High Throughput Plasma Proteomics and Risk of Heart Failure and Frailty in Late Life.

Importance: Heart failure (HF) and frailty frequently coexist and may share a common pathobiology, although the underlying mechanisms remain unclear. Understanding these mechanisms may provide guidance for preventing and treating both conditions. Objective: To identify shared pathways between incident HF and frailty in late life using large-scale proteomics. Design, Setting, and Participants: In this cohort study, 4877 aptamers (Somascan v4) were measured among participants in the community-based longitudinal Atherosclerosis Risk In Communities (ARIC) cohort study at visit 3 (V3; 1993-1995; n = 10 638) and at visit 5 (V5; 2011-2013; n = 3908). Analyses were externally replicated among 3189 participants in the Cardiovascular Health Study (CHS). Data analysis was conducted from February 2022 to June 2023. Exposures: Protein aptamers, measured at study V3 and V5. Main Outcomes and Measures: Outcomes assessed included incident HF hospitalization after V3 and after V5, prevalent frailty at V5, and incident frailty between V5 and visit 6 (V6; 2016-2017; n = 4131). Frailty was assessed using the Fried criteria. Analyses were adjusted for age, gender, race, field center, hypertension, diabetes, smoking status, body mass index, estimated glomerular filtration rate, prevalent coronary heart disease, prevalent atrial fibrillation, and history of myocardial infarction. Mendelian randomization (MR) analysis was performed to assess potential causal effects of candidate proteins on HF and frailty. Results: A total of 4877 protein aptamers were measured among 10 638 participants at V3 (mean [SD] age, 60 [6] years; 4886 [46%] men). Overall, 286 proteins were associated with incident HF after V3 (822 events; P < 1.0 × 10-5), 83 of which were also associated with incident after V5 (336 events; P < 1.7 × 10-4). Among HF-free participants at V5 (n = 3908; mean [SD] age, 75 [5] years; 1861 [42%] men), 48 of 83 HF-associated proteins were associated with prevalent frailty (223 cases; P < 6.0 × 10-4), 18 of which were also associated with incident frailty at V6 (152 cases; P < 1.0 × 10-3). These proteins enriched fibrosis and inflammation pathways and demonstrated stronger associations with incident HF with preserved ejection fraction (HFpEF) than HF with reduced ejection fraction. All 18 proteins were associated with both prevalent frailty and incident HF in CHS. MR identified potential causal effects of several proteins on frailty and HF. Conclusions and Relevance: In this study, the proteins associated with risk of HF and frailty enrich for pathways related to inflammation and fibrosis as well as risk of HFpEF. Several of these proteins could potentially contribute to the shared pathophysiology of frailty and HF.

Chronic Kidney Disease, Heart Failure, and Adverse Cardiac Remodeling in Older Adults: The ARIC Study.

BACKGROUND: The associations of kidney dysfunction and damage with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), as well as adverse cardiac remodeling, in late-life remain incompletely understood. OBJECTIVES: The authors sought to define the associations between kidney dysfunction and damage and incident HFrEF and HFpEF and cardiac structure and function in late-life. METHODS: This study included 5,170 adults initially free of a heart failure (HF) diagnosis who had estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) measured at visit 5 (2011-2013) of the ARIC (Atherosclerosis Risk In Communities) study. Multivariable Cox proportional hazards models were used to estimate the associations of eGFR and UACR with incident HF, HFrEF, and HFpEF through 2019. Multivariable linear regression models were used to investigate the associations of eGFR and UACR at visit 5 with changes in cardiac structure and function between visits 5 and 7 in 2,313 participants with available echocardiograms. RESULTS: The mean age of participants was 76 ± 5 years, and 2,225 (43%) were men. The mean eGFR and median UACR were 66 ± 18 mL/min/1.73 m2 and 11 mg/g (25th, 75th percentile: 6, 22 mg/g), respectively. In fully adjusted models, both lower eGFR and higher UACR were associated with greater risk of any HF, HFrEF, and HFpEF. Lower eGFR was associated with larger increases in left ventricular end-diastolic volume index and worsening of diastolic measures. UACR did not associate with changes in cardiac structure or function. CONCLUSIONS: Mild to moderate kidney dysfunction and damage associate with incident HF and adverse cardiac remodeling in late-life.

