News

TOPLINE:

Sleep-related daytime dysfunction is associated with an almost threefold higher risk for motoric cognitive risk (MCR) syndrome, a predementia condition characterized by slow gait and cognitive issues, a new study shows.

METHODOLOGY:

• Researchers included 445 older adults without dementia (mean age, 76 years; 57% women).
• Sleep components were assessed, and participants were classified as poor or good sleepers using the Pittsburgh Sleep Quality Index questionnaire.
• The primary outcome was incidence of MCR syndrome.
• The mean follow-up duration was 2.9 years.

TAKEAWAY:

• During the study period, 36 participants developed MCR syndrome.
• Poor sleepers had a higher risk for incident MCR syndrome, compared with good sleepers, after adjustment for age, sex, and educational level (adjusted hazard ratio [aHR], 2.6; 95% CI, 1.3-5.0; P < .05). However, this association was no longer significant after further adjustment for depressive symptoms.
• Sleep-related daytime dysfunction, defined as excessive sleepiness and lower enthusiasm for activities, was the only sleep component linked to a significant risk for MCR syndrome in fully adjusted models (aHR, 3.3; 95% CI, 1.5-7.4; P < .05).
• Prevalent MCR syndrome was not significantly associated with poor sleep quality (odds ratio, 1.1), suggesting that the relationship is unidirectional.

IN PRACTICE:

“Establishing the relationship between sleep dysfunction and MCR [syndrome] risk is important because early intervention may offer the best hope for preventing dementia,” the investigators wrote.

“Our findings emphasize the need for screening for sleep issues. There’s potential that people could get help with their sleep issues and prevent cognitive decline later in life,” lead author Victoire Leroy, MD, PhD, Albert Einstein College of Medicine, New York City, added in a press release. 

 

SOURCE:

The study was published online in Neurology.

LIMITATIONS: 

Study limitations included the lack of objective sleep measurements and potential recall bias in self-reported sleep complaints, particularly among participants with cognitive issues. In addition, the relatively short follow-up period may have resulted in a lower number of incident MCR syndrome cases. The sample population was also predominantly White (80%), which may have limited the generalizability of the findings to other populations.

DISCLOSURES:

The study was funded by the National Institute on Aging. No conflicts of interest were reported.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Sleep-related daytime dysfunction is associated with an almost threefold higher risk for motoric cognitive risk (MCR) syndrome, a predementia condition characterized by slow gait and cognitive issues, a new study shows.

METHODOLOGY:

• Researchers included 445 older adults without dementia (mean age, 76 years; 57% women).
• Sleep components were assessed, and participants were classified as poor or good sleepers using the Pittsburgh Sleep Quality Index questionnaire.
• The primary outcome was incidence of MCR syndrome.
• The mean follow-up duration was 2.9 years.

TAKEAWAY:

• During the study period, 36 participants developed MCR syndrome.
• Poor sleepers had a higher risk for incident MCR syndrome, compared with good sleepers, after adjustment for age, sex, and educational level (adjusted hazard ratio [aHR], 2.6; 95% CI, 1.3-5.0; P < .05). However, this association was no longer significant after further adjustment for depressive symptoms.
• Sleep-related daytime dysfunction, defined as excessive sleepiness and lower enthusiasm for activities, was the only sleep component linked to a significant risk for MCR syndrome in fully adjusted models (aHR, 3.3; 95% CI, 1.5-7.4; P < .05).
• Prevalent MCR syndrome was not significantly associated with poor sleep quality (odds ratio, 1.1), suggesting that the relationship is unidirectional.

IN PRACTICE:

“Establishing the relationship between sleep dysfunction and MCR [syndrome] risk is important because early intervention may offer the best hope for preventing dementia,” the investigators wrote.

“Our findings emphasize the need for screening for sleep issues. There’s potential that people could get help with their sleep issues and prevent cognitive decline later in life,” lead author Victoire Leroy, MD, PhD, Albert Einstein College of Medicine, New York City, added in a press release. 

 

SOURCE:

The study was published online in Neurology.

LIMITATIONS: 

Study limitations included the lack of objective sleep measurements and potential recall bias in self-reported sleep complaints, particularly among participants with cognitive issues. In addition, the relatively short follow-up period may have resulted in a lower number of incident MCR syndrome cases. The sample population was also predominantly White (80%), which may have limited the generalizability of the findings to other populations.

DISCLOSURES:

The study was funded by the National Institute on Aging. No conflicts of interest were reported.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Sleep-related daytime dysfunction is associated with an almost threefold higher risk for motoric cognitive risk (MCR) syndrome, a predementia condition characterized by slow gait and cognitive issues, a new study shows.

METHODOLOGY:

• Researchers included 445 older adults without dementia (mean age, 76 years; 57% women).
• Sleep components were assessed, and participants were classified as poor or good sleepers using the Pittsburgh Sleep Quality Index questionnaire.
• The primary outcome was incidence of MCR syndrome.
• The mean follow-up duration was 2.9 years.

TAKEAWAY:

• During the study period, 36 participants developed MCR syndrome.
• Poor sleepers had a higher risk for incident MCR syndrome, compared with good sleepers, after adjustment for age, sex, and educational level (adjusted hazard ratio [aHR], 2.6; 95% CI, 1.3-5.0; P < .05). However, this association was no longer significant after further adjustment for depressive symptoms.
• Sleep-related daytime dysfunction, defined as excessive sleepiness and lower enthusiasm for activities, was the only sleep component linked to a significant risk for MCR syndrome in fully adjusted models (aHR, 3.3; 95% CI, 1.5-7.4; P < .05).
• Prevalent MCR syndrome was not significantly associated with poor sleep quality (odds ratio, 1.1), suggesting that the relationship is unidirectional.

IN PRACTICE:

“Establishing the relationship between sleep dysfunction and MCR [syndrome] risk is important because early intervention may offer the best hope for preventing dementia,” the investigators wrote.

“Our findings emphasize the need for screening for sleep issues. There’s potential that people could get help with their sleep issues and prevent cognitive decline later in life,” lead author Victoire Leroy, MD, PhD, Albert Einstein College of Medicine, New York City, added in a press release. 

 

SOURCE:

The study was published online in Neurology.

LIMITATIONS: 

Study limitations included the lack of objective sleep measurements and potential recall bias in self-reported sleep complaints, particularly among participants with cognitive issues. In addition, the relatively short follow-up period may have resulted in a lower number of incident MCR syndrome cases. The sample population was also predominantly White (80%), which may have limited the generalizability of the findings to other populations.

DISCLOSURES:

The study was funded by the National Institute on Aging. No conflicts of interest were reported.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Sedentary time exceeding 10.6 h/d is linked to an increased risk for atrial fibrillation, heart failure, myocardial infarction, and cardiovascular (CV) mortality, researchers found. The risk persists even in individuals who meet recommended physical activity levels.

METHODOLOGY:

• Researchers used a validated machine learning approach to investigate the relationships between sedentary behavior and the future risks for CV illness and mortality in 89,530 middle-aged and older adults (mean age, 62 years; 56% women) from the UK Biobank.
• Participants provided data from a wrist-worn triaxial accelerometer that recorded their movements over a period of 7 days.
• Machine learning algorithms classified accelerometer signals into four classes of activities: Sleep, sedentary behavior, light physical activity, and moderate to vigorous physical activity.
• Participants were followed up for a median of 8 years through linkage to national health-related datasets in England, Scotland, and Wales.
• The median sedentary time was 9.4 h/d.

TAKEAWAY:

• During the follow-up period, 3638 individuals (4.9%) experienced incident atrial fibrillation, 1854 (2.09%) developed incident heart failure, 1610 (1.84%) experienced incident myocardial infarction, and 846 (0.94%) died from cardiovascular causes.
• The risks for atrial fibrillation and myocardial infarction increased steadily with an increase in sedentary time, with sedentary time greater than 10.6 h/d showing a modest increase in risk for atrial fibrillation (hazard ratio [HR], 1.11; 95% CI, 1.01-1.21).
• The risks for heart failure and CV mortality were low until sedentary time surpassed approximately 10.6 h/d, after which they rose by 45% (HR, 1.45; 95% CI, 1.28-1.65) and 62% (HR, 1.62; 95% CI, 1.34-1.96), respectively.
• The associations were attenuated but remained significant for CV mortality (HR, 1.33; 95% CI: 1.07-1.64) in individuals who met the recommended levels for physical activity yet were sedentary for more than 10.6 h/d. Reallocating 30 minutes of sedentary time to other activities reduced the risk for heart failure (HR, 0.93; 95% CI, 0.90-0.96) among those who were sedentary more than 10.6 h/d.

IN PRACTICE:

The study “highlights a complex interplay between sedentary behavior and physical activity, ultimately suggesting that sedentary behavior remains relevant for CV disease risk even among individuals meeting sufficient” levels of activity, the researchers reported.

“Individuals should move more and be less sedentary to reduce CV risk. ... Being a ‘weekend warrior’ and meeting guideline levels of [moderate to vigorous physical activity] of 150 minutes/week will not completely abolish the deleterious effects of extended sedentary time of > 10.6 hours per day,” Charles B. Eaton, MD, MS, of the Warren Alpert Medical School of Brown University in Providence, Rhode Island, wrote in an editorial accompanying the journal article.

 

SOURCE:

The study was led by Ezimamaka Ajufo, MD, of Brigham and Women’s Hospital in Boston. It was published online on November 15, 2024, in the Journal of the American College of Cardiology.

LIMITATIONS:

Wrist-based accelerometers cannot assess specific contexts for sedentary behavior and may misclassify standing time as sedentary time, and these limitations may have affected the findings. Physical activity was measured for 1 week only, which might not have fully represented habitual activity patterns. The sample included predominantly White participants and was enriched for health and socioeconomic status, which may have limited the generalizability of the findings.

DISCLOSURES:

The authors disclosed receiving research support, grants, and research fellowships and collaborations from various institutions and pharmaceutical companies, as well as serving on their advisory boards.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Sedentary time exceeding 10.6 h/d is linked to an increased risk for atrial fibrillation, heart failure, myocardial infarction, and cardiovascular (CV) mortality, researchers found. The risk persists even in individuals who meet recommended physical activity levels.

METHODOLOGY:

• Researchers used a validated machine learning approach to investigate the relationships between sedentary behavior and the future risks for CV illness and mortality in 89,530 middle-aged and older adults (mean age, 62 years; 56% women) from the UK Biobank.
• Participants provided data from a wrist-worn triaxial accelerometer that recorded their movements over a period of 7 days.
• Machine learning algorithms classified accelerometer signals into four classes of activities: Sleep, sedentary behavior, light physical activity, and moderate to vigorous physical activity.
• Participants were followed up for a median of 8 years through linkage to national health-related datasets in England, Scotland, and Wales.
• The median sedentary time was 9.4 h/d.

TAKEAWAY:

• During the follow-up period, 3638 individuals (4.9%) experienced incident atrial fibrillation, 1854 (2.09%) developed incident heart failure, 1610 (1.84%) experienced incident myocardial infarction, and 846 (0.94%) died from cardiovascular causes.
• The risks for atrial fibrillation and myocardial infarction increased steadily with an increase in sedentary time, with sedentary time greater than 10.6 h/d showing a modest increase in risk for atrial fibrillation (hazard ratio [HR], 1.11; 95% CI, 1.01-1.21).
• The risks for heart failure and CV mortality were low until sedentary time surpassed approximately 10.6 h/d, after which they rose by 45% (HR, 1.45; 95% CI, 1.28-1.65) and 62% (HR, 1.62; 95% CI, 1.34-1.96), respectively.
• The associations were attenuated but remained significant for CV mortality (HR, 1.33; 95% CI: 1.07-1.64) in individuals who met the recommended levels for physical activity yet were sedentary for more than 10.6 h/d. Reallocating 30 minutes of sedentary time to other activities reduced the risk for heart failure (HR, 0.93; 95% CI, 0.90-0.96) among those who were sedentary more than 10.6 h/d.

IN PRACTICE:

The study “highlights a complex interplay between sedentary behavior and physical activity, ultimately suggesting that sedentary behavior remains relevant for CV disease risk even among individuals meeting sufficient” levels of activity, the researchers reported.

“Individuals should move more and be less sedentary to reduce CV risk. ... Being a ‘weekend warrior’ and meeting guideline levels of [moderate to vigorous physical activity] of 150 minutes/week will not completely abolish the deleterious effects of extended sedentary time of > 10.6 hours per day,” Charles B. Eaton, MD, MS, of the Warren Alpert Medical School of Brown University in Providence, Rhode Island, wrote in an editorial accompanying the journal article.

 

SOURCE:

The study was led by Ezimamaka Ajufo, MD, of Brigham and Women’s Hospital in Boston. It was published online on November 15, 2024, in the Journal of the American College of Cardiology.

