL; normal range, 0-0.10 ng/mL), and white blood cell count (27.6 x 10³/µL). She also had evidence of acute renal injury, with blood urea nitrogen of 46 ­mg/dL (normal range, 7-18 mg/dL), creatinine of 2.0 mg/dL (normal range, 0.5-1.0 mg/dL), and potassium of 7.6 mmol/L (normal range, 3.5-5.1 mmol/L). Emergency delivery was induced by amniotomy, resulting in the birth of a baby girl weighing 5 lb 4 oz (Apgar scores 6, 8, and 9).

This case illustrates the successful use of lung ultrasound to identify a potentially fatal, elusive condition.

Following delivery, the patient was placed on a milrinone infusion and required dialysis. She was emergently transferred to a tertiary care hospital, where she was admitted to the cardiac intensive care unit by the cardiology/heart transplant service with nephrology and obstetric consultations. Hematology and infectious disease specialists were consulted to rule out HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome and sepsis, respectively. Her course of care remained complicated with further testing, including cardiac catheterization and biopsy, which was negative for additional pathology.

Continue to: One week after admission...

One week after admission, she was ­discharged home with a 24-hour wearable external cardiac defibrillator and a confirmed diagnosis of peripartum cardiomyopathy. Her medication regimen included digoxin (125 µg 3 times/wk), spironolactone (25 mg/d), carvedilol (3.125 mg twice daily), sacubitril/valsartan (24 mg/26 mg twice daily), furosemide (20 mg/d as needed for weight gain > 3-4 lb or leg swelling), magnesium oxide (400 mg twice daily), and ferrous sulfate (325 mg/d).

DISCUSSION

Peripartum cardiomyopathy is a rare, life-threatening, idiopathic cardiomyopathy that is responsible for one-half to two-thirds of cardiovascular disease–related maternal deaths in the United States.^1,2 It manifests in late pregnancy or early in the postpartum period and is characterized by left ven­tricular systolic dysfunction with resultant heart failure and an ejection fraction of less than 45%.^1,2

Recognized as early as the 1800s by ­Virchow,^2,3 the incidence of peripartum cardiomyopathy in the United States ranges from 1 in 1000 to 4000 live births and is increasing worldwide.^1,2 While the cause of peripartum cardiomyopathy remains unknown, risk factors include advanced maternal age, African descent, hypertension, preeclampsia, and multiple gestation ­pregnancy.^1,2

Early diagnosis of peripartum cardiomyopathy is imperative for survival of both mother and baby.⁴ This may be difficult because the signs and symptoms of heart failure—such as dyspnea, edema, orthopnea, cough, and chest and abdominal pain—overlap with those of a typical pregnancy, resulting in it ­often being missed on evaluation.^1,2

Dx with echocardiography; in a pinch, consider lung ultrasound

Usually a diagnosis of peripartum cardiomyopathy is established with echocardiography.^1,2 Thus, this case is of significant importance because it illustrates the successful use of lung ultrasound—a simple and easy test—by a rural family doctor to identify this potentially fatal, elusive condition with no additional studies.

Continue to: Use of lung ultrasound...

Use of lung ultrasound in the detection of acute decompensated heart failure is accepted in the medical literature.^5-7 Given clinical correlation, a positive scan is defined by the presence of at least 3 B-lines on a longitudinal plane between 2 ribs or, as seen in our case, by the presence of pleural effusion.^5-8 Lung ultrasound is readily available worldwide, is completely safe in pregnancy, and is considered one of the easiest studies to perform.^7-10

At the patient’s 9-month follow-up visit, she had made a full clinical recovery. Her ejection fraction was 59.8%, and she had stopped all medications. The patient and her child did not experience any continued complications.

THE TAKEAWAY

Family physicians should be aware of peripartum cardiomyopathy—one of the most elusive and life-threatening diseases of pregnancy. When managing a pregnant patient, it is imperative to follow up on complaints such as dyspnea, peripheral edema, and chest and/or abdominal pain. While these symptoms are not unusual during pregnancy, they should always prompt a more thorough evaluation. If peripartum cardiomyopathy is suspected, lung ultrasound is a valuable diagnostic tool for family physicians. Further research is needed before the findings of this case report can be universally applied in the routine prenatal care of women at risk for peripartum cardiomyopathy.

Acknowledgement
The authors thank their daughter, Nickel Cielo Abarbanell, for her help in the preparation of this manuscript.

CORRESPONDENCE
Neal Robert Abarbanell, MD, First Choice Healthcare, 1867 20th Avenue, Vero Beach, FL 32960; neal.abarbanell@ gmail.com

THE CASE

A 30-year-old woman sought care at her rural family physician’s office for progressive dyspnea and peripheral edema, which she had been experiencing for several weeks. She was G1P0 and in her 35th week of gestation.

Her medical history was remarkable for mild preeclampsia, which was being managed observantly by her obstetrician in consultation with a maternal-fetal medicine specialist. She had been evaluated by her local hospital’s labor and delivery department and her maternal-fetal medicine specialist earlier in the week and seen the previous day by her obstetrician for these signs and symptoms. They all reassured her and told her these symptoms were normal during pregnancy. No diagnostic studies were performed. However, she remained concerned and decided to see her family physician for another opinion.

Upon presentation to her family physician, the patient was afebrile. Her blood pressure was 135/98 mm Hg; heart rate, 96 beats/min; and respiration, 20 breaths/min and slightly labored. Edema of 2 to 3+ was noted in her lower extremities, hands, and face. Bibasilar breath sounds were diminished, and her abdomen was nontender.

The family physician suspected left ventricular systolic dysfunction. He worked in a small office that lacked access to a laboratory or radiographic studies. However, he did have an ultrasound machine available, and although he was not skilled in echocardiography to assess cardiac function, he was able to obtain a bedside lung ultrasound.

THE DIAGNOSIS

While no B-lines were seen on the lung ultrasound, bilateral plural effusions were noted (FIGURE). This finding, paired with the patient’s signs and symptoms, prompted the family physician to suspect a diagnosis of acute ­decompensated heart failure with presumptive peripartum cardiomyopathy. The patient was immediately driven to the hospital by her family physician for emergency admission with stat obstetric and cardiology ­consultations.

An in-hospital echocardiogram revealed severe global hypokinesia with a left ventricular ejection fraction of 25% to 30%, which confirmed the family physician’s ­suspicions. Laboratory studies were significant for elevated N-terminal pro-brain natriuretic peptide (43,449 pg/mL; normal, < 125 pg/mL), troponin (1.12 ng/mL; normal range, 0-0.10 ng/mL), and white blood cell count (27.6 x 10³/µL). She also had evidence of acute renal injury, with blood urea nitrogen of 46 ­mg/dL (normal range, 7-18 mg/dL), creatinine of 2.0 mg/dL (normal range, 0.5-1.0 mg/dL), and potassium of 7.6 mmol/L (normal range, 3.5-5.1 mmol/L). Emergency delivery was induced by amniotomy, resulting in the birth of a baby girl weighing 5 lb 4 oz (Apgar scores 6, 8, and 9).

This case illustrates the successful use of lung ultrasound to identify a potentially fatal, elusive condition.

Following delivery, the patient was placed on a milrinone infusion and required dialysis. She was emergently transferred to a tertiary care hospital, where she was admitted to the cardiac intensive care unit by the cardiology/heart transplant service with nephrology and obstetric consultations. Hematology and infectious disease specialists were consulted to rule out HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome and sepsis, respectively. Her course of care remained complicated with further testing, including cardiac catheterization and biopsy, which was negative for additional pathology.

Continue to: One week after admission...

One week after admission, she was ­discharged home with a 24-hour wearable external cardiac defibrillator and a confirmed diagnosis of peripartum cardiomyopathy. Her medication regimen included digoxin (125 µg 3 times/wk), spironolactone (25 mg/d), carvedilol (3.125 mg twice daily), sacubitril/valsartan (24 mg/26 mg twice daily), furosemide (20 mg/d as needed for weight gain > 3-4 lb or leg swelling), magnesium oxide (400 mg twice daily), and ferrous sulfate (325 mg/d).

DISCUSSION

Peripartum cardiomyopathy is a rare, life-threatening, idiopathic cardiomyopathy that is responsible for one-half to two-thirds of cardiovascular disease–related maternal deaths in the United States.^1,2 It manifests in late pregnancy or early in the postpartum period and is characterized by left ven­tricular systolic dysfunction with resultant heart failure and an ejection fraction of less than 45%.^1,2

Recognized as early as the 1800s by ­Virchow,^2,3 the incidence of peripartum cardiomyopathy in the United States ranges from 1 in 1000 to 4000 live births and is increasing worldwide.^1,2 While the cause of peripartum cardiomyopathy remains unknown, risk factors include advanced maternal age, African descent, hypertension, preeclampsia, and multiple gestation ­pregnancy.^1,2

Early diagnosis of peripartum cardiomyopathy is imperative for survival of both mother and baby.⁴ This may be difficult because the signs and symptoms of heart failure—such as dyspnea, edema, orthopnea, cough, and chest and abdominal pain—overlap with those of a typical pregnancy, resulting in it ­often being missed on evaluation.^1,2

Dx with echocardiography; in a pinch, consider lung ultrasound

Usually a diagnosis of peripartum cardiomyopathy is established with echocardiography.^1,2 Thus, this case is of significant importance because it illustrates the successful use of lung ultrasound—a simple and easy test—by a rural family doctor to identify this potentially fatal, elusive condition with no additional studies.

Continue to: Use of lung ultrasound...

Use of lung ultrasound in the detection of acute decompensated heart failure is accepted in the medical literature.^5-7 Given clinical correlation, a positive scan is defined by the presence of at least 3 B-lines on a longitudinal plane between 2 ribs or, as seen in our case, by the presence of pleural effusion.^5-8 Lung ultrasound is readily available worldwide, is completely safe in pregnancy, and is considered one of the easiest studies to perform.^7-10

At the patient’s 9-month follow-up visit, she had made a full clinical recovery. Her ejection fraction was 59.8%, and she had stopped all medications. The patient and her child did not experience any continued complications.

THE TAKEAWAY

Family physicians should be aware of peripartum cardiomyopathy—one of the most elusive and life-threatening diseases of pregnancy. When managing a pregnant patient, it is imperative to follow up on complaints such as dyspnea, peripheral edema, and chest and/or abdominal pain. While these symptoms are not unusual during pregnancy, they should always prompt a more thorough evaluation. If peripartum cardiomyopathy is suspected, lung ultrasound is a valuable diagnostic tool for family physicians. Further research is needed before the findings of this case report can be universally applied in the routine prenatal care of women at risk for peripartum cardiomyopathy.

Acknowledgement
The authors thank their daughter, Nickel Cielo Abarbanell, for her help in the preparation of this manuscript.

CORRESPONDENCE
Neal Robert Abarbanell, MD, First Choice Healthcare, 1867 20th Avenue, Vero Beach, FL 32960; neal.abarbanell@ gmail.com

THE CASE

A 30-year-old woman sought care at her rural family physician’s office for progressive dyspnea and peripheral edema, which she had been experiencing for several weeks. She was G1P0 and in her 35th week of gestation.

Her medical history was remarkable for mild preeclampsia, which was being managed observantly by her obstetrician in consultation with a maternal-fetal medicine specialist. She had been evaluated by her local hospital’s labor and delivery department and her maternal-fetal medicine specialist earlier in the week and seen the previous day by her obstetrician for these signs and symptoms. They all reassured her and told her these symptoms were normal during pregnancy. No diagnostic studies were performed. However, she remained concerned and decided to see her family physician for another opinion.

Upon presentation to her family physician, the patient was afebrile. Her blood pressure was 135/98 mm Hg; heart rate, 96 beats/min; and respiration, 20 breaths/min and slightly labored. Edema of 2 to 3+ was noted in her lower extremities, hands, and face. Bibasilar breath sounds were diminished, and her abdomen was nontender.

The family physician suspected left ventricular systolic dysfunction. He worked in a small office that lacked access to a laboratory or radiographic studies. However, he did have an ultrasound machine available, and although he was not skilled in echocardiography to assess cardiac function, he was able to obtain a bedside lung ultrasound.

THE DIAGNOSIS

While no B-lines were seen on the lung ultrasound, bilateral plural effusions were noted (FIGURE). This finding, paired with the patient’s signs and symptoms, prompted the family physician to suspect a diagnosis of acute ­decompensated heart failure with presumptive peripartum cardiomyopathy. The patient was immediately driven to the hospital by her family physician for emergency admission with stat obstetric and cardiology ­consultations.

An in-hospital echocardiogram revealed severe global hypokinesia with a left ventricular ejection fraction of 25% to 30%, which confirmed the family physician’s ­suspicions. Laboratory studies were significant for elevated N-terminal pro-brain natriuretic peptide (43,449 pg/mL; normal, < 125 pg/mL), troponin (1.12 ng/mL; normal range, 0-0.10 ng/mL), and white blood cell count (27.6 x 10³/µL). She also had evidence of acute renal injury, with blood urea nitrogen of 46 ­mg/dL (normal range, 7-18 mg/dL), creatinine of 2.0 mg/dL (normal range, 0.5-1.0 mg/dL), and potassium of 7.6 mmol/L (normal range, 3.5-5.1 mmol/L). Emergency delivery was induced by amniotomy, resulting in the birth of a baby girl weighing 5 lb 4 oz (Apgar scores 6, 8, and 9).

This case illustrates the successful use of lung ultrasound to identify a potentially fatal, elusive condition.

Following delivery, the patient was placed on a milrinone infusion and required dialysis. She was emergently transferred to a tertiary care hospital, where she was admitted to the cardiac intensive care unit by the cardiology/heart transplant service with nephrology and obstetric consultations. Hematology and infectious disease specialists were consulted to rule out HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome and sepsis, respectively. Her course of care remained complicated with further testing, including cardiac catheterization and biopsy, which was negative for additional pathology.

Continue to: One week after admission...

One week after admission, she was ­discharged home with a 24-hour wearable external cardiac defibrillator and a confirmed diagnosis of peripartum cardiomyopathy. Her medication regimen included digoxin (125 µg 3 times/wk), spironolactone (25 mg/d), carvedilol (3.125 mg twice daily), sacubitril/valsartan (24 mg/26 mg twice daily), furosemide (20 mg/d as needed for weight gain > 3-4 lb or leg swelling), magnesium oxide (400 mg twice daily), and ferrous sulfate (325 mg/d).

DISCUSSION

Peripartum cardiomyopathy is a rare, life-threatening, idiopathic cardiomyopathy that is responsible for one-half to two-thirds of cardiovascular disease–related maternal deaths in the United States.^1,2 It manifests in late pregnancy or early in the postpartum period and is characterized by left ven­tricular systolic dysfunction with resultant heart failure and an ejection fraction of less than 45%.^1,2

Recognized as early as the 1800s by ­Virchow,^2,3 the incidence of peripartum cardiomyopathy in the United States ranges from 1 in 1000 to 4000 live births and is increasing worldwide.^1,2 While the cause of peripartum cardiomyopathy remains unknown, risk factors include advanced maternal age, African descent, hypertension, preeclampsia, and multiple gestation ­pregnancy.^1,2

Early diagnosis of peripartum cardiomyopathy is imperative for survival of both mother and baby.⁴ This may be difficult because the signs and symptoms of heart failure—such as dyspnea, edema, orthopnea, cough, and chest and abdominal pain—overlap with those of a typical pregnancy, resulting in it ­often being missed on evaluation.^1,2

Dx with echocardiography; in a pinch, consider lung ultrasound

Usually a diagnosis of peripartum cardiomyopathy is established with echocardiography.^1,2 Thus, this case is of significant importance because it illustrates the successful use of lung ultrasound—a simple and easy test—by a rural family doctor to identify this potentially fatal, elusive condition with no additional studies.

Continue to: Use of lung ultrasound...

Use of lung ultrasound in the detection of acute decompensated heart failure is accepted in the medical literature.^5-7 Given clinical correlation, a positive scan is defined by the presence of at least 3 B-lines on a longitudinal plane between 2 ribs or, as seen in our case, by the presence of pleural effusion.^5-8 Lung ultrasound is readily available worldwide, is completely safe in pregnancy, and is considered one of the easiest studies to perform.^7-10

At the patient’s 9-month follow-up visit, she had made a full clinical recovery. Her ejection fraction was 59.8%, and she had stopped all medications. The patient and her child did not experience any continued complications.

THE TAKEAWAY

Family physicians should be aware of peripartum cardiomyopathy—one of the most elusive and life-threatening diseases of pregnancy. When managing a pregnant patient, it is imperative to follow up on complaints such as dyspnea, peripheral edema, and chest and/or abdominal pain. While these symptoms are not unusual during pregnancy, they should always prompt a more thorough evaluation. If peripartum cardiomyopathy is suspected, lung ultrasound is a valuable diagnostic tool for family physicians. Further research is needed before the findings of this case report can be universally applied in the routine prenatal care of women at risk for peripartum cardiomyopathy.

Acknowledgement
The authors thank their daughter, Nickel Cielo Abarbanell, for her help in the preparation of this manuscript.

CORRESPONDENCE
Neal Robert Abarbanell, MD, First Choice Healthcare, 1867 20th Avenue, Vero Beach, FL 32960; neal.abarbanell@ gmail.com

Moderate to vigorous physical activity (MVPA) is a familiar and established approach to reducing cardiovascular (CV) risk, but it’s often believed that the exercise should be spread out across the week rather than concentrated within a couple of days.

