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No effect of diet on dementia risk?
Contrary to some prior studies,
After adjusting for relevant demographic and other lifestyle measures, there was no association between adherence to healthy dietary advice or the Mediterranean diet on the future risk of dementia or amyloid-beta (Abeta) accumulation.
“While our study does not rule out a possible association between diet and dementia, we did not find a link in our study, which had a long follow-up period, included younger participants than some other studies and did not require people to remember what foods they had eaten regularly years before,” study investigator Isabelle Glans, MD, of Lund (Sweden) University, said in a news release.
The findings were published online in Neurology.
No risk reduction
Several studies have investigated how dietary habits affect dementia risk, with inconsistent results.
The new findings are based on 28,025 adults (61% women; mean age, 58 years at baseline) who were free of dementia at baseline and were followed over a 20-year period as part of the Swedish Malmö Diet and Cancer Study. Dietary habits were assessed with a 7-day food diary, detailed food frequency questionnaire, and in-person interview.
During follow-up, 1,943 individuals (6.9%) developed dementia.
Compared with those who did not develop dementia, those who did develop dementia during follow-up were older and had a lower level of education and more cardiovascular risk factors and comorbidities at baseline.
Individuals who adhered to conventional healthy dietary recommendations did not have a lower risk of developing all-cause dementia (hazard ratio comparing worst with best adherence, 0.93; 95% confidence interval, 0.81-1.08), Alzheimer’s disease (HR, 1.03; 95% CI, 0.85-1.23) or vascular dementia (HR, 0.93; 95% CI, 0.69-1.26).
Adherence to the modified Mediterranean diet also did not appear to lower the risk of all-cause dementia (HR, 0.93; 95% CI, 0.75-1.15), Alzheimer’s disease (HR, 0.90; 95% CI, 0.68-1.19), or vascular dementia (HR, 1.00; 95% CI, 0.65-1.55).
There was also no significant association between diet and Alzheimer’s disease–related pathology, as measured by cerebrospinal fluid analysis of Abeta42 in a subgroup of 738 participants. Various sensitivity analyses yielded similar results.
Diet still matters
The authors of an accompanying editorial noted that diet as a “singular factor may not have a strong enough effect on cognition, but is more likely to be considered as one factor embedded with various others, the sum of which may influence the course of cognitive function (diet, regular exercise, vascular risk factor control, avoiding cigarette smoking, drinking alcohol in moderation, etc).
“Diet should not be forgotten and it still matters” but should be regarded as “one part of a multidomain intervention with respect to cognitive performance,” wrote Nils Peters, MD, with the University of Basel (Switzerland), and Benedetta Nacmias, PhD, with the University of Florence (Italy)).
“Key questions that remain include how to provide evidence for promoting the implications of dietary habits on cognition? Overall, dietary strategies will most likely be implicated either in order to reduce the increasing number of older subjects with dementia, or to extend healthy life expectancy, or both,” Dr. Peters and Dr. Nacmias said.
The study had no commercial funding. Dr. Glans, Dr. Peters, and Dr. Nacmias disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Contrary to some prior studies,
After adjusting for relevant demographic and other lifestyle measures, there was no association between adherence to healthy dietary advice or the Mediterranean diet on the future risk of dementia or amyloid-beta (Abeta) accumulation.
“While our study does not rule out a possible association between diet and dementia, we did not find a link in our study, which had a long follow-up period, included younger participants than some other studies and did not require people to remember what foods they had eaten regularly years before,” study investigator Isabelle Glans, MD, of Lund (Sweden) University, said in a news release.
The findings were published online in Neurology.
No risk reduction
Several studies have investigated how dietary habits affect dementia risk, with inconsistent results.
The new findings are based on 28,025 adults (61% women; mean age, 58 years at baseline) who were free of dementia at baseline and were followed over a 20-year period as part of the Swedish Malmö Diet and Cancer Study. Dietary habits were assessed with a 7-day food diary, detailed food frequency questionnaire, and in-person interview.
During follow-up, 1,943 individuals (6.9%) developed dementia.
Compared with those who did not develop dementia, those who did develop dementia during follow-up were older and had a lower level of education and more cardiovascular risk factors and comorbidities at baseline.
Individuals who adhered to conventional healthy dietary recommendations did not have a lower risk of developing all-cause dementia (hazard ratio comparing worst with best adherence, 0.93; 95% confidence interval, 0.81-1.08), Alzheimer’s disease (HR, 1.03; 95% CI, 0.85-1.23) or vascular dementia (HR, 0.93; 95% CI, 0.69-1.26).
Adherence to the modified Mediterranean diet also did not appear to lower the risk of all-cause dementia (HR, 0.93; 95% CI, 0.75-1.15), Alzheimer’s disease (HR, 0.90; 95% CI, 0.68-1.19), or vascular dementia (HR, 1.00; 95% CI, 0.65-1.55).
There was also no significant association between diet and Alzheimer’s disease–related pathology, as measured by cerebrospinal fluid analysis of Abeta42 in a subgroup of 738 participants. Various sensitivity analyses yielded similar results.
Diet still matters
The authors of an accompanying editorial noted that diet as a “singular factor may not have a strong enough effect on cognition, but is more likely to be considered as one factor embedded with various others, the sum of which may influence the course of cognitive function (diet, regular exercise, vascular risk factor control, avoiding cigarette smoking, drinking alcohol in moderation, etc).
“Diet should not be forgotten and it still matters” but should be regarded as “one part of a multidomain intervention with respect to cognitive performance,” wrote Nils Peters, MD, with the University of Basel (Switzerland), and Benedetta Nacmias, PhD, with the University of Florence (Italy)).
“Key questions that remain include how to provide evidence for promoting the implications of dietary habits on cognition? Overall, dietary strategies will most likely be implicated either in order to reduce the increasing number of older subjects with dementia, or to extend healthy life expectancy, or both,” Dr. Peters and Dr. Nacmias said.
The study had no commercial funding. Dr. Glans, Dr. Peters, and Dr. Nacmias disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Contrary to some prior studies,
After adjusting for relevant demographic and other lifestyle measures, there was no association between adherence to healthy dietary advice or the Mediterranean diet on the future risk of dementia or amyloid-beta (Abeta) accumulation.
“While our study does not rule out a possible association between diet and dementia, we did not find a link in our study, which had a long follow-up period, included younger participants than some other studies and did not require people to remember what foods they had eaten regularly years before,” study investigator Isabelle Glans, MD, of Lund (Sweden) University, said in a news release.
The findings were published online in Neurology.
No risk reduction
Several studies have investigated how dietary habits affect dementia risk, with inconsistent results.
The new findings are based on 28,025 adults (61% women; mean age, 58 years at baseline) who were free of dementia at baseline and were followed over a 20-year period as part of the Swedish Malmö Diet and Cancer Study. Dietary habits were assessed with a 7-day food diary, detailed food frequency questionnaire, and in-person interview.
During follow-up, 1,943 individuals (6.9%) developed dementia.
Compared with those who did not develop dementia, those who did develop dementia during follow-up were older and had a lower level of education and more cardiovascular risk factors and comorbidities at baseline.
Individuals who adhered to conventional healthy dietary recommendations did not have a lower risk of developing all-cause dementia (hazard ratio comparing worst with best adherence, 0.93; 95% confidence interval, 0.81-1.08), Alzheimer’s disease (HR, 1.03; 95% CI, 0.85-1.23) or vascular dementia (HR, 0.93; 95% CI, 0.69-1.26).
Adherence to the modified Mediterranean diet also did not appear to lower the risk of all-cause dementia (HR, 0.93; 95% CI, 0.75-1.15), Alzheimer’s disease (HR, 0.90; 95% CI, 0.68-1.19), or vascular dementia (HR, 1.00; 95% CI, 0.65-1.55).
There was also no significant association between diet and Alzheimer’s disease–related pathology, as measured by cerebrospinal fluid analysis of Abeta42 in a subgroup of 738 participants. Various sensitivity analyses yielded similar results.
Diet still matters
The authors of an accompanying editorial noted that diet as a “singular factor may not have a strong enough effect on cognition, but is more likely to be considered as one factor embedded with various others, the sum of which may influence the course of cognitive function (diet, regular exercise, vascular risk factor control, avoiding cigarette smoking, drinking alcohol in moderation, etc).
“Diet should not be forgotten and it still matters” but should be regarded as “one part of a multidomain intervention with respect to cognitive performance,” wrote Nils Peters, MD, with the University of Basel (Switzerland), and Benedetta Nacmias, PhD, with the University of Florence (Italy)).
“Key questions that remain include how to provide evidence for promoting the implications of dietary habits on cognition? Overall, dietary strategies will most likely be implicated either in order to reduce the increasing number of older subjects with dementia, or to extend healthy life expectancy, or both,” Dr. Peters and Dr. Nacmias said.
The study had no commercial funding. Dr. Glans, Dr. Peters, and Dr. Nacmias disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY
Finerenone benefits T2D across spectrum of renal function
Treatment with finerenone produced roughly similar reductions in heart failure–related outcomes in people with type 2 diabetes and chronic kidney disease (CKD) across the spectrum of kidney function, compared with placebo, including those who had albuminuria but a preserved estimated glomerular filtration rate (eGFR), in a post hoc analysis of pooled data from more than 13,000 people.
The findings, from the two pivotal trials for the agent, “reinforce the importance of routine eGFR and UACR [urinary albumin-to-creatinine ratio] screening” in people with type 2 diabetes to identify new candidates for treatment with finerenone (Kerendia), Gerasimos Filippatos, MD, and coauthors said in a report published online in JACC: Heart Failure.
Among the 13,026 patients in the two combined trials, 40% had a preserved eGFR of greater than 60 mL/min per 1.73 m2 despite also having albuminuria with a UACR of at least 30 mg/g, showing how often this combination occurs. But many clinicians “do not follow the guidelines” and fail to measure the UACR in these patients in routine practice, noted Dr. Filippatos at the annual congress of the European Society of Cardiology in August.
“We now have something to do for these patients,” treat them with finerenone, said Dr. Filippatos, professor and director of heart failure at the Attikon University Hospital, Athens.
The availability of finerenone following its U.S. approval in 2021 means clinicians “must get used to measuring UACR” in people with type 2 diabetes even when their eGFR is normal, especially people with type 2 diabetes plus high cardiovascular disease risk, he said.
The Food and Drug Administration approved finerenone, a nonsteroidal mineralocorticoid receptor antagonist, for treating people with type 2 diabetes and CKD in July 2021, but its uptake has been slow, experts say. In a talk in September 2022 during the annual meeting of the European Association for the Study of Diabetes, Jennifer B. Green, MD, estimated that U.S. uptake of finerenone for appropriate people with type 2 diabetes had not advanced beyond 10%.
A recent review also noted that uptake of screening for elevated UACR in U.S. patients with type 2 diabetes was in the range of 10%-40% during 2017-2019, a “shockingly low rate,” said Dr. Green, a professor and diabetes specialist at Duke University, Durham, N.C.
A new reason to screen for albuminuria
“It’s an extremely important message,” Johann Bauersachs, MD, commented in an interview. Results from “many studies have shown that albuminuria is an excellent additional marker for cardiovascular disease risk. But measurement of albuminuria is not widely done, despite guidelines that recommend annual albuminuria testing in people with type 2 diabetes,” said Dr. Bauersachs, professor and head of the department of cardiology at Hannover (Germany) Medical School.
“Even before there was finerenone, there were reasons to measure UACR, but I hope adding finerenone will help, and more clinicians will incorporate UACR into their routine practice,” said Dr. Bauersachs, who was not involved with the finerenone studies.
The analyses reported by Dr. Filippatos and coauthors used data from two related trials of finerenone, FIDELIO-DKD and FIGARO-DKD, combined by prespecified design into a single dataset, FIDELITY, with a total of 13,026 participants eligible for analysis and followed for a median of 3 years. All had type 2 diabetes and CKD based on having a UACR of at least 30 mg/g. Their eGFR levels could run as high as 74 mL/min per 1.73 m2 in FIDELIO-DKD, and as high as 90 mL/min/1.73m2 in FIGARO-DKD. The two trials excluded people with heart failure with reduced ejection fraction, and those with a serum potassium greater than 4.8 mmol/L.
In the FIDELITY dataset treatment with finerenone led to a significant 17% reduction in the combined incidence of cardiovascular death or first hospitalization for heart failure relative to those who received placebo. This relative risk reduction was not affected by either eGFR or UACR values at baseline, the new analysis showed.
The analysis also demonstrated a nonsignificant trend toward greater reductions in heart failure–related outcomes among study participants who began with an eGFR in the normal range of at least 60 mL/min per 1.73 m2. The researchers also found a nonsignificant trend to a greater reduction in heart failure–related events among those with a UACR of less than 300 mg/g.
Finerenone favors patients with less advanced CKD
In short “the magnitude of the treatment benefit tended to favor patients with less advanced CKD,” concluded the researchers, suggesting that “earlier intervention [with finerenone] in the CKD course is likely to provide the greatest long-term benefit on heart failure–related outcomes.” This led them to further infer “the importance of not only routine assessing eGFR, but also perhaps more importantly, routinely screening for UACR to facilitate early diagnosis and early intervention in patients with type 2 diabetes.”
Findings from FIDELIO-DKD and FIGARO-DKD led to recent guideline additions for finerenone by several medical groups. In August 2022, the American Association of Clinical Endocrinologists released an update to its guideline for managing people with diabetes that recommended treating people with type 2 diabetes with finerenone when they have a UACR of at least 30 mg/g if they are already treated with a maximum-tolerated dose of a renin-angiotensin system inhibitor, have a normal serum potassium level, and have an eGFR of at least 25 mL/min per 1.73 m2. The identical recommendation also appeared in a Consensus Report from the American Diabetes Association and KDIGO, an international organization promoting evidence-based management of patients with CKD.
“Finerenone provides a very important contribution because it improves prognosis even in very well managed patients” with type 2 diabetes, commented Lars Rydén, MD, professor of cardiology at the Karolinska Institute in Stockholm, as designated discussant for the report by Dr. Filippatos at the ESC congress.
The findings from the FIDELITY analysis are “trustworthy, and clinically important,” Dr. Rydén said. When left untreated, diabetic kidney disease “reduces life expectancy by an average of 16 years.”
The finerenone trials were sponsored by Bayer, which markets finerenone (Kerendia). Dr. Filippatos has received lecture fees from Bayer as well as from Amgen, Medtronic, Novartis, Servier, and Vifor. Dr. Green has financial ties to Bayer as well as to Anji, AstraZeneca, Boehringer Ingelheim/Lilly, Hawthorne Effect/Omada, Merck, Novo Nordisk, Pfizer, Roche, Sanofi/Lexicon, and Valo. Dr. Bauersachs has been a consultant to Bayer as well as to Amgen, AstraZeneca, Boehringer Ingelheim, Cardior, Cervia, CVRx, Novartis, Pfizer, and Vifor, and he has received research funding from Abiomed. Dr. Rydén has financial ties to Bayer, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk.
Treatment with finerenone produced roughly similar reductions in heart failure–related outcomes in people with type 2 diabetes and chronic kidney disease (CKD) across the spectrum of kidney function, compared with placebo, including those who had albuminuria but a preserved estimated glomerular filtration rate (eGFR), in a post hoc analysis of pooled data from more than 13,000 people.
The findings, from the two pivotal trials for the agent, “reinforce the importance of routine eGFR and UACR [urinary albumin-to-creatinine ratio] screening” in people with type 2 diabetes to identify new candidates for treatment with finerenone (Kerendia), Gerasimos Filippatos, MD, and coauthors said in a report published online in JACC: Heart Failure.
Among the 13,026 patients in the two combined trials, 40% had a preserved eGFR of greater than 60 mL/min per 1.73 m2 despite also having albuminuria with a UACR of at least 30 mg/g, showing how often this combination occurs. But many clinicians “do not follow the guidelines” and fail to measure the UACR in these patients in routine practice, noted Dr. Filippatos at the annual congress of the European Society of Cardiology in August.
“We now have something to do for these patients,” treat them with finerenone, said Dr. Filippatos, professor and director of heart failure at the Attikon University Hospital, Athens.
The availability of finerenone following its U.S. approval in 2021 means clinicians “must get used to measuring UACR” in people with type 2 diabetes even when their eGFR is normal, especially people with type 2 diabetes plus high cardiovascular disease risk, he said.
The Food and Drug Administration approved finerenone, a nonsteroidal mineralocorticoid receptor antagonist, for treating people with type 2 diabetes and CKD in July 2021, but its uptake has been slow, experts say. In a talk in September 2022 during the annual meeting of the European Association for the Study of Diabetes, Jennifer B. Green, MD, estimated that U.S. uptake of finerenone for appropriate people with type 2 diabetes had not advanced beyond 10%.
A recent review also noted that uptake of screening for elevated UACR in U.S. patients with type 2 diabetes was in the range of 10%-40% during 2017-2019, a “shockingly low rate,” said Dr. Green, a professor and diabetes specialist at Duke University, Durham, N.C.
A new reason to screen for albuminuria
“It’s an extremely important message,” Johann Bauersachs, MD, commented in an interview. Results from “many studies have shown that albuminuria is an excellent additional marker for cardiovascular disease risk. But measurement of albuminuria is not widely done, despite guidelines that recommend annual albuminuria testing in people with type 2 diabetes,” said Dr. Bauersachs, professor and head of the department of cardiology at Hannover (Germany) Medical School.
“Even before there was finerenone, there were reasons to measure UACR, but I hope adding finerenone will help, and more clinicians will incorporate UACR into their routine practice,” said Dr. Bauersachs, who was not involved with the finerenone studies.
