Galectin-3, Metabolic Risk, and Incident Heart Failure: The ARIC Study.

BACKGROUND: It is unclear how metabolic syndrome (MetS) and diabetes affect Gal-3 (galectin 3) levels and the resulting implications for heart failure (HF) risk. We assessed relationships of MetS and diabetes with Gal-3, and their joint associations with incident HF. METHODS AND RESULTS: We included 8445 participants without HF (mean age, 63 years; 59% men; 16% Black race) at ARIC (Atherosclerosis Risk in Communities) study visit 4 (1996-1999). We categorized participants as having MetS only, MetS with diabetes, or neither, and by quartiles of MetS severity Z score. We assessed cross-sectional associations of metabolic risk categories with high Gal-3 level (≥75th percentile) using logistic regression. We used Cox regression to evaluate combined associations of metabolic risk categories and Gal-3 quartiles with HF. In cross-sectional analyses, compared with no MetS and no diabetes, MetS only (odds ratio [OR], 1.24 [95% CI, 1.10-1.41]) and MetS with diabetes (OR, 1.59 [95% CI, 1.32-1.92]) were associated with elevated Gal-3. Over a median follow-up of 20.5 years, there were 1749 HF events. Compared with individuals with neither diabetes nor MetS and with Gal-3 in the lowest quartile, the combination of MetS with diabetes and Gal-3 ≥75th percentile was associated with a 4-fold higher HF risk (hazard ratio, 4.35 [95% CI, 3.30-5.73]). Gal-3 provided HF prognostic information above and beyond MetS, NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity cardiac troponin T, and CRP (C-reactive protein) (ΔC statistic for models with versus without Gal-3: 0.003; P=0.004). CONCLUSIONS: MetS and diabetes are associated with elevated Gal-3. The HF risk significantly increased with the combination of greater metabolic risk and higher Gal-3.

Identification of Fatigue Subtypes and Their Correlates in Prevalent Heart Failure: A Secondary Analysis of the Atherosclerosis Risk in Communities Study.

BACKGROUND: Among patients with heart failure (HF), fatigue is common and linked to quality of life and functional status. Fatigue is hypothesized to manifest as multiple types, with general and exertional components. Unique subtypes of fatigue in HF may require differential assessment and treatment to improve outcomes. We conducted this study to identify fatigue subtypes in persons with prevalent HF in the ARIC study (Atherosclerosis Risk in Communities) and describe the distribution of characteristics across subtypes. METHODS: We performed a cross-sectional analysis of 1065 participants with prevalent HF at ARIC visit 5 (2011-2013). We measured exertional fatigue using the Modified Medical Research Council Breathlessness scale and general fatigue using the Patient Reported Outcomes Measurement Information System fatigue scale. We used latent class analysis to identify subtypes of fatigue. Number of classes was determined using model fit statistics, and classes were interpreted and assigned fatigue severity rating based on the conditional probability of endorsing survey items given class. We compared characteristics across classes using multinomial regression. RESULTS: Overall, participants were 54% female and 38% Black with a mean age of 77. We identified 4 latent classes (fatigue subtypes): (1) high general/high exertional fatigue (18%), (2) high general/low exertional fatigue (27%), (3) moderate general/moderate exertional fatigue (20%), and (4) low/no general and exertional fatigue (35%). Female sex, Black race, lower education level, higher body mass index, increased depressive symptoms, and higher prevalence of diabetes were associated with higher levels of general and exertional fatigue. CONCLUSIONS: We identified unique subtypes of fatigue in patients with HF who have not been previously described. Within subtype, general and exertional fatigue were mostly concordant in severity, and exertional fatigue only occurred in conjunction with general fatigue, not alone. Further understanding these fatigue types and their relationships to outcomes may enhance our understanding of the symptom experience and inform prognostication and secondary prevention efforts for persons with HF.

Performance of the pooled cohort equations in cancer survivors: the Atherosclerosis Risk in Communities study.

