Dataset Information

Evaluation of the Pooled Cohort Risk Equations for Cardiovascular Risk Prediction in a Multiethnic Cohort From the Women's Health Initiative.

ABSTRACT: Importance:Atherosclerotic cardiovascular disease (ASCVD) kills approximately 1 in every 3 US women. Current cholesterol, hypertension, and aspirin guidelines recommend calculating 10-year risk of ASCVD using the 2013 Pooled Cohort Equations (PCE). However, numerous studies have reported apparent overestimation of risk with the PCE, and reasons for overestimation are unclear. Objective:We evaluated the predictive accuracy of the PCE in the Women's Health Initiative (WHI), a multiethnic cohort of contemporary US postmenopausal women. We evaluated the effects of time-varying treatments such as aspirin and statins, and ascertainment of additional ASCVD events by linkage with the Centers for Medicare and Medicaid Services (CMS) claims. Design, Setting, and Participants:The WHI recruited the largest number of US women (n?=?161?808) with the racial/ethnic, geographic, and age diversity of the general population (1993-1998). For this study, we included women aged 50 to 79 (n?=?19?995) participating in the WHI with data on the risk equation variables at baseline and who met the guideline inclusion and exclusion criteria. Median follow-up was 10 years. Main Outcomes and Measures:For this study, ASCVD was defined as myocardial infarction, stroke, or cardiovascular death. Results:Among the 19?995 women (mean [SD] age, 64 [7.3] years; 8305 [41.5%] white, 7688 [38.5%] black, 3491 [17.5%] Hispanic, 103 [0.5%] American Indian, 321 [1.6%] Asian/Pacific Islander, and 87 [0.4%] other/unknown), a total of 1236 ASCVD events occurred in 10 years and were adjudicated through medical record review by WHI investigators. The WHI-adjudicated observed risks were lower than predicted. The observed (predicted) risks for baseline 10-year risk categories less than 5%, 5% to less than 7.5%, 7.5% to less than 10%, and 10% or more were 1.7 (2.8), 4.4 (6.2), 5.3 (8.7), and 12.4 (18.2), respectively. Small changes were noted after adjusting for time-dependent changes in statin and aspirin use. Among women 65 years or older enrolled in Medicare, WHI-adjudicated risks were also lower than predicted, but observed (predicted) risks became aligned after including events ascertained by linkage with CMS for additional surveillance for events: 3.8 (4.3), 7.1 (6.4), 8.3 (8.7), and 18.9 (18.7), respectively. Similar results were seen across ethnic/racial groups. Overall, the equations discriminated risk well (C statistic, 0.726; 95% CI, 0.714-0.738). Conclusions and Relevance:Without including surveillance for ASCVD events using CMS, observed risks in the WHI were lower than predicted by PCE as noted in several other US cohorts, but risks were better aligned after including CMS events. Trial Registration:ClinicalTrials.gov identifier: NCT00000611.

SUBMITTER: Mora S

PROVIDER: S-EPMC6142964 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Evaluation of the Pooled Cohort Risk Equations for Cardiovascular Risk Prediction in a Multiethnic Cohort From the Women's Health Initiative.

Mora Samia S Wenger Nanette K NK Cook Nancy R NR Liu Jingmin J Howard Barbara V BV Limacher Marian C MC Liu Simin S Margolis Karen L KL Martin Lisa W LW Paynter Nina P NP Ridker Paul M PM Robinson Jennifer G JG Rossouw Jacques E JE Safford Monika M MM Manson JoAnn E JE

JAMA internal medicine 20180901 9

<h4>Importance</h4>Atherosclerotic cardiovascular disease (ASCVD) kills approximately 1 in every 3 US women. Current cholesterol, hypertension, and aspirin guidelines recommend calculating 10-year risk of ASCVD using the 2013 Pooled Cohort Equations (PCE). However, numerous studies have reported apparent overestimation of risk with the PCE, and reasons for overestimation are unclear.<h4>Objective</h4>We evaluated the predictive accuracy of the PCE in the Women's Health Initiative (WHI), a multie ...[more]