A challenge to that view comes from an observational study of accelerometer-confirmed exercise in almost 90,000 people in their 60s. It suggests, among those who exercised at least 2.5 hours per week, similar CV-risk reductions in “weekend warriors” (WW) who focused their workouts on 1 or 2 days per week and those who spread their weekly exercise over more days.

Researchers compared three patterns of MVPA in their subjects who wore accelerometers on their wrists for 1 week. Active WW subjects obtained at least 2.5 hours of exercise weekly, with at least half the amount completed over 1-2 days; “active regular” subjects achieved that exercise level but not mostly during 1 or 2 days; and those who were “inactive” fell short of 2.5 hours of exercise during the week. The group used a median exercise threshold of 3 hours, 50 minutes in a separate analysis.

The “active” groups, compared with inactive subjects, achieved similar and significant reductions in risk for incident atrial fibrillation (AF), myocardial infarction (MI), stroke, and heart failure (HF) over a median follow-up of 6.3 years at both weekly exercise thresholds, the group reported.

“The take-home [message] is that efforts to optimize activity, even if concentrated within just a day or 2 each week, should be expected to result in improved cardiovascular risk profiles,” lead author Shaan Khurshid, MD, MPH, Massachusetts General Hospital, Boston, said in an interview.

The study was published online in JAMA.

The research “provides novel data on patterns of physical activity accumulation and the risk of developing cardiovascular diseases,” observed Peter Katzmarzyk, PhD, Pennington Biomedical Research Center, Baton Rouge, La., in an interview. He was not involved with the research. Its “marked strengths,” he noted, include a large sample population and “use of accelerometers to measure physical activity levels and patterns.”

Moreover, Dr. Katzmarzyk said, its findings are “important” for showing that physical activity “can be accumulated throughout the week in different ways, which opens up more options for busy people to get their physical activity in.”

Current guidelines from the World Health Organization and the American Heart Association recommend at least 150 minutes of MVPA weekly to lower risk for cardiovascular disease and death, but do not specify an optimal exercise time frame. The U.K. National Health Service recommends MVPA daily or spread evenly over perhaps 4-5 days.

“The weekend warrior pattern has been studied previously, but typically relying on self-reported data, which may be biased, or [in studies] too small to look at specific cardiovascular outcomes,” Dr. Khurshid explained.

In the UK Biobank database, he said, “We saw the opportunity to leverage the largest sample of measured activity to date” to address the question of whether exercise time pattern “affects specific major cardiovascular diseases differently,” Dr. Khurshid said

The primary analysis assessed exercise amount in a week based on the guideline-recommended threshold of at least 2.5 hours; a 3-hour, 50-minutes threshold was used in a secondary analysis. The group assessed multiple thresholds because optimal MVPS levels derived from wrist-based accelerometers are “unclear,” he said.

The sample consisted of 89,573 participants with a mean age 62; slightly more than half (56%) were women. Based on the weekly MVPA threshold of 2.5 hours , the WW, active regular, and inactive groups made up 42.2%, 24%, and 33.7% of the population, respectively.

Compared with the inactive group, the two active groups both showed significant risk reductions for the four clinical outcomes, to similar degrees, in multivariate analysis. The results were similar at the 230-minute weekly exercise threshold for incident AF, MI, and HF but not for stroke.

A version of this article appeared on Medscape.com.

Moderate to vigorous physical activity (MVPA) is a familiar and established approach to reducing cardiovascular (CV) risk, but it’s often believed that the exercise should be spread out across the week rather than concentrated within a couple of days.

A challenge to that view comes from an observational study of accelerometer-confirmed exercise in almost 90,000 people in their 60s. It suggests, among those who exercised at least 2.5 hours per week, similar CV-risk reductions in “weekend warriors” (WW) who focused their workouts on 1 or 2 days per week and those who spread their weekly exercise over more days.

Researchers compared three patterns of MVPA in their subjects who wore accelerometers on their wrists for 1 week. Active WW subjects obtained at least 2.5 hours of exercise weekly, with at least half the amount completed over 1-2 days; “active regular” subjects achieved that exercise level but not mostly during 1 or 2 days; and those who were “inactive” fell short of 2.5 hours of exercise during the week. The group used a median exercise threshold of 3 hours, 50 minutes in a separate analysis.

The “active” groups, compared with inactive subjects, achieved similar and significant reductions in risk for incident atrial fibrillation (AF), myocardial infarction (MI), stroke, and heart failure (HF) over a median follow-up of 6.3 years at both weekly exercise thresholds, the group reported.

“The take-home [message] is that efforts to optimize activity, even if concentrated within just a day or 2 each week, should be expected to result in improved cardiovascular risk profiles,” lead author Shaan Khurshid, MD, MPH, Massachusetts General Hospital, Boston, said in an interview.

The study was published online in JAMA.

The research “provides novel data on patterns of physical activity accumulation and the risk of developing cardiovascular diseases,” observed Peter Katzmarzyk, PhD, Pennington Biomedical Research Center, Baton Rouge, La., in an interview. He was not involved with the research. Its “marked strengths,” he noted, include a large sample population and “use of accelerometers to measure physical activity levels and patterns.”

Moreover, Dr. Katzmarzyk said, its findings are “important” for showing that physical activity “can be accumulated throughout the week in different ways, which opens up more options for busy people to get their physical activity in.”

Current guidelines from the World Health Organization and the American Heart Association recommend at least 150 minutes of MVPA weekly to lower risk for cardiovascular disease and death, but do not specify an optimal exercise time frame. The U.K. National Health Service recommends MVPA daily or spread evenly over perhaps 4-5 days.

“The weekend warrior pattern has been studied previously, but typically relying on self-reported data, which may be biased, or [in studies] too small to look at specific cardiovascular outcomes,” Dr. Khurshid explained.

In the UK Biobank database, he said, “We saw the opportunity to leverage the largest sample of measured activity to date” to address the question of whether exercise time pattern “affects specific major cardiovascular diseases differently,” Dr. Khurshid said

The primary analysis assessed exercise amount in a week based on the guideline-recommended threshold of at least 2.5 hours; a 3-hour, 50-minutes threshold was used in a secondary analysis. The group assessed multiple thresholds because optimal MVPS levels derived from wrist-based accelerometers are “unclear,” he said.

The sample consisted of 89,573 participants with a mean age 62; slightly more than half (56%) were women. Based on the weekly MVPA threshold of 2.5 hours , the WW, active regular, and inactive groups made up 42.2%, 24%, and 33.7% of the population, respectively.

Compared with the inactive group, the two active groups both showed significant risk reductions for the four clinical outcomes, to similar degrees, in multivariate analysis. The results were similar at the 230-minute weekly exercise threshold for incident AF, MI, and HF but not for stroke.

A version of this article appeared on Medscape.com.

Moderate to vigorous physical activity (MVPA) is a familiar and established approach to reducing cardiovascular (CV) risk, but it’s often believed that the exercise should be spread out across the week rather than concentrated within a couple of days.

A challenge to that view comes from an observational study of accelerometer-confirmed exercise in almost 90,000 people in their 60s. It suggests, among those who exercised at least 2.5 hours per week, similar CV-risk reductions in “weekend warriors” (WW) who focused their workouts on 1 or 2 days per week and those who spread their weekly exercise over more days.

Researchers compared three patterns of MVPA in their subjects who wore accelerometers on their wrists for 1 week. Active WW subjects obtained at least 2.5 hours of exercise weekly, with at least half the amount completed over 1-2 days; “active regular” subjects achieved that exercise level but not mostly during 1 or 2 days; and those who were “inactive” fell short of 2.5 hours of exercise during the week. The group used a median exercise threshold of 3 hours, 50 minutes in a separate analysis.

The “active” groups, compared with inactive subjects, achieved similar and significant reductions in risk for incident atrial fibrillation (AF), myocardial infarction (MI), stroke, and heart failure (HF) over a median follow-up of 6.3 years at both weekly exercise thresholds, the group reported.

“The take-home [message] is that efforts to optimize activity, even if concentrated within just a day or 2 each week, should be expected to result in improved cardiovascular risk profiles,” lead author Shaan Khurshid, MD, MPH, Massachusetts General Hospital, Boston, said in an interview.

The study was published online in JAMA.

The research “provides novel data on patterns of physical activity accumulation and the risk of developing cardiovascular diseases,” observed Peter Katzmarzyk, PhD, Pennington Biomedical Research Center, Baton Rouge, La., in an interview. He was not involved with the research. Its “marked strengths,” he noted, include a large sample population and “use of accelerometers to measure physical activity levels and patterns.”

Moreover, Dr. Katzmarzyk said, its findings are “important” for showing that physical activity “can be accumulated throughout the week in different ways, which opens up more options for busy people to get their physical activity in.”

Current guidelines from the World Health Organization and the American Heart Association recommend at least 150 minutes of MVPA weekly to lower risk for cardiovascular disease and death, but do not specify an optimal exercise time frame. The U.K. National Health Service recommends MVPA daily or spread evenly over perhaps 4-5 days.

“The weekend warrior pattern has been studied previously, but typically relying on self-reported data, which may be biased, or [in studies] too small to look at specific cardiovascular outcomes,” Dr. Khurshid explained.

In the UK Biobank database, he said, “We saw the opportunity to leverage the largest sample of measured activity to date” to address the question of whether exercise time pattern “affects specific major cardiovascular diseases differently,” Dr. Khurshid said

The primary analysis assessed exercise amount in a week based on the guideline-recommended threshold of at least 2.5 hours; a 3-hour, 50-minutes threshold was used in a secondary analysis. The group assessed multiple thresholds because optimal MVPS levels derived from wrist-based accelerometers are “unclear,” he said.

The sample consisted of 89,573 participants with a mean age 62; slightly more than half (56%) were women. Based on the weekly MVPA threshold of 2.5 hours , the WW, active regular, and inactive groups made up 42.2%, 24%, and 33.7% of the population, respectively.

Compared with the inactive group, the two active groups both showed significant risk reductions for the four clinical outcomes, to similar degrees, in multivariate analysis. The results were similar at the 230-minute weekly exercise threshold for incident AF, MI, and HF but not for stroke.

A version of this article appeared on Medscape.com.

TOPLINE:

A short bout of preoperative high-intensity interval training (HIIT) improves cardiorespiratory fitness (CRF) for patients slated for major surgery. It cuts the risk of postoperative complications and may shorten hospital length of stay and improve postoperative quality of life.

METHODOLOGY:

Evidence suggests CRF – which improves physical and cognitive function and is associated with a reduction in cardiovascular risk – can be enhanced before major surgeries, but reported postoperative outcomes in previous reviews have been inconsistent.

In the study, HIIT involved repeated aerobic high-intensity exercise intervals at about 80% of maximum heart rate, followed by active recovery.

The meta-analysis included 12 studies with 832 patients (mean age, 67) that compared preoperative HIIT – supervised at hospitals, gyms, or community or physical therapy centers, or unsupervised at home – with standard care for patients slated for major surgery, including liver, lung, colorectal, urologic, and mixed major abdominal operations.

The primary outcome was change in CRF by peak VO₂ or 6-minute walk test; other endpoints included change in endurance time and postoperative outcomes.
 

TAKEAWAY:

Preoperative HIIT (median total, 160 minutes; range, 80-240 minutes; intense exercise during 6-40 sessions) was associated with an increase in peak oxygen consumption (VO₂ peak) by 2.59 mL/kg/min (95% confidence interval, 1.52-3.65 mL/kg/min; P < .001), compared with standard care, which represents about a 10% increase in CRF.

In eight studies that involved 770 patients, there was moderate evidence that preoperative HIIT cut the odds ratio for postoperative complications by more than half (OR, 0.44; 95% CI, 0.32-0.60; P < .001); there was a similar apparent benefit in an analysis that was limited to patients who were slated for abdominal surgery (OR, 0.45; 95% CI, 0.29-0.68; P < .001).

An analysis that was limited to studies that reported hospital length of stay showed a clinically relevant but nonsignificant 3-day reduction among patients in the HIIT groups.

Most quality of life assessments did not show post-HIIT improvements; some showed a significant benefit 6 weeks after surgery.
 

IN PRACTICE:

The results suggest preoperative HIIT may improve postoperative outcomes. By extension, it could be cost-effective and “should be included in prehabilitation programs,” the report states.

SOURCE:

The study was carried out by Kari Clifford, PhD, Otago Medical School, University of Otago, Dunedin, New Zealand, and colleagues. It was published online June 30, 2023, in JAMA Network Open.

LIMITATIONS:

Included studies were heterogeneous in methodology; for example, HIIT definitions and protocols varied across almost every study. Data reporting was incomplete, the samples sizes in the studies were limited, and patients could not be blinded to their intervention. The patients could not be stratified on the basis of frailty. There were limited HIIT data from patients who underwent orthopedic surgeries.

DISCLOSURES:

The study received funding from the University of Otago. The authors reported no conflicts.

A version of this article first appeared on Medscape.com.

TOPLINE:

A short bout of preoperative high-intensity interval training (HIIT) improves cardiorespiratory fitness (CRF) for patients slated for major surgery. It cuts the risk of postoperative complications and may shorten hospital length of stay and improve postoperative quality of life.

METHODOLOGY:

Evidence suggests CRF – which improves physical and cognitive function and is associated with a reduction in cardiovascular risk – can be enhanced before major surgeries, but reported postoperative outcomes in previous reviews have been inconsistent.

In the study, HIIT involved repeated aerobic high-intensity exercise intervals at about 80% of maximum heart rate, followed by active recovery.

The meta-analysis included 12 studies with 832 patients (mean age, 67) that compared preoperative HIIT – supervised at hospitals, gyms, or community or physical therapy centers, or unsupervised at home – with standard care for patients slated for major surgery, including liver, lung, colorectal, urologic, and mixed major abdominal operations.

The primary outcome was change in CRF by peak VO₂ or 6-minute walk test; other endpoints included change in endurance time and postoperative outcomes.
 

TAKEAWAY:

Preoperative HIIT (median total, 160 minutes; range, 80-240 minutes; intense exercise during 6-40 sessions) was associated with an increase in peak oxygen consumption (VO₂ peak) by 2.59 mL/kg/min (95% confidence interval, 1.52-3.65 mL/kg/min; P < .001), compared with standard care, which represents about a 10% increase in CRF.

In eight studies that involved 770 patients, there was moderate evidence that preoperative HIIT cut the odds ratio for postoperative complications by more than half (OR, 0.44; 95% CI, 0.32-0.60; P < .001); there was a similar apparent benefit in an analysis that was limited to patients who were slated for abdominal surgery (OR, 0.45; 95% CI, 0.29-0.68; P < .001).

An analysis that was limited to studies that reported hospital length of stay showed a clinically relevant but nonsignificant 3-day reduction among patients in the HIIT groups.

Most quality of life assessments did not show post-HIIT improvements; some showed a significant benefit 6 weeks after surgery.
 

IN PRACTICE:

The results suggest preoperative HIIT may improve postoperative outcomes. By extension, it could be cost-effective and “should be included in prehabilitation programs,” the report states.

SOURCE:

The study was carried out by Kari Clifford, PhD, Otago Medical School, University of Otago, Dunedin, New Zealand, and colleagues. It was published online June 30, 2023, in JAMA Network Open.

LIMITATIONS:

Included studies were heterogeneous in methodology; for example, HIIT definitions and protocols varied across almost every study. Data reporting was incomplete, the samples sizes in the studies were limited, and patients could not be blinded to their intervention. The patients could not be stratified on the basis of frailty. There were limited HIIT data from patients who underwent orthopedic surgeries.

DISCLOSURES:

The study received funding from the University of Otago. The authors reported no conflicts.

A version of this article first appeared on Medscape.com.

TOPLINE:

A short bout of preoperative high-intensity interval training (HIIT) improves cardiorespiratory fitness (CRF) for patients slated for major surgery. It cuts the risk of postoperative complications and may shorten hospital length of stay and improve postoperative quality of life.

METHODOLOGY:

Evidence suggests CRF – which improves physical and cognitive function and is associated with a reduction in cardiovascular risk – can be enhanced before major surgeries, but reported postoperative outcomes in previous reviews have been inconsistent.

In the study, HIIT involved repeated aerobic high-intensity exercise intervals at about 80% of maximum heart rate, followed by active recovery.

The meta-analysis included 12 studies with 832 patients (mean age, 67) that compared preoperative HIIT – supervised at hospitals, gyms, or community or physical therapy centers, or unsupervised at home – with standard care for patients slated for major surgery, including liver, lung, colorectal, urologic, and mixed major abdominal operations.

The primary outcome was change in CRF by peak VO₂ or 6-minute walk test; other endpoints included change in endurance time and postoperative outcomes.
 

TAKEAWAY:

Preoperative HIIT (median total, 160 minutes; range, 80-240 minutes; intense exercise during 6-40 sessions) was associated with an increase in peak oxygen consumption (VO₂ peak) by 2.59 mL/kg/min (95% confidence interval, 1.52-3.65 mL/kg/min; P < .001), compared with standard care, which represents about a 10% increase in CRF.

In eight studies that involved 770 patients, there was moderate evidence that preoperative HIIT cut the odds ratio for postoperative complications by more than half (OR, 0.44; 95% CI, 0.32-0.60; P < .001); there was a similar apparent benefit in an analysis that was limited to patients who were slated for abdominal surgery (OR, 0.45; 95% CI, 0.29-0.68; P < .001).

An analysis that was limited to studies that reported hospital length of stay showed a clinically relevant but nonsignificant 3-day reduction among patients in the HIIT groups.