The analyses reported by Dr. Filippatos and coauthors used data from two related trials of finerenone, FIDELIO-DKD and FIGARO-DKD, combined by prespecified design into a single dataset, FIDELITY, with a total of 13,026 participants eligible for analysis and followed for a median of 3 years. All had type 2 diabetes and CKD based on having a UACR of at least 30 mg/g. Their eGFR levels could run as high as 74 mL/min per 1.73 m2 in FIDELIO-DKD, and as high as 90 mL/min/1.73m2 in FIGARO-DKD. The two trials excluded people with heart failure with reduced ejection fraction, and those with a serum potassium greater than 4.8 mmol/L.
In the FIDELITY dataset treatment with finerenone led to a significant 17% reduction in the combined incidence of cardiovascular death or first hospitalization for heart failure relative to those who received placebo. This relative risk reduction was not affected by either eGFR or UACR values at baseline, the new analysis showed.
The analysis also demonstrated a nonsignificant trend toward greater reductions in heart failure–related outcomes among study participants who began with an eGFR in the normal range of at least 60 mL/min per 1.73 m2. The researchers also found a nonsignificant trend to a greater reduction in heart failure–related events among those with a UACR of less than 300 mg/g.
Finerenone favors patients with less advanced CKD
In short “the magnitude of the treatment benefit tended to favor patients with less advanced CKD,” concluded the researchers, suggesting that “earlier intervention [with finerenone] in the CKD course is likely to provide the greatest long-term benefit on heart failure–related outcomes.” This led them to further infer “the importance of not only routine assessing eGFR, but also perhaps more importantly, routinely screening for UACR to facilitate early diagnosis and early intervention in patients with type 2 diabetes.”
Findings from FIDELIO-DKD and FIGARO-DKD led to recent guideline additions for finerenone by several medical groups. In August 2022, the American Association of Clinical Endocrinologists released an update to its guideline for managing people with diabetes that recommended treating people with type 2 diabetes with finerenone when they have a UACR of at least 30 mg/g if they are already treated with a maximum-tolerated dose of a renin-angiotensin system inhibitor, have a normal serum potassium level, and have an eGFR of at least 25 mL/min per 1.73 m2. The identical recommendation also appeared in a Consensus Report from the American Diabetes Association and KDIGO, an international organization promoting evidence-based management of patients with CKD.
“Finerenone provides a very important contribution because it improves prognosis even in very well managed patients” with type 2 diabetes, commented Lars Rydén, MD, professor of cardiology at the Karolinska Institute in Stockholm, as designated discussant for the report by Dr. Filippatos at the ESC congress.
The findings from the FIDELITY analysis are “trustworthy, and clinically important,” Dr. Rydén said. When left untreated, diabetic kidney disease “reduces life expectancy by an average of 16 years.”
The finerenone trials were sponsored by Bayer, which markets finerenone (Kerendia). Dr. Filippatos has received lecture fees from Bayer as well as from Amgen, Medtronic, Novartis, Servier, and Vifor. Dr. Green has financial ties to Bayer as well as to Anji, AstraZeneca, Boehringer Ingelheim/Lilly, Hawthorne Effect/Omada, Merck, Novo Nordisk, Pfizer, Roche, Sanofi/Lexicon, and Valo. Dr. Bauersachs has been a consultant to Bayer as well as to Amgen, AstraZeneca, Boehringer Ingelheim, Cardior, Cervia, CVRx, Novartis, Pfizer, and Vifor, and he has received research funding from Abiomed. Dr. Rydén has financial ties to Bayer, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk.
Treatment with finerenone produced roughly similar reductions in heart failure–related outcomes in people with type 2 diabetes and chronic kidney disease (CKD) across the spectrum of kidney function, compared with placebo, including those who had albuminuria but a preserved estimated glomerular filtration rate (eGFR), in a post hoc analysis of pooled data from more than 13,000 people.
The findings, from the two pivotal trials for the agent, “reinforce the importance of routine eGFR and UACR [urinary albumin-to-creatinine ratio] screening” in people with type 2 diabetes to identify new candidates for treatment with finerenone (Kerendia), Gerasimos Filippatos, MD, and coauthors said in a report published online in JACC: Heart Failure.
Among the 13,026 patients in the two combined trials, 40% had a preserved eGFR of greater than 60 mL/min per 1.73 m2 despite also having albuminuria with a UACR of at least 30 mg/g, showing how often this combination occurs. But many clinicians “do not follow the guidelines” and fail to measure the UACR in these patients in routine practice, noted Dr. Filippatos at the annual congress of the European Society of Cardiology in August.
“We now have something to do for these patients,” treat them with finerenone, said Dr. Filippatos, professor and director of heart failure at the Attikon University Hospital, Athens.
The availability of finerenone following its U.S. approval in 2021 means clinicians “must get used to measuring UACR” in people with type 2 diabetes even when their eGFR is normal, especially people with type 2 diabetes plus high cardiovascular disease risk, he said.
The Food and Drug Administration approved finerenone, a nonsteroidal mineralocorticoid receptor antagonist, for treating people with type 2 diabetes and CKD in July 2021, but its uptake has been slow, experts say. In a talk in September 2022 during the annual meeting of the European Association for the Study of Diabetes, Jennifer B. Green, MD, estimated that U.S. uptake of finerenone for appropriate people with type 2 diabetes had not advanced beyond 10%.
A recent review also noted that uptake of screening for elevated UACR in U.S. patients with type 2 diabetes was in the range of 10%-40% during 2017-2019, a “shockingly low rate,” said Dr. Green, a professor and diabetes specialist at Duke University, Durham, N.C.
A new reason to screen for albuminuria
“It’s an extremely important message,” Johann Bauersachs, MD, commented in an interview. Results from “many studies have shown that albuminuria is an excellent additional marker for cardiovascular disease risk. But measurement of albuminuria is not widely done, despite guidelines that recommend annual albuminuria testing in people with type 2 diabetes,” said Dr. Bauersachs, professor and head of the department of cardiology at Hannover (Germany) Medical School.
“Even before there was finerenone, there were reasons to measure UACR, but I hope adding finerenone will help, and more clinicians will incorporate UACR into their routine practice,” said Dr. Bauersachs, who was not involved with the finerenone studies.
The analyses reported by Dr. Filippatos and coauthors used data from two related trials of finerenone, FIDELIO-DKD and FIGARO-DKD, combined by prespecified design into a single dataset, FIDELITY, with a total of 13,026 participants eligible for analysis and followed for a median of 3 years. All had type 2 diabetes and CKD based on having a UACR of at least 30 mg/g. Their eGFR levels could run as high as 74 mL/min per 1.73 m2 in FIDELIO-DKD, and as high as 90 mL/min/1.73m2 in FIGARO-DKD. The two trials excluded people with heart failure with reduced ejection fraction, and those with a serum potassium greater than 4.8 mmol/L.
In the FIDELITY dataset treatment with finerenone led to a significant 17% reduction in the combined incidence of cardiovascular death or first hospitalization for heart failure relative to those who received placebo. This relative risk reduction was not affected by either eGFR or UACR values at baseline, the new analysis showed.
The analysis also demonstrated a nonsignificant trend toward greater reductions in heart failure–related outcomes among study participants who began with an eGFR in the normal range of at least 60 mL/min per 1.73 m2. The researchers also found a nonsignificant trend to a greater reduction in heart failure–related events among those with a UACR of less than 300 mg/g.
Finerenone favors patients with less advanced CKD
In short “the magnitude of the treatment benefit tended to favor patients with less advanced CKD,” concluded the researchers, suggesting that “earlier intervention [with finerenone] in the CKD course is likely to provide the greatest long-term benefit on heart failure–related outcomes.” This led them to further infer “the importance of not only routine assessing eGFR, but also perhaps more importantly, routinely screening for UACR to facilitate early diagnosis and early intervention in patients with type 2 diabetes.”
Findings from FIDELIO-DKD and FIGARO-DKD led to recent guideline additions for finerenone by several medical groups. In August 2022, the American Association of Clinical Endocrinologists released an update to its guideline for managing people with diabetes that recommended treating people with type 2 diabetes with finerenone when they have a UACR of at least 30 mg/g if they are already treated with a maximum-tolerated dose of a renin-angiotensin system inhibitor, have a normal serum potassium level, and have an eGFR of at least 25 mL/min per 1.73 m2. The identical recommendation also appeared in a Consensus Report from the American Diabetes Association and KDIGO, an international organization promoting evidence-based management of patients with CKD.
“Finerenone provides a very important contribution because it improves prognosis even in very well managed patients” with type 2 diabetes, commented Lars Rydén, MD, professor of cardiology at the Karolinska Institute in Stockholm, as designated discussant for the report by Dr. Filippatos at the ESC congress.
The findings from the FIDELITY analysis are “trustworthy, and clinically important,” Dr. Rydén said. When left untreated, diabetic kidney disease “reduces life expectancy by an average of 16 years.”
The finerenone trials were sponsored by Bayer, which markets finerenone (Kerendia). Dr. Filippatos has received lecture fees from Bayer as well as from Amgen, Medtronic, Novartis, Servier, and Vifor. Dr. Green has financial ties to Bayer as well as to Anji, AstraZeneca, Boehringer Ingelheim/Lilly, Hawthorne Effect/Omada, Merck, Novo Nordisk, Pfizer, Roche, Sanofi/Lexicon, and Valo. Dr. Bauersachs has been a consultant to Bayer as well as to Amgen, AstraZeneca, Boehringer Ingelheim, Cardior, Cervia, CVRx, Novartis, Pfizer, and Vifor, and he has received research funding from Abiomed. Dr. Rydén has financial ties to Bayer, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk.
FROM JACC: HEART FAILURE
Tirzepatide’s benefits expand: Lean mass up, serum lipids down
STOCKHOLM – New insights into the benefits of treatment with the “twincretin” tirzepatide for people with overweight or obesity – with or without diabetes – come from new findings reported at the annual meeting of the European Association for the Study of Diabetes.
Additional results from the SURMOUNT-1 trial, which matched tirzepatide against placebo in people with overweight or obesity, provide further details on the favorable changes produced by 72 weeks of tirzepatide treatment on outcomes that included fat and lean mass, insulin sensitivity, and patient-reported outcomes related to functional health and well being, reported Ania M. Jastreboff, MD, PhD.
And results from a meta-analysis of six trials that compared tirzepatide (Mounjaro) against several different comparators in patients with type 2 diabetes further confirm the drug’s ability to reliably produce positive changes in blood lipids, especially by significantly lowering levels of triglycerides, LDL cholesterol, and very LDL (VLDL) cholesterol, said Thomas Karagiannis, MD, PhD, in a separate report at the meeting.
Tirzepatide works as an agonist on receptors for both the glucagonlike peptide–1 (GLP-1), and for the glucose-dependent insulinotropic polypeptide, and received Food and Drug Administration approval for treating people with type 2 diabetes in May 2022. On the basis of results from SURMOUNT-1, the FDA on Oct. 6 granted tirzepatide fast-track designation for a proposed labeling of the agent for treating people with overweight or obesity. This FDA decision will likely remain pending at least until results from a second trial in people with overweight or obesity but without diabetes, SURMOUNT-2, become available in 2023.
SURMOUNT-1 randomized 2,539 people with obesity or overweight and at least one weight-related complication to a weekly injection of tirzepatide or placebo for 72 weeks. The study’s primary efficacy endpoints were the average reduction in weight from baseline, and the percentage of people in each treatment arm achieving weight loss of at least 5% from baseline.
For both endpoints, the outcomes with tirzepatide significantly surpassed placebo effects. Average weight loss ranged from 15%-21% from baseline, depending on dose, compared with 3% on placebo. The rate of participants with at least a 5% weight loss ranged from 85% to 91%, compared with 35% with placebo, as reported in July 2022 in the New England Journal of Medicine.
Cutting fat mass, boosting lean mass
New results from the trial reported by Dr. Jastreboff included a cut in fat mass from 46.2% of total body mass at baseline to 38.5% after 72 weeks, compared with a change from 46.8% at baseline to 44.7% after 72 weeks in the placebo group. Concurrently, lean mass increased with tirzepatide treatment from 51.0% at baseline to 58.1% after 72 weeks.
Participants who received tirzepatide, compared with those who received placebo, had “proportionately greater decrease in fat mass and proportionately greater increase in lean mass” compared with those who received placebo, said Dr. Jastreboff, an endocrinologist and obesity medicine specialist with Yale Medicine in New Haven, Conn. “I was impressed by the amount of visceral fat lost.”
These effects translated into a significant reduction in fat mass-to-lean mass ratio among the people treated with tirzepatide, with the greatest reduction in those who lost at least 15% of their starting weight. In that subgroup the fat-to-lean mass ratio dropped from 0.94 at baseline to 0.64 after 72 weeks of treatment, she said.
Focus on diet quality
People treated with tirzepatide “eat so little food that we need to improve the quality of what they eat to protect their muscle,” commented Carel le Roux, MBChB, PhD, a professor in the Diabetes Complications Research Centre of University College Dublin. “You no longer need a dietitian to help people lose weight, because the drug does that. You need dietitians to look after the nutritional health of patients while they lose weight,” Dr. le Roux said in a separate session at the meeting.
Additional tests showed that blood glucose and insulin levels were all significantly lower among trial participants on all three doses of tirzepatide compared with those on placebo, and the tirzepatide-treated subjects also had significant, roughly twofold elevations in their insulin sensitivity measured by the Matsuda Index.
The impact of tirzepatide on glucose and insulin levels and on insulin sensitivity was similar regardless of whether study participants had normoglycemia or prediabetes at entry. By design, no study participants had diabetes.
The trial assessed patient-reported quality-of-life outcomes using the 36-Item Short Form Survey (SF-36). Participants had significant increases in all eight domains within the SF-36 at all three tirzepatide doses, compared with placebo, at 72 weeks, Dr. Jastreboff reported. Improvements in the physical function domain increased most notably among study participants on tirzepatide who had functional limitations at baseline. Heart rate rose among participants who received either of the two highest tirzepatide doses by 2.3-2.5 beats/min, comparable with the effect of other injected incretin-based treatments.
Lipids improve in those with type 2 diabetes
Tirzepatide treatment also results in a “secondary effect” of improving levels of several lipids in people with type 2 diabetes, according to a meta-analysis of findings from six randomized trials. The meta-analysis collectively involved 4,502 participants treated for numerous weeks with one of three doses of tirzepatide and 2,144 people in comparator groups, reported Dr. Karagiannis, a diabetes researcher at Aristotle University of Thessaloniki (Greece).
Among the significant lipid changes linked with tirzepatide treatment, compared with placebo, were an average 13 mg/dL decrease in LDL cholesterol, an average 6 mg/dL decrease in VLDL cholesterol, and an average 50 mg/dL decrease in triglycerides. In comparison to a GLP-1 receptor agonist, an average 25 mg/dL decrease in triglycerides and an average 4 mg/dL reduction in VLDL cholesterol were seen. And trials comparing tirzepatide with basal insulin saw average reductions of 7% in LDL cholesterol, 15% in VLDL cholesterol, 15% in triglycerides, and an 8% increase in HDL cholesterol.
Dr. Karagiannis highlighted that the clinical impact of these effects is unclear, although he noted that the average reduction in LDL cholesterol relative to placebo is of a magnitude that could have a modest effect on long-term outcomes.
These lipid effects of tirzepatide “should be considered alongside” tirzepatide’s “key metabolic effects” on weight and hemoglobin A1c as well as the drug’s safety, concluded Dr. Karagiannis.
The tirzepatide trials were all funded by Eli Lilly, which markets tirzepatide (Mounjaro). Dr. Jastreboff has been an adviser and consultant to Eli Lilly, as well as to Intellihealth, Novo Nordisk, Pfizer, Rhythm Scholars, Roche, and Weight Watchers, and she has received research funding from Eli Lilly and Novo Nordisk. Dr. Karagiannis had no disclosures. Dr. le Roux has had financial relationships with Eli Lilly, as well as with Boehringer Ingelheim, Consilient Health, Covidion, Fractyl, GL Dynamics, Herbalife, Johnson & Johnson, Keyron, and Novo Nordisk.
STOCKHOLM – New insights into the benefits of treatment with the “twincretin” tirzepatide for people with overweight or obesity – with or without diabetes – come from new findings reported at the annual meeting of the European Association for the Study of Diabetes.
Additional results from the SURMOUNT-1 trial, which matched tirzepatide against placebo in people with overweight or obesity, provide further details on the favorable changes produced by 72 weeks of tirzepatide treatment on outcomes that included fat and lean mass, insulin sensitivity, and patient-reported outcomes related to functional health and well being, reported Ania M. Jastreboff, MD, PhD.
And results from a meta-analysis of six trials that compared tirzepatide (Mounjaro) against several different comparators in patients with type 2 diabetes further confirm the drug’s ability to reliably produce positive changes in blood lipids, especially by significantly lowering levels of triglycerides, LDL cholesterol, and very LDL (VLDL) cholesterol, said Thomas Karagiannis, MD, PhD, in a separate report at the meeting.
Tirzepatide works as an agonist on receptors for both the glucagonlike peptide–1 (GLP-1), and for the glucose-dependent insulinotropic polypeptide, and received Food and Drug Administration approval for treating people with type 2 diabetes in May 2022. On the basis of results from SURMOUNT-1, the FDA on Oct. 6 granted tirzepatide fast-track designation for a proposed labeling of the agent for treating people with overweight or obesity. This FDA decision will likely remain pending at least until results from a second trial in people with overweight or obesity but without diabetes, SURMOUNT-2, become available in 2023.
SURMOUNT-1 randomized 2,539 people with obesity or overweight and at least one weight-related complication to a weekly injection of tirzepatide or placebo for 72 weeks. The study’s primary efficacy endpoints were the average reduction in weight from baseline, and the percentage of people in each treatment arm achieving weight loss of at least 5% from baseline.
