Literature Review

TOPLINE:

Challenging conventional wisdom, new research suggests that hitting the snooze button does not lead to cognitive impairment on waking and may actually provide cognitive benefits.

METHODOLOGY:

• Researchers did two studies to determine why intermittent morning alarms are used and how they affect sleep, cognition, cortisol, and mood.
• Study 1 was a survey of 1,732 healthy adults (mean age 34 years; 66% women) designed to elucidate the characteristics of people who snooze and why they choose to delay their waking in this way.
• Study 2 was a within-subject polysomnography study of 31 healthy habitual snoozers (mean age 27 years; 18 women) designed to explore the acute effects of snoozing on sleep architecture, sleepiness, cognitive ability, mood, and cortisol awakening response.

TAKEAWAY:

• Overall, 69% reported using the snooze button or setting multiple alarms at least sometimes, most often on workdays (71%), with an average snooze time per morning of 22 minutes.
• Sleep quality did not differ between snoozers and nonsnoozers, but snoozers were more likely to feel mentally drowsy on waking (odds ratio, 3.0; P < .001) and had slightly shorter sleep time on workdays (13 minutes).
• In the polysomnography study, compared with waking up abruptly, 30 minutes of snoozing in the morning improved or did not affect performance on standard cognitive tests completed directly on final awakening.
• Snoozing resulted in about 6 minutes of lost sleep, but it prevented awakening from slow-wave sleep and had no clear effects on the cortisol awakening response, morning sleepiness, mood, or overnight sleep architecture.

IN PRACTICE:

“The findings indicate that there is no reason to stop snoozing in the morning if you enjoy it, at least not for snooze times around 30 minutes. In fact, it may even help those with morning drowsiness to be slightly more awake once they get up,” corresponding author Tina Sundelin, PhD, of Stockholm University, said in a statement.

SOURCE:

The study was published online in the Journal of Sleep Research.

LIMITATIONS:

Study 1 focused on waking preferences in a convenience sample of adults. Study 2 included only habitual snoozers making it difficult to generalize the findings to people who don’t usually snooze. The study investigated only the effect of 30 minutes of snoozing on the studied parameters. It’s possible that shorter or longer snooze times have different cognitive effects.

DISCLOSURES:

Support for the study was provided by the Stress Research Institute, Stockholm University, and a grant from Vetenskapsrådet. The authors disclosed no relevant conflicts of interest.

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

TOPLINE:

Challenging conventional wisdom, new research suggests that hitting the snooze button does not lead to cognitive impairment on waking and may actually provide cognitive benefits.

METHODOLOGY:

• Researchers did two studies to determine why intermittent morning alarms are used and how they affect sleep, cognition, cortisol, and mood.
• Study 1 was a survey of 1,732 healthy adults (mean age 34 years; 66% women) designed to elucidate the characteristics of people who snooze and why they choose to delay their waking in this way.
• Study 2 was a within-subject polysomnography study of 31 healthy habitual snoozers (mean age 27 years; 18 women) designed to explore the acute effects of snoozing on sleep architecture, sleepiness, cognitive ability, mood, and cortisol awakening response.

TAKEAWAY:

• Overall, 69% reported using the snooze button or setting multiple alarms at least sometimes, most often on workdays (71%), with an average snooze time per morning of 22 minutes.
• Sleep quality did not differ between snoozers and nonsnoozers, but snoozers were more likely to feel mentally drowsy on waking (odds ratio, 3.0; P < .001) and had slightly shorter sleep time on workdays (13 minutes).
• In the polysomnography study, compared with waking up abruptly, 30 minutes of snoozing in the morning improved or did not affect performance on standard cognitive tests completed directly on final awakening.
• Snoozing resulted in about 6 minutes of lost sleep, but it prevented awakening from slow-wave sleep and had no clear effects on the cortisol awakening response, morning sleepiness, mood, or overnight sleep architecture.

IN PRACTICE:

“The findings indicate that there is no reason to stop snoozing in the morning if you enjoy it, at least not for snooze times around 30 minutes. In fact, it may even help those with morning drowsiness to be slightly more awake once they get up,” corresponding author Tina Sundelin, PhD, of Stockholm University, said in a statement.

SOURCE:

The study was published online in the Journal of Sleep Research.

LIMITATIONS:

Study 1 focused on waking preferences in a convenience sample of adults. Study 2 included only habitual snoozers making it difficult to generalize the findings to people who don’t usually snooze. The study investigated only the effect of 30 minutes of snoozing on the studied parameters. It’s possible that shorter or longer snooze times have different cognitive effects.

DISCLOSURES:

Support for the study was provided by the Stress Research Institute, Stockholm University, and a grant from Vetenskapsrådet. The authors disclosed no relevant conflicts of interest.

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

TOPLINE:

Challenging conventional wisdom, new research suggests that hitting the snooze button does not lead to cognitive impairment on waking and may actually provide cognitive benefits.

METHODOLOGY:

• Researchers did two studies to determine why intermittent morning alarms are used and how they affect sleep, cognition, cortisol, and mood.
• Study 1 was a survey of 1,732 healthy adults (mean age 34 years; 66% women) designed to elucidate the characteristics of people who snooze and why they choose to delay their waking in this way.
• Study 2 was a within-subject polysomnography study of 31 healthy habitual snoozers (mean age 27 years; 18 women) designed to explore the acute effects of snoozing on sleep architecture, sleepiness, cognitive ability, mood, and cortisol awakening response.

TAKEAWAY:

• Overall, 69% reported using the snooze button or setting multiple alarms at least sometimes, most often on workdays (71%), with an average snooze time per morning of 22 minutes.
• Sleep quality did not differ between snoozers and nonsnoozers, but snoozers were more likely to feel mentally drowsy on waking (odds ratio, 3.0; P < .001) and had slightly shorter sleep time on workdays (13 minutes).
• In the polysomnography study, compared with waking up abruptly, 30 minutes of snoozing in the morning improved or did not affect performance on standard cognitive tests completed directly on final awakening.
• Snoozing resulted in about 6 minutes of lost sleep, but it prevented awakening from slow-wave sleep and had no clear effects on the cortisol awakening response, morning sleepiness, mood, or overnight sleep architecture.

IN PRACTICE:

“The findings indicate that there is no reason to stop snoozing in the morning if you enjoy it, at least not for snooze times around 30 minutes. In fact, it may even help those with morning drowsiness to be slightly more awake once they get up,” corresponding author Tina Sundelin, PhD, of Stockholm University, said in a statement.

SOURCE:

The study was published online in the Journal of Sleep Research.

LIMITATIONS:

Study 1 focused on waking preferences in a convenience sample of adults. Study 2 included only habitual snoozers making it difficult to generalize the findings to people who don’t usually snooze. The study investigated only the effect of 30 minutes of snoozing on the studied parameters. It’s possible that shorter or longer snooze times have different cognitive effects.

DISCLOSURES:

Support for the study was provided by the Stress Research Institute, Stockholm University, and a grant from Vetenskapsrådet. The authors disclosed no relevant conflicts of interest.

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

Prescribing patterns of preventive migraine medications for young adults do not appear to vary based on whether the provider is a pediatric or adult neurologist, but researchers say preventive medications may be underused for this group, according to recent research published in the journal Headache.

“Approximately two-fifths of young adults with migraine were prescribed preventive medications, and this did not differ between pediatric and adult neurologists,” Hannah F. J. Shapiro MD, of the department of neurology at the University of California, San Francisco, and the UCSF Benioff Children’s Hospitals, and colleagues wrote in their study. “This finding suggests that pediatric neurologists are providing comparable care to adult neurologists for young adults with migraine; however, this may represent the underuse of preventive medications in this patient population.”

Dr. Shapiro and colleagues conducted a retrospective study of 767 patients (mean age 20.3 years) at Mass General Brigham Hospital in Boston between 2017 and 2021 who received care from a pediatric or adult neurologist for episodic migraine. The majority of patients in the study were white (72.2%), non-Hispanic (82.1%) women (80.3%) with episodic migraine (72.8%), some of whom experienced a psychiatric comorbidity (12.7%), and had a 3.88 mean clinic visits for migraine. Researchers assessed prescription of migraine preventive medication as a primary outcome, with a secondary outcome of comparing the rate of migraine preventive prescriptions written by pediatric and adult neurologists.

Overall, 290 patients (37.8%) received care from a pediatric neurologist, and 131 of those 290 patients (45.2%) received preventive medications (95% confidence interval, 39.5%-51.0%). The remaining 477 patients received care from an adult neurologist; of these, 206 patients (43.2%) received preventive medications (95% CI, 39.0%-47.7%; P = .591). The most common preventive medication prescribed was topiramate, which was prescribed in 19.1% of cases by adult neurologists and 15.2% of cases by pediatric neurologists. Other preventive medications included tricyclic antidepressants such as amitriptyline and nortriptyline; pediatric neurologists prescribed amitriptyline more often than adult neurologists (14.5% vs. 5.5%; P <  .001), and adult neurologists prescribed nortriptyline more often than pediatric neurologists (12.8% vs. 2.4%; P < .001).

Dr. Shapiro and colleagues performed a mixed effects logistic regression analysis of potential confounders, and found no significant association between clinician specialty and use of preventive medication (adjusted odds ratio, 1.20; 95% CI, 0.62­-2.31), while factors such as female sex (aOR, 1.69; 95% CI, 1.07-2.66) and number of visits (aOR, 1.64; 95% CI, 1.49-1.80) carried associations with preventive medication use.

The finding that pediatric and adult neurologists use similar preventive medications is a positive one because “patients who continue care into adulthood with a pediatric neurologist should receive comparable care to the care they would receive with an adult neurologist,” Dr. Shapiro and colleagues said. “It is even more pertinent now for pediatric neurologists to have comfort prescribing preventive medication to young adults, as the newer calcitonin gene-related peptide (CGRP) pathway antagonists are currently only FDA approved for use in patients aged 18 years or older.”
 

Roadblocks may prevent adoption

M. Cristina Victorio, MD, a pediatric neurologist and director of the headache program at Akron (Ohio) Children’s, said in an interview that the study is well-designed, but the results cannot be generalized as the study is retrospective, was conducted at a single institution, and data about nutraceuticals and drug-free neuromodulation devices were excluded from the analysis.

Another aspect of the study to consider is that episodic migraine, defined as between 0 and 14 migraine days per month, comprised most of the diagnoses in this study, while preventive medication is usually considered in patients with migraines occurring at least 6 days per month. “[I]f migraine is only once every other month or once a month, preventive treatment may not be recommended,” she said.

There is also the element of patient preference, which is “difficult to obtain” in a retrospective study, she noted.

Citing the authors’ comments about pediatric neurologists’ comfortability prescribing preventive medications, including CGRP antagonists, Dr. Victorio said she offers CGRP antagonists to “young adult patients who have failed at least two of the guideline-recommended preventive medications.”

However, pediatric neurologists may encounter roadblocks to prescribing these medications. “A big challenge is access, as it requires prior authorization as well as writing a letter of appeal or medical necessity, which can be a nuisance for clinicians who are already inundated with clinical responsibilities,” she said.
 

More education is needed

“As a pediatric headache specialist and knowing the results of this study, my colleagues and I have a role in educating all clinicians as well as trainees on headache management to improve and provide optimal care for young adult patients with migraine,” Dr. Victorio said.

In her experience, more clinic visits usually mean a need for preventative medication, and psychiatric morbidities are common. “I differ in the sense that as a headache specialist I am comfortable offering various preventive treatment options when indicated, so I do not believe I am underutilizing,” she said.

Dr. Victorio said she prescribes topiramate, amitriptyline, and propranolol as migraine preventatives for adolescents and young adults, but recommends cyproheptadine for younger children “due to lesser side effects, tolerability, and convenience of formulation (both liquid and tablet forms are available), which can be challenging for younger children who are unable to swallow pills.”

“Cognizant that there are patients who are reluctant to take daily prescription medication and that consideration for preventive treatment includes patient’s preference, I include the use of nutraceuticals and drug-free neuromodulation devices when discussing preventive treatment options,” she added, noting that children and adolescents “[m]ore often than not” prefer nutraceuticals like magnesium and vitamin B2.

“I think the bottom line is that all clinicians managing young adults with migraine should know when to consider starting preventive migraine medication,” Dr. Victorio said. “Not offering preventive treatment to young adults specifically for those who have frequent migraine attacks, or those who have severe migraine despite adequate acute treatment, or those with significant adverse reactions to acute medications will only put these patients at risk to progression to chronic migraine (meaning having migraine more often than not – at least 15 days per month), and increases headache-related disability and reduces quality of life.”

The authors report no relevant financial disclosures. This study was supported by Harvard University and an award from the National Institutes of Health. Dr. Victorio reports being on the advisory board for Theranica Bio-electronics, has received honorarium serving as an author of the Merck Manual, and is involved in industry-sponsored clinical trials through Akron Children’s Hospital.

Prescribing patterns of preventive migraine medications for young adults do not appear to vary based on whether the provider is a pediatric or adult neurologist, but researchers say preventive medications may be underused for this group, according to recent research published in the journal Headache.

“Approximately two-fifths of young adults with migraine were prescribed preventive medications, and this did not differ between pediatric and adult neurologists,” Hannah F. J. Shapiro MD, of the department of neurology at the University of California, San Francisco, and the UCSF Benioff Children’s Hospitals, and colleagues wrote in their study. “This finding suggests that pediatric neurologists are providing comparable care to adult neurologists for young adults with migraine; however, this may represent the underuse of preventive medications in this patient population.”

Dr. Shapiro and colleagues conducted a retrospective study of 767 patients (mean age 20.3 years) at Mass General Brigham Hospital in Boston between 2017 and 2021 who received care from a pediatric or adult neurologist for episodic migraine. The majority of patients in the study were white (72.2%), non-Hispanic (82.1%) women (80.3%) with episodic migraine (72.8%), some of whom experienced a psychiatric comorbidity (12.7%), and had a 3.88 mean clinic visits for migraine. Researchers assessed prescription of migraine preventive medication as a primary outcome, with a secondary outcome of comparing the rate of migraine preventive prescriptions written by pediatric and adult neurologists.

Overall, 290 patients (37.8%) received care from a pediatric neurologist, and 131 of those 290 patients (45.2%) received preventive medications (95% confidence interval, 39.5%-51.0%). The remaining 477 patients received care from an adult neurologist; of these, 206 patients (43.2%) received preventive medications (95% CI, 39.0%-47.7%; P = .591). The most common preventive medication prescribed was topiramate, which was prescribed in 19.1% of cases by adult neurologists and 15.2% of cases by pediatric neurologists. Other preventive medications included tricyclic antidepressants such as amitriptyline and nortriptyline; pediatric neurologists prescribed amitriptyline more often than adult neurologists (14.5% vs. 5.5%; P <  .001), and adult neurologists prescribed nortriptyline more often than pediatric neurologists (12.8% vs. 2.4%; P < .001).

Dr. Shapiro and colleagues performed a mixed effects logistic regression analysis of potential confounders, and found no significant association between clinician specialty and use of preventive medication (adjusted odds ratio, 1.20; 95% CI, 0.62­-2.31), while factors such as female sex (aOR, 1.69; 95% CI, 1.07-2.66) and number of visits (aOR, 1.64; 95% CI, 1.49-1.80) carried associations with preventive medication use.

The finding that pediatric and adult neurologists use similar preventive medications is a positive one because “patients who continue care into adulthood with a pediatric neurologist should receive comparable care to the care they would receive with an adult neurologist,” Dr. Shapiro and colleagues said. “It is even more pertinent now for pediatric neurologists to have comfort prescribing preventive medication to young adults, as the newer calcitonin gene-related peptide (CGRP) pathway antagonists are currently only FDA approved for use in patients aged 18 years or older.”
 

Roadblocks may prevent adoption

M. Cristina Victorio, MD, a pediatric neurologist and director of the headache program at Akron (Ohio) Children’s, said in an interview that the study is well-designed, but the results cannot be generalized as the study is retrospective, was conducted at a single institution, and data about nutraceuticals and drug-free neuromodulation devices were excluded from the analysis.

Another aspect of the study to consider is that episodic migraine, defined as between 0 and 14 migraine days per month, comprised most of the diagnoses in this study, while preventive medication is usually considered in patients with migraines occurring at least 6 days per month. “[I]f migraine is only once every other month or once a month, preventive treatment may not be recommended,” she said.

There is also the element of patient preference, which is “difficult to obtain” in a retrospective study, she noted.

Citing the authors’ comments about pediatric neurologists’ comfortability prescribing preventive medications, including CGRP antagonists, Dr. Victorio said she offers CGRP antagonists to “young adult patients who have failed at least two of the guideline-recommended preventive medications.”