LIMITATIONS:

Wrist-based accelerometers cannot assess specific contexts for sedentary behavior and may misclassify standing time as sedentary time, and these limitations may have affected the findings. Physical activity was measured for 1 week only, which might not have fully represented habitual activity patterns. The sample included predominantly White participants and was enriched for health and socioeconomic status, which may have limited the generalizability of the findings.

DISCLOSURES:

The authors disclosed receiving research support, grants, and research fellowships and collaborations from various institutions and pharmaceutical companies, as well as serving on their advisory boards.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Sedentary time exceeding 10.6 h/d is linked to an increased risk for atrial fibrillation, heart failure, myocardial infarction, and cardiovascular (CV) mortality, researchers found. The risk persists even in individuals who meet recommended physical activity levels.

METHODOLOGY:

• Researchers used a validated machine learning approach to investigate the relationships between sedentary behavior and the future risks for CV illness and mortality in 89,530 middle-aged and older adults (mean age, 62 years; 56% women) from the UK Biobank.
• Participants provided data from a wrist-worn triaxial accelerometer that recorded their movements over a period of 7 days.
• Machine learning algorithms classified accelerometer signals into four classes of activities: Sleep, sedentary behavior, light physical activity, and moderate to vigorous physical activity.
• Participants were followed up for a median of 8 years through linkage to national health-related datasets in England, Scotland, and Wales.
• The median sedentary time was 9.4 h/d.

TAKEAWAY:

• During the follow-up period, 3638 individuals (4.9%) experienced incident atrial fibrillation, 1854 (2.09%) developed incident heart failure, 1610 (1.84%) experienced incident myocardial infarction, and 846 (0.94%) died from cardiovascular causes.
• The risks for atrial fibrillation and myocardial infarction increased steadily with an increase in sedentary time, with sedentary time greater than 10.6 h/d showing a modest increase in risk for atrial fibrillation (hazard ratio [HR], 1.11; 95% CI, 1.01-1.21).
• The risks for heart failure and CV mortality were low until sedentary time surpassed approximately 10.6 h/d, after which they rose by 45% (HR, 1.45; 95% CI, 1.28-1.65) and 62% (HR, 1.62; 95% CI, 1.34-1.96), respectively.
• The associations were attenuated but remained significant for CV mortality (HR, 1.33; 95% CI: 1.07-1.64) in individuals who met the recommended levels for physical activity yet were sedentary for more than 10.6 h/d. Reallocating 30 minutes of sedentary time to other activities reduced the risk for heart failure (HR, 0.93; 95% CI, 0.90-0.96) among those who were sedentary more than 10.6 h/d.

IN PRACTICE:

The study “highlights a complex interplay between sedentary behavior and physical activity, ultimately suggesting that sedentary behavior remains relevant for CV disease risk even among individuals meeting sufficient” levels of activity, the researchers reported.

“Individuals should move more and be less sedentary to reduce CV risk. ... Being a ‘weekend warrior’ and meeting guideline levels of [moderate to vigorous physical activity] of 150 minutes/week will not completely abolish the deleterious effects of extended sedentary time of > 10.6 hours per day,” Charles B. Eaton, MD, MS, of the Warren Alpert Medical School of Brown University in Providence, Rhode Island, wrote in an editorial accompanying the journal article.

 

SOURCE:

The study was led by Ezimamaka Ajufo, MD, of Brigham and Women’s Hospital in Boston. It was published online on November 15, 2024, in the Journal of the American College of Cardiology.

LIMITATIONS:

Wrist-based accelerometers cannot assess specific contexts for sedentary behavior and may misclassify standing time as sedentary time, and these limitations may have affected the findings. Physical activity was measured for 1 week only, which might not have fully represented habitual activity patterns. The sample included predominantly White participants and was enriched for health and socioeconomic status, which may have limited the generalizability of the findings.

DISCLOSURES:

The authors disclosed receiving research support, grants, and research fellowships and collaborations from various institutions and pharmaceutical companies, as well as serving on their advisory boards.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

SAN ANTONIO — Oral semaglutide 25 mg appears to be just as effective in promoting weight loss and other beneficial outcomes as are the investigational 50-mg oral dose and the injectable 2.4-mg dose (Wegovy), in new research.

Data from Novo Nordisk’s OASIS 4 trial suggest that “oral semaglutide 25 mg may represent an efficacious option for the treatment of overweight and obesity, particularly in patients who prefer oral administration,” W. Timothy Garvey, MD, professor in the Department of Nutrition Sciences at the University of Alabama at Birmingham (UAB), said at the Obesity Society’s Obesity Week 2024 meeting.

In an interview, Garvey, who is also senior scientist at the UAB Nutrition Obesity Research Center, added: “There’s a principle in medicine that you always use the lowest dose that has highest efficacy, and for oral semaglutide for obesity, that appears to be the 25-mg dose. We need oral medicines to offer as an option for patients that could lead to a longer persistence in adherence to obesity medications, which is a big problem. Less than half the people maintain their adherence after a year.”

Asked to comment, session moderator and obesity researcher Joseph A. Skelton, MD, professor of pediatrics at Wake Forest University School of Medicine, Winston-Salem, North Carolina, said that OASIS 4 was “extremely well done, especially given that we’re all concerned about the high prevalence of people stopping these medications at a year. ... I love the idea of trying to find these lower doses and increasing options for people.”

(The oral semaglutide approved for treating type 2 diabetes [Rybelsus] is sold in 7-mg and 14-mg doses.)

 

With Oral Semaglutide, Lower May Be Better

OASIS 4 was a double-blind, randomized, placebo-controlled 64-week multicenter trial involving a total of 307 participants with overweight/obesity randomized 2:1 to oral semaglutide 25 mg or placebo. Of those, 167 in the semaglutide 25 mg and 76 in the placebo groups completed the trial.

For the co–primary endpoint change in body weight at week 64 (including 52-week maintenance and 7-week follow-up periods), there was a drop of 13.6% with oral semaglutide vs just 2.2% with placebo (P < .0001), based on in-trial observation regardless of adherence. For the analysis including just the on-treatment period, those reductions were 16.6% and 2.7%, respectively (P < .0001).

For the other co–primary endpoint, 79.2% semaglutide vs 31.1% placebo lost at least 5% of their body weight, 63.0% vs 14.4% lost ≥ 10%, 50.0% vs 5.6% lost ≥ 15%, and 29.7% vs 3.3% lost ≥ 20%. All were statistically significant differences, at P < .0001.

On the Impact of Weight on Quality of Life-Lite Clinical Trials Version, change from baseline scores were 16.2 with oral semaglutide vs 8.4 for placebo (P = .0006) and the proportion of participants achieving clinically meaningful increases in those scores (≥ 14.6 points) were 55.3% vs 34.8% (P = .0022).

Waist circumference was also significantly reduced from baseline with oral semaglutide, by 12.2 cm vs 2.8 cm (P < .0001). Both systolic and diastolic blood pressure dropped more with semaglutide than placebo, but not significantly. However, the inflammatory marker C-reactive protein dropped from baseline by 46.4% vs just 4.2% with placebo, a significant difference (P < .0001).

Hemoglobin A1c dropped by 0.29 percentage points vs just 0.06 with placebo (P = .0012) and fasting plasma glucose by 6.6 mg/dL, while rising by 0.4 mg/dL in the placebo group (P = .0012). Lipid levels also improved more with oral semaglutide.

Overall adverse events occurred in 93.1% on oral semaglutide and 85.3% with placebo, and gastrointestinal adverse events in 74% and 42.2%, respectively. Other types of adverse events didn’t differ between the groups. The proportions experiencing severe adverse events were less in the semaglutide group (3.9% vs 8.8%), although adverse events leading to permanent treatment discontinuation were slightly higher with oral semaglutide (6.9% vs 5.9%). There were no deaths.

The estimated treatment difference from placebo in body weight change of −11.4% in OASIS 4 (P < .0001) was similar to the –12.7% (P < .0001) seen with the 50-mg oral semaglutide dose studied in OASIS 1 and the –12.4% (P < .0001) difference with subcutaneous semaglutide 2.4 mg in the STEP 1 trial. “All had pretty comparable efficacy,” Garvey noted.

The side-effect profiles, including frequency of gastrointestinal side effects, were also similar across the three trials. However, Garvey added, “the mean duration of nausea in those patients that experienced nausea was shorter in patients on a 25-mg dose, 13 days, whereas the mean duration of nausea was greater, 19 days, in those in OASIS 1 taking 50 mg a day.”

Garvey has consulted for Boehringer Ingelheim, Carmot Therapeutics/Roche, Eli Lilly, Fractyl Laboratories, Inogen, Lilly, Merck, Novo Nordisk, and Zealand Pharma; has ownership interest (stock, stock options in a publicly owned company) for Bristol-Myers Squibb, Isis, Lilly, and Novartis; serves as site principal investigator for Carmot Therapeutics/Roche, Eli Lilly, Epitomee Medical, Lilly, Neurovalens, Novo Nordisk, and Zealand Pharmaceuticals; and as a data monitoring committee member for Boehringer Ingelheim and Eli Lilly. Skelton is editor in chief of the journal Childhood Obesity.

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

SAN ANTONIO — Oral semaglutide 25 mg appears to be just as effective in promoting weight loss and other beneficial outcomes as are the investigational 50-mg oral dose and the injectable 2.4-mg dose (Wegovy), in new research.

Data from Novo Nordisk’s OASIS 4 trial suggest that “oral semaglutide 25 mg may represent an efficacious option for the treatment of overweight and obesity, particularly in patients who prefer oral administration,” W. Timothy Garvey, MD, professor in the Department of Nutrition Sciences at the University of Alabama at Birmingham (UAB), said at the Obesity Society’s Obesity Week 2024 meeting.

In an interview, Garvey, who is also senior scientist at the UAB Nutrition Obesity Research Center, added: “There’s a principle in medicine that you always use the lowest dose that has highest efficacy, and for oral semaglutide for obesity, that appears to be the 25-mg dose. We need oral medicines to offer as an option for patients that could lead to a longer persistence in adherence to obesity medications, which is a big problem. Less than half the people maintain their adherence after a year.”

Asked to comment, session moderator and obesity researcher Joseph A. Skelton, MD, professor of pediatrics at Wake Forest University School of Medicine, Winston-Salem, North Carolina, said that OASIS 4 was “extremely well done, especially given that we’re all concerned about the high prevalence of people stopping these medications at a year. ... I love the idea of trying to find these lower doses and increasing options for people.”

(The oral semaglutide approved for treating type 2 diabetes [Rybelsus] is sold in 7-mg and 14-mg doses.)

 

With Oral Semaglutide, Lower May Be Better

OASIS 4 was a double-blind, randomized, placebo-controlled 64-week multicenter trial involving a total of 307 participants with overweight/obesity randomized 2:1 to oral semaglutide 25 mg or placebo. Of those, 167 in the semaglutide 25 mg and 76 in the placebo groups completed the trial.

For the co–primary endpoint change in body weight at week 64 (including 52-week maintenance and 7-week follow-up periods), there was a drop of 13.6% with oral semaglutide vs just 2.2% with placebo (P < .0001), based on in-trial observation regardless of adherence. For the analysis including just the on-treatment period, those reductions were 16.6% and 2.7%, respectively (P < .0001).

For the other co–primary endpoint, 79.2% semaglutide vs 31.1% placebo lost at least 5% of their body weight, 63.0% vs 14.4% lost ≥ 10%, 50.0% vs 5.6% lost ≥ 15%, and 29.7% vs 3.3% lost ≥ 20%. All were statistically significant differences, at P < .0001.

On the Impact of Weight on Quality of Life-Lite Clinical Trials Version, change from baseline scores were 16.2 with oral semaglutide vs 8.4 for placebo (P = .0006) and the proportion of participants achieving clinically meaningful increases in those scores (≥ 14.6 points) were 55.3% vs 34.8% (P = .0022).

Waist circumference was also significantly reduced from baseline with oral semaglutide, by 12.2 cm vs 2.8 cm (P < .0001). Both systolic and diastolic blood pressure dropped more with semaglutide than placebo, but not significantly. However, the inflammatory marker C-reactive protein dropped from baseline by 46.4% vs just 4.2% with placebo, a significant difference (P < .0001).

Hemoglobin A1c dropped by 0.29 percentage points vs just 0.06 with placebo (P = .0012) and fasting plasma glucose by 6.6 mg/dL, while rising by 0.4 mg/dL in the placebo group (P = .0012). Lipid levels also improved more with oral semaglutide.