For both endpoints, the outcomes with tirzepatide significantly surpassed placebo effects. Average weight loss ranged from 15%-21% from baseline, depending on dose, compared with 3% on placebo. The rate of participants with at least a 5% weight loss ranged from 85% to 91%, compared with 35% with placebo, as reported in July 2022 in the New England Journal of Medicine.
Cutting fat mass, boosting lean mass
New results from the trial reported by Dr. Jastreboff included a cut in fat mass from 46.2% of total body mass at baseline to 38.5% after 72 weeks, compared with a change from 46.8% at baseline to 44.7% after 72 weeks in the placebo group. Concurrently, lean mass increased with tirzepatide treatment from 51.0% at baseline to 58.1% after 72 weeks.
Participants who received tirzepatide, compared with those who received placebo, had “proportionately greater decrease in fat mass and proportionately greater increase in lean mass” compared with those who received placebo, said Dr. Jastreboff, an endocrinologist and obesity medicine specialist with Yale Medicine in New Haven, Conn. “I was impressed by the amount of visceral fat lost.”
These effects translated into a significant reduction in fat mass-to-lean mass ratio among the people treated with tirzepatide, with the greatest reduction in those who lost at least 15% of their starting weight. In that subgroup the fat-to-lean mass ratio dropped from 0.94 at baseline to 0.64 after 72 weeks of treatment, she said.
Focus on diet quality
People treated with tirzepatide “eat so little food that we need to improve the quality of what they eat to protect their muscle,” commented Carel le Roux, MBChB, PhD, a professor in the Diabetes Complications Research Centre of University College Dublin. “You no longer need a dietitian to help people lose weight, because the drug does that. You need dietitians to look after the nutritional health of patients while they lose weight,” Dr. le Roux said in a separate session at the meeting.
Additional tests showed that blood glucose and insulin levels were all significantly lower among trial participants on all three doses of tirzepatide compared with those on placebo, and the tirzepatide-treated subjects also had significant, roughly twofold elevations in their insulin sensitivity measured by the Matsuda Index.
The impact of tirzepatide on glucose and insulin levels and on insulin sensitivity was similar regardless of whether study participants had normoglycemia or prediabetes at entry. By design, no study participants had diabetes.
The trial assessed patient-reported quality-of-life outcomes using the 36-Item Short Form Survey (SF-36). Participants had significant increases in all eight domains within the SF-36 at all three tirzepatide doses, compared with placebo, at 72 weeks, Dr. Jastreboff reported. Improvements in the physical function domain increased most notably among study participants on tirzepatide who had functional limitations at baseline. Heart rate rose among participants who received either of the two highest tirzepatide doses by 2.3-2.5 beats/min, comparable with the effect of other injected incretin-based treatments.
Lipids improve in those with type 2 diabetes
Tirzepatide treatment also results in a “secondary effect” of improving levels of several lipids in people with type 2 diabetes, according to a meta-analysis of findings from six randomized trials. The meta-analysis collectively involved 4,502 participants treated for numerous weeks with one of three doses of tirzepatide and 2,144 people in comparator groups, reported Dr. Karagiannis, a diabetes researcher at Aristotle University of Thessaloniki (Greece).
Among the significant lipid changes linked with tirzepatide treatment, compared with placebo, were an average 13 mg/dL decrease in LDL cholesterol, an average 6 mg/dL decrease in VLDL cholesterol, and an average 50 mg/dL decrease in triglycerides. In comparison to a GLP-1 receptor agonist, an average 25 mg/dL decrease in triglycerides and an average 4 mg/dL reduction in VLDL cholesterol were seen. And trials comparing tirzepatide with basal insulin saw average reductions of 7% in LDL cholesterol, 15% in VLDL cholesterol, 15% in triglycerides, and an 8% increase in HDL cholesterol.
Dr. Karagiannis highlighted that the clinical impact of these effects is unclear, although he noted that the average reduction in LDL cholesterol relative to placebo is of a magnitude that could have a modest effect on long-term outcomes.
These lipid effects of tirzepatide “should be considered alongside” tirzepatide’s “key metabolic effects” on weight and hemoglobin A1c as well as the drug’s safety, concluded Dr. Karagiannis.
The tirzepatide trials were all funded by Eli Lilly, which markets tirzepatide (Mounjaro). Dr. Jastreboff has been an adviser and consultant to Eli Lilly, as well as to Intellihealth, Novo Nordisk, Pfizer, Rhythm Scholars, Roche, and Weight Watchers, and she has received research funding from Eli Lilly and Novo Nordisk. Dr. Karagiannis had no disclosures. Dr. le Roux has had financial relationships with Eli Lilly, as well as with Boehringer Ingelheim, Consilient Health, Covidion, Fractyl, GL Dynamics, Herbalife, Johnson & Johnson, Keyron, and Novo Nordisk.
STOCKHOLM – New insights into the benefits of treatment with the “twincretin” tirzepatide for people with overweight or obesity – with or without diabetes – come from new findings reported at the annual meeting of the European Association for the Study of Diabetes.
Additional results from the SURMOUNT-1 trial, which matched tirzepatide against placebo in people with overweight or obesity, provide further details on the favorable changes produced by 72 weeks of tirzepatide treatment on outcomes that included fat and lean mass, insulin sensitivity, and patient-reported outcomes related to functional health and well being, reported Ania M. Jastreboff, MD, PhD.
And results from a meta-analysis of six trials that compared tirzepatide (Mounjaro) against several different comparators in patients with type 2 diabetes further confirm the drug’s ability to reliably produce positive changes in blood lipids, especially by significantly lowering levels of triglycerides, LDL cholesterol, and very LDL (VLDL) cholesterol, said Thomas Karagiannis, MD, PhD, in a separate report at the meeting.
Tirzepatide works as an agonist on receptors for both the glucagonlike peptide–1 (GLP-1), and for the glucose-dependent insulinotropic polypeptide, and received Food and Drug Administration approval for treating people with type 2 diabetes in May 2022. On the basis of results from SURMOUNT-1, the FDA on Oct. 6 granted tirzepatide fast-track designation for a proposed labeling of the agent for treating people with overweight or obesity. This FDA decision will likely remain pending at least until results from a second trial in people with overweight or obesity but without diabetes, SURMOUNT-2, become available in 2023.
SURMOUNT-1 randomized 2,539 people with obesity or overweight and at least one weight-related complication to a weekly injection of tirzepatide or placebo for 72 weeks. The study’s primary efficacy endpoints were the average reduction in weight from baseline, and the percentage of people in each treatment arm achieving weight loss of at least 5% from baseline.
For both endpoints, the outcomes with tirzepatide significantly surpassed placebo effects. Average weight loss ranged from 15%-21% from baseline, depending on dose, compared with 3% on placebo. The rate of participants with at least a 5% weight loss ranged from 85% to 91%, compared with 35% with placebo, as reported in July 2022 in the New England Journal of Medicine.
Cutting fat mass, boosting lean mass
New results from the trial reported by Dr. Jastreboff included a cut in fat mass from 46.2% of total body mass at baseline to 38.5% after 72 weeks, compared with a change from 46.8% at baseline to 44.7% after 72 weeks in the placebo group. Concurrently, lean mass increased with tirzepatide treatment from 51.0% at baseline to 58.1% after 72 weeks.
Participants who received tirzepatide, compared with those who received placebo, had “proportionately greater decrease in fat mass and proportionately greater increase in lean mass” compared with those who received placebo, said Dr. Jastreboff, an endocrinologist and obesity medicine specialist with Yale Medicine in New Haven, Conn. “I was impressed by the amount of visceral fat lost.”
These effects translated into a significant reduction in fat mass-to-lean mass ratio among the people treated with tirzepatide, with the greatest reduction in those who lost at least 15% of their starting weight. In that subgroup the fat-to-lean mass ratio dropped from 0.94 at baseline to 0.64 after 72 weeks of treatment, she said.
Focus on diet quality
People treated with tirzepatide “eat so little food that we need to improve the quality of what they eat to protect their muscle,” commented Carel le Roux, MBChB, PhD, a professor in the Diabetes Complications Research Centre of University College Dublin. “You no longer need a dietitian to help people lose weight, because the drug does that. You need dietitians to look after the nutritional health of patients while they lose weight,” Dr. le Roux said in a separate session at the meeting.
Additional tests showed that blood glucose and insulin levels were all significantly lower among trial participants on all three doses of tirzepatide compared with those on placebo, and the tirzepatide-treated subjects also had significant, roughly twofold elevations in their insulin sensitivity measured by the Matsuda Index.
The impact of tirzepatide on glucose and insulin levels and on insulin sensitivity was similar regardless of whether study participants had normoglycemia or prediabetes at entry. By design, no study participants had diabetes.
The trial assessed patient-reported quality-of-life outcomes using the 36-Item Short Form Survey (SF-36). Participants had significant increases in all eight domains within the SF-36 at all three tirzepatide doses, compared with placebo, at 72 weeks, Dr. Jastreboff reported. Improvements in the physical function domain increased most notably among study participants on tirzepatide who had functional limitations at baseline. Heart rate rose among participants who received either of the two highest tirzepatide doses by 2.3-2.5 beats/min, comparable with the effect of other injected incretin-based treatments.
Lipids improve in those with type 2 diabetes
Tirzepatide treatment also results in a “secondary effect” of improving levels of several lipids in people with type 2 diabetes, according to a meta-analysis of findings from six randomized trials. The meta-analysis collectively involved 4,502 participants treated for numerous weeks with one of three doses of tirzepatide and 2,144 people in comparator groups, reported Dr. Karagiannis, a diabetes researcher at Aristotle University of Thessaloniki (Greece).
Among the significant lipid changes linked with tirzepatide treatment, compared with placebo, were an average 13 mg/dL decrease in LDL cholesterol, an average 6 mg/dL decrease in VLDL cholesterol, and an average 50 mg/dL decrease in triglycerides. In comparison to a GLP-1 receptor agonist, an average 25 mg/dL decrease in triglycerides and an average 4 mg/dL reduction in VLDL cholesterol were seen. And trials comparing tirzepatide with basal insulin saw average reductions of 7% in LDL cholesterol, 15% in VLDL cholesterol, 15% in triglycerides, and an 8% increase in HDL cholesterol.
Dr. Karagiannis highlighted that the clinical impact of these effects is unclear, although he noted that the average reduction in LDL cholesterol relative to placebo is of a magnitude that could have a modest effect on long-term outcomes.
These lipid effects of tirzepatide “should be considered alongside” tirzepatide’s “key metabolic effects” on weight and hemoglobin A1c as well as the drug’s safety, concluded Dr. Karagiannis.
The tirzepatide trials were all funded by Eli Lilly, which markets tirzepatide (Mounjaro). Dr. Jastreboff has been an adviser and consultant to Eli Lilly, as well as to Intellihealth, Novo Nordisk, Pfizer, Rhythm Scholars, Roche, and Weight Watchers, and she has received research funding from Eli Lilly and Novo Nordisk. Dr. Karagiannis had no disclosures. Dr. le Roux has had financial relationships with Eli Lilly, as well as with Boehringer Ingelheim, Consilient Health, Covidion, Fractyl, GL Dynamics, Herbalife, Johnson & Johnson, Keyron, and Novo Nordisk.
AT EASD 2022
Headache for inpatients with COVID-19 may predict better survival
, according to recent research published in the journal Headache.
In the systematic review and meta-analysis, Víctor J. Gallardo, MSc, of the headache and neurologic pain research group, Vall d’Hebron Research Institute at the Universitat Autònoma de Barcelona, and colleagues performed a search of studies in PubMed involving headache symptoms, disease survival, and inpatient COVID-19 cases published between December 2019 and December 2020. Overall, 48 studies were identified, consisting of 43,169 inpatients with COVID-19. Using random-effects pooling models, Mr. Gallardo and colleagues estimated the prevalence of headache for inpatients who survived COVID-19, compared with those who did not survive.
Within those studies, 35,132 inpatients (81.4%) survived, while 8,037 inpatients (18.6%) died from COVID-19. The researchers found that inpatients with COVID-19 and headache symptoms had a significantly higher survival rate compared with inpatients with COVID-19 without headache symptoms (risk ratio, 1.90; 95% confidence interval, 1.46-2.47; P < .0001). There was an overall pooled prevalence of headache as a COVID-19 symptom in 10.4% of inpatients, which was reduced to an estimated pooled prevalence of 9.7% after the researchers removed outlier studies in a sensitivity analysis.
Other COVID-19 symptoms that led to improved rates of survival among inpatients were anosmia (RR, 2.94; 95% CI, 1.94-4.45) and myalgia (RR, 1.57; 95% CI, 1.34-1.83) as well as nausea or vomiting (RR, 1.41; 95% CI, 1.08-1.82), while symptoms such as dyspnea, diabetes, chronic liver diseases, chronic respiratory diseases, and chronic kidney diseases were more likely to increase the risk of dying from COVID-19.
The researchers noted several limitations in their meta-analysis that may make their findings less generalizable to future SARS-CoV-2 variants, such as including only studies that were published before COVID-19 vaccines were available and before more infectious SARS-CoV-2 variants like the B.1.617.2 (Delta) variant emerged. They also included studies where inpatients were not tested for COVID-19 because access to testing was not widely available.
“Our meta-analysis points toward a novel possibility: Headache arising secondary to an infection is not a ‘nonspecific’ symptom, but rather it may be a marker of enhanced likelihood of survival. That is, we find that patients reporting headache in the setting of COVID-19 are at reduced risk of death,” Mr. Gallardo and colleagues wrote.
More data needed on association between headache and COVID-19
While headache appeared to affect a small proportion of overall inpatients with COVID-19, the researchers noted this might be because individuals with COVID-19 and headache symptoms are less likely to require hospitalization or a visit to the ED. Another potential explanation is that “people with primary headache disorders, including migraine, may be more likely to report symptoms of COVID-19, but they also may be relatively less likely to experience a life-threatening COVID-19 disease course.”
The researchers said this potential association should be explored in future studies as well as in other viral infections or postviral syndromes such as long COVID. “Defining specific headache mechanisms that could enhance survival from viral infections represents an opportunity for the potential discovery of improved viral therapeutics, as well as for understanding whether, and how, primary headache disorders may be adaptive.”
In a comment, Morris Levin, MD, director of the University of California San Francisco Headache Center, said the findings “of this very thought-provoking review suggest that reporting a headache during a COVID-19 infection seems to be associated with better recovery in hospitalized patients.”
Dr. Levin, who was not involved with the study, acknowledged the researchers’ explanation for the overall low rate of headache in these inpatients as one possible explanation.
“Another could be that sick COVID patients were much more troubled by other symptoms like respiratory distress, which overshadowed their headache symptoms, particularly if they were very ill or if the headache pain was of only mild to moderate severity,” he said. “That could also be an alternate explanation for why less dangerously ill hospitalized patients seemed to have more headaches.”
One limitation he saw in the meta-analysis was how clearly the clinicians characterized headache symptoms in each reviewed study. Dr. Levin suggested a retrospective assessment of premorbid migraine history in hospitalized patients with COVID-19, including survivors and fatalities, might have helped clarify this issue. “The headaches themselves were not characterized so drawing conclusions regarding migraine is challenging.”
Dr. Levin noted it is still not well understood how acute and persistent headaches and other neurological symptoms like mental fog occur in patients with COVID-19. We also do not fully understand the natural history of post-COVID headaches and other neurologic sequelae and the management options for acute and persistent neurological sequelae.
Three authors reported personal and institutional relationships in the form of grants, consultancies, speaker’s bureau positions, guidelines committee member appointments, and editorial board positions for a variety of pharmaceutical companies, agencies, societies, and other organizations. Mr. Gallardo reported no relevant financial disclosures. Dr. Levin reported no relevant financial disclosures.
, according to recent research published in the journal Headache.
In the systematic review and meta-analysis, Víctor J. Gallardo, MSc, of the headache and neurologic pain research group, Vall d’Hebron Research Institute at the Universitat Autònoma de Barcelona, and colleagues performed a search of studies in PubMed involving headache symptoms, disease survival, and inpatient COVID-19 cases published between December 2019 and December 2020. Overall, 48 studies were identified, consisting of 43,169 inpatients with COVID-19. Using random-effects pooling models, Mr. Gallardo and colleagues estimated the prevalence of headache for inpatients who survived COVID-19, compared with those who did not survive.
Within those studies, 35,132 inpatients (81.4%) survived, while 8,037 inpatients (18.6%) died from COVID-19. The researchers found that inpatients with COVID-19 and headache symptoms had a significantly higher survival rate compared with inpatients with COVID-19 without headache symptoms (risk ratio, 1.90; 95% confidence interval, 1.46-2.47; P < .0001). There was an overall pooled prevalence of headache as a COVID-19 symptom in 10.4% of inpatients, which was reduced to an estimated pooled prevalence of 9.7% after the researchers removed outlier studies in a sensitivity analysis.
Other COVID-19 symptoms that led to improved rates of survival among inpatients were anosmia (RR, 2.94; 95% CI, 1.94-4.45) and myalgia (RR, 1.57; 95% CI, 1.34-1.83) as well as nausea or vomiting (RR, 1.41; 95% CI, 1.08-1.82), while symptoms such as dyspnea, diabetes, chronic liver diseases, chronic respiratory diseases, and chronic kidney diseases were more likely to increase the risk of dying from COVID-19.
The researchers noted several limitations in their meta-analysis that may make their findings less generalizable to future SARS-CoV-2 variants, such as including only studies that were published before COVID-19 vaccines were available and before more infectious SARS-CoV-2 variants like the B.1.617.2 (Delta) variant emerged. They also included studies where inpatients were not tested for COVID-19 because access to testing was not widely available.
“Our meta-analysis points toward a novel possibility: Headache arising secondary to an infection is not a ‘nonspecific’ symptom, but rather it may be a marker of enhanced likelihood of survival. That is, we find that patients reporting headache in the setting of COVID-19 are at reduced risk of death,” Mr. Gallardo and colleagues wrote.