Most quality of life assessments did not show post-HIIT improvements; some showed a significant benefit 6 weeks after surgery.
 

IN PRACTICE:

The results suggest preoperative HIIT may improve postoperative outcomes. By extension, it could be cost-effective and “should be included in prehabilitation programs,” the report states.

SOURCE:

The study was carried out by Kari Clifford, PhD, Otago Medical School, University of Otago, Dunedin, New Zealand, and colleagues. It was published online June 30, 2023, in JAMA Network Open.

LIMITATIONS:

Included studies were heterogeneous in methodology; for example, HIIT definitions and protocols varied across almost every study. Data reporting was incomplete, the samples sizes in the studies were limited, and patients could not be blinded to their intervention. The patients could not be stratified on the basis of frailty. There were limited HIIT data from patients who underwent orthopedic surgeries.

DISCLOSURES:

The study received funding from the University of Otago. The authors reported no conflicts.

A version of this article first appeared on Medscape.com.

Regular consumption of fish and other foods rich in omega-3 fatty acids (FA) won’t raise an individual’s risk for developing atrial fibrillation (AFib), suggests a meta-analysis of population-based studies.

Lynda Banzi/MDedge News

The finding may alleviate recent concerns about higher-dose omega-3 FA supplement intake in clinical-trial patients at elevated cardiovascular (CV) risk, researchers say.

Indeed, across the 17 cohort studies in the meta-analysis, risk for incident AFib was unaffected by elevated circulating and adipose tissue levels of eicosapentaenoic acid (EPA) from dietary intake. Moreover, the risk appeared to drop significantly with such levels of docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), and EPA plus DHA.

The signals of AFib risk associated with high-dose omega-3 FA in supplements or prescription form in some clinical trials “may not necessarily be generalizable to lower-dose habitual dietary omega-3 intakes,” concludes the study’s report published in the Journal of the American College of Cardiology.

Other recent research suggests that any elevated AFib risk from omega-3 FA intake is dose-related and may be associated with omega-3 FA supplement or medication intake in high doses, such as 4 g/day.

“Coupled with the more consistent benefits of these fatty acids in the prevention of adverse coronary events, our study suggests that current dietary guidelines recommending fish/omega-3 fatty acid consumption should be maintained,” conclude the authors of the report, led by Frank Qian, MD, MPH, Harvard T.H. Chan School of Public Health and Beth Israel Deaconess Medical Center, Boston.

The current study is “important in showing that physiologic levels of omega-3s that would accumulate through diet don’t seem to increase the risk of arrhythmia,” preventive cardiologist Sean Heffron, MD, NYU Langone Health and Grossman School of Medicine, told this news organization.

“It also lends credence to the fact that the increased risk is specific to the high dose supplementation, because that’s the only instance in which we’ve seen increased atrial fibrillation in association with omega-3s,” said Dr. Heffron, who wasn’t involved in the meta-analysis.

An accompanying editorial agrees. “Based on present evidence, moderate dietary intake of fish and seafood is unlikely to achieve sufficiently high levels of omega-3-FAs in blood or tissue that would result in increased AFib risk as observed in clinical trials of fish oil supplements and high-dose prescriptions,” write Christie Ballantyne, MD, and Xiaoming Jia, MD, Baylor College of Medicine, Houston.

Therefore, they conclude, “fish should continue to be an important part of the menu of a heart-healthy diet.”

The meta-analysis comprised 54,799 participants from 21 countries worldwide in 17 prospective cohort studies that yielded data on incident AFib, in which there were 7,720 cases of the arrhythmia over a median follow-up of 13 years. It looked at associations between such cases and levels of omega-3 FA in blood and adipose tissue samples.

In multivariable analysis, EPA levels were not associated with incident AFib, with a hazard ratio of 1.00 (95% confidence interval, 0.95-1.05) per interquintile range, which the report describes as the difference between the 90th and 10th percentiles.

In contrast, levels of DPA, DHA, and EPA plus DHA were all associated with reduced AFib incidence at interquintile-range HRs of 0.89 (95% CI, 0.83-0.95) for DPA, 0.90 (95% CI, 0.85-0.96) for DHA and 0.93 (95% CI, 0.87-0.99) for EPA and DHA combined.

“We found little evidence that the associations significantly varied by age, sex, or global region, or across the various lipid compartments,” the report states. “Moreover, the relationship between omega-3 fatty acids and AFib did not significantly differ among individuals at higher CV risk.”

The authors observe that the prevalence of omega-3 FA supplement use in the cohorts was very low, suggesting that the omega-3 FA biomarker levels largely reflected habitual dietary intake.

Most of the meta-analysis population were free of CV disease or at relatively low CV risk, they write, and “it is conceivable that the effects of omega-3 fatty acids on atrial arrhythmias may differ in those with existing CV disease versus without.”

However, they note, in a prespecified subgroup analysis of participants mirroring the REDUCE-IT cohort of people with established CV disease or at elevated CV risk, no association with incident AFib was observed for EPA and inverse associations emerged for DPA, DHA, and EPA plus DHA.

In their editorial, Dr. Ballantyne and Dr. Jia say the meta-analysis “represents the largest epidemiological study assessing laboratory-measured omega-3 fatty acid concentrations and AFib risk in the general population.”

But significant heterogeneity across the studies and their populations is a major limitation of the analysis, they write, and made for differences in protocols, sample preparation, outcomes ascertainment, follow-up time, and other variables.

“Despite a rigorous approach to harmonize the data across cohorts and adjusting for multiple confounders,” note Dr. Ballantyne and Dr. Jia, “observational studies always have potential for residual confounders.”

The findings support fish consumption as heart-healthy, they write, but “clinicians should be aware of and discuss with patients the risks versus benefits when prescribing high-dose omega-3 FA therapies.”

The Fatty Acid Research Institute retrospectively provided a small honorarium to a subset of the analysts who participated in this study, but it had no role in its design, analysis, manuscript writing, or decision to submit for publication, the report states. Dr. Ballantyne received grant/research support through his institution from Akcea, Amgen, Arrowhead, Esperion, Ionis, Merck, Novartis, and Regeneron, as well as consulting fees from Alnylam Pharmaceuticals, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Esperion, Genentech, Gilead, Matinas BioPharma, Merck, New Amsterdam, Novartis, Pfizer, and Regeneron. Dr. Heffron and Dr. Jia have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Regular consumption of fish and other foods rich in omega-3 fatty acids (FA) won’t raise an individual’s risk for developing atrial fibrillation (AFib), suggests a meta-analysis of population-based studies.

Lynda Banzi/MDedge News

The finding may alleviate recent concerns about higher-dose omega-3 FA supplement intake in clinical-trial patients at elevated cardiovascular (CV) risk, researchers say.

Indeed, across the 17 cohort studies in the meta-analysis, risk for incident AFib was unaffected by elevated circulating and adipose tissue levels of eicosapentaenoic acid (EPA) from dietary intake. Moreover, the risk appeared to drop significantly with such levels of docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), and EPA plus DHA.

The signals of AFib risk associated with high-dose omega-3 FA in supplements or prescription form in some clinical trials “may not necessarily be generalizable to lower-dose habitual dietary omega-3 intakes,” concludes the study’s report published in the Journal of the American College of Cardiology.

Other recent research suggests that any elevated AFib risk from omega-3 FA intake is dose-related and may be associated with omega-3 FA supplement or medication intake in high doses, such as 4 g/day.

“Coupled with the more consistent benefits of these fatty acids in the prevention of adverse coronary events, our study suggests that current dietary guidelines recommending fish/omega-3 fatty acid consumption should be maintained,” conclude the authors of the report, led by Frank Qian, MD, MPH, Harvard T.H. Chan School of Public Health and Beth Israel Deaconess Medical Center, Boston.

The current study is “important in showing that physiologic levels of omega-3s that would accumulate through diet don’t seem to increase the risk of arrhythmia,” preventive cardiologist Sean Heffron, MD, NYU Langone Health and Grossman School of Medicine, told this news organization.

“It also lends credence to the fact that the increased risk is specific to the high dose supplementation, because that’s the only instance in which we’ve seen increased atrial fibrillation in association with omega-3s,” said Dr. Heffron, who wasn’t involved in the meta-analysis.

An accompanying editorial agrees. “Based on present evidence, moderate dietary intake of fish and seafood is unlikely to achieve sufficiently high levels of omega-3-FAs in blood or tissue that would result in increased AFib risk as observed in clinical trials of fish oil supplements and high-dose prescriptions,” write Christie Ballantyne, MD, and Xiaoming Jia, MD, Baylor College of Medicine, Houston.

Therefore, they conclude, “fish should continue to be an important part of the menu of a heart-healthy diet.”

The meta-analysis comprised 54,799 participants from 21 countries worldwide in 17 prospective cohort studies that yielded data on incident AFib, in which there were 7,720 cases of the arrhythmia over a median follow-up of 13 years. It looked at associations between such cases and levels of omega-3 FA in blood and adipose tissue samples.

In multivariable analysis, EPA levels were not associated with incident AFib, with a hazard ratio of 1.00 (95% confidence interval, 0.95-1.05) per interquintile range, which the report describes as the difference between the 90th and 10th percentiles.

In contrast, levels of DPA, DHA, and EPA plus DHA were all associated with reduced AFib incidence at interquintile-range HRs of 0.89 (95% CI, 0.83-0.95) for DPA, 0.90 (95% CI, 0.85-0.96) for DHA and 0.93 (95% CI, 0.87-0.99) for EPA and DHA combined.

“We found little evidence that the associations significantly varied by age, sex, or global region, or across the various lipid compartments,” the report states. “Moreover, the relationship between omega-3 fatty acids and AFib did not significantly differ among individuals at higher CV risk.”

The authors observe that the prevalence of omega-3 FA supplement use in the cohorts was very low, suggesting that the omega-3 FA biomarker levels largely reflected habitual dietary intake.

Most of the meta-analysis population were free of CV disease or at relatively low CV risk, they write, and “it is conceivable that the effects of omega-3 fatty acids on atrial arrhythmias may differ in those with existing CV disease versus without.”

However, they note, in a prespecified subgroup analysis of participants mirroring the REDUCE-IT cohort of people with established CV disease or at elevated CV risk, no association with incident AFib was observed for EPA and inverse associations emerged for DPA, DHA, and EPA plus DHA.

In their editorial, Dr. Ballantyne and Dr. Jia say the meta-analysis “represents the largest epidemiological study assessing laboratory-measured omega-3 fatty acid concentrations and AFib risk in the general population.”

But significant heterogeneity across the studies and their populations is a major limitation of the analysis, they write, and made for differences in protocols, sample preparation, outcomes ascertainment, follow-up time, and other variables.

“Despite a rigorous approach to harmonize the data across cohorts and adjusting for multiple confounders,” note Dr. Ballantyne and Dr. Jia, “observational studies always have potential for residual confounders.”

The findings support fish consumption as heart-healthy, they write, but “clinicians should be aware of and discuss with patients the risks versus benefits when prescribing high-dose omega-3 FA therapies.”

The Fatty Acid Research Institute retrospectively provided a small honorarium to a subset of the analysts who participated in this study, but it had no role in its design, analysis, manuscript writing, or decision to submit for publication, the report states. Dr. Ballantyne received grant/research support through his institution from Akcea, Amgen, Arrowhead, Esperion, Ionis, Merck, Novartis, and Regeneron, as well as consulting fees from Alnylam Pharmaceuticals, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Esperion, Genentech, Gilead, Matinas BioPharma, Merck, New Amsterdam, Novartis, Pfizer, and Regeneron. Dr. Heffron and Dr. Jia have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Regular consumption of fish and other foods rich in omega-3 fatty acids (FA) won’t raise an individual’s risk for developing atrial fibrillation (AFib), suggests a meta-analysis of population-based studies.

Lynda Banzi/MDedge News

The finding may alleviate recent concerns about higher-dose omega-3 FA supplement intake in clinical-trial patients at elevated cardiovascular (CV) risk, researchers say.

Indeed, across the 17 cohort studies in the meta-analysis, risk for incident AFib was unaffected by elevated circulating and adipose tissue levels of eicosapentaenoic acid (EPA) from dietary intake. Moreover, the risk appeared to drop significantly with such levels of docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), and EPA plus DHA.

The signals of AFib risk associated with high-dose omega-3 FA in supplements or prescription form in some clinical trials “may not necessarily be generalizable to lower-dose habitual dietary omega-3 intakes,” concludes the study’s report published in the Journal of the American College of Cardiology.

Other recent research suggests that any elevated AFib risk from omega-3 FA intake is dose-related and may be associated with omega-3 FA supplement or medication intake in high doses, such as 4 g/day.

“Coupled with the more consistent benefits of these fatty acids in the prevention of adverse coronary events, our study suggests that current dietary guidelines recommending fish/omega-3 fatty acid consumption should be maintained,” conclude the authors of the report, led by Frank Qian, MD, MPH, Harvard T.H. Chan School of Public Health and Beth Israel Deaconess Medical Center, Boston.

The current study is “important in showing that physiologic levels of omega-3s that would accumulate through diet don’t seem to increase the risk of arrhythmia,” preventive cardiologist Sean Heffron, MD, NYU Langone Health and Grossman School of Medicine, told this news organization.

“It also lends credence to the fact that the increased risk is specific to the high dose supplementation, because that’s the only instance in which we’ve seen increased atrial fibrillation in association with omega-3s,” said Dr. Heffron, who wasn’t involved in the meta-analysis.

An accompanying editorial agrees. “Based on present evidence, moderate dietary intake of fish and seafood is unlikely to achieve sufficiently high levels of omega-3-FAs in blood or tissue that would result in increased AFib risk as observed in clinical trials of fish oil supplements and high-dose prescriptions,” write Christie Ballantyne, MD, and Xiaoming Jia, MD, Baylor College of Medicine, Houston.

Therefore, they conclude, “fish should continue to be an important part of the menu of a heart-healthy diet.”

The meta-analysis comprised 54,799 participants from 21 countries worldwide in 17 prospective cohort studies that yielded data on incident AFib, in which there were 7,720 cases of the arrhythmia over a median follow-up of 13 years. It looked at associations between such cases and levels of omega-3 FA in blood and adipose tissue samples.

In multivariable analysis, EPA levels were not associated with incident AFib, with a hazard ratio of 1.00 (95% confidence interval, 0.95-1.05) per interquintile range, which the report describes as the difference between the 90th and 10th percentiles.

In contrast, levels of DPA, DHA, and EPA plus DHA were all associated with reduced AFib incidence at interquintile-range HRs of 0.89 (95% CI, 0.83-0.95) for DPA, 0.90 (95% CI, 0.85-0.96) for DHA and 0.93 (95% CI, 0.87-0.99) for EPA and DHA combined.

“We found little evidence that the associations significantly varied by age, sex, or global region, or across the various lipid compartments,” the report states. “Moreover, the relationship between omega-3 fatty acids and AFib did not significantly differ among individuals at higher CV risk.”

The authors observe that the prevalence of omega-3 FA supplement use in the cohorts was very low, suggesting that the omega-3 FA biomarker levels largely reflected habitual dietary intake.

Most of the meta-analysis population were free of CV disease or at relatively low CV risk, they write, and “it is conceivable that the effects of omega-3 fatty acids on atrial arrhythmias may differ in those with existing CV disease versus without.”

However, they note, in a prespecified subgroup analysis of participants mirroring the REDUCE-IT cohort of people with established CV disease or at elevated CV risk, no association with incident AFib was observed for EPA and inverse associations emerged for DPA, DHA, and EPA plus DHA.

In their editorial, Dr. Ballantyne and Dr. Jia say the meta-analysis “represents the largest epidemiological study assessing laboratory-measured omega-3 fatty acid concentrations and AFib risk in the general population.”

But significant heterogeneity across the studies and their populations is a major limitation of the analysis, they write, and made for differences in protocols, sample preparation, outcomes ascertainment, follow-up time, and other variables.

“Despite a rigorous approach to harmonize the data across cohorts and adjusting for multiple confounders,” note Dr. Ballantyne and Dr. Jia, “observational studies always have potential for residual confounders.”

The findings support fish consumption as heart-healthy, they write, but “clinicians should be aware of and discuss with patients the risks versus benefits when prescribing high-dose omega-3 FA therapies.”

The Fatty Acid Research Institute retrospectively provided a small honorarium to a subset of the analysts who participated in this study, but it had no role in its design, analysis, manuscript writing, or decision to submit for publication, the report states. Dr. Ballantyne received grant/research support through his institution from Akcea, Amgen, Arrowhead, Esperion, Ionis, Merck, Novartis, and Regeneron, as well as consulting fees from Alnylam Pharmaceuticals, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Esperion, Genentech, Gilead, Matinas BioPharma, Merck, New Amsterdam, Novartis, Pfizer, and Regeneron. Dr. Heffron and Dr. Jia have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

MADRID – A late diagnosis of chronic kidney disease is cause for concern. Scientific societies are therefore advocating for screening at younger ages to reverse this trend and slow the progression of the disease. Nearly all patients seen in primary care are candidates for screening because of their risk factors for kidney disease.

During the 29th National Conference of General and Family Medicine of the Spanish Society for General and Family Physicians, Teresa Benedito, MD, family doctor and member of the society’s cardiovascular group, and Roberto Alcázar, MD, nephrologist at the Infanta Leonor University Hospital, Madrid, presented a clinical case encountered in primary care. They used this case to frame a strong argument for the importance of early screening for chronic kidney disease, and they discussed how to properly manage such screening.

