In utero efavirenz, dolutegravir exposure linked to childhood neurologic problems

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SAN FRANCISCOChildren exposed to efavirenz in utero were 60% more likely than were those exposed to other antiretrovirals to later develop seizures, eye problems, and other neurologic abnormalities, according to a review of 3,747 children in the Surveillance Monitoring for ART Toxicities (SMARTT) study, an ongoing effort to monitor children exposed to antiretrovirals in the womb.

Overall, 237 children developed a neurologic complication at a mean age of 2; 16 of them were exposed to efavirenz. The study team estimated that 9.6% of children exposed to efavirenz had a neurological complication, versus 6.2% born to women on ART regimens without efavirenz. There was also a nonsignificant trend toward dolutegravir exposure and later neurological abnormalities, which occurred in four of 94 children exposed to the drug. Results were adjusted for maternal smoking and other risk factors.

No other safety signals were detected with the 19 other antiretrovirals analyzed in the study, lead investigator Claudia S. Crowell, MD, assistant professor of pediatrics at the University of Washington, Seattle, said at the annual scientific meeting on infectious diseases.

Efavirenz isn’t used much in the United States because there are more effective options with fewer side effects, but current guidelines recommend that women who are doing well on the drug stay on it while pregnant. Meanwhile, dolutegravir exposure at the time of conception was recently linked to an increased risk of neural tube defects in infants. The drug is commonly used in the United States, and guidelines have been strengthened to highlight the need for contraception use by women taking dolutegravir.

Dr. Crowell said she was surprised by her study’s findings, in part because efavirenz is not a teratogen. The work highlights how important it is to look beyond birth defects and follow children exposed to antiretrovirals for later problems. “We still haven’t determined what the safest regimen is for use in pregnancy,” she said.

[email protected]

SOURCE: Crowell C et al. ID Week 2018 abstract LB5.

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SAN FRANCISCOChildren exposed to efavirenz in utero were 60% more likely than were those exposed to other antiretrovirals to later develop seizures, eye problems, and other neurologic abnormalities, according to a review of 3,747 children in the Surveillance Monitoring for ART Toxicities (SMARTT) study, an ongoing effort to monitor children exposed to antiretrovirals in the womb.

Overall, 237 children developed a neurologic complication at a mean age of 2; 16 of them were exposed to efavirenz. The study team estimated that 9.6% of children exposed to efavirenz had a neurological complication, versus 6.2% born to women on ART regimens without efavirenz. There was also a nonsignificant trend toward dolutegravir exposure and later neurological abnormalities, which occurred in four of 94 children exposed to the drug. Results were adjusted for maternal smoking and other risk factors.

No other safety signals were detected with the 19 other antiretrovirals analyzed in the study, lead investigator Claudia S. Crowell, MD, assistant professor of pediatrics at the University of Washington, Seattle, said at the annual scientific meeting on infectious diseases.

Efavirenz isn’t used much in the United States because there are more effective options with fewer side effects, but current guidelines recommend that women who are doing well on the drug stay on it while pregnant. Meanwhile, dolutegravir exposure at the time of conception was recently linked to an increased risk of neural tube defects in infants. The drug is commonly used in the United States, and guidelines have been strengthened to highlight the need for contraception use by women taking dolutegravir.

Dr. Crowell said she was surprised by her study’s findings, in part because efavirenz is not a teratogen. The work highlights how important it is to look beyond birth defects and follow children exposed to antiretrovirals for later problems. “We still haven’t determined what the safest regimen is for use in pregnancy,” she said.

[email protected]

SOURCE: Crowell C et al. ID Week 2018 abstract LB5.

SAN FRANCISCOChildren exposed to efavirenz in utero were 60% more likely than were those exposed to other antiretrovirals to later develop seizures, eye problems, and other neurologic abnormalities, according to a review of 3,747 children in the Surveillance Monitoring for ART Toxicities (SMARTT) study, an ongoing effort to monitor children exposed to antiretrovirals in the womb.