More data needed on association between headache and COVID-19
While headache appeared to affect a small proportion of overall inpatients with COVID-19, the researchers noted this might be because individuals with COVID-19 and headache symptoms are less likely to require hospitalization or a visit to the ED. Another potential explanation is that “people with primary headache disorders, including migraine, may be more likely to report symptoms of COVID-19, but they also may be relatively less likely to experience a life-threatening COVID-19 disease course.”
The researchers said this potential association should be explored in future studies as well as in other viral infections or postviral syndromes such as long COVID. “Defining specific headache mechanisms that could enhance survival from viral infections represents an opportunity for the potential discovery of improved viral therapeutics, as well as for understanding whether, and how, primary headache disorders may be adaptive.”
In a comment, Morris Levin, MD, director of the University of California San Francisco Headache Center, said the findings “of this very thought-provoking review suggest that reporting a headache during a COVID-19 infection seems to be associated with better recovery in hospitalized patients.”
Dr. Levin, who was not involved with the study, acknowledged the researchers’ explanation for the overall low rate of headache in these inpatients as one possible explanation.
“Another could be that sick COVID patients were much more troubled by other symptoms like respiratory distress, which overshadowed their headache symptoms, particularly if they were very ill or if the headache pain was of only mild to moderate severity,” he said. “That could also be an alternate explanation for why less dangerously ill hospitalized patients seemed to have more headaches.”
One limitation he saw in the meta-analysis was how clearly the clinicians characterized headache symptoms in each reviewed study. Dr. Levin suggested a retrospective assessment of premorbid migraine history in hospitalized patients with COVID-19, including survivors and fatalities, might have helped clarify this issue. “The headaches themselves were not characterized so drawing conclusions regarding migraine is challenging.”
Dr. Levin noted it is still not well understood how acute and persistent headaches and other neurological symptoms like mental fog occur in patients with COVID-19. We also do not fully understand the natural history of post-COVID headaches and other neurologic sequelae and the management options for acute and persistent neurological sequelae.
Three authors reported personal and institutional relationships in the form of grants, consultancies, speaker’s bureau positions, guidelines committee member appointments, and editorial board positions for a variety of pharmaceutical companies, agencies, societies, and other organizations. Mr. Gallardo reported no relevant financial disclosures. Dr. Levin reported no relevant financial disclosures.
, according to recent research published in the journal Headache.
In the systematic review and meta-analysis, Víctor J. Gallardo, MSc, of the headache and neurologic pain research group, Vall d’Hebron Research Institute at the Universitat Autònoma de Barcelona, and colleagues performed a search of studies in PubMed involving headache symptoms, disease survival, and inpatient COVID-19 cases published between December 2019 and December 2020. Overall, 48 studies were identified, consisting of 43,169 inpatients with COVID-19. Using random-effects pooling models, Mr. Gallardo and colleagues estimated the prevalence of headache for inpatients who survived COVID-19, compared with those who did not survive.
Within those studies, 35,132 inpatients (81.4%) survived, while 8,037 inpatients (18.6%) died from COVID-19. The researchers found that inpatients with COVID-19 and headache symptoms had a significantly higher survival rate compared with inpatients with COVID-19 without headache symptoms (risk ratio, 1.90; 95% confidence interval, 1.46-2.47; P < .0001). There was an overall pooled prevalence of headache as a COVID-19 symptom in 10.4% of inpatients, which was reduced to an estimated pooled prevalence of 9.7% after the researchers removed outlier studies in a sensitivity analysis.
Other COVID-19 symptoms that led to improved rates of survival among inpatients were anosmia (RR, 2.94; 95% CI, 1.94-4.45) and myalgia (RR, 1.57; 95% CI, 1.34-1.83) as well as nausea or vomiting (RR, 1.41; 95% CI, 1.08-1.82), while symptoms such as dyspnea, diabetes, chronic liver diseases, chronic respiratory diseases, and chronic kidney diseases were more likely to increase the risk of dying from COVID-19.
The researchers noted several limitations in their meta-analysis that may make their findings less generalizable to future SARS-CoV-2 variants, such as including only studies that were published before COVID-19 vaccines were available and before more infectious SARS-CoV-2 variants like the B.1.617.2 (Delta) variant emerged. They also included studies where inpatients were not tested for COVID-19 because access to testing was not widely available.
“Our meta-analysis points toward a novel possibility: Headache arising secondary to an infection is not a ‘nonspecific’ symptom, but rather it may be a marker of enhanced likelihood of survival. That is, we find that patients reporting headache in the setting of COVID-19 are at reduced risk of death,” Mr. Gallardo and colleagues wrote.
More data needed on association between headache and COVID-19
While headache appeared to affect a small proportion of overall inpatients with COVID-19, the researchers noted this might be because individuals with COVID-19 and headache symptoms are less likely to require hospitalization or a visit to the ED. Another potential explanation is that “people with primary headache disorders, including migraine, may be more likely to report symptoms of COVID-19, but they also may be relatively less likely to experience a life-threatening COVID-19 disease course.”
The researchers said this potential association should be explored in future studies as well as in other viral infections or postviral syndromes such as long COVID. “Defining specific headache mechanisms that could enhance survival from viral infections represents an opportunity for the potential discovery of improved viral therapeutics, as well as for understanding whether, and how, primary headache disorders may be adaptive.”
In a comment, Morris Levin, MD, director of the University of California San Francisco Headache Center, said the findings “of this very thought-provoking review suggest that reporting a headache during a COVID-19 infection seems to be associated with better recovery in hospitalized patients.”
Dr. Levin, who was not involved with the study, acknowledged the researchers’ explanation for the overall low rate of headache in these inpatients as one possible explanation.
“Another could be that sick COVID patients were much more troubled by other symptoms like respiratory distress, which overshadowed their headache symptoms, particularly if they were very ill or if the headache pain was of only mild to moderate severity,” he said. “That could also be an alternate explanation for why less dangerously ill hospitalized patients seemed to have more headaches.”
One limitation he saw in the meta-analysis was how clearly the clinicians characterized headache symptoms in each reviewed study. Dr. Levin suggested a retrospective assessment of premorbid migraine history in hospitalized patients with COVID-19, including survivors and fatalities, might have helped clarify this issue. “The headaches themselves were not characterized so drawing conclusions regarding migraine is challenging.”
Dr. Levin noted it is still not well understood how acute and persistent headaches and other neurological symptoms like mental fog occur in patients with COVID-19. We also do not fully understand the natural history of post-COVID headaches and other neurologic sequelae and the management options for acute and persistent neurological sequelae.
Three authors reported personal and institutional relationships in the form of grants, consultancies, speaker’s bureau positions, guidelines committee member appointments, and editorial board positions for a variety of pharmaceutical companies, agencies, societies, and other organizations. Mr. Gallardo reported no relevant financial disclosures. Dr. Levin reported no relevant financial disclosures.
FROM HEADACHE
New advice on artificial pancreas insulin delivery systems
A new consensus statement summarizes the benefits, limitations, and challenges of using automated insulin delivery (AID) systems and provides recommendations for use by people with diabetes.
“Automated insulin delivery systems” is becoming the standard terminology – including by the U.S. Food and Drug Administration – to refer to systems that integrate data from a continuous glucose monitoring (CGM) system via a control algorithm into an insulin pump in order to automate subcutaneous insulin delivery. “Hybrid AID” or “hybrid closed-loop” refers to the current status of these systems, which still require some degree of user input to control glucose levels.
The term “artificial pancreas” was used interchangeably with AID in the past, but it doesn’t take into account exocrine pancreatic function. The term “bionic pancreas” refers to a specific system in development that would ultimately include glucagon along with insulin.
The new consensus report, titled “Automated insulin delivery: Benefits, challenges, and recommendations,” was published online in Diabetes Care and Diabetologia.
The document is geared toward not only diabetologists and other specialists, but also diabetes nurses and specialist dietitians. Colleagues working at regulatory agencies, health care organizations, and related media might also benefit from reading it.
It is endorsed by two professional societies – the European Association for the Study of Diabetes and the American Diabetes Association – and contrasts with other statements about AID systems that are sponsored by their manufacturers, noted document co-author Mark Evans, PhD, professor of diabetic medicine, University of Cambridge, England, in a statement.
“Many clinically relevant aspects, including safety, are addressed in this report. The aim ... is to encourage ongoing improvement of this technology, its safe and effective use, and its accessibility to all who can benefit from it,” Dr. Evans said.
Lead author Jennifer Sherr, MD, PhD, pediatric endocrinology, Yale University, New Haven, Conn., commented that the report “addresses the clinical usage of AID systems from a practical point of view rather than as ... a meta-analysis or a review of all relevant clinical studies. ... As such, the benefits and limitations of systems are discussed while also considering safety, regulatory pathways, and access to this technology.”
AID systems do not mean diabetes is “cured”
Separate recommendations provided at the end of the document are aimed at specific stakeholders, including health care providers, patients and their caregivers, manufacturers, regulatory agencies, and the research community.
The authors make clear in the introduction that, while representing “a significant movement toward optimizing glucose management for individuals with diabetes,” the use of AID systems doesn’t mean that diabetes is “cured.” Rather, “expectations need to be set adequately so that individuals with diabetes and providers understand what such systems can and cannot do.”
In particular, current commercially available AID systems require user input for mealtime insulin dosing and sometimes for correction doses of high blood glucose levels, although the systems at least partially automate that.
“When integrated into care, AID systems hold promise to relieve some of the daily burdens of diabetes care,” the authors write.
The statement also details problems that may arise with the physical devices, including skin irritation from adhesives, occlusion of insulin infusion sets, early CGM sensor failure, and inadequate dosing algorithms.
“Individuals with diabetes who are considering this type of advanced diabetes therapy should not only have appropriate technical understanding of the system but also be able to revert to standard diabetes treatment (that is, nonautomated subcutaneous insulin delivery by pump or injections) in case the AID system fails. They should be able to independently troubleshoot and have access to their health care provider if needed.”
To monitor the impact of the technology, the authors emphasize the importance of the time-in-range metric derived from CGM, with the goal of achieving 70% or greater time in target blood glucose range.
Separate sections of the document address the benefits and limitations of AID systems, education and expectations for both patients and providers, and patient and provider perspectives, including how to handle urgent questions.
Other sections cover special populations such as pregnant women and people with type 2 diabetes, considerations for patient selection for current AID systems, safety, improving access to the technology, liability, and do-it-yourself systems.
Recommendations for health care professionals
A table near the end of the document provides specific recommendations for health care professionals, including the following:
- Be knowledgeable about AID systems and nuances of different systems, including their distinguishing features as well as strengths and weaknesses.
- Inform patients with diabetes about AID systems, including review of currently available systems, and create realistic expectations for device use.
- Involve patients with diabetes in shared decision-making when considering use of AID systems.
- Share information with patients with diabetes, as well as their peers, about general standards set by national and international guidelines on AID systems.
- Provide an on-call number or method by which a person with diabetes can always access support from a health care provider at the practice, including weekends and nights.
- Implement, potentially, protocols on times when AID systems should not be used.
- Use an individual’s health data to improve quality of care and health outcomes.
Most members of the ADA/EASD Diabetes Technology Working Group work with industry, but industry had no input on the project. Dr. Sherr has reported conducting clinical trials for Eli Lilly, Insulet, and Medtronic, and has received in-kind support for research studies from Dexcom and Medtronic. She has also reported consulting for Eli Lilly, Lexicon, Medtronic, and Sanofi, and being an advisory board member for Bigfoot Biomedical, Cecelia Health, Eli Lilly, Insulet, T1D Fund, and Vertex Pharmaceuticals. Dr. Evans has reported conducting clinical trials or research collaborations for, serving on advisory boards for, or receiving speakers fees or travel support from Medtronic, Roche, Abbott Diabetes Care, Dexcom, Novo Nordisk, Eli Lilly, Sanofi, Zucara Therapeutics, Pila Pharma, and AstraZeneca. The University of Cambridge has received salary support for Dr. Evans from the National Health Service.
A version of this article first appeared on Medscape.com.
A new consensus statement summarizes the benefits, limitations, and challenges of using automated insulin delivery (AID) systems and provides recommendations for use by people with diabetes.
“Automated insulin delivery systems” is becoming the standard terminology – including by the U.S. Food and Drug Administration – to refer to systems that integrate data from a continuous glucose monitoring (CGM) system via a control algorithm into an insulin pump in order to automate subcutaneous insulin delivery. “Hybrid AID” or “hybrid closed-loop” refers to the current status of these systems, which still require some degree of user input to control glucose levels.
The term “artificial pancreas” was used interchangeably with AID in the past, but it doesn’t take into account exocrine pancreatic function. The term “bionic pancreas” refers to a specific system in development that would ultimately include glucagon along with insulin.
The new consensus report, titled “Automated insulin delivery: Benefits, challenges, and recommendations,” was published online in Diabetes Care and Diabetologia.
The document is geared toward not only diabetologists and other specialists, but also diabetes nurses and specialist dietitians. Colleagues working at regulatory agencies, health care organizations, and related media might also benefit from reading it.
It is endorsed by two professional societies – the European Association for the Study of Diabetes and the American Diabetes Association – and contrasts with other statements about AID systems that are sponsored by their manufacturers, noted document co-author Mark Evans, PhD, professor of diabetic medicine, University of Cambridge, England, in a statement.
“Many clinically relevant aspects, including safety, are addressed in this report. The aim ... is to encourage ongoing improvement of this technology, its safe and effective use, and its accessibility to all who can benefit from it,” Dr. Evans said.
Lead author Jennifer Sherr, MD, PhD, pediatric endocrinology, Yale University, New Haven, Conn., commented that the report “addresses the clinical usage of AID systems from a practical point of view rather than as ... a meta-analysis or a review of all relevant clinical studies. ... As such, the benefits and limitations of systems are discussed while also considering safety, regulatory pathways, and access to this technology.”
AID systems do not mean diabetes is “cured”
Separate recommendations provided at the end of the document are aimed at specific stakeholders, including health care providers, patients and their caregivers, manufacturers, regulatory agencies, and the research community.
The authors make clear in the introduction that, while representing “a significant movement toward optimizing glucose management for individuals with diabetes,” the use of AID systems doesn’t mean that diabetes is “cured.” Rather, “expectations need to be set adequately so that individuals with diabetes and providers understand what such systems can and cannot do.”
In particular, current commercially available AID systems require user input for mealtime insulin dosing and sometimes for correction doses of high blood glucose levels, although the systems at least partially automate that.
“When integrated into care, AID systems hold promise to relieve some of the daily burdens of diabetes care,” the authors write.
The statement also details problems that may arise with the physical devices, including skin irritation from adhesives, occlusion of insulin infusion sets, early CGM sensor failure, and inadequate dosing algorithms.
“Individuals with diabetes who are considering this type of advanced diabetes therapy should not only have appropriate technical understanding of the system but also be able to revert to standard diabetes treatment (that is, nonautomated subcutaneous insulin delivery by pump or injections) in case the AID system fails. They should be able to independently troubleshoot and have access to their health care provider if needed.”
To monitor the impact of the technology, the authors emphasize the importance of the time-in-range metric derived from CGM, with the goal of achieving 70% or greater time in target blood glucose range.
Separate sections of the document address the benefits and limitations of AID systems, education and expectations for both patients and providers, and patient and provider perspectives, including how to handle urgent questions.
Other sections cover special populations such as pregnant women and people with type 2 diabetes, considerations for patient selection for current AID systems, safety, improving access to the technology, liability, and do-it-yourself systems.
Recommendations for health care professionals
A table near the end of the document provides specific recommendations for health care professionals, including the following:
- Be knowledgeable about AID systems and nuances of different systems, including their distinguishing features as well as strengths and weaknesses.
- Inform patients with diabetes about AID systems, including review of currently available systems, and create realistic expectations for device use.
- Involve patients with diabetes in shared decision-making when considering use of AID systems.
- Share information with patients with diabetes, as well as their peers, about general standards set by national and international guidelines on AID systems.
- Provide an on-call number or method by which a person with diabetes can always access support from a health care provider at the practice, including weekends and nights.
- Implement, potentially, protocols on times when AID systems should not be used.
- Use an individual’s health data to improve quality of care and health outcomes.
Most members of the ADA/EASD Diabetes Technology Working Group work with industry, but industry had no input on the project. Dr. Sherr has reported conducting clinical trials for Eli Lilly, Insulet, and Medtronic, and has received in-kind support for research studies from Dexcom and Medtronic. She has also reported consulting for Eli Lilly, Lexicon, Medtronic, and Sanofi, and being an advisory board member for Bigfoot Biomedical, Cecelia Health, Eli Lilly, Insulet, T1D Fund, and Vertex Pharmaceuticals. Dr. Evans has reported conducting clinical trials or research collaborations for, serving on advisory boards for, or receiving speakers fees or travel support from Medtronic, Roche, Abbott Diabetes Care, Dexcom, Novo Nordisk, Eli Lilly, Sanofi, Zucara Therapeutics, Pila Pharma, and AstraZeneca. The University of Cambridge has received salary support for Dr. Evans from the National Health Service.
A version of this article first appeared on Medscape.com.
A new consensus statement summarizes the benefits, limitations, and challenges of using automated insulin delivery (AID) systems and provides recommendations for use by people with diabetes.
“Automated insulin delivery systems” is becoming the standard terminology – including by the U.S. Food and Drug Administration – to refer to systems that integrate data from a continuous glucose monitoring (CGM) system via a control algorithm into an insulin pump in order to automate subcutaneous insulin delivery. “Hybrid AID” or “hybrid closed-loop” refers to the current status of these systems, which still require some degree of user input to control glucose levels.
The term “artificial pancreas” was used interchangeably with AID in the past, but it doesn’t take into account exocrine pancreatic function. The term “bionic pancreas” refers to a specific system in development that would ultimately include glucagon along with insulin.
