@article {5861, title = {Lifetime risk and years lived free of total cardiovascular disease.}, journal = {JAMA}, volume = {308}, year = {2012}, month = {2012 Nov 07}, pages = {1795-801}, abstract = {

CONTEXT: Estimates of lifetime risk for total cardiovascular disease (CVD) may provide projections of the future population burden of CVD and may assist in clinician-patient risk communication. To date, no lifetime risk estimates of total CVD have been reported.

OBJECTIVES: To calculate lifetime risk estimates of total CVD by index age (45, 55, 65, 75 years) and risk factor strata and to estimate years lived free of CVD across risk factor strata.

DESIGN, SETTING, AND PARTICIPANTS: Pooled survival analysis of as many as 905,115 person-years of data from 1964 through 2008 from 5 National Heart, Lung, and Blood Institute-funded community-based cohorts: Framingham Heart Study, Framingham Offspring Study, Atherosclerosis Risk in Communities Study, Chicago Heart Association Detection Project in Industry Study, and Cardiovascular Health Study. All participants were free of CVD at baseline with risk factor data (blood pressure [BP], total cholesterol [TC], diabetes, and smoking status) and total CVD outcome data.

MAIN OUTCOME MEASURES: Any total CVD event (including fatal and nonfatal coronary heart disease, all forms of stroke, congestive heart failure, and other CVD deaths).

RESULTS: At an index age of 45 years, overall lifetime risk for total CVD was 60.3\% (95\% CI, 59.3\%-61.2\%) for men and 55.6\% (95\% CI, 54.5\%-56.7\%) for women. Men had higher lifetime risk estimates than women across all index ages. At index ages 55 and 65 years, men and women with at least 1 elevated risk factor (BP, 140-149/90-99 mm Hg; or TC, 200-239 mg/dL; but no diabetes or smoking), 1 major risk factor, or at least 2 major risk factors (BP, >=160/100 mm Hg or receiving treatment; TC, >=240 mg/dL or receiving treatment; diabetes mellitus; or current smoking) had lifetime risk estimates to age 95 years that exceeded 50\%. Despite an optimal risk factor profile (BP, <120/80 mm Hg; TC, <180 mg/dL; and no smoking or diabetes), men and women at the index age of 55 years had lifetime risks (through 85 years of age) for total CVD of greater than 40\% and 30\%, respectively. Compared with participants with at least 2 major risk factors, those with an optimal risk factor profile lived up to 14 years longer free of total CVD.

CONCLUSIONS: Lifetime risk estimates for total CVD were high (>30\%) for all individuals, even those with optimal risk factors in middle age. However, maintenance of optimal risk factor levels in middle age was associated with substantially longer morbidity-free survival.

}, keywords = {Adult, Aged, Blood Pressure, Cardiovascular Diseases, Cohort Studies, Diabetes Mellitus, Female, Forecasting, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Morbidity, Risk, Risk Factors, Smoking}, issn = {1538-3598}, doi = {10.1001/jama.2012.14312}, author = {Wilkins, John T and Ning, Hongyan and Berry, Jarett and Zhao, Lihui and Dyer, Alan R and Lloyd-Jones, Donald M} } @article {6366, title = {Coronary heart disease risks associated with high levels of HDL cholesterol.}, journal = {J Am Heart Assoc}, volume = {3}, year = {2014}, month = {2014 Mar 13}, pages = {e000519}, abstract = {

BACKGROUND: The association between high-density lipoprotein cholesterol (HDL-C) and coronary heart disease (CHD) events is not well described in individuals with very high levels of HDL-C (>80 mg/dL).

METHODS AND RESULTS: Using pooled data from 6 community-based cohorts we examined CHD and total mortality risks across a broad range of HDL-C, including values in excess of 80 mg/dL. We used Cox proportional hazards models with penalized splines to assess multivariable, adjusted, sex-stratified associations of HDL-C with the hazard for CHD events and total mortality, using HDL-C 45 mg/dL and 55 mg/dL as the referent in men and women, respectively. Analyses included 11 515 men and 12 925 women yielding 307 245 person-years of follow-up. In men, the association between HDL-C and CHD events was inverse and linear across most HDL-C values; however at HDL-C values >90 mg/dL there was a plateau effect in the pattern of association. In women, the association between HDL-C and CHD events was inverse and linear across lower values of HDL-C, however at HDL-C values >75 mg/dL there were no further reductions in the hazard ratio point estimates for CHD. In unadjusted models there were increased total mortality risks in men with very high HDL-C, however mortality risks observed in participants with very high HDL-C were attenuated after adjustment for traditional risk factors.

CONCLUSIONS: We did not observe further reductions in CHD risk with HDL-C values higher than 90 mg/dL in men and 75 mg/dL in women.

}, keywords = {Aged, Biomarkers, Cholesterol, HDL, Coronary Disease, Female, Humans, Linear Models, Male, Middle Aged, Multivariate Analysis, Prognosis, Proportional Hazards Models, Risk Assessment, Risk Factors, Time Factors, United States, Up-Regulation}, issn = {2047-9980}, doi = {10.1161/JAHA.113.000519}, author = {Wilkins, John T and Ning, Hongyan and Stone, Neil J and Criqui, Michael H and Zhao, Lihui and Greenland, Philip and Lloyd-Jones, Donald M} } @article {8703, title = {Association of Midlife Cardiovascular Risk Factors With the Risk of Heart Failure Subtypes Later in Life.}, journal = {J Card Fail}, volume = {27}, year = {2021}, month = {2021 Apr}, pages = {435-444}, abstract = {

BACKGROUND: Independent associations between cardiovascular risk factor exposures during midlife and later life development of heart failure (HF) with preserved ejection fraction (HFpEF) versus reduced EF (HFrEF) have not been previously studied.