BACKGROUND: Cancer survivors may have elevated atherosclerotic cardiovascular disease (ASCVD) risk. Therefore, we tested how accurately the American College of Cardiology/American Heart Association 2013 pooled cohort equations (PCEs) predict 10-year ASCVD risk in cancer survivors. OBJECTIVES: To estimate the calibration and discrimination of the PCEs in cancer survivors compared to non-cancer participants in the Atherosclerosis Risk in Communities (ARIC) study. METHODS: We evaluated the PCEs' performance among 1244 cancer survivors and 3849 cancer-free participants who were free of ASCVD at the start of follow-up. Each cancer survivor was incidence-density matched with up to five controls by age, race, sex, and study center. Follow-up began at the first study visit at least 1 year after the diagnosis date of the cancer survivor and finished at the ASCVD event, death, or end of follow-up. Calibration and discrimination were assessed and compared between cancer survivors and cancer-free participants. RESULTS: Cancer survivors had higher PCE-predicted risk, at 26.1%, compared with 23.1% for cancer-free participants. There were 110 ASCVD events in cancer survivors and 332 ASCVD events in cancer-free participants. The PCEs overestimated ASCVD risk in cancer survivors and cancer-free participants by 45.6% and 47.4%, respectively, with poor discrimination in both groups (C-statistic for cancer survivors = 0.623; for cancer-free participants, C = 0.671). CONCLUSIONS: The PCEs overestimated ASCVD risk in all participants. The performance of the PCEs was similar in cancer survivors and cancer-free participants. IMPLICATIONS FOR CANCER SURVIVORS: Our findings suggest that ASCVD risk prediction tools tailored to survivors of adult cancers may not be needed.

Overweight-years and cancer risk: A prospective study of the association and comparison of predictive performance with body mass index (Atherosclerosis Risk in Communities Study).

Excess body mass index (BMI) is associated with a higher risk of at least 13 cancers, but it is usually measured at a single time point. We tested whether the overweight-years metric, which incorporates exposure time to BMI ≥25 kg/m2 , is associated with cancer risk and compared this with a single BMI measure. We used adulthood BMI readings in the Atherosclerosis Risk in Communities (ARIC) study to derive the overweight-years metric. We calculated associations between the metric and BMI and the risk of cancers using Cox proportional hazards models. Models that either included the metric or BMI were compared using Harrell's C-statistic. We included 13,463 participants, with 3,876 first primary cancers over a mean of 19 years (SD 7) of cancer follow-up. Hazard ratios for obesity-related cancers per standard deviation overweight-years were 1.15 (95% CI: 1.05-1.25) in men and 1.14 (95% CI: 1.08-1.20) in women. The difference in the C-statistic between models that incorporated BMI, or the overweight-years metric was non-significant in men and women. Overweight-years was associated with the risk of obesity-related cancers but did not outperform a single BMI measure in association performance characteristics.

Diabetes Duration and Subclinical Myocardial Injury: The Atherosclerosis Risk in Communities Study (ARIC).

BACKGROUND: Diabetes exerts adverse effects on the heart, and a longer diabetes duration is associated with greater heart failure risk. We studied diabetes duration and subclinical myocardial injury, as reflected by high-sensitivity cardiac troponin (hs-cTnT). METHODS: We analyzed 9052 participants without heart failure or coronary heart disease (mean age 63 years, 58% female, 21% Black, 15% with diabetes) at The Atherosclerosis Risk in Communities Study (ARIC) Visit 4 (1996 to 1998). Diabetes duration was calculated based on diabetes status at Visits 1 (1987 to 1989) through 4, or using self-reported age of diabetes diagnosis prior to Visit 1. We used multinomial logistic regression to determine the association of diabetes duration with increased (≥14 ng/L) or detectable (≥6 ng/L) Visit 4 hs-cTnT, relative to undetectable hs-cTnT, adjusted for demographics and cardiovascular risk factors. RESULTS: The prevalence of increased Visit 4 hs-cTnT was higher in persons with longer diabetes duration, from 12% for those with diabetes 0 to <5 years up to 31% among those with diabetes for ≥15 years (P for trend <0.0001). New onset diabetes at Visit 4 was associated with 1.92× higher relative risk (95% CI, 1.27-2.91) of increased hs-cTnT than no diabetes. Longer diabetes duration was associated with greater myocardial injury, with duration ≥15 years associated with 9.29× higher risk (95% CI, 5.65-15.29) for increased hs-cTnT and 2.07× (95% CI, 1.24-3.16) for detectable hs-cTnT, compared to no diabetes. CONCLUSIONS: Longer diabetes duration is strongly associated with subclinical myocardial injury. Interventional studies are needed to assess whether the prevention and delay of diabetes onset can mitigate early myocardial damage.

Diabetes and Progression of Heart Failure: The Atherosclerosis Risk In Communities (ARIC) Study.