The new consensus report, titled “Automated insulin delivery: Benefits, challenges, and recommendations,” was published online in Diabetes Care and Diabetologia.
The document is geared toward not only diabetologists and other specialists, but also diabetes nurses and specialist dietitians. Colleagues working at regulatory agencies, health care organizations, and related media might also benefit from reading it.
It is endorsed by two professional societies – the European Association for the Study of Diabetes and the American Diabetes Association – and contrasts with other statements about AID systems that are sponsored by their manufacturers, noted document co-author Mark Evans, PhD, professor of diabetic medicine, University of Cambridge, England, in a statement.
“Many clinically relevant aspects, including safety, are addressed in this report. The aim ... is to encourage ongoing improvement of this technology, its safe and effective use, and its accessibility to all who can benefit from it,” Dr. Evans said.
Lead author Jennifer Sherr, MD, PhD, pediatric endocrinology, Yale University, New Haven, Conn., commented that the report “addresses the clinical usage of AID systems from a practical point of view rather than as ... a meta-analysis or a review of all relevant clinical studies. ... As such, the benefits and limitations of systems are discussed while also considering safety, regulatory pathways, and access to this technology.”
AID systems do not mean diabetes is “cured”
Separate recommendations provided at the end of the document are aimed at specific stakeholders, including health care providers, patients and their caregivers, manufacturers, regulatory agencies, and the research community.
The authors make clear in the introduction that, while representing “a significant movement toward optimizing glucose management for individuals with diabetes,” the use of AID systems doesn’t mean that diabetes is “cured.” Rather, “expectations need to be set adequately so that individuals with diabetes and providers understand what such systems can and cannot do.”
In particular, current commercially available AID systems require user input for mealtime insulin dosing and sometimes for correction doses of high blood glucose levels, although the systems at least partially automate that.
“When integrated into care, AID systems hold promise to relieve some of the daily burdens of diabetes care,” the authors write.
The statement also details problems that may arise with the physical devices, including skin irritation from adhesives, occlusion of insulin infusion sets, early CGM sensor failure, and inadequate dosing algorithms.
“Individuals with diabetes who are considering this type of advanced diabetes therapy should not only have appropriate technical understanding of the system but also be able to revert to standard diabetes treatment (that is, nonautomated subcutaneous insulin delivery by pump or injections) in case the AID system fails. They should be able to independently troubleshoot and have access to their health care provider if needed.”
To monitor the impact of the technology, the authors emphasize the importance of the time-in-range metric derived from CGM, with the goal of achieving 70% or greater time in target blood glucose range.
Separate sections of the document address the benefits and limitations of AID systems, education and expectations for both patients and providers, and patient and provider perspectives, including how to handle urgent questions.
Other sections cover special populations such as pregnant women and people with type 2 diabetes, considerations for patient selection for current AID systems, safety, improving access to the technology, liability, and do-it-yourself systems.
Recommendations for health care professionals
A table near the end of the document provides specific recommendations for health care professionals, including the following:
- Be knowledgeable about AID systems and nuances of different systems, including their distinguishing features as well as strengths and weaknesses.
- Inform patients with diabetes about AID systems, including review of currently available systems, and create realistic expectations for device use.
- Involve patients with diabetes in shared decision-making when considering use of AID systems.
- Share information with patients with diabetes, as well as their peers, about general standards set by national and international guidelines on AID systems.
- Provide an on-call number or method by which a person with diabetes can always access support from a health care provider at the practice, including weekends and nights.
- Implement, potentially, protocols on times when AID systems should not be used.
- Use an individual’s health data to improve quality of care and health outcomes.
Most members of the ADA/EASD Diabetes Technology Working Group work with industry, but industry had no input on the project. Dr. Sherr has reported conducting clinical trials for Eli Lilly, Insulet, and Medtronic, and has received in-kind support for research studies from Dexcom and Medtronic. She has also reported consulting for Eli Lilly, Lexicon, Medtronic, and Sanofi, and being an advisory board member for Bigfoot Biomedical, Cecelia Health, Eli Lilly, Insulet, T1D Fund, and Vertex Pharmaceuticals. Dr. Evans has reported conducting clinical trials or research collaborations for, serving on advisory boards for, or receiving speakers fees or travel support from Medtronic, Roche, Abbott Diabetes Care, Dexcom, Novo Nordisk, Eli Lilly, Sanofi, Zucara Therapeutics, Pila Pharma, and AstraZeneca. The University of Cambridge has received salary support for Dr. Evans from the National Health Service.
A version of this article first appeared on Medscape.com.
FROM DIABETES CARE AND DIABETOLOGIA
Dapagliflozin DELIVERs regardless of systolic pressure in HFpEF
Whatever the mechanism of benefit from dapagliflozin (Farxiga) in patients with heart failure (HF) – and potentially also other sodium-glucose cotransporter 2 (SGLT2) inhibitors – its blood pressure lowering effects aren’t likely to contribute much.
Indeed, at least in patients with HF and non-reduced ejection fractions, dapagliflozin has only a modest BP-lowering effect and cuts cardiovascular (CV) risk regardless of baseline pressure or change in systolic BP, suggests a secondary analysis from the large placebo-controlled DELIVER trial.
Systolic BP fell over 1 month by just under 2 mmHg, on average, in trial patients with either mildly reduced or preserved ejection fraction (HFmrEF or HFpEF, respectively) assigned to take dapagliflozin versus placebo.
The effect was achieved without increasing the risk for adverse events from dapagliflozin, even among patients with the lowest baseline systolic pressures. Adverse outcomes overall, however, were more common at the lowest systolic BP level than at higher pressures, researchers reported.
They say the findings should help alleviate long-standing concerns that initiating SGLT2 inhibitors, with their recognized diuretic effects, might present a hazard in patients with HF and low systolic BP.
“It is a consistent theme in heart failure trials that the blood pressure–lowering effect of SGLT2 inhibitors is more modest than it is in non–heart-failure populations,” Senthil Selvaraj, MD, Duke University, Durham, N.C., told this news organization.
Changes to antihypertensive drug therapy throughout the trial, which presumably enhanced BP responses and “might occur more frequently in the placebo group,” Dr. Selvaraj said, “might explain why the blood pressure effect is a little bit more modest in this population.”
Dr. Selvaraj presented the analysis at the Annual Scientific Meeting of the Heart Failure Society of America, held in National Harbor, Md., and is lead author on its same-day publication in JACC: Heart Failure.
The findings “reinforce the clinical benefits of SGLT2 inhibitors in patients with heart failure across the full spectrum of ejection fractions and large range of systolic blood pressures,” said Gregg C. Fonarow, MD, University of California, Los Angeles Medical Center, who was not part of the DELIVER analysis.
The study’s greater adjusted risks for CV and all-cause mortality risks at the lowest baseline systolic pressures “parallels a series of observational analyses from registries, including OPTIMIZE-HF,” Dr. Fonarow observed.
In those prior studies of patients with established HFpEF, “systolic BP less than 120 mmHg or even 130 mmHg was associated with worse outcomes than those with higher systolic BP.”
The current findings, therefore, “highlight how optimal blood pressure targets in patients with established heart failure have not been well established,” Dr. Fonarow said.
The analysis included all 6,263 participants in DELIVER, outpatients or patients hospitalized for worsening HF who were in NYHA class 2-4 with a left ventricular ejection fraction (LVEF) greater than 40%. They averaged 72 in age, and 44% were women. Their mean baseline systolic BP was 128 mmHg.
After 1 month, mean systolic BP had fallen by 1.8 mmHg (P < .001) in patients who had been randomly assigned to dapagliflozin versus placebo. The effect was consistent (interaction P = .16) across all systolic BP categories (less than 120 mmHg, 120-129 mmHg, 130-139 mmHg, and 140 mmHg or higher).
The effect was similarly independent of estimated glomerular filtration rate (eGFR) and LVEF (interaction P = .30 and P = .33, respectively), Dr. Selvaraj reported.
In an analysis adjusted for both baseline and 1-month change in systolic BP, the effect of dapagliflozin on the primary endpoint was “minimally attenuated,” compared with the primary analysis, he said. That suggests the clinical benefits “did not significantly relate to the blood pressure–lowering effect” of the SGLT2 inhibitor.
In that analysis, the hazard ratio for CV death or worsening HF for dapagliflozin versus placebo was 0.85 (95% confidence interval, 0.75-0.96; P = .010). The HR had been 0.82 (95% CI, 0.73-0.92; P < .001) overall in the DELIVER primary analysis.
The current study doesn’t shed further light on the main SGLT2 inhibitor mechanism of clinical benefit in nondiabetics with HF, which remains a mystery.
“There is a diuretic effect, but it’s not incredibly robust,” Dr. Selvaraj observed. It may contribute to the drugs’ benefits, “but it’s definitely more than that – a lot more than that.”
DELIVER was funded by AstraZeneca. Dr. Selvaraj reported no relevant conflicts. Disclosures for the other authors are in the report. Dr. Fonarow has reported receiving personal fees from Abbott, Amgen, AstraZeneca, Bayer, Cytokinetics, Edwards, Janssen, Medtronic, Merck, and Novartis.
A version of this article first appeared on Medscape.com.
Whatever the mechanism of benefit from dapagliflozin (Farxiga) in patients with heart failure (HF) – and potentially also other sodium-glucose cotransporter 2 (SGLT2) inhibitors – its blood pressure lowering effects aren’t likely to contribute much.
Indeed, at least in patients with HF and non-reduced ejection fractions, dapagliflozin has only a modest BP-lowering effect and cuts cardiovascular (CV) risk regardless of baseline pressure or change in systolic BP, suggests a secondary analysis from the large placebo-controlled DELIVER trial.
Systolic BP fell over 1 month by just under 2 mmHg, on average, in trial patients with either mildly reduced or preserved ejection fraction (HFmrEF or HFpEF, respectively) assigned to take dapagliflozin versus placebo.
The effect was achieved without increasing the risk for adverse events from dapagliflozin, even among patients with the lowest baseline systolic pressures. Adverse outcomes overall, however, were more common at the lowest systolic BP level than at higher pressures, researchers reported.
They say the findings should help alleviate long-standing concerns that initiating SGLT2 inhibitors, with their recognized diuretic effects, might present a hazard in patients with HF and low systolic BP.
“It is a consistent theme in heart failure trials that the blood pressure–lowering effect of SGLT2 inhibitors is more modest than it is in non–heart-failure populations,” Senthil Selvaraj, MD, Duke University, Durham, N.C., told this news organization.
Changes to antihypertensive drug therapy throughout the trial, which presumably enhanced BP responses and “might occur more frequently in the placebo group,” Dr. Selvaraj said, “might explain why the blood pressure effect is a little bit more modest in this population.”
Dr. Selvaraj presented the analysis at the Annual Scientific Meeting of the Heart Failure Society of America, held in National Harbor, Md., and is lead author on its same-day publication in JACC: Heart Failure.
The findings “reinforce the clinical benefits of SGLT2 inhibitors in patients with heart failure across the full spectrum of ejection fractions and large range of systolic blood pressures,” said Gregg C. Fonarow, MD, University of California, Los Angeles Medical Center, who was not part of the DELIVER analysis.
The study’s greater adjusted risks for CV and all-cause mortality risks at the lowest baseline systolic pressures “parallels a series of observational analyses from registries, including OPTIMIZE-HF,” Dr. Fonarow observed.
In those prior studies of patients with established HFpEF, “systolic BP less than 120 mmHg or even 130 mmHg was associated with worse outcomes than those with higher systolic BP.”
The current findings, therefore, “highlight how optimal blood pressure targets in patients with established heart failure have not been well established,” Dr. Fonarow said.
The analysis included all 6,263 participants in DELIVER, outpatients or patients hospitalized for worsening HF who were in NYHA class 2-4 with a left ventricular ejection fraction (LVEF) greater than 40%. They averaged 72 in age, and 44% were women. Their mean baseline systolic BP was 128 mmHg.
After 1 month, mean systolic BP had fallen by 1.8 mmHg (P < .001) in patients who had been randomly assigned to dapagliflozin versus placebo. The effect was consistent (interaction P = .16) across all systolic BP categories (less than 120 mmHg, 120-129 mmHg, 130-139 mmHg, and 140 mmHg or higher).
The effect was similarly independent of estimated glomerular filtration rate (eGFR) and LVEF (interaction P = .30 and P = .33, respectively), Dr. Selvaraj reported.
In an analysis adjusted for both baseline and 1-month change in systolic BP, the effect of dapagliflozin on the primary endpoint was “minimally attenuated,” compared with the primary analysis, he said. That suggests the clinical benefits “did not significantly relate to the blood pressure–lowering effect” of the SGLT2 inhibitor.
In that analysis, the hazard ratio for CV death or worsening HF for dapagliflozin versus placebo was 0.85 (95% confidence interval, 0.75-0.96; P = .010). The HR had been 0.82 (95% CI, 0.73-0.92; P < .001) overall in the DELIVER primary analysis.
The current study doesn’t shed further light on the main SGLT2 inhibitor mechanism of clinical benefit in nondiabetics with HF, which remains a mystery.
“There is a diuretic effect, but it’s not incredibly robust,” Dr. Selvaraj observed. It may contribute to the drugs’ benefits, “but it’s definitely more than that – a lot more than that.”
DELIVER was funded by AstraZeneca. Dr. Selvaraj reported no relevant conflicts. Disclosures for the other authors are in the report. Dr. Fonarow has reported receiving personal fees from Abbott, Amgen, AstraZeneca, Bayer, Cytokinetics, Edwards, Janssen, Medtronic, Merck, and Novartis.
A version of this article first appeared on Medscape.com.
Whatever the mechanism of benefit from dapagliflozin (Farxiga) in patients with heart failure (HF) – and potentially also other sodium-glucose cotransporter 2 (SGLT2) inhibitors – its blood pressure lowering effects aren’t likely to contribute much.
Indeed, at least in patients with HF and non-reduced ejection fractions, dapagliflozin has only a modest BP-lowering effect and cuts cardiovascular (CV) risk regardless of baseline pressure or change in systolic BP, suggests a secondary analysis from the large placebo-controlled DELIVER trial.
Systolic BP fell over 1 month by just under 2 mmHg, on average, in trial patients with either mildly reduced or preserved ejection fraction (HFmrEF or HFpEF, respectively) assigned to take dapagliflozin versus placebo.
The effect was achieved without increasing the risk for adverse events from dapagliflozin, even among patients with the lowest baseline systolic pressures. Adverse outcomes overall, however, were more common at the lowest systolic BP level than at higher pressures, researchers reported.
They say the findings should help alleviate long-standing concerns that initiating SGLT2 inhibitors, with their recognized diuretic effects, might present a hazard in patients with HF and low systolic BP.
“It is a consistent theme in heart failure trials that the blood pressure–lowering effect of SGLT2 inhibitors is more modest than it is in non–heart-failure populations,” Senthil Selvaraj, MD, Duke University, Durham, N.C., told this news organization.
Changes to antihypertensive drug therapy throughout the trial, which presumably enhanced BP responses and “might occur more frequently in the placebo group,” Dr. Selvaraj said, “might explain why the blood pressure effect is a little bit more modest in this population.”
Dr. Selvaraj presented the analysis at the Annual Scientific Meeting of the Heart Failure Society of America, held in National Harbor, Md., and is lead author on its same-day publication in JACC: Heart Failure.
The findings “reinforce the clinical benefits of SGLT2 inhibitors in patients with heart failure across the full spectrum of ejection fractions and large range of systolic blood pressures,” said Gregg C. Fonarow, MD, University of California, Los Angeles Medical Center, who was not part of the DELIVER analysis.
The study’s greater adjusted risks for CV and all-cause mortality risks at the lowest baseline systolic pressures “parallels a series of observational analyses from registries, including OPTIMIZE-HF,” Dr. Fonarow observed.
In those prior studies of patients with established HFpEF, “systolic BP less than 120 mmHg or even 130 mmHg was associated with worse outcomes than those with higher systolic BP.”
The current findings, therefore, “highlight how optimal blood pressure targets in patients with established heart failure have not been well established,” Dr. Fonarow said.
The analysis included all 6,263 participants in DELIVER, outpatients or patients hospitalized for worsening HF who were in NYHA class 2-4 with a left ventricular ejection fraction (LVEF) greater than 40%. They averaged 72 in age, and 44% were women. Their mean baseline systolic BP was 128 mmHg.
After 1 month, mean systolic BP had fallen by 1.8 mmHg (P < .001) in patients who had been randomly assigned to dapagliflozin versus placebo. The effect was consistent (interaction P = .16) across all systolic BP categories (less than 120 mmHg, 120-129 mmHg, 130-139 mmHg, and 140 mmHg or higher).
The effect was similarly independent of estimated glomerular filtration rate (eGFR) and LVEF (interaction P = .30 and P = .33, respectively), Dr. Selvaraj reported.
In an analysis adjusted for both baseline and 1-month change in systolic BP, the effect of dapagliflozin on the primary endpoint was “minimally attenuated,” compared with the primary analysis, he said. That suggests the clinical benefits “did not significantly relate to the blood pressure–lowering effect” of the SGLT2 inhibitor.
In that analysis, the hazard ratio for CV death or worsening HF for dapagliflozin versus placebo was 0.85 (95% confidence interval, 0.75-0.96; P = .010). The HR had been 0.82 (95% CI, 0.73-0.92; P < .001) overall in the DELIVER primary analysis.
The current study doesn’t shed further light on the main SGLT2 inhibitor mechanism of clinical benefit in nondiabetics with HF, which remains a mystery.
“There is a diuretic effect, but it’s not incredibly robust,” Dr. Selvaraj observed. It may contribute to the drugs’ benefits, “but it’s definitely more than that – a lot more than that.”