Overall, 237 children developed a neurologic complication at a mean age of 2; 16 of them were exposed to efavirenz. The study team estimated that 9.6% of children exposed to efavirenz had a neurological complication, versus 6.2% born to women on ART regimens without efavirenz. There was also a nonsignificant trend toward dolutegravir exposure and later neurological abnormalities, which occurred in four of 94 children exposed to the drug. Results were adjusted for maternal smoking and other risk factors.

No other safety signals were detected with the 19 other antiretrovirals analyzed in the study, lead investigator Claudia S. Crowell, MD, assistant professor of pediatrics at the University of Washington, Seattle, said at the annual scientific meeting on infectious diseases.

Efavirenz isn’t used much in the United States because there are more effective options with fewer side effects, but current guidelines recommend that women who are doing well on the drug stay on it while pregnant. Meanwhile, dolutegravir exposure at the time of conception was recently linked to an increased risk of neural tube defects in infants. The drug is commonly used in the United States, and guidelines have been strengthened to highlight the need for contraception use by women taking dolutegravir.

Dr. Crowell said she was surprised by her study’s findings, in part because efavirenz is not a teratogen. The work highlights how important it is to look beyond birth defects and follow children exposed to antiretrovirals for later problems. “We still haven’t determined what the safest regimen is for use in pregnancy,” she said.

[email protected]

SOURCE: Crowell C et al. ID Week 2018 abstract LB5.

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It’s time for universal CMV screening at birth

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SAN FRANCISCOThere’s an increasing push in the United States to screen all newborns for congenital cytomegalovirus.

The reason is because most of the time the diagnosis of congenital cytomegalovirus is missed. Only about 10% of infants infected with the virus present with enlarged livers and other classic signs. Too often, the infection isn’t caught until later, when hearing loss and other neurologic sequelae reveal themselves, according to Fatima Kakkar, MD, a pediatric infectious disease specialist and researcher at the University of Montreal.

There are effective treatments – intravenous ganciclovir for 6 weeks or oral valganciclovir (Valcyte) for 6 months – that control the infection and reverse its effects.

People have tried to address the situation by screening children with hearing loss, in utero HIV exposure, or cytomegalovirus symptoms, but in a study Dr. Kakkar presented at IDWeek, an annual scientific meeting on infectious diseases, such targeted efforts still missed a lot of children.

[email protected]

SOURCE: Kakkar F et al. IDWeek 2018, Abstract 115.

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SAN FRANCISCOThere’s an increasing push in the United States to screen all newborns for congenital cytomegalovirus.

The reason is because most of the time the diagnosis of congenital cytomegalovirus is missed. Only about 10% of infants infected with the virus present with enlarged livers and other classic signs. Too often, the infection isn’t caught until later, when hearing loss and other neurologic sequelae reveal themselves, according to Fatima Kakkar, MD, a pediatric infectious disease specialist and researcher at the University of Montreal.

There are effective treatments – intravenous ganciclovir for 6 weeks or oral valganciclovir (Valcyte) for 6 months – that control the infection and reverse its effects.

People have tried to address the situation by screening children with hearing loss, in utero HIV exposure, or cytomegalovirus symptoms, but in a study Dr. Kakkar presented at IDWeek, an annual scientific meeting on infectious diseases, such targeted efforts still missed a lot of children.

[email protected]

SOURCE: Kakkar F et al. IDWeek 2018, Abstract 115.

SAN FRANCISCOThere’s an increasing push in the United States to screen all newborns for congenital cytomegalovirus.

The reason is because most of the time the diagnosis of congenital cytomegalovirus is missed. Only about 10% of infants infected with the virus present with enlarged livers and other classic signs. Too often, the infection isn’t caught until later, when hearing loss and other neurologic sequelae reveal themselves, according to Fatima Kakkar, MD, a pediatric infectious disease specialist and researcher at the University of Montreal.