However, pediatric neurologists may encounter roadblocks to prescribing these medications. “A big challenge is access, as it requires prior authorization as well as writing a letter of appeal or medical necessity, which can be a nuisance for clinicians who are already inundated with clinical responsibilities,” she said.
 

More education is needed

“As a pediatric headache specialist and knowing the results of this study, my colleagues and I have a role in educating all clinicians as well as trainees on headache management to improve and provide optimal care for young adult patients with migraine,” Dr. Victorio said.

In her experience, more clinic visits usually mean a need for preventative medication, and psychiatric morbidities are common. “I differ in the sense that as a headache specialist I am comfortable offering various preventive treatment options when indicated, so I do not believe I am underutilizing,” she said.

Dr. Victorio said she prescribes topiramate, amitriptyline, and propranolol as migraine preventatives for adolescents and young adults, but recommends cyproheptadine for younger children “due to lesser side effects, tolerability, and convenience of formulation (both liquid and tablet forms are available), which can be challenging for younger children who are unable to swallow pills.”

“Cognizant that there are patients who are reluctant to take daily prescription medication and that consideration for preventive treatment includes patient’s preference, I include the use of nutraceuticals and drug-free neuromodulation devices when discussing preventive treatment options,” she added, noting that children and adolescents “[m]ore often than not” prefer nutraceuticals like magnesium and vitamin B2.

“I think the bottom line is that all clinicians managing young adults with migraine should know when to consider starting preventive migraine medication,” Dr. Victorio said. “Not offering preventive treatment to young adults specifically for those who have frequent migraine attacks, or those who have severe migraine despite adequate acute treatment, or those with significant adverse reactions to acute medications will only put these patients at risk to progression to chronic migraine (meaning having migraine more often than not – at least 15 days per month), and increases headache-related disability and reduces quality of life.”

The authors report no relevant financial disclosures. This study was supported by Harvard University and an award from the National Institutes of Health. Dr. Victorio reports being on the advisory board for Theranica Bio-electronics, has received honorarium serving as an author of the Merck Manual, and is involved in industry-sponsored clinical trials through Akron Children’s Hospital.

Prescribing patterns of preventive migraine medications for young adults do not appear to vary based on whether the provider is a pediatric or adult neurologist, but researchers say preventive medications may be underused for this group, according to recent research published in the journal Headache.

“Approximately two-fifths of young adults with migraine were prescribed preventive medications, and this did not differ between pediatric and adult neurologists,” Hannah F. J. Shapiro MD, of the department of neurology at the University of California, San Francisco, and the UCSF Benioff Children’s Hospitals, and colleagues wrote in their study. “This finding suggests that pediatric neurologists are providing comparable care to adult neurologists for young adults with migraine; however, this may represent the underuse of preventive medications in this patient population.”

Dr. Shapiro and colleagues conducted a retrospective study of 767 patients (mean age 20.3 years) at Mass General Brigham Hospital in Boston between 2017 and 2021 who received care from a pediatric or adult neurologist for episodic migraine. The majority of patients in the study were white (72.2%), non-Hispanic (82.1%) women (80.3%) with episodic migraine (72.8%), some of whom experienced a psychiatric comorbidity (12.7%), and had a 3.88 mean clinic visits for migraine. Researchers assessed prescription of migraine preventive medication as a primary outcome, with a secondary outcome of comparing the rate of migraine preventive prescriptions written by pediatric and adult neurologists.

Overall, 290 patients (37.8%) received care from a pediatric neurologist, and 131 of those 290 patients (45.2%) received preventive medications (95% confidence interval, 39.5%-51.0%). The remaining 477 patients received care from an adult neurologist; of these, 206 patients (43.2%) received preventive medications (95% CI, 39.0%-47.7%; P = .591). The most common preventive medication prescribed was topiramate, which was prescribed in 19.1% of cases by adult neurologists and 15.2% of cases by pediatric neurologists. Other preventive medications included tricyclic antidepressants such as amitriptyline and nortriptyline; pediatric neurologists prescribed amitriptyline more often than adult neurologists (14.5% vs. 5.5%; P <  .001), and adult neurologists prescribed nortriptyline more often than pediatric neurologists (12.8% vs. 2.4%; P < .001).

Dr. Shapiro and colleagues performed a mixed effects logistic regression analysis of potential confounders, and found no significant association between clinician specialty and use of preventive medication (adjusted odds ratio, 1.20; 95% CI, 0.62­-2.31), while factors such as female sex (aOR, 1.69; 95% CI, 1.07-2.66) and number of visits (aOR, 1.64; 95% CI, 1.49-1.80) carried associations with preventive medication use.

The finding that pediatric and adult neurologists use similar preventive medications is a positive one because “patients who continue care into adulthood with a pediatric neurologist should receive comparable care to the care they would receive with an adult neurologist,” Dr. Shapiro and colleagues said. “It is even more pertinent now for pediatric neurologists to have comfort prescribing preventive medication to young adults, as the newer calcitonin gene-related peptide (CGRP) pathway antagonists are currently only FDA approved for use in patients aged 18 years or older.”
 

Roadblocks may prevent adoption

M. Cristina Victorio, MD, a pediatric neurologist and director of the headache program at Akron (Ohio) Children’s, said in an interview that the study is well-designed, but the results cannot be generalized as the study is retrospective, was conducted at a single institution, and data about nutraceuticals and drug-free neuromodulation devices were excluded from the analysis.

Another aspect of the study to consider is that episodic migraine, defined as between 0 and 14 migraine days per month, comprised most of the diagnoses in this study, while preventive medication is usually considered in patients with migraines occurring at least 6 days per month. “[I]f migraine is only once every other month or once a month, preventive treatment may not be recommended,” she said.

There is also the element of patient preference, which is “difficult to obtain” in a retrospective study, she noted.

Citing the authors’ comments about pediatric neurologists’ comfortability prescribing preventive medications, including CGRP antagonists, Dr. Victorio said she offers CGRP antagonists to “young adult patients who have failed at least two of the guideline-recommended preventive medications.”

However, pediatric neurologists may encounter roadblocks to prescribing these medications. “A big challenge is access, as it requires prior authorization as well as writing a letter of appeal or medical necessity, which can be a nuisance for clinicians who are already inundated with clinical responsibilities,” she said.
 

More education is needed

“As a pediatric headache specialist and knowing the results of this study, my colleagues and I have a role in educating all clinicians as well as trainees on headache management to improve and provide optimal care for young adult patients with migraine,” Dr. Victorio said.

In her experience, more clinic visits usually mean a need for preventative medication, and psychiatric morbidities are common. “I differ in the sense that as a headache specialist I am comfortable offering various preventive treatment options when indicated, so I do not believe I am underutilizing,” she said.

Dr. Victorio said she prescribes topiramate, amitriptyline, and propranolol as migraine preventatives for adolescents and young adults, but recommends cyproheptadine for younger children “due to lesser side effects, tolerability, and convenience of formulation (both liquid and tablet forms are available), which can be challenging for younger children who are unable to swallow pills.”

“Cognizant that there are patients who are reluctant to take daily prescription medication and that consideration for preventive treatment includes patient’s preference, I include the use of nutraceuticals and drug-free neuromodulation devices when discussing preventive treatment options,” she added, noting that children and adolescents “[m]ore often than not” prefer nutraceuticals like magnesium and vitamin B2.

“I think the bottom line is that all clinicians managing young adults with migraine should know when to consider starting preventive migraine medication,” Dr. Victorio said. “Not offering preventive treatment to young adults specifically for those who have frequent migraine attacks, or those who have severe migraine despite adequate acute treatment, or those with significant adverse reactions to acute medications will only put these patients at risk to progression to chronic migraine (meaning having migraine more often than not – at least 15 days per month), and increases headache-related disability and reduces quality of life.”

The authors report no relevant financial disclosures. This study was supported by Harvard University and an award from the National Institutes of Health. Dr. Victorio reports being on the advisory board for Theranica Bio-electronics, has received honorarium serving as an author of the Merck Manual, and is involved in industry-sponsored clinical trials through Akron Children’s Hospital.

TOPLINE:

Nearly one in five adolescents are living with prediabetes, a condition where blood glucose levels are elevated, but are not high enough for a type 2 diabetes (T2D) diagnosis. According to a new study, higher levels of nonfasting glucose and hemoglobin A1c, and worsening obesity are important predictors of progression to T2D. In addition, metformin and weight stabilization may prove to be important interventions for preventing T2D in kids.

METHODOLOGY:

• Researchers did a retrospective chart review of patient data from Vanderbilt University Medical Center Pediatric Prediabetes Clinic, Nashville, Tenn., from May 2015 to August 2022.
• The study included 552 children with prediabetes, defined as abnormal blood glucose (fasting plasma glucose [FPG] ≥ 100 mg/dL, random glucose ≥ 150 mg/dL), or hemoglobin A1c equal to or greater than 5.9%.
• Based on follow-up visits, patients were classified as having progressed to T2D, or nonprogression.
• Researchers analyzed the patients’ initial visit A1c, fasting C-peptide, 2-hour glucose, fasting glucose, and body mass index (BMI), among other baseline characteristics.

TAKEAWAY:

• Thirty-six children (6.5%) progressed to T2D during the duration of the study period.
• The average time to T2D diagnosis was much longer in patients taking metformin (43 months), compared with those not taking the prescribed medication (28 months).
• Worsening obesity was strongly associated with T2D progression – patients who progressed to T2D had a higher BMI at baseline and had continued weight gain.
• A higher baseline A1c, fasting C-peptide, and 2-hour glucose were also associated with progression to T2D.
• In the multivariable analysis, both A1c and 2-hour glucose were strong independent predictors of progression.
• Fasting plasma glucose was not associated with progression to T2D.

IN PRACTICE:

“Weight stabilization and metformin therapy could be important interventions for diabetes prevention in children,” study author Ashley H. Shoemaker, MD, MSci, a pediatric endocrinologist at Vanderbilt University Medical Center in Nashville, Tenn., said in a press release.

In addition, A1c plus a nonfasting glucose may be a feasible way to identify high-risk pediatric patients in a clinical setting.
 

SOURCE:

This study was performed by Natasha Belsky, Jaclyn Tamaroff, and Ashley H. Shoemaker of the Vanderbilt University Medical Center and the Vanderbilt University School of Medicine in Nashville, Tenn. It was published October 12, 2023, in the Journal of the Endocrine Society

LIMITATIONS:

Additional patients who developed T2D may have been lost to follow-up, since the authors did not contact patients to confirm their disease status. The authors were also unable to establish racial differences in the progression to T2D because of missing data.

DISCLOSURES:

Funding for this study was provided by the National Center for Advancing Translational Sciences. One author has research contracts with Novo Nordisk and Boehringer Ingelheim.

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

TOPLINE:

Nearly one in five adolescents are living with prediabetes, a condition where blood glucose levels are elevated, but are not high enough for a type 2 diabetes (T2D) diagnosis. According to a new study, higher levels of nonfasting glucose and hemoglobin A1c, and worsening obesity are important predictors of progression to T2D. In addition, metformin and weight stabilization may prove to be important interventions for preventing T2D in kids.

METHODOLOGY:

• Researchers did a retrospective chart review of patient data from Vanderbilt University Medical Center Pediatric Prediabetes Clinic, Nashville, Tenn., from May 2015 to August 2022.
• The study included 552 children with prediabetes, defined as abnormal blood glucose (fasting plasma glucose [FPG] ≥ 100 mg/dL, random glucose ≥ 150 mg/dL), or hemoglobin A1c equal to or greater than 5.9%.
• Based on follow-up visits, patients were classified as having progressed to T2D, or nonprogression.
• Researchers analyzed the patients’ initial visit A1c, fasting C-peptide, 2-hour glucose, fasting glucose, and body mass index (BMI), among other baseline characteristics.

TAKEAWAY:

• Thirty-six children (6.5%) progressed to T2D during the duration of the study period.
• The average time to T2D diagnosis was much longer in patients taking metformin (43 months), compared with those not taking the prescribed medication (28 months).
• Worsening obesity was strongly associated with T2D progression – patients who progressed to T2D had a higher BMI at baseline and had continued weight gain.
• A higher baseline A1c, fasting C-peptide, and 2-hour glucose were also associated with progression to T2D.
• In the multivariable analysis, both A1c and 2-hour glucose were strong independent predictors of progression.
• Fasting plasma glucose was not associated with progression to T2D.

IN PRACTICE:

“Weight stabilization and metformin therapy could be important interventions for diabetes prevention in children,” study author Ashley H. Shoemaker, MD, MSci, a pediatric endocrinologist at Vanderbilt University Medical Center in Nashville, Tenn., said in a press release.

In addition, A1c plus a nonfasting glucose may be a feasible way to identify high-risk pediatric patients in a clinical setting.
 

SOURCE:

This study was performed by Natasha Belsky, Jaclyn Tamaroff, and Ashley H. Shoemaker of the Vanderbilt University Medical Center and the Vanderbilt University School of Medicine in Nashville, Tenn. It was published October 12, 2023, in the Journal of the Endocrine Society

LIMITATIONS:

Additional patients who developed T2D may have been lost to follow-up, since the authors did not contact patients to confirm their disease status. The authors were also unable to establish racial differences in the progression to T2D because of missing data.

DISCLOSURES:

Funding for this study was provided by the National Center for Advancing Translational Sciences. One author has research contracts with Novo Nordisk and Boehringer Ingelheim.

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

TOPLINE:

Nearly one in five adolescents are living with prediabetes, a condition where blood glucose levels are elevated, but are not high enough for a type 2 diabetes (T2D) diagnosis. According to a new study, higher levels of nonfasting glucose and hemoglobin A1c, and worsening obesity are important predictors of progression to T2D. In addition, metformin and weight stabilization may prove to be important interventions for preventing T2D in kids.

METHODOLOGY:

• Researchers did a retrospective chart review of patient data from Vanderbilt University Medical Center Pediatric Prediabetes Clinic, Nashville, Tenn., from May 2015 to August 2022.
• The study included 552 children with prediabetes, defined as abnormal blood glucose (fasting plasma glucose [FPG] ≥ 100 mg/dL, random glucose ≥ 150 mg/dL), or hemoglobin A1c equal to or greater than 5.9%.
• Based on follow-up visits, patients were classified as having progressed to T2D, or nonprogression.
• Researchers analyzed the patients’ initial visit A1c, fasting C-peptide, 2-hour glucose, fasting glucose, and body mass index (BMI), among other baseline characteristics.

TAKEAWAY:

• Thirty-six children (6.5%) progressed to T2D during the duration of the study period.
• The average time to T2D diagnosis was much longer in patients taking metformin (43 months), compared with those not taking the prescribed medication (28 months).
• Worsening obesity was strongly associated with T2D progression – patients who progressed to T2D had a higher BMI at baseline and had continued weight gain.
• A higher baseline A1c, fasting C-peptide, and 2-hour glucose were also associated with progression to T2D.
• In the multivariable analysis, both A1c and 2-hour glucose were strong independent predictors of progression.
• Fasting plasma glucose was not associated with progression to T2D.

IN PRACTICE:

“Weight stabilization and metformin therapy could be important interventions for diabetes prevention in children,” study author Ashley H. Shoemaker, MD, MSci, a pediatric endocrinologist at Vanderbilt University Medical Center in Nashville, Tenn., said in a press release.

In addition, A1c plus a nonfasting glucose may be a feasible way to identify high-risk pediatric patients in a clinical setting.
 

SOURCE:

This study was performed by Natasha Belsky, Jaclyn Tamaroff, and Ashley H. Shoemaker of the Vanderbilt University Medical Center and the Vanderbilt University School of Medicine in Nashville, Tenn. It was published October 12, 2023, in the Journal of the Endocrine Society

LIMITATIONS:

Additional patients who developed T2D may have been lost to follow-up, since the authors did not contact patients to confirm their disease status. The authors were also unable to establish racial differences in the progression to T2D because of missing data.

DISCLOSURES:

Funding for this study was provided by the National Center for Advancing Translational Sciences. One author has research contracts with Novo Nordisk and Boehringer Ingelheim.

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

Deaths and disability because of stroke are expected to rise alarmingly over the next 30 years, with almost 10 million stroke deaths forecast annually by 2050, according to a new report from the World Stroke Organization–Lancet Neurology Commission Stroke Collaboration Group.

“This highlights the need for urgent measures to reduce stroke burden worldwide, with an emphasis on low- and middle-income countries,” the report authors stated.

These measures include an increase in trained health care workers who can implement effective primary prevention strategies, including the early detection and adequate management of hypertension.