DELIVER was funded by AstraZeneca. Dr. Selvaraj reported no relevant conflicts. Disclosures for the other authors are in the report. Dr. Fonarow has reported receiving personal fees from Abbott, Amgen, AstraZeneca, Bayer, Cytokinetics, Edwards, Janssen, Medtronic, Merck, and Novartis.
A version of this article first appeared on Medscape.com.
Bariatric surgery prompts visceral fat reduction, cardiac changes
Weight loss after bariatric surgery was linked with visceral fat reduction as well as reduced blood pressure, fasting glucose, and left ventricular remodeling, based an imaging study in 213 patients.
“We found that ventricular function measured by strain imaging improved in both the left and right sides of the heart, but function measured in the traditional method using endocardial motion [in other words, ejection fraction] actually worsened,” senior investigator Barry A. Borlaug, MD, said in an interview.
Although previous studies have shown positive effects of weight loss on the heart after bariatric surgery, most have been short term and have not specifically examined the effects of visceral fat reduction, wrote the investigators.
“We are in the middle of an increasing epidemic of obesity worldwide, but particularly in the United States, where it is currently projected that one in two adults will be obese by 2030,” added Dr. Borlaug of Mayo Clinic, Rochester, Minn. “Heart failure with preserved ejection fraction (HFpEF) is growing in tandem, and numerous recent studies have shown that obesity is one of the strongest risk factors for developing HFpEF, and that the severity of HFpEF is intimately linked to excess body fat. This suggests that therapies to reduce body fat could improve the cardiac abnormalities that cause HFpEF, which was our focus in this study,” he explained.
In the study, published in the Journal of the American College of Cardiology, the researchers reviewed echocardiography data from 213 obese patients before and more than 180 days after bariatric surgery. They also measured abdominal visceral adipose tissue (VAT) of 52 patients via computed tomography. The average age of the patients was 54 years, the average body mass index was 45 kg/m2, and 67% were women. Comorbidities included hypertension, diabetes, dyslipidemia, and obstructive sleep apnea.
The primary outcome was changes in cardiac structure and function.
After a median follow-up of 5.3 years, patients overall averaged a 23% reduction in body weight and a 22% reduction in BMI. In the 52 patients with abdominal scans, the VAT area decreased by 30% overall. Changes in left ventricular mass were significantly correlated to changes in the VAT.
Epicardial adipose thickness decreased by 14% overall. Left and right ventricular longitudinal strains improved at follow-up, but left atrial strain deteriorated, the researchers noted.
Although the mechanism of action remains unclear, the results suggest that left ventricular remodeling was associated with visceral adiposity rather than subcutaneous fat, the researchers wrote.
They also found that right ventricular strain was negatively correlated with VAT, but not with body weight or BMI.
“These findings suggest that weight loss, particularly reduction in visceral adiposity, benefits [right ventricular] structure and function in a manner akin to that observed in the [left ventricle],” the researchers noted.
Some surprises and limitations
Dr. Borlaug said he found some, but not all, of the results surprising. “Earlier studies had shown evidence for benefit from weight loss on cardiac structure and function, but had been limited by smaller sample sizes, shorter durations of evaluation, and variable methods used,” he said in an interview.
The findings that strain imaging showed both left and right ventricular function improved while EF declined “shows some of the problems with using EF, as it is affected by chamber size and geometry. We have previously shown that patients with HFpEF display an increase in fat around the heart, and this affects cardiac function and interaction between the left and right sides of the heart, so we expected to see that this fat depot would be reduced, and this was indeed the case,” Dr. Borlaug added.
In the current study, “visceral fat was most strongly tied to the heart remodeling in obesity, and changes in visceral fat were most strongly tied to improvements in cardiac structure following weight loss,” Dr. Borlaug told this news organization. “This further supports this concept that excess visceral fat plays a key role in HFpEF, especially in the abdomen and around the heart,” he said.
However, “The biggest surprise was the discordant effects in the left atrium,” Dr. Borlaug said. “Left atrial remodeling and dysfunction play a crucial role in HFpEF as well, and we expected that this would improve following weight loss, but in fact we observed that left atrial function deteriorated, and other indicators of atrial myopathy worsened, including higher estimates of left atrial pressures and increased prevalence of atrial fibrillation,” he said.
This difference emphasizes that weight loss may not address all abnormalities that lead to HFpEF, although a key limitation of the current study was the lack of a control group of patients with the same degree of obesity and no weight-loss intervention, and the deterioration in left atrial function might have been even greater in the absence of weight loss, Dr. Borlaug added.
Larger numbers support effects
Previous research shows that structural heart changes associated with obesity can be reversed through weight loss, but the current study fills a gap by providing long-term data in a larger sample than previously studied, wrote Paul Heidenreich, MD, of Stanford (Calif.) University in an accompanying editorial).
“There has been uncertainty regarding the prolonged effect of weight loss on cardiac function; this study was larger than many prior studies and provided a longer follow-up,” Dr. Heidenreich said in an interview.
“One unusual finding was that, while weight loss led to left ventricle reverse remodeling (reduction in wall thickness), the same effect was not seen for the left atrium; the left atrial size continued to increase,” he said. “I would have expected the left atrial changes to mirror the changes in the left ventricle,” he noted.
The findings support the greater cardiac risk of visceral vs. subcutaneous adipose tissue, and although body mass index will retain prognostic value, measures of central obesity are more likely predictors of cardiac structural changes and events and should be reported in clinical studies, Dr. Heidenreich wrote.
However, “We need a better understanding of the factors that influence left atrial remodeling and reverse remodeling,” Dr. Heidenreich told this news organization. “While left ventricular compliance and pressure play a role, there are other factors that need to be elucidated,” he said.
Studies in progress may inform practice
The current data call for further study to test novel treatments to facilitate weight loss in patients with HFpEF and those at risk for HFpEF, and some of these studies with medicines are underway, Dr. Borlaug said in the interview.
“Until such studies are completed, we will not truly understand the effects of weight loss on the heart, but the present data certainly provide strong support that patients who have obesity and HFpEF or are at risk for HFpEF should try to lose weight through lifestyle interventions,” he said.
Whether the cardiac changes seen in the current study would be different with nonsurgical weight loss remains a key question because many obese patients are reluctant to undergo bariatric surgery, Dr. Borlaug said. “We cannot assess whether the effects would differ with nonsurgical weight loss, and this requires further study,” he added.
As for additional research, “Randomized, controlled trials of weight-loss interventions, with appropriate controls and comprehensive assessments of cardiac structure, function, and hemodynamics will be most informative,” said Dr. Borlaug. “Larger trials powered to evaluate cardiovascular outcomes such as heart failure hospitalization or cardiovascular death also are critically important to better understand the role of weight loss to treat and prevent HFpEF, the ultimate form of obesity-related heart disease,” he emphasized.
The study was supported in part by grants to lead author Dr. Hidemi Sorimachi of the Mayo Clinic from the Uehara Memorial Foundation, Japan, and to corresponding author Dr. Borlaug from the National Institutes of Health. Dr. Borlaug also disclosed previous grants from National Institutes of Health/National Heart, Lung, and Blood Institute, AstraZeneca, Corvia, Medtronic, GlaxoSmithKline, Mesoblast, Novartis, and Tenax Therapeutics; and consulting fees from Actelion, Amgen, Aria, Axon Therapies, Boehringer Ingelheim, Edwards Lifesciences, Eli Lilly, Imbria, Janssen, Merck, Novo Nordisk, and VADovations. Dr. Heidenreich had no financial disclosures.
Weight loss after bariatric surgery was linked with visceral fat reduction as well as reduced blood pressure, fasting glucose, and left ventricular remodeling, based an imaging study in 213 patients.
“We found that ventricular function measured by strain imaging improved in both the left and right sides of the heart, but function measured in the traditional method using endocardial motion [in other words, ejection fraction] actually worsened,” senior investigator Barry A. Borlaug, MD, said in an interview.
Although previous studies have shown positive effects of weight loss on the heart after bariatric surgery, most have been short term and have not specifically examined the effects of visceral fat reduction, wrote the investigators.
“We are in the middle of an increasing epidemic of obesity worldwide, but particularly in the United States, where it is currently projected that one in two adults will be obese by 2030,” added Dr. Borlaug of Mayo Clinic, Rochester, Minn. “Heart failure with preserved ejection fraction (HFpEF) is growing in tandem, and numerous recent studies have shown that obesity is one of the strongest risk factors for developing HFpEF, and that the severity of HFpEF is intimately linked to excess body fat. This suggests that therapies to reduce body fat could improve the cardiac abnormalities that cause HFpEF, which was our focus in this study,” he explained.
In the study, published in the Journal of the American College of Cardiology, the researchers reviewed echocardiography data from 213 obese patients before and more than 180 days after bariatric surgery. They also measured abdominal visceral adipose tissue (VAT) of 52 patients via computed tomography. The average age of the patients was 54 years, the average body mass index was 45 kg/m2, and 67% were women. Comorbidities included hypertension, diabetes, dyslipidemia, and obstructive sleep apnea.
The primary outcome was changes in cardiac structure and function.
After a median follow-up of 5.3 years, patients overall averaged a 23% reduction in body weight and a 22% reduction in BMI. In the 52 patients with abdominal scans, the VAT area decreased by 30% overall. Changes in left ventricular mass were significantly correlated to changes in the VAT.
Epicardial adipose thickness decreased by 14% overall. Left and right ventricular longitudinal strains improved at follow-up, but left atrial strain deteriorated, the researchers noted.
Although the mechanism of action remains unclear, the results suggest that left ventricular remodeling was associated with visceral adiposity rather than subcutaneous fat, the researchers wrote.
They also found that right ventricular strain was negatively correlated with VAT, but not with body weight or BMI.
“These findings suggest that weight loss, particularly reduction in visceral adiposity, benefits [right ventricular] structure and function in a manner akin to that observed in the [left ventricle],” the researchers noted.
Some surprises and limitations
Dr. Borlaug said he found some, but not all, of the results surprising. “Earlier studies had shown evidence for benefit from weight loss on cardiac structure and function, but had been limited by smaller sample sizes, shorter durations of evaluation, and variable methods used,” he said in an interview.
The findings that strain imaging showed both left and right ventricular function improved while EF declined “shows some of the problems with using EF, as it is affected by chamber size and geometry. We have previously shown that patients with HFpEF display an increase in fat around the heart, and this affects cardiac function and interaction between the left and right sides of the heart, so we expected to see that this fat depot would be reduced, and this was indeed the case,” Dr. Borlaug added.
In the current study, “visceral fat was most strongly tied to the heart remodeling in obesity, and changes in visceral fat were most strongly tied to improvements in cardiac structure following weight loss,” Dr. Borlaug told this news organization. “This further supports this concept that excess visceral fat plays a key role in HFpEF, especially in the abdomen and around the heart,” he said.
However, “The biggest surprise was the discordant effects in the left atrium,” Dr. Borlaug said. “Left atrial remodeling and dysfunction play a crucial role in HFpEF as well, and we expected that this would improve following weight loss, but in fact we observed that left atrial function deteriorated, and other indicators of atrial myopathy worsened, including higher estimates of left atrial pressures and increased prevalence of atrial fibrillation,” he said.
This difference emphasizes that weight loss may not address all abnormalities that lead to HFpEF, although a key limitation of the current study was the lack of a control group of patients with the same degree of obesity and no weight-loss intervention, and the deterioration in left atrial function might have been even greater in the absence of weight loss, Dr. Borlaug added.
Larger numbers support effects
Previous research shows that structural heart changes associated with obesity can be reversed through weight loss, but the current study fills a gap by providing long-term data in a larger sample than previously studied, wrote Paul Heidenreich, MD, of Stanford (Calif.) University in an accompanying editorial).
“There has been uncertainty regarding the prolonged effect of weight loss on cardiac function; this study was larger than many prior studies and provided a longer follow-up,” Dr. Heidenreich said in an interview.
“One unusual finding was that, while weight loss led to left ventricle reverse remodeling (reduction in wall thickness), the same effect was not seen for the left atrium; the left atrial size continued to increase,” he said. “I would have expected the left atrial changes to mirror the changes in the left ventricle,” he noted.
The findings support the greater cardiac risk of visceral vs. subcutaneous adipose tissue, and although body mass index will retain prognostic value, measures of central obesity are more likely predictors of cardiac structural changes and events and should be reported in clinical studies, Dr. Heidenreich wrote.
However, “We need a better understanding of the factors that influence left atrial remodeling and reverse remodeling,” Dr. Heidenreich told this news organization. “While left ventricular compliance and pressure play a role, there are other factors that need to be elucidated,” he said.
Studies in progress may inform practice
The current data call for further study to test novel treatments to facilitate weight loss in patients with HFpEF and those at risk for HFpEF, and some of these studies with medicines are underway, Dr. Borlaug said in the interview.
“Until such studies are completed, we will not truly understand the effects of weight loss on the heart, but the present data certainly provide strong support that patients who have obesity and HFpEF or are at risk for HFpEF should try to lose weight through lifestyle interventions,” he said.
Whether the cardiac changes seen in the current study would be different with nonsurgical weight loss remains a key question because many obese patients are reluctant to undergo bariatric surgery, Dr. Borlaug said. “We cannot assess whether the effects would differ with nonsurgical weight loss, and this requires further study,” he added.
As for additional research, “Randomized, controlled trials of weight-loss interventions, with appropriate controls and comprehensive assessments of cardiac structure, function, and hemodynamics will be most informative,” said Dr. Borlaug. “Larger trials powered to evaluate cardiovascular outcomes such as heart failure hospitalization or cardiovascular death also are critically important to better understand the role of weight loss to treat and prevent HFpEF, the ultimate form of obesity-related heart disease,” he emphasized.
The study was supported in part by grants to lead author Dr. Hidemi Sorimachi of the Mayo Clinic from the Uehara Memorial Foundation, Japan, and to corresponding author Dr. Borlaug from the National Institutes of Health. Dr. Borlaug also disclosed previous grants from National Institutes of Health/National Heart, Lung, and Blood Institute, AstraZeneca, Corvia, Medtronic, GlaxoSmithKline, Mesoblast, Novartis, and Tenax Therapeutics; and consulting fees from Actelion, Amgen, Aria, Axon Therapies, Boehringer Ingelheim, Edwards Lifesciences, Eli Lilly, Imbria, Janssen, Merck, Novo Nordisk, and VADovations. Dr. Heidenreich had no financial disclosures.
Weight loss after bariatric surgery was linked with visceral fat reduction as well as reduced blood pressure, fasting glucose, and left ventricular remodeling, based an imaging study in 213 patients.
“We found that ventricular function measured by strain imaging improved in both the left and right sides of the heart, but function measured in the traditional method using endocardial motion [in other words, ejection fraction] actually worsened,” senior investigator Barry A. Borlaug, MD, said in an interview.
Although previous studies have shown positive effects of weight loss on the heart after bariatric surgery, most have been short term and have not specifically examined the effects of visceral fat reduction, wrote the investigators.
“We are in the middle of an increasing epidemic of obesity worldwide, but particularly in the United States, where it is currently projected that one in two adults will be obese by 2030,” added Dr. Borlaug of Mayo Clinic, Rochester, Minn. “Heart failure with preserved ejection fraction (HFpEF) is growing in tandem, and numerous recent studies have shown that obesity is one of the strongest risk factors for developing HFpEF, and that the severity of HFpEF is intimately linked to excess body fat. This suggests that therapies to reduce body fat could improve the cardiac abnormalities that cause HFpEF, which was our focus in this study,” he explained.
In the study, published in the Journal of the American College of Cardiology, the researchers reviewed echocardiography data from 213 obese patients before and more than 180 days after bariatric surgery. They also measured abdominal visceral adipose tissue (VAT) of 52 patients via computed tomography. The average age of the patients was 54 years, the average body mass index was 45 kg/m2, and 67% were women. Comorbidities included hypertension, diabetes, dyslipidemia, and obstructive sleep apnea.
The primary outcome was changes in cardiac structure and function.
After a median follow-up of 5.3 years, patients overall averaged a 23% reduction in body weight and a 22% reduction in BMI. In the 52 patients with abdominal scans, the VAT area decreased by 30% overall. Changes in left ventricular mass were significantly correlated to changes in the VAT.
Epicardial adipose thickness decreased by 14% overall. Left and right ventricular longitudinal strains improved at follow-up, but left atrial strain deteriorated, the researchers noted.
Although the mechanism of action remains unclear, the results suggest that left ventricular remodeling was associated with visceral adiposity rather than subcutaneous fat, the researchers wrote.
They also found that right ventricular strain was negatively correlated with VAT, but not with body weight or BMI.
“These findings suggest that weight loss, particularly reduction in visceral adiposity, benefits [right ventricular] structure and function in a manner akin to that observed in the [left ventricle],” the researchers noted.
Some surprises and limitations
Dr. Borlaug said he found some, but not all, of the results surprising. “Earlier studies had shown evidence for benefit from weight loss on cardiac structure and function, but had been limited by smaller sample sizes, shorter durations of evaluation, and variable methods used,” he said in an interview.
The findings that strain imaging showed both left and right ventricular function improved while EF declined “shows some of the problems with using EF, as it is affected by chamber size and geometry. We have previously shown that patients with HFpEF display an increase in fat around the heart, and this affects cardiac function and interaction between the left and right sides of the heart, so we expected to see that this fat depot would be reduced, and this was indeed the case,” Dr. Borlaug added.
In the current study, “visceral fat was most strongly tied to the heart remodeling in obesity, and changes in visceral fat were most strongly tied to improvements in cardiac structure following weight loss,” Dr. Borlaug told this news organization. “This further supports this concept that excess visceral fat plays a key role in HFpEF, especially in the abdomen and around the heart,” he said.
