@article {6085, title = {Impact of blood pressure and blood pressure change during middle age on the remaining lifetime risk for cardiovascular disease: the cardiovascular lifetime risk pooling project.}, journal = {Circulation}, volume = {125}, year = {2012}, month = {2012 Jan 03}, pages = {37-44}, abstract = {

BACKGROUND: Prior estimates of lifetime risk (LTR) for cardiovascular disease (CVD) examined the impact of blood pressure (BP) at the index age and did not account for changes in BP over time. We examined how changes in BP during middle age affect LTR for CVD, coronary heart disease, and stroke.

METHODS AND RESULTS: Data from 7 diverse US cohort studies were pooled. Remaining LTRs for CVD, coronary heart disease, and stroke were estimated for white and black men and women with death free of CVD as a competing event. LTRs for CVD by BP strata and by changes in BP over an average of 14 years were estimated. Starting at 55 years of age, we followed up 61 585 men and women for 700 000 person-years. LTR for CVD was 52.5\% (95\% confidence interval, 51.3-53.7) for men and 39.9\% (95\% confidence interval, 38.7-41.0) for women. LTR for CVD was higher for blacks and increased with increasing BP at index age. Individuals who maintained or decreased their BP to normal levels had the lowest remaining LTR for CVD, 22\% to 41\%, compared with individuals who had or developed hypertension by 55 years of age, 42\% to 69\%, suggesting a dose-response effect for the length of time at high BP levels.

CONCLUSIONS: Individuals who experience increases or decreases in BP in middle age have associated higher and lower remaining LTR for CVD. Prevention efforts should continue to emphasize the importance of lowering BP and avoiding or delaying the incidence of hypertension to reduce the LTR for CVD.

}, keywords = {Aged, Aged, 80 and over, Blood Pressure, Cardiovascular Diseases, Cohort Studies, Female, Follow-Up Studies, Humans, Hypertension, Life Tables, Longitudinal Studies, Male, Middle Aged, Risk Factors}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.110.002774}, author = {Allen, Norrina and Berry, Jarett D and Ning, Hongyan and Van Horn, Linda and Dyer, Alan and Lloyd-Jones, Donald M} } @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 {1541, title = {Lifetime risks of cardiovascular disease.}, journal = {N Engl J Med}, volume = {366}, year = {2012}, month = {2012 Jan 26}, pages = {321-9}, abstract = {

BACKGROUND: The lifetime risks of cardiovascular disease have not been reported across the age spectrum in black adults and white adults.

METHODS: We conducted a meta-analysis at the individual level using data from 18 cohort studies involving a total of 257,384 black men and women and white men and women whose risk factors for cardiovascular disease were measured at the ages of 45, 55, 65, and 75 years. Blood pressure, cholesterol level, smoking status, and diabetes status were used to stratify participants according to risk factors into five mutually exclusive categories. The remaining lifetime risks of cardiovascular events were estimated for participants in each category at each age, with death free of cardiovascular disease treated as a competing event.

RESULTS: We observed marked differences in the lifetime risks of cardiovascular disease across risk-factor strata. Among participants who were 55 years of age, those with an optimal risk-factor profile (total cholesterol level, <180 mg per deciliter [4.7 mmol per liter]; blood pressure, <120 mm Hg systolic and 80 mm Hg diastolic; nonsmoking status; and nondiabetic status) had substantially lower risks of death from cardiovascular disease through the age of 80 years than participants with two or more major risk factors (4.7\% vs. 29.6\% among men, 6.4\% vs. 20.5\% among women). Those with an optimal risk-factor profile also had lower lifetime risks of fatal coronary heart disease or nonfatal myocardial infarction (3.6\% vs. 37.5\% among men, <1\% vs. 18.3\% among women) and fatal or nonfatal stroke (2.3\% vs. 8.3\% among men, 5.3\% vs. 10.7\% among women). Similar trends within risk-factor strata were observed among blacks and whites and across diverse birth cohorts.

CONCLUSIONS: Differences in risk-factor burden translate into marked differences in the lifetime risk of cardiovascular disease, and these differences are consistent across race and birth cohorts. (Funded by the National Heart, Lung, and Blood Institute.).

