@article {7356, title = {Relationship Between Physical Activity, Body Mass Index, and Risk of Heart Failure.}, journal = {J Am Coll Cardiol}, volume = {69}, year = {2017}, month = {2017 Mar 07}, pages = {1129-1142}, abstract = {

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{\textquoteright}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.

}, issn = {1558-3597}, doi = {10.1016/j.jacc.2016.11.081}, author = {Pandey, Ambarish and LaMonte, Michael and Klein, Liviu and Ayers, Colby and Psaty, Bruce M and Eaton, Charles B and Allen, Norrina B and de Lemos, James A and Carnethon, Mercedes and Greenland, Philip and Berry, Jarett D} } @article {7812, title = {The Association of Obesity and Cardiometabolic Traits With Incident~HFpEF and HFrEF.}, journal = {JACC Heart Fail}, volume = {6}, year = {2018}, month = {2018 Aug}, pages = {701-709}, abstract = {

OBJECTIVES: This study evaluated the associations of obesity and cardiometabolic traits with incident heart failure with preserved versus reduced ejection fraction (HFpEF vs. HFrEF). Given known sex differences in HF subtype, we examined men and women separately.

BACKGROUND: Recent studies suggest that obesity confers greater risk of HFpEF versus HFrEF. Contributions of associated metabolic traits to HFpEF are less clear.

METHODS: We studied 22,681 participants from 4 community-based cohorts followed for incident HFpEF versus HFrEF (ejection fraction >=50\% vs.~<50\%). We evaluated the association of body mass index (BMI) and cardiometabolic traits with incident HF subtype using Cox models.

RESULTS: The mean age was 60 {\textpm} 13 years, and 53\% were women. Over a median follow-up of 12 years, 628 developed incident HFpEF and 835 HFrEF. Greater BMI portended higher risk of HFpEF compared with HFrEF (hazard ratio [HR]: 1.34 per 1-SD increase in BMI; 95\% confidence interval [CI]: 1.24 to 1.45 vs. HR: 1.18; 95\% CI: 1.10 to 1.27). Similarly, insulin resistance (homeostatic model assessment of insulin resistance) was associated with HFpEF (HR: 1.20 per 1-SD; 95\% CI: 1.05 to 1.37), but not HFrEF (HR: 0.99; 95\% CI: 0.88 to 1.11; p~< 0.05 for difference HFpEF vs. HFrEF). We found that the differential association of BMI with HFpEF versus HFrEF was more pronounced among women (p for difference HFpEF vs. HFrEF~= 0.01) when compared with men (p~= 0.34).

CONCLUSIONS: Obesity and related cardiometabolic traits including insulin resistance are more strongly associated with risk of future HFpEF versus HFrEF. The differential risk of HFpEF with obesity seems particularly pronounced among~women and may underlie sex differences in HF subtypes.

}, issn = {2213-1787}, doi = {10.1016/j.jchf.2018.05.018}, author = {Savji, Nazir and Meijers, Wouter C and Bartz, Traci M and Bhambhani, Vijeta and Cushman, Mary and Nayor, Matthew and Kizer, Jorge R and Sarma, Amy and Blaha, Michael J and Gansevoort, Ron T and Gardin, Julius M and Hillege, Hans L and Ji, Fei and Kop, Willem J and Lau, Emily S and Lee, Douglas S and Sadreyev, Ruslan and van Gilst, Wiek H and Wang, Thomas J and Zanni, Markella V and Vasan, Ramachandran S and Allen, Norrina B and Psaty, Bruce M and van der Harst, Pim and Levy, Daniel and Larson, Martin and Shah, Sanjiv J and de Boer, Rudolf A and Gottdiener, John S and Ho, Jennifer E} } @article {7685, title = {Sex and Race Differences in Lifetime Risk of Heart Failure With Preserved Ejection Fraction and Heart Failure With Reduced Ejection Fraction.}, journal = {Circulation}, volume = {137}, year = {2018}, month = {2018 Apr 24}, pages = {1814-1823}, abstract = {

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.