There are effective treatments – intravenous ganciclovir for 6 weeks or oral valganciclovir (Valcyte) for 6 months – that control the infection and reverse its effects.

People have tried to address the situation by screening children with hearing loss, in utero HIV exposure, or cytomegalovirus symptoms, but in a study Dr. Kakkar presented at IDWeek, an annual scientific meeting on infectious diseases, such targeted efforts still missed a lot of children.

[email protected]

SOURCE: Kakkar F et al. IDWeek 2018, Abstract 115.

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Encourage influenza vaccination in pregnant women

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– Influenza season is upon us, and Helen Chu, MD, MPH, is here at ID Week 2018 to talk vaccines, especially for pregnant women.

They are at greater risk for more severe illness, and influenza can lead to adverse outcomes in infants. The good news is that recent studies have shown that flu vaccines are safe and effective in pregnant women.

The bad news is that many women are hesitant to be vaccinated out of concerns over safety, in a trend that reflects broader societal worries over vaccination, said Dr. Chu, of the University of Washington, Seattle. In a video interview at an annual scientific meeting on infectious diseases, Dr. Chu advised steps to ensure that pregnant women are aware of the safety and efficacy of flu vaccines, and the benefits to the infant who acquires immunity through the mother. It’s also a good idea to have vaccine on hand to be able to offer it immediately during an office visit.

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– Influenza season is upon us, and Helen Chu, MD, MPH, is here at ID Week 2018 to talk vaccines, especially for pregnant women.

They are at greater risk for more severe illness, and influenza can lead to adverse outcomes in infants. The good news is that recent studies have shown that flu vaccines are safe and effective in pregnant women.

The bad news is that many women are hesitant to be vaccinated out of concerns over safety, in a trend that reflects broader societal worries over vaccination, said Dr. Chu, of the University of Washington, Seattle. In a video interview at an annual scientific meeting on infectious diseases, Dr. Chu advised steps to ensure that pregnant women are aware of the safety and efficacy of flu vaccines, and the benefits to the infant who acquires immunity through the mother. It’s also a good idea to have vaccine on hand to be able to offer it immediately during an office visit.

– Influenza season is upon us, and Helen Chu, MD, MPH, is here at ID Week 2018 to talk vaccines, especially for pregnant women.

They are at greater risk for more severe illness, and influenza can lead to adverse outcomes in infants. The good news is that recent studies have shown that flu vaccines are safe and effective in pregnant women.

The bad news is that many women are hesitant to be vaccinated out of concerns over safety, in a trend that reflects broader societal worries over vaccination, said Dr. Chu, of the University of Washington, Seattle. In a video interview at an annual scientific meeting on infectious diseases, Dr. Chu advised steps to ensure that pregnant women are aware of the safety and efficacy of flu vaccines, and the benefits to the infant who acquires immunity through the mother. It’s also a good idea to have vaccine on hand to be able to offer it immediately during an office visit.

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October 2018 Highlights

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Ultrasound can’t rule out pulmonary embolism in the ED

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SAN DIEGO – In the ICU, ultrasound has been shown to reduce the need for CT to evaluate potential pulmonary embolism. But in the ED, this strategy hasn’t worked out so far, according to Joseph Brown, MD, of the department of emergency medicine at the University of California, San Francisco.

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Based on the data so far, the ED patients were less likely than the ICU patients to have another etiology identified on ultrasound that explained their symptoms. Further, ultrasound alone missed small subsegmental pulmonary emboli that were detected on subsequent CT scans in 2 of 11 patients.

The study is continuing, and Dr. Brown explains in this interview how ultrasound might be combined with other risk stratification measures to safely achieve reductions in CT scans.

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SAN DIEGO – In the ICU, ultrasound has been shown to reduce the need for CT to evaluate potential pulmonary embolism. But in the ED, this strategy hasn’t worked out so far, according to Joseph Brown, MD, of the department of emergency medicine at the University of California, San Francisco.