}, keywords = {Adult, African Americans, Aged, Cardiovascular Diseases, Cohort Effect, European Continental Ancestry Group, Female, Humans, Male, Middle Aged, Risk, Risk Assessment, Risk Factors, United States}, issn = {1533-4406}, doi = {10.1056/NEJMoa1012848}, author = {Berry, Jarett D and Dyer, Alan and Cai, Xuan and Garside, Daniel B and Ning, Hongyan and Thomas, Avis and Greenland, Philip and Van Horn, Linda and Tracy, Russell P and Lloyd-Jones, Donald M} } @article {1390, title = {Racial differences in risks for first cardiovascular events and noncardiovascular death: the Atherosclerosis Risk in Communities study, the Cardiovascular Health Study, and the Multi-Ethnic Study of Atherosclerosis.}, journal = {Circulation}, volume = {126}, year = {2012}, month = {2012 Jul 03}, pages = {50-9}, abstract = {

BACKGROUND: No studies have compared first cardiovascular disease (CVD) events and non-CVD death between races in a competing risks framework, which examines risks for numerous events simultaneously.

METHODS AND RESULTS: We used competing Cox models to estimate hazards for first CVD events and non-CVD death within and between races in 3 multicenter, National Heart, Lung, and Blood Institute-sponsored cohorts. Of 14 569 Atherosclerosis Risk in Communities (ARIC) study participants aged 45 to 64 years with mean follow-up of 10.5 years, 11.6\% had CVD and 5.0\% had non-CVD death as first events; among 4237 Cardiovascular Health Study (CHS) study participants aged 65 to 84 years and followed for 8.5 years, these figures were 43.2\% and 15.7\%, respectively. Middle-aged blacks were significantly more likely than whites to experience any CVD as a first event; this disparity disappeared by older adulthood and after adjustment for CVD risk factors. The pattern of results was similar for Multi-Ethnic Study of Atherosclerosis (MESA) participants. Traditional Cox and competing risks models yielded different results for coronary heart disease risk. Black men appeared somewhat more likely than white men to experience coronary heart disease with use of a standard Cox model (hazard ratio 1.06; 95\% CI 0.90, 1.26), whereas they appeared less likely than white men to have a first coronary heart disease event with use of a competing risks model (hazard ratio, 0.77; 95\% CI, 0.60, 1.00).

CONCLUSIONS: CVD affects blacks at an earlier age than whites; this may be attributable in part to elevated CVD risk factor levels among blacks. Racial disparities in first CVD incidence disappear by older adulthood. Competing risks analyses may yield somewhat different results than traditional Cox models and provide a complementary approach to examining risks for first CVD events.

}, keywords = {African Continental Ancestry Group, Age Factors, Aged, Aged, 80 and over, Atherosclerosis, Cardiovascular Diseases, Cohort Studies, Continental Population Groups, Ethnic Groups, European Continental Ancestry Group, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Middle Aged, Residence Characteristics, Risk Factors}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.111.057232}, author = {Feinstein, Matthew and Ning, Hongyan and Kang, Joseph and Bertoni, Alain and Carnethon, Mercedes and Lloyd-Jones, Donald M} } @article {5847, title = {Lifetime risk for heart failure among white and black Americans: cardiovascular lifetime risk pooling project.}, journal = {J Am Coll Cardiol}, volume = {61}, year = {2013}, month = {2013 Apr 09}, pages = {1510-7}, chapter = {1510}, abstract = {

OBJECTIVES: This study sought to estimate lifetime risk for heart failure (HF) by sex and race.

BACKGROUND: Prior estimates of lifetime risk for developing HF range from 20\% to 33\% in predominantly white cohorts. Short-term risks for HF appear higher for blacks than whites, but only limited comparisons of lifetime risk for HF have been made.

METHODS: Using public-release and internal datasets from National Heart, Lung, and Blood Institute-sponsored cohorts, we estimated lifetime risks for developing HF to age 95 years, with death free of HF as the competing event, among participants in the CHA (Chicago Heart Association Detection Project in Industry), ARIC (Atherosclerosis Risk in Communities), and CHS (Cardiovascular Health Study) cohorts.

RESULTS: There were 39,578 participants (33,652 [85\%] white; 5,926 [15\%] black) followed for 716,976 person-years; 5,983 participants developed HF. At age 45 years, lifetime risks for HF through age 95 years in CHA and CHS were 30\% to 42\% in white men, 20\% to 29\% in black men, 32\% to 39\% in white women, and 24\% to 46\% in black women. Results for ARIC demonstrated similar lifetime risks for HF in blacks and whites through age 75 years (limit of follow-up). Lifetime risk for HF was higher with higher blood pressure and body mass index at all ages in both blacks and whites, and did not diminish substantially with advancing index age.