Coronary Artery Disease and Heart Failure With Preserved Ejection Fraction: The ARIC Study.

Background Whether coronary artery disease (CAD) is a significant risk factor for heart failure (HF) with preserved ejection fraction (HFpEF) is unclear. Methods and Results Among 9902 participants in the ARIC (Atherosclerosis Risk in Communities) study, we assessed the association of incident CAD with subsequent incident HFpEF (left ventricular ejection fraction [≥50%]) and HF with reduced ejection fraction (HFrEF; left ventricular ejection fraction <50%) using survival models with time-updated variables. We also assessed the extent to which echocardiographic correlates of prevalent CAD account for the relationship between CAD and incident HFpEF. Over 13-year follow-up, incident CAD developed in 892 participants and 178 subsequently developed HF (86 HFrEF, 71 HFpEF). Incident HFrEF and HFpEF risk were both greatest early after the CAD event. At >1 year post-CAD event, adjusted incidence of HFrEF and HFpEF were similar (7.2 [95% CI, 5.2-10.0] and 6.7 [4.8-9.2] per 1000 person-years, respectively) and CAD remained predictive of both (HFrEF: hazard ratio, 2.76 [95% CI, 1.99-3.84]; HFpEF: 1.85 [1.35-2.54]) after adjusting for demographics and common comorbidities. Among 4779 HF-free participants at Visit 5 (2011-2013), the 490 with prevalent CAD had lower left ventricular ejection fraction and higher left ventricular mass index, E/e', and left atrial volume index (all P<0.01). The association of prevalent CAD with incident HFpEF post-Visit 5 was not significant after adjusting for echocardiographic measures, with the greatest attenuation observed for left ventricular diastolic function. Conclusions CAD is a significant risk factor for incident HFpEF after adjustment for demographics and common comorbidities. This relationship is partially accounted for by echocardiographic alterations, particularly left ventricular diastolic function.

Race- and Gender-Based Differences in Cardiac Structure and Function and Risk of Heart Failure.

BACKGROUND: Although heart failure (HF) risk and cardiac structure/function reportedly differ according to race and gender, limited data exist in late life when risk of HF is highest. OBJECTIVES: The goal of this study was to evaluate race/gender-based differences in HF risk factors, cardiac structure/function, and incident HF in late life. METHODS: This analysis included 5,149 HF-free participants from ARIC (Atherosclerosis Risk In Communities), a prospective epidemiologic cohort study, who attended visit 5 (2011-2013) and underwent echocardiography. Participants were subsequently followed up for a median 5.5 years for incident HF/death. RESULTS: Patients' mean age was 75 ± 5 years, 59% were women, and 20% were Black. Male gender and Black race were associated with lower mean left ventricular ejection fraction. Black race was also associated with greater left ventricular wall thickness and concentricity, differences that persisted after adjusting for cardiovascular comorbidities. After adjusting for cardiovascular comorbidities, men were at higher risk for HF and heart failure with reduced ejection fraction (HFrEF) in Black participants compared with White participants (HF: HR of 2.36 [95% CI: 1.37-4.08] vs 1.16 [95% CI: 0.89-1.51], interaction P = 0.016; HFrEF: HR of 3.70 [95% CI: 1.72-7.95] vs 1.55 [95% CI: 1.01-2.37] respectively, interaction P = 0.039). Black race was associated with a higher incidence of HF overall and HFrEF in men only (HF: 1.65 [95% CI: 1.07-2.53] vs 0.76 [95% CI: 0.49-1.17]; HFrEF: HR of 2.55 [95% CI: 1.46-4.44] vs 0.91 [95% CI: 0.46-1.83]). No race/gender-based differences were observed in risk of incident heart failure with preserved ejection fraction. CONCLUSIONS: Among older persons free of HF, men and Black participants exhibit worse systolic performance and are at heightened risk for HFrEF, whereas the risk of heart failure with preserved ejection fraction is similar across gender and race groups.

