Pooled Cohort Equations and the competing risk of cardiovascular disease versus cancer: Multi-Ethnic study of atherosclerosis.
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ABSTRACT: Background
many of the modifiable variables in the Pooled Cohort Equations (PCE) are shared risk factors for cardiovascular disease (CVD) and cancer, which are the two leading causes of death in the United States. We sought to determine the utility of the PCE risk for the synergistic risk prediction of CVD and cancer.Methods
we identified 5,773 participants (61.5 years and 53% women) without baseline CVD or cancer from the Multi-Ethnic study of atherosclerosis. The primary outcome was time to first event of either incident CVD or incident cancer. We calculated competing risk and cause-specific hazard models to examine the association of the PCE groups (<7.5%, 7.5-<20%, ≥20%) with the competing risk of CVD and cancer.Results
the rate of incident CVD and cancer was higher with higher PCE risk, but the absolute event rate was low for both CVD and cancer when the PCE risk was <7.5%. Participants with a PCE <7.5% had a higher rate of cancer (4.8) compared to CVD (3.3) per 1000 person-years, while the rate of CVD (11.5) was higher than cancer (8.6) for PCE between 7.5 and <20%. The ratio of CVD to cancer increased in a logarithmic manner and at a PCE risk of approximately 7.2% the risk for CVD and cancer was equal. In adjusted competing risk modeling, a PCE risk of ≥20% compared to <7.5% was associated with a greater risk of both CVD [7.18 (95% CI 5.77-8.94)] and cancer [3.59 (95% CI 2.91-4.43)].Conclusions
these findings highlight the importance of age and modifiable risk factors for CVD and cancer prevention. In addition, it suggests that the PCE can provide important information for both CVD and cancer risk stratification, which may guide a synergistic approach to screening and preventive therapies for the two leading causes of death in the United States.
SUBMITTER: Whelton SP
PROVIDER: S-EPMC8387297 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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.
| S-EPMC4189930 | biostudies-literature
Project description:Background Assessment of atherosclerotic cardiovascular disease (ASCVD) risk is crucial for prevention and management, but the performance of the pooled cohort equations in older adults with frailty and multimorbidity is unknown. We evaluated the pooled cohort equations in these subgroups and the impact of competing risks. Methods and Results In 4249 community-dwelling adults, aged ≥65 years, from the CHS (Cardiovascular Health Study), we calculated 10-year risk of hard ASCVD. Frailty was determined using the Fried phenotype. Latent class analysis was used to identify individuals with multimorbidity patterns using chronic conditions. We assessed discrimination using the C-statistic and calibration by comparing predicted ASCVD risks with estimated risk using cause-specific and cumulative incidence models, by multimorbidity patterns and frailty status. A total of 917 (21.6%) participants had an ASCVD event, and 706 (16.6%) had a competing event of death. C-statistic was 0.68 in men and 0.69 in women; calibration was good when compared with cause-specific and cumulative incidence estimated risks (males, -0.1% and 3.3%; females, 0.6% and 1.4%). Latent class analysis identified 4 patterns: minimal disease, cardiometabolic, low cognition, musculoskeletal-lung depression. In the cardiometabolic pattern, ASCVD risk was overpredicted compared with cumulative incidence risk in men (7.4%) and women (6.8%). Risk was underpredicted in men (-10.7%) and women (-8.2%) with frailty compared with cause-specific risk. Miscalibration occurred mostly at high predicted risk ranges. Conclusions ASCVD prediction was good in this cohort of adults aged ≥65 years. Although calibration varied by multimorbidity patterns, frailty, and competing risks, miscalibration was mostly present at high predicted risk ranges and thus less likely to alter decision making for primary prevention therapy.
| S-EPMC7727000 | biostudies-literature
Project description:BackgroundThe atherosclerosis cardiovascular disease (ASCVD) Pooled Cohort risk equations have shown different calibration across US populations with varied levels of social deprivation.Methods and resultsWe analyzed the calibration and discrimination of the Pooled Cohort risk equations by social deprivation status among 9066 REGARDS (REasons for Geographic And Racial Differences in Stroke) study participants not taking statins for whom ASCVD risk may lead to statin initiation. Patients were aged 45 to 79 years, had no ASCVD or diabetes mellitus, and had a low-density lipoprotein cholesterol level 70 to 189 mg/dL. Social deprivation was defined using 3 indicators: annual household income <$25 000, less than a high school education, and living without a partner. At baseline in 2003-2007, 54.6%, 27.4%, and 18.0% of participants had 0, 1, and 2 or 3 indicators showing deprivation, respectively. From baseline through December 2012, 457 participants developed ASCVD (nonfatal/fatal stroke, myocardial infarction, or coronary heart disease death). Predicted and observed ASCVD incidence per 1000 person-years were 8.02 and 6.23 (95% CI, 5.31-7.31), respectively, among participants with 0 indicators of deprivation (Hosmer-Lemeshow P=0.01); 8.05 and 6.61 (95% CI, 5.29-8.24), respectively, with 1 indicator (P=0.09); and 9.83 and 11.40 (95% CI, 9.23-14.05), respectively, with 2 or 3 indicators (P=0.12). The C-index (95% CI) was 0.72 (0.69-0.75), 0.73 (0.69-0.78), and 0.70 (0.65-0.75) among participants with 0, 1, and 2 or 3 indicators of deprivation, respectively. The net reclassification improvement after adding deprivation data to the Pooled Cohort risk equations was modest (0.12; 95% CI, 0.03-0.21).ConclusionsThe Pooled Cohort risk equations have good calibration among individuals with social deprivation but overestimate ASCVD risk among those with less social deprivation.