The presentation followed the guidelines in the SEMG publication regarding the management and referral of patients with type 2 diabetes. Dr. Benedito explained that the first thing to ask oneself during a patient visit is “whether they present risk factors for kidney disease. If so, we can’t let them leave before we do a kidney screening.” She then listed the factors in question: age older than 60 years, African heritage, family history of chronic kidney disease, decreased kidney mass, weight loss at birth, hypertension, diabetes, smoking, obesity, and low socioeconomic status.

For his part, Dr. Alcázar mentioned how these factors are similar to cardiovascular risk factors, because “the kidneys are a ball of vessels with double capillarization for purifying blood. They’re the organs with the most arteries per unit of weight, so anything that can damage the arteries can damage the kidneys.”
 

Candidates for screening

“Chronic kidney disease develops in 15% of the adult population in Spain. So, it’s worth asking how many patients have been diagnosed and who should we should be screening.” To the factors listed above, Dr. Alcázar added treatment with nephrotoxic drugs (including nonsteroidal anti-inflammatory drugs) for patients with obstructive urinary tract disease, and a history of acute kidney injury for patients with chronic autoimmune disease or neoplasms. “Thus, nearly all patients seen in primary care would need to be screened.”

Another fundamental question raised was whether patients should be screened before age 60 years. “As a nephrologist, I feel that we have been diagnosing chronic kidney disease late, even though we’ve been doing everything by the book,” said Dr. Alcázar. In his opinion, “the answer to whether we should be screening earlier ... is yes, for two reasons: first, because it’s cost-effective, and second, because it’s very inexpensive.”

Dr. Benedito explained in detail the process for diagnosing this disease. She began by defining the disease as changes in kidney structure and function that last longer than 3 months. These changes are identified by use of two criteria: glomerular filtration rate less than 60 mL/min and kidney injury or lesions with or without reduced filtration rate (renal biopsy, albumin/creatinine ratio greater than 30 mg/g, proteinuria, alterations in urinary sediment or in imaging tests). Thus, “if one of these two criteria persists for more than 3 months, the diagnosis is chronic kidney disease. Also, high creatinine levels are not diagnostic for the disease,” she emphasized.
 

Two related parameters

Glomerular filtration and albuminuria “are highly relevant, because screening for chronic kidney disease is based on these two parameters,” said Dr. Benedito. Glomerular filtration rate varies with age, sex, ethnicity, and body mass. It is useful for identifying the stage of the disease and for monitoring disease progression. Albuminuria, on the other hand, is an indication of the severity of the disease. It’s an early marker for kidney injury and systemic disease and is more sensitive than proteinuria. Therefore, “this factor, together with glomerular filtration rate, allows us to detect, classify, and monitor the progression of chronic kidney disease.”

On this point, Dr. Alcázar emphasized the importance of trends, since variation in glomerular filtration depends on serum creatinine, which can vary by nearly 9%. He explained that glomerular filtration rate is related to the number of nephrons remaining. A glomerular filtration rate of less than 60 mL/min implies that more than half of the nephrons in each kidney have been lost. Albuminuria informs about structural damage (that is, the condition of the remaining nephrons). It’s therefore essential to test for both parameters. “We need to be actively monitoring and then making our decisions based on trends and not on isolated results. We need to be aware of albuminuria when we make our decisions,” said Dr. Alcázar. Some studies have shown the importance of testing for albuminuria whenever creatinine level is assessed. “We need to buy into this. If we don’t do this, we’ll only ever have half the information we need.”
 

Reducing late diagnosis

According to the IBERICAN study, 14% of patients seen in primary care in Spain have chronic kidney disease. “This statistic should make us stop and think, own our responsibility, and ask ourselves why this screening isn’t taking place [earlier],” said Dr. Benedito. She added, “We need to head off this trend toward late diagnosis. As the disease progresses, it significantly increases cardiovascular risk and leads to higher mortality, going on dialysis, transplants, et cetera.”

Dr. Alcázar noted that 80% of nephrology cases that are referred to him come from primary care. He explained the need to understand that “these patients have a sevenfold greater risk of suffering a serious cardiovascular event within the next year than people without kidney problems.” Most of these patients will experience an event, even if they don’t undergo dialysis (stage 3 and those near stage 4).
 

Correct staging

Also fundamental is having a detailed understanding of how staging is performed. Dr. Benedito explained that a chart that pairs glomerular filtration rate (six categories) with the level of albuminuria (three categories) should be used during the visit. For example, a case might be classified as G3a-A2. However, the simplified form of the chart may prove more practical. It classifies chronic kidney disease as being associated with mild, moderate, and severe risk, using different colors to aid comprehension.

Dr. Alcázar noted that the latest guidelines from the European Society of Hypertension for 2023 include albuminuria as an important parameter. The guidelines indicate that for a patient with moderate or severe risk, it is not necessary to calculate their score. “It’s considered high cardiovascular risk, and steps would need to be taken for intervention.”

He then listed the tools available for reversing albuminuria. The process begins by reducing salt consumption and involves the use of medications (angiotensin-converting enzyme inhibitors/angiotensin II receptor antagonists, aldosterone receptor antagonists, glucagon-like peptide-1 analogues, and sodium-glucose cotransporter-2 inhibitors, which slow kidney damage regardless of other measures) and strict management of cardiovascular risk factors (smoking, weight management, blood glucose, hypertension, and moderate physical activity).
 

Reducing cardiovascular risk

Dr. Alcázar highlighted important factors to keep in mind when managing each of the cardiovascular risk factors. For hypertension, the aim is to achieve levels less than 130/80 mm Hg, although recommendations vary, depending on the guidelines consulted. “KDIGO (Kidney Disease: Improving Global Outcomes) 2021 states that there is no evidence for monitoring diastolic blood pressure, only systolic blood pressure. If we measure it according to the standardized form, SBP should be less than 120 mm Hg, and if not, we would fall back on readings of 130/80 mm Hg.”

For lipid control (specifically, low-density lipoprotein cholesterol), the staging chart indicates that for patients at mild risk, levels should be less than 100 mg/dL; for those at moderate risk, less than 70 mg/dL; and for those at severe risk, less than 55 mg/dL. Hypertriglyceridemia “should only be treated with fibrates if it comes in over 1,000 mg/dL. Also, care must be taken, because these drugs interfere with creatinine excretion, increasing it,” said Dr. Alcázar.

Guidelines from the KDIGO and the American Diabetes Association state that anyone with diabetes and chronic kidney disease should receive a sodium-glucose cotransporter-2 inhibitor if their glomerular filtration rate exceeds 20 mL/min, “which may contradict slightly what it says on the label. Also, if they have hypertension, they should take an angiotensin-converting enzyme inhibitor,” said Dr. Alcázar. He added that “oral antidiabetics, including metformin, must be adjusted based on renal function if glomerular filtration rate is under 30 mL/min.”
 

Act immediately

When asked whether the course of chronic kidney disease can be changed, Dr. Alcázar responded with an emphatic yes and added that cardiovascular risk can also be substantially reduced. “As nephrologists, we don’t have access to patients in early stages. But family doctors do. Hence the importance of early screening, because going on dialysis at age 60 isn’t the same as at 80.” Currently, “scientific societies are encouraging authorities to screen for chronic kidney disease at earlier ages.”

Regarding drug-based therapy, Dr. Alcázar said that “empagliflozin is not currently indicated for chronic kidney disease in adults.” This sodium-glucose cotransporter-2 inhibitor delays kidney disease and reduces morbidity. Both benefits were highlighted in two recent studies (DAPA-CKD and CREDENCE). Published in January, EMPA-KIDNEY presents a new twist on nephroprotection for patients with chronic kidney disease (diabetic or not) whose glomerular filtration rates are between 20 and 40 mL/min without albuminuria or whose glomerular filtration rates are between 45 and 90 mL/min with albuminuria. For more than 6,000 patients, empagliflozin was observed “to clearly reduce kidney disease progression, cardiovascular mortality and all-cause mortality, and the need to go on dialysis,” stated Dr. Alcázar.
 

What professionals expect

Dr. Benedito also explained the criteria for referral to a specialist: glomerular filtration rate less than 30 mL/min (unless the patient is older than 80 years and does not have progressively worsening renal function), albumin/creatinine ratio greater than 300 mg/g, acute worsening of renal function, progressive worsening of renal function of greater than 5 mL/min/yr, chronic kidney disease, hypertension treated with triple therapy (including a diuretic) at maximum doses, anemia of less than 10 g/dL, and nonurologic hematuria, especially in combination with albuminuria.

Dr. Benedito explained what nephrologists expect from family doctors in the management of chronic kidney disease: “screening for early detection, identifying and treating risk factors for chronic kidney disease, detecting progression and complications, adjusting drugs based on glomerular filtration rate, and ensuring that our patients are benefiting from sodium-glucose cotransporter-2 inhibitors. These are among the most important steps to be taken.”

Dr. Alcázar mentioned what family doctors expect from nephrologists: “two-way communication, accessibility, coordination of actions to be taken, and using shared and mutually agreed-upon protocols.”

This article was translated from the Medscape Spanish Edition and a version appeared on Medscape.com.

MADRID – A late diagnosis of chronic kidney disease is cause for concern. Scientific societies are therefore advocating for screening at younger ages to reverse this trend and slow the progression of the disease. Nearly all patients seen in primary care are candidates for screening because of their risk factors for kidney disease.

During the 29th National Conference of General and Family Medicine of the Spanish Society for General and Family Physicians, Teresa Benedito, MD, family doctor and member of the society’s cardiovascular group, and Roberto Alcázar, MD, nephrologist at the Infanta Leonor University Hospital, Madrid, presented a clinical case encountered in primary care. They used this case to frame a strong argument for the importance of early screening for chronic kidney disease, and they discussed how to properly manage such screening.

The presentation followed the guidelines in the SEMG publication regarding the management and referral of patients with type 2 diabetes. Dr. Benedito explained that the first thing to ask oneself during a patient visit is “whether they present risk factors for kidney disease. If so, we can’t let them leave before we do a kidney screening.” She then listed the factors in question: age older than 60 years, African heritage, family history of chronic kidney disease, decreased kidney mass, weight loss at birth, hypertension, diabetes, smoking, obesity, and low socioeconomic status.

For his part, Dr. Alcázar mentioned how these factors are similar to cardiovascular risk factors, because “the kidneys are a ball of vessels with double capillarization for purifying blood. They’re the organs with the most arteries per unit of weight, so anything that can damage the arteries can damage the kidneys.”
 

Candidates for screening

“Chronic kidney disease develops in 15% of the adult population in Spain. So, it’s worth asking how many patients have been diagnosed and who should we should be screening.” To the factors listed above, Dr. Alcázar added treatment with nephrotoxic drugs (including nonsteroidal anti-inflammatory drugs) for patients with obstructive urinary tract disease, and a history of acute kidney injury for patients with chronic autoimmune disease or neoplasms. “Thus, nearly all patients seen in primary care would need to be screened.”

Another fundamental question raised was whether patients should be screened before age 60 years. “As a nephrologist, I feel that we have been diagnosing chronic kidney disease late, even though we’ve been doing everything by the book,” said Dr. Alcázar. In his opinion, “the answer to whether we should be screening earlier ... is yes, for two reasons: first, because it’s cost-effective, and second, because it’s very inexpensive.”

Dr. Benedito explained in detail the process for diagnosing this disease. She began by defining the disease as changes in kidney structure and function that last longer than 3 months. These changes are identified by use of two criteria: glomerular filtration rate less than 60 mL/min and kidney injury or lesions with or without reduced filtration rate (renal biopsy, albumin/creatinine ratio greater than 30 mg/g, proteinuria, alterations in urinary sediment or in imaging tests). Thus, “if one of these two criteria persists for more than 3 months, the diagnosis is chronic kidney disease. Also, high creatinine levels are not diagnostic for the disease,” she emphasized.
 

Two related parameters

Glomerular filtration and albuminuria “are highly relevant, because screening for chronic kidney disease is based on these two parameters,” said Dr. Benedito. Glomerular filtration rate varies with age, sex, ethnicity, and body mass. It is useful for identifying the stage of the disease and for monitoring disease progression. Albuminuria, on the other hand, is an indication of the severity of the disease. It’s an early marker for kidney injury and systemic disease and is more sensitive than proteinuria. Therefore, “this factor, together with glomerular filtration rate, allows us to detect, classify, and monitor the progression of chronic kidney disease.”

On this point, Dr. Alcázar emphasized the importance of trends, since variation in glomerular filtration depends on serum creatinine, which can vary by nearly 9%. He explained that glomerular filtration rate is related to the number of nephrons remaining. A glomerular filtration rate of less than 60 mL/min implies that more than half of the nephrons in each kidney have been lost. Albuminuria informs about structural damage (that is, the condition of the remaining nephrons). It’s therefore essential to test for both parameters. “We need to be actively monitoring and then making our decisions based on trends and not on isolated results. We need to be aware of albuminuria when we make our decisions,” said Dr. Alcázar. Some studies have shown the importance of testing for albuminuria whenever creatinine level is assessed. “We need to buy into this. If we don’t do this, we’ll only ever have half the information we need.”
 

Reducing late diagnosis

According to the IBERICAN study, 14% of patients seen in primary care in Spain have chronic kidney disease. “This statistic should make us stop and think, own our responsibility, and ask ourselves why this screening isn’t taking place [earlier],” said Dr. Benedito. She added, “We need to head off this trend toward late diagnosis. As the disease progresses, it significantly increases cardiovascular risk and leads to higher mortality, going on dialysis, transplants, et cetera.”

Dr. Alcázar noted that 80% of nephrology cases that are referred to him come from primary care. He explained the need to understand that “these patients have a sevenfold greater risk of suffering a serious cardiovascular event within the next year than people without kidney problems.” Most of these patients will experience an event, even if they don’t undergo dialysis (stage 3 and those near stage 4).
 

Correct staging

Also fundamental is having a detailed understanding of how staging is performed. Dr. Benedito explained that a chart that pairs glomerular filtration rate (six categories) with the level of albuminuria (three categories) should be used during the visit. For example, a case might be classified as G3a-A2. However, the simplified form of the chart may prove more practical. It classifies chronic kidney disease as being associated with mild, moderate, and severe risk, using different colors to aid comprehension.

Dr. Alcázar noted that the latest guidelines from the European Society of Hypertension for 2023 include albuminuria as an important parameter. The guidelines indicate that for a patient with moderate or severe risk, it is not necessary to calculate their score. “It’s considered high cardiovascular risk, and steps would need to be taken for intervention.”

He then listed the tools available for reversing albuminuria. The process begins by reducing salt consumption and involves the use of medications (angiotensin-converting enzyme inhibitors/angiotensin II receptor antagonists, aldosterone receptor antagonists, glucagon-like peptide-1 analogues, and sodium-glucose cotransporter-2 inhibitors, which slow kidney damage regardless of other measures) and strict management of cardiovascular risk factors (smoking, weight management, blood glucose, hypertension, and moderate physical activity).
 

Reducing cardiovascular risk

Dr. Alcázar highlighted important factors to keep in mind when managing each of the cardiovascular risk factors. For hypertension, the aim is to achieve levels less than 130/80 mm Hg, although recommendations vary, depending on the guidelines consulted. “KDIGO (Kidney Disease: Improving Global Outcomes) 2021 states that there is no evidence for monitoring diastolic blood pressure, only systolic blood pressure. If we measure it according to the standardized form, SBP should be less than 120 mm Hg, and if not, we would fall back on readings of 130/80 mm Hg.”

For lipid control (specifically, low-density lipoprotein cholesterol), the staging chart indicates that for patients at mild risk, levels should be less than 100 mg/dL; for those at moderate risk, less than 70 mg/dL; and for those at severe risk, less than 55 mg/dL. Hypertriglyceridemia “should only be treated with fibrates if it comes in over 1,000 mg/dL. Also, care must be taken, because these drugs interfere with creatinine excretion, increasing it,” said Dr. Alcázar.

Guidelines from the KDIGO and the American Diabetes Association state that anyone with diabetes and chronic kidney disease should receive a sodium-glucose cotransporter-2 inhibitor if their glomerular filtration rate exceeds 20 mL/min, “which may contradict slightly what it says on the label. Also, if they have hypertension, they should take an angiotensin-converting enzyme inhibitor,” said Dr. Alcázar. He added that “oral antidiabetics, including metformin, must be adjusted based on renal function if glomerular filtration rate is under 30 mL/min.”
 

Act immediately

When asked whether the course of chronic kidney disease can be changed, Dr. Alcázar responded with an emphatic yes and added that cardiovascular risk can also be substantially reduced. “As nephrologists, we don’t have access to patients in early stages. But family doctors do. Hence the importance of early screening, because going on dialysis at age 60 isn’t the same as at 80.” Currently, “scientific societies are encouraging authorities to screen for chronic kidney disease at earlier ages.”

Regarding drug-based therapy, Dr. Alcázar said that “empagliflozin is not currently indicated for chronic kidney disease in adults.” This sodium-glucose cotransporter-2 inhibitor delays kidney disease and reduces morbidity. Both benefits were highlighted in two recent studies (DAPA-CKD and CREDENCE). Published in January, EMPA-KIDNEY presents a new twist on nephroprotection for patients with chronic kidney disease (diabetic or not) whose glomerular filtration rates are between 20 and 40 mL/min without albuminuria or whose glomerular filtration rates are between 45 and 90 mL/min with albuminuria. For more than 6,000 patients, empagliflozin was observed “to clearly reduce kidney disease progression, cardiovascular mortality and all-cause mortality, and the need to go on dialysis,” stated Dr. Alcázar.
 