Overall adverse events occurred in 93.1% on oral semaglutide and 85.3% with placebo, and gastrointestinal adverse events in 74% and 42.2%, respectively. Other types of adverse events didn’t differ between the groups. The proportions experiencing severe adverse events were less in the semaglutide group (3.9% vs 8.8%), although adverse events leading to permanent treatment discontinuation were slightly higher with oral semaglutide (6.9% vs 5.9%). There were no deaths.

The estimated treatment difference from placebo in body weight change of −11.4% in OASIS 4 (P < .0001) was similar to the –12.7% (P < .0001) seen with the 50-mg oral semaglutide dose studied in OASIS 1 and the –12.4% (P < .0001) difference with subcutaneous semaglutide 2.4 mg in the STEP 1 trial. “All had pretty comparable efficacy,” Garvey noted.

The side-effect profiles, including frequency of gastrointestinal side effects, were also similar across the three trials. However, Garvey added, “the mean duration of nausea in those patients that experienced nausea was shorter in patients on a 25-mg dose, 13 days, whereas the mean duration of nausea was greater, 19 days, in those in OASIS 1 taking 50 mg a day.”

Garvey has consulted for Boehringer Ingelheim, Carmot Therapeutics/Roche, Eli Lilly, Fractyl Laboratories, Inogen, Lilly, Merck, Novo Nordisk, and Zealand Pharma; has ownership interest (stock, stock options in a publicly owned company) for Bristol-Myers Squibb, Isis, Lilly, and Novartis; serves as site principal investigator for Carmot Therapeutics/Roche, Eli Lilly, Epitomee Medical, Lilly, Neurovalens, Novo Nordisk, and Zealand Pharmaceuticals; and as a data monitoring committee member for Boehringer Ingelheim and Eli Lilly. Skelton is editor in chief of the journal Childhood Obesity.

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

SAN ANTONIO — Oral semaglutide 25 mg appears to be just as effective in promoting weight loss and other beneficial outcomes as are the investigational 50-mg oral dose and the injectable 2.4-mg dose (Wegovy), in new research.

Data from Novo Nordisk’s OASIS 4 trial suggest that “oral semaglutide 25 mg may represent an efficacious option for the treatment of overweight and obesity, particularly in patients who prefer oral administration,” W. Timothy Garvey, MD, professor in the Department of Nutrition Sciences at the University of Alabama at Birmingham (UAB), said at the Obesity Society’s Obesity Week 2024 meeting.

In an interview, Garvey, who is also senior scientist at the UAB Nutrition Obesity Research Center, added: “There’s a principle in medicine that you always use the lowest dose that has highest efficacy, and for oral semaglutide for obesity, that appears to be the 25-mg dose. We need oral medicines to offer as an option for patients that could lead to a longer persistence in adherence to obesity medications, which is a big problem. Less than half the people maintain their adherence after a year.”

Asked to comment, session moderator and obesity researcher Joseph A. Skelton, MD, professor of pediatrics at Wake Forest University School of Medicine, Winston-Salem, North Carolina, said that OASIS 4 was “extremely well done, especially given that we’re all concerned about the high prevalence of people stopping these medications at a year. ... I love the idea of trying to find these lower doses and increasing options for people.”

(The oral semaglutide approved for treating type 2 diabetes [Rybelsus] is sold in 7-mg and 14-mg doses.)

 

With Oral Semaglutide, Lower May Be Better

OASIS 4 was a double-blind, randomized, placebo-controlled 64-week multicenter trial involving a total of 307 participants with overweight/obesity randomized 2:1 to oral semaglutide 25 mg or placebo. Of those, 167 in the semaglutide 25 mg and 76 in the placebo groups completed the trial.

For the co–primary endpoint change in body weight at week 64 (including 52-week maintenance and 7-week follow-up periods), there was a drop of 13.6% with oral semaglutide vs just 2.2% with placebo (P < .0001), based on in-trial observation regardless of adherence. For the analysis including just the on-treatment period, those reductions were 16.6% and 2.7%, respectively (P < .0001).

For the other co–primary endpoint, 79.2% semaglutide vs 31.1% placebo lost at least 5% of their body weight, 63.0% vs 14.4% lost ≥ 10%, 50.0% vs 5.6% lost ≥ 15%, and 29.7% vs 3.3% lost ≥ 20%. All were statistically significant differences, at P < .0001.

On the Impact of Weight on Quality of Life-Lite Clinical Trials Version, change from baseline scores were 16.2 with oral semaglutide vs 8.4 for placebo (P = .0006) and the proportion of participants achieving clinically meaningful increases in those scores (≥ 14.6 points) were 55.3% vs 34.8% (P = .0022).

Waist circumference was also significantly reduced from baseline with oral semaglutide, by 12.2 cm vs 2.8 cm (P < .0001). Both systolic and diastolic blood pressure dropped more with semaglutide than placebo, but not significantly. However, the inflammatory marker C-reactive protein dropped from baseline by 46.4% vs just 4.2% with placebo, a significant difference (P < .0001).

Hemoglobin A1c dropped by 0.29 percentage points vs just 0.06 with placebo (P = .0012) and fasting plasma glucose by 6.6 mg/dL, while rising by 0.4 mg/dL in the placebo group (P = .0012). Lipid levels also improved more with oral semaglutide.

Overall adverse events occurred in 93.1% on oral semaglutide and 85.3% with placebo, and gastrointestinal adverse events in 74% and 42.2%, respectively. Other types of adverse events didn’t differ between the groups. The proportions experiencing severe adverse events were less in the semaglutide group (3.9% vs 8.8%), although adverse events leading to permanent treatment discontinuation were slightly higher with oral semaglutide (6.9% vs 5.9%). There were no deaths.

The estimated treatment difference from placebo in body weight change of −11.4% in OASIS 4 (P < .0001) was similar to the –12.7% (P < .0001) seen with the 50-mg oral semaglutide dose studied in OASIS 1 and the –12.4% (P < .0001) difference with subcutaneous semaglutide 2.4 mg in the STEP 1 trial. “All had pretty comparable efficacy,” Garvey noted.

The side-effect profiles, including frequency of gastrointestinal side effects, were also similar across the three trials. However, Garvey added, “the mean duration of nausea in those patients that experienced nausea was shorter in patients on a 25-mg dose, 13 days, whereas the mean duration of nausea was greater, 19 days, in those in OASIS 1 taking 50 mg a day.”

Garvey has consulted for Boehringer Ingelheim, Carmot Therapeutics/Roche, Eli Lilly, Fractyl Laboratories, Inogen, Lilly, Merck, Novo Nordisk, and Zealand Pharma; has ownership interest (stock, stock options in a publicly owned company) for Bristol-Myers Squibb, Isis, Lilly, and Novartis; serves as site principal investigator for Carmot Therapeutics/Roche, Eli Lilly, Epitomee Medical, Lilly, Neurovalens, Novo Nordisk, and Zealand Pharmaceuticals; and as a data monitoring committee member for Boehringer Ingelheim and Eli Lilly. Skelton is editor in chief of the journal Childhood Obesity.

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

Whether you’re gearing up for an ABIM exam or quarterly check-in test, or just updating your knowledge to provide exceptional care, DDSEP Plus is here to support your educational needs.

Challenge yourself with these practice questions! This is just a sample of the nearly 900 questions available with an annual DDSEP Plus subscription. AGA member trainees receive a discounted subscription.

Purchase a subscription to continue learning.

 

Practice Question #1

A 45-year-old woman diagnosed with irritable bowel syndrome with diarrhea presents to your clinic. Her diarrhea is well controlled with loperamide, but her abdominal pain persists.

Her primary care provider previously prescribed dicyclomine, but this did not improve her abdominal pain symptoms.

What is the next best medication to treat her abdominal pain?

A. Amitriptyline

B. Codeine/acetaminophen

C. Hydrocodone

D. Meloxicam

Correct answer:

A. Amitriptyline

Commentary:

Amitriptyline is a tricyclic antidepressant medication that functions as a central neuromodulator. A systematic review of randomized controlled trials of 6-12 weeks’ duration showed a modest improvement in global symptom relief and abdominal pain in patients with IBS treated with tricyclic anti-depressants. Opioid medications and nonsteroidal anti-inflammatory medications are not recommended to treat abdominal pain in patients with IBS.

Practice Question #2

A 52-year-old man with hypertension and diabetes mellitus type 2 is referred to you for 8 months of troublesome regurgitation and heartburn. He has a body mass index of 29 kg/m².

He had minimal relief with single-dose proton pump inhibitor (PPI) therapy before breakfast and partial response with double-dose PPI therapy taken before breakfast and before dinner. Regurgitation after dinner and at bedtime is his most troublesome symptom.

What is the next best step in management?

A. Counsel on weight management

B. Increase PPI to quadruple dose

C. Perform gastric emptying study

D. Refer for bariatric surgery evaluation

E. Switch PPI to before bedtime

Correct answer:

A. Counsel on weight management

Commentary:

This presentation represents typical symptoms of gastroesophageal reflux disease that are not responsive to an optimized regimen of PPI therapy.

Management of refractory gastroesophageal reflux disease symptoms begins with optimizing lifestyle and weight loss. 

Quadruple-dose PPI therapy has no established role. A gastric emptying study would be recommended if gastroparesis was suspected. 

This patient does not meet criteria for bariatric surgery as his body mass index is less than 30 kg/m². 

PPI therapy optimization with before-meal dosing (30-60 min before breakfast for single-dose therapy and before breakfast and dinner for double-dose therapy) would be the next step after weight management.







 

Whether you’re gearing up for an ABIM exam or quarterly check-in test, or just updating your knowledge to provide exceptional care, DDSEP Plus is here to support your educational needs.

Challenge yourself with these practice questions! This is just a sample of the nearly 900 questions available with an annual DDSEP Plus subscription. AGA member trainees receive a discounted subscription.

Purchase a subscription to continue learning.

 

Practice Question #1

A 45-year-old woman diagnosed with irritable bowel syndrome with diarrhea presents to your clinic. Her diarrhea is well controlled with loperamide, but her abdominal pain persists.

Her primary care provider previously prescribed dicyclomine, but this did not improve her abdominal pain symptoms.

What is the next best medication to treat her abdominal pain?

A. Amitriptyline

B. Codeine/acetaminophen

C. Hydrocodone

D. Meloxicam

Correct answer:

A. Amitriptyline

Commentary:

Amitriptyline is a tricyclic antidepressant medication that functions as a central neuromodulator. A systematic review of randomized controlled trials of 6-12 weeks’ duration showed a modest improvement in global symptom relief and abdominal pain in patients with IBS treated with tricyclic anti-depressants. Opioid medications and nonsteroidal anti-inflammatory medications are not recommended to treat abdominal pain in patients with IBS.

Practice Question #2

A 52-year-old man with hypertension and diabetes mellitus type 2 is referred to you for 8 months of troublesome regurgitation and heartburn. He has a body mass index of 29 kg/m².

He had minimal relief with single-dose proton pump inhibitor (PPI) therapy before breakfast and partial response with double-dose PPI therapy taken before breakfast and before dinner. Regurgitation after dinner and at bedtime is his most troublesome symptom.

What is the next best step in management?

A. Counsel on weight management

B. Increase PPI to quadruple dose

C. Perform gastric emptying study

D. Refer for bariatric surgery evaluation

E. Switch PPI to before bedtime

Correct answer:

A. Counsel on weight management

Commentary:

This presentation represents typical symptoms of gastroesophageal reflux disease that are not responsive to an optimized regimen of PPI therapy.

Management of refractory gastroesophageal reflux disease symptoms begins with optimizing lifestyle and weight loss. 

Quadruple-dose PPI therapy has no established role. A gastric emptying study would be recommended if gastroparesis was suspected. 

This patient does not meet criteria for bariatric surgery as his body mass index is less than 30 kg/m². 

PPI therapy optimization with before-meal dosing (30-60 min before breakfast for single-dose therapy and before breakfast and dinner for double-dose therapy) would be the next step after weight management.







 

Whether you’re gearing up for an ABIM exam or quarterly check-in test, or just updating your knowledge to provide exceptional care, DDSEP Plus is here to support your educational needs.

Challenge yourself with these practice questions! This is just a sample of the nearly 900 questions available with an annual DDSEP Plus subscription. AGA member trainees receive a discounted subscription.

Purchase a subscription to continue learning.

 

Practice Question #1

A 45-year-old woman diagnosed with irritable bowel syndrome with diarrhea presents to your clinic. Her diarrhea is well controlled with loperamide, but her abdominal pain persists.

Her primary care provider previously prescribed dicyclomine, but this did not improve her abdominal pain symptoms.

What is the next best medication to treat her abdominal pain?