However, “The biggest surprise was the discordant effects in the left atrium,” Dr. Borlaug said. “Left atrial remodeling and dysfunction play a crucial role in HFpEF as well, and we expected that this would improve following weight loss, but in fact we observed that left atrial function deteriorated, and other indicators of atrial myopathy worsened, including higher estimates of left atrial pressures and increased prevalence of atrial fibrillation,” he said.
This difference emphasizes that weight loss may not address all abnormalities that lead to HFpEF, although a key limitation of the current study was the lack of a control group of patients with the same degree of obesity and no weight-loss intervention, and the deterioration in left atrial function might have been even greater in the absence of weight loss, Dr. Borlaug added.
Larger numbers support effects
Previous research shows that structural heart changes associated with obesity can be reversed through weight loss, but the current study fills a gap by providing long-term data in a larger sample than previously studied, wrote Paul Heidenreich, MD, of Stanford (Calif.) University in an accompanying editorial).
“There has been uncertainty regarding the prolonged effect of weight loss on cardiac function; this study was larger than many prior studies and provided a longer follow-up,” Dr. Heidenreich said in an interview.
“One unusual finding was that, while weight loss led to left ventricle reverse remodeling (reduction in wall thickness), the same effect was not seen for the left atrium; the left atrial size continued to increase,” he said. “I would have expected the left atrial changes to mirror the changes in the left ventricle,” he noted.
The findings support the greater cardiac risk of visceral vs. subcutaneous adipose tissue, and although body mass index will retain prognostic value, measures of central obesity are more likely predictors of cardiac structural changes and events and should be reported in clinical studies, Dr. Heidenreich wrote.
However, “We need a better understanding of the factors that influence left atrial remodeling and reverse remodeling,” Dr. Heidenreich told this news organization. “While left ventricular compliance and pressure play a role, there are other factors that need to be elucidated,” he said.
Studies in progress may inform practice
The current data call for further study to test novel treatments to facilitate weight loss in patients with HFpEF and those at risk for HFpEF, and some of these studies with medicines are underway, Dr. Borlaug said in the interview.
“Until such studies are completed, we will not truly understand the effects of weight loss on the heart, but the present data certainly provide strong support that patients who have obesity and HFpEF or are at risk for HFpEF should try to lose weight through lifestyle interventions,” he said.
Whether the cardiac changes seen in the current study would be different with nonsurgical weight loss remains a key question because many obese patients are reluctant to undergo bariatric surgery, Dr. Borlaug said. “We cannot assess whether the effects would differ with nonsurgical weight loss, and this requires further study,” he added.
As for additional research, “Randomized, controlled trials of weight-loss interventions, with appropriate controls and comprehensive assessments of cardiac structure, function, and hemodynamics will be most informative,” said Dr. Borlaug. “Larger trials powered to evaluate cardiovascular outcomes such as heart failure hospitalization or cardiovascular death also are critically important to better understand the role of weight loss to treat and prevent HFpEF, the ultimate form of obesity-related heart disease,” he emphasized.
The study was supported in part by grants to lead author Dr. Hidemi Sorimachi of the Mayo Clinic from the Uehara Memorial Foundation, Japan, and to corresponding author Dr. Borlaug from the National Institutes of Health. Dr. Borlaug also disclosed previous grants from National Institutes of Health/National Heart, Lung, and Blood Institute, AstraZeneca, Corvia, Medtronic, GlaxoSmithKline, Mesoblast, Novartis, and Tenax Therapeutics; and consulting fees from Actelion, Amgen, Aria, Axon Therapies, Boehringer Ingelheim, Edwards Lifesciences, Eli Lilly, Imbria, Janssen, Merck, Novo Nordisk, and VADovations. Dr. Heidenreich had no financial disclosures.
FROM JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Burnout Is Rampant, But Oncologists Can Turn the Tide
SAN DIEGO—Before the pandemic, an estimated one-third of oncologists worldwide suffered a high level of burnout. Cancer physicians face many of the same risk factors as their colleagues—high workloads, lack of autonomy, and no support—along with the added pressure of working in a medical field where patients often die. Then COVID-19 hit, and the burnout crisis got even worse.
This tide can be reversed with a focus on best practices and resilience, a mental health researcher told cancer professionals at the September 2022 annual meeting of the Association of VA Hematology/Oncology. Assessments, long-term interventions, and communication are all key, said Fay J. Hlubocky, PhD, MA, a clinical health psychologist and ethicist at the University of Chicago.
Even simple actions like taking time for “mindful moments” and checking in with a colleague can make a difference, she said. But institutions must act, she said. “Long-term tailored strategies are incredibly important to promote well-being.”
Hlubocky, who led an American Society of Clinical Oncology committee on burnout prior to the pandemic, noted that statistics about burnout in American medicine and oncology specifically, are grim. In 2017, a systematic review and meta-analysis found that significant numbers of oncologists suffered from high burnout (32%), high psychiatric morbidity (27%), depression (at least 12%), and alcohol misuse (as many as 30%).
The pandemic piled on more stressors. In the second half of 2020, researchers interviewed 25 American oncologists in focus groups and found that their “underlying oncologist burnout exacerbated stressors associated with disruptions in care, education, research, financial practice health, and telemedicine. Many feared delays in cancer screening, diagnosis, and treatment [and] strongly considered working part-time or taking early retirement.”
As one participant put it, “everyone is seeing a lot of death and heartache and social isolation and anger that they’re not used to encountering and in very new and different ways.”
Major contributors to oncologist burnout, Hlubocky said, include moral distress, moral injury, and compassion fatigue. “Moral distress occurs when that individual believes he or she knows the right thing to do, but institutional constraints make it really difficult to do what is right,” Hlubocky said. “The individual is aware of the moral problem, acknowledges and takes moral responsibility, makes some moral judgments, but yet—as a result of these constraints — participates in perceived moral wrongdoing.”
Moral injury refers to the damage that can be caused by moral distress or by witnessing acts that violate morals, such as during military service. Compassion fatigue, meanwhile, is defined by the American Stress Institute as “a low level, chronic clouding of caring and concern for others in your life.”
What can be done? Hlubocky highlighted multiple interventions, such as adjustment of work patterns, cognitive behavioral therapy, and training in mindfulness, relaxation, and communication. One strategy is to adopt multiple in-person interventions simultaneously.
But first it’s crucial for administrators to understand the problem in a specific workplace: “You have to know what’s going on in your organization to intervene on it,” she said. “There are multiple tools that have been validated in other health care fields and can be used on a regular basis over time to measure burnout, satisfaction, and engagement.”
For individuals, other strategies include daily check-ins with colleagues to catch signs of stress, she said, as Toronto oncologists started doing amid the pandemic. The check-ins can include simple questions like: How are you doing? How are you feeling? Are you sleeping, eating and exercising? Do you need help?
As for resilience, Hlubocky said it must grow at the individual level. “We can't rely so much on the organization. We need to develop our personal resilience in order for professional resilience to flourish again, and we have to do a lot to protect ourselves. It’s about focusing on the strength of the individual—that empowerment to rise above adversity, that vitality, that engagement, that self-efficacy. It supports health and enhances coping, and it is the key element of physician and clinician well-being.”
Research into resilience offers guidance about how to achieve it, she said. A 2013 German study of 200 physicians found that the most resilient physicians change their attitudes and behaviors, take time off, set boundaries, spend time with family and friends, and ask colleagues for help. And they gained resilience, the study found, by getting older and becoming more experienced.
Hlubocky pointed to several useful resources for burned-out medical professionals, including mindfulness, cognitive behavioral therapy and breathing apps: She highlighted Breathe2Relax, Headspace, MoodGYM, Stress Gym, and guided audio files from the University of California at San Diego. And she said ASCO has resources on combatting burnout and promoting well-being.
Hlubocky has no relevant disclosures.
SAN DIEGO—Before the pandemic, an estimated one-third of oncologists worldwide suffered a high level of burnout. Cancer physicians face many of the same risk factors as their colleagues—high workloads, lack of autonomy, and no support—along with the added pressure of working in a medical field where patients often die. Then COVID-19 hit, and the burnout crisis got even worse.
This tide can be reversed with a focus on best practices and resilience, a mental health researcher told cancer professionals at the September 2022 annual meeting of the Association of VA Hematology/Oncology. Assessments, long-term interventions, and communication are all key, said Fay J. Hlubocky, PhD, MA, a clinical health psychologist and ethicist at the University of Chicago.
Even simple actions like taking time for “mindful moments” and checking in with a colleague can make a difference, she said. But institutions must act, she said. “Long-term tailored strategies are incredibly important to promote well-being.”
Hlubocky, who led an American Society of Clinical Oncology committee on burnout prior to the pandemic, noted that statistics about burnout in American medicine and oncology specifically, are grim. In 2017, a systematic review and meta-analysis found that significant numbers of oncologists suffered from high burnout (32%), high psychiatric morbidity (27%), depression (at least 12%), and alcohol misuse (as many as 30%).
The pandemic piled on more stressors. In the second half of 2020, researchers interviewed 25 American oncologists in focus groups and found that their “underlying oncologist burnout exacerbated stressors associated with disruptions in care, education, research, financial practice health, and telemedicine. Many feared delays in cancer screening, diagnosis, and treatment [and] strongly considered working part-time or taking early retirement.”
As one participant put it, “everyone is seeing a lot of death and heartache and social isolation and anger that they’re not used to encountering and in very new and different ways.”
Major contributors to oncologist burnout, Hlubocky said, include moral distress, moral injury, and compassion fatigue. “Moral distress occurs when that individual believes he or she knows the right thing to do, but institutional constraints make it really difficult to do what is right,” Hlubocky said. “The individual is aware of the moral problem, acknowledges and takes moral responsibility, makes some moral judgments, but yet—as a result of these constraints — participates in perceived moral wrongdoing.”
Moral injury refers to the damage that can be caused by moral distress or by witnessing acts that violate morals, such as during military service. Compassion fatigue, meanwhile, is defined by the American Stress Institute as “a low level, chronic clouding of caring and concern for others in your life.”
What can be done? Hlubocky highlighted multiple interventions, such as adjustment of work patterns, cognitive behavioral therapy, and training in mindfulness, relaxation, and communication. One strategy is to adopt multiple in-person interventions simultaneously.
But first it’s crucial for administrators to understand the problem in a specific workplace: “You have to know what’s going on in your organization to intervene on it,” she said. “There are multiple tools that have been validated in other health care fields and can be used on a regular basis over time to measure burnout, satisfaction, and engagement.”
For individuals, other strategies include daily check-ins with colleagues to catch signs of stress, she said, as Toronto oncologists started doing amid the pandemic. The check-ins can include simple questions like: How are you doing? How are you feeling? Are you sleeping, eating and exercising? Do you need help?
As for resilience, Hlubocky said it must grow at the individual level. “We can't rely so much on the organization. We need to develop our personal resilience in order for professional resilience to flourish again, and we have to do a lot to protect ourselves. It’s about focusing on the strength of the individual—that empowerment to rise above adversity, that vitality, that engagement, that self-efficacy. It supports health and enhances coping, and it is the key element of physician and clinician well-being.”
Research into resilience offers guidance about how to achieve it, she said. A 2013 German study of 200 physicians found that the most resilient physicians change their attitudes and behaviors, take time off, set boundaries, spend time with family and friends, and ask colleagues for help. And they gained resilience, the study found, by getting older and becoming more experienced.
Hlubocky pointed to several useful resources for burned-out medical professionals, including mindfulness, cognitive behavioral therapy and breathing apps: She highlighted Breathe2Relax, Headspace, MoodGYM, Stress Gym, and guided audio files from the University of California at San Diego. And she said ASCO has resources on combatting burnout and promoting well-being.
Hlubocky has no relevant disclosures.
SAN DIEGO—Before the pandemic, an estimated one-third of oncologists worldwide suffered a high level of burnout. Cancer physicians face many of the same risk factors as their colleagues—high workloads, lack of autonomy, and no support—along with the added pressure of working in a medical field where patients often die. Then COVID-19 hit, and the burnout crisis got even worse.
This tide can be reversed with a focus on best practices and resilience, a mental health researcher told cancer professionals at the September 2022 annual meeting of the Association of VA Hematology/Oncology. Assessments, long-term interventions, and communication are all key, said Fay J. Hlubocky, PhD, MA, a clinical health psychologist and ethicist at the University of Chicago.
Even simple actions like taking time for “mindful moments” and checking in with a colleague can make a difference, she said. But institutions must act, she said. “Long-term tailored strategies are incredibly important to promote well-being.”
Hlubocky, who led an American Society of Clinical Oncology committee on burnout prior to the pandemic, noted that statistics about burnout in American medicine and oncology specifically, are grim. In 2017, a systematic review and meta-analysis found that significant numbers of oncologists suffered from high burnout (32%), high psychiatric morbidity (27%), depression (at least 12%), and alcohol misuse (as many as 30%).
The pandemic piled on more stressors. In the second half of 2020, researchers interviewed 25 American oncologists in focus groups and found that their “underlying oncologist burnout exacerbated stressors associated with disruptions in care, education, research, financial practice health, and telemedicine. Many feared delays in cancer screening, diagnosis, and treatment [and] strongly considered working part-time or taking early retirement.”
As one participant put it, “everyone is seeing a lot of death and heartache and social isolation and anger that they’re not used to encountering and in very new and different ways.”
Major contributors to oncologist burnout, Hlubocky said, include moral distress, moral injury, and compassion fatigue. “Moral distress occurs when that individual believes he or she knows the right thing to do, but institutional constraints make it really difficult to do what is right,” Hlubocky said. “The individual is aware of the moral problem, acknowledges and takes moral responsibility, makes some moral judgments, but yet—as a result of these constraints — participates in perceived moral wrongdoing.”
Moral injury refers to the damage that can be caused by moral distress or by witnessing acts that violate morals, such as during military service. Compassion fatigue, meanwhile, is defined by the American Stress Institute as “a low level, chronic clouding of caring and concern for others in your life.”
What can be done? Hlubocky highlighted multiple interventions, such as adjustment of work patterns, cognitive behavioral therapy, and training in mindfulness, relaxation, and communication. One strategy is to adopt multiple in-person interventions simultaneously.
But first it’s crucial for administrators to understand the problem in a specific workplace: “You have to know what’s going on in your organization to intervene on it,” she said. “There are multiple tools that have been validated in other health care fields and can be used on a regular basis over time to measure burnout, satisfaction, and engagement.”
For individuals, other strategies include daily check-ins with colleagues to catch signs of stress, she said, as Toronto oncologists started doing amid the pandemic. The check-ins can include simple questions like: How are you doing? How are you feeling? Are you sleeping, eating and exercising? Do you need help?
As for resilience, Hlubocky said it must grow at the individual level. “We can't rely so much on the organization. We need to develop our personal resilience in order for professional resilience to flourish again, and we have to do a lot to protect ourselves. It’s about focusing on the strength of the individual—that empowerment to rise above adversity, that vitality, that engagement, that self-efficacy. It supports health and enhances coping, and it is the key element of physician and clinician well-being.”
Research into resilience offers guidance about how to achieve it, she said. A 2013 German study of 200 physicians found that the most resilient physicians change their attitudes and behaviors, take time off, set boundaries, spend time with family and friends, and ask colleagues for help. And they gained resilience, the study found, by getting older and becoming more experienced.
Hlubocky pointed to several useful resources for burned-out medical professionals, including mindfulness, cognitive behavioral therapy and breathing apps: She highlighted Breathe2Relax, Headspace, MoodGYM, Stress Gym, and guided audio files from the University of California at San Diego. And she said ASCO has resources on combatting burnout and promoting well-being.
Hlubocky has no relevant disclosures.
Air pollution tied to stroke risk, subsequent CV events, and death
Results of a UK biobank study show high levels of air pollution were associated with an increased risk of transition from health to a first stroke and subsequent progression to cardiovascular (CV) events and death.
“These results indicate that understanding and reducing the effects of air pollutants on different transition stages in stroke will be beneficial in managing people’s health and preventing the occurrence and progression of stroke,” study investigator Hualiang Lin, PhD, of Sun Yat-sen University School of Public Health, Guangzhou, China, said in a news release.
The study was published online in the journal Neurology.
A way to stop stroke progression?
The researchers assessed air pollution exposure in 318,752 people (mean age, 56) from the UK biobank database. None had a history of stroke or heart disease at the start of the study. Annual concentrations of air pollution near where people lived were estimated through land-use regressions.
During an average follow-up of 12 years, 5,967 people had a stroke, 2,985 developed post-stroke CVD, and 1,020 died.
After adjusting for confounding factors, every 5 µg/m3 increase in exposure to fine particulate matter (PM2.5) was associated with a 24% increase in transition from healthy to first stroke (hazard ratio, 1.24; 95% confidence interval, 1.10-1.40) and a 30% increase in transition from being healthy to dying (HR, 1.30; 95% CI, 1.21-1.40).
PM2.5 is less than 2.5 microns in diameter and includes fly ash from coal combustion. The World Health Organization recommends that annual PM2.5 exposure should not exceed 5 µg/m3.
Those who had a stroke during the study had an average exposure of 10.03 µg/m3 of PM2.5, compared with 9.97 µg/m3 for those who did not have a stroke.
The air pollutants nitrogen oxide and nitrogen dioxide were also associated with an increased risk of stroke and death, but the associations were weaker.
“More research is needed, but it’s possible that decreasing exposure to heavy levels of air pollution could play a role in reducing the progression of stroke,” Dr. Lin said.
“People can reduce their exposure by staying indoors on heavy pollution days, reducing their outdoor exercise, wearing masks to filter out particulate matter, and using air purifiers,” Dr. Lin added.
Public policy implications
Reached for comment, Steffen E. Petersen, MD, MPH, professor of cardiovascular medicine, Barts Health NHS Trust, London, said the study “elegantly confirms the increased risk of stroke due to air pollution in the UK Biobank population study but interestingly suggests that the impact of air pollution may continue to adversely impact cardiovascular health even after the stroke occurred.”