On the basis of a review of evidence-based guidelines, recent surveys, and in-depth interviews with stroke experts around the world, the WSO–Lancet Neurology Commission made evidence-based pragmatic recommendations to reduce the global burden of stroke, including measures to improve surveillance, prevention, acute care, and rehabilitation.

The report was announced on Oct. 10 by WSO President, Sheila Martins, MD, at the World Stroke Conference in Toronto. The report was also published online in The Lancet Neurology.

“Stroke care has changed a lot in the last few years,” said Dr. Martins, who is chief of neurology and neurosurgery at Hospital Moinhos de Vento, Porto Alegre, Brazil, and founder and president of the Brazilian Stroke Network. “We know what we need to do to reduce the global burden of stroke, and high-income countries are making progress in that regard. But the situation in low- and middle-income countries is catastrophic, with mortality rates of up to 80% in individuals who have had a stroke in some countries. There is a very large gap between knowledge and implementation.”

Dr. Martins said that the commission is offering potential innovative suggestions on how to change this reality.

“While we have the knowledge on the strategies needed to reduce stroke burden, the mechanisms needed to implement this knowledge will be different in different countries and cultures. Our commission includes several representatives from low- and middle-income countries, and we will be working with local stakeholders in these countries to try and implement our recommendations,” Dr. Martins explained.
 

Stroke mortality and disability is on the rise

In the report, the authors pointed out that the global burden of stroke is “huge.” In 2020, stroke was the second leading cause of death (6.6 million deaths) and the third leading cause of disability – responsible for 143 million disability-adjusted life-years – after neonatal disorders and ischemic heart disease. Stroke is also a leading cause of depression and dementia.

The absolute number of people affected by stroke, which includes those who die or remain disabled, has almost doubled in the past 30 years, the report authors noted. Most of the contemporary stroke burden is in low- and middle-income countries, and the burden of disability after a stroke is increasing at a faster pace in low- and middle-income countries than in high-income countries. Alarmingly, the incidence of stroke is increasing in young and middle-aged people globally.

The commission forecasts the burden of stroke from 2020 to 2050, with projections estimating that stroke mortality will increase by 50% to 9.7 million and disability-adjusted life-years growing to over 189.3 million by 2050.

“Stroke exerts an enormous toll on the world’s population, leading to the death and permanent disability of millions of people each year, and costing billions of dollars,” said Valery L. Feigin, MD, of Auckland (New Zealand) University of Technology, and commission cochair. “Precisely forecasting the health and economic impacts of stroke decades into the future is inherently challenging given the levels of uncertainty involved, but these estimates are indicative of the ever-increasing burden we will see in the years ahead unless urgent, effective action is taken.”

The report authors explained that multiple factors contribute to the high burden of stroke in low- and middle-income countries, including undetected and uncontrolled hypertension; lack of easily accessible, high-quality health services; insufficient attention to and investment in prevention, air pollution; population growth; unhealthy lifestyles (for example, poor diet, smoking, sedentary lifestyle, obesity); an earlier age of stroke onset and greater proportion of hemorrhagic strokes than in high-income countries; and the burden of infectious diseases resulting in competition for limited health care resources.
 

The enormous financial cost of stroke

The total cost of stroke (both direct treatment and rehabilitation costs and indirect costs due to loss of income) is estimated to rise from $891 billion per year in 2017 to as much as $2.31 trillion by 2050. “These substantial increases in the costs associated with stroke will cause distressing financial circumstances for many communities and national health systems,” the authors said.

However, this increase can be avoided because stroke is highly preventable and treatable, they stressed. “These unsustainable trends in burden and costs of stroke underline the importance of identifying interventions to prevent and manage stroke more effectively.”

The Commission pointed out that population-wide primary prevention across the lifespan is extremely cost effective. It has been estimated that for every $1 spent on the prevention of stroke and cardiovascular disease, there is a more than $10 return on investment.

Additionally, primary prevention efforts directed at stroke would probably yield large gains because of the secondary effects of reducing the risk for heart disease, type 2 diabetes, dementia, and some types of cancer that share common risk factors, the authors noted.

“One of the most common problems in implementing stroke prevention and care recommendations is the lack of funding. Our commission recommends introducing legislative regulations and taxations of unhealthy products (such as salt, alcohol, sugary drinks, trans fats) by each and every government in the world,” Dr. Feigin said.

“Such taxation would not only reduce consumption of these products – and therefore lead to the reduction of burden from stroke and major other noncommunicable diseases – but also generate a large revenue sufficient to fund not only prevention programs and services for stroke and other major disorders, but also reduce poverty, inequality in health service provision, and improve wellbeing of the population,” he added.
 

Recommendations

The commission authors made the following recommendations for key priorities to reduce the burden of stroke:

Surveillance and prevention

• Incorporate stroke events and risk factor surveillance into national stroke action plans.
• Establish a system for population-wide primary and secondary stroke prevention, with emphasis on lifestyle modification for people at any level of risk of stroke and cardiovascular disease.
• Primary and secondary stroke prevention services should be freely accessible and supported by universal health coverage, with access to affordable drugs for management of hypertension, dyslipidemia, diabetes, and clotting disorders.
• Governments must allocate a fixed proportion of their annual health care funding for prevention of stroke and related noncommunicable diseases. This funding could come from taxation of tobacco, salt, alcohol, and sugar.
• Raise public awareness and take action to encourage a healthy lifestyle and prevent stroke via population-wide deployment of digital technologies with simple, inexpensive screening for cardiovascular disease and modifiable risk factors.
• Establish protocol-based shifting of tasks from highly trained health care professionals to supervised paramedical health care workers, to facilitate population-wide primary stroke prevention interventions across rural and urban settings.

Acute care

• Prioritize effective planning of acute stroke care services; capacity building, training, and certification of a multidisciplinary workforce; provision of evidence-based equipment and affordable medicines; and adequate resource allocation at national and regional levels.
• Establish regional networks and protocol-driven services, including community-wide awareness campaigns for early recognition of a stroke, regionally coordinated prehospital services, telemedicine networks, and stroke centers that can triage and treat all cases of acute stroke, and facilitate timely access to reperfusion therapy.
• Integrate acute care networks into the four pillars of the stroke “quadrangle” of resources, including surveillance, prevention, and rehabilitation services, by involving all relevant stakeholders (that is, communities, policy makers, nongovernmental organizations, national and regional stroke organizations, and public and private health care providers) in the stroke care continuum.

Rehabilitation

• Establish multidisciplinary rehabilitation services and adapt evidence-based recommendations to the local context, including the training, support, and supervision of community health care workers and caregivers to assist in long-term care.
• Invest in research to generate innovative low-cost interventions, in public awareness to improve demand for rehabilitation services, and in advocacy to mobilize resources for multidisciplinary rehabilitation.
• Promote the training of stroke rehabilitation professionals. Use digital portals to improve training and to extend the use of assessment tools – such as the Modified Rankin Scale and the U.S. National Institutes of Health Stroke Scale – and quality of life measures to assess functional impairment and monitor recovery.

The commission concluded that, “overall, if the recommendations of this Commission are implemented, the burden of stroke will be reduced substantially ... which will improve brain health and overall wellbeing worldwide.”

Dr. Martins said that the WSO is committed to supporting and accelerating the implementation of these recommendations globally through the WSO Implementation Task Force, with stroke experts to advise the establishment of stroke prevention and care and to contribute with educational programs, and through Global Stroke Alliance meetings facilitating the discussions between stroke experts and policy makers, giving technical support to governments to elaborate national plans for stroke and to include stroke care in universal health coverage packages.

The Commission received funding from the WSO, Bill and Melinda Gates Foundation, Health Research Council of New Zealand, and National Health & Medical Research Council of Australia and was supported by the NIH.

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

Deaths and disability because of stroke are expected to rise alarmingly over the next 30 years, with almost 10 million stroke deaths forecast annually by 2050, according to a new report from the World Stroke Organization–Lancet Neurology Commission Stroke Collaboration Group.

“This highlights the need for urgent measures to reduce stroke burden worldwide, with an emphasis on low- and middle-income countries,” the report authors stated.

These measures include an increase in trained health care workers who can implement effective primary prevention strategies, including the early detection and adequate management of hypertension.

On the basis of a review of evidence-based guidelines, recent surveys, and in-depth interviews with stroke experts around the world, the WSO–Lancet Neurology Commission made evidence-based pragmatic recommendations to reduce the global burden of stroke, including measures to improve surveillance, prevention, acute care, and rehabilitation.

The report was announced on Oct. 10 by WSO President, Sheila Martins, MD, at the World Stroke Conference in Toronto. The report was also published online in The Lancet Neurology.

“Stroke care has changed a lot in the last few years,” said Dr. Martins, who is chief of neurology and neurosurgery at Hospital Moinhos de Vento, Porto Alegre, Brazil, and founder and president of the Brazilian Stroke Network. “We know what we need to do to reduce the global burden of stroke, and high-income countries are making progress in that regard. But the situation in low- and middle-income countries is catastrophic, with mortality rates of up to 80% in individuals who have had a stroke in some countries. There is a very large gap between knowledge and implementation.”

Dr. Martins said that the commission is offering potential innovative suggestions on how to change this reality.

“While we have the knowledge on the strategies needed to reduce stroke burden, the mechanisms needed to implement this knowledge will be different in different countries and cultures. Our commission includes several representatives from low- and middle-income countries, and we will be working with local stakeholders in these countries to try and implement our recommendations,” Dr. Martins explained.
 

Stroke mortality and disability is on the rise

In the report, the authors pointed out that the global burden of stroke is “huge.” In 2020, stroke was the second leading cause of death (6.6 million deaths) and the third leading cause of disability – responsible for 143 million disability-adjusted life-years – after neonatal disorders and ischemic heart disease. Stroke is also a leading cause of depression and dementia.

The absolute number of people affected by stroke, which includes those who die or remain disabled, has almost doubled in the past 30 years, the report authors noted. Most of the contemporary stroke burden is in low- and middle-income countries, and the burden of disability after a stroke is increasing at a faster pace in low- and middle-income countries than in high-income countries. Alarmingly, the incidence of stroke is increasing in young and middle-aged people globally.

The commission forecasts the burden of stroke from 2020 to 2050, with projections estimating that stroke mortality will increase by 50% to 9.7 million and disability-adjusted life-years growing to over 189.3 million by 2050.

“Stroke exerts an enormous toll on the world’s population, leading to the death and permanent disability of millions of people each year, and costing billions of dollars,” said Valery L. Feigin, MD, of Auckland (New Zealand) University of Technology, and commission cochair. “Precisely forecasting the health and economic impacts of stroke decades into the future is inherently challenging given the levels of uncertainty involved, but these estimates are indicative of the ever-increasing burden we will see in the years ahead unless urgent, effective action is taken.”

The report authors explained that multiple factors contribute to the high burden of stroke in low- and middle-income countries, including undetected and uncontrolled hypertension; lack of easily accessible, high-quality health services; insufficient attention to and investment in prevention, air pollution; population growth; unhealthy lifestyles (for example, poor diet, smoking, sedentary lifestyle, obesity); an earlier age of stroke onset and greater proportion of hemorrhagic strokes than in high-income countries; and the burden of infectious diseases resulting in competition for limited health care resources.
 

The enormous financial cost of stroke

The total cost of stroke (both direct treatment and rehabilitation costs and indirect costs due to loss of income) is estimated to rise from $891 billion per year in 2017 to as much as $2.31 trillion by 2050. “These substantial increases in the costs associated with stroke will cause distressing financial circumstances for many communities and national health systems,” the authors said.

However, this increase can be avoided because stroke is highly preventable and treatable, they stressed. “These unsustainable trends in burden and costs of stroke underline the importance of identifying interventions to prevent and manage stroke more effectively.”

The Commission pointed out that population-wide primary prevention across the lifespan is extremely cost effective. It has been estimated that for every $1 spent on the prevention of stroke and cardiovascular disease, there is a more than $10 return on investment.

Additionally, primary prevention efforts directed at stroke would probably yield large gains because of the secondary effects of reducing the risk for heart disease, type 2 diabetes, dementia, and some types of cancer that share common risk factors, the authors noted.

“One of the most common problems in implementing stroke prevention and care recommendations is the lack of funding. Our commission recommends introducing legislative regulations and taxations of unhealthy products (such as salt, alcohol, sugary drinks, trans fats) by each and every government in the world,” Dr. Feigin said.

“Such taxation would not only reduce consumption of these products – and therefore lead to the reduction of burden from stroke and major other noncommunicable diseases – but also generate a large revenue sufficient to fund not only prevention programs and services for stroke and other major disorders, but also reduce poverty, inequality in health service provision, and improve wellbeing of the population,” he added.
 

Recommendations

The commission authors made the following recommendations for key priorities to reduce the burden of stroke:

Surveillance and prevention

• Incorporate stroke events and risk factor surveillance into national stroke action plans.
• Establish a system for population-wide primary and secondary stroke prevention, with emphasis on lifestyle modification for people at any level of risk of stroke and cardiovascular disease.
• Primary and secondary stroke prevention services should be freely accessible and supported by universal health coverage, with access to affordable drugs for management of hypertension, dyslipidemia, diabetes, and clotting disorders.
• Governments must allocate a fixed proportion of their annual health care funding for prevention of stroke and related noncommunicable diseases. This funding could come from taxation of tobacco, salt, alcohol, and sugar.
• Raise public awareness and take action to encourage a healthy lifestyle and prevent stroke via population-wide deployment of digital technologies with simple, inexpensive screening for cardiovascular disease and modifiable risk factors.
• Establish protocol-based shifting of tasks from highly trained health care professionals to supervised paramedical health care workers, to facilitate population-wide primary stroke prevention interventions across rural and urban settings.

Acute care

• Prioritize effective planning of acute stroke care services; capacity building, training, and certification of a multidisciplinary workforce; provision of evidence-based equipment and affordable medicines; and adequate resource allocation at national and regional levels.
• Establish regional networks and protocol-driven services, including community-wide awareness campaigns for early recognition of a stroke, regionally coordinated prehospital services, telemedicine networks, and stroke centers that can triage and treat all cases of acute stroke, and facilitate timely access to reperfusion therapy.
• Integrate acute care networks into the four pillars of the stroke “quadrangle” of resources, including surveillance, prevention, and rehabilitation services, by involving all relevant stakeholders (that is, communities, policy makers, nongovernmental organizations, national and regional stroke organizations, and public and private health care providers) in the stroke care continuum.

Rehabilitation

• Establish multidisciplinary rehabilitation services and adapt evidence-based recommendations to the local context, including the training, support, and supervision of community health care workers and caregivers to assist in long-term care.
• Invest in research to generate innovative low-cost interventions, in public awareness to improve demand for rehabilitation services, and in advocacy to mobilize resources for multidisciplinary rehabilitation.
• Promote the training of stroke rehabilitation professionals. Use digital portals to improve training and to extend the use of assessment tools – such as the Modified Rankin Scale and the U.S. National Institutes of Health Stroke Scale – and quality of life measures to assess functional impairment and monitor recovery.

The commission concluded that, “overall, if the recommendations of this Commission are implemented, the burden of stroke will be reduced substantially ... which will improve brain health and overall wellbeing worldwide.”

Dr. Martins said that the WSO is committed to supporting and accelerating the implementation of these recommendations globally through the WSO Implementation Task Force, with stroke experts to advise the establishment of stroke prevention and care and to contribute with educational programs, and through Global Stroke Alliance meetings facilitating the discussions between stroke experts and policy makers, giving technical support to governments to elaborate national plans for stroke and to include stroke care in universal health coverage packages.

The Commission received funding from the WSO, Bill and Melinda Gates Foundation, Health Research Council of New Zealand, and National Health & Medical Research Council of Australia and was supported by the NIH.

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

Deaths and disability because of stroke are expected to rise alarmingly over the next 30 years, with almost 10 million stroke deaths forecast annually by 2050, according to a new report from the World Stroke Organization–Lancet Neurology Commission Stroke Collaboration Group.

“This highlights the need for urgent measures to reduce stroke burden worldwide, with an emphasis on low- and middle-income countries,” the report authors stated.

These measures include an increase in trained health care workers who can implement effective primary prevention strategies, including the early detection and adequate management of hypertension.

On the basis of a review of evidence-based guidelines, recent surveys, and in-depth interviews with stroke experts around the world, the WSO–Lancet Neurology Commission made evidence-based pragmatic recommendations to reduce the global burden of stroke, including measures to improve surveillance, prevention, acute care, and rehabilitation.

The report was announced on Oct. 10 by WSO President, Sheila Martins, MD, at the World Stroke Conference in Toronto. The report was also published online in The Lancet Neurology.