A. Amitriptyline

B. Codeine/acetaminophen

C. Hydrocodone

D. Meloxicam

Correct answer:

A. Amitriptyline

Commentary:

Amitriptyline is a tricyclic antidepressant medication that functions as a central neuromodulator. A systematic review of randomized controlled trials of 6-12 weeks’ duration showed a modest improvement in global symptom relief and abdominal pain in patients with IBS treated with tricyclic anti-depressants. Opioid medications and nonsteroidal anti-inflammatory medications are not recommended to treat abdominal pain in patients with IBS.

Practice Question #2

A 52-year-old man with hypertension and diabetes mellitus type 2 is referred to you for 8 months of troublesome regurgitation and heartburn. He has a body mass index of 29 kg/m².

He had minimal relief with single-dose proton pump inhibitor (PPI) therapy before breakfast and partial response with double-dose PPI therapy taken before breakfast and before dinner. Regurgitation after dinner and at bedtime is his most troublesome symptom.

What is the next best step in management?

A. Counsel on weight management

B. Increase PPI to quadruple dose

C. Perform gastric emptying study

D. Refer for bariatric surgery evaluation

E. Switch PPI to before bedtime

Correct answer:

A. Counsel on weight management

Commentary:

This presentation represents typical symptoms of gastroesophageal reflux disease that are not responsive to an optimized regimen of PPI therapy.

Management of refractory gastroesophageal reflux disease symptoms begins with optimizing lifestyle and weight loss. 

Quadruple-dose PPI therapy has no established role. A gastric emptying study would be recommended if gastroparesis was suspected. 

This patient does not meet criteria for bariatric surgery as his body mass index is less than 30 kg/m². 

PPI therapy optimization with before-meal dosing (30-60 min before breakfast for single-dose therapy and before breakfast and dinner for double-dose therapy) would be the next step after weight management.







 

SAN DIEGO — The prevalence of and number of deaths from alcohol-associated liver disease (ALD) and alcohol use disorder (AUD) are growing among people age 70 and older in the United States, according to the results of a new study.

Even as mortality rates decline globally, AUD deaths rose in the United States, increasing 1.63% per year between 2010 and 2019. Deaths from cirrhosis increased by 0.56% each year, and deaths from primary liver cancer associated with alcohol increased by 3.09% per year.

Several factors, such as an aging US population and increasing alcohol consumption, play a major role in the uptick in mortality, said lead author Pojsakorn Danpanichkul, MD, an internal medicine resident at Texas Tech University Health Sciences Center, Lubbock, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).

“Healthcare providers should increase screening for alcohol use among older adults and consider the added risks of alcohol consumption. Public health strategies should target alcohol prevention and treatment programs tailored to older adults,” he said.

“Older adults are more vulnerable to the harmful effects of alcohol due to natural declines in liver function and metabolism, leading to a higher risk of liver disease and complications,” he explained. However, “little research has focused on this issue.”

 

Trends in US Not Seen Globally

Danpanichkul and colleagues analyzed data from the Global Burden of Disease Study for 2010-2019, calculating the annual percent change for the burden of AUD, ALD, and liver cancer from alcohol in patients age 70 and older. The research team then compared data in the United States to global estimates for these same diseases.

In 2019, there were 556,340 cases of AUD, 112,560 cases of ALD, and 3720 cases of liver cancer from alcohol in older adults in the United States. In addition, there were 1750 deaths attributed to AUD, 4860 deaths from ALD, and 3010 deaths caused by primary liver cancer from alcohol.

The age-standardized prevalence rates (ASPRs) per 100,000 people were 1547 cases of AUD, 313 cases of ALD, and 10 cases of primary liver cancer caused by alcohol.

The age-standardized death rates (ASDRs) per 100,000 people were 4.88 for AUD, 13.52 for ALD, and 8.38 for primary liver cancer.

During the time period studied, upward trends occurred in the United States, with annual ASPRs increasing by 2.52% for AUD, 1.78% for ALD, and 3.31% for primary liver cancer due to alcohol. Globally, the trends were lower, with annual increases of 0.2% for AUD, 0.38% for ALD, and 0.67% for primary liver cancer from alcohol.

During the same time, ASDRs also increased in all three categories in the United States, while global trends showed a 0.91% decline in AUD deaths and 0.6% decline in ALD deaths. Liver cancer deaths, however, increased by 0.3% worldwide.

Targeted strategies are essential to reduce this growing health burden, especially in an aging population, Danpanichkul said. “These interventions should focus on early detection, intervention, and management for individuals at risk or already affected by ALD and AUD.”

Future studies should investigate alcohol consumption and mortality trends in other age groups, including by sex, location (such as state or territory), and race and ethnicity, he said. Data for more recent years would be compelling as well.

 

Increased Alcohol Use During and After Pandemic

Numerous studies have indicated that alcohol use increased in 2020 during the COVID-19 pandemic and has remained elevated since then. 

In a study published in the Annals of Internal Medicine, for instance, alcohol use per 100 people increased 2.69% in 2020 and 2.96% in 2022, as compared with 2018. Increases occurred across all subgroups, including age, sex, race, ethnicity, and US region.

“During the COVID-19 pandemic, many people stayed at home, watched the television, and increased their alcohol intake” — in the United States and also in Japan — said Hisanori Muto, MD, senior assistant professor of gastroenterology at Fujita Health University in Nagoya, Japan, who wasn’t involved with this study.

“Although the global numbers may appear lower, we’re also seeing an increase in AUD and ALD in Japan, similar to the United States,” he said. “It’s very important to watch these trends and address these diseases.”

Danpanichkul and Muto reported no relevant disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — The prevalence of and number of deaths from alcohol-associated liver disease (ALD) and alcohol use disorder (AUD) are growing among people age 70 and older in the United States, according to the results of a new study.

Even as mortality rates decline globally, AUD deaths rose in the United States, increasing 1.63% per year between 2010 and 2019. Deaths from cirrhosis increased by 0.56% each year, and deaths from primary liver cancer associated with alcohol increased by 3.09% per year.

Several factors, such as an aging US population and increasing alcohol consumption, play a major role in the uptick in mortality, said lead author Pojsakorn Danpanichkul, MD, an internal medicine resident at Texas Tech University Health Sciences Center, Lubbock, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).

“Healthcare providers should increase screening for alcohol use among older adults and consider the added risks of alcohol consumption. Public health strategies should target alcohol prevention and treatment programs tailored to older adults,” he said.

“Older adults are more vulnerable to the harmful effects of alcohol due to natural declines in liver function and metabolism, leading to a higher risk of liver disease and complications,” he explained. However, “little research has focused on this issue.”

 

Trends in US Not Seen Globally

Danpanichkul and colleagues analyzed data from the Global Burden of Disease Study for 2010-2019, calculating the annual percent change for the burden of AUD, ALD, and liver cancer from alcohol in patients age 70 and older. The research team then compared data in the United States to global estimates for these same diseases.

In 2019, there were 556,340 cases of AUD, 112,560 cases of ALD, and 3720 cases of liver cancer from alcohol in older adults in the United States. In addition, there were 1750 deaths attributed to AUD, 4860 deaths from ALD, and 3010 deaths caused by primary liver cancer from alcohol.

The age-standardized prevalence rates (ASPRs) per 100,000 people were 1547 cases of AUD, 313 cases of ALD, and 10 cases of primary liver cancer caused by alcohol.

The age-standardized death rates (ASDRs) per 100,000 people were 4.88 for AUD, 13.52 for ALD, and 8.38 for primary liver cancer.

During the time period studied, upward trends occurred in the United States, with annual ASPRs increasing by 2.52% for AUD, 1.78% for ALD, and 3.31% for primary liver cancer due to alcohol. Globally, the trends were lower, with annual increases of 0.2% for AUD, 0.38% for ALD, and 0.67% for primary liver cancer from alcohol.

During the same time, ASDRs also increased in all three categories in the United States, while global trends showed a 0.91% decline in AUD deaths and 0.6% decline in ALD deaths. Liver cancer deaths, however, increased by 0.3% worldwide.

Targeted strategies are essential to reduce this growing health burden, especially in an aging population, Danpanichkul said. “These interventions should focus on early detection, intervention, and management for individuals at risk or already affected by ALD and AUD.”

Future studies should investigate alcohol consumption and mortality trends in other age groups, including by sex, location (such as state or territory), and race and ethnicity, he said. Data for more recent years would be compelling as well.

 

Increased Alcohol Use During and After Pandemic

Numerous studies have indicated that alcohol use increased in 2020 during the COVID-19 pandemic and has remained elevated since then. 

In a study published in the Annals of Internal Medicine, for instance, alcohol use per 100 people increased 2.69% in 2020 and 2.96% in 2022, as compared with 2018. Increases occurred across all subgroups, including age, sex, race, ethnicity, and US region.

“During the COVID-19 pandemic, many people stayed at home, watched the television, and increased their alcohol intake” — in the United States and also in Japan — said Hisanori Muto, MD, senior assistant professor of gastroenterology at Fujita Health University in Nagoya, Japan, who wasn’t involved with this study.

“Although the global numbers may appear lower, we’re also seeing an increase in AUD and ALD in Japan, similar to the United States,” he said. “It’s very important to watch these trends and address these diseases.”

Danpanichkul and Muto reported no relevant disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — The prevalence of and number of deaths from alcohol-associated liver disease (ALD) and alcohol use disorder (AUD) are growing among people age 70 and older in the United States, according to the results of a new study.

Even as mortality rates decline globally, AUD deaths rose in the United States, increasing 1.63% per year between 2010 and 2019. Deaths from cirrhosis increased by 0.56% each year, and deaths from primary liver cancer associated with alcohol increased by 3.09% per year.

Several factors, such as an aging US population and increasing alcohol consumption, play a major role in the uptick in mortality, said lead author Pojsakorn Danpanichkul, MD, an internal medicine resident at Texas Tech University Health Sciences Center, Lubbock, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).

“Healthcare providers should increase screening for alcohol use among older adults and consider the added risks of alcohol consumption. Public health strategies should target alcohol prevention and treatment programs tailored to older adults,” he said.

“Older adults are more vulnerable to the harmful effects of alcohol due to natural declines in liver function and metabolism, leading to a higher risk of liver disease and complications,” he explained. However, “little research has focused on this issue.”

 

Trends in US Not Seen Globally

Danpanichkul and colleagues analyzed data from the Global Burden of Disease Study for 2010-2019, calculating the annual percent change for the burden of AUD, ALD, and liver cancer from alcohol in patients age 70 and older. The research team then compared data in the United States to global estimates for these same diseases.

In 2019, there were 556,340 cases of AUD, 112,560 cases of ALD, and 3720 cases of liver cancer from alcohol in older adults in the United States. In addition, there were 1750 deaths attributed to AUD, 4860 deaths from ALD, and 3010 deaths caused by primary liver cancer from alcohol.

The age-standardized prevalence rates (ASPRs) per 100,000 people were 1547 cases of AUD, 313 cases of ALD, and 10 cases of primary liver cancer caused by alcohol.

The age-standardized death rates (ASDRs) per 100,000 people were 4.88 for AUD, 13.52 for ALD, and 8.38 for primary liver cancer.

During the time period studied, upward trends occurred in the United States, with annual ASPRs increasing by 2.52% for AUD, 1.78% for ALD, and 3.31% for primary liver cancer due to alcohol. Globally, the trends were lower, with annual increases of 0.2% for AUD, 0.38% for ALD, and 0.67% for primary liver cancer from alcohol.

During the same time, ASDRs also increased in all three categories in the United States, while global trends showed a 0.91% decline in AUD deaths and 0.6% decline in ALD deaths. Liver cancer deaths, however, increased by 0.3% worldwide.

Targeted strategies are essential to reduce this growing health burden, especially in an aging population, Danpanichkul said. “These interventions should focus on early detection, intervention, and management for individuals at risk or already affected by ALD and AUD.”

Future studies should investigate alcohol consumption and mortality trends in other age groups, including by sex, location (such as state or territory), and race and ethnicity, he said. Data for more recent years would be compelling as well.

 

Increased Alcohol Use During and After Pandemic

Numerous studies have indicated that alcohol use increased in 2020 during the COVID-19 pandemic and has remained elevated since then. 

In a study published in the Annals of Internal Medicine, for instance, alcohol use per 100 people increased 2.69% in 2020 and 2.96% in 2022, as compared with 2018. Increases occurred across all subgroups, including age, sex, race, ethnicity, and US region.

“During the COVID-19 pandemic, many people stayed at home, watched the television, and increased their alcohol intake” — in the United States and also in Japan — said Hisanori Muto, MD, senior assistant professor of gastroenterology at Fujita Health University in Nagoya, Japan, who wasn’t involved with this study.

“Although the global numbers may appear lower, we’re also seeing an increase in AUD and ALD in Japan, similar to the United States,” he said. “It’s very important to watch these trends and address these diseases.”

Danpanichkul and Muto reported no relevant disclosures.