Associations of Cardiac Mechanics With Exercise Capacity: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Lower exercise capacity, as measured by 6-minute walk distance (6MWD), is associated with incident heart failure (HF). Among those without HF, the associations of measures of cardiac function with 6MWD are unclear, and may provide insight regarding the risk of incident HF. OBJECTIVES: The purpose of this study was to understand the relationships between cardiac function and exercise capacity. METHODS: This study evaluated the associations of cardiac mechanics with 6MWD in the sixth examination of the Multi-Ethnic Study of Atherosclerosis. Echocardiography (2-dimensional, Doppler, and speckle-tracking) was performed at rest and after passive leg raise to evaluate functional reserve after intravascular volume challenge. RESULTS: Of 2,096 participants without HF (mean age 73 years, 48% men, 58% non-White), individuals with lower (worse) left atrial (LA) reservoir strain were older and had higher blood pressure. Lower resting LA reservoir strain (ß coefficient per SD decrease: -5.0; 95% confidence interval [CI]: -8.8 to -1.3 m; p = 0.009), inability to augment LA reservoir strain after passive leg raise (ß coefficient per SD decrease: -5.8; 95% CI: -9.1 to -2.5 m; p < 0.001), and lower right atrial reservoir strain (ß coefficient per SD decrease: -4.4; 95% CI: -7.8 to -1.1 m; p = 0.01) were associated with shorter 6MWD. Worse left ventricular (LV) diastolic function was also associated with lower 6MWD. There were no independent associations of measures of LV systolic function (global longitudinal strain, circumferential strain, ejection fraction) with 6MWD. CONCLUSIONS: Among individuals without HF, worse biatrial function, lack of LA functional reserve, and worse LV diastolic function were associated with reduced submaximal exercise capacity. Therapies aimed to improve these functional domains may increase exercise capacity and prevent HF.

Association of Sickle Cell Trait With Incidence of Coronary Heart Disease Among African American Individuals.

Importance: The incidence of and mortality from coronary heart disease (CHD) are substantially higher among African American individuals compared with non-Hispanic White individuals, even after adjusting for traditional factors associated with CHD. The unexplained excess risk might be due to genetic factors related to African ancestry that are associated with a higher risk of CHD, such as the heterozygous state for the sickle cell variant or sickle cell trait (SCT). Objective: To evaluate whether there is an association between SCT and the incidence of myocardial infarction (MI) or composite CHD outcomes in African American individuals. Design, Setting, and Participants: This cohort study included 5 large, prospective, population-based cohorts of African American individuals in the Women's Health Initiative (WHI) study, the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, the Multi-Ethnic Study of Atherosclerosis (MESA), the Jackson Heart Study (JHS), and the Atherosclerosis Risk in Communities (ARIC) study. The follow-up periods included in this study were 1993 and 1998 to 2014 for the WHI study, 2003 to 2014 for the REGARDS study, 2002 to 2016 for the MESA, 2002 to 2015 for the JHS, and 1987 to 2016 for the ARIC study. Data analysis began in October 2013 and was completed in October 2020. Exposures: Sickle cell trait status was evaluated by either direct genotyping or high-quality imputation of rs334 (the sickle cell variant). Participants with sickle cell disease and those with a history of CHD were excluded from the analyses. Main Outcomes and Measures: Incident MI, defined as adjudicated nonfatal or fatal MI, and incident CHD, defined as adjudicated nonfatal MI, fatal MI, coronary revascularization procedures, or death due to CHD. Cox proportional hazards regression models were used to estimate the hazard ratio for incident MI or CHD comparing SCT carriers with noncarriers. Models were adjusted for age, sex (except for the WHI study), study site or region of residence, hypertension status or systolic blood pressure, type 1 or 2 diabetes, serum high-density lipoprotein level, total cholesterol level, and global ancestry (estimated from principal components analysis). Results: A total of 23 197 African American men (29.8%) and women (70.2%) were included in the combined sample, of whom 1781 had SCT (7.7% prevalence). Mean (SD) ages at baseline were 61.2 (6.9) years in the WHI study (n = 5904), 64.0 (9.3) years in the REGARDS study (n = 10 714), 62.0 (10.0) years in the MESA (n = 1556), 50.3 (12.0) years in the JHS (n = 2175), and 53.2 (5.8) years in the ARIC study (n = 2848). There were no significant differences in the distribution of traditional factors associated with cardiovascular disease by SCT status within cohorts. A combined total of 1034 participants (76 with SCT) had incident MI, and 1714 (137 with SCT) had the composite CHD outcome. The meta-analyzed crude incidence rate of MI did not differ by SCT status and was 3.8 per 1000 person-years (95% CI, 3.3-4.5 per 1000 person-years) among those with SCT and 3.6 per 1000 person-years (95% CI, 2.7-5.1 per 1000 person-years) among those without SCT. For the composite CHD outcome, these rates were 7.3 per 1000 person-years (95% CI, 5.5-9.7 per 1000 person-years) among those with SCT and 6.0 per 1000 person-years (95% CI, 4.9-7.4 per 1000 person-years) among those without SCT. Meta-analysis of the 5 study results showed that SCT status was not significantly associated with MI (hazard ratio, 1.03; 95% CI, 0.81-1.32) or the composite CHD outcome (hazard ratio, 1.16; 95% CI, 0.92-1.47). Conclusions and Relevance: In this cohort study, there was not an association between SCT and increased risk of MI or CHD in African American individuals. These disorders may not be associated with sickle cell trait-related sudden death in this population.