“Stroke care has changed a lot in the last few years,” said Dr. Martins, who is chief of neurology and neurosurgery at Hospital Moinhos de Vento, Porto Alegre, Brazil, and founder and president of the Brazilian Stroke Network. “We know what we need to do to reduce the global burden of stroke, and high-income countries are making progress in that regard. But the situation in low- and middle-income countries is catastrophic, with mortality rates of up to 80% in individuals who have had a stroke in some countries. There is a very large gap between knowledge and implementation.”

Dr. Martins said that the commission is offering potential innovative suggestions on how to change this reality.

“While we have the knowledge on the strategies needed to reduce stroke burden, the mechanisms needed to implement this knowledge will be different in different countries and cultures. Our commission includes several representatives from low- and middle-income countries, and we will be working with local stakeholders in these countries to try and implement our recommendations,” Dr. Martins explained.
 

Stroke mortality and disability is on the rise

In the report, the authors pointed out that the global burden of stroke is “huge.” In 2020, stroke was the second leading cause of death (6.6 million deaths) and the third leading cause of disability – responsible for 143 million disability-adjusted life-years – after neonatal disorders and ischemic heart disease. Stroke is also a leading cause of depression and dementia.

The absolute number of people affected by stroke, which includes those who die or remain disabled, has almost doubled in the past 30 years, the report authors noted. Most of the contemporary stroke burden is in low- and middle-income countries, and the burden of disability after a stroke is increasing at a faster pace in low- and middle-income countries than in high-income countries. Alarmingly, the incidence of stroke is increasing in young and middle-aged people globally.

The commission forecasts the burden of stroke from 2020 to 2050, with projections estimating that stroke mortality will increase by 50% to 9.7 million and disability-adjusted life-years growing to over 189.3 million by 2050.

“Stroke exerts an enormous toll on the world’s population, leading to the death and permanent disability of millions of people each year, and costing billions of dollars,” said Valery L. Feigin, MD, of Auckland (New Zealand) University of Technology, and commission cochair. “Precisely forecasting the health and economic impacts of stroke decades into the future is inherently challenging given the levels of uncertainty involved, but these estimates are indicative of the ever-increasing burden we will see in the years ahead unless urgent, effective action is taken.”

The report authors explained that multiple factors contribute to the high burden of stroke in low- and middle-income countries, including undetected and uncontrolled hypertension; lack of easily accessible, high-quality health services; insufficient attention to and investment in prevention, air pollution; population growth; unhealthy lifestyles (for example, poor diet, smoking, sedentary lifestyle, obesity); an earlier age of stroke onset and greater proportion of hemorrhagic strokes than in high-income countries; and the burden of infectious diseases resulting in competition for limited health care resources.
 

The enormous financial cost of stroke

The total cost of stroke (both direct treatment and rehabilitation costs and indirect costs due to loss of income) is estimated to rise from $891 billion per year in 2017 to as much as $2.31 trillion by 2050. “These substantial increases in the costs associated with stroke will cause distressing financial circumstances for many communities and national health systems,” the authors said.

However, this increase can be avoided because stroke is highly preventable and treatable, they stressed. “These unsustainable trends in burden and costs of stroke underline the importance of identifying interventions to prevent and manage stroke more effectively.”

The Commission pointed out that population-wide primary prevention across the lifespan is extremely cost effective. It has been estimated that for every $1 spent on the prevention of stroke and cardiovascular disease, there is a more than $10 return on investment.

Additionally, primary prevention efforts directed at stroke would probably yield large gains because of the secondary effects of reducing the risk for heart disease, type 2 diabetes, dementia, and some types of cancer that share common risk factors, the authors noted.

“One of the most common problems in implementing stroke prevention and care recommendations is the lack of funding. Our commission recommends introducing legislative regulations and taxations of unhealthy products (such as salt, alcohol, sugary drinks, trans fats) by each and every government in the world,” Dr. Feigin said.

“Such taxation would not only reduce consumption of these products – and therefore lead to the reduction of burden from stroke and major other noncommunicable diseases – but also generate a large revenue sufficient to fund not only prevention programs and services for stroke and other major disorders, but also reduce poverty, inequality in health service provision, and improve wellbeing of the population,” he added.
 

Recommendations

The commission authors made the following recommendations for key priorities to reduce the burden of stroke:

Surveillance and prevention

• Incorporate stroke events and risk factor surveillance into national stroke action plans.
• Establish a system for population-wide primary and secondary stroke prevention, with emphasis on lifestyle modification for people at any level of risk of stroke and cardiovascular disease.
• Primary and secondary stroke prevention services should be freely accessible and supported by universal health coverage, with access to affordable drugs for management of hypertension, dyslipidemia, diabetes, and clotting disorders.
• Governments must allocate a fixed proportion of their annual health care funding for prevention of stroke and related noncommunicable diseases. This funding could come from taxation of tobacco, salt, alcohol, and sugar.
• Raise public awareness and take action to encourage a healthy lifestyle and prevent stroke via population-wide deployment of digital technologies with simple, inexpensive screening for cardiovascular disease and modifiable risk factors.
• Establish protocol-based shifting of tasks from highly trained health care professionals to supervised paramedical health care workers, to facilitate population-wide primary stroke prevention interventions across rural and urban settings.

Acute care

• Prioritize effective planning of acute stroke care services; capacity building, training, and certification of a multidisciplinary workforce; provision of evidence-based equipment and affordable medicines; and adequate resource allocation at national and regional levels.
• Establish regional networks and protocol-driven services, including community-wide awareness campaigns for early recognition of a stroke, regionally coordinated prehospital services, telemedicine networks, and stroke centers that can triage and treat all cases of acute stroke, and facilitate timely access to reperfusion therapy.
• Integrate acute care networks into the four pillars of the stroke “quadrangle” of resources, including surveillance, prevention, and rehabilitation services, by involving all relevant stakeholders (that is, communities, policy makers, nongovernmental organizations, national and regional stroke organizations, and public and private health care providers) in the stroke care continuum.

Rehabilitation

• Establish multidisciplinary rehabilitation services and adapt evidence-based recommendations to the local context, including the training, support, and supervision of community health care workers and caregivers to assist in long-term care.
• Invest in research to generate innovative low-cost interventions, in public awareness to improve demand for rehabilitation services, and in advocacy to mobilize resources for multidisciplinary rehabilitation.
• Promote the training of stroke rehabilitation professionals. Use digital portals to improve training and to extend the use of assessment tools – such as the Modified Rankin Scale and the U.S. National Institutes of Health Stroke Scale – and quality of life measures to assess functional impairment and monitor recovery.

The commission concluded that, “overall, if the recommendations of this Commission are implemented, the burden of stroke will be reduced substantially ... which will improve brain health and overall wellbeing worldwide.”

Dr. Martins said that the WSO is committed to supporting and accelerating the implementation of these recommendations globally through the WSO Implementation Task Force, with stroke experts to advise the establishment of stroke prevention and care and to contribute with educational programs, and through Global Stroke Alliance meetings facilitating the discussions between stroke experts and policy makers, giving technical support to governments to elaborate national plans for stroke and to include stroke care in universal health coverage packages.

The Commission received funding from the WSO, Bill and Melinda Gates Foundation, Health Research Council of New Zealand, and National Health & Medical Research Council of Australia and was supported by the NIH.

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

New guidelines on determining brain death offer the first updated recommendations in more than a decade for adult and pediatric patients.

The consensus practice guideline on brain death, also known as death by neurologic criteria (BD/DNC), was developed by a panel of 20 experts from different specialties, institutions, and medical societies.

As with previous guidelines, the updated version stipulates that brain death should be declared when a patient with a known cause of catastrophic brain injury has permanent loss of function of the brain, including the brain stem, which results in coma, brain stem areflexia, and apnea in the setting of an adequate stimulus.

But the updated version also clarifies questions on neurological examinations and apnea testing and offers new guidance on pre-evaluation targets for blood pressure and body temperature and evaluating brain death in patients who are pregnant, are on extracorporeal membrane oxygenation, or have an injury to the base of the brain.

Also, for the first time, the guidance clarifies that clinicians don’t need to obtain consent before performing a brain death evaluation, unless institutional policy, state laws, or regulations stipulate otherwise.

“The 2023 guidelines will be considered the standard of care in the U.S.,” lead author David M. Greer, MD, chair and chief of neurology, Boston University, and chief of neurology, Boston Medical Center, said in an interview. “Each hospital in the U.S. is responsible for its own policy for BD/DNC determination, and our hope is that they will quickly revise their policies in accordance with this new national standard.”

The guidelines, which are accompanied by a three-page checklist and a free digital app, were published online in Neurology.
 

Four years in the making

Work on the 85 recommendations in the new report began more than 4 years ago as a collaborative effort by the American Academy of Neurology, the American Academy of Pediatrics, the Child Neurology Society, and the Society of Critical Care Medicine.

A lack of high-quality evidence on brain death determination led panelists to devise an evidence-informed formal consensus process to develop the guidelines, which involved three rounds of anonymous voting on each recommendation and the rationales behind them.

The strength of each recommendation was based on the level of consensus reached through voting, with Level A denoting a recommendation that “must” be followed, Level B one that “should” be followed, and Level C one that “may” be followed.

The majority of recommendations received an A or B rating. Only one recommendation, about whether a second clinical exam is needed in adults, garnered a C rating.

In children, the guidelines recommend that clinicians must perform two clinical examinations and two apnea tests 12 hours apart. In adults, only one exam is required. Both of those recommendations were rated Level A. A recommendation for a second exam in adults received the single Level C rating.
 

A uniform set of guidelines?

The new guidelines replace adult practice guidance published by AAN in 2010 and guideline for infants and children released in 2011 by AAP, CNS, and SCCM, and for the first time combine brain death guidelines for adult and pediatric patients into one document.

“It is important for clinicians to review the new guideline carefully and ensure their hospital brain death guidelines are updated to be consistent with the new guideline in order to prevent inaccurate determinations of death,” guidelines coauthor Ariane Lewis, MD, NYU Langone Health, New York, said in an interview.

The 1981 Uniform Determination of Death Act (UDDA) is the legal foundation for the declaration of BD/DNC in the United States, but it only stipulates that brain death determination must be made in accordance with accepted medical standards.

There is no single national standard, and states and hospitals are free to adopt their own, which many have done. One goal of the new guidelines was to create a uniform set of guidelines that all institutions follow.

“This is a step toward having a set of guidelines that are accepted by most of the societies and clinical specialties involved in this sort of diagnosis,” that could lead to a national-level policy, Fernando Goldenberg, MD, professor of neurology and director of neuroscience critical care, University of Chicago Medicine, said in an interview.

Dr. Goldenberg was not part of the panel that developed the updated guidelines, but was a coauthor of a consensus statement from the World Brain Death Project in 2020.

Developing a singular global guideline for brain death determination is unlikely, Dr. Goldenberg said. Policies vary widely across the world, and some countries don’t even recognize brain death.

“But this attempts to unify things at the U.S. level, which is very important,” he said.
 

Permanent vs. irreversible

Dr. Goldenberg said that combining adult and pediatric guidelines into one document will be very helpful for clinicians like him who treat patients from age 16 years and up.

The expanded guidance on apnea testing, recommendations on specific ancillary tests to use or avoid, and inclusion of language stipulating that prior consent is not needed to perform a brain death evaluation are also useful.

He also noted that the section on credentialing and training of clinicians who perform BD/DNC evaluations recognizes advanced practice providers, the first time he recalls seeing these professionals included in brain death guidelines.

However, the panel’s decision to use the term “permanent” to describe loss of brain function instead of “irreversible” gave Dr. Goldenberg pause.

The UDDA provides that an individual is declared legally dead when “circulatory and respiratory functions irreversibly stop; or all functions of the entire brain, including the brain stem, irreversibly stop.”

Earlier in October, the American College of Physicians released a position paper on cardiorespiratory death determination that called for a revision of the UDDA language.

The ACP suggested that “irreversibly” be replaced with “permanently” with regard to the cessation of circulatory and respiratory functions, but that “irreversible” be kept in the description of brain death.

“Permanent means that there is damage that is potentially reversible and irreversible means that the damage is so profound, it cannot be reversed even if an attempt to do so is performed,” Dr. Goldenberg said.

Even though the World Brain Death Project, on which he worked, also used “permanent” to describe brain function loss, Dr. Goldenberg said he aligns with ACP’s position.

“The understanding of brain death is that the damage is so profound, it is irreversible, even if you were to try,” he said. “Therefore, I think that the most appropriate term for brain death should be irreversible as opposed to permanent.”

The report was funded by the American Academy of Neurology. Dr. Greer has received travel funding from Boston University; serves as editor-in-chief for Seminars in Neurology; receives publishing royalties for 50 Studies Every Neurologist Should Know and Successful Leadership in Academic Medicine; has received honoraria from AAN; has received research funding from Becton, Dickinson, and Company; and has served as expert witness in legal proceedings. Dr. Lewis has received honoraria from AAN and Neurodiem, serves as Neurology deputy editor of disputes and debates, and serves as deputy editor of seminars in Neurology. Dr. Goldenberg reported no relevant financial relationships.

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

New guidelines on determining brain death offer the first updated recommendations in more than a decade for adult and pediatric patients.

The consensus practice guideline on brain death, also known as death by neurologic criteria (BD/DNC), was developed by a panel of 20 experts from different specialties, institutions, and medical societies.

As with previous guidelines, the updated version stipulates that brain death should be declared when a patient with a known cause of catastrophic brain injury has permanent loss of function of the brain, including the brain stem, which results in coma, brain stem areflexia, and apnea in the setting of an adequate stimulus.

But the updated version also clarifies questions on neurological examinations and apnea testing and offers new guidance on pre-evaluation targets for blood pressure and body temperature and evaluating brain death in patients who are pregnant, are on extracorporeal membrane oxygenation, or have an injury to the base of the brain.

Also, for the first time, the guidance clarifies that clinicians don’t need to obtain consent before performing a brain death evaluation, unless institutional policy, state laws, or regulations stipulate otherwise.

“The 2023 guidelines will be considered the standard of care in the U.S.,” lead author David M. Greer, MD, chair and chief of neurology, Boston University, and chief of neurology, Boston Medical Center, said in an interview. “Each hospital in the U.S. is responsible for its own policy for BD/DNC determination, and our hope is that they will quickly revise their policies in accordance with this new national standard.”

The guidelines, which are accompanied by a three-page checklist and a free digital app, were published online in Neurology.
 

Four years in the making

Work on the 85 recommendations in the new report began more than 4 years ago as a collaborative effort by the American Academy of Neurology, the American Academy of Pediatrics, the Child Neurology Society, and the Society of Critical Care Medicine.

A lack of high-quality evidence on brain death determination led panelists to devise an evidence-informed formal consensus process to develop the guidelines, which involved three rounds of anonymous voting on each recommendation and the rationales behind them.

The strength of each recommendation was based on the level of consensus reached through voting, with Level A denoting a recommendation that “must” be followed, Level B one that “should” be followed, and Level C one that “may” be followed.

The majority of recommendations received an A or B rating. Only one recommendation, about whether a second clinical exam is needed in adults, garnered a C rating.

In children, the guidelines recommend that clinicians must perform two clinical examinations and two apnea tests 12 hours apart. In adults, only one exam is required. Both of those recommendations were rated Level A. A recommendation for a second exam in adults received the single Level C rating.
 

A uniform set of guidelines?

The new guidelines replace adult practice guidance published by AAN in 2010 and guideline for infants and children released in 2011 by AAP, CNS, and SCCM, and for the first time combine brain death guidelines for adult and pediatric patients into one document.

“It is important for clinicians to review the new guideline carefully and ensure their hospital brain death guidelines are updated to be consistent with the new guideline in order to prevent inaccurate determinations of death,” guidelines coauthor Ariane Lewis, MD, NYU Langone Health, New York, said in an interview.

The 1981 Uniform Determination of Death Act (UDDA) is the legal foundation for the declaration of BD/DNC in the United States, but it only stipulates that brain death determination must be made in accordance with accepted medical standards.

There is no single national standard, and states and hospitals are free to adopt their own, which many have done. One goal of the new guidelines was to create a uniform set of guidelines that all institutions follow.

“This is a step toward having a set of guidelines that are accepted by most of the societies and clinical specialties involved in this sort of diagnosis,” that could lead to a national-level policy, Fernando Goldenberg, MD, professor of neurology and director of neuroscience critical care, University of Chicago Medicine, said in an interview.

Dr. Goldenberg was not part of the panel that developed the updated guidelines, but was a coauthor of a consensus statement from the World Brain Death Project in 2020.

Developing a singular global guideline for brain death determination is unlikely, Dr. Goldenberg said. Policies vary widely across the world, and some countries don’t even recognize brain death.