“This is further evidence to inform policymakers to tackle air pollution and get levels below the recommended levels,” Dr. Petersen said.
“On a personal level, everyone, including stroke patients, may wish to consider personal measures to reduce exposure to air pollution, such as avoiding walking along polluted streets and rather take a less polluted route away from the main roads,” Dr. Petersen added.
The study had no targeted funding. Dr. Lin and Dr. Petersen report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Results of a UK biobank study show high levels of air pollution were associated with an increased risk of transition from health to a first stroke and subsequent progression to cardiovascular (CV) events and death.
“These results indicate that understanding and reducing the effects of air pollutants on different transition stages in stroke will be beneficial in managing people’s health and preventing the occurrence and progression of stroke,” study investigator Hualiang Lin, PhD, of Sun Yat-sen University School of Public Health, Guangzhou, China, said in a news release.
The study was published online in the journal Neurology.
A way to stop stroke progression?
The researchers assessed air pollution exposure in 318,752 people (mean age, 56) from the UK biobank database. None had a history of stroke or heart disease at the start of the study. Annual concentrations of air pollution near where people lived were estimated through land-use regressions.
During an average follow-up of 12 years, 5,967 people had a stroke, 2,985 developed post-stroke CVD, and 1,020 died.
After adjusting for confounding factors, every 5 µg/m3 increase in exposure to fine particulate matter (PM2.5) was associated with a 24% increase in transition from healthy to first stroke (hazard ratio, 1.24; 95% confidence interval, 1.10-1.40) and a 30% increase in transition from being healthy to dying (HR, 1.30; 95% CI, 1.21-1.40).
PM2.5 is less than 2.5 microns in diameter and includes fly ash from coal combustion. The World Health Organization recommends that annual PM2.5 exposure should not exceed 5 µg/m3.
Those who had a stroke during the study had an average exposure of 10.03 µg/m3 of PM2.5, compared with 9.97 µg/m3 for those who did not have a stroke.
The air pollutants nitrogen oxide and nitrogen dioxide were also associated with an increased risk of stroke and death, but the associations were weaker.
“More research is needed, but it’s possible that decreasing exposure to heavy levels of air pollution could play a role in reducing the progression of stroke,” Dr. Lin said.
“People can reduce their exposure by staying indoors on heavy pollution days, reducing their outdoor exercise, wearing masks to filter out particulate matter, and using air purifiers,” Dr. Lin added.
Public policy implications
Reached for comment, Steffen E. Petersen, MD, MPH, professor of cardiovascular medicine, Barts Health NHS Trust, London, said the study “elegantly confirms the increased risk of stroke due to air pollution in the UK Biobank population study but interestingly suggests that the impact of air pollution may continue to adversely impact cardiovascular health even after the stroke occurred.”
“This is further evidence to inform policymakers to tackle air pollution and get levels below the recommended levels,” Dr. Petersen said.
“On a personal level, everyone, including stroke patients, may wish to consider personal measures to reduce exposure to air pollution, such as avoiding walking along polluted streets and rather take a less polluted route away from the main roads,” Dr. Petersen added.
The study had no targeted funding. Dr. Lin and Dr. Petersen report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Results of a UK biobank study show high levels of air pollution were associated with an increased risk of transition from health to a first stroke and subsequent progression to cardiovascular (CV) events and death.
“These results indicate that understanding and reducing the effects of air pollutants on different transition stages in stroke will be beneficial in managing people’s health and preventing the occurrence and progression of stroke,” study investigator Hualiang Lin, PhD, of Sun Yat-sen University School of Public Health, Guangzhou, China, said in a news release.
The study was published online in the journal Neurology.
A way to stop stroke progression?
The researchers assessed air pollution exposure in 318,752 people (mean age, 56) from the UK biobank database. None had a history of stroke or heart disease at the start of the study. Annual concentrations of air pollution near where people lived were estimated through land-use regressions.
During an average follow-up of 12 years, 5,967 people had a stroke, 2,985 developed post-stroke CVD, and 1,020 died.
After adjusting for confounding factors, every 5 µg/m3 increase in exposure to fine particulate matter (PM2.5) was associated with a 24% increase in transition from healthy to first stroke (hazard ratio, 1.24; 95% confidence interval, 1.10-1.40) and a 30% increase in transition from being healthy to dying (HR, 1.30; 95% CI, 1.21-1.40).
PM2.5 is less than 2.5 microns in diameter and includes fly ash from coal combustion. The World Health Organization recommends that annual PM2.5 exposure should not exceed 5 µg/m3.
Those who had a stroke during the study had an average exposure of 10.03 µg/m3 of PM2.5, compared with 9.97 µg/m3 for those who did not have a stroke.
The air pollutants nitrogen oxide and nitrogen dioxide were also associated with an increased risk of stroke and death, but the associations were weaker.
“More research is needed, but it’s possible that decreasing exposure to heavy levels of air pollution could play a role in reducing the progression of stroke,” Dr. Lin said.
“People can reduce their exposure by staying indoors on heavy pollution days, reducing their outdoor exercise, wearing masks to filter out particulate matter, and using air purifiers,” Dr. Lin added.
Public policy implications
Reached for comment, Steffen E. Petersen, MD, MPH, professor of cardiovascular medicine, Barts Health NHS Trust, London, said the study “elegantly confirms the increased risk of stroke due to air pollution in the UK Biobank population study but interestingly suggests that the impact of air pollution may continue to adversely impact cardiovascular health even after the stroke occurred.”
“This is further evidence to inform policymakers to tackle air pollution and get levels below the recommended levels,” Dr. Petersen said.
“On a personal level, everyone, including stroke patients, may wish to consider personal measures to reduce exposure to air pollution, such as avoiding walking along polluted streets and rather take a less polluted route away from the main roads,” Dr. Petersen added.
The study had no targeted funding. Dr. Lin and Dr. Petersen report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
‘Plethora’ of new MCL treatment options
Specific research needs include comparative studies of novel treatment combinations like ibrutinib plus venetoclax, which has shown singular promise in clinical trials, and further investigation of emerging immunotherapies like bi-specific T-cell engagers (BiTEs), said review author Mubarak Al-Mansour, MD.
The review article, published online in Clinical Lymphoma, Myeloma & Leukemia, includes a proposed treatment algorithm based on the latest data.
“Since the introduction of [Bruton’s tyrosine kinase] inhibitors, the treatment algorithm and response of R/RMCL patients have dramatically changed. Nevertheless, Bruton's tyrosine kinase resistance is common, which necessitated further investigations to develop novel agents with a more durable response,” explained Dr. Al-Mansour a medical oncologist at Princess Noorah Oncology Center, Jeddah, Saudi Arabia.
Modest clinical activity and tolerability observed with novel agents that targeted B-cell receptor signaling led to investigation of combination strategies in preclinical and early clinical settings, in order to assess whether more durable response rates could be achieved than with single-agent therapy, he said.
“[Of] these combinations, ibrutinib plus venetoclax had the highest response rates in the setting of clinical trials, even in high-risk patients,” Dr. Al-Mansour noted.
Other promising therapies include chimeric antigen receptor (CAR) T-cell therapies (CAR-T) and BiTEs, which “appear to be powerful agents in the therapeutic arsenals of R/RMCL, especially among heavily pretreated patients,” he said, adding, however, that “further investigations are still warranted to assess the clinical activity of CAR-T or BiTEs therapies in combination with other agents.”
Comparative studies also will be needed to assess the relative advantages of various treatment approaches, he said.
These investigations are important given the generally short duration of remission among patients with MCL, which now accounts for between 2% and 6% of all non-Hodgkin lymphoma cases, an incidence that has risen steadily over the past few decades, Dr. Al-Mansour pointed out.
Although many patients achieve an adequate response in the upfront treatment setting, with overall response rates ranging from 60% to 97%, remission is generally short-lived, and the rapid relapses that occur pose a challenge. Additionally, most patients are elderly and have a poor prognosis: Reported progression-free survival in older patients ranges from 2 to 3 years and median overall survival ranges from 28.8 to 52 months, compared with 62 and 139 months, respectively, in young, fit patients, he said.
Furthermore, there is no consensus on the best treatment options in the relapsed/refractory setting, and international guidelines vary widely, he added.
For the current review, Dr. Al-Mansour conducted an online bibliographic search for relevant clinical trial data and meeting abstracts published through the end of March 2022. The data addressed treatment pathways, resistance mechanisms, various approved and investigational agents and treatments used alone or in combination regimens, and stem cell transplant (SCT).
Based on the evidence, Dr. Al-Mansour proposed the following “general algorithm” for the management of R/RMCL:
“Fit patients should be categorized according to their time until disease progression into early (< 24 months) and late (> 24 months) groups. In patients with early progression of the disease, Bruton's tyrosine kinase inhibitors should be offered. Other alternatives should be offered in case of relapse or failure, including CAR-T, [allogeneic-SCT (allo-SCT)], or enrollment in a clinical trial.”
For patients with late disease progression, the algorithm calls for offering Bruton's tyrosine kinase inhibitors, rituximab-bendamustine–based chemotherapy, or rituximab-lenalidomide.
“Other alternatives should be offered in case of relapse or failure, including CAR-T, allo-SCT, or enrollment in a clinical trial. Unfit patients can be offered Bruton's tyrosine kinase inhibitors, considering CAR-T or enrollment in a clinical trial in case of failure.”
Dr. Al-Mansour also noted COVID-19 pandemic–related caveats for the management of R/RMCL.
“Recent epidemiological figures demonstrated that cancer patients are at excessive risk of severe COVID-19. In the case of hematological malignancies, patients are usually on immunosuppressants, which further increase the risk of severe disease and death,” he wrote.
For this reason, and because current treatments consist mainly of targeted agents, which “exert negative effects on patients’ humoral and cell-mediated immunity,” the timing and schedules of treatment regimens should be determined with consideration of COVID-19–related risks, he advised.
Specific research needs include comparative studies of novel treatment combinations like ibrutinib plus venetoclax, which has shown singular promise in clinical trials, and further investigation of emerging immunotherapies like bi-specific T-cell engagers (BiTEs), said review author Mubarak Al-Mansour, MD.
The review article, published online in Clinical Lymphoma, Myeloma & Leukemia, includes a proposed treatment algorithm based on the latest data.
“Since the introduction of [Bruton’s tyrosine kinase] inhibitors, the treatment algorithm and response of R/RMCL patients have dramatically changed. Nevertheless, Bruton's tyrosine kinase resistance is common, which necessitated further investigations to develop novel agents with a more durable response,” explained Dr. Al-Mansour a medical oncologist at Princess Noorah Oncology Center, Jeddah, Saudi Arabia.
Modest clinical activity and tolerability observed with novel agents that targeted B-cell receptor signaling led to investigation of combination strategies in preclinical and early clinical settings, in order to assess whether more durable response rates could be achieved than with single-agent therapy, he said.
“[Of] these combinations, ibrutinib plus venetoclax had the highest response rates in the setting of clinical trials, even in high-risk patients,” Dr. Al-Mansour noted.
Other promising therapies include chimeric antigen receptor (CAR) T-cell therapies (CAR-T) and BiTEs, which “appear to be powerful agents in the therapeutic arsenals of R/RMCL, especially among heavily pretreated patients,” he said, adding, however, that “further investigations are still warranted to assess the clinical activity of CAR-T or BiTEs therapies in combination with other agents.”
Comparative studies also will be needed to assess the relative advantages of various treatment approaches, he said.
These investigations are important given the generally short duration of remission among patients with MCL, which now accounts for between 2% and 6% of all non-Hodgkin lymphoma cases, an incidence that has risen steadily over the past few decades, Dr. Al-Mansour pointed out.
Although many patients achieve an adequate response in the upfront treatment setting, with overall response rates ranging from 60% to 97%, remission is generally short-lived, and the rapid relapses that occur pose a challenge. Additionally, most patients are elderly and have a poor prognosis: Reported progression-free survival in older patients ranges from 2 to 3 years and median overall survival ranges from 28.8 to 52 months, compared with 62 and 139 months, respectively, in young, fit patients, he said.
Furthermore, there is no consensus on the best treatment options in the relapsed/refractory setting, and international guidelines vary widely, he added.
For the current review, Dr. Al-Mansour conducted an online bibliographic search for relevant clinical trial data and meeting abstracts published through the end of March 2022. The data addressed treatment pathways, resistance mechanisms, various approved and investigational agents and treatments used alone or in combination regimens, and stem cell transplant (SCT).
Based on the evidence, Dr. Al-Mansour proposed the following “general algorithm” for the management of R/RMCL:
“Fit patients should be categorized according to their time until disease progression into early (< 24 months) and late (> 24 months) groups. In patients with early progression of the disease, Bruton's tyrosine kinase inhibitors should be offered. Other alternatives should be offered in case of relapse or failure, including CAR-T, [allogeneic-SCT (allo-SCT)], or enrollment in a clinical trial.”
For patients with late disease progression, the algorithm calls for offering Bruton's tyrosine kinase inhibitors, rituximab-bendamustine–based chemotherapy, or rituximab-lenalidomide.
“Other alternatives should be offered in case of relapse or failure, including CAR-T, allo-SCT, or enrollment in a clinical trial. Unfit patients can be offered Bruton's tyrosine kinase inhibitors, considering CAR-T or enrollment in a clinical trial in case of failure.”
Dr. Al-Mansour also noted COVID-19 pandemic–related caveats for the management of R/RMCL.
“Recent epidemiological figures demonstrated that cancer patients are at excessive risk of severe COVID-19. In the case of hematological malignancies, patients are usually on immunosuppressants, which further increase the risk of severe disease and death,” he wrote.
For this reason, and because current treatments consist mainly of targeted agents, which “exert negative effects on patients’ humoral and cell-mediated immunity,” the timing and schedules of treatment regimens should be determined with consideration of COVID-19–related risks, he advised.
Specific research needs include comparative studies of novel treatment combinations like ibrutinib plus venetoclax, which has shown singular promise in clinical trials, and further investigation of emerging immunotherapies like bi-specific T-cell engagers (BiTEs), said review author Mubarak Al-Mansour, MD.
The review article, published online in Clinical Lymphoma, Myeloma & Leukemia, includes a proposed treatment algorithm based on the latest data.
“Since the introduction of [Bruton’s tyrosine kinase] inhibitors, the treatment algorithm and response of R/RMCL patients have dramatically changed. Nevertheless, Bruton's tyrosine kinase resistance is common, which necessitated further investigations to develop novel agents with a more durable response,” explained Dr. Al-Mansour a medical oncologist at Princess Noorah Oncology Center, Jeddah, Saudi Arabia.
Modest clinical activity and tolerability observed with novel agents that targeted B-cell receptor signaling led to investigation of combination strategies in preclinical and early clinical settings, in order to assess whether more durable response rates could be achieved than with single-agent therapy, he said.
“[Of] these combinations, ibrutinib plus venetoclax had the highest response rates in the setting of clinical trials, even in high-risk patients,” Dr. Al-Mansour noted.
Other promising therapies include chimeric antigen receptor (CAR) T-cell therapies (CAR-T) and BiTEs, which “appear to be powerful agents in the therapeutic arsenals of R/RMCL, especially among heavily pretreated patients,” he said, adding, however, that “further investigations are still warranted to assess the clinical activity of CAR-T or BiTEs therapies in combination with other agents.”
Comparative studies also will be needed to assess the relative advantages of various treatment approaches, he said.
These investigations are important given the generally short duration of remission among patients with MCL, which now accounts for between 2% and 6% of all non-Hodgkin lymphoma cases, an incidence that has risen steadily over the past few decades, Dr. Al-Mansour pointed out.
Although many patients achieve an adequate response in the upfront treatment setting, with overall response rates ranging from 60% to 97%, remission is generally short-lived, and the rapid relapses that occur pose a challenge. Additionally, most patients are elderly and have a poor prognosis: Reported progression-free survival in older patients ranges from 2 to 3 years and median overall survival ranges from 28.8 to 52 months, compared with 62 and 139 months, respectively, in young, fit patients, he said.
Furthermore, there is no consensus on the best treatment options in the relapsed/refractory setting, and international guidelines vary widely, he added.
For the current review, Dr. Al-Mansour conducted an online bibliographic search for relevant clinical trial data and meeting abstracts published through the end of March 2022. The data addressed treatment pathways, resistance mechanisms, various approved and investigational agents and treatments used alone or in combination regimens, and stem cell transplant (SCT).
Based on the evidence, Dr. Al-Mansour proposed the following “general algorithm” for the management of R/RMCL:
“Fit patients should be categorized according to their time until disease progression into early (< 24 months) and late (> 24 months) groups. In patients with early progression of the disease, Bruton's tyrosine kinase inhibitors should be offered. Other alternatives should be offered in case of relapse or failure, including CAR-T, [allogeneic-SCT (allo-SCT)], or enrollment in a clinical trial.”
For patients with late disease progression, the algorithm calls for offering Bruton's tyrosine kinase inhibitors, rituximab-bendamustine–based chemotherapy, or rituximab-lenalidomide.
“Other alternatives should be offered in case of relapse or failure, including CAR-T, allo-SCT, or enrollment in a clinical trial. Unfit patients can be offered Bruton's tyrosine kinase inhibitors, considering CAR-T or enrollment in a clinical trial in case of failure.”
Dr. Al-Mansour also noted COVID-19 pandemic–related caveats for the management of R/RMCL.
“Recent epidemiological figures demonstrated that cancer patients are at excessive risk of severe COVID-19. In the case of hematological malignancies, patients are usually on immunosuppressants, which further increase the risk of severe disease and death,” he wrote.
For this reason, and because current treatments consist mainly of targeted agents, which “exert negative effects on patients’ humoral and cell-mediated immunity,” the timing and schedules of treatment regimens should be determined with consideration of COVID-19–related risks, he advised.
FROM CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA