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Performance of the Pooled Cohort Equations to Estimate Atherosclerotic Cardiovascular Disease Risk by Body Mass Index.

TitlePerformance of the Pooled Cohort Equations to Estimate Atherosclerotic Cardiovascular Disease Risk by Body Mass Index.
Publication TypeJournal Article
Year of Publication2020
AuthorsKhera, R, Pandey, A, Ayers, CR, Carnethon, MR, Greenland, P, Ndumele, CE, Nambi, V, Seliger, SL, Chaves, PHM, Safford, MM, Cushman, M, Xanthakis, V, Vasan, RS, Mentz, RJ, Correa, A, Lloyd-Jones, DM, Berry, JD, de Lemos, JA, Neeland, IJ
JournalJAMA Netw Open
Volume3
Issue10
Paginatione2023242
Date Published2020 10 01
ISSN2574-3805
KeywordsAdult, Aged, Body Mass Index, Cardiovascular Diseases, Cohort Studies, Correlation of Data, Female, Humans, Longitudinal Studies, Male, Middle Aged, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors
Abstract<p><b>Importance: </b>Obesity is a global health challenge and a risk factor for atherosclerotic cardiovascular disease (ASVCD). Performance of the pooled cohort equations (PCE) for ASCVD risk by body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is unknown.</p><p><b>Objective: </b>To assess performance of the PCE across clinical BMI categories.</p><p><b>Design, Setting, and Participants: </b>This cohort study used pooled individual-level data from 8 community-based, prospective, longitudinal cohort studies with 10-year ASCVD event follow-up from 1996 to 2016. We included all adults ages 40 to 79 years without baseline ASCVD or statin use, resulting in a sample size of 37 311 participants. Data were analyzed from August 2017 to July 2020.</p><p><b>Exposures: </b>Participant BMI category: underweight (<18.5), normal weight (18.5 to <25), overweight (25 to <30), mild obesity (30 to <35), and moderate to severe obesity (≥35).</p><p><b>Main Outcomes and Measures: </b>Discrimination (Harrell C statistic) and calibration (Nam-D'Agostino χ2 goodness-of-fit test) of the PCE across BMI categories. Improvement in discrimination and net reclassification with addition of BMI, waist circumference, and high-sensitivity C-reactive protein (hsCRP) to the PCE.</p><p><b>Results: </b>Among 37 311 participants (mean [SD] age, 58.6 [11.8] years; 21 897 [58.7%] women), 380 604 person-years of follow-up were conducted. Mean (SD) baseline BMI was 29.0 (6.2), and 360 individuals (1.0%) were in the underweight category, 9937 individuals (26.6%) were in the normal weight category, 13 601 individuals (36.4%) were in the overweight category, 7783 individuals (20.9%) were in the mild obesity category, and 5630 individuals (15.1%) were in the moderate to severe obesity category. Median (interquartile range [IQR]) 10-year estimated ASCVD risk was 7.1% (2.5%-15.4%), and 3709 individuals (9.9%) developed ASCVD over a median (IQR) 10.8 [8.5-12.6] years. The PCE overestimated ASCVD risk in the overall cohort (estimated/observed [E/O] risk ratio, 1.22; 95% CI, 1.18-1.26) and across all BMI categories except the underweight category. Calibration was better near the clinical decision threshold in all BMI groups but worse among individuals with moderate or severe obesity (E/O risk ratio, 1.36; 95% CI, 1.25-1.47) and among those with the highest estimated ASCVD risk ≥20%. The PCE C statistic overall was 0.760 (95% CI, 0.753-0.767), with lower discrimination in the moderate or severe obesity group (C statistic, 0.742; 95% CI, 0.721-0.763) compared with the normal-range BMI group (C statistic, 0.785; 95% CI, 0.772-0.798). Waist circumference (hazard ratio, 1.07 per 1-SD increase; 95% CI, 1.03-1.11) and hsCRP (hazard ratio, 1.07 per 1-SD increase; 95% CI, 1.05-1.09), but not BMI, were associated with increased ASCVD risk when added to the PCE. However, these factors did not improve model performance (C statistic, 0.760; 95% CI, 0.753-0.767) with or without added metrics.