A version of this article appeared on Medscape.com.

PHILADELPHIA — Patients with inflammatory bowel disease (IBD) don’t appear to face an increased risk of major adverse cardiovascular events (MACE) or venous thromboembolism (VTE) when taking Janus kinase inhibitors (JAKi), compared with anti–tumor necrosis factor (TNF) agents, according to a study presented at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.

In particular, 1.76% of patients taking JAKi and 1.94% of patients taking anti-TNF developed MACE. There also weren’t significant differences when comparing ulcerative colitis with Crohn’s disease, upadacitinib with tofacitinib, or JAKi with infliximab.

“IBD is associated with an increased risk of cardiovascular diseases, and with the emergence of JAK inhibitors and anti-TNF therapies, there is a concern about the increased risk of MACE,” said lead author Saqr Alsakarneh, MD, an internal medicine resident at the University of Missouri–Kansas City School of Medicine.

Previous randomized controlled trials have indicated increased risks of MACE with JAKi and anti-TNF agents, compared with placebo, but researchers haven’t conducted a head-to-head comparison, he said.

“A potential explanation for previous associations could be linked to immune modulation and inflammation that can increase coagulation risk, as well as fluctuation in disease severity while patients are on the medications, which can impact cardiovascular risk factors,” he added.

Alsakarneh and colleagues conducted a retrospective cohort study using the TriNetX database to identify adult patients with IBD who were treated with JAKi or anti-TNF therapy after diagnosis. After matching patients in the JAKi cohort with patients in the anti-TNF cohort, the research team looked for MACE and VTE within a year of medication initiation, as well as associations by age, sex, and IBD type.

Overall, 3740 patients in the JAKi cohort had a mean age of 43.1 and were 48.9% women and 75.3% White individuals, while 3,740 patients in the anti-TNF cohort had a mean age of 43 and were 48.9% women and 75.3% White individuals.

After excluding those with a history of a prior cardiovascular event, 57 patients (1.76%) in the JAKi cohort developed MACE, compared with 63 patients (1.94%) in the anti-TNF cohort. There weren’t significant differences between the groups in MACE (adjusted hazard ratio [aHR], 0.99) or VTE (aHR, 0.9).

Among patients aged ≥ 65, 25 patients (5.3%) in the JAKi cohort developed MACE, as compared with 30 patients (6.4%) in the anti-TNF cohort. There weren’t significant differences between the groups in MACE (aHR, 0.83) or VTE (aHR, 0.77).

In addition, there were no differences when comparing Crohn’s disease with ulcerative colitis for MACE (aHR, 1.69) or VTE (aHR, 0.85); upadacitinib with tofacitinib for MACE (aHR, 1.1) or VTE (aHR, 1.13); or JAKi medications with infliximab for MACE (aHR, 0.85) or VTE (aHR, 0.8).

Patients in the JAKi group were more likely to undergo intestinal resection surgery (aHR, 1.32), but there wasn’t a statistically significant difference in systematic corticosteroid use (aHR, 0.99).

The study limitations included the inability to assess for disease severity, dose-dependent risk for MACE or VTE, or long-term outcomes among the two cohorts, Alsakarneh said. Prospective controlled trials are needed to confirm findings.

 

“This is a wonderful study and nice to see. We presented the same thing at Digestive Disease Week that’s being confirmed in this data,” said Miguel Regueiro, MD, AGAF, chief of Cleveland Clinic’s Digestive Disease Institute in Ohio. Regueiro, who wasn’t involved with the study, attended the conference session.

“Looking ahead, all of us are wondering if the regulatory guidance by the FDA [Food and Drug Administration] is going to change the label so we don’t need to step through a TNF,” he said. “I think we’re seeing study after study showing safety or at least not an increased risk with JAK.”

The study was awarded an ACG Noteworthy Abstract. Alsakarneh and Regueiro reported no relevant disclosures.

A version of this article appeared on Medscape.com.

PHILADELPHIA — Patients with inflammatory bowel disease (IBD) don’t appear to face an increased risk of major adverse cardiovascular events (MACE) or venous thromboembolism (VTE) when taking Janus kinase inhibitors (JAKi), compared with anti–tumor necrosis factor (TNF) agents, according to a study presented at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.

In particular, 1.76% of patients taking JAKi and 1.94% of patients taking anti-TNF developed MACE. There also weren’t significant differences when comparing ulcerative colitis with Crohn’s disease, upadacitinib with tofacitinib, or JAKi with infliximab.

“IBD is associated with an increased risk of cardiovascular diseases, and with the emergence of JAK inhibitors and anti-TNF therapies, there is a concern about the increased risk of MACE,” said lead author Saqr Alsakarneh, MD, an internal medicine resident at the University of Missouri–Kansas City School of Medicine.

Previous randomized controlled trials have indicated increased risks of MACE with JAKi and anti-TNF agents, compared with placebo, but researchers haven’t conducted a head-to-head comparison, he said.

“A potential explanation for previous associations could be linked to immune modulation and inflammation that can increase coagulation risk, as well as fluctuation in disease severity while patients are on the medications, which can impact cardiovascular risk factors,” he added.

Alsakarneh and colleagues conducted a retrospective cohort study using the TriNetX database to identify adult patients with IBD who were treated with JAKi or anti-TNF therapy after diagnosis. After matching patients in the JAKi cohort with patients in the anti-TNF cohort, the research team looked for MACE and VTE within a year of medication initiation, as well as associations by age, sex, and IBD type.

Overall, 3740 patients in the JAKi cohort had a mean age of 43.1 and were 48.9% women and 75.3% White individuals, while 3,740 patients in the anti-TNF cohort had a mean age of 43 and were 48.9% women and 75.3% White individuals.

After excluding those with a history of a prior cardiovascular event, 57 patients (1.76%) in the JAKi cohort developed MACE, compared with 63 patients (1.94%) in the anti-TNF cohort. There weren’t significant differences between the groups in MACE (adjusted hazard ratio [aHR], 0.99) or VTE (aHR, 0.9).

Among patients aged ≥ 65, 25 patients (5.3%) in the JAKi cohort developed MACE, as compared with 30 patients (6.4%) in the anti-TNF cohort. There weren’t significant differences between the groups in MACE (aHR, 0.83) or VTE (aHR, 0.77).

In addition, there were no differences when comparing Crohn’s disease with ulcerative colitis for MACE (aHR, 1.69) or VTE (aHR, 0.85); upadacitinib with tofacitinib for MACE (aHR, 1.1) or VTE (aHR, 1.13); or JAKi medications with infliximab for MACE (aHR, 0.85) or VTE (aHR, 0.8).

Patients in the JAKi group were more likely to undergo intestinal resection surgery (aHR, 1.32), but there wasn’t a statistically significant difference in systematic corticosteroid use (aHR, 0.99).

The study limitations included the inability to assess for disease severity, dose-dependent risk for MACE or VTE, or long-term outcomes among the two cohorts, Alsakarneh said. Prospective controlled trials are needed to confirm findings.

 

“This is a wonderful study and nice to see. We presented the same thing at Digestive Disease Week that’s being confirmed in this data,” said Miguel Regueiro, MD, AGAF, chief of Cleveland Clinic’s Digestive Disease Institute in Ohio. Regueiro, who wasn’t involved with the study, attended the conference session.

“Looking ahead, all of us are wondering if the regulatory guidance by the FDA [Food and Drug Administration] is going to change the label so we don’t need to step through a TNF,” he said. “I think we’re seeing study after study showing safety or at least not an increased risk with JAK.”

The study was awarded an ACG Noteworthy Abstract. Alsakarneh and Regueiro reported no relevant disclosures.

A version of this article appeared on Medscape.com.

PHILADELPHIA — Patients with inflammatory bowel disease (IBD) don’t appear to face an increased risk of major adverse cardiovascular events (MACE) or venous thromboembolism (VTE) when taking Janus kinase inhibitors (JAKi), compared with anti–tumor necrosis factor (TNF) agents, according to a study presented at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.

In particular, 1.76% of patients taking JAKi and 1.94% of patients taking anti-TNF developed MACE. There also weren’t significant differences when comparing ulcerative colitis with Crohn’s disease, upadacitinib with tofacitinib, or JAKi with infliximab.

“IBD is associated with an increased risk of cardiovascular diseases, and with the emergence of JAK inhibitors and anti-TNF therapies, there is a concern about the increased risk of MACE,” said lead author Saqr Alsakarneh, MD, an internal medicine resident at the University of Missouri–Kansas City School of Medicine.

Previous randomized controlled trials have indicated increased risks of MACE with JAKi and anti-TNF agents, compared with placebo, but researchers haven’t conducted a head-to-head comparison, he said.

“A potential explanation for previous associations could be linked to immune modulation and inflammation that can increase coagulation risk, as well as fluctuation in disease severity while patients are on the medications, which can impact cardiovascular risk factors,” he added.

Alsakarneh and colleagues conducted a retrospective cohort study using the TriNetX database to identify adult patients with IBD who were treated with JAKi or anti-TNF therapy after diagnosis. After matching patients in the JAKi cohort with patients in the anti-TNF cohort, the research team looked for MACE and VTE within a year of medication initiation, as well as associations by age, sex, and IBD type.

Overall, 3740 patients in the JAKi cohort had a mean age of 43.1 and were 48.9% women and 75.3% White individuals, while 3,740 patients in the anti-TNF cohort had a mean age of 43 and were 48.9% women and 75.3% White individuals.

After excluding those with a history of a prior cardiovascular event, 57 patients (1.76%) in the JAKi cohort developed MACE, compared with 63 patients (1.94%) in the anti-TNF cohort. There weren’t significant differences between the groups in MACE (adjusted hazard ratio [aHR], 0.99) or VTE (aHR, 0.9).

Among patients aged ≥ 65, 25 patients (5.3%) in the JAKi cohort developed MACE, as compared with 30 patients (6.4%) in the anti-TNF cohort. There weren’t significant differences between the groups in MACE (aHR, 0.83) or VTE (aHR, 0.77).

In addition, there were no differences when comparing Crohn’s disease with ulcerative colitis for MACE (aHR, 1.69) or VTE (aHR, 0.85); upadacitinib with tofacitinib for MACE (aHR, 1.1) or VTE (aHR, 1.13); or JAKi medications with infliximab for MACE (aHR, 0.85) or VTE (aHR, 0.8).

Patients in the JAKi group were more likely to undergo intestinal resection surgery (aHR, 1.32), but there wasn’t a statistically significant difference in systematic corticosteroid use (aHR, 0.99).

The study limitations included the inability to assess for disease severity, dose-dependent risk for MACE or VTE, or long-term outcomes among the two cohorts, Alsakarneh said. Prospective controlled trials are needed to confirm findings.

 

“This is a wonderful study and nice to see. We presented the same thing at Digestive Disease Week that’s being confirmed in this data,” said Miguel Regueiro, MD, AGAF, chief of Cleveland Clinic’s Digestive Disease Institute in Ohio. Regueiro, who wasn’t involved with the study, attended the conference session.

“Looking ahead, all of us are wondering if the regulatory guidance by the FDA [Food and Drug Administration] is going to change the label so we don’t need to step through a TNF,” he said. “I think we’re seeing study after study showing safety or at least not an increased risk with JAK.”

The study was awarded an ACG Noteworthy Abstract. Alsakarneh and Regueiro reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Muvalaplin, a novel oral medication, safely and effectively lowers high levels of lipoprotein(a), or Lp(a), results from the phase 2 KRAKEN trial show.

Concentrations of Lp(a) cholesterol are genetically determined and remain steady throughout life. Levels of 125 nmol/L or higher promote clotting and inflammation, significantly increasing the risk for heart attack, stroke, aortic stenosis, and peripheral artery disease. This affects about 20% of the population, particularly people of Black African and South Asian descent.

There are currently no approved therapies that lower Lp(a), said study author Stephen Nicholls, MBBS, PhD, director of the Victorian Heart Institute at Monash University in Melbourne, Australia. Several injectable therapies are currently in clinical trials, but muvalaplin is the only oral option. The new drug lowers Lp(a) levels by disrupting the bond between the two parts of the Lp(a) particle.

 

The KRAKEN Trial

In the KRAKEN trial, 233 adults from around the world with very high Lp(a) levels (> 175 nmol/L) were randomized either to one of three daily doses of muvalaplin — 10, 60, or 240 mg — or to placebo for 12 weeks.

The researchers measured Lp(a) levels with a standard blood test and with a novel test designed to specifically measure levels of intact Lp(a) particles in the blood. In addition to Lp(a), the standard test detects one of its components, apolipoprotein A particles, that are bound to the drug, which can lead to an underestimation of Lp(a) reductions.