“But this attempts to unify things at the U.S. level, which is very important,” he said.
 

Permanent vs. irreversible

Dr. Goldenberg said that combining adult and pediatric guidelines into one document will be very helpful for clinicians like him who treat patients from age 16 years and up.

The expanded guidance on apnea testing, recommendations on specific ancillary tests to use or avoid, and inclusion of language stipulating that prior consent is not needed to perform a brain death evaluation are also useful.

He also noted that the section on credentialing and training of clinicians who perform BD/DNC evaluations recognizes advanced practice providers, the first time he recalls seeing these professionals included in brain death guidelines.

However, the panel’s decision to use the term “permanent” to describe loss of brain function instead of “irreversible” gave Dr. Goldenberg pause.

The UDDA provides that an individual is declared legally dead when “circulatory and respiratory functions irreversibly stop; or all functions of the entire brain, including the brain stem, irreversibly stop.”

Earlier in October, the American College of Physicians released a position paper on cardiorespiratory death determination that called for a revision of the UDDA language.

The ACP suggested that “irreversibly” be replaced with “permanently” with regard to the cessation of circulatory and respiratory functions, but that “irreversible” be kept in the description of brain death.

“Permanent means that there is damage that is potentially reversible and irreversible means that the damage is so profound, it cannot be reversed even if an attempt to do so is performed,” Dr. Goldenberg said.

Even though the World Brain Death Project, on which he worked, also used “permanent” to describe brain function loss, Dr. Goldenberg said he aligns with ACP’s position.

“The understanding of brain death is that the damage is so profound, it is irreversible, even if you were to try,” he said. “Therefore, I think that the most appropriate term for brain death should be irreversible as opposed to permanent.”

The report was funded by the American Academy of Neurology. Dr. Greer has received travel funding from Boston University; serves as editor-in-chief for Seminars in Neurology; receives publishing royalties for 50 Studies Every Neurologist Should Know and Successful Leadership in Academic Medicine; has received honoraria from AAN; has received research funding from Becton, Dickinson, and Company; and has served as expert witness in legal proceedings. Dr. Lewis has received honoraria from AAN and Neurodiem, serves as Neurology deputy editor of disputes and debates, and serves as deputy editor of seminars in Neurology. Dr. Goldenberg reported no relevant financial relationships.

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

New guidelines on determining brain death offer the first updated recommendations in more than a decade for adult and pediatric patients.

The consensus practice guideline on brain death, also known as death by neurologic criteria (BD/DNC), was developed by a panel of 20 experts from different specialties, institutions, and medical societies.

As with previous guidelines, the updated version stipulates that brain death should be declared when a patient with a known cause of catastrophic brain injury has permanent loss of function of the brain, including the brain stem, which results in coma, brain stem areflexia, and apnea in the setting of an adequate stimulus.

But the updated version also clarifies questions on neurological examinations and apnea testing and offers new guidance on pre-evaluation targets for blood pressure and body temperature and evaluating brain death in patients who are pregnant, are on extracorporeal membrane oxygenation, or have an injury to the base of the brain.

Also, for the first time, the guidance clarifies that clinicians don’t need to obtain consent before performing a brain death evaluation, unless institutional policy, state laws, or regulations stipulate otherwise.

“The 2023 guidelines will be considered the standard of care in the U.S.,” lead author David M. Greer, MD, chair and chief of neurology, Boston University, and chief of neurology, Boston Medical Center, said in an interview. “Each hospital in the U.S. is responsible for its own policy for BD/DNC determination, and our hope is that they will quickly revise their policies in accordance with this new national standard.”

The guidelines, which are accompanied by a three-page checklist and a free digital app, were published online in Neurology.
 

Four years in the making

Work on the 85 recommendations in the new report began more than 4 years ago as a collaborative effort by the American Academy of Neurology, the American Academy of Pediatrics, the Child Neurology Society, and the Society of Critical Care Medicine.

A lack of high-quality evidence on brain death determination led panelists to devise an evidence-informed formal consensus process to develop the guidelines, which involved three rounds of anonymous voting on each recommendation and the rationales behind them.

The strength of each recommendation was based on the level of consensus reached through voting, with Level A denoting a recommendation that “must” be followed, Level B one that “should” be followed, and Level C one that “may” be followed.

The majority of recommendations received an A or B rating. Only one recommendation, about whether a second clinical exam is needed in adults, garnered a C rating.

In children, the guidelines recommend that clinicians must perform two clinical examinations and two apnea tests 12 hours apart. In adults, only one exam is required. Both of those recommendations were rated Level A. A recommendation for a second exam in adults received the single Level C rating.
 

A uniform set of guidelines?

The new guidelines replace adult practice guidance published by AAN in 2010 and guideline for infants and children released in 2011 by AAP, CNS, and SCCM, and for the first time combine brain death guidelines for adult and pediatric patients into one document.

“It is important for clinicians to review the new guideline carefully and ensure their hospital brain death guidelines are updated to be consistent with the new guideline in order to prevent inaccurate determinations of death,” guidelines coauthor Ariane Lewis, MD, NYU Langone Health, New York, said in an interview.

The 1981 Uniform Determination of Death Act (UDDA) is the legal foundation for the declaration of BD/DNC in the United States, but it only stipulates that brain death determination must be made in accordance with accepted medical standards.

There is no single national standard, and states and hospitals are free to adopt their own, which many have done. One goal of the new guidelines was to create a uniform set of guidelines that all institutions follow.

“This is a step toward having a set of guidelines that are accepted by most of the societies and clinical specialties involved in this sort of diagnosis,” that could lead to a national-level policy, Fernando Goldenberg, MD, professor of neurology and director of neuroscience critical care, University of Chicago Medicine, said in an interview.

Dr. Goldenberg was not part of the panel that developed the updated guidelines, but was a coauthor of a consensus statement from the World Brain Death Project in 2020.

Developing a singular global guideline for brain death determination is unlikely, Dr. Goldenberg said. Policies vary widely across the world, and some countries don’t even recognize brain death.

“But this attempts to unify things at the U.S. level, which is very important,” he said.
 

Permanent vs. irreversible

Dr. Goldenberg said that combining adult and pediatric guidelines into one document will be very helpful for clinicians like him who treat patients from age 16 years and up.

The expanded guidance on apnea testing, recommendations on specific ancillary tests to use or avoid, and inclusion of language stipulating that prior consent is not needed to perform a brain death evaluation are also useful.

He also noted that the section on credentialing and training of clinicians who perform BD/DNC evaluations recognizes advanced practice providers, the first time he recalls seeing these professionals included in brain death guidelines.

However, the panel’s decision to use the term “permanent” to describe loss of brain function instead of “irreversible” gave Dr. Goldenberg pause.

The UDDA provides that an individual is declared legally dead when “circulatory and respiratory functions irreversibly stop; or all functions of the entire brain, including the brain stem, irreversibly stop.”

Earlier in October, the American College of Physicians released a position paper on cardiorespiratory death determination that called for a revision of the UDDA language.

The ACP suggested that “irreversibly” be replaced with “permanently” with regard to the cessation of circulatory and respiratory functions, but that “irreversible” be kept in the description of brain death.

“Permanent means that there is damage that is potentially reversible and irreversible means that the damage is so profound, it cannot be reversed even if an attempt to do so is performed,” Dr. Goldenberg said.

Even though the World Brain Death Project, on which he worked, also used “permanent” to describe brain function loss, Dr. Goldenberg said he aligns with ACP’s position.

“The understanding of brain death is that the damage is so profound, it is irreversible, even if you were to try,” he said. “Therefore, I think that the most appropriate term for brain death should be irreversible as opposed to permanent.”

The report was funded by the American Academy of Neurology. Dr. Greer has received travel funding from Boston University; serves as editor-in-chief for Seminars in Neurology; receives publishing royalties for 50 Studies Every Neurologist Should Know and Successful Leadership in Academic Medicine; has received honoraria from AAN; has received research funding from Becton, Dickinson, and Company; and has served as expert witness in legal proceedings. Dr. Lewis has received honoraria from AAN and Neurodiem, serves as Neurology deputy editor of disputes and debates, and serves as deputy editor of seminars in Neurology. Dr. Goldenberg reported no relevant financial relationships.

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

Each additional decade of type 2 diabetes shortens lives by about 3.5 years, compared with not having diabetes, researchers estimate on the basis of data from studies conducted in 19 high-income countries.

They estimated that, among 50-year-olds, life expectancy of those diagnosed with type 2 diabetes at age 30 is 14 years shorter than that of their peers without diabetes. Among those diagnosed at age 50, life expectancy is 6 years shorter.

The study was recently published in The Lancet – Diabetes and Endocrinology.

The team analyzed data from the Emerging Risk Factors Collaboration and the UK Biobank. The data were from 97 long-term, prospective cohorts and involved 1.5 million participants who were followed for 23.1 million person-years.

“The strongest associations with earlier age at diagnosis of diabetes were for vascular (for example, myocardial infarction and stroke) and other causes of death – mainly respiratory, neurological, and infectious diseases and external causes,” they reported.

Their findings are consistent with previous studies that suggested that younger individuals who develop type 2 diabetes might have higher body mass index (BMI), blood pressure, and lipid levels and that they might experience faster deterioration in glycemic control than individuals who develop diabetes later, potentially leading to premature mortality.

Asked to comment, Anne Peters, MD, director of clinical diabetes programs at the University of Southern California, Los Angeles, who was not involved with this study, said: “We’ve long known that diabetes reduces life expectancy, and the younger you get it the more years you lose. However, this study was from a broader and larger population base than prior studies.

“In this study, the major reason for death was vascular disease, and undertreatment of cardiovascular risk factors may have occurred in the younger individuals. We also don’t know about glucose control.

“I personally think the findings show that we should treat cardiovascular risk factors more aggressively in people diagnosed with [type 2] diabetes in their 30s and 40s,” urged Dr. Peters.
 

High priority should be given to prevention globally

“Type 2 diabetes used to be seen as a disease that affected older adults, but we’re increasingly seeing people diagnosed earlier in life,” senior author Emanuele Di Angelantonio, MD, PhD, from the University of Cambridge (England), explained in a press release. “As we’ve shown, this means they are at risk of a much shorter life expectancy than they would otherwise have.”

The findings suggest that “high priority should be given to developing and implementing interventions that prevent or delay the onset of [type 2 diabetes], especially as its prevalence among younger age groups is increasing globally,” the study authors wrote.

The results “support the idea that the younger an individual is when they develop type 2 diabetes, the more damage their body accumulates from its impaired metabolism,” added co–senior author Naveed Sattar, MD, PhD, of the University of Glasgow,

Dr. Peters agreed: “People who develop type 2 diabetes at a younger age might have a different, potentially more aggressive type of type 2 diabetes and perhaps need treatment targets that are lower than people who develop type 2 diabetes when they are older.”

“The findings ... suggest that early detection of diabetes by screening followed by intensive glucose management could help prevent long-term complications from the condition,” Dr. Sattar said.

Dr. Peters added: “An issue for some is pregnancy. ... Many of the medications taken for management of CVD [cardiovascular disease] risk factors are contraindicated in pregnancy (as are many of the medications [for treating type 2 diabetes]).

“We need to be careful to risk reduce but take care of the ‘whole person,’ and if of childbearing age, consider the safest approaches to healthy management,” she emphasized.
 

Study results: Type 2 diabetes diagnosed at age 30, 40, and 50

Previous studies estimated that adults with type 2 diabetes die 6 years earlier on average in comparison with their counterparts who do not have diabetes, but it was not known how diabetes duration affects life span.

To investigate this, the team analyzed individual records from the Emerging Risk Factors Collaboration and the UK Biobank. The primary outcome was all-cause mortality. Other outcomes were deaths from CVD, cancer, and other causes.

Over a median follow-up of 12.5 years, there were 246,670 deaths: 84,443 from cardiovascular causes, 150, 972 from noncardiovascular causes, and 11,255 from unknown/ill-defined causes.

Compared with participants who did not have a history of type 2 diabetes, the hazard ratios for all-cause mortality, adjusted for age and sex, were 2.69 for participants diagnosed at age 30-39, 2.26 for those diagnosed aged 40-49, 1.84 aged 50-59, 1.57 for those aged 60-69, and 1.39 for those diagnosed 70 and older.

These hazard ratios were similar after adjusting for BMI, systolic blood pressure, and total cholesterol, but they were substantially attenuated after further adjusting for fasting glucose or hemoglobin A1c level.

Similar patterns were observed for cause-specific mortality.

“Every decade of earlier diagnosis of diabetes was associated with about 3-4 years of lower life expectancy, highlighting the need to develop and implement interventions that prevent or delay the onset of diabetes and to intensify the treatment of risk factors among young adults diagnosed with diabetes,” the researchers wrote.

The study was funded the British Heart Foundation, the Medical Research Council, the National Institute for Health and Care Research, and Health Data Research UK. Dr. Peters is on advisory boards for Vertex, Eli Lilly, and Medscape, receives research funding from Abbott Diabetes Care and Insulet, and has stock options for Omada Health.

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

Each additional decade of type 2 diabetes shortens lives by about 3.5 years, compared with not having diabetes, researchers estimate on the basis of data from studies conducted in 19 high-income countries.

They estimated that, among 50-year-olds, life expectancy of those diagnosed with type 2 diabetes at age 30 is 14 years shorter than that of their peers without diabetes. Among those diagnosed at age 50, life expectancy is 6 years shorter.

The study was recently published in The Lancet – Diabetes and Endocrinology.

The team analyzed data from the Emerging Risk Factors Collaboration and the UK Biobank. The data were from 97 long-term, prospective cohorts and involved 1.5 million participants who were followed for 23.1 million person-years.

“The strongest associations with earlier age at diagnosis of diabetes were for vascular (for example, myocardial infarction and stroke) and other causes of death – mainly respiratory, neurological, and infectious diseases and external causes,” they reported.

Their findings are consistent with previous studies that suggested that younger individuals who develop type 2 diabetes might have higher body mass index (BMI), blood pressure, and lipid levels and that they might experience faster deterioration in glycemic control than individuals who develop diabetes later, potentially leading to premature mortality.

Asked to comment, Anne Peters, MD, director of clinical diabetes programs at the University of Southern California, Los Angeles, who was not involved with this study, said: “We’ve long known that diabetes reduces life expectancy, and the younger you get it the more years you lose. However, this study was from a broader and larger population base than prior studies.

“In this study, the major reason for death was vascular disease, and undertreatment of cardiovascular risk factors may have occurred in the younger individuals. We also don’t know about glucose control.

“I personally think the findings show that we should treat cardiovascular risk factors more aggressively in people diagnosed with [type 2] diabetes in their 30s and 40s,” urged Dr. Peters.
 

High priority should be given to prevention globally

“Type 2 diabetes used to be seen as a disease that affected older adults, but we’re increasingly seeing people diagnosed earlier in life,” senior author Emanuele Di Angelantonio, MD, PhD, from the University of Cambridge (England), explained in a press release. “As we’ve shown, this means they are at risk of a much shorter life expectancy than they would otherwise have.”

The findings suggest that “high priority should be given to developing and implementing interventions that prevent or delay the onset of [type 2 diabetes], especially as its prevalence among younger age groups is increasing globally,” the study authors wrote.

The results “support the idea that the younger an individual is when they develop type 2 diabetes, the more damage their body accumulates from its impaired metabolism,” added co–senior author Naveed Sattar, MD, PhD, of the University of Glasgow,

Dr. Peters agreed: “People who develop type 2 diabetes at a younger age might have a different, potentially more aggressive type of type 2 diabetes and perhaps need treatment targets that are lower than people who develop type 2 diabetes when they are older.”

“The findings ... suggest that early detection of diabetes by screening followed by intensive glucose management could help prevent long-term complications from the condition,” Dr. Sattar said.

Dr. Peters added: “An issue for some is pregnancy. ... Many of the medications taken for management of CVD [cardiovascular disease] risk factors are contraindicated in pregnancy (as are many of the medications [for treating type 2 diabetes]).

“We need to be careful to risk reduce but take care of the ‘whole person,’ and if of childbearing age, consider the safest approaches to healthy management,” she emphasized.
 

Study results: Type 2 diabetes diagnosed at age 30, 40, and 50

Previous studies estimated that adults with type 2 diabetes die 6 years earlier on average in comparison with their counterparts who do not have diabetes, but it was not known how diabetes duration affects life span.

To investigate this, the team analyzed individual records from the Emerging Risk Factors Collaboration and the UK Biobank. The primary outcome was all-cause mortality. Other outcomes were deaths from CVD, cancer, and other causes.