BACKGROUND: The influence of diabetes on progression from preclinical heart failure (HF) stages to overt HF is poorly understood. OBJECTIVES: The purpose of this study was to characterize the influence of diabetes on the progression from preclinical HF stages (A or B based on the 2021 Universal Definition) to overt HF. METHODS: We included 4,774 adults with preclinical HF (stage A [n = 1,551] or B [n = 3,223]) who attended the ARIC (Atherosclerosis Risk In Communities) study Visit 5 (2011-2013). Within each stage (A or B), we assessed the associations of diabetes and glycemic control (hemoglobin A1C [HbA1C] <7% vs ≥7%) with progression to HF, and of cross-categories of HF stages (A vs B), diabetes, and glycemic control with incident HF. RESULTS: Among the participants (mean age 75.4 years, 58% women, 20% Black), there were 470 HF events during 8.6 years of follow-up. Stage B participants with HbA1C ≥7% experienced clinical HF at a younger age than those with controlled diabetes or without diabetes (mean age 80 years vs 83 years vs 82 years; P < 0.001). HbA1C ≥7% was more strongly associated with HF in stage B (HR: 1.83; 95% CI: 1.33-2.51) compared with stage A (HR: 1.52; 95% CI: 0.53-4.38). In cross-categories of preclinical HF stage and HbA1C, participants with stage B and HbA1C ≥7% had increased risk of HF progression compared with stage A without diabetes (HR: 7.56; 95% CI: 4.68-12.20). CONCLUSIONS: Among older adults with preclinical HF stages, uncontrolled diabetes was associated with substantial risk of HF progression. Our results suggest that targeting diabetes early in the HF process is critical.

Cardiovascular Disease Risk Among Cancer Survivors: The Atherosclerosis Risk In Communities (ARIC) Study.

BACKGROUND: More than 80% of adult patients diagnosed with cancer survive long term. Long-term complications of cancer and its therapies may increase the risk of cardiovascular disease (CVD), but prospective studies using adjudicated cancer and CVD events are lacking. OBJECTIVES: The aim of this study was to assess the risk of CVD in cancer survivors in a prospective community-based study. METHODS: We included 12,414 ARIC (Atherosclerosis Risk In Communities) study participants. Cancer diagnoses were ascertained via linkage with state registries supplemented with medical records. Incident CVD outcomes were coronary heart disease (CHD), heart failure (HF), stroke, and a composite of these. We used multivariable Poisson and Cox regressions to estimate the association of cancer with incident CVD. RESULTS: Mean age was 54 years, 55% were female, and 25% were Black. A total of 3,250 participants (25%) had incident cancer over a median 13.6 years of follow-up. Age-adjusted incidence rates of CVD (per 1,000 person-years) were 23.1 (95% CI: 24.7-29.1) for cancer survivors and 12.0 (95% CI: 11.5-12.4) for subjects without cancer. After adjustment for cardiovascular risk factors, cancer survivors had significantly higher risks of CVD (HR: 1.37; 95% CI: 1.26-1.50), HF (HR: 1.52; 95% CI: 1.38-1.68), and stroke (HR: 1.22; 95% CI: 1.03-1.44), but not CHD (HR: 1.11; 95% CI: 0.97-1.28). Breast, lung, colorectal, and hematologic/lymphatic cancers, but not prostate cancer, were significantly associated with CVD risk. CONCLUSIONS: Compared with persons without cancer, adult cancer survivors have significantly higher risk of CVD, especially HF, independent of traditional cardiovascular risk factors. There is an unmet need to define strategies for CVD prevention in this high-risk population.

Obesity, Galectin-3, and Incident Heart Failure: The ARIC Study.