Common mechanistic pathways in cancer and heart failure. A scientific roadmap on behalf of the Translational Research Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC).

The co-occurrence of cancer and heart failure (HF) represents a significant clinical drawback as each disease interferes with the treatment of the other. In addition to shared risk factors, a growing body of experimental and clinical evidence reveals numerous commonalities in the biology underlying both pathologies. Inflammation emerges as a common hallmark for both diseases as it contributes to the initiation and progression of both HF and cancer. Under stress, malignant and cardiac cells change their metabolic preferences to survive, which makes these metabolic derangements a great basis to develop intersection strategies and therapies to combat both diseases. Furthermore, genetic predisposition and clonal haematopoiesis are common drivers for both conditions and they hold great clinical relevance in the context of personalized medicine. Additionally, altered angiogenesis is a common hallmark for failing hearts and tumours and represents a promising substrate to target in both diseases. Cardiac cells and malignant cells interact with their surrounding environment called stroma. This interaction mediates the progression of the two pathologies and understanding the structure and function of each stromal component may pave the way for innovative therapeutic strategies and improved outcomes in patients. The interdisciplinary collaboration between cardiologists and oncologists is essential to establish unified guidelines. To this aim, pre-clinical models that mimic the human situation, where both pathologies coexist, are needed to understand all the aspects of the bidirectional relationship between cancer and HF. Finally, adequately powered clinical studies, including patients from all ages, and men and women, with proper adjudication of both cancer and cardiovascular endpoints, are essential to accurately study these two pathologies at the same time.

Association of Left Atrial Enlargement and Atrial Fibrillation With Cognitive Function and Decline: The ARIC-NCS.

Background Atrial fibrillation (AF) is associated with cognitive decline. Whether left atrial enlargement (LAE), a critical substrate for AF, is also associated is less well established. Therefore, we assessed the association of LAE and AF with cognitive decline in the ARIC-NCS (Atherosclerosis Risk in Communities Neurocognitive Study). Methods and Results Participants (n=3391; mean age, 75±5 years; 59% women) underwent cognitive tests and 2-dimensional echocardiograms at visit 5 (2011-2013) and follow-up cognitive tests at visit 6 (2016-2017). LAE was defined as left atrium volume index ≥34 mL/m2. AF was ascertained using study ECGs and hospitalization discharge codes. We assessed the association of AF and LAE with (a) cognitive domain scores at visit 5 and (b) cognitive domain score changes between visit 5 and visit 6. At visit 5, compared with the reference group (without AF, normal left atrium), participants with LAE and AF had significantly lower global cognition (Z score, -0.24; 95% CI, -0.38 to -0.10), whereas participants with AF and without LAE and participants with LAE and without AF did not have lower global cognition. In longitudinal analysis, compared with the reference group, participants with AF but without LAE had significantly greater decline in global cognition (Z score, -0.13; 95% CI, -0.21 to -0.06). However, LAE, with or without AF, was not associated with greater cognitive decline. Conclusion Although LAE with AF was significantly associated with lower cognitive function in cross-sectional analysis, LAE, with or without AF, was not associated with greater cognitive decline over 5 years, highlighting the importance of evaluating longitudinal cognitive function. Future studies should have longer follow-up and evaluate left atrium function.