What professionals expect

Dr. Benedito also explained the criteria for referral to a specialist: glomerular filtration rate less than 30 mL/min (unless the patient is older than 80 years and does not have progressively worsening renal function), albumin/creatinine ratio greater than 300 mg/g, acute worsening of renal function, progressive worsening of renal function of greater than 5 mL/min/yr, chronic kidney disease, hypertension treated with triple therapy (including a diuretic) at maximum doses, anemia of less than 10 g/dL, and nonurologic hematuria, especially in combination with albuminuria.

Dr. Benedito explained what nephrologists expect from family doctors in the management of chronic kidney disease: “screening for early detection, identifying and treating risk factors for chronic kidney disease, detecting progression and complications, adjusting drugs based on glomerular filtration rate, and ensuring that our patients are benefiting from sodium-glucose cotransporter-2 inhibitors. These are among the most important steps to be taken.”

Dr. Alcázar mentioned what family doctors expect from nephrologists: “two-way communication, accessibility, coordination of actions to be taken, and using shared and mutually agreed-upon protocols.”

This article was translated from the Medscape Spanish Edition and a version appeared on Medscape.com.

MADRID – A late diagnosis of chronic kidney disease is cause for concern. Scientific societies are therefore advocating for screening at younger ages to reverse this trend and slow the progression of the disease. Nearly all patients seen in primary care are candidates for screening because of their risk factors for kidney disease.

During the 29th National Conference of General and Family Medicine of the Spanish Society for General and Family Physicians, Teresa Benedito, MD, family doctor and member of the society’s cardiovascular group, and Roberto Alcázar, MD, nephrologist at the Infanta Leonor University Hospital, Madrid, presented a clinical case encountered in primary care. They used this case to frame a strong argument for the importance of early screening for chronic kidney disease, and they discussed how to properly manage such screening.

The presentation followed the guidelines in the SEMG publication regarding the management and referral of patients with type 2 diabetes. Dr. Benedito explained that the first thing to ask oneself during a patient visit is “whether they present risk factors for kidney disease. If so, we can’t let them leave before we do a kidney screening.” She then listed the factors in question: age older than 60 years, African heritage, family history of chronic kidney disease, decreased kidney mass, weight loss at birth, hypertension, diabetes, smoking, obesity, and low socioeconomic status.

For his part, Dr. Alcázar mentioned how these factors are similar to cardiovascular risk factors, because “the kidneys are a ball of vessels with double capillarization for purifying blood. They’re the organs with the most arteries per unit of weight, so anything that can damage the arteries can damage the kidneys.”
 

Candidates for screening

“Chronic kidney disease develops in 15% of the adult population in Spain. So, it’s worth asking how many patients have been diagnosed and who should we should be screening.” To the factors listed above, Dr. Alcázar added treatment with nephrotoxic drugs (including nonsteroidal anti-inflammatory drugs) for patients with obstructive urinary tract disease, and a history of acute kidney injury for patients with chronic autoimmune disease or neoplasms. “Thus, nearly all patients seen in primary care would need to be screened.”

Another fundamental question raised was whether patients should be screened before age 60 years. “As a nephrologist, I feel that we have been diagnosing chronic kidney disease late, even though we’ve been doing everything by the book,” said Dr. Alcázar. In his opinion, “the answer to whether we should be screening earlier ... is yes, for two reasons: first, because it’s cost-effective, and second, because it’s very inexpensive.”

Dr. Benedito explained in detail the process for diagnosing this disease. She began by defining the disease as changes in kidney structure and function that last longer than 3 months. These changes are identified by use of two criteria: glomerular filtration rate less than 60 mL/min and kidney injury or lesions with or without reduced filtration rate (renal biopsy, albumin/creatinine ratio greater than 30 mg/g, proteinuria, alterations in urinary sediment or in imaging tests). Thus, “if one of these two criteria persists for more than 3 months, the diagnosis is chronic kidney disease. Also, high creatinine levels are not diagnostic for the disease,” she emphasized.
 

Two related parameters

Glomerular filtration and albuminuria “are highly relevant, because screening for chronic kidney disease is based on these two parameters,” said Dr. Benedito. Glomerular filtration rate varies with age, sex, ethnicity, and body mass. It is useful for identifying the stage of the disease and for monitoring disease progression. Albuminuria, on the other hand, is an indication of the severity of the disease. It’s an early marker for kidney injury and systemic disease and is more sensitive than proteinuria. Therefore, “this factor, together with glomerular filtration rate, allows us to detect, classify, and monitor the progression of chronic kidney disease.”

On this point, Dr. Alcázar emphasized the importance of trends, since variation in glomerular filtration depends on serum creatinine, which can vary by nearly 9%. He explained that glomerular filtration rate is related to the number of nephrons remaining. A glomerular filtration rate of less than 60 mL/min implies that more than half of the nephrons in each kidney have been lost. Albuminuria informs about structural damage (that is, the condition of the remaining nephrons). It’s therefore essential to test for both parameters. “We need to be actively monitoring and then making our decisions based on trends and not on isolated results. We need to be aware of albuminuria when we make our decisions,” said Dr. Alcázar. Some studies have shown the importance of testing for albuminuria whenever creatinine level is assessed. “We need to buy into this. If we don’t do this, we’ll only ever have half the information we need.”
 

Reducing late diagnosis

According to the IBERICAN study, 14% of patients seen in primary care in Spain have chronic kidney disease. “This statistic should make us stop and think, own our responsibility, and ask ourselves why this screening isn’t taking place [earlier],” said Dr. Benedito. She added, “We need to head off this trend toward late diagnosis. As the disease progresses, it significantly increases cardiovascular risk and leads to higher mortality, going on dialysis, transplants, et cetera.”

Dr. Alcázar noted that 80% of nephrology cases that are referred to him come from primary care. He explained the need to understand that “these patients have a sevenfold greater risk of suffering a serious cardiovascular event within the next year than people without kidney problems.” Most of these patients will experience an event, even if they don’t undergo dialysis (stage 3 and those near stage 4).
 

Correct staging

Also fundamental is having a detailed understanding of how staging is performed. Dr. Benedito explained that a chart that pairs glomerular filtration rate (six categories) with the level of albuminuria (three categories) should be used during the visit. For example, a case might be classified as G3a-A2. However, the simplified form of the chart may prove more practical. It classifies chronic kidney disease as being associated with mild, moderate, and severe risk, using different colors to aid comprehension.

Dr. Alcázar noted that the latest guidelines from the European Society of Hypertension for 2023 include albuminuria as an important parameter. The guidelines indicate that for a patient with moderate or severe risk, it is not necessary to calculate their score. “It’s considered high cardiovascular risk, and steps would need to be taken for intervention.”

He then listed the tools available for reversing albuminuria. The process begins by reducing salt consumption and involves the use of medications (angiotensin-converting enzyme inhibitors/angiotensin II receptor antagonists, aldosterone receptor antagonists, glucagon-like peptide-1 analogues, and sodium-glucose cotransporter-2 inhibitors, which slow kidney damage regardless of other measures) and strict management of cardiovascular risk factors (smoking, weight management, blood glucose, hypertension, and moderate physical activity).
 

Reducing cardiovascular risk

Dr. Alcázar highlighted important factors to keep in mind when managing each of the cardiovascular risk factors. For hypertension, the aim is to achieve levels less than 130/80 mm Hg, although recommendations vary, depending on the guidelines consulted. “KDIGO (Kidney Disease: Improving Global Outcomes) 2021 states that there is no evidence for monitoring diastolic blood pressure, only systolic blood pressure. If we measure it according to the standardized form, SBP should be less than 120 mm Hg, and if not, we would fall back on readings of 130/80 mm Hg.”

For lipid control (specifically, low-density lipoprotein cholesterol), the staging chart indicates that for patients at mild risk, levels should be less than 100 mg/dL; for those at moderate risk, less than 70 mg/dL; and for those at severe risk, less than 55 mg/dL. Hypertriglyceridemia “should only be treated with fibrates if it comes in over 1,000 mg/dL. Also, care must be taken, because these drugs interfere with creatinine excretion, increasing it,” said Dr. Alcázar.

Guidelines from the KDIGO and the American Diabetes Association state that anyone with diabetes and chronic kidney disease should receive a sodium-glucose cotransporter-2 inhibitor if their glomerular filtration rate exceeds 20 mL/min, “which may contradict slightly what it says on the label. Also, if they have hypertension, they should take an angiotensin-converting enzyme inhibitor,” said Dr. Alcázar. He added that “oral antidiabetics, including metformin, must be adjusted based on renal function if glomerular filtration rate is under 30 mL/min.”
 

Act immediately

When asked whether the course of chronic kidney disease can be changed, Dr. Alcázar responded with an emphatic yes and added that cardiovascular risk can also be substantially reduced. “As nephrologists, we don’t have access to patients in early stages. But family doctors do. Hence the importance of early screening, because going on dialysis at age 60 isn’t the same as at 80.” Currently, “scientific societies are encouraging authorities to screen for chronic kidney disease at earlier ages.”

Regarding drug-based therapy, Dr. Alcázar said that “empagliflozin is not currently indicated for chronic kidney disease in adults.” This sodium-glucose cotransporter-2 inhibitor delays kidney disease and reduces morbidity. Both benefits were highlighted in two recent studies (DAPA-CKD and CREDENCE). Published in January, EMPA-KIDNEY presents a new twist on nephroprotection for patients with chronic kidney disease (diabetic or not) whose glomerular filtration rates are between 20 and 40 mL/min without albuminuria or whose glomerular filtration rates are between 45 and 90 mL/min with albuminuria. For more than 6,000 patients, empagliflozin was observed “to clearly reduce kidney disease progression, cardiovascular mortality and all-cause mortality, and the need to go on dialysis,” stated Dr. Alcázar.
 

What professionals expect

Dr. Benedito also explained the criteria for referral to a specialist: glomerular filtration rate less than 30 mL/min (unless the patient is older than 80 years and does not have progressively worsening renal function), albumin/creatinine ratio greater than 300 mg/g, acute worsening of renal function, progressive worsening of renal function of greater than 5 mL/min/yr, chronic kidney disease, hypertension treated with triple therapy (including a diuretic) at maximum doses, anemia of less than 10 g/dL, and nonurologic hematuria, especially in combination with albuminuria.

Dr. Benedito explained what nephrologists expect from family doctors in the management of chronic kidney disease: “screening for early detection, identifying and treating risk factors for chronic kidney disease, detecting progression and complications, adjusting drugs based on glomerular filtration rate, and ensuring that our patients are benefiting from sodium-glucose cotransporter-2 inhibitors. These are among the most important steps to be taken.”

Dr. Alcázar mentioned what family doctors expect from nephrologists: “two-way communication, accessibility, coordination of actions to be taken, and using shared and mutually agreed-upon protocols.”

This article was translated from the Medscape Spanish Edition and a version appeared on Medscape.com.

The antiplatelet of choice for long-term, secondary prevention for patients with established coronary artery disease (CAD) may well be a P2Y12 inhibitor such as clopidogrel or ticagrelor rather than aspirin, suggests a patient-level meta-analysis of seven randomized trials.

The more than 24,000 patients in the meta-analysis, called PANTHER, had documented stable CAD, prior myocardial infarction (MI), or recent or remote surgical or percutaneous coronary revascularization.

About half of patients in each antiplatelet monotherapy trial received clopidogrel or ticagrelor, and the other half received aspirin. Follow-ups ranged from 6 months to 3 years.

Those taking a P2Y12 inhibitor showed a 12% reduction in risk (P = .012) for the primary efficacy outcome, a composite of cardiovascular (CV) death, MI, and stroke, over a median of about 1.35 years. The difference was driven primarily by a 23% reduction in risk for MI (P < .001); mortality seemed unaffected by antiplatelet treatment assignment.

Although the P2Y12 inhibitor and aspirin groups were similar with respect to risk of major bleeding, the P2Y12 inhibitor group showed significant reductions in risk for gastrointestinal (GI) bleeding, definite stent thrombosis, and hemorrhagic stroke; rates of hemorrhagic stroke were well under 1% in both groups.

The treatment effects were consistent across patient subgroups, including whether the aspirin comparison was with clopidogrel or ticagrelor.

“Taken together, our data challenge the central role of aspirin in secondary prevention and support a paradigm shift toward P2Y12 inhibitor monotherapy as long-term antiplatelet strategy in the sizable population of patients with coronary atherosclerosis,” Felice Gragnano, MD, PhD, said in an interview. “Given [their] superior efficacy and similar overall safety, P2Y12 inhibitors may be preferred [over] aspirin for the prevention of cardiovascular events in patients with CAD.”

Dr. Gragnano, of the University of Campania Luigi Vanvitelli, Caserta, Italy, who called PANTHER “the largest and most comprehensive synthesis of individual patient data from randomized trials comparing P2Y12 inhibitor monotherapy with aspirin monotherapy,” is lead author of the study, which was published online in the Journal of the American College of Cardiology.

Current guidelines recommend aspirin for antiplatelet monotherapy for patients with established CAD, Dr. Gragnano said, but “the primacy of aspirin in secondary prevention is based on historical trials conducted in the 1970s and 1980s and may not apply to contemporary practice.”

Moreover, later trials that compared P2Y12 inhibitors with aspirin for secondary prevention produced “inconsistent results,” possibly owing to their heterogeneous populations of patients with coronary, cerebrovascular, or peripheral vascular disease, he said. Study-level meta-analyses in this area “provide inconclusive evidence” because they haven’t evaluated treatment effects exclusively in patients with established CAD.

Most of the seven trials’ 24,325 participants had a history of MI, and some had peripheral artery disease (PAD); the rates were 56.2% and 9.1%, respectively. Coronary revascularization, either percutaneous or surgical, had been performed for about 70%. Most (61%) had presented with acute coronary syndromes, and the remainder had presented with chronic CAD.

About 76% of the combined cohorts were from Europe or North America; the rest were from Asia. The mean age of the patients was 64 years, and about 22% were women.

In all, 12,175 had been assigned to P2Y12 inhibitor monotherapy (62% received clopidogrel and 38% received ticagrelor); 12,147 received aspirin at dosages ranging from 75 mg to 325 mg daily.

The hazard ratio (HR) for the primary efficacy outcome, P2Y12 inhibitors vs. aspirin, was significantly reduced, at 0.88 (95% confidence interval [CI], 0.79-0.97; P = .012); the number needed to treat (NNT) to prevent one primary event over 2 years was 121, the report states.

The corresponding HR for MI was 0.77 (95% CI, 0.66-0.90; P < .001), for an NNT benefit of 136. For net adverse clinical events, the HR was 0.89 (95% CI, 0.81-0.98; P = .020), for an NNT benefit of 121.

Risk for major bleeding was not significantly different (HR, 0.87; 95% CI, 0.70-1.09; P = .23), nor were risks for stroke (HR, 0.84; 95% CI, 0.70-1.02; P = .076) or cardiovascular death (HR, 1.02; 95% CI, 0.86-1.20; P = .82).

Still, the P2Y12 inhibitor group showed significant risk reductions for the following:

• GI bleeding: HR, 0.75 (95% CI, 0.57-0.97; P = .027)
• Definite stent thrombosis: HR, 0.42 (95% CI, 0.19-0.97; P = .028)
• Hemorrhagic stroke: HR, 0.43 (95% CI, 0.23-0.83; P = .012)

The current findings are “hypothesis-generating but not definitive,” Dharam Kumbhani, MD, University of Texas Southwestern, Dallas, said in an interview.

It remains unclear “whether aspirin or P2Y12 inhibitor monotherapy is better for long-term maintenance use among patients with established CAD. Aspirin has historically been the agent of choice for this indication,” said Dr. Kumbhani, who with James A. de Lemos, MD, of the same institution, wrote an editorial accompanying the PANTHER report.

“It certainly would be appropriate to consider P2Y12 monotherapy preferentially for patients with prior or currently at high risk for GI or intracranial bleeding, for instance,” Dr. Kumbhani said. For the remainder, aspirin and P2Y12 inhibitors are both “reasonable alternatives.”

In their editorial, Dr. Kumbhani and Dr. de Lemos call the PANTHER meta-analysis “a well-done study with potentially important clinical implications.” The findings “make biological sense: P2Y12 inhibitors are more potent antiplatelet agents than aspirin and have less effect on gastrointestinal mucosal integrity.”

But for now, they wrote, “both aspirin and P2Y12 inhibitors remain viable alternatives for prevention of atherothrombotic events among patients with established CAD.”

Dr. Gragnano had no disclosures; potential conflicts for the other authors are in the report. Dr. Kumbhani reports no relevant relationships; Dr. de Lemos has received honoraria for participation in data safety monitoring boards from Eli Lilly, Novo Nordisk, AstraZeneca, and Janssen.

A version of this article first appeared on Medscape.com.

The antiplatelet of choice for long-term, secondary prevention for patients with established coronary artery disease (CAD) may well be a P2Y12 inhibitor such as clopidogrel or ticagrelor rather than aspirin, suggests a patient-level meta-analysis of seven randomized trials.

The more than 24,000 patients in the meta-analysis, called PANTHER, had documented stable CAD, prior myocardial infarction (MI), or recent or remote surgical or percutaneous coronary revascularization.