Lp(a) levels were up to 70.0% lower in the muvalaplin group than in the placebo group when measured with the traditional blood test and by up to 85.5% lower when measured with the new test. Approximately 82% of participants achieved an Lp(a) level lower than 125 nmol/L when measured with the traditional blood test, and 97% achieved that level when the new test was used. Patients who received either 60 or 240 mg of muvalaplin had similar reductions in Lp(a) levels, which were greater than the reductions seen in the 10 mg group. The drug was safe and generally well tolerated.

“This is a very reassuring phase 2 result,” Nicholls said when he presented the KRAKEN findings at the American Heart Association (AHA) Scientific Sessions 2024 in Chicago, which were simultaneously published online in JAMA. “It encourages the ongoing development of this agent.”

Lp(a) levels are not affected by changes in lifestyle or diet or by traditional lipid-lowering treatments like statins, said Erin Michos, MD, a cardiologist at the Johns Hopkins University School of Medicine in Baltimore, Maryland, who was not involved in the study.

And high Lp(a) levels confer significant cardiovascular risk even when other risks are reduced. So muvalaplin is “a highly promising approach to treat a previously untreatable disorder,” she explained.

Larger and longer studies, with more diverse patient populations, are needed to confirm the results and to determine whether reducing Lp(a) also improves cardiovascular outcomes, Michos pointed out.

“While muvalaplin appears to be an effective approach to lowering Lp(a) levels, we still need to study whether Lp(a) lowering will result in fewer heart attacks and strokes,” Nicholls added.

A version of this article appeared on Medscape.com.

Muvalaplin, a novel oral medication, safely and effectively lowers high levels of lipoprotein(a), or Lp(a), results from the phase 2 KRAKEN trial show.

Concentrations of Lp(a) cholesterol are genetically determined and remain steady throughout life. Levels of 125 nmol/L or higher promote clotting and inflammation, significantly increasing the risk for heart attack, stroke, aortic stenosis, and peripheral artery disease. This affects about 20% of the population, particularly people of Black African and South Asian descent.

There are currently no approved therapies that lower Lp(a), said study author Stephen Nicholls, MBBS, PhD, director of the Victorian Heart Institute at Monash University in Melbourne, Australia. Several injectable therapies are currently in clinical trials, but muvalaplin is the only oral option. The new drug lowers Lp(a) levels by disrupting the bond between the two parts of the Lp(a) particle.

 

The KRAKEN Trial

In the KRAKEN trial, 233 adults from around the world with very high Lp(a) levels (> 175 nmol/L) were randomized either to one of three daily doses of muvalaplin — 10, 60, or 240 mg — or to placebo for 12 weeks.

The researchers measured Lp(a) levels with a standard blood test and with a novel test designed to specifically measure levels of intact Lp(a) particles in the blood. In addition to Lp(a), the standard test detects one of its components, apolipoprotein A particles, that are bound to the drug, which can lead to an underestimation of Lp(a) reductions.

Lp(a) levels were up to 70.0% lower in the muvalaplin group than in the placebo group when measured with the traditional blood test and by up to 85.5% lower when measured with the new test. Approximately 82% of participants achieved an Lp(a) level lower than 125 nmol/L when measured with the traditional blood test, and 97% achieved that level when the new test was used. Patients who received either 60 or 240 mg of muvalaplin had similar reductions in Lp(a) levels, which were greater than the reductions seen in the 10 mg group. The drug was safe and generally well tolerated.

“This is a very reassuring phase 2 result,” Nicholls said when he presented the KRAKEN findings at the American Heart Association (AHA) Scientific Sessions 2024 in Chicago, which were simultaneously published online in JAMA. “It encourages the ongoing development of this agent.”

Lp(a) levels are not affected by changes in lifestyle or diet or by traditional lipid-lowering treatments like statins, said Erin Michos, MD, a cardiologist at the Johns Hopkins University School of Medicine in Baltimore, Maryland, who was not involved in the study.

And high Lp(a) levels confer significant cardiovascular risk even when other risks are reduced. So muvalaplin is “a highly promising approach to treat a previously untreatable disorder,” she explained.

Larger and longer studies, with more diverse patient populations, are needed to confirm the results and to determine whether reducing Lp(a) also improves cardiovascular outcomes, Michos pointed out.

“While muvalaplin appears to be an effective approach to lowering Lp(a) levels, we still need to study whether Lp(a) lowering will result in fewer heart attacks and strokes,” Nicholls added.

A version of this article appeared on Medscape.com.

Muvalaplin, a novel oral medication, safely and effectively lowers high levels of lipoprotein(a), or Lp(a), results from the phase 2 KRAKEN trial show.

Concentrations of Lp(a) cholesterol are genetically determined and remain steady throughout life. Levels of 125 nmol/L or higher promote clotting and inflammation, significantly increasing the risk for heart attack, stroke, aortic stenosis, and peripheral artery disease. This affects about 20% of the population, particularly people of Black African and South Asian descent.

There are currently no approved therapies that lower Lp(a), said study author Stephen Nicholls, MBBS, PhD, director of the Victorian Heart Institute at Monash University in Melbourne, Australia. Several injectable therapies are currently in clinical trials, but muvalaplin is the only oral option. The new drug lowers Lp(a) levels by disrupting the bond between the two parts of the Lp(a) particle.

 

The KRAKEN Trial

In the KRAKEN trial, 233 adults from around the world with very high Lp(a) levels (> 175 nmol/L) were randomized either to one of three daily doses of muvalaplin — 10, 60, or 240 mg — or to placebo for 12 weeks.

The researchers measured Lp(a) levels with a standard blood test and with a novel test designed to specifically measure levels of intact Lp(a) particles in the blood. In addition to Lp(a), the standard test detects one of its components, apolipoprotein A particles, that are bound to the drug, which can lead to an underestimation of Lp(a) reductions.

Lp(a) levels were up to 70.0% lower in the muvalaplin group than in the placebo group when measured with the traditional blood test and by up to 85.5% lower when measured with the new test. Approximately 82% of participants achieved an Lp(a) level lower than 125 nmol/L when measured with the traditional blood test, and 97% achieved that level when the new test was used. Patients who received either 60 or 240 mg of muvalaplin had similar reductions in Lp(a) levels, which were greater than the reductions seen in the 10 mg group. The drug was safe and generally well tolerated.

“This is a very reassuring phase 2 result,” Nicholls said when he presented the KRAKEN findings at the American Heart Association (AHA) Scientific Sessions 2024 in Chicago, which were simultaneously published online in JAMA. “It encourages the ongoing development of this agent.”

Lp(a) levels are not affected by changes in lifestyle or diet or by traditional lipid-lowering treatments like statins, said Erin Michos, MD, a cardiologist at the Johns Hopkins University School of Medicine in Baltimore, Maryland, who was not involved in the study.

And high Lp(a) levels confer significant cardiovascular risk even when other risks are reduced. So muvalaplin is “a highly promising approach to treat a previously untreatable disorder,” she explained.

Larger and longer studies, with more diverse patient populations, are needed to confirm the results and to determine whether reducing Lp(a) also improves cardiovascular outcomes, Michos pointed out.

“While muvalaplin appears to be an effective approach to lowering Lp(a) levels, we still need to study whether Lp(a) lowering will result in fewer heart attacks and strokes,” Nicholls added.

A version of this article appeared on Medscape.com.

TOPLINE:

Light-intensity walking reduces postprandial glucose and diastolic blood pressure in young adults with obesity and can improve insulin levels, depending on the walking pattern.

METHODOLOGY:

• Researchers conducted a randomized crossover trial with 16 young adults aged 18-34 years with body mass index (BMI) ≥ 25 in Bangkok, Thailand, to examine the effects of different light-intensity walking patterns on postprandial cardiometabolic responses.
• Participants (mean age, 25; mean BMI, 29.8) engaged in four 7-hour experimental conditions, each involving a different activity: Uninterrupted sitting, 30-minutes of light-intensity walking, 3-minute light-intensity walking every 30 minutes, or a combination of both walking regimens. There was a 7- to 20-day washout period between each experiment period.
• Baseline and 6-hour postprandial concentrations of glucose, insulin, triglycerides, and blood pressure were measured.
• Incremental areas under the curve (iAUC) for each outcome and average blood pressure were compared between sitting and walking conditions.

TAKEAWAY:

• All the walking interventions reduced postprandial glucose concentrations and diastolic blood pressure compared with uninterrupted sitting.
• Continuous 30-minute light-intensity walking alone or combined with brief 3-minute bouts also attenuated postprandial insulin concentrations.
• No significant differences were found for triglycerides iAUC and systolic blood pressure between the four experiment conditions.

IN PRACTICE:

“These findings support the notion that engaging in light-intensity walking, regardless of the pattern, provides benefits to glycemic control. Moreover, the timing and patterns of light-intensity physical activity may be an important factor in reducing postprandial insulin concentrations,” the authors wrote.

SOURCE:

The study, led by Waris Wongpipit, PhD, Division of Health and Physical Education, Chulalongkorn University in Bangkok, Thailand, was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The study’s small sample size of 16 participants may limit the generalizability of the findings. The short duration of the study (7-hour experimental conditions) may not reflect long-term effects. The prescribed activities and dietary profiles, along with the controlled laboratory setting, may not accurately represent real-world conditions. The lack of objective physical activity/sedentary behavior measurement to confirm compliance between conditions is a limitation.

DISCLOSURES:

This study was supported by grants from the Office of the Permanent Secretary, Ministry of Higher Education, Science, Research and Innovation, Thailand Science Research and Innovation, and Chulalongkorn University. Wongpipit received grant support from these organizations. Paddy C. Dempsey is supported by a National Health and Medical Research Council of Australia research fellowship. The other authors had no disclosures.

 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Light-intensity walking reduces postprandial glucose and diastolic blood pressure in young adults with obesity and can improve insulin levels, depending on the walking pattern.

METHODOLOGY:

• Researchers conducted a randomized crossover trial with 16 young adults aged 18-34 years with body mass index (BMI) ≥ 25 in Bangkok, Thailand, to examine the effects of different light-intensity walking patterns on postprandial cardiometabolic responses.
• Participants (mean age, 25; mean BMI, 29.8) engaged in four 7-hour experimental conditions, each involving a different activity: Uninterrupted sitting, 30-minutes of light-intensity walking, 3-minute light-intensity walking every 30 minutes, or a combination of both walking regimens. There was a 7- to 20-day washout period between each experiment period.
• Baseline and 6-hour postprandial concentrations of glucose, insulin, triglycerides, and blood pressure were measured.
• Incremental areas under the curve (iAUC) for each outcome and average blood pressure were compared between sitting and walking conditions.

TAKEAWAY:

• All the walking interventions reduced postprandial glucose concentrations and diastolic blood pressure compared with uninterrupted sitting.
• Continuous 30-minute light-intensity walking alone or combined with brief 3-minute bouts also attenuated postprandial insulin concentrations.
• No significant differences were found for triglycerides iAUC and systolic blood pressure between the four experiment conditions.

IN PRACTICE:

“These findings support the notion that engaging in light-intensity walking, regardless of the pattern, provides benefits to glycemic control. Moreover, the timing and patterns of light-intensity physical activity may be an important factor in reducing postprandial insulin concentrations,” the authors wrote.

SOURCE:

The study, led by Waris Wongpipit, PhD, Division of Health and Physical Education, Chulalongkorn University in Bangkok, Thailand, was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The study’s small sample size of 16 participants may limit the generalizability of the findings. The short duration of the study (7-hour experimental conditions) may not reflect long-term effects. The prescribed activities and dietary profiles, along with the controlled laboratory setting, may not accurately represent real-world conditions. The lack of objective physical activity/sedentary behavior measurement to confirm compliance between conditions is a limitation.

DISCLOSURES:

This study was supported by grants from the Office of the Permanent Secretary, Ministry of Higher Education, Science, Research and Innovation, Thailand Science Research and Innovation, and Chulalongkorn University. Wongpipit received grant support from these organizations. Paddy C. Dempsey is supported by a National Health and Medical Research Council of Australia research fellowship. The other authors had no disclosures.

 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Light-intensity walking reduces postprandial glucose and diastolic blood pressure in young adults with obesity and can improve insulin levels, depending on the walking pattern.

METHODOLOGY:

• Researchers conducted a randomized crossover trial with 16 young adults aged 18-34 years with body mass index (BMI) ≥ 25 in Bangkok, Thailand, to examine the effects of different light-intensity walking patterns on postprandial cardiometabolic responses.
• Participants (mean age, 25; mean BMI, 29.8) engaged in four 7-hour experimental conditions, each involving a different activity: Uninterrupted sitting, 30-minutes of light-intensity walking, 3-minute light-intensity walking every 30 minutes, or a combination of both walking regimens. There was a 7- to 20-day washout period between each experiment period.
• Baseline and 6-hour postprandial concentrations of glucose, insulin, triglycerides, and blood pressure were measured.
• Incremental areas under the curve (iAUC) for each outcome and average blood pressure were compared between sitting and walking conditions.