CONCLUSIONS: These are among the first data to compare lifetime risks for HF between blacks and whites. Lifetime risks for HF are high and appear similar for black and white women, yet are somewhat lower for black compared with white men due to competing risks.

}, keywords = {Adolescent, Adult, African Americans, Age Factors, Aged, Anthropometry, Body Mass Index, Cardiovascular Diseases, Cohort Studies, European Continental Ancestry Group, Female, Health Surveys, Heart Failure, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Predictive Value of Tests, Prognosis, Risk Assessment, Severity of Illness Index, Sex Factors, Survival Analysis, Time Factors, United States, Young Adult}, issn = {1558-3597}, doi = {10.1016/j.jacc.2013.01.022}, author = {Huffman, Mark D and Berry, Jarett D and Ning, Hongyan and Dyer, Alan R and Garside, Daniel B and Cai, Xuan and Daviglus, Martha L 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 {7442, title = {Association of Coronary Artery Calcium Score vs Age With Cardiovascular Risk in Older Adults: An Analysis of Pooled Population-Based Studies.}, journal = {JAMA Cardiol}, year = {2017}, month = {2017 Jul 26}, abstract = {

Importance: Besides age, other discriminators of atherosclerotic cardiovascular disease (ASCVD) risk are needed in older adults.

Objectives: To examine the predictive ability of coronary artery calcium (CAC) score vs age for incident ASCVD and how risk prediction changes by adding CAC score and removing only age from prediction models.

Design, Setting, and Participants: We conducted an analysis of pooled US population-based studies, including the Framingham Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Cardiovascular Health Study. Results were compared with 2 European cohorts, the Rotterdam Study and the Heinz Nixdorf Recall Study. Participants underwent CAC scoring between 1998 and 2006 using cardiac computed tomography. The participants included adults older than 60 years without known ASCVD at baseline.

Exposures: Coronary artery calcium scores.

Main Outcomes and Measures: Incident ASCVD events including coronary heart disease (CHD) and stroke.

Results: The study included 4778 participants from 3 US cohorts, with a mean age of 70.1 years; 2582 (54.0\%) were women, and 2431 (50.9\%) were nonwhite. Over 11 years of follow-up (44 152 person-years), 405 CHD and 228 stroke events occurred. Coronary artery calcium score (vs age) had a greater association with incident CHD (C statistic, 0.733 vs 0.690; C statistics difference, 0.043; 95\% CI of difference, 0.009-0.075) and modestly improved prediction of incident stroke (C statistic, 0.695 vs 0.670; C statistics difference, 0.025; 95\% CI of difference, -0.015 to 0.064). Adding CAC score to models including traditional cardiovascular risk factors, with only age being removed, provided improved discrimination for incident CHD (C statistic, 0.735 vs 0.703; C statistics difference, 0.032; 95\% CI of difference, 0.002-0.062) but not for stroke. Coronary artery calcium score was more likely than age to provide higher category-free net reclassification improvement among participants who experienced an ASCVD event (0.390; 95\% CI, 0.312-0.467 vs 0.08; 95\% CI -0.001 to 0.181) and to result in more accurate reclassification of risk for ASCVD events among these individuals. The findings were similar in the 2 European cohorts (n = 4990).

Conclusions and Relevance: Coronary artery calcium may be an alternative marker besides age to better discriminate between lower and higher CHD risk in older adults. Whether CAC score can assist in guiding the decision to initiate statin treatment for primary prevention in older adults requires further investigation.

}, issn = {2380-6591}, doi = {10.1001/jamacardio.2017.2498}, author = {Yano, Yuichiro and O{\textquoteright}Donnell, Christopher J and Kuller, Lewis and Kavousi, Maryam and Erbel, Raimund and Ning, Hongyan and D{\textquoteright}Agostino, Ralph and Newman, Anne B and Nasir, Khurram and Hofman, Albert and Lehmann, Nils and Dhana, Klodian and Blankstein, Ron and Hoffmann, Udo and M{\"o}hlenkamp, Stefan and Massaro, Joseph M and Mahabadi, Amir-Abbas and Lima, Jo{\~a}o A C and Ikram, M Arfan and J{\"o}ckel, Karl-Heinz and Franco, Oscar H and Liu, Kiang and Lloyd-Jones, Donald and Greenland, Philip} } @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} }