METHODS: We pooled data from 4 US cohort studies (Atherosclerosis Risk in Communities, Cardiovascular Health, Health , Aging and Body Composition, and Multi-Ethnic Study of Atherosclerosis) and imputed annual risk factor trajectories for body mass index, systolic and diastolic blood pressure, low-density lipoprotein and high-density lipoprotein cholesterol, and glucose starting from age 40 years. Time-weighted average exposures to each risk factor during midlife and later life were calculated and analyzed for associations with the development of HFpEF or HFrEF.

RESULTS: A total of 23,861 participants were included (mean age at first in-person visit, 61.8 {\textpm}1 0.2 years; 56.6\% female). During a median follow-up of 12 years, there were 3666 incident HF events, of which 51\% had EF measured, including 934 with HFpEF and 739 with HFrEF. A high midlife systolic blood pressure and low midlife high-density lipoprotein cholesterol were associated with HFrEF, and a high midlife body mass index, systolic blood pressure, pulse pressure, and glucose were associated with HFpEF. After adjusting for later life exposures, only midlife pulse pressure remained independently associated with HFpEF.

CONCLUSIONS: Midlife exposure to cardiovascular risk factors are differentially associated with HFrEF and HFpEF later in life. Having a higher pulse pressure during midlife is associated with a greater risk for HFpEF but not HFrEF, independent of later life exposures.

}, issn = {1532-8414}, doi = {10.1016/j.cardfail.2020.11.008}, author = {Cohen, Laura P and Vittinghoff, Eric and Pletcher, Mark J and Allen, Norrina B and Shah, Sanjiv J and Wilkins, John T and Chang, Patricia P and Ndumele, Chiadi E and Newman, Anne B and Ives, Diane and Maurer, Mathew S and Oelsner, Elizabeth C and Moran, Andrew E and Zhang, Yiyi} } @article {8788, title = {Performance of the American Heart Association/American College of Cardiology Pooled Cohort Equations to Estimate Atherosclerotic Cardiovascular Disease Risk by Self-reported Physical Activity Levels.}, journal = {JAMA Cardiol}, volume = {6}, year = {2021}, month = {2021 Jun 01}, pages = {690-696}, abstract = {

Importance: The American Heart Association/American College of Cardiology pooled cohort equations (PCEs) are used for predicting 10-year atherosclerotic cardiovascular disease (ASCVD) risk. Pooled cohort equation risk prediction capabilities across self-reported leisure-time physical activity (LTPA) levels and the change in model performance with addition of LTPA to the PCE are unclear.

Objective: To evaluate PCE risk prediction performance across self-reported LTPA levels and the change in model performance by adding LTPA to the existing PCE model.

Design, Setting, and Participants: Individual-level pooling of data from 3 longitudinal cohort studies-Atherosclerosis Risk in Communities, Multi-Ethnic Study of Atherosclerosis, and Cardiovascular Health Study-was performed. A total of 18 824 participants were stratified into 4 groups based on self-reported LTPA levels: inactive (0 metabolic equivalent of task [MET]-min/wk), less than guideline-recommended (<500 MET-min/wk), guideline-recommended (500-1000 MET-min/week), and greater than guideline-recommended (>1000 MET-min/wk). Pooled cohort equation risk discrimination was studied using the C statistic and reclassification capabilities were studied using the Greenwood Nam-D{\textquoteright}Agostino χ2 goodness-of-fit test. Change in risk discrimination and reclassification on adding LTPA to PCEs was evaluated using change in C statistic, integrated discrimination index, and categorical net reclassification index.

Main Outcomes and Measures: Adjudicated ASCVD events during 10-year follow-up.

Results: Among 18 824 participants studied, 10 302 were women (54.7\%); mean (SD) age was 57.6 (8.2) years. A total of 5868 participants (31.2\%) were inactive, 3849 (20.4\%) had less than guideline-recommended LTPA, 3372 (17.9\%) had guideline-recommended LTPA, and 5735 (30.5\%) had greater than guideline-recommended LTPA level. Higher LTPA levels were associated with a lower risk of ASCVD after adjustment for risk factors (hazard ratio [HR] per 1-SD higher LTPA, 0.91; 95\% CI, 0.86-0.96). Across LTPA groups, PCE risk discrimination (C statistic, 0.76-0.78) and risk calibration (all χ2 P > .10) was similar. Addition of LTPA to the PCE model resulted in no significant change in the C statistic (0.0005; 95\% CI, -0.0004 to 0.0015; P = .28) and categorical net reclassification index (-0.003; 95\% CI, -0.010 to 0.010; P = .95), but a minimal improvement in the integrated discrimination index (0.0008; 95\% CI, 0.0002-0.0013; P = .005) was observed. Similar results were noted when cohort-specific coefficients were used for creating the baseline model.

Conclusions and Relevance: Higher self-reported LTPA levels appear to be associated with lower ASCVD risk and increasing LTPA promotes cardiovascular wellness. These findings suggest the American Heart Association/American College of Cardiology PCEs are accurate at estimating the probability of 10-year ASCVD risk regardless of LTPA level. The addition of self-reported LTPA to PCEs does not appear to be associated with improvement in risk prediction model performance.

}, issn = {2380-6591}, doi = {10.1001/jamacardio.2021.0948}, author = {Pandey, Ambarish and Mehta, Anurag and Paluch, Amanda and Ning, Hongyan and Carnethon, Mercedes R and Allen, Norrina B and Michos, Erin D and Berry, Jarett D and Lloyd-Jones, Donald M and Wilkins, John T} }