Pooled cohort equations may overestimate ASCVD risk across spectrum of BMI
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The pooled cohort equations for atherosclerotic CVD prediction can be used as a risk-estimation tool for adults across BMI categories, but may overestimate ASCVD risk for individuals in overweight and obese categories.
The addition of other clinical measures of obesity to the pooled cohort equations, including waist circumference and high sensitivity C-reactive protein, failed to improve prognostic ability, according to data published in JAMA Network Open.
"The PCE had acceptable model discrimination but were not optimally calibrated and overestimated risk of ASCVD across the range of BMI categories except the underweight category," Rohan Khera, MD, MS, assistant professor in the section of cardiovascular medicine at the Yale School of Medicine and general cardiologist at the Yale New Haven Hospital, and colleagues wrote. "Calibration was better near the decision threshold in all BMI groups but worse among individuals with moderate to severe obesity and among those with the highest estimated ASCVD risk."
Khera and colleagues assessed performance of the pooled cohort equations across clinical BMI categories in 37,311 adults (mean age, 59 years; 59% women) from eight community-based, prospective, longitudinal cohort studies with 10-year ASCVD follow-up from 1996 to 2016. Individuals were categorized based on BMI: underweight (1%; BMI < 18.5 kg/m2), normal weight (26.6%; BMI, 18.5-25 kg/m2), overweight (36.4%; 25-30 kg/m2), mild obesity (20.9%; 30-35 kg/m2) and moderate to severe obesity (15.1%; 35 kg/m2).
“[G]iven the rising prevalence of obesity in the U.S. and globally, there is a question whether the PCE perform adequately in more contemporary obese populations given that the equations were derived from population cohorts when obesity was less prevalent,” the researchers wrote
Predictive ability across BMI
The median 10-year estimated ASCVD risk was 7.1%. Nearly 10% of individuals developed ASCVD during a median of 10.8 years, according to the results.
The pooled cohort equations overestimated risk for ASCVD in the overall cohort (RR = 1.22; 95% CI, 1.18-1.26) and across patients in all BMI categories, except for those categorized as underwent.
Additionally, calibration of the pooled cohort equations was better near the clinical decision threshold in all BMI groups, but was worse among those with moderate or severe obesity (RR = 1.36; 95% CI, 1.25-1.47) and among those with the highest estimated risk for ASCVD of 20% or greater, according to the results.
Discrimination of the pooled cohort equations was lower in individuals categorized with moderate or severe obesity (Harrell C statistic, 0.742; 95% CI, 0.721-0.763) compared with those with normal-range BMI (Harrell C statistic, 0.785; 95% CI, 0.772-0.798).
Incorporation of other clinical measures of obesity
The researchers also assessed improvement in discrimination and classification with the addition of BMI, waist circumference and high-sensitivity C-reactive protein to the pooled cohort equations.
Waist circumference (HR per 1-SD increase = 1.07; 95% CI, 1.03-1.11) and high-sensitivity CRP (HR per 1-SD increase = 1.07; 95% CI, 1.05-1.09) were associated with increased ASCVD risk when added to the pooled cohort equations, but the same was not observed when BMI was added. According to the researchers, these factors were not associated with improved model performance with or without added metrics.
“The observation that obesity metrics did not substantially improve performance of the pooled cohort equations model does not exclude the possibility that pooled cohort equation model performance could be improved by using obesity-related risk factors that more robustly reflect cardiometabolic risk (eg, imaging-based assessments of visceral fat) and that are not uniformly captured in most cohorts. Future studies will be needed to elucidate whether clinical assessment of body fat distribution or alternative biomarkers associated with obesity augment ASCVD risk estimation in contemporary populations,” the researchers wrote. “Although the additional obesity-related metrics evaluated in our study did not improve performance of the pooled cohort equations for ASCVD risk estimation, our results should not be misinterpreted to suggest that obesity is benign and unimportant for ASCVD risk assessment.”
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