Over a median follow-up of 12.5 years, there were 246,670 deaths: 84,443 from cardiovascular causes, 150, 972 from noncardiovascular causes, and 11,255 from unknown/ill-defined causes.

Compared with participants who did not have a history of type 2 diabetes, the hazard ratios for all-cause mortality, adjusted for age and sex, were 2.69 for participants diagnosed at age 30-39, 2.26 for those diagnosed aged 40-49, 1.84 aged 50-59, 1.57 for those aged 60-69, and 1.39 for those diagnosed 70 and older.

These hazard ratios were similar after adjusting for BMI, systolic blood pressure, and total cholesterol, but they were substantially attenuated after further adjusting for fasting glucose or hemoglobin A1c level.

Similar patterns were observed for cause-specific mortality.

“Every decade of earlier diagnosis of diabetes was associated with about 3-4 years of lower life expectancy, highlighting the need to develop and implement interventions that prevent or delay the onset of diabetes and to intensify the treatment of risk factors among young adults diagnosed with diabetes,” the researchers wrote.

The study was funded the British Heart Foundation, the Medical Research Council, the National Institute for Health and Care Research, and Health Data Research UK. Dr. Peters is on advisory boards for Vertex, Eli Lilly, and Medscape, receives research funding from Abbott Diabetes Care and Insulet, and has stock options for Omada Health.

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

Each additional decade of type 2 diabetes shortens lives by about 3.5 years, compared with not having diabetes, researchers estimate on the basis of data from studies conducted in 19 high-income countries.

They estimated that, among 50-year-olds, life expectancy of those diagnosed with type 2 diabetes at age 30 is 14 years shorter than that of their peers without diabetes. Among those diagnosed at age 50, life expectancy is 6 years shorter.

The study was recently published in The Lancet – Diabetes and Endocrinology.

The team analyzed data from the Emerging Risk Factors Collaboration and the UK Biobank. The data were from 97 long-term, prospective cohorts and involved 1.5 million participants who were followed for 23.1 million person-years.

“The strongest associations with earlier age at diagnosis of diabetes were for vascular (for example, myocardial infarction and stroke) and other causes of death – mainly respiratory, neurological, and infectious diseases and external causes,” they reported.

Their findings are consistent with previous studies that suggested that younger individuals who develop type 2 diabetes might have higher body mass index (BMI), blood pressure, and lipid levels and that they might experience faster deterioration in glycemic control than individuals who develop diabetes later, potentially leading to premature mortality.

Asked to comment, Anne Peters, MD, director of clinical diabetes programs at the University of Southern California, Los Angeles, who was not involved with this study, said: “We’ve long known that diabetes reduces life expectancy, and the younger you get it the more years you lose. However, this study was from a broader and larger population base than prior studies.

“In this study, the major reason for death was vascular disease, and undertreatment of cardiovascular risk factors may have occurred in the younger individuals. We also don’t know about glucose control.

“I personally think the findings show that we should treat cardiovascular risk factors more aggressively in people diagnosed with [type 2] diabetes in their 30s and 40s,” urged Dr. Peters.
 

High priority should be given to prevention globally

“Type 2 diabetes used to be seen as a disease that affected older adults, but we’re increasingly seeing people diagnosed earlier in life,” senior author Emanuele Di Angelantonio, MD, PhD, from the University of Cambridge (England), explained in a press release. “As we’ve shown, this means they are at risk of a much shorter life expectancy than they would otherwise have.”

The findings suggest that “high priority should be given to developing and implementing interventions that prevent or delay the onset of [type 2 diabetes], especially as its prevalence among younger age groups is increasing globally,” the study authors wrote.

The results “support the idea that the younger an individual is when they develop type 2 diabetes, the more damage their body accumulates from its impaired metabolism,” added co–senior author Naveed Sattar, MD, PhD, of the University of Glasgow,

Dr. Peters agreed: “People who develop type 2 diabetes at a younger age might have a different, potentially more aggressive type of type 2 diabetes and perhaps need treatment targets that are lower than people who develop type 2 diabetes when they are older.”

“The findings ... suggest that early detection of diabetes by screening followed by intensive glucose management could help prevent long-term complications from the condition,” Dr. Sattar said.

Dr. Peters added: “An issue for some is pregnancy. ... Many of the medications taken for management of CVD [cardiovascular disease] risk factors are contraindicated in pregnancy (as are many of the medications [for treating type 2 diabetes]).

“We need to be careful to risk reduce but take care of the ‘whole person,’ and if of childbearing age, consider the safest approaches to healthy management,” she emphasized.
 

Study results: Type 2 diabetes diagnosed at age 30, 40, and 50

Previous studies estimated that adults with type 2 diabetes die 6 years earlier on average in comparison with their counterparts who do not have diabetes, but it was not known how diabetes duration affects life span.

To investigate this, the team analyzed individual records from the Emerging Risk Factors Collaboration and the UK Biobank. The primary outcome was all-cause mortality. Other outcomes were deaths from CVD, cancer, and other causes.

Over a median follow-up of 12.5 years, there were 246,670 deaths: 84,443 from cardiovascular causes, 150, 972 from noncardiovascular causes, and 11,255 from unknown/ill-defined causes.

Compared with participants who did not have a history of type 2 diabetes, the hazard ratios for all-cause mortality, adjusted for age and sex, were 2.69 for participants diagnosed at age 30-39, 2.26 for those diagnosed aged 40-49, 1.84 aged 50-59, 1.57 for those aged 60-69, and 1.39 for those diagnosed 70 and older.

These hazard ratios were similar after adjusting for BMI, systolic blood pressure, and total cholesterol, but they were substantially attenuated after further adjusting for fasting glucose or hemoglobin A1c level.

Similar patterns were observed for cause-specific mortality.

“Every decade of earlier diagnosis of diabetes was associated with about 3-4 years of lower life expectancy, highlighting the need to develop and implement interventions that prevent or delay the onset of diabetes and to intensify the treatment of risk factors among young adults diagnosed with diabetes,” the researchers wrote.

The study was funded the British Heart Foundation, the Medical Research Council, the National Institute for Health and Care Research, and Health Data Research UK. Dr. Peters is on advisory boards for Vertex, Eli Lilly, and Medscape, receives research funding from Abbott Diabetes Care and Insulet, and has stock options for Omada Health.

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

TOPLINE:

The risk for dementia before age 90 years was significantly higher among people with a history of proton pump inhibitor (PPI) use and was highest among those diagnosed before age 70 years regardless of when PPI treatment was initiated.

METHODOLOGY:

• Researchers used four Danish registries to collect data on dementia diagnoses and prescription PPI use among 1,983,785 individuals aged 60-75 years between 2000 and 2018.
• The median follow-up time was 10.3 years.

TAKEAWAY:

• There were 99,384 (5.0%) cases of all-cause dementia during follow-up, with a median age of diagnosis of 79 years.
• Twenty-one-point-two percent of dementia cases and 18.9% of controls reported a history of PPI use.
• Risk for all-cause dementia before age 90 years was 36% higher with PPI use in people aged 60-69 years at baseline (adjusted incidence rate ratio, 1.36; 95% confidence interval, 1.29-1.43) and 6% higher in those who were age 80-89 years at baseline (aIRR, 1.06; 95% CI, 1.03-1.09).
• Investigators found significant increased dementia risk before age 90 years with PPI use regardless of when PPI treatment began and found no link between PPI use and dementia diagnoses after age 90 years.

IN PRACTICE:

“The association between PPI use and dementia was unambiguously largest among the youngest cases of dementia, potentially suggestive of a critical window of exposure where midlife PPI use affects dementia risk to a larger degree compared to late-life use,” the authors wrote. “Further, the finding could signify a declining impact of individual risk factors with advancing age owing to lengthy ongoing neuropathological processes.”

SOURCE:

Lead author of the study was Nelsan Pourhadi, MD, Danish Dementia Research Centre, department of neurology, Copenhagen University Hospital–Rigshospitalet. It was published online in Alzheimer’s and Dementia.

LIMITATIONS:

The study did not include data on PPI prescriptions before 1995, over-the-counter PPI use, and in-hospital intravenous use of PPI during the study period.

DISCLOSURES:

The study was funded by the Danish Ministry of Health. The authors reported no relevant conflicts.

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

TOPLINE:

The risk for dementia before age 90 years was significantly higher among people with a history of proton pump inhibitor (PPI) use and was highest among those diagnosed before age 70 years regardless of when PPI treatment was initiated.

METHODOLOGY:

• Researchers used four Danish registries to collect data on dementia diagnoses and prescription PPI use among 1,983,785 individuals aged 60-75 years between 2000 and 2018.
• The median follow-up time was 10.3 years.

TAKEAWAY:

• There were 99,384 (5.0%) cases of all-cause dementia during follow-up, with a median age of diagnosis of 79 years.
• Twenty-one-point-two percent of dementia cases and 18.9% of controls reported a history of PPI use.
• Risk for all-cause dementia before age 90 years was 36% higher with PPI use in people aged 60-69 years at baseline (adjusted incidence rate ratio, 1.36; 95% confidence interval, 1.29-1.43) and 6% higher in those who were age 80-89 years at baseline (aIRR, 1.06; 95% CI, 1.03-1.09).
• Investigators found significant increased dementia risk before age 90 years with PPI use regardless of when PPI treatment began and found no link between PPI use and dementia diagnoses after age 90 years.

IN PRACTICE:

“The association between PPI use and dementia was unambiguously largest among the youngest cases of dementia, potentially suggestive of a critical window of exposure where midlife PPI use affects dementia risk to a larger degree compared to late-life use,” the authors wrote. “Further, the finding could signify a declining impact of individual risk factors with advancing age owing to lengthy ongoing neuropathological processes.”

SOURCE:

Lead author of the study was Nelsan Pourhadi, MD, Danish Dementia Research Centre, department of neurology, Copenhagen University Hospital–Rigshospitalet. It was published online in Alzheimer’s and Dementia.

LIMITATIONS:

The study did not include data on PPI prescriptions before 1995, over-the-counter PPI use, and in-hospital intravenous use of PPI during the study period.

DISCLOSURES:

The study was funded by the Danish Ministry of Health. The authors reported no relevant conflicts.

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

TOPLINE:

The risk for dementia before age 90 years was significantly higher among people with a history of proton pump inhibitor (PPI) use and was highest among those diagnosed before age 70 years regardless of when PPI treatment was initiated.

METHODOLOGY:

• Researchers used four Danish registries to collect data on dementia diagnoses and prescription PPI use among 1,983,785 individuals aged 60-75 years between 2000 and 2018.
• The median follow-up time was 10.3 years.

TAKEAWAY:

• There were 99,384 (5.0%) cases of all-cause dementia during follow-up, with a median age of diagnosis of 79 years.
• Twenty-one-point-two percent of dementia cases and 18.9% of controls reported a history of PPI use.
• Risk for all-cause dementia before age 90 years was 36% higher with PPI use in people aged 60-69 years at baseline (adjusted incidence rate ratio, 1.36; 95% confidence interval, 1.29-1.43) and 6% higher in those who were age 80-89 years at baseline (aIRR, 1.06; 95% CI, 1.03-1.09).
• Investigators found significant increased dementia risk before age 90 years with PPI use regardless of when PPI treatment began and found no link between PPI use and dementia diagnoses after age 90 years.

IN PRACTICE:

“The association between PPI use and dementia was unambiguously largest among the youngest cases of dementia, potentially suggestive of a critical window of exposure where midlife PPI use affects dementia risk to a larger degree compared to late-life use,” the authors wrote. “Further, the finding could signify a declining impact of individual risk factors with advancing age owing to lengthy ongoing neuropathological processes.”

SOURCE:

Lead author of the study was Nelsan Pourhadi, MD, Danish Dementia Research Centre, department of neurology, Copenhagen University Hospital–Rigshospitalet. It was published online in Alzheimer’s and Dementia.

LIMITATIONS:

The study did not include data on PPI prescriptions before 1995, over-the-counter PPI use, and in-hospital intravenous use of PPI during the study period.

DISCLOSURES:

The study was funded by the Danish Ministry of Health. The authors reported no relevant conflicts.

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

Citing the strong overlap between heart disease, kidney disease, type 2 diabetes, and obesity, the American Heart Association has for the first time formally defined what they are calling cardiovascular-kidney-metabolic (CKM) syndrome.

“This work was prompted by the fact that CKM syndrome leads to premature morbidity and mortality, primarily because of a higher burden of CVD,” writing committee chair Chiadi Ndumele, MD, PhD, said in an interview.

“While CKM syndrome is a public health emergency, there is also great potential for improving CKM health in the population, with an increasing number of therapies that favorably impact metabolic risk factors, risk for adverse kidney events, or both, which also protect against CVD,” added Dr. Ndumele, director of obesity and cardiometabolic research in the division of cardiology at Johns Hopkins University, Baltimore.

The AHA presidential advisory and accompanying scientific statement, which provides a synopsis of evidence for the science and clinical management of CKM, were published online in the journal Circulation.
 

CKM syndrome staging

According to the AHA, one in three U.S. adults have three or more risk factors that contribute to CVD, metabolic disorders, and/or kidney disease.

In addition to defining CKM syndrome, the advisory provides a “staging construct, to be used in both adults and youth, that reflects the progressive pathophysiology and risk within CKM syndrome, with therapeutic guidance tied to CKM stages,” Dr. Ndumele told this news organization.

The AHA outlines four stages of CKM syndrome:

Stage 0: At this stage, no CKM risk factors are present, and the goal is to prevent CKM syndrome (particularly unhealthy weight gain) by achieving and maintaining ideal health based on the AHA’s Life’s Essential 8 recommendations. Adults in this stage should be screened every 3-5 years to assess lipids, blood pressure, and blood sugar.

Stage 1: At this stage, excess weight, abdominal obesity, or dysfunctional adipose tissue (clinically manifest as impaired glucose tolerance or prediabetes) is present without other metabolic risk factors or CVD. Management includes providing support for healthy lifestyle changes (healthy eating and regular physical activity), with a goal of at least 5% weight loss and addressing glucose intolerance if needed. Screening adults with stage 1 CKM every 2-3 years is advised to assess blood pressure, triglycerides, cholesterol, and blood sugar.

Stage 2: At this stage, metabolic risk factors (hypertriglyceridemia, hypertension, metabolic syndrome, diabetes) and kidney disease are present. The goal is to address risk factors to prevent progression to CVD and kidney failure. Screening for stage 2 CKM syndrome aligns with AHA/ACC guidelines, which include yearly assessment of blood pressure, triglycerides, cholesterol, blood sugar, and kidney function. More frequent kidney screening is recommended for individuals with increased risk of kidney failure based on kidney function assessments.

Stage 3: This stage describes individuals with subclinical CVD with metabolic risk factors or kidney disease or those at high predicted risk for CVD. The goal is to intensify efforts to prevent progression to symptomatic CVD and kidney failure. This may involve increasing or changing medications, and additional focus on lifestyle changes. Coronary artery calcium (CAC) measurement in some adults is recommended to assess narrowing of the arteries when treatment decisions are unclear.

Stage 4: Individuals with stage 4 CKM syndrome have symptomatic CVD, excess body fat, metabolic risk factors, or kidney disease. Stage 4 CKM syndrome is divided into two subcategories: (4a) no kidney failure and (4b) kidney failure. In this stage, patients may have already had a myocardial infarction (MI) or stroke or may already have heart failure. They also may have additional CV conditions such as peripheral artery disease or atrial fibrillation. The goal of care is individualized treatment for CVD with consideration for CKM syndrome conditions.

The advisory also describes CKM syndrome regression, “an important concept and public health message in which people making healthy lifestyle changes and achieving weight loss may regress to lower CKM syndrome stages and a better state of health,” the AHA says in a news release.

They note that a “critical” next step is to update the pooled cohort equation (PCE) risk prediction algorithm to include measures of kidney function, type 2 diabetes control, and social determinants of health for a more comprehensive risk estimate.

The advisory also recommends risk calculator updates be expanded to assess risk in people as young as age 30 and to calculate both 10- and 30-year CVD risk.

“Clearly defining the patient with CKM syndrome, and providing new approaches for CKM syndrome staging and risk prediction, will help health care professionals to identify these individuals earlier and to provide timely, holistic, and patient-centered care,” Dr. Ndumele said.

This presidential advisory was prepared by the volunteer writing group on behalf of the AHA . The authors have reported no relevant financial relationships.

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

Citing the strong overlap between heart disease, kidney disease, type 2 diabetes, and obesity, the American Heart Association has for the first time formally defined what they are calling cardiovascular-kidney-metabolic (CKM) syndrome.

“This work was prompted by the fact that CKM syndrome leads to premature morbidity and mortality, primarily because of a higher burden of CVD,” writing committee chair Chiadi Ndumele, MD, PhD, said in an interview.

“While CKM syndrome is a public health emergency, there is also great potential for improving CKM health in the population, with an increasing number of therapies that favorably impact metabolic risk factors, risk for adverse kidney events, or both, which also protect against CVD,” added Dr. Ndumele, director of obesity and cardiometabolic research in the division of cardiology at Johns Hopkins University, Baltimore.

The AHA presidential advisory and accompanying scientific statement, which provides a synopsis of evidence for the science and clinical management of CKM, were published online in the journal Circulation.
 

CKM syndrome staging

According to the AHA, one in three U.S. adults have three or more risk factors that contribute to CVD, metabolic disorders, and/or kidney disease.

In addition to defining CKM syndrome, the advisory provides a “staging construct, to be used in both adults and youth, that reflects the progressive pathophysiology and risk within CKM syndrome, with therapeutic guidance tied to CKM stages,” Dr. Ndumele told this news organization.

The AHA outlines four stages of CKM syndrome:

Stage 0: At this stage, no CKM risk factors are present, and the goal is to prevent CKM syndrome (particularly unhealthy weight gain) by achieving and maintaining ideal health based on the AHA’s Life’s Essential 8 recommendations. Adults in this stage should be screened every 3-5 years to assess lipids, blood pressure, and blood sugar.

Stage 1: At this stage, excess weight, abdominal obesity, or dysfunctional adipose tissue (clinically manifest as impaired glucose tolerance or prediabetes) is present without other metabolic risk factors or CVD. Management includes providing support for healthy lifestyle changes (healthy eating and regular physical activity), with a goal of at least 5% weight loss and addressing glucose intolerance if needed. Screening adults with stage 1 CKM every 2-3 years is advised to assess blood pressure, triglycerides, cholesterol, and blood sugar.

Stage 2: At this stage, metabolic risk factors (hypertriglyceridemia, hypertension, metabolic syndrome, diabetes) and kidney disease are present. The goal is to address risk factors to prevent progression to CVD and kidney failure. Screening for stage 2 CKM syndrome aligns with AHA/ACC guidelines, which include yearly assessment of blood pressure, triglycerides, cholesterol, blood sugar, and kidney function. More frequent kidney screening is recommended for individuals with increased risk of kidney failure based on kidney function assessments.

Stage 3: This stage describes individuals with subclinical CVD with metabolic risk factors or kidney disease or those at high predicted risk for CVD. The goal is to intensify efforts to prevent progression to symptomatic CVD and kidney failure. This may involve increasing or changing medications, and additional focus on lifestyle changes. Coronary artery calcium (CAC) measurement in some adults is recommended to assess narrowing of the arteries when treatment decisions are unclear.

Stage 4: Individuals with stage 4 CKM syndrome have symptomatic CVD, excess body fat, metabolic risk factors, or kidney disease. Stage 4 CKM syndrome is divided into two subcategories: (4a) no kidney failure and (4b) kidney failure. In this stage, patients may have already had a myocardial infarction (MI) or stroke or may already have heart failure. They also may have additional CV conditions such as peripheral artery disease or atrial fibrillation. The goal of care is individualized treatment for CVD with consideration for CKM syndrome conditions.

The advisory also describes CKM syndrome regression, “an important concept and public health message in which people making healthy lifestyle changes and achieving weight loss may regress to lower CKM syndrome stages and a better state of health,” the AHA says in a news release.

They note that a “critical” next step is to update the pooled cohort equation (PCE) risk prediction algorithm to include measures of kidney function, type 2 diabetes control, and social determinants of health for a more comprehensive risk estimate.

The advisory also recommends risk calculator updates be expanded to assess risk in people as young as age 30 and to calculate both 10- and 30-year CVD risk.

“Clearly defining the patient with CKM syndrome, and providing new approaches for CKM syndrome staging and risk prediction, will help health care professionals to identify these individuals earlier and to provide timely, holistic, and patient-centered care,” Dr. Ndumele said.

This presidential advisory was prepared by the volunteer writing group on behalf of the AHA . The authors have reported no relevant financial relationships.

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

Citing the strong overlap between heart disease, kidney disease, type 2 diabetes, and obesity, the American Heart Association has for the first time formally defined what they are calling cardiovascular-kidney-metabolic (CKM) syndrome.

“This work was prompted by the fact that CKM syndrome leads to premature morbidity and mortality, primarily because of a higher burden of CVD,” writing committee chair Chiadi Ndumele, MD, PhD, said in an interview.

“While CKM syndrome is a public health emergency, there is also great potential for improving CKM health in the population, with an increasing number of therapies that favorably impact metabolic risk factors, risk for adverse kidney events, or both, which also protect against CVD,” added Dr. Ndumele, director of obesity and cardiometabolic research in the division of cardiology at Johns Hopkins University, Baltimore.

The AHA presidential advisory and accompanying scientific statement, which provides a synopsis of evidence for the science and clinical management of CKM, were published online in the journal Circulation.
 

CKM syndrome staging

According to the AHA, one in three U.S. adults have three or more risk factors that contribute to CVD, metabolic disorders, and/or kidney disease.

In addition to defining CKM syndrome, the advisory provides a “staging construct, to be used in both adults and youth, that reflects the progressive pathophysiology and risk within CKM syndrome, with therapeutic guidance tied to CKM stages,” Dr. Ndumele told this news organization.

The AHA outlines four stages of CKM syndrome:

Stage 0: At this stage, no CKM risk factors are present, and the goal is to prevent CKM syndrome (particularly unhealthy weight gain) by achieving and maintaining ideal health based on the AHA’s Life’s Essential 8 recommendations. Adults in this stage should be screened every 3-5 years to assess lipids, blood pressure, and blood sugar.

Stage 1: At this stage, excess weight, abdominal obesity, or dysfunctional adipose tissue (clinically manifest as impaired glucose tolerance or prediabetes) is present without other metabolic risk factors or CVD. Management includes providing support for healthy lifestyle changes (healthy eating and regular physical activity), with a goal of at least 5% weight loss and addressing glucose intolerance if needed. Screening adults with stage 1 CKM every 2-3 years is advised to assess blood pressure, triglycerides, cholesterol, and blood sugar.

Stage 2: At this stage, metabolic risk factors (hypertriglyceridemia, hypertension, metabolic syndrome, diabetes) and kidney disease are present. The goal is to address risk factors to prevent progression to CVD and kidney failure. Screening for stage 2 CKM syndrome aligns with AHA/ACC guidelines, which include yearly assessment of blood pressure, triglycerides, cholesterol, blood sugar, and kidney function. More frequent kidney screening is recommended for individuals with increased risk of kidney failure based on kidney function assessments.

Stage 3: This stage describes individuals with subclinical CVD with metabolic risk factors or kidney disease or those at high predicted risk for CVD. The goal is to intensify efforts to prevent progression to symptomatic CVD and kidney failure. This may involve increasing or changing medications, and additional focus on lifestyle changes. Coronary artery calcium (CAC) measurement in some adults is recommended to assess narrowing of the arteries when treatment decisions are unclear.

Stage 4: Individuals with stage 4 CKM syndrome have symptomatic CVD, excess body fat, metabolic risk factors, or kidney disease. Stage 4 CKM syndrome is divided into two subcategories: (4a) no kidney failure and (4b) kidney failure. In this stage, patients may have already had a myocardial infarction (MI) or stroke or may already have heart failure. They also may have additional CV conditions such as peripheral artery disease or atrial fibrillation. The goal of care is individualized treatment for CVD with consideration for CKM syndrome conditions.

The advisory also describes CKM syndrome regression, “an important concept and public health message in which people making healthy lifestyle changes and achieving weight loss may regress to lower CKM syndrome stages and a better state of health,” the AHA says in a news release.

They note that a “critical” next step is to update the pooled cohort equation (PCE) risk prediction algorithm to include measures of kidney function, type 2 diabetes control, and social determinants of health for a more comprehensive risk estimate.

The advisory also recommends risk calculator updates be expanded to assess risk in people as young as age 30 and to calculate both 10- and 30-year CVD risk.

“Clearly defining the patient with CKM syndrome, and providing new approaches for CKM syndrome staging and risk prediction, will help health care professionals to identify these individuals earlier and to provide timely, holistic, and patient-centered care,” Dr. Ndumele said.

This presidential advisory was prepared by the volunteer writing group on behalf of the AHA . The authors have reported no relevant financial relationships.

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

TOPLINE:

Use of a novel clinical-decision support tool and shared decision-making in elderly patients with type 2 diabetes managed in a primary care practice and at high risk for hypoglycemic episodes led to a 46% decrease in the number of at-risk patients and discontinuation of hypoglycemic agents in 20% in a prospective, 6-month, single-arm study with 94 patients.

METHODOLOGY:

• The HypoPrevent study enrolled 94 people from a Pennsylvania primary care practice who were at least 65 years old with type 2 diabetes and at risk for hypoglycemia because of treatment with insulin or sulfonylureas, and having a hemoglobin A1c of less than 7.0%.
• Clinicians and patients used a newly devised hypoglycemia reduction clinical-decision support tool developed by the Endocrine Society and a health care consulting company to help guide shared decision-making for a goal A1c level, potential changes to treatment, and other steps to reduce the risk of hypoglycemia.
• Primary outcomes during 6-month follow-up were impact of the intervention on A1c, changes in use of insulin or sulfonylureas, change in the number of study patients at risk for hypoglycemia, and impact on the incidence of nonsevere hypoglycemic events (NSHEs) measured with the Treatment-Related Impact Measure–Non-severe Hypoglycemic Events (TRIM-HYPO) survey.

TAKEAWAY:

• Patients averaged 74 years old, 57% were women, 95% were White, 61% had diabetes for more than 10 years, 48% had chronic kidney disease, 51% were on insulin, 47% on a sulfonylurea, and 80 of the 94 enrolled patients completed all three study visits.
• Nineteen patients (20%) reduced their dose of or discontinued insulin or sulfonylurea.
• In patients with both baseline and follow-up A1c measures, A1c rose from 6.29% at baseline to 6.82%.
• Fifty patients set an A1c goal and had a timely follow-up A1c measurement, and in this subgroup the number of patients at risk for hypoglycemia decreased by 46%, a significant change.
• Patients who reported at least one NSHE at baseline had a significant reduction between the baseline survey and follow-up visits in both the total score as well as each of the five scored domains.

IN PRACTICE:

The HypoPrevent study results “show the potential of a decision support tool and shared decision making to reduce the risk of hypoglycemia in older persons with type 2 diabetes,” and that “the tested decision tool can be effectively used by a busy primary care practice with positive results,” concluded the researchers in their report.

SOURCE:

The HypoPrevent study was funded and organized by the Endocrine Society in collaboration with a multicenter team of researchers. The report appeared in the Journal of the American Geriatrics Society.

LIMITATIONS:

Lack of a control group makes it impossible to conclusively determine whether the intervention led to the observed increases in A1c levels, nor can the study exclude regression to the mean as the cause for lowered A1c levels.

DISCLOSURES:

The study received funding from Abbott, Lilly, Merck, Novo Nordisk, and Sanofi. Two coauthors had individual disclosures listed in the report; the other six coauthors had no disclosures.

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

TOPLINE:

Use of a novel clinical-decision support tool and shared decision-making in elderly patients with type 2 diabetes managed in a primary care practice and at high risk for hypoglycemic episodes led to a 46% decrease in the number of at-risk patients and discontinuation of hypoglycemic agents in 20% in a prospective, 6-month, single-arm study with 94 patients.

METHODOLOGY:

• The HypoPrevent study enrolled 94 people from a Pennsylvania primary care practice who were at least 65 years old with type 2 diabetes and at risk for hypoglycemia because of treatment with insulin or sulfonylureas, and having a hemoglobin A1c of less than 7.0%.
• Clinicians and patients used a newly devised hypoglycemia reduction clinical-decision support tool developed by the Endocrine Society and a health care consulting company to help guide shared decision-making for a goal A1c level, potential changes to treatment, and other steps to reduce the risk of hypoglycemia.
• Primary outcomes during 6-month follow-up were impact of the intervention on A1c, changes in use of insulin or sulfonylureas, change in the number of study patients at risk for hypoglycemia, and impact on the incidence of nonsevere hypoglycemic events (NSHEs) measured with the Treatment-Related Impact Measure–Non-severe Hypoglycemic Events (TRIM-HYPO) survey.

TAKEAWAY:

• Patients averaged 74 years old, 57% were women, 95% were White, 61% had diabetes for more than 10 years, 48% had chronic kidney disease, 51% were on insulin, 47% on a sulfonylurea, and 80 of the 94 enrolled patients completed all three study visits.
• Nineteen patients (20%) reduced their dose of or discontinued insulin or sulfonylurea.
• In patients with both baseline and follow-up A1c measures, A1c rose from 6.29% at baseline to 6.82%.
• Fifty patients set an A1c goal and had a timely follow-up A1c measurement, and in this subgroup the number of patients at risk for hypoglycemia decreased by 46%, a significant change.
• Patients who reported at least one NSHE at baseline had a significant reduction between the baseline survey and follow-up visits in both the total score as well as each of the five scored domains.

IN PRACTICE:

The HypoPrevent study results “show the potential of a decision support tool and shared decision making to reduce the risk of hypoglycemia in older persons with type 2 diabetes,” and that “the tested decision tool can be effectively used by a busy primary care practice with positive results,” concluded the researchers in their report.

SOURCE:

The HypoPrevent study was funded and organized by the Endocrine Society in collaboration with a multicenter team of researchers. The report appeared in the Journal of the American Geriatrics Society.

LIMITATIONS:

Lack of a control group makes it impossible to conclusively determine whether the intervention led to the observed increases in A1c levels, nor can the study exclude regression to the mean as the cause for lowered A1c levels.

DISCLOSURES:

The study received funding from Abbott, Lilly, Merck, Novo Nordisk, and Sanofi. Two coauthors had individual disclosures listed in the report; the other six coauthors had no disclosures.

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

TOPLINE:

Use of a novel clinical-decision support tool and shared decision-making in elderly patients with type 2 diabetes managed in a primary care practice and at high risk for hypoglycemic episodes led to a 46% decrease in the number of at-risk patients and discontinuation of hypoglycemic agents in 20% in a prospective, 6-month, single-arm study with 94 patients.

METHODOLOGY:

• The HypoPrevent study enrolled 94 people from a Pennsylvania primary care practice who were at least 65 years old with type 2 diabetes and at risk for hypoglycemia because of treatment with insulin or sulfonylureas, and having a hemoglobin A1c of less than 7.0%.
• Clinicians and patients used a newly devised hypoglycemia reduction clinical-decision support tool developed by the Endocrine Society and a health care consulting company to help guide shared decision-making for a goal A1c level, potential changes to treatment, and other steps to reduce the risk of hypoglycemia.
• Primary outcomes during 6-month follow-up were impact of the intervention on A1c, changes in use of insulin or sulfonylureas, change in the number of study patients at risk for hypoglycemia, and impact on the incidence of nonsevere hypoglycemic events (NSHEs) measured with the Treatment-Related Impact Measure–Non-severe Hypoglycemic Events (TRIM-HYPO) survey.

TAKEAWAY:

• Patients averaged 74 years old, 57% were women, 95% were White, 61% had diabetes for more than 10 years, 48% had chronic kidney disease, 51% were on insulin, 47% on a sulfonylurea, and 80 of the 94 enrolled patients completed all three study visits.
• Nineteen patients (20%) reduced their dose of or discontinued insulin or sulfonylurea.
• In patients with both baseline and follow-up A1c measures, A1c rose from 6.29% at baseline to 6.82%.
• Fifty patients set an A1c goal and had a timely follow-up A1c measurement, and in this subgroup the number of patients at risk for hypoglycemia decreased by 46%, a significant change.
• Patients who reported at least one NSHE at baseline had a significant reduction between the baseline survey and follow-up visits in both the total score as well as each of the five scored domains.

IN PRACTICE:

The HypoPrevent study results “show the potential of a decision support tool and shared decision making to reduce the risk of hypoglycemia in older persons with type 2 diabetes,” and that “the tested decision tool can be effectively used by a busy primary care practice with positive results,” concluded the researchers in their report.

SOURCE:

The HypoPrevent study was funded and organized by the Endocrine Society in collaboration with a multicenter team of researchers. The report appeared in the Journal of the American Geriatrics Society.

LIMITATIONS:

Lack of a control group makes it impossible to conclusively determine whether the intervention led to the observed increases in A1c levels, nor can the study exclude regression to the mean as the cause for lowered A1c levels.

DISCLOSURES:

The study received funding from Abbott, Lilly, Merck, Novo Nordisk, and Sanofi. Two coauthors had individual disclosures listed in the report; the other six coauthors had no disclosures.