About half of patients in each antiplatelet monotherapy trial received clopidogrel or ticagrelor, and the other half received aspirin. Follow-ups ranged from 6 months to 3 years.

Those taking a P2Y12 inhibitor showed a 12% reduction in risk (P = .012) for the primary efficacy outcome, a composite of cardiovascular (CV) death, MI, and stroke, over a median of about 1.35 years. The difference was driven primarily by a 23% reduction in risk for MI (P < .001); mortality seemed unaffected by antiplatelet treatment assignment.

Although the P2Y12 inhibitor and aspirin groups were similar with respect to risk of major bleeding, the P2Y12 inhibitor group showed significant reductions in risk for gastrointestinal (GI) bleeding, definite stent thrombosis, and hemorrhagic stroke; rates of hemorrhagic stroke were well under 1% in both groups.

The treatment effects were consistent across patient subgroups, including whether the aspirin comparison was with clopidogrel or ticagrelor.

“Taken together, our data challenge the central role of aspirin in secondary prevention and support a paradigm shift toward P2Y12 inhibitor monotherapy as long-term antiplatelet strategy in the sizable population of patients with coronary atherosclerosis,” Felice Gragnano, MD, PhD, said in an interview. “Given [their] superior efficacy and similar overall safety, P2Y12 inhibitors may be preferred [over] aspirin for the prevention of cardiovascular events in patients with CAD.”

Dr. Gragnano, of the University of Campania Luigi Vanvitelli, Caserta, Italy, who called PANTHER “the largest and most comprehensive synthesis of individual patient data from randomized trials comparing P2Y12 inhibitor monotherapy with aspirin monotherapy,” is lead author of the study, which was published online in the Journal of the American College of Cardiology.

Current guidelines recommend aspirin for antiplatelet monotherapy for patients with established CAD, Dr. Gragnano said, but “the primacy of aspirin in secondary prevention is based on historical trials conducted in the 1970s and 1980s and may not apply to contemporary practice.”

Moreover, later trials that compared P2Y12 inhibitors with aspirin for secondary prevention produced “inconsistent results,” possibly owing to their heterogeneous populations of patients with coronary, cerebrovascular, or peripheral vascular disease, he said. Study-level meta-analyses in this area “provide inconclusive evidence” because they haven’t evaluated treatment effects exclusively in patients with established CAD.

Most of the seven trials’ 24,325 participants had a history of MI, and some had peripheral artery disease (PAD); the rates were 56.2% and 9.1%, respectively. Coronary revascularization, either percutaneous or surgical, had been performed for about 70%. Most (61%) had presented with acute coronary syndromes, and the remainder had presented with chronic CAD.

About 76% of the combined cohorts were from Europe or North America; the rest were from Asia. The mean age of the patients was 64 years, and about 22% were women.

In all, 12,175 had been assigned to P2Y12 inhibitor monotherapy (62% received clopidogrel and 38% received ticagrelor); 12,147 received aspirin at dosages ranging from 75 mg to 325 mg daily.

The hazard ratio (HR) for the primary efficacy outcome, P2Y12 inhibitors vs. aspirin, was significantly reduced, at 0.88 (95% confidence interval [CI], 0.79-0.97; P = .012); the number needed to treat (NNT) to prevent one primary event over 2 years was 121, the report states.

The corresponding HR for MI was 0.77 (95% CI, 0.66-0.90; P < .001), for an NNT benefit of 136. For net adverse clinical events, the HR was 0.89 (95% CI, 0.81-0.98; P = .020), for an NNT benefit of 121.

Risk for major bleeding was not significantly different (HR, 0.87; 95% CI, 0.70-1.09; P = .23), nor were risks for stroke (HR, 0.84; 95% CI, 0.70-1.02; P = .076) or cardiovascular death (HR, 1.02; 95% CI, 0.86-1.20; P = .82).

Still, the P2Y12 inhibitor group showed significant risk reductions for the following:

• GI bleeding: HR, 0.75 (95% CI, 0.57-0.97; P = .027)
• Definite stent thrombosis: HR, 0.42 (95% CI, 0.19-0.97; P = .028)
• Hemorrhagic stroke: HR, 0.43 (95% CI, 0.23-0.83; P = .012)

The current findings are “hypothesis-generating but not definitive,” Dharam Kumbhani, MD, University of Texas Southwestern, Dallas, said in an interview.

It remains unclear “whether aspirin or P2Y12 inhibitor monotherapy is better for long-term maintenance use among patients with established CAD. Aspirin has historically been the agent of choice for this indication,” said Dr. Kumbhani, who with James A. de Lemos, MD, of the same institution, wrote an editorial accompanying the PANTHER report.

“It certainly would be appropriate to consider P2Y12 monotherapy preferentially for patients with prior or currently at high risk for GI or intracranial bleeding, for instance,” Dr. Kumbhani said. For the remainder, aspirin and P2Y12 inhibitors are both “reasonable alternatives.”

In their editorial, Dr. Kumbhani and Dr. de Lemos call the PANTHER meta-analysis “a well-done study with potentially important clinical implications.” The findings “make biological sense: P2Y12 inhibitors are more potent antiplatelet agents than aspirin and have less effect on gastrointestinal mucosal integrity.”

But for now, they wrote, “both aspirin and P2Y12 inhibitors remain viable alternatives for prevention of atherothrombotic events among patients with established CAD.”

Dr. Gragnano had no disclosures; potential conflicts for the other authors are in the report. Dr. Kumbhani reports no relevant relationships; Dr. de Lemos has received honoraria for participation in data safety monitoring boards from Eli Lilly, Novo Nordisk, AstraZeneca, and Janssen.

A version of this article first appeared on Medscape.com.

The antiplatelet of choice for long-term, secondary prevention for patients with established coronary artery disease (CAD) may well be a P2Y12 inhibitor such as clopidogrel or ticagrelor rather than aspirin, suggests a patient-level meta-analysis of seven randomized trials.

The more than 24,000 patients in the meta-analysis, called PANTHER, had documented stable CAD, prior myocardial infarction (MI), or recent or remote surgical or percutaneous coronary revascularization.

About half of patients in each antiplatelet monotherapy trial received clopidogrel or ticagrelor, and the other half received aspirin. Follow-ups ranged from 6 months to 3 years.

Those taking a P2Y12 inhibitor showed a 12% reduction in risk (P = .012) for the primary efficacy outcome, a composite of cardiovascular (CV) death, MI, and stroke, over a median of about 1.35 years. The difference was driven primarily by a 23% reduction in risk for MI (P < .001); mortality seemed unaffected by antiplatelet treatment assignment.

Although the P2Y12 inhibitor and aspirin groups were similar with respect to risk of major bleeding, the P2Y12 inhibitor group showed significant reductions in risk for gastrointestinal (GI) bleeding, definite stent thrombosis, and hemorrhagic stroke; rates of hemorrhagic stroke were well under 1% in both groups.

The treatment effects were consistent across patient subgroups, including whether the aspirin comparison was with clopidogrel or ticagrelor.

“Taken together, our data challenge the central role of aspirin in secondary prevention and support a paradigm shift toward P2Y12 inhibitor monotherapy as long-term antiplatelet strategy in the sizable population of patients with coronary atherosclerosis,” Felice Gragnano, MD, PhD, said in an interview. “Given [their] superior efficacy and similar overall safety, P2Y12 inhibitors may be preferred [over] aspirin for the prevention of cardiovascular events in patients with CAD.”

Dr. Gragnano, of the University of Campania Luigi Vanvitelli, Caserta, Italy, who called PANTHER “the largest and most comprehensive synthesis of individual patient data from randomized trials comparing P2Y12 inhibitor monotherapy with aspirin monotherapy,” is lead author of the study, which was published online in the Journal of the American College of Cardiology.

Current guidelines recommend aspirin for antiplatelet monotherapy for patients with established CAD, Dr. Gragnano said, but “the primacy of aspirin in secondary prevention is based on historical trials conducted in the 1970s and 1980s and may not apply to contemporary practice.”

Moreover, later trials that compared P2Y12 inhibitors with aspirin for secondary prevention produced “inconsistent results,” possibly owing to their heterogeneous populations of patients with coronary, cerebrovascular, or peripheral vascular disease, he said. Study-level meta-analyses in this area “provide inconclusive evidence” because they haven’t evaluated treatment effects exclusively in patients with established CAD.

Most of the seven trials’ 24,325 participants had a history of MI, and some had peripheral artery disease (PAD); the rates were 56.2% and 9.1%, respectively. Coronary revascularization, either percutaneous or surgical, had been performed for about 70%. Most (61%) had presented with acute coronary syndromes, and the remainder had presented with chronic CAD.

About 76% of the combined cohorts were from Europe or North America; the rest were from Asia. The mean age of the patients was 64 years, and about 22% were women.

In all, 12,175 had been assigned to P2Y12 inhibitor monotherapy (62% received clopidogrel and 38% received ticagrelor); 12,147 received aspirin at dosages ranging from 75 mg to 325 mg daily.

The hazard ratio (HR) for the primary efficacy outcome, P2Y12 inhibitors vs. aspirin, was significantly reduced, at 0.88 (95% confidence interval [CI], 0.79-0.97; P = .012); the number needed to treat (NNT) to prevent one primary event over 2 years was 121, the report states.

The corresponding HR for MI was 0.77 (95% CI, 0.66-0.90; P < .001), for an NNT benefit of 136. For net adverse clinical events, the HR was 0.89 (95% CI, 0.81-0.98; P = .020), for an NNT benefit of 121.

Risk for major bleeding was not significantly different (HR, 0.87; 95% CI, 0.70-1.09; P = .23), nor were risks for stroke (HR, 0.84; 95% CI, 0.70-1.02; P = .076) or cardiovascular death (HR, 1.02; 95% CI, 0.86-1.20; P = .82).

Still, the P2Y12 inhibitor group showed significant risk reductions for the following:

• GI bleeding: HR, 0.75 (95% CI, 0.57-0.97; P = .027)
• Definite stent thrombosis: HR, 0.42 (95% CI, 0.19-0.97; P = .028)
• Hemorrhagic stroke: HR, 0.43 (95% CI, 0.23-0.83; P = .012)

The current findings are “hypothesis-generating but not definitive,” Dharam Kumbhani, MD, University of Texas Southwestern, Dallas, said in an interview.

It remains unclear “whether aspirin or P2Y12 inhibitor monotherapy is better for long-term maintenance use among patients with established CAD. Aspirin has historically been the agent of choice for this indication,” said Dr. Kumbhani, who with James A. de Lemos, MD, of the same institution, wrote an editorial accompanying the PANTHER report.

“It certainly would be appropriate to consider P2Y12 monotherapy preferentially for patients with prior or currently at high risk for GI or intracranial bleeding, for instance,” Dr. Kumbhani said. For the remainder, aspirin and P2Y12 inhibitors are both “reasonable alternatives.”

In their editorial, Dr. Kumbhani and Dr. de Lemos call the PANTHER meta-analysis “a well-done study with potentially important clinical implications.” The findings “make biological sense: P2Y12 inhibitors are more potent antiplatelet agents than aspirin and have less effect on gastrointestinal mucosal integrity.”

But for now, they wrote, “both aspirin and P2Y12 inhibitors remain viable alternatives for prevention of atherothrombotic events among patients with established CAD.”

Dr. Gragnano had no disclosures; potential conflicts for the other authors are in the report. Dr. Kumbhani reports no relevant relationships; Dr. de Lemos has received honoraria for participation in data safety monitoring boards from Eli Lilly, Novo Nordisk, AstraZeneca, and Janssen.

A version of this article first appeared on Medscape.com.

Stop me if you’ve heard this before. There’s a controversy over blood pressure targets. Some argue for 140/90 mm Hg, others for 130/80 mm Hg, and some super ambitious folks think that we should aim for 120/80 mm Hg. If this sounds familiar, it should. We did it in 2017. It’s unclear what, if anything, we learned from the experience. On the upside, it’s not as bad as it was 100 years ago.

When high blood pressure was a ‘good’ thing

Back then, many believed that you needed higher blood pressure as you got older to push the blood through your progressively stiffened and hardened arteries. Hence the name “essential” hypertension. The concern was that lowering blood pressure would hypoperfuse your organs and be dangerous. In the 1930s, John Hay told an audience at a British Medical Association lecture: “The greatest danger to a man with high blood pressure lies in its discovery, because then some fool is certain to try and reduce it.”

The 1900s were a simpler time when people had fatal strokes in their 50s, and their families were consoled by the knowledge that they had lived a good life.

If our thinking around blood pressure had evolved slightly faster, perhaps President Roosevelt wouldn’t have died of a stroke during World War II as his doctors watched his systolic blood pressure climb above 200 mm Hg and suggested massages and barbiturates to take the edge off.
 

The current controversy

Not that long ago, 180 mm Hg was considered mild hypertension. Now, we are arguing about a systolic blood pressure of 140 versus 130 mm Hg.

The American Academy of Family Physicians takes the view that 140/90 mm Hg is good enough for most people. Their most recent clinical practice guideline, based primarily on two 2020 Cochrane Reviews of blood pressure targets in patients with and without cardiovascular disease, did not find any mortality benefit for a lower blood pressure threshold.

This puts the AAFP guideline in conflict with the 2017 guideline issued jointly by the American College of Cardiology, American Heart Association, and nine other groups, which recommended a target of 130/80 mm Hg for pretty much everyone. Though they say greater than 140/90 mm Hg should be the threshold for low-risk patients or for starting therapy post stroke, we often forget those nuances. The main point of contention is that the AAFP guideline was looking for a mortality benefit, whereas the ACC/AHA/everyone else guideline was looking at preventing cardiovascular events. The latter guideline was driven mainly by the results of the SPRINT trial. ACC/AHA argue for more aggressive targets to prevent the things that cardiologists care about, namely heart attacks.

The AAFP guideline conceded that more aggressive control will result in fewer myocardial infarctions but warn that it comes with more adverse events. Treating 1,000 patients to this lower target would theoretically prevent four MIs, possibly prevent three strokes, but result in 30 adverse events.

In the end, what we are seeing here is not so much a debate over the evidence as a debate over priorities. The AAFP’s main focus is all-cause mortality; the ACC/AHA’s is cardiovascular events. Interventions that don’t improve mortality can be questioned in terms of their cost effectiveness. But you probably don’t want to have a heart attack (even a nonfatal one). And you certainly don’t want to have a stroke. However, lower blood pressure targets inevitably require more medications. Notwithstanding the economic costs, the dangers of polypharmacy, medication interactions, side effects, and syncope leading to falls cannot be ignored. Falls are not benign adverse events, especially in older adults.

The counter argument is that physicians are human and often let things slide. Set the target at 140/90 mm Hg, and many physicians won’t jump on a systolic blood pressure of 144 mm Hg. Set the target at 130 mm Hg, and maybe they’ll be more likely to react. There’s a fine line between permissiveness and complacency.

If you zoom out and look at the multitude of blood pressure guidelines, you start to notice an important fact. There is not much daylight between them. There are subtle differences in what constitutes high risk and different definitions of older (older should be defined as 10 years older than the reader’s current age). But otherwise, the blood pressure targets are not that different.

Does that final 10 mm Hg really matter when barriers to care mean that tens of millions in the United States are unaware they have hypertension? Even among those diagnosed, many are either untreated or inadequately treated.

With this context, perhaps the most insightful thing that can be said about the blood pressure guideline controversy is that it’s not all that controversial. We can likely all agree that we need to be better at treating hypertension and that creative solutions to reach underserved communities are necessary.

Arguing about 140/90 mm Hg or 130/80 mm Hg is less important than acknowledging that we should be aggressive in screening for and treating hypertension. We should acknowledge that beyond a certain point any cardiovascular benefit comes at the cost of hypotension and side effects. That tipping point will be different for different groups, and probably at a higher set point in older patients.

Individualizing care isn’t difficult. We do it all the time. We just shouldn’t be letting people walk around with untreated hypertension. It’s not the 1900s anymore.

Dr. Labos is a cardiologist at Hôpital Notre-Dame, Montreal. He reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

Stop me if you’ve heard this before. There’s a controversy over blood pressure targets. Some argue for 140/90 mm Hg, others for 130/80 mm Hg, and some super ambitious folks think that we should aim for 120/80 mm Hg. If this sounds familiar, it should. We did it in 2017. It’s unclear what, if anything, we learned from the experience. On the upside, it’s not as bad as it was 100 years ago.

When high blood pressure was a ‘good’ thing

Back then, many believed that you needed higher blood pressure as you got older to push the blood through your progressively stiffened and hardened arteries. Hence the name “essential” hypertension. The concern was that lowering blood pressure would hypoperfuse your organs and be dangerous. In the 1930s, John Hay told an audience at a British Medical Association lecture: “The greatest danger to a man with high blood pressure lies in its discovery, because then some fool is certain to try and reduce it.”

The 1900s were a simpler time when people had fatal strokes in their 50s, and their families were consoled by the knowledge that they had lived a good life.

If our thinking around blood pressure had evolved slightly faster, perhaps President Roosevelt wouldn’t have died of a stroke during World War II as his doctors watched his systolic blood pressure climb above 200 mm Hg and suggested massages and barbiturates to take the edge off.
 

The current controversy

Not that long ago, 180 mm Hg was considered mild hypertension. Now, we are arguing about a systolic blood pressure of 140 versus 130 mm Hg.

The American Academy of Family Physicians takes the view that 140/90 mm Hg is good enough for most people. Their most recent clinical practice guideline, based primarily on two 2020 Cochrane Reviews of blood pressure targets in patients with and without cardiovascular disease, did not find any mortality benefit for a lower blood pressure threshold.