TAKEAWAY:

• All the walking interventions reduced postprandial glucose concentrations and diastolic blood pressure compared with uninterrupted sitting.
• Continuous 30-minute light-intensity walking alone or combined with brief 3-minute bouts also attenuated postprandial insulin concentrations.
• No significant differences were found for triglycerides iAUC and systolic blood pressure between the four experiment conditions.

IN PRACTICE:

“These findings support the notion that engaging in light-intensity walking, regardless of the pattern, provides benefits to glycemic control. Moreover, the timing and patterns of light-intensity physical activity may be an important factor in reducing postprandial insulin concentrations,” the authors wrote.

SOURCE:

The study, led by Waris Wongpipit, PhD, Division of Health and Physical Education, Chulalongkorn University in Bangkok, Thailand, was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The study’s small sample size of 16 participants may limit the generalizability of the findings. The short duration of the study (7-hour experimental conditions) may not reflect long-term effects. The prescribed activities and dietary profiles, along with the controlled laboratory setting, may not accurately represent real-world conditions. The lack of objective physical activity/sedentary behavior measurement to confirm compliance between conditions is a limitation.

DISCLOSURES:

This study was supported by grants from the Office of the Permanent Secretary, Ministry of Higher Education, Science, Research and Innovation, Thailand Science Research and Innovation, and Chulalongkorn University. Wongpipit received grant support from these organizations. Paddy C. Dempsey is supported by a National Health and Medical Research Council of Australia research fellowship. The other authors had no disclosures.

 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Replacing animal-based protein sources with plant-based alternatives in older adults reduced both the quality and quantity of protein intake only when all animal-based foods were eliminated for a vegan scenario, finds a simulation study that suggests a switch to 60% plant-based protein seems to be safe.

METHODOLOGY:

• For environmental and health reasons, the Dutch Health Council advises a switch to an animal-based to plant-based protein ratio of 40:60, but older adults also need adequate protein intake to prevent muscle loss and maintain health, and it’s uncertain if they can meet their protein requirements through a more sustainable diet.
• This simulation study evaluated the impact of more sustainable eating patterns on protein quantity and quality by using data of 607 community-dwelling older adults aged 65-79 years from the Dutch National Food Consumption Survey 2019-2021.
• Data on food consumption were collected via two 24-hour dietary recalls per participant on nonconsecutive days and calculated as three main meals and four in-between moments each day.
• In the simulation, certain food products in the original diet were replaced from a list of similar plant-based alternatives, using a random number generator, to create scenarios for two flexitarian diets (40% and 80% meat and fish were replaced), one pescetarian diet (meat was replaced, but not fish and other animal-based products), one vegetarian diet (meat and fish were replaced, but not other animal-based products), and one vegan diet (fish, meat, and animal-based products were replaced).
• Protein intake was calculated in three ways for each meal moment, including by total protein intake (quantity) and by the proportion of indispensable amino acids that must be eaten together within a limited timeframe (quality).

TAKEAWAY:

• In the reference diet, the total daily plant-based protein intake was 39.0% in men and 37.7% in women, while in the vegetarian scenario, it was 59.1% in men and 54.2% in women.
• In the flexitarian, pescetarian, and vegetarian scenarios, the usable protein intake was comparable; in the vegan scenario, both total protein intake and usable protein intake were lower, leading to nearly 50% less usable protein than in the original diet.
• In the original diet, 7.5% of men and 11.1% of women did not meet the estimated average requirements (EARs) for utilizable protein; in the vegan scenario, 83.3% of both sexes had a protein intake below the EAR.
• The loss in protein intake (quantity) in all scenarios was mainly observed at dinner; the loss in protein quality was greatest at breakfast and lunch, especially in lysine (found in beans or soy milk).

IN PRACTICE:

“Changing protein intake to 60% plant-based protein seems to be safe for older adults in terms of protein intake. In contrast, a vegan pattern was associated with a substantial decline in protein availability, leading to a majority of older adults not reaching the recommended protein levels,” the authors wrote.

SOURCE:

The study was led by Jos W. Borkent, HAN University of Applied Sciences, Nijmegen, the Netherlands. It was published online in The Journal of Nutrition, Health and Aging.

LIMITATIONS:

Study limitations included the use of a simulation model, which may not fully reflect real-life dietary practices. The strict timeframe for assessing protein quality (optimal combinations of indispensible amino acids) within one meal moment may have led to an underestimation of protein availability, especially in the vegan scenario. Additionally, the choice of processed meat replacements in the vegan scenario may not have represented protein sources of the highest quality available. Higher protein quality per meal in the vegan scenario is possible when smart combinations are made in multiple meal components.

DISCLOSURES:

The study was partly funded by a grant from the Taskforce for Applied Research SIA, which is part of the Netherlands Organisation for Scientific Research and financed by the Dutch Ministry of Education, Culture and Science and by a fund of the Dutch Dairy Association. The authors declared that they had no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Replacing animal-based protein sources with plant-based alternatives in older adults reduced both the quality and quantity of protein intake only when all animal-based foods were eliminated for a vegan scenario, finds a simulation study that suggests a switch to 60% plant-based protein seems to be safe.

METHODOLOGY:

• For environmental and health reasons, the Dutch Health Council advises a switch to an animal-based to plant-based protein ratio of 40:60, but older adults also need adequate protein intake to prevent muscle loss and maintain health, and it’s uncertain if they can meet their protein requirements through a more sustainable diet.
• This simulation study evaluated the impact of more sustainable eating patterns on protein quantity and quality by using data of 607 community-dwelling older adults aged 65-79 years from the Dutch National Food Consumption Survey 2019-2021.
• Data on food consumption were collected via two 24-hour dietary recalls per participant on nonconsecutive days and calculated as three main meals and four in-between moments each day.
• In the simulation, certain food products in the original diet were replaced from a list of similar plant-based alternatives, using a random number generator, to create scenarios for two flexitarian diets (40% and 80% meat and fish were replaced), one pescetarian diet (meat was replaced, but not fish and other animal-based products), one vegetarian diet (meat and fish were replaced, but not other animal-based products), and one vegan diet (fish, meat, and animal-based products were replaced).
• Protein intake was calculated in three ways for each meal moment, including by total protein intake (quantity) and by the proportion of indispensable amino acids that must be eaten together within a limited timeframe (quality).

TAKEAWAY:

• In the reference diet, the total daily plant-based protein intake was 39.0% in men and 37.7% in women, while in the vegetarian scenario, it was 59.1% in men and 54.2% in women.
• In the flexitarian, pescetarian, and vegetarian scenarios, the usable protein intake was comparable; in the vegan scenario, both total protein intake and usable protein intake were lower, leading to nearly 50% less usable protein than in the original diet.
• In the original diet, 7.5% of men and 11.1% of women did not meet the estimated average requirements (EARs) for utilizable protein; in the vegan scenario, 83.3% of both sexes had a protein intake below the EAR.
• The loss in protein intake (quantity) in all scenarios was mainly observed at dinner; the loss in protein quality was greatest at breakfast and lunch, especially in lysine (found in beans or soy milk).

IN PRACTICE:

“Changing protein intake to 60% plant-based protein seems to be safe for older adults in terms of protein intake. In contrast, a vegan pattern was associated with a substantial decline in protein availability, leading to a majority of older adults not reaching the recommended protein levels,” the authors wrote.

SOURCE:

The study was led by Jos W. Borkent, HAN University of Applied Sciences, Nijmegen, the Netherlands. It was published online in The Journal of Nutrition, Health and Aging.

LIMITATIONS:

Study limitations included the use of a simulation model, which may not fully reflect real-life dietary practices. The strict timeframe for assessing protein quality (optimal combinations of indispensible amino acids) within one meal moment may have led to an underestimation of protein availability, especially in the vegan scenario. Additionally, the choice of processed meat replacements in the vegan scenario may not have represented protein sources of the highest quality available. Higher protein quality per meal in the vegan scenario is possible when smart combinations are made in multiple meal components.

DISCLOSURES:

The study was partly funded by a grant from the Taskforce for Applied Research SIA, which is part of the Netherlands Organisation for Scientific Research and financed by the Dutch Ministry of Education, Culture and Science and by a fund of the Dutch Dairy Association. The authors declared that they had no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Replacing animal-based protein sources with plant-based alternatives in older adults reduced both the quality and quantity of protein intake only when all animal-based foods were eliminated for a vegan scenario, finds a simulation study that suggests a switch to 60% plant-based protein seems to be safe.

METHODOLOGY:

• For environmental and health reasons, the Dutch Health Council advises a switch to an animal-based to plant-based protein ratio of 40:60, but older adults also need adequate protein intake to prevent muscle loss and maintain health, and it’s uncertain if they can meet their protein requirements through a more sustainable diet.
• This simulation study evaluated the impact of more sustainable eating patterns on protein quantity and quality by using data of 607 community-dwelling older adults aged 65-79 years from the Dutch National Food Consumption Survey 2019-2021.
• Data on food consumption were collected via two 24-hour dietary recalls per participant on nonconsecutive days and calculated as three main meals and four in-between moments each day.
• In the simulation, certain food products in the original diet were replaced from a list of similar plant-based alternatives, using a random number generator, to create scenarios for two flexitarian diets (40% and 80% meat and fish were replaced), one pescetarian diet (meat was replaced, but not fish and other animal-based products), one vegetarian diet (meat and fish were replaced, but not other animal-based products), and one vegan diet (fish, meat, and animal-based products were replaced).
• Protein intake was calculated in three ways for each meal moment, including by total protein intake (quantity) and by the proportion of indispensable amino acids that must be eaten together within a limited timeframe (quality).

TAKEAWAY:

• In the reference diet, the total daily plant-based protein intake was 39.0% in men and 37.7% in women, while in the vegetarian scenario, it was 59.1% in men and 54.2% in women.
• In the flexitarian, pescetarian, and vegetarian scenarios, the usable protein intake was comparable; in the vegan scenario, both total protein intake and usable protein intake were lower, leading to nearly 50% less usable protein than in the original diet.
• In the original diet, 7.5% of men and 11.1% of women did not meet the estimated average requirements (EARs) for utilizable protein; in the vegan scenario, 83.3% of both sexes had a protein intake below the EAR.
• The loss in protein intake (quantity) in all scenarios was mainly observed at dinner; the loss in protein quality was greatest at breakfast and lunch, especially in lysine (found in beans or soy milk).

IN PRACTICE:

“Changing protein intake to 60% plant-based protein seems to be safe for older adults in terms of protein intake. In contrast, a vegan pattern was associated with a substantial decline in protein availability, leading to a majority of older adults not reaching the recommended protein levels,” the authors wrote.

SOURCE:

The study was led by Jos W. Borkent, HAN University of Applied Sciences, Nijmegen, the Netherlands. It was published online in The Journal of Nutrition, Health and Aging.

LIMITATIONS:

Study limitations included the use of a simulation model, which may not fully reflect real-life dietary practices. The strict timeframe for assessing protein quality (optimal combinations of indispensible amino acids) within one meal moment may have led to an underestimation of protein availability, especially in the vegan scenario. Additionally, the choice of processed meat replacements in the vegan scenario may not have represented protein sources of the highest quality available. Higher protein quality per meal in the vegan scenario is possible when smart combinations are made in multiple meal components.

DISCLOSURES:

The study was partly funded by a grant from the Taskforce for Applied Research SIA, which is part of the Netherlands Organisation for Scientific Research and financed by the Dutch Ministry of Education, Culture and Science and by a fund of the Dutch Dairy Association. The authors declared that they had no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

WASHINGTON — A diagnostic test to predict preeclampsia does not effectively rule in or out this pregnancy complication in women with systemic lupus erythematosus (SLE) and proteinuria, according to new research presented at the annual meeting of the American College of Rheumatology (ACR).

“If you have a patient who has proteinuria during pregnancy, I’m not sure we know what to do with this test,” said Megan Clowse, MD, MPH, associate professor of medicine and chief of the Division of Rheumatology and Immunology at Duke University School of Medicine in Durham, North Carolina. She led the research and presented the work.

The results “are probably a step in the right direction to understanding that we need more biochemical markers for differentiating preeclampsia [in this patient population],” Leanna Wise, MD, of the Keck School of Medicine at the University of Southern California, Los Angeles, said in an interview. She comoderated the session where the research was presented. “It exposed that we have a lot of gray areas in which we need to do more research.”