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

For most symptomatic patients with atherosclerotic occlusion of the internal carotid artery (ICA) or middle cerebral artery (MCA), adding extracranial-intracranial (EC-IC) bypass surgery to medical therapy did not reduce stroke or death in comparison with medical therapy alone in the latest randomized trial comparing the two interventions.

However, subgroup analyses suggest a potential benefit of surgery for certain patients, such as those with MCA vs. ICA occlusion, mean transit time greater than 6 seconds, or regional blood flow of 0.8 or less.

“We were disappointed by the results,” Liqun Jiao, MD, of the National Center for Neurological Disorders in Beijing, told this news organization. “We were expecting to demonstrate a benefit from EC-IC bypass surgery over medical treatment alone in symptomatic patients with ICA or MCA occlusion and hemodynamic insufficiency, per our original hypothesis.”

Although the study showed improved efficacy and safety for the surgical procedure, he said, “The progress of medical treatment is even better.”

The study was published online in JAMA.
 

Subgroup analyses promising

Previous randomized clinical trials, including the EC/IC Bypass Study and the Carotid Occlusion Surgery Study (COSS), showed no benefit in stroke prevention for patients with atherosclerotic occlusion of the ICA or MCA.

However, in light of improvements over the years in surgical techniques and patient selection, the authors conducted the Carotid and Middle Cerebral Artery Occlusion Surgery Study (CMOSS), a multicenter, randomized, open-label trial comparing EC-IC bypass surgery plus medical therapy, consisting of antiplatelet therapy and control of stroke risk factors, with medical therapy alone in symptomatic patients with ICA or MCA occlusion and hemodynamic insufficiency, with refined patient and operator selection.

A total of 324 patients (median age, 52.7 years; 79% men) in 13 centers in China were included; 309 patients (95%) completed the study.

The primary outcome was a composite of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years after randomization.

Secondary outcomes included, among others, any stroke or death within 2 years and fatal stroke within 2 years.

No significant difference was found for the primary outcome between the surgical group (8.6%) and the medical group (12.3%).

The 30-day risk of stroke or death was 6.2% in the surgery group, versus 1.8% (3/163) for the medical group. The risk of ipsilateral ischemic stroke beyond 30 days through 2 years was 2%, versus 10.3% – nonsignificant differences.

Furthermore, none of the prespecified secondary endpoints showed a significant difference, including any stroke or death within 2 years (9.9% vs. 15.3%; hazard ratio, 0.69) and fatal stroke within 2 years (2% vs. none).

Despite the findings, “We are encouraged by the subgroup analysis and the trend of long-term outcomes,” Dr. Jiao said. “We will continue to finish 5-10 years of follow-up to see whether the benefit of bypass surgery can be identified.”

The team has also launched the CMOSS-2 trial with a refined study design based on the results of subgroup analysis of the CMOSS study.

CMOSS-2 is recruiting patients with symptomatic chronic occlusion of the MCA and severe hemodynamic insufficiency in 13 sites in China. The primary outcome is ischemic stroke in the territory of the target artery within 24 months after randomization.
 

Can’t exclude benefit

Thomas Jeerakathil, MD, a professor at the University of Alberta and Northern Stroke Lead, Cardiovascular and Stroke Strategic Clinical Network, Alberta Health Services, Edmonton, commented on the study for this news organization. Like the authors, he said, “I don’t consider this study to definitively exclude the benefit of EC/IC bypass. More studies are required.”

Dr. Jeerakathil would like to see a study of a higher-risk group based on both clinical and hemodynamic blood flow criteria. In the current study, he said, “The trial group overall may not have been at high enough stroke risk to justify the up-front risks of the EC-IC bypass procedure.”

In addition, “The analysis method of Cox proportional hazards regression for the primary outcome did not fit the data when the perioperative period was combined with the period beyond 30 days,” he noted. “The researchers were open about this and did pivot and included a post hoc relative risk-based analysis, but the validity of their primary analysis is questionable.”

Furthermore, the study was “somewhat underpowered with a relatively small sample size and had the potential to miss clinically significant differences between groups,” he said. “It would be good to see a longer follow-up period of at least 5 years added to this trial and used in future trials, rather than 2 years.”

“Lastly,” he said, “it’s difficult to ignore the reduction in recurrent stroke events over the 30-day to 2-year time period associated with EC-IC bypass (from 10.3% down to 2%). This reduction alone shows the procedure has some potential to prevent stroke and would argue for more trials.”

EC-IC could be considered for patients who have failed other medical therapies and have more substantial evidence of compromised blood flow to the brain than those in the CMOSS trial, he noted, as many of these patients have few other options. “In our center and many other centers, the approach to EC-IC bypass is probably much more selective than used in the trial.”

Dr. Jeerakathil concluded, “Clinicians should be cautious about offering the procedure to patients with just mildly delayed blood flow in the hemisphere affected by the occluded artery and those who have not yet failed maximal medical therapy.”

But Seemant Chaturvedi, MD, and J. Marc Simard, MD, PhD, both of the University of Maryland, Baltimore, are not as optimistic about the potential for EC-IC.

Writing in a related editorial, they conclude that the results with EC-IC bypass surgery in randomized trials “remain unimpressive. Until a better understanding of the unique hemodynamic features of the brain is achieved, it will be difficult for neurosurgeons to continue offering this procedure to patients with ICA or MCA occlusion. Intensive, multifaceted medical therapy remains the first-line treatment for [these] patients.”

The study was supported by a research grant from the National Health Commission of the People’s Republic of China. Dr. Jiao, Dr. Jeerakathil, Dr. Chaturvedi, and Dr. Simard reported no conflicts of interest.

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

For most symptomatic patients with atherosclerotic occlusion of the internal carotid artery (ICA) or middle cerebral artery (MCA), adding extracranial-intracranial (EC-IC) bypass surgery to medical therapy did not reduce stroke or death in comparison with medical therapy alone in the latest randomized trial comparing the two interventions.

However, subgroup analyses suggest a potential benefit of surgery for certain patients, such as those with MCA vs. ICA occlusion, mean transit time greater than 6 seconds, or regional blood flow of 0.8 or less.

“We were disappointed by the results,” Liqun Jiao, MD, of the National Center for Neurological Disorders in Beijing, told this news organization. “We were expecting to demonstrate a benefit from EC-IC bypass surgery over medical treatment alone in symptomatic patients with ICA or MCA occlusion and hemodynamic insufficiency, per our original hypothesis.”

Although the study showed improved efficacy and safety for the surgical procedure, he said, “The progress of medical treatment is even better.”

The study was published online in JAMA.
 

Subgroup analyses promising

Previous randomized clinical trials, including the EC/IC Bypass Study and the Carotid Occlusion Surgery Study (COSS), showed no benefit in stroke prevention for patients with atherosclerotic occlusion of the ICA or MCA.

However, in light of improvements over the years in surgical techniques and patient selection, the authors conducted the Carotid and Middle Cerebral Artery Occlusion Surgery Study (CMOSS), a multicenter, randomized, open-label trial comparing EC-IC bypass surgery plus medical therapy, consisting of antiplatelet therapy and control of stroke risk factors, with medical therapy alone in symptomatic patients with ICA or MCA occlusion and hemodynamic insufficiency, with refined patient and operator selection.

A total of 324 patients (median age, 52.7 years; 79% men) in 13 centers in China were included; 309 patients (95%) completed the study.

The primary outcome was a composite of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years after randomization.

Secondary outcomes included, among others, any stroke or death within 2 years and fatal stroke within 2 years.

No significant difference was found for the primary outcome between the surgical group (8.6%) and the medical group (12.3%).

The 30-day risk of stroke or death was 6.2% in the surgery group, versus 1.8% (3/163) for the medical group. The risk of ipsilateral ischemic stroke beyond 30 days through 2 years was 2%, versus 10.3% – nonsignificant differences.

Furthermore, none of the prespecified secondary endpoints showed a significant difference, including any stroke or death within 2 years (9.9% vs. 15.3%; hazard ratio, 0.69) and fatal stroke within 2 years (2% vs. none).

Despite the findings, “We are encouraged by the subgroup analysis and the trend of long-term outcomes,” Dr. Jiao said. “We will continue to finish 5-10 years of follow-up to see whether the benefit of bypass surgery can be identified.”

The team has also launched the CMOSS-2 trial with a refined study design based on the results of subgroup analysis of the CMOSS study.

CMOSS-2 is recruiting patients with symptomatic chronic occlusion of the MCA and severe hemodynamic insufficiency in 13 sites in China. The primary outcome is ischemic stroke in the territory of the target artery within 24 months after randomization.
 

Can’t exclude benefit

Thomas Jeerakathil, MD, a professor at the University of Alberta and Northern Stroke Lead, Cardiovascular and Stroke Strategic Clinical Network, Alberta Health Services, Edmonton, commented on the study for this news organization. Like the authors, he said, “I don’t consider this study to definitively exclude the benefit of EC/IC bypass. More studies are required.”

Dr. Jeerakathil would like to see a study of a higher-risk group based on both clinical and hemodynamic blood flow criteria. In the current study, he said, “The trial group overall may not have been at high enough stroke risk to justify the up-front risks of the EC-IC bypass procedure.”

In addition, “The analysis method of Cox proportional hazards regression for the primary outcome did not fit the data when the perioperative period was combined with the period beyond 30 days,” he noted. “The researchers were open about this and did pivot and included a post hoc relative risk-based analysis, but the validity of their primary analysis is questionable.”

Furthermore, the study was “somewhat underpowered with a relatively small sample size and had the potential to miss clinically significant differences between groups,” he said. “It would be good to see a longer follow-up period of at least 5 years added to this trial and used in future trials, rather than 2 years.”

“Lastly,” he said, “it’s difficult to ignore the reduction in recurrent stroke events over the 30-day to 2-year time period associated with EC-IC bypass (from 10.3% down to 2%). This reduction alone shows the procedure has some potential to prevent stroke and would argue for more trials.”

EC-IC could be considered for patients who have failed other medical therapies and have more substantial evidence of compromised blood flow to the brain than those in the CMOSS trial, he noted, as many of these patients have few other options. “In our center and many other centers, the approach to EC-IC bypass is probably much more selective than used in the trial.”

Dr. Jeerakathil concluded, “Clinicians should be cautious about offering the procedure to patients with just mildly delayed blood flow in the hemisphere affected by the occluded artery and those who have not yet failed maximal medical therapy.”

But Seemant Chaturvedi, MD, and J. Marc Simard, MD, PhD, both of the University of Maryland, Baltimore, are not as optimistic about the potential for EC-IC.

Writing in a related editorial, they conclude that the results with EC-IC bypass surgery in randomized trials “remain unimpressive. Until a better understanding of the unique hemodynamic features of the brain is achieved, it will be difficult for neurosurgeons to continue offering this procedure to patients with ICA or MCA occlusion. Intensive, multifaceted medical therapy remains the first-line treatment for [these] patients.”

The study was supported by a research grant from the National Health Commission of the People’s Republic of China. Dr. Jiao, Dr. Jeerakathil, Dr. Chaturvedi, and Dr. Simard reported no conflicts of interest.

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

For most symptomatic patients with atherosclerotic occlusion of the internal carotid artery (ICA) or middle cerebral artery (MCA), adding extracranial-intracranial (EC-IC) bypass surgery to medical therapy did not reduce stroke or death in comparison with medical therapy alone in the latest randomized trial comparing the two interventions.

However, subgroup analyses suggest a potential benefit of surgery for certain patients, such as those with MCA vs. ICA occlusion, mean transit time greater than 6 seconds, or regional blood flow of 0.8 or less.

“We were disappointed by the results,” Liqun Jiao, MD, of the National Center for Neurological Disorders in Beijing, told this news organization. “We were expecting to demonstrate a benefit from EC-IC bypass surgery over medical treatment alone in symptomatic patients with ICA or MCA occlusion and hemodynamic insufficiency, per our original hypothesis.”

Although the study showed improved efficacy and safety for the surgical procedure, he said, “The progress of medical treatment is even better.”

The study was published online in JAMA.
 

Subgroup analyses promising

Previous randomized clinical trials, including the EC/IC Bypass Study and the Carotid Occlusion Surgery Study (COSS), showed no benefit in stroke prevention for patients with atherosclerotic occlusion of the ICA or MCA.

However, in light of improvements over the years in surgical techniques and patient selection, the authors conducted the Carotid and Middle Cerebral Artery Occlusion Surgery Study (CMOSS), a multicenter, randomized, open-label trial comparing EC-IC bypass surgery plus medical therapy, consisting of antiplatelet therapy and control of stroke risk factors, with medical therapy alone in symptomatic patients with ICA or MCA occlusion and hemodynamic insufficiency, with refined patient and operator selection.

A total of 324 patients (median age, 52.7 years; 79% men) in 13 centers in China were included; 309 patients (95%) completed the study.

The primary outcome was a composite of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years after randomization.

Secondary outcomes included, among others, any stroke or death within 2 years and fatal stroke within 2 years.

No significant difference was found for the primary outcome between the surgical group (8.6%) and the medical group (12.3%).

The 30-day risk of stroke or death was 6.2% in the surgery group, versus 1.8% (3/163) for the medical group. The risk of ipsilateral ischemic stroke beyond 30 days through 2 years was 2%, versus 10.3% – nonsignificant differences.

Furthermore, none of the prespecified secondary endpoints showed a significant difference, including any stroke or death within 2 years (9.9% vs. 15.3%; hazard ratio, 0.69) and fatal stroke within 2 years (2% vs. none).

Despite the findings, “We are encouraged by the subgroup analysis and the trend of long-term outcomes,” Dr. Jiao said. “We will continue to finish 5-10 years of follow-up to see whether the benefit of bypass surgery can be identified.”

The team has also launched the CMOSS-2 trial with a refined study design based on the results of subgroup analysis of the CMOSS study.

CMOSS-2 is recruiting patients with symptomatic chronic occlusion of the MCA and severe hemodynamic insufficiency in 13 sites in China. The primary outcome is ischemic stroke in the territory of the target artery within 24 months after randomization.
 

Can’t exclude benefit

Thomas Jeerakathil, MD, a professor at the University of Alberta and Northern Stroke Lead, Cardiovascular and Stroke Strategic Clinical Network, Alberta Health Services, Edmonton, commented on the study for this news organization. Like the authors, he said, “I don’t consider this study to definitively exclude the benefit of EC/IC bypass. More studies are required.”

Dr. Jeerakathil would like to see a study of a higher-risk group based on both clinical and hemodynamic blood flow criteria. In the current study, he said, “The trial group overall may not have been at high enough stroke risk to justify the up-front risks of the EC-IC bypass procedure.”

In addition, “The analysis method of Cox proportional hazards regression for the primary outcome did not fit the data when the perioperative period was combined with the period beyond 30 days,” he noted. “The researchers were open about this and did pivot and included a post hoc relative risk-based analysis, but the validity of their primary analysis is questionable.”

Furthermore, the study was “somewhat underpowered with a relatively small sample size and had the potential to miss clinically significant differences between groups,” he said. “It would be good to see a longer follow-up period of at least 5 years added to this trial and used in future trials, rather than 2 years.”

“Lastly,” he said, “it’s difficult to ignore the reduction in recurrent stroke events over the 30-day to 2-year time period associated with EC-IC bypass (from 10.3% down to 2%). This reduction alone shows the procedure has some potential to prevent stroke and would argue for more trials.”

EC-IC could be considered for patients who have failed other medical therapies and have more substantial evidence of compromised blood flow to the brain than those in the CMOSS trial, he noted, as many of these patients have few other options. “In our center and many other centers, the approach to EC-IC bypass is probably much more selective than used in the trial.”

Dr. Jeerakathil concluded, “Clinicians should be cautious about offering the procedure to patients with just mildly delayed blood flow in the hemisphere affected by the occluded artery and those who have not yet failed maximal medical therapy.”

But Seemant Chaturvedi, MD, and J. Marc Simard, MD, PhD, both of the University of Maryland, Baltimore, are not as optimistic about the potential for EC-IC.

Writing in a related editorial, they conclude that the results with EC-IC bypass surgery in randomized trials “remain unimpressive. Until a better understanding of the unique hemodynamic features of the brain is achieved, it will be difficult for neurosurgeons to continue offering this procedure to patients with ICA or MCA occlusion. Intensive, multifaceted medical therapy remains the first-line treatment for [these] patients.”

The study was supported by a research grant from the National Health Commission of the People’s Republic of China. Dr. Jiao, Dr. Jeerakathil, Dr. Chaturvedi, and Dr. Simard reported no conflicts of interest.

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