Vidyard Video


Based on the data so far, the ED patients were less likely than the ICU patients to have another etiology identified on ultrasound that explained their symptoms. Further, ultrasound alone missed small subsegmental pulmonary emboli that were detected on subsequent CT scans in 2 of 11 patients.

The study is continuing, and Dr. Brown explains in this interview how ultrasound might be combined with other risk stratification measures to safely achieve reductions in CT scans.

SAN DIEGO – In the ICU, ultrasound has been shown to reduce the need for CT to evaluate potential pulmonary embolism. But in the ED, this strategy hasn’t worked out so far, according to Joseph Brown, MD, of the department of emergency medicine at the University of California, San Francisco.

Vidyard Video


Based on the data so far, the ED patients were less likely than the ICU patients to have another etiology identified on ultrasound that explained their symptoms. Further, ultrasound alone missed small subsegmental pulmonary emboli that were detected on subsequent CT scans in 2 of 11 patients.

The study is continuing, and Dr. Brown explains in this interview how ultrasound might be combined with other risk stratification measures to safely achieve reductions in CT scans.

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Syncope alone after age 60 does not require admission

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SAN DIEGO – Unless the cause of syncope has been identified after a thorough workup in the emergency department, there is no advantage to admitting patients aged 60 years and older who complain of syncope, an ED-based study has found.

Almost 2,500 patients aged 60 or older with unexplained syncope after a thorough workup had similar 30-day outcomes whether they were admitted to the hospital or sent home from the ED, based on the results of a retrospective study presented at the annual meeting of the American College of Emergency Physicians.

Dr. Marc A. Probst of the Icahn School of Medicine at Mount Sinai, New York, who presented the data, reported that many centers admit older patients with syncope, although the benefit of this practice has not been well established.

In a video interview, Dr. Probst points out how the findings may be useful in guiding clinical decisions or counseling patients when admission is being considered.

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SAN DIEGO – Unless the cause of syncope has been identified after a thorough workup in the emergency department, there is no advantage to admitting patients aged 60 years and older who complain of syncope, an ED-based study has found.

Almost 2,500 patients aged 60 or older with unexplained syncope after a thorough workup had similar 30-day outcomes whether they were admitted to the hospital or sent home from the ED, based on the results of a retrospective study presented at the annual meeting of the American College of Emergency Physicians.

Dr. Marc A. Probst of the Icahn School of Medicine at Mount Sinai, New York, who presented the data, reported that many centers admit older patients with syncope, although the benefit of this practice has not been well established.

In a video interview, Dr. Probst points out how the findings may be useful in guiding clinical decisions or counseling patients when admission is being considered.

SAN DIEGO – Unless the cause of syncope has been identified after a thorough workup in the emergency department, there is no advantage to admitting patients aged 60 years and older who complain of syncope, an ED-based study has found.

Almost 2,500 patients aged 60 or older with unexplained syncope after a thorough workup had similar 30-day outcomes whether they were admitted to the hospital or sent home from the ED, based on the results of a retrospective study presented at the annual meeting of the American College of Emergency Physicians.

Dr. Marc A. Probst of the Icahn School of Medicine at Mount Sinai, New York, who presented the data, reported that many centers admit older patients with syncope, although the benefit of this practice has not been well established.

In a video interview, Dr. Probst points out how the findings may be useful in guiding clinical decisions or counseling patients when admission is being considered.

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Get ready for high-sensitivity troponin tests in the ED

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SAN DIEGO – The rule-in cutoff level for high-sensitivity cardiac troponin measures in the diagnosis of acute MI have been established by the European Society of Cardiology, but the value might not be applicable to a U.S. population.

In a video interview at the annual scientific assembly of the American College of Emergency Physicians, Richard M. Nowak, MD, of the department of emergency medicine at Henry Ford Hospital, Detroit, explains why the rule-in cutoff is not likely to apply to American patients and may be associated with a higher risk of false positives.

Since high-sensitivity troponin measures will soon be coming to every ED, each institution may have to arrive at their own rule-in cutoff value in order to diagnose acute MI with an acceptable number of false positives, he said. Dr. Nowak explains how to begin addressing that process.

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SAN DIEGO – The rule-in cutoff level for high-sensitivity cardiac troponin measures in the diagnosis of acute MI have been established by the European Society of Cardiology, but the value might not be applicable to a U.S. population.

In a video interview at the annual scientific assembly of the American College of Emergency Physicians, Richard M. Nowak, MD, of the department of emergency medicine at Henry Ford Hospital, Detroit, explains why the rule-in cutoff is not likely to apply to American patients and may be associated with a higher risk of false positives.

Since high-sensitivity troponin measures will soon be coming to every ED, each institution may have to arrive at their own rule-in cutoff value in order to diagnose acute MI with an acceptable number of false positives, he said. Dr. Nowak explains how to begin addressing that process.

SAN DIEGO – The rule-in cutoff level for high-sensitivity cardiac troponin measures in the diagnosis of acute MI have been established by the European Society of Cardiology, but the value might not be applicable to a U.S. population.

In a video interview at the annual scientific assembly of the American College of Emergency Physicians, Richard M. Nowak, MD, of the department of emergency medicine at Henry Ford Hospital, Detroit, explains why the rule-in cutoff is not likely to apply to American patients and may be associated with a higher risk of false positives.

Since high-sensitivity troponin measures will soon be coming to every ED, each institution may have to arrive at their own rule-in cutoff value in order to diagnose acute MI with an acceptable number of false positives, he said. Dr. Nowak explains how to begin addressing that process.

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How to manage difficult dislocations

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– Being prepared to manage difficult dislocations is key to maintaining the flow of patient care in any emergency department.

In a video interview at the annual meeting of the American College of Emergency Physicians, Danielle D. Campagne, MD, FACEP, shared her clinical pearls for managing dislocations of the jaw, hip, ankle, and shoulder.

Dr. Campagne is an emergency medicine physician who practices at Community Regional Medical Center in Fresno, Calif. She is also vice chief of emergency medicine at University of California, San Francisco, Fresno. She reported having no financial disclosures.

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– Being prepared to manage difficult dislocations is key to maintaining the flow of patient care in any emergency department.

In a video interview at the annual meeting of the American College of Emergency Physicians, Danielle D. Campagne, MD, FACEP, shared her clinical pearls for managing dislocations of the jaw, hip, ankle, and shoulder.

Dr. Campagne is an emergency medicine physician who practices at Community Regional Medical Center in Fresno, Calif. She is also vice chief of emergency medicine at University of California, San Francisco, Fresno. She reported having no financial disclosures.

– Being prepared to manage difficult dislocations is key to maintaining the flow of patient care in any emergency department.

In a video interview at the annual meeting of the American College of Emergency Physicians, Danielle D. Campagne, MD, FACEP, shared her clinical pearls for managing dislocations of the jaw, hip, ankle, and shoulder.

Dr. Campagne is an emergency medicine physician who practices at Community Regional Medical Center in Fresno, Calif. She is also vice chief of emergency medicine at University of California, San Francisco, Fresno. She reported having no financial disclosures.

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Vaginal and bilateral thigh removal of a transobturator sling

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Ms. Pan is a medical student, Baylor College of Medicine, Houston, Texas.

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Ms. Pan is a medical student, Baylor College of Medicine, Houston, Texas.

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Swings in four metabolic measures predicted death in healthy people

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Fluctuations in body weight, systolic blood pressure, total cholesterol, and fasting blood glucose in healthy people were associated with an increased risk of myocardial infarction, stroke, and death from any cause, and the effects are additive, based on data from a 5.5-year population-based study in Korea.