PMID: 30039172

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Project description:ImportanceThe American College of Cardiology/American Heart Association (ACC/AHA) Pooled Cohort risk equations were developed to estimate atherosclerotic cardiovascular disease (CVD) risk and guide statin initiation.ObjectiveTo assess calibration and discrimination of the Pooled Cohort risk equations in a contemporary US population.Design, setting, and participantsAdults aged 45 to 79 years enrolled in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study between January 2003 and October 2007 and followed up through December 2010. We studied participants for whom atherosclerotic CVD risk may trigger a discussion of statin initiation (those without clinical atherosclerotic CVD or diabetes, low-density lipoprotein cholesterol level between 70 and 189 mg/dL, and not taking statins; n = 10,997).Main outcomes and measuresPredicted risk and observed adjudicated atherosclerotic CVD incidence (nonfatal myocardial infarction, coronary heart disease [CHD] death, nonfatal or fatal stroke) at 5 years because REGARDS participants have not been followed up for 10 years. Additional analyses, limited to Medicare beneficiaries (n = 3333), added atherosclerotic CVD events identified in Medicare claims data.ResultsThere were 338 adjudicated events (192 CHD events, 146 strokes). The observed and predicted 5-year atherosclerotic CVD incidence per 1000 person-years for participants with a 10-year predicted atherosclerotic CVD risk of less than 5% was 1.9 (95% CI, 1.3-2.7) and 1.9, respectively, risk of 5% to less than 7.5% was 4.8 (95% CI, 3.4-6.7) and 4.8, risk of 7.5% to less than 10% was 6.1 (95% CI, 4.4-8.6) and 6.9, and risk of 10% or greater was 12.0 (95% CI, 10.6-13.6) and 15.1 (Hosmer-Lemeshow χ2 = 19.9, P = .01). The C index was 0.72 (95% CI, 0.70-0.75). There were 234 atherosclerotic CVD events (120 CHD events, 114 strokes) among Medicare-linked participants and the observed and predicted 5-year atherosclerotic CVD incidence per 1000 person-years for participants with a predicted risk of less than 7.5% was 5.3 (95% CI, 2.8-10.1) and 4.0, respectively, risk of 7.5% to less than 10% was 7.9 (95% CI, 4.6-13.5) and 6.4, and risk of 10% or greater was 17.4 (95% CI, 15.3-19.8) and 16.4 (Hosmer-Lemeshow χ2 = 5.4, P = .71). The C index was 0.67 (95% CI, 0.64-0.71).Conclusions and relevanceIn this cohort of US adults for whom statin initiation is considered based on the ACC/AHA Pooled Cohort risk equations, observed and predicted 5-year atherosclerotic CVD risks were similar, indicating that these risk equations were well calibrated in the population for which they were designed to be used, and demonstrated moderate to good discrimination.

Project description:BackgroundThe Pooled Cohort Equations (PCEs) are race- and sex-specific Cox proportional hazards (PH)-based models used for 10-year atherosclerotic cardiovascular disease (ASCVD) risk prediction with acceptable discrimination. In recent years, neural network models have gained increasing popularity with their success in image recognition and text classification. Various survival neural network models have been proposed by combining survival analysis and neural network architecture to take advantage of the strengths from both. However, the performance of these survival neural network models compared to each other and to PCEs in ASCVD prediction is unknown.MethodsIn this study, we used 6 cohorts from the Lifetime Risk Pooling Project (with 5 cohorts as training/internal validation and one cohort as external validation) and compared the performance of the PCEs in 10-year ASCVD risk prediction with an all two-way interactions Cox PH model (Cox PH-TWI) and three state-of-the-art neural network survival models including Nnet-survival, Deepsurv, and Cox-nnet. For all the models, we used the same 7 covariates as used in the PCEs. We fitted each of the aforementioned models in white females, white males, black females, and black males, respectively. We evaluated models' internal and external discrimination power and calibration.ResultsThe training/internal validation sample comprised 23216 individuals. The average age at baseline was 57.8 years old (SD = 9.6); 16% developed ASCVD during average follow-up of 10.50 (SD = 3.02) years. Based on 10 × 10 cross-validation, the method that had the highest C-statistics was Deepsurv (0.7371) for white males, Deepsurv and Cox PH-TWI (0.7972) for white females, PCE (0.6981) for black males, and Deepsurv (0.7886) for black females. In the external validation dataset, Deepsurv (0.7032), Cox-nnet (0.7282), PCE (0.6811), and Deepsurv (0.7316) had the highest C-statistics for white male, white female, black male, and black female population, respectively. Calibration plots showed that in 10 × 10 validation, all models had good calibration in all race and sex groups. In external validation, all models overestimated the risk for 10-year ASCVD.ConclusionsWe demonstrated the use of the state-of-the-art neural network survival models in ASCVD risk prediction. Neural network survival models had similar if not superior discrimination and calibration compared to PCEs.