</p><p><b>Conclusions and Relevance: </b>These findings suggest that the PCE had acceptable model discrimination and were well calibrated at clinical decision thresholds but overestimated risk of ASCVD for individuals in overweight and obese categories, particularly individuals with high estimated risk. Incorporation of the usual clinical measures of obesity did not improve risk estimation of the PCE. Future research is needed to determine whether incorporation of alternative high-risk obesity markers (eg, weight trajectory or measures of visceral or ectopic fat) into the PCE may improve risk prediction.</p>
DOI10.1001/jamanetworkopen.2020.23242
Alternate JournalJAMA Netw Open
PubMed ID33119108
PubMed Central IDPMC7596579
Grant ListUL1 TR001105 / TR / NCATS NIH HHS / United States
K23 DK106520 / DK / NIDDK NIH HHS / United States
HHSN268201700001I / HL / NHLBI NIH HHS / United States
HHSN268201700002I / HL / NHLBI NIH HHS / United States
HHSN268201700003I / HL / NHLBI NIH HHS / United States
HHSN268201700005I / HL / NHLBI NIH HHS / United States
HHSN268201700004I / HL / NHLBI NIH HHS / United States
HHSN268201300025C / HL / NHLBI NIH HHS / United States
HHSN268201300026C / HL / NHLBI NIH HHS / United States
HHSN268201300027C / HL / NHLBI NIH HHS / United States
HHSN268201300028C / HL / NHLBI NIH HHS / United States
HHSN268201300029C / HL / NHLBI NIH HHS / United States
HHSN268200900041C / HL / NHLBI NIH HHS / United States
HHSN268201200036C / HL / NHLBI NIH HHS / United States
HHSN268200800007C / HL / NHLBI NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
N01HC85080 / HL / NHLBI NIH HHS / United States
N01HC85081 / HL / NHLBI NIH HHS / United States
N01HC85082 / HL / NHLBI NIH HHS / United States
N01HC85083 / HL / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
U01 HL130114 / HL / NHLBI NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
UL1 TR001105 / TR / NCATS NIH HHS / United States
HHSN268201500001I / HL / NHLBI NIH HHS / United States
HHSN268201300049C / HL / NHLBI NIH HHS / United States
HHSN268201300050C / HL / NHLBI NIH HHS / United States
HHSN268201300048C / HL / NHLBI NIH HHS / United States
HHSN268201300046C / HL / NHLBI NIH HHS / United States
HHSN268201300047C / HL / NHLBI NIH HHS / United States
HHSN268201500003I / HL / NHLBI NIH HHS / United States
N01HC95159 / HL / NHLBI NIH HHS / United States
N01HC95160 / HL / NHLBI NIH HHS / United States
N01HC95161 / HL / NHLBI NIH HHS / United States
N01HC95162 / HL / NHLBI NIH HHS / United States
N01HC95163 / HL / NHLBI NIH HHS / United States
N01HC95164 / HL / NHLBI NIH HHS / United States
N01HC95165 / HL / NHLBI NIH HHS / United States
N01HC95166 / HL / NHLBI NIH HHS / United States
N01HC95167 / HL / NHLBI NIH HHS / United States
N01HC95168 / HL / NHLBI NIH HHS / United States
N01HC95169 / HL / NHLBI NIH HHS / United States
UL1 TR000040 / TR / NCATS NIH HHS / United States
UL1 TR001079 / TR / NCATS NIH HHS / United States
UL1 TR001420 / TR / NCATS NIH HHS / United States
U01 NS041588 / NS / NINDS NIH HHS / United States
R01 HL080477 / HL / NHLBI NIH HHS / United States
K24 HL111154 / HL / NHLBI NIH HHS / United States
ePub date: 
20/10