Association Between Statin Use and Sex Hormone in the Multi-Ethnic Study of Atherosclerosis Cohort.

PURPOSE: Based on the 2018 American College of Cardiology/American Heart Association cholesterol guidelines, the number of individuals eligible for statin therapy to reduce atherosclerotic cardiovascular disease risk has greatly expanded. Statins inhibit cholesterol biosynthesis, which can impair gonadal steroidogenesis. We evaluated the effect of statins on endogenous sex hormones in a large epidemiological study. METHODS: A total of 6814 Multi-Ethnic Study of Atherosclerosis (MESA) participants underwent the baseline examination. Of these, 6171 had measurements of serum sex hormones available: dehydroepiandrosterone (DHEA), SHBG, estradiol, and total and bioavailable testosterone. Multivariable linear regression models were used to assess the relationship of statin use with each sex hormone. RESULTS: A total of 345 women (17.4%) and 464 men (14.7%) were statin users (mean age, 67 years; 41% white, 29% black, 11% Chinese, and 19% Hispanic). Among the users vs nonusers of statins, the mean SHBG was 3.54 nmol/L (P < 0.01) lower in women and 3.37 nmol/L (P < 0.001) lower in men; the mean DHEA was 1.06 nmol/L (P < 0.05) lower in women and 0.70 nmol/L (P < 0.01) lower in men, after adjustment for potential confounders. With further propensity score adjustment, the mean DHEA and SHBG levels were 0.67 nmol/L (P < 0.05) and 3.49 nmol/L (P < 0.001) lower, respectively, for statin users vs nonusers. No statistically significant association was noted between estradiol, total testosterone, and bioavailable testosterone and statin use. CONCLUSION: Statin users have lower levels of SHBG and DHEA. This is especially relevant owing to the increasing use of statin therapy.

Arterial elasticity as a risk factor for early cardiovascular disease among testicular cancer survivors treated with platinum-based chemotherapy: a cross-sectional pilot study.

PURPOSE: Testicular cancer survivors who have received platinum-based chemotherapy are at risk for premature cardiovascular disease. The etiology of this risk is not well understood. This pilot study explores the impact of platinum-based chemotherapy on endothelial function. METHODS: Testicular cancer survivors <30 years old at the time of diagnosis who received platinum-based chemotherapy between 2002 and 2012, as well as 17 similarly aged male controls, were identified. Consented subjects underwent vascular assessment using the HDI/PulseWave CR-2000 Cardiovascular Profiling System and the Endo-PAT2000 system. Biomarkers and functional test markers were compared among cases, controls, and a group of historical controls using two sided two-sampled t-tests and Wilcoxon rank-sum tests. RESULTS: Thirteen survivors with a median age of 30.2 years and body mass index of 27.3 were enrolled, along with 17 healthy controls with a median age of 27.1 years and body mass index of 24.8. Median time from chemotherapy was 4.7 (range: 0.8-14) years. There was no statistical difference in reactive hyperemia peripheral arterial tonometry ratio between cases and controls (p = 0.574). There was no statistical difference in small or large artery elasticity between cases and controls (p = 0.086) or between cases and historical controls (p = 0.729). There was also no statistical difference in the blood levels of circulating endothelial cells, von Willebrand factor, and vascular cell adhesion molecules. There was a trend toward increased metabolic syndrome in cases (15%) as compared to recruited controls (6%), though this difference was not statistically significant (p = 0.565). CONCLUSION: Testicular cancer survivors have no clinically significant difference in endothelial function compared to controls 4 years after the completion of chemotherapy. Further research is needed to explore the secondary modifiable causes that may contribute to the risk of premature cardiovascular disease.