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The relationship between the number of high-variability parameters and all-cause mortality was greater than the relationship for MI or stroke.

In a model adjusted for age, sex, smoking, alcohol consumption, regular exercise, and income status the group with high variability for all four parameters had a significantly higher risk for all-cause mortality (hazard ratio, 2.27; 95% confidence interval, 2.13-2.42), for MI (HR, 1.43; 95% CI, 1.25-1.64), and for stroke (HR, 1.41; 95% CI, 1.25-1.60), compared with the group with low variability for all four parameters. The association with risk was graded and persisted after multivariable adjustment.

“Variability in metabolic parameters may be prognostic surrogate markers for predicting mortality and cardiovascular outcomes,” wrote senior author Seung-Hwan Lee, MD, PhD, and professor of endocrinology at the College of Medicine of the Catholic University of Korea in Seoul, South Korea, and colleagues. “High variability in metabolic parameters (may be) associated with adverse health outcomes not only in a diseased population, but also in the relatively healthy population although the mechanism could be somewhat different.”

Korea has a single-payer system, the Korean National Health Insurance system, that includes health information on its entire population. The researchers selected data from 6,748,773 people who were free of diabetes mellitus, hypertension, and dyslipidemia, and who underwent three or more health examinations during 2005-2012 that documented body mass index (BMI), fasting blood glucose, systolic blood pressure, and total cholesterol. Participants were followed to the end of 2015, for a median follow-up of 5.5 years. There were 54,785 deaths (0.8%), 22,498 cases of stroke (0.3%), and 21,452 MIs (0.3%).

The research team defined high variability as the highest quartile, classifying participants according to the number of high-variability parameters. A score of 4 indicated high variability in all four metabolic parameters – body weight, systolic blood pressure, total cholesterol, and fasting blood glucose.

In the highest quartile in fasting blood glucose variability, compared with the lowest quartile, the risk of all-cause mortality increased by 20% (HR, 1.20; 95% CI, 1.18-1.23), MI by 16% (HR, 1.16; 95% CI, 1.12-1.21), and stroke by 13% (HR, 1.13; 95% CI, 1.09-1.17).

For the highest quartile in total cholesterol variability, compared with the lowest quartile, the risk of all-cause mortality increased by 31% (HR, 1.31; 95% CI, 1.28-1.34), MI by 10% (HR, 1.10; 95% CI, 1.06-1.14), and stroke by 6% (HR, 1.06; 95% CI, 1.03-1.10).

For the highest quartile in systolic BP variability, compared with the lowest quartile, the risk of all-cause mortality increased by 19% (HR, 1.19; 95% CI, 1.16-1.22), MI by 7% (HR, 1.07; 95% CI, 1.03-1.11), and stroke by 14% (HR, 1.14; 95% CI, 1.10-1.18).

For the highest quartile in BMI variability, compared with the lowest quartile, the risk of all-cause mortality increased by 53% (HR, 1.53; 95% CI, 1.50-1.57), MI by 14% (HR, 1.14; 95% CI, 1.09-1.18), and stroke by 14% (HR, 1.14; 95% CI, 1.10-1.18).

“It is not certain whether these results from Korea would apply to the United States. However, several previous studies on variability were performed in other populations, suggesting that it is likely to be a common phenomenon,” the authors wrote.

The study was supported in part by the National Research Foundation of Korea Grant funded by the Korean Government. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

SOURCE: Lee S-H et al. Circulation. 2018 Oct.

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Fluctuations in body weight, systolic blood pressure, total cholesterol, and fasting blood glucose in healthy people were associated with an increased risk of myocardial infarction, stroke, and death from any cause, and the effects are additive, based on data from a 5.5-year population-based study in Korea.

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The relationship between the number of high-variability parameters and all-cause mortality was greater than the relationship for MI or stroke.