This puts the AAFP guideline in conflict with the 2017 guideline issued jointly by the American College of Cardiology, American Heart Association, and nine other groups, which recommended a target of 130/80 mm Hg for pretty much everyone. Though they say greater than 140/90 mm Hg should be the threshold for low-risk patients or for starting therapy post stroke, we often forget those nuances. The main point of contention is that the AAFP guideline was looking for a mortality benefit, whereas the ACC/AHA/everyone else guideline was looking at preventing cardiovascular events. The latter guideline was driven mainly by the results of the SPRINT trial. ACC/AHA argue for more aggressive targets to prevent the things that cardiologists care about, namely heart attacks.

The AAFP guideline conceded that more aggressive control will result in fewer myocardial infarctions but warn that it comes with more adverse events. Treating 1,000 patients to this lower target would theoretically prevent four MIs, possibly prevent three strokes, but result in 30 adverse events.

In the end, what we are seeing here is not so much a debate over the evidence as a debate over priorities. The AAFP’s main focus is all-cause mortality; the ACC/AHA’s is cardiovascular events. Interventions that don’t improve mortality can be questioned in terms of their cost effectiveness. But you probably don’t want to have a heart attack (even a nonfatal one). And you certainly don’t want to have a stroke. However, lower blood pressure targets inevitably require more medications. Notwithstanding the economic costs, the dangers of polypharmacy, medication interactions, side effects, and syncope leading to falls cannot be ignored. Falls are not benign adverse events, especially in older adults.

The counter argument is that physicians are human and often let things slide. Set the target at 140/90 mm Hg, and many physicians won’t jump on a systolic blood pressure of 144 mm Hg. Set the target at 130 mm Hg, and maybe they’ll be more likely to react. There’s a fine line between permissiveness and complacency.

If you zoom out and look at the multitude of blood pressure guidelines, you start to notice an important fact. There is not much daylight between them. There are subtle differences in what constitutes high risk and different definitions of older (older should be defined as 10 years older than the reader’s current age). But otherwise, the blood pressure targets are not that different.

Does that final 10 mm Hg really matter when barriers to care mean that tens of millions in the United States are unaware they have hypertension? Even among those diagnosed, many are either untreated or inadequately treated.

With this context, perhaps the most insightful thing that can be said about the blood pressure guideline controversy is that it’s not all that controversial. We can likely all agree that we need to be better at treating hypertension and that creative solutions to reach underserved communities are necessary.

Arguing about 140/90 mm Hg or 130/80 mm Hg is less important than acknowledging that we should be aggressive in screening for and treating hypertension. We should acknowledge that beyond a certain point any cardiovascular benefit comes at the cost of hypotension and side effects. That tipping point will be different for different groups, and probably at a higher set point in older patients.

Individualizing care isn’t difficult. We do it all the time. We just shouldn’t be letting people walk around with untreated hypertension. It’s not the 1900s anymore.

Dr. Labos is a cardiologist at Hôpital Notre-Dame, Montreal. He reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

Stop me if you’ve heard this before. There’s a controversy over blood pressure targets. Some argue for 140/90 mm Hg, others for 130/80 mm Hg, and some super ambitious folks think that we should aim for 120/80 mm Hg. If this sounds familiar, it should. We did it in 2017. It’s unclear what, if anything, we learned from the experience. On the upside, it’s not as bad as it was 100 years ago.

When high blood pressure was a ‘good’ thing

Back then, many believed that you needed higher blood pressure as you got older to push the blood through your progressively stiffened and hardened arteries. Hence the name “essential” hypertension. The concern was that lowering blood pressure would hypoperfuse your organs and be dangerous. In the 1930s, John Hay told an audience at a British Medical Association lecture: “The greatest danger to a man with high blood pressure lies in its discovery, because then some fool is certain to try and reduce it.”

The 1900s were a simpler time when people had fatal strokes in their 50s, and their families were consoled by the knowledge that they had lived a good life.

If our thinking around blood pressure had evolved slightly faster, perhaps President Roosevelt wouldn’t have died of a stroke during World War II as his doctors watched his systolic blood pressure climb above 200 mm Hg and suggested massages and barbiturates to take the edge off.
 

The current controversy

Not that long ago, 180 mm Hg was considered mild hypertension. Now, we are arguing about a systolic blood pressure of 140 versus 130 mm Hg.

The American Academy of Family Physicians takes the view that 140/90 mm Hg is good enough for most people. Their most recent clinical practice guideline, based primarily on two 2020 Cochrane Reviews of blood pressure targets in patients with and without cardiovascular disease, did not find any mortality benefit for a lower blood pressure threshold.

This puts the AAFP guideline in conflict with the 2017 guideline issued jointly by the American College of Cardiology, American Heart Association, and nine other groups, which recommended a target of 130/80 mm Hg for pretty much everyone. Though they say greater than 140/90 mm Hg should be the threshold for low-risk patients or for starting therapy post stroke, we often forget those nuances. The main point of contention is that the AAFP guideline was looking for a mortality benefit, whereas the ACC/AHA/everyone else guideline was looking at preventing cardiovascular events. The latter guideline was driven mainly by the results of the SPRINT trial. ACC/AHA argue for more aggressive targets to prevent the things that cardiologists care about, namely heart attacks.

The AAFP guideline conceded that more aggressive control will result in fewer myocardial infarctions but warn that it comes with more adverse events. Treating 1,000 patients to this lower target would theoretically prevent four MIs, possibly prevent three strokes, but result in 30 adverse events.

In the end, what we are seeing here is not so much a debate over the evidence as a debate over priorities. The AAFP’s main focus is all-cause mortality; the ACC/AHA’s is cardiovascular events. Interventions that don’t improve mortality can be questioned in terms of their cost effectiveness. But you probably don’t want to have a heart attack (even a nonfatal one). And you certainly don’t want to have a stroke. However, lower blood pressure targets inevitably require more medications. Notwithstanding the economic costs, the dangers of polypharmacy, medication interactions, side effects, and syncope leading to falls cannot be ignored. Falls are not benign adverse events, especially in older adults.

The counter argument is that physicians are human and often let things slide. Set the target at 140/90 mm Hg, and many physicians won’t jump on a systolic blood pressure of 144 mm Hg. Set the target at 130 mm Hg, and maybe they’ll be more likely to react. There’s a fine line between permissiveness and complacency.

If you zoom out and look at the multitude of blood pressure guidelines, you start to notice an important fact. There is not much daylight between them. There are subtle differences in what constitutes high risk and different definitions of older (older should be defined as 10 years older than the reader’s current age). But otherwise, the blood pressure targets are not that different.

Does that final 10 mm Hg really matter when barriers to care mean that tens of millions in the United States are unaware they have hypertension? Even among those diagnosed, many are either untreated or inadequately treated.

With this context, perhaps the most insightful thing that can be said about the blood pressure guideline controversy is that it’s not all that controversial. We can likely all agree that we need to be better at treating hypertension and that creative solutions to reach underserved communities are necessary.

Arguing about 140/90 mm Hg or 130/80 mm Hg is less important than acknowledging that we should be aggressive in screening for and treating hypertension. We should acknowledge that beyond a certain point any cardiovascular benefit comes at the cost of hypotension and side effects. That tipping point will be different for different groups, and probably at a higher set point in older patients.

Individualizing care isn’t difficult. We do it all the time. We just shouldn’t be letting people walk around with untreated hypertension. It’s not the 1900s anymore.

Dr. Labos is a cardiologist at Hôpital Notre-Dame, Montreal. He reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

Diets containing higher amounts of certain food categories appear to be protective against cardiovascular (CV) disease and premature death, suggests a new study with a broad international scope. Most of the protective food categories are in line with standard dietary guidelines for good health, but one that may be heart-protective is not usually included in such recommendations.

fcafotodigital/Getty Images

The food categories that were found to be protective include fruit, vegetables, nuts, legumes, and fish but also dairy, “mainly whole-fat,” in an analysis based on the international Prospective Urban and Rural Epidemiological (PURE) study and data from five other international trials that encompassed more than 240,000 people.

A healthy diet scoring system was derived from dietary patterns and clinical events observed in the PURE study and was applied to the populations of the other trials. Higher scores, corresponding to greater consumption of the six food categories, tracked with significantly reduced risks for death, myocardial infarction (MI), and stroke.

Reductions in mortality and CV-disease risk that were linked to the higher scores were especially pronounced in lower-income countries in the study published onlinein the European Heart Journal with lead author Andrew Mente, PhD, Population Health Research Institute, McMaster University, Hamilton, Ont.

The study in part refutes the frequent preference for low-fat or no-fat dairy foods over whole-fat dairy in healthy-diet recommendations. But it is consistent with earlier findings from PURE of reduced mortality risk with increased consumption of dietary fat, including saturated fat.

Whereas healthy-diet recommendations tend to emphasize reduced intake of fat, especially saturated fat, the report notes that “there are almost no national or international strategies and policies to increase a number of protective foods,” such as nuts, fish, and dairy.

“Therefore, while the findings from PURE are largely consistent with the nutrition science and modern dietary recommendations to focus on protective foods, the public’s understanding of healthy eating and relevant global policies have not yet caught up to this science,” it states.

“Guidelines and policy actions need to be updated with this newer evidence,” Dr. Mente said in an interview. “For example, the World Health Organization remains mainly focused on reducing certain nutrients, such as fat, saturated fat, added sugar, and salt,” he said. “These recommendations are echoed by government policy actions and industry, as evident by the continued focus on the usual nutrients in food labels of many countries.”

The current findings, Dr. Mente said, “can be used to ensure that the public’s understanding of healthy eating and relevant global policies are able to catch up to the science.”
 

Healthy diet score

PURE investigators developed their healthy diet score using data from 147,642 people from the general population in 21 countries. The investigators compared self-reported dietary intakes with long-term clinical outcomes.

The scoring system assigned a value of 1 for each of the six health-food categories when individuals’ intake exceeded the entire cohort’s median intake. It assigned a 0 when intake was below the median. The total PURE healthy diet score consisted of the sum of the six values, with higher scores corresponding to a healthier diet. The mean score for cohort was 2.95.

There were 15,707 deaths and 40,764 CV events during a median follow-up of 9.3 years. A score of at least 5 points, compared with 0 or 1 point, was associated with significantly reduced hazard ratios for mortality, MI, and stroke in multivariable analysis:

• Mortality: HR, 0.70 (95% CI, 0.63-0.77; P < .0001).
• Major CV disease: HR, 0.82 (95% CI, 0.75-0.91; P < .0001).
• MI: HR, 0.86 (95% CI, 0.75-0.99; P = .0014).
• Stroke: HR, 0.81 (95% CI, 0.71-0.93; P = .0034).

The healthy diet score’s relationship to clinical outcomes was explored in five other large independent studies, including three prospective trials of patients with CV disease that spanned 50 countries, a case-control study with MI patients in 52 countries, and a case-control study with stroke patients in 33 countries.

In the three prospective trials, higher scores were associated with reduced mortality, CV disease events, and MI:

• Mortality: HR, 0.73 (95% CI, 0.66-0.81).
• Major CV disease: HR, 0.79 (95% CI, 0.72-0.87).
• MI: HR, 0.85 (95% CI, 0.71-0.99).

In the two case-control studies, a higher diet score was associated with reduced odds ratios for first MI and for stroke:

• MI: OR, 0.72 (95% CI, 0.65-0.80).
• Stroke: OR, 0.57 (95% CI, 0.50-0.65).

In an analysis based on the PURE cohort, incorporation of unprocessed red meat or whole grains into the health diet score produced similar results, suggesting that a “modest amount” of meat or whole grains can be part of a healthy diet, the authors contend.

The results were similar in a combined analysis of all the prospective studies. In particular, improvement in diet score by one quintile was associated with significantly reduced risks for the following:

• Mortality: HR, 0.92 (95% CI, 0.90-0.93).
• Major CV disease: HR, 0.94 (95% CI, 0.93-0.95).
• MI: HR, 0.94 (95% CI, 0.92-0.96).
• Stroke: HR, 0.94 (95% CI, 0.89-0.99).
• Death or CV disease: HR, 0.93 (95% CI, 0.92-0.94).

“This strongly indicates that the take-home message for patients is the same as for general populations,” Dr. Mente said. “Eat plenty of fruits, vegetables, nuts, legumes, and a moderate amount of fish and whole-fat dairy to lower risk of CV disease and mortality.”

Dairy foods are not widely consumed in some cultures, he said, “but availability and cost are also factors in determining consumption.” Nonetheless, a high-quality diet can be achieved without including or excluding dairy foods. Context-specific policies and priorities are needed for different populations, “rather than a one-size-fits-all global policy.”

Food labels in many countries mainly focus on “reducing certain nutrients as the end-all, be-all,” Dr. Mente observed. “Our findings can be used as a basis for recommendations regarding what a healthy diet should be globally and then modified for each region based on the specific types of foods that are available and affordable in each region.”

Moreover, he said, “targeted food policies are needed to increase the availability and affordability of healthy foods, especially in lower-income countries where intakes are low.”
 

Common human biology

The current results from PURE “confirm prior observations from mostly Western nations that low intakes of fruits, vegetables, nuts, legumes, and fish are major risk factors for poor health,” observes Dariush Mozaffarian, MD, DrPH, MPH, Tufts University, Boston, in an accompanying editorial. “This suggests that common human biology, not merely confounding, explains these observed diet–disease relationships, strengthening causal inference on the power of nutrition.”

Moreover, “These findings provide further support that dairy foods, including whole-fat dairy, can be part of a healthy diet,” Dr. Mozaffarian writes. “The new results in PURE, in combination with prior reports, call for a re-evaluation of unrelenting guidelines to avoid whole-fat dairy products.”

Such studies “remind us of the continuing and devastating rise in diet-related chronic diseases globally, and of the power of protective foods to help address these burdens,” the editorial continues. “It is time for national nutrition guidelines, private sector innovations, government tax policy and agricultural incentives, food procurement policies, labeling and other regulatory priorities, and food-based health care interventions to catch up to the science.”
 

Not automatically superior

“I do not believe guidelines should be changed based on this single study,” contends Howard D. Sesso, ScD, MPH, associate director of the division of preventive medicine at Brigham and Women’s Hospital, Boston, who isn’t part of PURE. “But I welcome the scientific dialog that should come out of any study that challenges what we think we know,” he told this news organization.

“Many other dietary patterns have been identified over the years that also do a great job in predicting disease risk in observational studies,” observed Dr. Sesso. “Is PURE that much better? Maybe, maybe not. But not enough to dismiss other dietary patterns that are already the basis of dietary recommendations in the U.S., Europe, and worldwide.”

The PURE healthy diet score, he said, “appears to work well within the confines of their large pooling of studies around the world, but that doesn’t automatically make it superior to other dietary patterns.” The score “was only modestly, but not greatly, better than existing dietary patterns evaluated.”

Randomized controlled trials are needed, Dr. Sesso said, to “delve into more specific dietary components,” including unprocessed red meat, whole grains, and high-fat dairy foods. And, he said, more observational studies are needed to examine the score’s association with other cardiometabolic outcomes.

The PURE study is funded by the Population Health Research Institute, the Hamilton Health Sciences Research Institute, the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Ontario; with support from Canadian Institutes of Health Research’s Strategy for Patient Oriented Research through the Ontario SPOR Support Unit, as well as the Ontario Ministry of Health and Long-Term Care; and through unrestricted grants from several pharmaceutical companies, with major contributions from AstraZeneca, Sanofi-Aventis, Boehringer Ingelheim, Servier, and GlaxoSmithKline. Additional contributions are from Novartis and King Pharma. Dr. Mente, Dr. Mozaffarian, and Dr. Sesso have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Diets containing higher amounts of certain food categories appear to be protective against cardiovascular (CV) disease and premature death, suggests a new study with a broad international scope. Most of the protective food categories are in line with standard dietary guidelines for good health, but one that may be heart-protective is not usually included in such recommendations.

fcafotodigital/Getty Images

The food categories that were found to be protective include fruit, vegetables, nuts, legumes, and fish but also dairy, “mainly whole-fat,” in an analysis based on the international Prospective Urban and Rural Epidemiological (PURE) study and data from five other international trials that encompassed more than 240,000 people.

A healthy diet scoring system was derived from dietary patterns and clinical events observed in the PURE study and was applied to the populations of the other trials. Higher scores, corresponding to greater consumption of the six food categories, tracked with significantly reduced risks for death, myocardial infarction (MI), and stroke.

Reductions in mortality and CV-disease risk that were linked to the higher scores were especially pronounced in lower-income countries in the study published onlinein the European Heart Journal with lead author Andrew Mente, PhD, Population Health Research Institute, McMaster University, Hamilton, Ont.

The study in part refutes the frequent preference for low-fat or no-fat dairy foods over whole-fat dairy in healthy-diet recommendations. But it is consistent with earlier findings from PURE of reduced mortality risk with increased consumption of dietary fat, including saturated fat.

Whereas healthy-diet recommendations tend to emphasize reduced intake of fat, especially saturated fat, the report notes that “there are almost no national or international strategies and policies to increase a number of protective foods,” such as nuts, fish, and dairy.

“Therefore, while the findings from PURE are largely consistent with the nutrition science and modern dietary recommendations to focus on protective foods, the public’s understanding of healthy eating and relevant global policies have not yet caught up to this science,” it states.