Background Laboratory data suggest obesity is linked to myocardial inflammation and fibrosis, but clinical data are limited. We aimed to examine the association of obesity with galectin-3, a biomarker of cardiac inflammation and fibrosis, and the related implications for heart failure (HF) risk. Methods and Results We evaluated 8687 participants (mean age 63 years; 21% Black) at ARIC (Atherosclerosis Risk in Communities) Visit 4 (1996-1998) who were free of heart disease. We used adjusted logistic regression to estimate the association of body mass index (BMI) categories with elevated galectin-3 (≥75th sex-specific percentile) overall and across demographic subgroups, with tests for interaction. We used Cox proportional hazards models to assess the combined associations of galectin-3 and BMI with incident HF (through December 31, 2019). Higher BMI was associated with higher odds of elevated galectin-3 (odds ratio [OR], 2.32; 95% CI, 1.88-2.86) for severe obesity ([BMI ≥35 kg/m2] versus normal weight [BMI 18.5-<25 kg/m2]). There were stronger associations of BMI with elevated galectin-3 among women versus men and White versus Black participants (both P-for-interaction <0.05). Elevated galectin-3 was similarly associated with incident HF among people with and without obesity (HR, 1.49; 95% CI, 1.18-1.88; and HR, 1.71; 95% CI, 1.38-2.11, respectively). People with severe obesity and elevated galectin-3 had >4-fold higher risk of HF (HR, 4.19; 95% CI, 2.98-5.88) than those with normal weight and galectin-3 <25th percentile. Conclusions Obesity is strongly associated with elevated galectin-3. Additionally, the combination of obesity and elevated galectin-3 is associated with marked HF risk, underscoring the importance of elucidating pathways linking obesity with cardiac inflammation and fibrosis.

Heart transplantation outcomes in arrhythmogenic right ventricular cardiomyopathy: a contemporary national analysis.

AIMS: Heart failure is an increasingly recognized later stage manifestation of arrhythmogenic right ventricular cardiomyopathy (ARVC) that can require heart transplantation (HT) to appropriately treat. We aimed to study contemporary ARVC HT outcomes in a national registry. METHODS AND RESULTS: The United Network for Organ Sharing registry was queried for HT recipients from 1/1994 through 2/2020. ARVC patients were compared with non-ARVC dilated, restrictive, and hypertrophic cardiomyopathy HT patients (HT for ischaemic and valvular disease was excluded from analysis). Post-HT survival was assessed using Kaplan-Meier estimates. A total of 189 of 252 (75%) waitlisted ARVC patients (median age 48 years, 65% male) underwent HT, representing 0.3% of the total 65 559 HT during the study time period. Annual frequency of HT for ARVC increased significantly over time. ARVC patients had less diabetes (5% vs. 17%, P < 0.001), less cigarette use (15% vs. 23%, P < 0.001), lower pulmonary artery and pulmonary capillary wedge pressures, and lower cardiac output than the 33 659 non-ARVC patients (P < 0.001). Ventricular assist device use was significantly lower in ARVC patients (8% vs. 32%, P < 0.001); 1 and 5 year post-HT survival was 97% and 93% for ARVC vs. 95% and 82% for non-ARVC HT recipients (P < 0.001). On adjusted multivariable Cox regression, ARVC had decreased risk of post-HT death compared with non-ARVC aetiologies (hazard ratio 0.48, 95% confidence interval 0.28-0.82, P = 0.008). Patients with ARVC also had lower risk of death or graft failure than non-ARVC patients (hazard ratio 0.51, 95% confidence interval 0.32-0.81, P = 0.004). CONCLUSIONS: In the largest series of HT in ARVC, we found that HT is increasingly performed in ARVC, with higher survival compared with other cardiomyopathy aetiologies. The right ventricular predominant pathophysiology may require unique considerations for heart failure management, including HT.

Duration of Diabetes and Incident Heart Failure: The ARIC (Atherosclerosis Risk In Communities) Study.

OBJECTIVES: This study assessed the association of diabetes duration with incident heart failure (HF). BACKGROUND: Diabetes increases HF risk. However, the independent effect of diabetes duration on incident HF is unknown. METHODS: We included 9,734 participants (mean age 63 years, 58% women, 22% Black) at ARIC (Atherosclerosis Risk In Communities) Visit 4 (1996-1998) without HF or coronary heart disease. We calculated diabetes duration at Visit 4 (baseline), utilizing diabetes status at the first 4 ARIC visits spaced 3 years apart, and self-reported diagnosis date for those with diabetes diagnosed before Visit 1. We used Cox regression to estimate associations of diabetes duration with incident HF, accounting for intercurrent coronary heart disease and other risk factors. We performed analyses stratified by age (<65 years or ≥65 years), race, sex, and glycemic control (hemoglobin A1C [HbA1C] consistently <7%, vs HbA1C ≥7%), with tests for interaction. RESULTS: Over 22.5 years of follow-up, there were 1,968 HF events. Compared to those without diabetes, HF risk rose with longer diabetes duration, with the highest risk among those with ≥15 y diabetes duration (HR: 2.82; 95% CI: 2.25-3.63). Each 5-year increase in diabetes duration was associated with a 17% (95% CI: 11-22) relative increase in HF risk. Similar results were observed across HF subtypes. The HF and diabetes duration associations were stronger among those aged <65 years, those with HbA1C ≥7%, those with a body mass index ≥30 kg/m2, women, and Blacks (all P interactions <0.05). CONCLUSIONS: Delaying diabetes onset may augment HF prevention efforts, and therapies to improve HF outcomes might target those with long diabetes duration.