Trends in Hospitalizations and Survival of Acute Decompensated Heart Failure in Four US Communities (2005-2014): ARIC Study Community Surveillance.

BACKGROUND: Community trends of acute decompensated heart failure (ADHF) in diverse populations may differ by race and sex. METHODS: The ARIC study (Atherosclerosis Risk in Communities) sampled heart failure-related hospitalizations (≥55 years of age) in 4 US communities from 2005 to 2014 using International Classification of Diseases, Ninth Revision, Clinical Modification codes. ADHF hospitalizations were validated by standardized physician review and computer algorithm, yielding 40 173 events after accounting for sampling design (unweighted n=8746). RESULTS: Of the ADHF hospitalizations, 50% had reduced ejection fraction, and 39% had preserved EF (HFpEF). HF with reduced ejection fraction was more common in black men and white men, whereas HFpEF was most common in white women. Average age-adjusted rates of ADHF were highest in blacks (38.1 per 1000 black men, 30.5 per 1000 black women), with rates differing by HF type and sex. ADHF rates increased over the 10 years (average annual percentage change: black women +4.3%, black men +3.7%, white women +1.9%, white men +2.6%), mostly reflecting more acute HFpEF. Age-adjusted 28-day and 1-year case fatality proportions were ≈10% and 30%, respectively, similar across race-sex groups and HF types. Only blacks showed decreased 1-year mortality over time (average annual percentage change: black women -5.4%, black men -4.6%), with rates differing by HF type (average annual percentage change: black women HFpEF -7.1%, black men HF with reduced ejection fraction -4.7%). CONCLUSIONS: Between 2005 and 2014, trends in ADHF hospitalizations increased in 4 US communities, primarily driven by acute HFpEF. Survival at 1 year was poor regardless of EF but improved over time for black women and black men.

Cardiac safety profile of patients receiving high cumulative doses of pegylated-liposomal doxorubicin: use of left ventricular ejection fraction is of unproven value.

PURPOSE: One of the great conundrums for both oncologists and cardiologists is how to best monitor the potential and actual cardiotoxicity of doxorubicin. Pegylated-liposomal doxorubicin (PLD) has a safer cardiotoxicity profile than bolus administration of doxorubicin. Although ejection fraction (EF) is commonly performed to monitor doxorubicin-induced cardiotoxicity, evidence for its predictive utility is limited. We examined the incidence of doxorubicin-induced heart failure (HF) in patients who received a large cumulative dose of doxorubicin as PLD and its relation to EF and HF. METHODS: A retrospective chart review of patients who received a large cumulative dose of PLD, sometimes after previous free doxorubicin treatment, was performed to examine the incidence of doxorubicin-induced heart failure (HF) and its relation to EF and development of HF. RESULTS: No definite doxorubicin-induced clinical HF was observed among 56 patients (median age 54; 15-93) who received a cumulative doxorubicin dose (free + PLD) of >450 mg/m2. Of these, 49 received >500 mg/m2, 28 > 700 mg/m2, 19 > 800 mg/m2, 14 > 1000 mg/m2, and 5 > 1400 mg/m2. The EF varied greatly over time in some patients treated with PLD in the absence of symptoms or signs of heart failure, and was not particularly useful in making decisions regarding further dosing. CONCLUSIONS: Pegylated-liposomal doxorubicin was associated with a low risk of doxorubicin-induced HF in a retrospective cohort of patients receiving large cumulative doses of doxorubicin and long-term follow-up. EF did not predict doxorubicin-induced cardiotoxicity in our cohort of adult patients receiving PLD. Given the lack of prognostic clarity regarding modest EF changes, regular EF monitoring may not be warranted, at least when PLD is used in adults. Modest changes in EF should probably not be used to limit a patient's access to PLD, but may warrant cardiology consultation for long-term follow-up after completion of therapy.

Race-Related Differences in Left Ventricular Structural and Functional Remodeling in Response to Increased Afterload: The ARIC Study.