}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.117.031622}, author = {Pandey, Ambarish and Omar, Wally and Ayers, Colby and LaMonte, Michael and Klein, Liviu and Allen, Norrina B and Kuller, Lewis H and Greenland, Philip and Eaton, Charles B and Gottdiener, John S and Lloyd-Jones, Donald M and Berry, Jarett D} } @article {8488, title = {Sex-Specific Associations of Cardiovascular Risk Factors and Biomarkers With Incident Heart~Failure.}, journal = {J Am Coll Cardiol}, volume = {76}, year = {2020}, month = {2020 Sep 22}, pages = {1455-1465}, abstract = {

BACKGROUND: Whether cardiovascular (CV) disease risk factors and biomarkers associate differentially with heart failure (HF) risk in men and women is unclear.

OBJECTIVES: The purpose of this study was to evaluate sex-specific associations of CV risk factors and biomarkers with incident HF.

METHODS: The analysis was performed using data from 4 community-based cohorts with 12.5 years of follow-up. Participants (recruited between 1989 and 2002) were free of HF at baseline. Biomarker measurements included natriuretic peptides, cardiac troponins, plasminogen activator inhibitor-1, D-dimer, fibrinogen, C-reactive protein, sST2, galectin-3, cystatin-C, and urinary albumin-to-creatinine ratio.

RESULTS: Among 22,756 participants (mean age 60 {\textpm} 13 years, 53\% women), HF occurred in 2,095 participants (47\% women). Age, smoking, type 2 diabetes mellitus, hypertension, body mass index, atrial fibrillation, myocardial infarction, left ventricular hypertrophy, and left bundle branch block were strongly associated with HF in both sexes (p~<~0.001), and the combined clinical model had good discrimination in men (C-statistic~=~0.80) and in women (C-statistic~=~0.83). The majority of biomarkers were strongly and similarly associated with HF in both sexes. The clinical model improved modestly after adding natriuretic peptides in men (ΔC-statistic~=~0.006; likelihood ratio chi-square~=~146; p~<~0.001), and after adding cardiac troponins in women (ΔC-statistic~=~0.003; likelihood ratio chi-square~=~73; p~<~0.001).

CONCLUSIONS: CV risk factors are strongly and similarly associated with incident HF in both sexes, highlighting the similar importance of risk factor control in reducing HF risk in the community. There are subtle sex-related differences in the predictive value of individual biomarkers, but the overall improvement in HF risk estimation when included in~a~clinical HF risk prediction model is limited in both sexes.

}, issn = {1558-3597}, doi = {10.1016/j.jacc.2020.07.044}, author = {Suthahar, Navin and Lau, Emily S and Blaha, Michael J and Paniagua, Samantha M and Larson, Martin G and Psaty, Bruce M and Benjamin, Emelia J and Allison, Matthew A and Bartz, Traci M and Januzzi, James L and Levy, Daniel and Meems, Laura M G and Bakker, Stephan J L and Lima, Jo{\~a}o A C and Cushman, Mary and Lee, Douglas S and Wang, Thomas J and deFilippi, Christopher R and Herrington, David M and Nayor, Matthew and Vasan, Ramachandran S and Gardin, Julius M and Kizer, Jorge R and Bertoni, Alain G and Allen, Norrina B and Gansevoort, Ron T and Shah, Sanjiv J and Gottdiener, John S and Ho, Jennifer E and de Boer, Rudolf A} } @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 {9000, title = {Associations of Body Mass Index and Waist Circumference in Young Adulthood with Later Life Incident Diabetes.}, journal = {J Clin Endocrinol Metab}, volume = {106}, year = {2021}, month = {2021 11 19}, pages = {e5011-e5020}, abstract = {

CONTEXT: The independent contribution of young adult exposure to overweight and obesity to later-life incident diabetes is not well studied.

OBJECTIVE: To assess the associations of exposures to elevated body mass index (BMI) and waist circumference (WC) in young adulthood (ages 18-39 years) with incident diabetes later in life (>=40 years).

DESIGN: Pooled data from 6 US prospective cohorts (Atherosclerosis Risk in Communities Study, Cardiovascular Risk Development in Young Adults Study, Cardiovascular Health Study, (4) Framingham Heart Study Offspring Cohort, (5) Health, Aging and Body Composition Study, and (6) Multi-Ethnic Study of Atherosclerosis.

SETTING: Population-based cohort studies.

PARTICIPANTS: 30 780 participants (56.1\% female, 69.8\% non-Hispanic white) without a diagnosis of diabetes by age 40.