Angiotensin Receptor-Neprilysin Inhibition Improves Blood Pressure and Heart Failure Control in Left Ventricular Assist Device Patients.

Angiotensin receptor-neprilysin inhibitors (ARNIs) greatly benefit functional capacity and longevity in heart failure with reduced ejection fraction (HFrEF). Angiotensin receptor-neprilysin inhibitors remain underutilized and unstudied, however, in left ventricular assist device (LVAD) recipients, in spite of their underlying HFrEF. In this case series, we studied the feasibility and short-term efficacy of ARNI utilization in 21 LVAD patients. Angiotensin receptor-neprilysin inhibitor initiation was successful in most, resulting in significant consolidation of blood pressure (BP) medical management and marked improvements in both functional capacity and diuretic requirements. Angiotensin receptor-neprilysin inhibitors are safe, feasible, and within a short timeframe benefit BP and heart failure control in LVAD recipients.

Physical Activity and Incident Heart Failure in High-Risk Subgroups: The ARIC Study.

Background Greater physical activity (PA) is associated with lower heart failure (HF) risk. However, it is unclear whether this inverse association exists across all subgroups at high risk for HF, particularly among those with preexisting atherosclerotic cardiovascular disease. Methods and Results We followed 13 810 ARIC (Atherosclerosis Risk in Communities) study participants (mean age 55 years, 54% women, 26% black) without HF at baseline (visit 1; 1987-1989). PA was assessed using a modified Baecke questionnaire and categorized according to American Heart Association guidelines: recommended, intermediate, or poor. We constructed Cox models to estimate associations between PA categories and incident HF within each high-risk subgroup at baseline, with tests for interaction. We performed additional analyses modeling incident coronary heart disease as a time-varying covariate. Over a median of 26 years of follow-up, there were 2994 HF events. Compared with poor PA, recommended PA was associated with lower HF risk among participants with hypertension, obesity, diabetes mellitus, and metabolic syndrome (all P<0.01), but not among those with prevalent atherosclerotic cardiovascular disease (coronary heart disease, stroke, or peripheral arterial disease) (hazard ratio, 0.91; 95% CI, 0.74-1.13 [P interaction=0.02]). Recommended PA was associated with lower risk of incident coronary heart disease (hazard ratio, 0.79; 95% CI, 0.72-0.86), but not with lower HF risk in those with interim coronary heart disease events (hazard ratio, 0.90; 95% CI, 0.78-1.04 [P interaction=0.04]). Conclusions PA was associated with decreased HF risk in patients with hypertension, obesity, diabetes mellitus, and metabolic syndrome. Despite a myriad of benefits in patients with atherosclerotic cardiovascular disease, PA may have weaker associations with HF prevention after ischemic disease is established.

Safety and Utility of Cardiopulmonary Exercise Testing in Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia.

Background Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is characterized by high arrhythmic burden and progressive heart failure, which can prompt referral for heart transplantation. Cardiopulmonary exercise testing (CPET) has an established role in risk stratification for advanced heart failure therapies, but has not been described in ARVC/D. This study sought to determine the safety and prognostic utility of CPET in patients with ARVC/D. Methods and Results Using the Johns Hopkins ARVC/D Registry, we examined patients with ARVC/D undergoing CPET. Baseline characteristics and transplant-free survival were compared on the basis of peak oxygen consumption (pVO2) (≤14 or >14 mL/kg per minute) and ventilatory efficiency (Ve/VCO2 slope ≤34 or >34). Thirty-eight patients underwent 50 CPETs. There were no sustained arrhythmic events. Twenty-nine patients achieved a maximal test. Patients with pVO2 ≤14 mL/kg per minute were more often men (P=0.042) compared with patients with pVO2 >14 mL/kg per minute. Patients with Ve/VCO2 slope >34 tended to have more moderate/severe right ventricular dilation (7/9 [78%] versus 10/26 [38%]; P=0.060) and clinical heart failure (8/9 [89%] versus 13/26 [50%]; P=0.056) compared with patients with Ve/VCO2 slope ≤34. Patients who underwent heart transplantation were more likely to have clinical heart failure (10/10 [100%] versus 13/28 [46%]; P=0.003). Patients with Ve/VCO2 slope >34 had worse transplant-free survival compared with patients with Ve/VCO2 slope ≤34 (n=35; hazard ratio, 6.57 [95% CI, 1.28-33.72]; log-rank P=0.010), whereas transplant-free survival was similar on the basis of pVO2 groups (n=29; hazard ratio, 3.38 [95% CI, 0.75-15.19]; log-rank P=0.092). Conclusions CPET is safe to perform in patients with ARVC/D. Ve/VCO2 slope may be used for risk stratification and guide referral for heart transplantation in ARVC/D.