OBJECTIVES: The aim of this study was to evaluate racial differences in arterial elastance (Ea), which reflects the arterial afterload faced by the left ventricle, and its associations with cardiac structure and function. The hypothesis under study was that the left ventricle in blacks displays heightened afterload sensitivity compared with whites. BACKGROUND: Chronic increasing in arterial afterload may be an important trigger for left ventricular (LV) remodeling and dysfunction that lead to heart failure. Racial differences in the predisposition to heart failure are well described, but the underlying mechanisms remain unclear. METHODS: In total, 5,727 community-based, older ARIC (Atherosclerosis Risk In Community) study participants (22% black) who underwent echocardiography between 2011 and 2013 were studied. RESULTS: Blacks were younger (mean age 75 ± 5 years vs. 76 ± 5 years), were more frequently female (66% vs. 57%), and had higher prevalence rates of obesity (46% vs. 31%), hypertension (94% vs. 80%), and diabetes mellitus (47% vs. 34%) than whites. Adjusting for these baseline differences, Ea was higher among blacks (1.96 ± 0.01 mm Hg/ml vs. 1.80 ± 0.01 mm Hg/ml). In blacks, Ea was associated with greater LV remodeling (LV mass index, ß = 3.21 ± 0.55 g/m2, p < 0.001) and higher LV filling pressures (E/e' ratio, ß = 0.42 ± 0.11, p < 0.001). These relationships were not observed in whites (LV mass, ß = 0.16 ± 0.32 g/m2, p = 0.61, p for interaction <0.001; E/e' ratio, ß = -0.32 ± 0.06, p < 0.001, p for interaction <0.001). CONCLUSIONS: These community-based data suggest that black Americans display heightened afterload sensitivity as a stimulus for LV structural and functional remodeling, which may contribute to their greater risk for heart failure compared with white Americans.

Echocardiographic Predictors of Sudden Cardiac Death: The Atherosclerosis Risk in Communities Study and Cardiovascular Health Study.

BACKGROUND: This study assessed the echocardiographic predictors of sudden cardiac death (SCD) within 2 population-based cohorts. METHODS AND RESULTS: Echocardiograms were obtained on 2383 participants (1993-1995) from the ARIC study (Atherosclerosis Risk in Communities; 100% black) and 5366 participants (1987-1989 and 1994-1995) from the CHS (Cardiovascular Health Study). The main outcome was physician-adjudicated SCD. We used Cox proportional-hazards models with incident coronary heart disease and heart failure as time-dependent covariates to assess the association between echocardiographic variables and SCD, adjusting for Framingham risk score variables, coronary heart disease, and renal function. Cohort-specific results were meta-analyzed. During a median follow-up of 7.3 and 13.1 years, 44 ARIC study participants and 275 CHS participants had SCD, respectively. In the meta-analyzed results, the adjusted hazard ratios (95% confidence intervals) for predictors of SCD were 3.07 (2.29-4.11) for reduced left ventricular ejection fraction; 1.85 (1.36-2.52) for mitral annular calcification; 1.64 (1.07-2.51) for mitral E/A >1.5, and 1.52 (1.14-2.02) for mitral E/A <0.7 (versus mitral E/A 0.7-1.5); 1.30 (1.15-1.48) per 1 SD increase in left ventricular mass; and 1.15 (1.02-1.30) per 1 SD increase in left atrial diameter. A receiver-operating characteristic model for prediction of SCD using Framingham risk score variables had a C statistic of 0.61 for ARIC study and 0.67 for CHS; the full multivariable model including all echocardiographic variables had a C statistic of 0.76 for ARIC study and 0.74 for CHS. CONCLUSIONS: In addition to reduced left ventricular ejection fraction, we identified other echocardiographic-derived variables predictive for SCD that provided incremental value compared with clinical risk factors.

Shared Risk Factors in Cardiovascular Disease and Cancer.