In a model adjusted for age, sex, smoking, alcohol consumption, regular exercise, and income status the group with high variability for all four parameters had a significantly higher risk for all-cause mortality (hazard ratio, 2.27; 95% confidence interval, 2.13-2.42), for MI (HR, 1.43; 95% CI, 1.25-1.64), and for stroke (HR, 1.41; 95% CI, 1.25-1.60), compared with the group with low variability for all four parameters. The association with risk was graded and persisted after multivariable adjustment.

“Variability in metabolic parameters may be prognostic surrogate markers for predicting mortality and cardiovascular outcomes,” wrote senior author Seung-Hwan Lee, MD, PhD, and professor of endocrinology at the College of Medicine of the Catholic University of Korea in Seoul, South Korea, and colleagues. “High variability in metabolic parameters (may be) associated with adverse health outcomes not only in a diseased population, but also in the relatively healthy population although the mechanism could be somewhat different.”

Korea has a single-payer system, the Korean National Health Insurance system, that includes health information on its entire population. The researchers selected data from 6,748,773 people who were free of diabetes mellitus, hypertension, and dyslipidemia, and who underwent three or more health examinations during 2005-2012 that documented body mass index (BMI), fasting blood glucose, systolic blood pressure, and total cholesterol. Participants were followed to the end of 2015, for a median follow-up of 5.5 years. There were 54,785 deaths (0.8%), 22,498 cases of stroke (0.3%), and 21,452 MIs (0.3%).

The research team defined high variability as the highest quartile, classifying participants according to the number of high-variability parameters. A score of 4 indicated high variability in all four metabolic parameters – body weight, systolic blood pressure, total cholesterol, and fasting blood glucose.

In the highest quartile in fasting blood glucose variability, compared with the lowest quartile, the risk of all-cause mortality increased by 20% (HR, 1.20; 95% CI, 1.18-1.23), MI by 16% (HR, 1.16; 95% CI, 1.12-1.21), and stroke by 13% (HR, 1.13; 95% CI, 1.09-1.17).

For the highest quartile in total cholesterol variability, compared with the lowest quartile, the risk of all-cause mortality increased by 31% (HR, 1.31; 95% CI, 1.28-1.34), MI by 10% (HR, 1.10; 95% CI, 1.06-1.14), and stroke by 6% (HR, 1.06; 95% CI, 1.03-1.10).

For the highest quartile in systolic BP variability, compared with the lowest quartile, the risk of all-cause mortality increased by 19% (HR, 1.19; 95% CI, 1.16-1.22), MI by 7% (HR, 1.07; 95% CI, 1.03-1.11), and stroke by 14% (HR, 1.14; 95% CI, 1.10-1.18).

For the highest quartile in BMI variability, compared with the lowest quartile, the risk of all-cause mortality increased by 53% (HR, 1.53; 95% CI, 1.50-1.57), MI by 14% (HR, 1.14; 95% CI, 1.09-1.18), and stroke by 14% (HR, 1.14; 95% CI, 1.10-1.18).

“It is not certain whether these results from Korea would apply to the United States. However, several previous studies on variability were performed in other populations, suggesting that it is likely to be a common phenomenon,” the authors wrote.

The study was supported in part by the National Research Foundation of Korea Grant funded by the Korean Government. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

SOURCE: Lee S-H et al. Circulation. 2018 Oct.

 

Fluctuations in body weight, systolic blood pressure, total cholesterol, and fasting blood glucose in healthy people were associated with an increased risk of myocardial infarction, stroke, and death from any cause, and the effects are additive, based on data from a 5.5-year population-based study in Korea.

Fuse/ThinkStock
The relationship between the number of high-variability parameters and all-cause mortality was greater than the relationship for MI or stroke.