Crossing the Bridge to Heart Transplantation: Biventricular Impella to Support an Unstable LVAD Patient.

We report the first case of a patient with a durable left ventricular assist device admitted with cardiogenic shock and managed with biventricular Impella support as a successful bridge to heart transplantation. (Level of Difficulty: Advanced.).

Change in Physical Activity and Cardiac Structure over 10 Years: The Multi-Ethnic Study of Atherosclerosis.

INTRODUCTION: Physical activity (PA) is inversely associated with risk of heart failure and cardiovascular disease (CVD), whereas increased left ventricular (LV) mass and mass to volume (m:v) ratio are unfavorable CVD risk factors. We assessed whether changes in leisure time PA were associated with longitudinal changes in cardiac structure in a community-based population. METHODS: We included 2779 Multi-Ethnic Study of Atherosclerosis participants, free of baseline CVD, who had available data on PA and cardiac magnetic resonance imaging at examinations 1 (2000-2002) and 5 (2010-2012). Physical activity was measured by a Typical Week PA Survey and converted to MET-minutes per week of moderate+vigorous activity. We used linear mixed effect models to estimate the associations of baseline and change in PA with baseline and change in cardiac structure, adjusting for CVD risk factors and body size. RESULTS: At baseline, the mean age was 59 yr, 53% were women, and 58% of nonwhite race/ethnicity. During average 10-yr follow-up, and after accounting for baseline PA levels, the highest quintiles of PA increase were significantly associated with increases in LV mass (2.3 g; 95% confidence interval [CI], 0.4-4.2), LV end-diastolic volume (4.7 mL; 95% CI, 2.4-7.0), and stroke volume (3.3 mL; 95% CI, 1.6-5.1), but lower M:V ratio (-2.9; 95% CI, -5.0 to -0.8) compared with the lowest quintiles. Increasing exercise PA was associated with increases in LV diameter and reductions in M:V ratio, whereas occupational PA was associated with increases in m:v ratio. Increasing PA over 10 yr was also associated with greater risk of eccentric dilated LV hypertrophy at examination 5. CONCLUSIONS: After accounting for baseline PA, greater positive changes in leisure-time PA levels were associated with a more eccentric-type of LV remodeling pattern over 10 yr. The clinical implications of such findings remain to be determined.

The Association of Sport and Exercise Activities With Cardiovascular Disease Risk: The Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: This study assessed the independent associations between participation in self-reported sport and exercise activities and incident cardiovascular disease (CVD). METHODS: Data were from 13,204 participants in the Atherosclerosis Risk in Communities Study cohort (1987-2015). Baseline sport and exercise activities were assessed via the modified Baecke questionnaire. Incident CVD included coronary heart disease, heart failure, or stroke. Multivariable-adjusted Cox proportional hazard models assessed the association of participation in specific sport and exercise activities at enrollment with risk of CVD. RESULTS: During a median follow-up time of 25.2 years, 30% of the analytic sample (n = 3966) was diagnosed with incident CVD. In fully adjusted models, participation in racquet sports (hazard ratio [HR] 0.75; 95% confidence interval [CI], 0.61-0.93), aerobics (HR 0.75; 95% CI, 0.63-0.88), running (HR 0.68; 95% CI, 0.54-0.85), and walking (HR 0.89; 95% CI, 0.83-0.95) was significantly associated with a lower risk of CVD. There were no significant associations for bicycling, softball/baseball, gymnastics, swimming, basketball, calisthenics exercises, golfing with cart, golfing with walking, bowling, or weight training. CONCLUSIONS: Participation in specific sport and exercises may substantially reduce the risk for CVD.