| S-EPMC5524046 | biostudies-literature
Project description:Equations predicting the risk of occurrence of cardiovascular disease (CVD) are used in primary care to identify high-risk individuals among the general population. To improve the predictive performance of such equations, we updated the Framingham general CVD 1991 and 2008 equations and the Pooled Cohort equations for atherosclerotic CVD within five years in a contemporary cohort of individuals who participated in the Austrian health-screening program from 2009-2014. The cohort comprised 1.7?M individuals aged 30-79 without documented CVD history. CVD was defined by hospitalization or death from cardiovascular cause. Using baseline and follow-up data, we recalibrated and re-estimated the equations. We evaluated the gain in discrimination and calibration and assessed explained variation. A five-year general CVD risk of 4.61% was observed. As expected, discrimination c-statistics increased only slightly and ranged from 0.73-0.79. The two original Framingham equations overestimated the CVD risk, whereas the original Pooled Cohort equations underestimated it. Re-estimation improved calibration of all equations adequately, especially for high-risk individuals. Half of the individuals were reclassified into another risk category using the re-estimated equations. Predictors in the re-estimated Framingham equations explained 7.37% of the variation, whereas the Pooled Cohort equations explained 5.81%. Age was the most important predictor.
| S-EPMC7235230 | biostudies-literature
Project description: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.
| S-EPMC6142964 | biostudies-literature
Project description:BackgroundThe cardiovascular system exhibits strong circadian rhythms to maintain normal functioning. Irregular sleep schedules, characterized by high day-to-day variability in sleep duration or timing, represent possibly milder but much more common and chronic disruption of circadian rhythms in the general population than shift work.ObjectivesThis study aimed to prospectively examine the association between sleep regularity and risk of cardiovascular disease (CVD).MethodsIn MESA (Multi-Ethnic Study of Atherosclerosis), 1,992 participants free of CVD completed 7-day wrist actigraphy for sleep assessment from 2010 to 2013 and were prospectively followed through 2016. The study assessed sleep regularity using the SD of actigraphy-measured sleep duration and sleep-onset timing across 7 days. Incident CVD included nonfatal and fatal cardiovascular events. A Cox proportional hazards model was used to estimate hazard ratios (HRs) for incident CVD according to SD of sleep duration and timing, adjusted for traditional CVD risk factors (including CVD biomarkers) and other sleep-related factors (including average sleep duration).ResultsDuring a median follow-up of 4.9 years, 111 participants developed CVD events. The multivariable-adjusted HRs (95% confidence intervals) for CVD across categories of sleep duration SD were 1.00 (reference) for ?60 min, 1.09 (0.62 to 1.92) for 61 to 90 min, 1.59 (0.91 to 2.76) for 91 to 120 min, and 2.14 (1.24 to 3.68) for >120 min (p trend = 0.002). Similarly, compared with participants with a sleep timing SD ?30 min, the HRs (95% confidence intervals) for CVD were 1.16 (0.64 to 2.13) for 31 to 60 min, 1.52 (0.81 to 2.88) for 61 to 90 min, and 2.11 (1.13 to 3.91) for >90 min (p trend = 0.002). Exclusion of current shift workers yielded similar results.ConclusionsIrregular sleep duration and timing may be novel risk factors for CVD, independent of traditional CVD risk factors and sleep quantity and/or quality.
| S-EPMC7237955 | biostudies-literature
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.
| S-EPMC7596579 | biostudies-literature
Project description:ObjectivesExamine the associations of sleep measures with kidney function changes over time among individuals from a community-based study.MethodsThe sample includes 1657 participants (287 with chronic kidney disease [CKD]) in the Multi-Ethnic Study of Atherosclerosis Sleep Cohort (mean age: 57.7 years, male: 46.0%). We examined associations between a large set of sleep variables (polysomnography, actigraphy, and questionnaires) and cardiovascular disease risk factors and changes in estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio over approximately 5 years using high-dimensional regression. We investigated the modifying effect of sleep on the associations between cardiovascular disease risk factors and kidney function.ResultsSleep metrics predicted kidney function decline only among individuals with baseline CKD. Among this group, eGFR decline was associated with decreased stage N3 sleep (0.32 mL/min/1.73 m2/y per 10% decrease in N3, p < .001); increased actigraphy napping frequency (beta: -0.20 [-0.30, -0.07]); and actigraphy sleep midpoint trajectory in early morning (ref: midnight, beta: -0.84 [-1.19, -0.50]). Urinary albumin-to-creatinine ratio increase was associated with high wake bouts trajectory (ref: low, beta: 0.97 [0.28, 1.67]) and increased sleep-related hypoxemia (oxygen saturation %time<90 [≥5%], beta: 2.17 [1.26, 3.08]). Sleep metrics--N3 sleep, naps, and midpoint trajectory--significantly modified associations between hemoglobin A1C and eGFR decline.ConclusionsReduced deep sleep, daytime napping, increased wake bouts, delayed sleep rhythms, and overnight hypoxemia are associated with longitudinal kidney function decline, with effects most apparent in individuals with CKD. Deep sleep, napping, and sleep timing modified the association between hemoglobin A1C and kidney function.