Project description:ImportanceObesity 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.ObjectiveTo assess performance of the PCE across clinical BMI categories.Design, setting, and participantsThis 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.ExposuresParticipant 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).Main outcomes and measuresDiscrimination (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.ResultsAmong 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.Conclusions and relevanceThese 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.

Project description:UNLABELLED:To examine the association between renal function and fracture in multiethnic women, we studied postmenopausal women enrolled in the Women's Health Initiative. Postmenopausal White women with mild renal dysfunction were at increased risk of nonvertebral fracture; this association was at least partially explained by effects of renal dysfunction on chronic inflammation. Reduced renal function appeared to increase fracture risk among Black women, but there was little evidence to support this association among other racial/ethnic groups. INTRODUCTION:The purpose of this study was to determine whether renal function is associated with fracture risk within racial/ethnic groups. METHODS:A nested case-control study was conducted among 93,673 postmenopausal women; incident nonvertebral fractures were identified in 362 Black, 183 Hispanic, 110 Asian, and 45 American-Indian women. A random sample of 395 White women with incident nonvertebral fracture was chosen. One nonfracture control for each case was selected (matched on age, race/ethnicity, and blood draw date). Cystatin C levels were measured using baseline serum, and estimated glomerular filtration rate calculated (eGFR(cys-c)). RESULTS:Each 1 SD increase in cystatin C was associated with a 1.2-fold increased risk of fracture among White women (adjusted odds ratios [OR], 1.23; 95% confidence intervals [CI], 1.04-1.46). The OR of fracture was 1.16 (95% CI, 0.85-1.58) among women with eGFR(cys-c) 60-90 mL/min/1.73 m(2) and 2.46 (95% CI, 1.16-5.21) among those with eGFR(cys-c) <60 mL/min/1.73 m(2) compared to the reference group (eGFR(cys-c) >90 mL/min/1.73 m(2)) (p trend = 0.05). The association was reduced after adjustment for cytokine TNF? soluble receptors (OR, 1.62; 95% CI, 0.59-4.46 for eGFR(cys-c) <60 mL/min/1.73 m(2)). Among Blacks, there was an association between cystatin C and fracture risk (OR per 1 SD increase, 1.15; 95% CI, 1.00-1.32); after adjustment, this association was only modestly attenuated, but no longer statistically significant. There was no evidence of significant associations among Hispanic, Asian, or American-Indian women. CONCLUSION:Postmenopausal White women with mild renal dysfunction are at increased risk of nonvertebral fracture. Effects of renal function on chronic inflammation may mediate this association. Reduced renal function may increase fracture risk among Black women, but there was little evidence to support this association among other racial/ethnic groups.

Dataset Information

Evaluation of the Pooled Cohort Risk Equations for Cardiovascular Risk Prediction in a Multiethnic Cohort From the Women's Health Initiative.

Publications

Evaluation of the Pooled Cohort Risk Equations for Cardiovascular Risk Prediction in a Multiethnic Cohort From the Women's Health Initiative.

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