02648nas a2200373 4500008004100000022001400041245018200055210006900237260001600306300001000322490000800332520153700340653000901877653002201886653001901908653002801927653001901955653001101974653002201985653001102007653001702018653001602035653002502051653000902076653001602085653001702101100001902118700002102137700001802158700002002176700001502196700002702211856003602238 2012 eng d a1524-453900aImpact of blood pressure and blood pressure change during middle age on the remaining lifetime risk for cardiovascular disease: the cardiovascular lifetime risk pooling project.0 aImpact of blood pressure and blood pressure change during middle c2012 Jan 03 a37-440 v1253 a

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.

10aAged10aAged, 80 and over10aBlood Pressure10aCardiovascular Diseases10aCohort Studies10aFemale10aFollow-Up Studies10aHumans10aHypertension10aLife Tables10aLongitudinal Studies10aMale10aMiddle Aged10aRisk Factors1 aAllen, Norrina1 aBerry, Jarett, D1 aNing, Hongyan1 aVan Horn, Linda1 aDyer, Alan1 aLloyd-Jones, Donald, M uhttps://chs-nhlbi.org/node/608503127nas a2200421 4500008004100000022001400041245004600055210004500101260001600146300001000162490000800172520205200180653001002232653002202242653000902264653002802273653001802301653004002319653001102359653001102370653000902381653001602390653000902406653002002415653001702435653001802452100002102470700001502491700001402506700002302520700001802543700001702561700002202578700002002600700002202620700002702642856003602669 2012 eng d a1533-440600aLifetime risks of cardiovascular disease.0 aLifetime risks of cardiovascular disease c2012 Jan 26 a321-90 v3663 a

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.).

10aAdult10aAfrican Americans10aAged10aCardiovascular Diseases10aCohort Effect10aEuropean Continental Ancestry Group10aFemale10aHumans10aMale10aMiddle Aged10aRisk10aRisk Assessment10aRisk Factors10aUnited States1 aBerry, Jarett, D1 aDyer, Alan1 aCai, Xuan1 aGarside, Daniel, B1 aNing, Hongyan1 aThomas, Avis1 aGreenland, Philip1 aVan Horn, Linda1 aTracy, Russell, P1 aLloyd-Jones, Donald, M uhttps://chs-nhlbi.org/node/154103229nas a2200541 4500008004100000022001400041245011500055210006900170260001600239300001100255490000700266520172200273653001501995653001002010653002202020653001602042653000902058653001802067653002002085653002802105653001902133653004002152653001102192653001902203653001802222653001102240653002602251653000902277653001602286653003002302653001402332653002002346653003002366653001602396653002202412653001702434653001802451653001602469100002102485700002102506700001802527700001802545700002302563700001402586700002402600700002702624856003602651 2013 eng d a1558-359700aLifetime risk for heart failure among white and black Americans: cardiovascular lifetime risk pooling project.0 aLifetime risk for heart failure among white and black Americans  c2013 Apr 09 a1510-70 v613 a

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.

10aAdolescent10aAdult10aAfrican Americans10aAge Factors10aAged10aAnthropometry10aBody Mass Index10aCardiovascular Diseases10aCohort Studies10aEuropean Continental Ancestry Group10aFemale10aHealth Surveys10aHeart Failure10aHumans10aKaplan-Meier Estimate10aMale10aMiddle Aged10aPredictive Value of Tests10aPrognosis10aRisk Assessment10aSeverity of Illness Index10aSex Factors10aSurvival Analysis10aTime Factors10aUnited States10aYoung Adult1 aHuffman, Mark, D1 aBerry, Jarett, D1 aNing, Hongyan1 aDyer, Alan, R1 aGarside, Daniel, B1 aCai, Xuan1 aDaviglus, Martha, L1 aLloyd-Jones, Donald, M uhttps://chs-nhlbi.org/node/584703009nas a2200265 4500008004100000022001400041245008800055210006900143260001600212300001400228490000700242520222800249100002102477700002102498700001702519700001702536700002002553700002202573700002202595700002302617700002402640700002202664700002102686856003602707 2017 eng d a1558-359700aRelationship Between Physical Activity, Body Mass Index, and Risk of Heart Failure.0 aRelationship Between Physical Activity Body Mass Index and Risk  c2017 Mar 07 a1129-11420 v693 a

BACKGROUND: Lower leisure-time physical activity (LTPA) and higher body mass index (BMI) are independently associated with risk of heart failure (HF). However, it is unclear if this relationship is consistent for both heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF).