The test is a ratio of two biomarkers that measure spiral artery and placental health: Soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF). In the general population, a sFlt-1/PlGF ratio ≤ 38 effectively rules out the short-term risk for preeclampsia, whereas a ratio ≥ 85 is moderately predictive of preeclampsia. However, it was not known how this test would fare in pregnant women with SLE who are already at a higher risk for the complication.

To answer this question, Clowse and colleagues pulled patient data from an ongoing prospective registry of lupus pregnancies. The analysis included patients with a confirmed SLE diagnosis who had enrolled in the registry prior to 30 weeks’ gestation. All participants had provided a serum sample prior to 16 weeks’ gestation and had singleton pregnancies.

In an extensive chart review, preeclampsia was determined by a roundtable of six experts: Two rheumatologists, two maternal-fetal medicine doctors, and two nephrologists.

The analysis included 79 pregnancies, of which 30% developed preeclampsia. Nearly half (47%) of the participants identified as Black or African American. About 30% had a history of lupus nephritis, and half of these patients had active disease during their pregnancy. About half of the women reported that this was their first pregnancy, and an additional 17% of women reported a prior episode of preeclampsia. Most patients were on aspirin (92%) and hydroxychloroquine (87%), and another 43% were prescribed prednisone and 37% were taking azathioprine.

Researchers assessed whether a low sFlt-1/PlGF ratio (≤ 38) was associated with the absence of preeclampsia at 4- and 8-weeks post–blood draw, as well as during the entire pregnancy. They also tested if a high ratio (≥ 85) was associated with the development of preeclampsia within 4- and 8-weeks post–blood draw and through the entire pregnancy.

Across all pregnancies in the cohort, those with sFlt-1/PlGF ≤ 38 were unlikely to develop preeclampsia at 4 weeks post draw (negative predictive value [NPV], 98%) and 8 weeks post draw (NPV, 96%). Still, 20% of patients with this low ratio went on to develop preeclampsia at some point during their pregnancy.

Similar to the general population, sFlt-1/PlGF ≥ 85 was only moderately predictive of preeclampsia. Over half of all patients with this high ratio developed preeclampsia, but more than 40% did not.

Researchers also stratified patients by urine protein:creatinine ratio (UPCR) at the time of their rheumatology visit, defining proteinuria as a UPCR ≥ 300 mg/g.

In patients without proteinuria (n = 63), a low sFlt-1/PlGF ratio ruled out preeclampsia over the next 8 weeks, but a high sFlt-1/PlGF ratio was not usefully predictive of preeclampsia.

 

Low Ratio to Rule Out Preeclampsia ‘Reassuring’

The high reliability in ruling out preeclampsia in this subset of patients with a low sFlt-1/PlGF ratio is “reassuring,” Wise said, and suggests that these patients are “relatively safe moving forward,” given regular follow-up.

In the small group of patients with proteinuria (n = 16), 44% ultimately developed preeclampsia. One third of patients with sFlt-1/PlGF ≤ 38 developed preeclampsia in 8 weeks, and half experienced preeclampsia at some point during their pregnancy. Among the patients with sFlt-1:PlGF ≥ 85, 56% developed preeclampsia during their pregnancy.

“The negative predictive values are not really great, and the positive predictive values are not really very useful,” Clowse said. For a pregnant patient with proteinuria, “I don’t think that a high [ratio] is going to tell us that she definitely has preeclampsia today or tomorrow. I also am not convinced yet that a low [ratio] tells us that she’s out of the woods. So, I think we definitely need more research on what to do with this test in patients with proteinuria.”

Clowse is a consultant and has received research support/grants from GSK and UCB. She also reported consulting for AstraZeneca. Wise is a consultant for Aurinia Pharmaceuticals and has received honoraria from AstraZeneca, Aurinia Pharmaceuticals, and GSK.

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

WASHINGTON — A diagnostic test to predict preeclampsia does not effectively rule in or out this pregnancy complication in women with systemic lupus erythematosus (SLE) and proteinuria, according to new research presented at the annual meeting of the American College of Rheumatology (ACR).

“If you have a patient who has proteinuria during pregnancy, I’m not sure we know what to do with this test,” said Megan Clowse, MD, MPH, associate professor of medicine and chief of the Division of Rheumatology and Immunology at Duke University School of Medicine in Durham, North Carolina. She led the research and presented the work.

The results “are probably a step in the right direction to understanding that we need more biochemical markers for differentiating preeclampsia [in this patient population],” Leanna Wise, MD, of the Keck School of Medicine at the University of Southern California, Los Angeles, said in an interview. She comoderated the session where the research was presented. “It exposed that we have a lot of gray areas in which we need to do more research.”

The test is a ratio of two biomarkers that measure spiral artery and placental health: Soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF). In the general population, a sFlt-1/PlGF ratio ≤ 38 effectively rules out the short-term risk for preeclampsia, whereas a ratio ≥ 85 is moderately predictive of preeclampsia. However, it was not known how this test would fare in pregnant women with SLE who are already at a higher risk for the complication.

To answer this question, Clowse and colleagues pulled patient data from an ongoing prospective registry of lupus pregnancies. The analysis included patients with a confirmed SLE diagnosis who had enrolled in the registry prior to 30 weeks’ gestation. All participants had provided a serum sample prior to 16 weeks’ gestation and had singleton pregnancies.

In an extensive chart review, preeclampsia was determined by a roundtable of six experts: Two rheumatologists, two maternal-fetal medicine doctors, and two nephrologists.

The analysis included 79 pregnancies, of which 30% developed preeclampsia. Nearly half (47%) of the participants identified as Black or African American. About 30% had a history of lupus nephritis, and half of these patients had active disease during their pregnancy. About half of the women reported that this was their first pregnancy, and an additional 17% of women reported a prior episode of preeclampsia. Most patients were on aspirin (92%) and hydroxychloroquine (87%), and another 43% were prescribed prednisone and 37% were taking azathioprine.

Researchers assessed whether a low sFlt-1/PlGF ratio (≤ 38) was associated with the absence of preeclampsia at 4- and 8-weeks post–blood draw, as well as during the entire pregnancy. They also tested if a high ratio (≥ 85) was associated with the development of preeclampsia within 4- and 8-weeks post–blood draw and through the entire pregnancy.

Across all pregnancies in the cohort, those with sFlt-1/PlGF ≤ 38 were unlikely to develop preeclampsia at 4 weeks post draw (negative predictive value [NPV], 98%) and 8 weeks post draw (NPV, 96%). Still, 20% of patients with this low ratio went on to develop preeclampsia at some point during their pregnancy.

Similar to the general population, sFlt-1/PlGF ≥ 85 was only moderately predictive of preeclampsia. Over half of all patients with this high ratio developed preeclampsia, but more than 40% did not.

Researchers also stratified patients by urine protein:creatinine ratio (UPCR) at the time of their rheumatology visit, defining proteinuria as a UPCR ≥ 300 mg/g.

In patients without proteinuria (n = 63), a low sFlt-1/PlGF ratio ruled out preeclampsia over the next 8 weeks, but a high sFlt-1/PlGF ratio was not usefully predictive of preeclampsia.

 

Low Ratio to Rule Out Preeclampsia ‘Reassuring’

The high reliability in ruling out preeclampsia in this subset of patients with a low sFlt-1/PlGF ratio is “reassuring,” Wise said, and suggests that these patients are “relatively safe moving forward,” given regular follow-up.

In the small group of patients with proteinuria (n = 16), 44% ultimately developed preeclampsia. One third of patients with sFlt-1/PlGF ≤ 38 developed preeclampsia in 8 weeks, and half experienced preeclampsia at some point during their pregnancy. Among the patients with sFlt-1:PlGF ≥ 85, 56% developed preeclampsia during their pregnancy.

“The negative predictive values are not really great, and the positive predictive values are not really very useful,” Clowse said. For a pregnant patient with proteinuria, “I don’t think that a high [ratio] is going to tell us that she definitely has preeclampsia today or tomorrow. I also am not convinced yet that a low [ratio] tells us that she’s out of the woods. So, I think we definitely need more research on what to do with this test in patients with proteinuria.”

Clowse is a consultant and has received research support/grants from GSK and UCB. She also reported consulting for AstraZeneca. Wise is a consultant for Aurinia Pharmaceuticals and has received honoraria from AstraZeneca, Aurinia Pharmaceuticals, and GSK.

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

WASHINGTON — A diagnostic test to predict preeclampsia does not effectively rule in or out this pregnancy complication in women with systemic lupus erythematosus (SLE) and proteinuria, according to new research presented at the annual meeting of the American College of Rheumatology (ACR).

“If you have a patient who has proteinuria during pregnancy, I’m not sure we know what to do with this test,” said Megan Clowse, MD, MPH, associate professor of medicine and chief of the Division of Rheumatology and Immunology at Duke University School of Medicine in Durham, North Carolina. She led the research and presented the work.

The results “are probably a step in the right direction to understanding that we need more biochemical markers for differentiating preeclampsia [in this patient population],” Leanna Wise, MD, of the Keck School of Medicine at the University of Southern California, Los Angeles, said in an interview. She comoderated the session where the research was presented. “It exposed that we have a lot of gray areas in which we need to do more research.”

The test is a ratio of two biomarkers that measure spiral artery and placental health: Soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF). In the general population, a sFlt-1/PlGF ratio ≤ 38 effectively rules out the short-term risk for preeclampsia, whereas a ratio ≥ 85 is moderately predictive of preeclampsia. However, it was not known how this test would fare in pregnant women with SLE who are already at a higher risk for the complication.

To answer this question, Clowse and colleagues pulled patient data from an ongoing prospective registry of lupus pregnancies. The analysis included patients with a confirmed SLE diagnosis who had enrolled in the registry prior to 30 weeks’ gestation. All participants had provided a serum sample prior to 16 weeks’ gestation and had singleton pregnancies.

In an extensive chart review, preeclampsia was determined by a roundtable of six experts: Two rheumatologists, two maternal-fetal medicine doctors, and two nephrologists.

The analysis included 79 pregnancies, of which 30% developed preeclampsia. Nearly half (47%) of the participants identified as Black or African American. About 30% had a history of lupus nephritis, and half of these patients had active disease during their pregnancy. About half of the women reported that this was their first pregnancy, and an additional 17% of women reported a prior episode of preeclampsia. Most patients were on aspirin (92%) and hydroxychloroquine (87%), and another 43% were prescribed prednisone and 37% were taking azathioprine.

Researchers assessed whether a low sFlt-1/PlGF ratio (≤ 38) was associated with the absence of preeclampsia at 4- and 8-weeks post–blood draw, as well as during the entire pregnancy. They also tested if a high ratio (≥ 85) was associated with the development of preeclampsia within 4- and 8-weeks post–blood draw and through the entire pregnancy.

Across all pregnancies in the cohort, those with sFlt-1/PlGF ≤ 38 were unlikely to develop preeclampsia at 4 weeks post draw (negative predictive value [NPV], 98%) and 8 weeks post draw (NPV, 96%). Still, 20% of patients with this low ratio went on to develop preeclampsia at some point during their pregnancy.

Similar to the general population, sFlt-1/PlGF ≥ 85 was only moderately predictive of preeclampsia. Over half of all patients with this high ratio developed preeclampsia, but more than 40% did not.

Researchers also stratified patients by urine protein:creatinine ratio (UPCR) at the time of their rheumatology visit, defining proteinuria as a UPCR ≥ 300 mg/g.

In patients without proteinuria (n = 63), a low sFlt-1/PlGF ratio ruled out preeclampsia over the next 8 weeks, but a high sFlt-1/PlGF ratio was not usefully predictive of preeclampsia.

 

Low Ratio to Rule Out Preeclampsia ‘Reassuring’

The high reliability in ruling out preeclampsia in this subset of patients with a low sFlt-1/PlGF ratio is “reassuring,” Wise said, and suggests that these patients are “relatively safe moving forward,” given regular follow-up.

In the small group of patients with proteinuria (n = 16), 44% ultimately developed preeclampsia. One third of patients with sFlt-1/PlGF ≤ 38 developed preeclampsia in 8 weeks, and half experienced preeclampsia at some point during their pregnancy. Among the patients with sFlt-1:PlGF ≥ 85, 56% developed preeclampsia during their pregnancy.

“The negative predictive values are not really great, and the positive predictive values are not really very useful,” Clowse said. For a pregnant patient with proteinuria, “I don’t think that a high [ratio] is going to tell us that she definitely has preeclampsia today or tomorrow. I also am not convinced yet that a low [ratio] tells us that she’s out of the woods. So, I think we definitely need more research on what to do with this test in patients with proteinuria.”

Clowse is a consultant and has received research support/grants from GSK and UCB. She also reported consulting for AstraZeneca. Wise is a consultant for Aurinia Pharmaceuticals and has received honoraria from AstraZeneca, Aurinia Pharmaceuticals, and GSK.

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