Cardiovascular disease (CVD) and cancer are the 2 leading causes of death worldwide. Although commonly thought of as 2 separate disease entities, CVD and cancer possess various similarities and possible interactions, including a number of similar risk factors (eg, obesity, diabetes mellitus), suggesting a shared biology for which there is emerging evidence. Although chronic inflammation is an indispensable feature of the pathogenesis and progression of both CVD and cancer, additional mechanisms can be found at their intersection. Therapeutic advances, despite improving longevity, have increased the overlap between these diseases, with millions of cancer survivors now at risk of developing CVD. Cardiac risk factors have a major impact on subsequent treatment-related cardiotoxicity. In this review, we explore the risk factors common to both CVD and cancer, highlighting the major epidemiological studies and potential biological mechanisms that account for them.

Association of Gestational Diabetes Mellitus With Left Ventricular Structure and Function: The CARDIA Study.

OBJECTIVE: Gestational diabetes mellitus (GDM) predicts incident cardiovascular disease (CVD). However, mechanisms linking GDM to CVD beyond intervening incident diabetes are not well understood. We examined the relation of GDM with echocardiographic parameters of left ventricular (LV) structure and function, which are important predictors of future CVD risk. RESEARCH DESIGN AND METHODS: We studied 609 women (43% black) from the Coronary Artery Risk Development in Young Adults (CARDIA) study who delivered one or more births during follow-up and had echocardiograms in 1990-1991 (mean age 28.8 years) and 2010-2011. RESULTS: During the 20-year follow-up, 965 births were reported, with GDM developing in 64 women (10.5%). In linear regression models adjusted for sociodemographic factors, BMI, physical activity, parity, smoking, use of oral contraceptives, alcohol intake, family history of coronary heart disease, systolic blood pressure, and lipid levels, women with GDM had impaired longitudinal peak strain (-15.0 vs. -15.7%, P = 0.025), circumferential peak strain (-14.8 vs. -15.6%, P = 0.028), lateral e' wave velocity (11.0 vs. 11.8 cm/s, P = 0.012), and septal e' wave velocity (8.6 vs. 9.3 cm/s, P = 0.015) in 2010-2011 and a greater 20-year increase in LV mass indexed to body surface area (14.3 vs. 6.0 g/m(2), P = 0.006) compared with women with non-GDM pregnancies. Further adjustment for incident type 2 diabetes after pregnancy did not attenuate these associations. CONCLUSIONS: Pregnancy complicated by GDM is independently associated with increased LV mass and impaired LV relaxation and systolic function. Implementation of postpartum cardiovascular health interventions in women with a history of GDM may offer an additional opportunity to reduce future CVD risk.

Usefulness of N-terminal Pro-brain Natriuretic Peptide and Myocardial Perfusion in Asymptomatic Adults (from the Multi-Ethnic Study of Atherosclerosis).

This study sought to investigate the relation between myocardial perfusion and N-terminal pro-brain natriuretic peptide (NT-proBNP) in asymptomatic adults without overt coronary artery disease. NT-proBNP is a cardiac neurohormone secreted from the ventricles in response to ventricular volume expansion and pressure overload and may also be elevated in the setting of reduced myocardial perfusion. We hypothesized that reduced myocardial perfusion reserve (MPR) would be associated with elevated NT-proBNP in participants free of overt cardiovascular disease. MPR was measured by cardiac magnetic resonance, before and after adenosine infusion, in 184 MESA participants (mean age 60 ± 10.4, 58% white, 42% Hispanic, 44% women) without overt cardiovascular disease. MPR was modeled as hyperemic myocardial blood flow (MBF) adjusted for MBF at rest. A linear regression analysis, adjusted for demographics, established cardiovascular risk factors, left ventricular mass, coronary calcium score, body mass index, and medications, was used to determine the association between MPR and NT-proBNP. Participants with low hyperemic MBF were more likely to be older, male, diabetic, and have higher blood pressure and higher coronary artery calcium score. Mean hyperemic MBF was 3.04 ± 0.829 ml/min/g. MPR was inversely associated with NT-proBNP levels. In a fully adjusted model, every 1-SD decrement in MPR was associated with a 21% increment in NT-proBNP (p = 0.04). In conclusion, MPR is inversely associated with NT-proBNP level in this cross-sectional study of asymptomatic adults free of overt coronary artery disease, suggesting that higher NT-proBNP levels may reflect subclinical myocardial microvascular dysfunction.