OBJECTIVES: This study sought to quantify dose-response associations between LTPA, BMI, and the risk of different HF subtypes.

METHODS: Individual-level data from 3 cohort studies (WHI [Women's Health Initiative], MESA [Multi-Ethnic Study of Atherosclerosis], and CHS [Cardiovascular Health Study]) were pooled and participants were stratified into guideline-recommended categories of LTPA and BMI. Associations between LTPA, BMI, and risk of overall HF, HFpEF (ejection fraction ≥45%), and HFrEF (ejection fraction <45%) were assessed by using multivariable adjusted Cox models and restricted cubic splines.

RESULTS: The study included 51,451 participants with 3,180 HF events (1,252 HFpEF, 914 HFrEF, and 1,014 unclassified HF). In the adjusted analysis, there was a dose-dependent association between higher LTPA levels, lower BMI, and overall HF risk. Among HF subtypes, LTPA in any dose range was not associated with HFrEF risk. In contrast, lower levels of LTPA (<500 MET-min/week) were not associated with HFpEF risk, and dose-dependent associations with lower HFpEF risk were observed at higher levels. Compared with no LTPA, higher than twice the guideline-recommended minimum LTPA levels (>1,000 MET-min/week) were associated with an 19% lower risk of HFpEF (hazard ratio: 0.81; 95% confidence interval: 0.68 to 0.97). The dose-response relationship for BMI with HFpEF risk was also more consistent than with HFrEF risk, such that increasing BMI above the normal range (≥25 kg/m(2)) was associated with a greater increase in risk of HFpEF than HFrEF.

CONCLUSIONS: Our study findings show strong, dose-dependent associations between LTPA levels, BMI, and risk of overall HF. Among HF subtypes, higher LTPA levels and lower BMI were more consistently associated with lower risk of HFpEF compared with HFrEF.

1 aPandey, Ambarish1 aLaMonte, Michael1 aKlein, Liviu1 aAyers, Colby1 aPsaty, Bruce, M1 aEaton, Charles, B1 aAllen, Norrina, B1 ade Lemos, James, A1 aCarnethon, Mercedes1 aGreenland, Philip1 aBerry, Jarett, D uhttps://chs-nhlbi.org/node/735602992nas a2200277 4500008004100000022001400041245014600055210006900201260001600270300001400286490000800300520211900308100002102427700001602448700001702464700002102481700001702502700002202519700002102541700002202562700002202584700002402606700002702630700002102657856003602678 2018 eng d a1524-453900aSex and Race Differences in Lifetime Risk of Heart Failure With Preserved Ejection Fraction and Heart Failure With Reduced Ejection Fraction.0 aSex and Race Differences in Lifetime Risk of Heart Failure With  c2018 Apr 24 a1814-18230 v1373 a

BACKGROUND: Lifetime risk of heart failure has been estimated to range from 20% to 46% in diverse sex and race groups. However, lifetime risk estimates for the 2 HF phenotypes, HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF), are not known.

METHODS: Participant-level data from 2 large prospective cohort studies, the CHS (Cardiovascular Health Study) and MESA (Multiethnic Study of Atherosclerosis), were pooled, excluding individuals with prevalent HF at baseline. Remaining lifetime risk estimates for HFpEF (EF ≥45%) and HFrEF (EF <45%) were determined at different index ages with the use of a modified Kaplan-Meier method with mortality and the other HF subtype as competing risks.