“Guidelines and policy actions need to be updated with this newer evidence,” Dr. Mente said in an interview. “For example, the World Health Organization remains mainly focused on reducing certain nutrients, such as fat, saturated fat, added sugar, and salt,” he said. “These recommendations are echoed by government policy actions and industry, as evident by the continued focus on the usual nutrients in food labels of many countries.”

The current findings, Dr. Mente said, “can be used to ensure that the public’s understanding of healthy eating and relevant global policies are able to catch up to the science.”
 

Healthy diet score

PURE investigators developed their healthy diet score using data from 147,642 people from the general population in 21 countries. The investigators compared self-reported dietary intakes with long-term clinical outcomes.

The scoring system assigned a value of 1 for each of the six health-food categories when individuals’ intake exceeded the entire cohort’s median intake. It assigned a 0 when intake was below the median. The total PURE healthy diet score consisted of the sum of the six values, with higher scores corresponding to a healthier diet. The mean score for cohort was 2.95.

There were 15,707 deaths and 40,764 CV events during a median follow-up of 9.3 years. A score of at least 5 points, compared with 0 or 1 point, was associated with significantly reduced hazard ratios for mortality, MI, and stroke in multivariable analysis:

• Mortality: HR, 0.70 (95% CI, 0.63-0.77; P < .0001).
• Major CV disease: HR, 0.82 (95% CI, 0.75-0.91; P < .0001).
• MI: HR, 0.86 (95% CI, 0.75-0.99; P = .0014).
• Stroke: HR, 0.81 (95% CI, 0.71-0.93; P = .0034).

The healthy diet score’s relationship to clinical outcomes was explored in five other large independent studies, including three prospective trials of patients with CV disease that spanned 50 countries, a case-control study with MI patients in 52 countries, and a case-control study with stroke patients in 33 countries.

In the three prospective trials, higher scores were associated with reduced mortality, CV disease events, and MI:

• Mortality: HR, 0.73 (95% CI, 0.66-0.81).
• Major CV disease: HR, 0.79 (95% CI, 0.72-0.87).
• MI: HR, 0.85 (95% CI, 0.71-0.99).

In the two case-control studies, a higher diet score was associated with reduced odds ratios for first MI and for stroke:

• MI: OR, 0.72 (95% CI, 0.65-0.80).
• Stroke: OR, 0.57 (95% CI, 0.50-0.65).

In an analysis based on the PURE cohort, incorporation of unprocessed red meat or whole grains into the health diet score produced similar results, suggesting that a “modest amount” of meat or whole grains can be part of a healthy diet, the authors contend.

The results were similar in a combined analysis of all the prospective studies. In particular, improvement in diet score by one quintile was associated with significantly reduced risks for the following:

• Mortality: HR, 0.92 (95% CI, 0.90-0.93).
• Major CV disease: HR, 0.94 (95% CI, 0.93-0.95).
• MI: HR, 0.94 (95% CI, 0.92-0.96).
• Stroke: HR, 0.94 (95% CI, 0.89-0.99).
• Death or CV disease: HR, 0.93 (95% CI, 0.92-0.94).

“This strongly indicates that the take-home message for patients is the same as for general populations,” Dr. Mente said. “Eat plenty of fruits, vegetables, nuts, legumes, and a moderate amount of fish and whole-fat dairy to lower risk of CV disease and mortality.”

Dairy foods are not widely consumed in some cultures, he said, “but availability and cost are also factors in determining consumption.” Nonetheless, a high-quality diet can be achieved without including or excluding dairy foods. Context-specific policies and priorities are needed for different populations, “rather than a one-size-fits-all global policy.”

Food labels in many countries mainly focus on “reducing certain nutrients as the end-all, be-all,” Dr. Mente observed. “Our findings can be used as a basis for recommendations regarding what a healthy diet should be globally and then modified for each region based on the specific types of foods that are available and affordable in each region.”

Moreover, he said, “targeted food policies are needed to increase the availability and affordability of healthy foods, especially in lower-income countries where intakes are low.”
 

Common human biology

The current results from PURE “confirm prior observations from mostly Western nations that low intakes of fruits, vegetables, nuts, legumes, and fish are major risk factors for poor health,” observes Dariush Mozaffarian, MD, DrPH, MPH, Tufts University, Boston, in an accompanying editorial. “This suggests that common human biology, not merely confounding, explains these observed diet–disease relationships, strengthening causal inference on the power of nutrition.”

Moreover, “These findings provide further support that dairy foods, including whole-fat dairy, can be part of a healthy diet,” Dr. Mozaffarian writes. “The new results in PURE, in combination with prior reports, call for a re-evaluation of unrelenting guidelines to avoid whole-fat dairy products.”

Such studies “remind us of the continuing and devastating rise in diet-related chronic diseases globally, and of the power of protective foods to help address these burdens,” the editorial continues. “It is time for national nutrition guidelines, private sector innovations, government tax policy and agricultural incentives, food procurement policies, labeling and other regulatory priorities, and food-based health care interventions to catch up to the science.”
 

Not automatically superior

“I do not believe guidelines should be changed based on this single study,” contends Howard D. Sesso, ScD, MPH, associate director of the division of preventive medicine at Brigham and Women’s Hospital, Boston, who isn’t part of PURE. “But I welcome the scientific dialog that should come out of any study that challenges what we think we know,” he told this news organization.

“Many other dietary patterns have been identified over the years that also do a great job in predicting disease risk in observational studies,” observed Dr. Sesso. “Is PURE that much better? Maybe, maybe not. But not enough to dismiss other dietary patterns that are already the basis of dietary recommendations in the U.S., Europe, and worldwide.”

The PURE healthy diet score, he said, “appears to work well within the confines of their large pooling of studies around the world, but that doesn’t automatically make it superior to other dietary patterns.” The score “was only modestly, but not greatly, better than existing dietary patterns evaluated.”

Randomized controlled trials are needed, Dr. Sesso said, to “delve into more specific dietary components,” including unprocessed red meat, whole grains, and high-fat dairy foods. And, he said, more observational studies are needed to examine the score’s association with other cardiometabolic outcomes.

The PURE study is funded by the Population Health Research Institute, the Hamilton Health Sciences Research Institute, the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Ontario; with support from Canadian Institutes of Health Research’s Strategy for Patient Oriented Research through the Ontario SPOR Support Unit, as well as the Ontario Ministry of Health and Long-Term Care; and through unrestricted grants from several pharmaceutical companies, with major contributions from AstraZeneca, Sanofi-Aventis, Boehringer Ingelheim, Servier, and GlaxoSmithKline. Additional contributions are from Novartis and King Pharma. Dr. Mente, Dr. Mozaffarian, and Dr. Sesso have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Diets containing higher amounts of certain food categories appear to be protective against cardiovascular (CV) disease and premature death, suggests a new study with a broad international scope. Most of the protective food categories are in line with standard dietary guidelines for good health, but one that may be heart-protective is not usually included in such recommendations.

fcafotodigital/Getty Images

The food categories that were found to be protective include fruit, vegetables, nuts, legumes, and fish but also dairy, “mainly whole-fat,” in an analysis based on the international Prospective Urban and Rural Epidemiological (PURE) study and data from five other international trials that encompassed more than 240,000 people.

A healthy diet scoring system was derived from dietary patterns and clinical events observed in the PURE study and was applied to the populations of the other trials. Higher scores, corresponding to greater consumption of the six food categories, tracked with significantly reduced risks for death, myocardial infarction (MI), and stroke.

Reductions in mortality and CV-disease risk that were linked to the higher scores were especially pronounced in lower-income countries in the study published onlinein the European Heart Journal with lead author Andrew Mente, PhD, Population Health Research Institute, McMaster University, Hamilton, Ont.

The study in part refutes the frequent preference for low-fat or no-fat dairy foods over whole-fat dairy in healthy-diet recommendations. But it is consistent with earlier findings from PURE of reduced mortality risk with increased consumption of dietary fat, including saturated fat.

Whereas healthy-diet recommendations tend to emphasize reduced intake of fat, especially saturated fat, the report notes that “there are almost no national or international strategies and policies to increase a number of protective foods,” such as nuts, fish, and dairy.

“Therefore, while the findings from PURE are largely consistent with the nutrition science and modern dietary recommendations to focus on protective foods, the public’s understanding of healthy eating and relevant global policies have not yet caught up to this science,” it states.

“Guidelines and policy actions need to be updated with this newer evidence,” Dr. Mente said in an interview. “For example, the World Health Organization remains mainly focused on reducing certain nutrients, such as fat, saturated fat, added sugar, and salt,” he said. “These recommendations are echoed by government policy actions and industry, as evident by the continued focus on the usual nutrients in food labels of many countries.”

The current findings, Dr. Mente said, “can be used to ensure that the public’s understanding of healthy eating and relevant global policies are able to catch up to the science.”
 

Healthy diet score

PURE investigators developed their healthy diet score using data from 147,642 people from the general population in 21 countries. The investigators compared self-reported dietary intakes with long-term clinical outcomes.

The scoring system assigned a value of 1 for each of the six health-food categories when individuals’ intake exceeded the entire cohort’s median intake. It assigned a 0 when intake was below the median. The total PURE healthy diet score consisted of the sum of the six values, with higher scores corresponding to a healthier diet. The mean score for cohort was 2.95.

There were 15,707 deaths and 40,764 CV events during a median follow-up of 9.3 years. A score of at least 5 points, compared with 0 or 1 point, was associated with significantly reduced hazard ratios for mortality, MI, and stroke in multivariable analysis:

• Mortality: HR, 0.70 (95% CI, 0.63-0.77; P < .0001).
• Major CV disease: HR, 0.82 (95% CI, 0.75-0.91; P < .0001).
• MI: HR, 0.86 (95% CI, 0.75-0.99; P = .0014).
• Stroke: HR, 0.81 (95% CI, 0.71-0.93; P = .0034).

The healthy diet score’s relationship to clinical outcomes was explored in five other large independent studies, including three prospective trials of patients with CV disease that spanned 50 countries, a case-control study with MI patients in 52 countries, and a case-control study with stroke patients in 33 countries.

In the three prospective trials, higher scores were associated with reduced mortality, CV disease events, and MI:

• Mortality: HR, 0.73 (95% CI, 0.66-0.81).
• Major CV disease: HR, 0.79 (95% CI, 0.72-0.87).
• MI: HR, 0.85 (95% CI, 0.71-0.99).

In the two case-control studies, a higher diet score was associated with reduced odds ratios for first MI and for stroke:

• MI: OR, 0.72 (95% CI, 0.65-0.80).
• Stroke: OR, 0.57 (95% CI, 0.50-0.65).

In an analysis based on the PURE cohort, incorporation of unprocessed red meat or whole grains into the health diet score produced similar results, suggesting that a “modest amount” of meat or whole grains can be part of a healthy diet, the authors contend.

The results were similar in a combined analysis of all the prospective studies. In particular, improvement in diet score by one quintile was associated with significantly reduced risks for the following:

• Mortality: HR, 0.92 (95% CI, 0.90-0.93).
• Major CV disease: HR, 0.94 (95% CI, 0.93-0.95).
• MI: HR, 0.94 (95% CI, 0.92-0.96).
• Stroke: HR, 0.94 (95% CI, 0.89-0.99).
• Death or CV disease: HR, 0.93 (95% CI, 0.92-0.94).

“This strongly indicates that the take-home message for patients is the same as for general populations,” Dr. Mente said. “Eat plenty of fruits, vegetables, nuts, legumes, and a moderate amount of fish and whole-fat dairy to lower risk of CV disease and mortality.”

Dairy foods are not widely consumed in some cultures, he said, “but availability and cost are also factors in determining consumption.” Nonetheless, a high-quality diet can be achieved without including or excluding dairy foods. Context-specific policies and priorities are needed for different populations, “rather than a one-size-fits-all global policy.”

Food labels in many countries mainly focus on “reducing certain nutrients as the end-all, be-all,” Dr. Mente observed. “Our findings can be used as a basis for recommendations regarding what a healthy diet should be globally and then modified for each region based on the specific types of foods that are available and affordable in each region.”

Moreover, he said, “targeted food policies are needed to increase the availability and affordability of healthy foods, especially in lower-income countries where intakes are low.”
 

Common human biology

The current results from PURE “confirm prior observations from mostly Western nations that low intakes of fruits, vegetables, nuts, legumes, and fish are major risk factors for poor health,” observes Dariush Mozaffarian, MD, DrPH, MPH, Tufts University, Boston, in an accompanying editorial. “This suggests that common human biology, not merely confounding, explains these observed diet–disease relationships, strengthening causal inference on the power of nutrition.”

Moreover, “These findings provide further support that dairy foods, including whole-fat dairy, can be part of a healthy diet,” Dr. Mozaffarian writes. “The new results in PURE, in combination with prior reports, call for a re-evaluation of unrelenting guidelines to avoid whole-fat dairy products.”

Such studies “remind us of the continuing and devastating rise in diet-related chronic diseases globally, and of the power of protective foods to help address these burdens,” the editorial continues. “It is time for national nutrition guidelines, private sector innovations, government tax policy and agricultural incentives, food procurement policies, labeling and other regulatory priorities, and food-based health care interventions to catch up to the science.”
 

Not automatically superior

“I do not believe guidelines should be changed based on this single study,” contends Howard D. Sesso, ScD, MPH, associate director of the division of preventive medicine at Brigham and Women’s Hospital, Boston, who isn’t part of PURE. “But I welcome the scientific dialog that should come out of any study that challenges what we think we know,” he told this news organization.

“Many other dietary patterns have been identified over the years that also do a great job in predicting disease risk in observational studies,” observed Dr. Sesso. “Is PURE that much better? Maybe, maybe not. But not enough to dismiss other dietary patterns that are already the basis of dietary recommendations in the U.S., Europe, and worldwide.”

The PURE healthy diet score, he said, “appears to work well within the confines of their large pooling of studies around the world, but that doesn’t automatically make it superior to other dietary patterns.” The score “was only modestly, but not greatly, better than existing dietary patterns evaluated.”

Randomized controlled trials are needed, Dr. Sesso said, to “delve into more specific dietary components,” including unprocessed red meat, whole grains, and high-fat dairy foods. And, he said, more observational studies are needed to examine the score’s association with other cardiometabolic outcomes.

The PURE study is funded by the Population Health Research Institute, the Hamilton Health Sciences Research Institute, the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Ontario; with support from Canadian Institutes of Health Research’s Strategy for Patient Oriented Research through the Ontario SPOR Support Unit, as well as the Ontario Ministry of Health and Long-Term Care; and through unrestricted grants from several pharmaceutical companies, with major contributions from AstraZeneca, Sanofi-Aventis, Boehringer Ingelheim, Servier, and GlaxoSmithKline. Additional contributions are from Novartis and King Pharma. Dr. Mente, Dr. Mozaffarian, and Dr. Sesso have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved a labeling update for the injectable LDL cholesterol–lowering agent inclisiran (Leqvio) that expands its indications to include primary prevention for patients with elevated LDL cholesterol, Novartis has announced.

The first-in-class small interfering RNA (siRNA) agent was approved in 2021 as an adjunct to statins for patients with clinical cardiovascular disease or heterozygous familial hypercholesterolemia. The indications now include patients taking statins for primary dyslipidemia who have high-risk comorbidities such as diabetes but who do not have a history of cardiovascular events, the company said.

Inclisiran, with a mechanism of action unique among drugs for dyslipidemia, works by “silencing” RNA involved in the synthesis of proprotein convertase subtilisin/kexin type 9. The protein helps regulate the number of LDL cholesterol cell-surface receptors.

Novartis said it has “global rights to develop, manufacture and commercialize Leqvio under a license and collaboration agreement with Alnylam Pharmaceuticals.”

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved a labeling update for the injectable LDL cholesterol–lowering agent inclisiran (Leqvio) that expands its indications to include primary prevention for patients with elevated LDL cholesterol, Novartis has announced.

The first-in-class small interfering RNA (siRNA) agent was approved in 2021 as an adjunct to statins for patients with clinical cardiovascular disease or heterozygous familial hypercholesterolemia. The indications now include patients taking statins for primary dyslipidemia who have high-risk comorbidities such as diabetes but who do not have a history of cardiovascular events, the company said.

Inclisiran, with a mechanism of action unique among drugs for dyslipidemia, works by “silencing” RNA involved in the synthesis of proprotein convertase subtilisin/kexin type 9. The protein helps regulate the number of LDL cholesterol cell-surface receptors.

Novartis said it has “global rights to develop, manufacture and commercialize Leqvio under a license and collaboration agreement with Alnylam Pharmaceuticals.”

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved a labeling update for the injectable LDL cholesterol–lowering agent inclisiran (Leqvio) that expands its indications to include primary prevention for patients with elevated LDL cholesterol, Novartis has announced.

The first-in-class small interfering RNA (siRNA) agent was approved in 2021 as an adjunct to statins for patients with clinical cardiovascular disease or heterozygous familial hypercholesterolemia. The indications now include patients taking statins for primary dyslipidemia who have high-risk comorbidities such as diabetes but who do not have a history of cardiovascular events, the company said.

Inclisiran, with a mechanism of action unique among drugs for dyslipidemia, works by “silencing” RNA involved in the synthesis of proprotein convertase subtilisin/kexin type 9. The protein helps regulate the number of LDL cholesterol cell-surface receptors.

Novartis said it has “global rights to develop, manufacture and commercialize Leqvio under a license and collaboration agreement with Alnylam Pharmaceuticals.”

A version of this article first appeared on Medscape.com.