INTERVENTIONS: We imputed BMI and WC trajectories from age 18 for every participant and estimated time-weighted average exposures to BMI or WC during young adulthood and later life.

MAIN OUTCOME MEASURE(S): Incident diabetes defined as fasting glucose >=126 mg/dL, nonfasting glucose >=200 mg/dL, or use of diabetes medications.

RESULTS: During a 9-year median follow-up, 4323 participants developed incident diabetes. Young adult BMI and WC were associated with later-life incident diabetes after controlling for later-life exposures [hazard ratios (HR) 1.99 for BMI >= 30 kg/m2 and 2.13 for WC > 88cm (women)/>102cm (men) compared to normal ranges]. Young adult homeostatic model of insulin resistance mediated 49\% and 44\% of the association between BMI and WC with later-life incident diabetes. High-density lipoproteins and triglycerides mediated a smaller proportion of these associations.

CONCLUSIONS: Elevated BMI and WC during young adulthood were independently associated with later-life incident diabetes. Insulin resistance may be a key mediator.

}, keywords = {Adolescent, Adult, Biomarkers, Body Mass Index, Diabetes Mellitus, Female, Follow-Up Studies, Humans, Male, Obesity, Overweight, Prognosis, Prospective Studies, Risk Factors, United States, Waist Circumference, Young Adult}, issn = {1945-7197}, doi = {10.1210/clinem/dgab551}, author = {Nair, Nandini and Vittinghoff, Eric and Pletcher, Mark J and Oelsner, Elizabeth C and Allen, Norrina B and Ndumele, Chiadi E and West, Nancy A and Strotmeyer, Elsa S and Mukamal, Kenneth J and Siscovick, David S and Biggs, Mary L and Laferr{\`e}re, Blandine 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} } @article {9241, title = {Multiple Prior Live Births are Associated with Cardiac Remodeling and Heart Failure Risk in Women.}, journal = {J Card Fail}, year = {2023}, month = {2023 Jan 10}, abstract = {

INTRODUCTION: Greater parity has been associated with cardiovascular disease risk, though effects on cardiac remodeling and heart failure risk remain unclear.

METHODS: We examined the association of number of live births and echocardiographic measures of cardiac structure and function in participants of the Framingham Heart Study (FHS) using multivariable linear regression. We next examined the association of parity with incident heart failure with preserved (HFpEF) or reduced (HFrEF) ejection fraction using a Fine-Gray subdistribution hazards model in a pooled analysis of n=12,635 participants of FHS, the Cardiovascular Health Study, the Multi-Ethnic Study of Atherosclerosis, and Prevention of Renal and Vascular Endstage Disease. Secondary analyses included major CVD, MI, and stroke.

RESULTS: Among n=3931 FHS participants (mean age 48 {\textpm} 13 years), higher number of live births was associated with worse LV fractional shortening (multivariable β -1.11 (0.31), p= 0.0005 in >= 5 live births vs nulliparous women) and worse cardiac mechanics including global circumferential strain and longitudinal and radial dyssynchrony (p< 0.01 for all comparing >= 5 live births vs nulliparity). When examining HF subtypes, women with >=5 live births were at higher risk of developing future HFrEF compared with nulliparous women (HR 1.93, 95\% CI 1.19-3.12, p=0.008); by contrast, a lower risk of HFpEF was observed (HR 0.58, 95\% CI 0.37-0.91, p=0.02).

CONCLUSIONS: Greater number of live births are associated with worse cardiac structure and function. While there was no association with overall HF, a higher number of live births was associated with greater risk for incident HFrEF.

}, issn = {1532-8414}, doi = {10.1016/j.cardfail.2022.12.014}, author = {Sarma, Amy A and Paniagua, Samantha M and Lau, Emily S and Wang, Dongyu and Liu, Elizabeth E and Larson, Martin G and Hamburg, Naomi M and Mitchell, Gary F and Kizer, Jorge and Psaty, Bruce M and Allen, Norrina B and Lely, A Titia and Gansevoort, Ronald T and Rosenberg, Emily and Mukamal, Kenneth and Benjamin, Emelia J and Vasan, Ramachandran S and Cheng, Susan and Levy, Daniel and de Boer, Rudolf A and Gottdiener, John S and Shah, Sanjiv J and Ho, Jennifer E} }