RESULTS: We included 12 417 participants >45 years of age (22.2% blacks, 44.8% men) who were followed up for median duration of 11.6 years with 2178 overall incident HF events with 561 HFrEF events and 726 HFpEF events. At the index age of 45 years, the lifetime risk for any HF through 90 years of age was higher in men than women (27.4% versus 23.8%). Among HF subtypes, the lifetime risk for HFrEF was higher in men than women (10.6% versus 5.8%). In contrast, the lifetime risk for HFpEF was similar in men and women. In race-stratified analyses, lifetime risk for overall HF was higher in nonblacks than blacks (25.9% versus 22.4%). Among HF subtypes, the lifetime risk for HFpEF was higher in nonblacks than blacks (11.2% versus 7.7%), whereas that for HFrEF was similar across the 2 groups. Among participants with antecedent myocardial infarction before HF diagnosis, the remaining lifetime risks for HFpEF and HFrEF were up to 2.5-fold and 4-fold higher, respectively, compared with those without antecedent myocardial infarction.

CONCLUSIONS: Lifetime risks for HFpEF and HFrEF vary by sex, race, and history of antecedent myocardial infarction. These insights into the distribution of HF risk and its subtypes could inform the development of targeted strategies to improve population-level HF prevention and control.

1 aPandey, Ambarish1 aOmar, Wally1 aAyers, Colby1 aLaMonte, Michael1 aKlein, Liviu1 aAllen, Norrina, B1 aKuller, Lewis, H1 aGreenland, Philip1 aEaton, Charles, B1 aGottdiener, John, S1 aLloyd-Jones, Donald, M1 aBerry, Jarett, D uhttps://chs-nhlbi.org/node/768505208nas a2200541 4500008004100000022001400041245012300055210006900178260001500247300001300262490000600275520365800281653001003939653000903949653002003958653002803978653001904006653002404025653001104049653001104060653002504071653000904096653001604105653003204121653002404153653002004177653001704197100001704214700002104231700002004252700002704272700002204299700002304321700001704344700002404361700002304385700002304408700001804431700002304449700002704472700002104499700001904520700002704539700002104566700002304587700002004610856003604630 2020 eng d a2574-380500aPerformance of the Pooled Cohort Equations to Estimate Atherosclerotic Cardiovascular Disease Risk by Body Mass Index.0 aPerformance of the Pooled Cohort Equations to Estimate Atheroscl c2020 10 01 ae20232420 v33 a

Importance: 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.

Objective: To assess performance of the PCE across clinical BMI categories.

Design, Setting, and Participants: 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.

Exposures: 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).

Main Outcomes and Measures: 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.

Results: 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.

Conclusions and Relevance: 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.

10aAdult10aAged10aBody Mass Index10aCardiovascular Diseases10aCohort Studies10aCorrelation of Data10aFemale10aHumans10aLongitudinal Studies10aMale10aMiddle Aged10aProportional Hazards Models10aProspective Studies10aRisk Assessment10aRisk Factors1 aKhera, Rohan1 aPandey, Ambarish1 aAyers, Colby, R1 aCarnethon, Mercedes, R1 aGreenland, Philip1 aNdumele, Chiadi, E1 aNambi, Vijay1 aSeliger, Stephen, L1 aChaves, Paulo, H M1 aSafford, Monika, M1 aCushman, Mary1 aXanthakis, Vanessa1 aVasan, Ramachandran, S1 aMentz, Robert, J1 aCorrea, Adolfo1 aLloyd-Jones, Donald, M1 aBerry, Jarett, D1 ade Lemos, James, A1 aNeeland, Ian, J uhttps://chs-nhlbi.org/node/862604049nas a2200253 4500008004100000022001400041245020400055210006900259260001600328300001200344490000600356520318300362100002103545700001803566700001903584700001803603700002703621700002203648700002003670700002103690700002703711700002103738856003603759 2021 eng d a2380-659100aPerformance of the American Heart Association/American College of Cardiology Pooled Cohort Equations to Estimate Atherosclerotic Cardiovascular Disease Risk by Self-reported Physical Activity Levels.0 aPerformance of the American Heart AssociationAmerican College of c2021 Jun 01 a690-6960 v63 a

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'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.

1 aPandey, Ambarish1 aMehta, Anurag1 aPaluch, Amanda1 aNing, Hongyan1 aCarnethon, Mercedes, R1 aAllen, Norrina, B1 aMichos, Erin, D1 aBerry, Jarett, D1 aLloyd-Jones, Donald, M1 aWilkins, John, T uhttps://chs-nhlbi.org/node/8788