In a model adjusted for age, sex, smoking, alcohol consumption, regular exercise, and income status the group with high variability for all four parameters had a significantly higher risk for all-cause mortality (hazard ratio, 2.27; 95% confidence interval, 2.13-2.42), for MI (HR, 1.43; 95% CI, 1.25-1.64), and for stroke (HR, 1.41; 95% CI, 1.25-1.60), compared with the group with low variability for all four parameters. The association with risk was graded and persisted after multivariable adjustment.

“Variability in metabolic parameters may be prognostic surrogate markers for predicting mortality and cardiovascular outcomes,” wrote senior author Seung-Hwan Lee, MD, PhD, and professor of endocrinology at the College of Medicine of the Catholic University of Korea in Seoul, South Korea, and colleagues. “High variability in metabolic parameters (may be) associated with adverse health outcomes not only in a diseased population, but also in the relatively healthy population although the mechanism could be somewhat different.”

Korea has a single-payer system, the Korean National Health Insurance system, that includes health information on its entire population. The researchers selected data from 6,748,773 people who were free of diabetes mellitus, hypertension, and dyslipidemia, and who underwent three or more health examinations during 2005-2012 that documented body mass index (BMI), fasting blood glucose, systolic blood pressure, and total cholesterol. Participants were followed to the end of 2015, for a median follow-up of 5.5 years. There were 54,785 deaths (0.8%), 22,498 cases of stroke (0.3%), and 21,452 MIs (0.3%).

The research team defined high variability as the highest quartile, classifying participants according to the number of high-variability parameters. A score of 4 indicated high variability in all four metabolic parameters – body weight, systolic blood pressure, total cholesterol, and fasting blood glucose.

In the highest quartile in fasting blood glucose variability, compared with the lowest quartile, the risk of all-cause mortality increased by 20% (HR, 1.20; 95% CI, 1.18-1.23), MI by 16% (HR, 1.16; 95% CI, 1.12-1.21), and stroke by 13% (HR, 1.13; 95% CI, 1.09-1.17).

For the highest quartile in total cholesterol variability, compared with the lowest quartile, the risk of all-cause mortality increased by 31% (HR, 1.31; 95% CI, 1.28-1.34), MI by 10% (HR, 1.10; 95% CI, 1.06-1.14), and stroke by 6% (HR, 1.06; 95% CI, 1.03-1.10).

For the highest quartile in systolic BP variability, compared with the lowest quartile, the risk of all-cause mortality increased by 19% (HR, 1.19; 95% CI, 1.16-1.22), MI by 7% (HR, 1.07; 95% CI, 1.03-1.11), and stroke by 14% (HR, 1.14; 95% CI, 1.10-1.18).

For the highest quartile in BMI variability, compared with the lowest quartile, the risk of all-cause mortality increased by 53% (HR, 1.53; 95% CI, 1.50-1.57), MI by 14% (HR, 1.14; 95% CI, 1.09-1.18), and stroke by 14% (HR, 1.14; 95% CI, 1.10-1.18).

“It is not certain whether these results from Korea would apply to the United States. However, several previous studies on variability were performed in other populations, suggesting that it is likely to be a common phenomenon,” the authors wrote.

The study was supported in part by the National Research Foundation of Korea Grant funded by the Korean Government. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

SOURCE: Lee S-H et al. Circulation. 2018 Oct.

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Key clinical point: Fluctuations in fasting glucose and cholesterol levels, systolic blood pressure, and body mass index are associated with a higher risk for all-cause mortality, myocardial infarction, and stroke in otherwise healthy people.

Major finding: The hazard ratios  were 2.27 (95% CI, 2.13-2.42) for all-cause mortality, 1.43 (95% CI, 1.25-1.64) for MI, and 1.41 (95% CI, 1.25-1.60) for stroke.

Study details:  An observational population-based study involving more than 6.7 million Koreans age 20 and older.

Disclosures: The study was funded by the National Research Foundation of Korea. The authors had no relevant conflicts of interest to declare.

Source: Lee S-H et al. Circulation. 2018 Oct.
 

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