| S-EPMC9772248 | biostudies-literature
Project description:BackgroundSex-specific and race-specific pooled cohort equations (PCEs) are recommended for estimating the 10-year risk of cardiovascular disease, with an absolute risk of more than 7·5% indicating a clinical decision threshold. We compared differences between Black and White individuals in PCE-estimated absolute cardiovascular disease risk across various plausible risk factor combinations with the aim of evaluating if using the PCE might result in different clinical decisions in Black versus White individuals with identical risk profiles.MethodsWe generated in silico patient risk profiles by combining numerical risk factors (age [5-year intervals], total cholesterol [20-mg/dl intervals], HDL cholesterol [5-mg/dl intervals], systolic blood pressure [10-mm Hg intervals]) and binary risk factors (smoking, diabetes, and antihypertensive treatment). We compared PCE-estimated 10-year cardiovascular disease risk in Black versus White individuals with identical risk profiles. We did similar comparisons using eligible participants in the Framingham Heart Study (FHS) third generation cohort and the National Health and Nutrition Examination Survey (NHANES) 2017-18.FindingsFor our in silico analysis, we evaluated 29 515 risk factor combinations for women and 30 565 for men, after excluding profiles that generated 10-year cardiovascular disease risk estimates below 1% or above 30%. There were 6357 risk profiles associated with 10-year cardiovascular disease risk above 7·5% for Black men but not for White men (median risk difference [RD] 6·25%, range 0·15-22·8; median relative risk [RR] 2·40, range 1·02-12·6). There were 391 profiles with 10-year cardiovascular disease risk above 7·5% for White men but not Black men (median RD 2·68%, range 0·07-16·9%; median RR 1·42, range 1·01-3·57). There were 6543 risk profiles associated with 10-year estimated cardiovascular disease risk above 7·5% for Black women but not for White women (median RD 6·14%, range 0·35-26·8%; median RR 2·29, range 1·05-12·6). There were 318 profiles with 10-year cardiovascular disease risk above 7·5% for White women but not Black women (median RD 3·71%, range 0·22-20·1%; median RR 1·66, range 1·03-5·46). For the population-based samples, we calculated the PCE-based 10-year cardiovascular disease risk for 1272 eligible participants (378 women; median age 48 years [IQR 44-52]; 100% White) in the FHS third generation cohort and 550 participants (223 women [36·8% Black] and 327 men [40·4% Black]; median age 61 years [IQR 52-67]) in the NHANES cohort. The population-based samples showed similar risk differences to that of the in silico analyses.InterpretationThe PCE might generate substantially divergent cardiovascular disease risk estimates for Black versus White individuals with identical risk profiles, which could introduce race-related variations in clinical recommendations for cardiovascular disease prevention.FundingUS National Institutes of Health.
| S-EPMC8715354 | biostudies-literature
Project description:The American College of Cardiology/American Heart Association developed Pooled Cohort equations to estimate atherosclerotic cardiovascular disease (ASCVD) risk. It is unclear how well the equations predict ASCVD mortality in a nationally representative cohort. We used the National Health and Nutrition Examination Survey (NHANES) 1988-1994 and Linked Mortality through 2006 (n = 6,644). Among participants aged 40-79 years without ASCVD at baseline, we used Cox proportional hazard models to estimate the 10-year probability of ASCVD death by sex and race-ethnicity (non-Hispanic white (NHW), non-Hispanic black (NHB) and Mexican American (MA)). We estimated the discrimination and calibration for each sex-race-ethnicity model. We documented 288 ASCVD deaths during 62,335 person years. The Pooled Cohort equations demonstrated moderate to good discrimination for ASCVD mortality, with modified C-statistics of 0.716 (95% CI 0.663-0.770), 0.794 (0.734-0.854), and 0.733 (0.654-0.811) for NHW, NHB and MA men, respectively. The corresponding C-statistics for women were 0.781 (0.718-0.844), 0.702 (0.633-0.771), and 0.789 (CI 0.721-0.857). Modified Hosmer-Lemeshow χ2 suggested adequate calibration for NHW, NHB and MA men, and MA women (p-values: 0.128, 0.295, 0.104 and 0.163 respectively). The calibration was inadequate for NHW and NHB women (p<0.05). In this nationally representative cohort, the Pooled Cohort equations performed adequately to predict 10-year ASCVD mortality for NHW and NHB men, and MA population, but not for NHW and NHB women.
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