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Background: Blood urea nitrogen (BUN) has been shown as a potent predictor of morbidity and mortality in patients with heart failure (HF). Whether BUN levels are associated with incident HF in the general population is unknown. Methods: Among 14,263 ARIC participants without a history of HF at baseline (1987-1989) (mean age 54 [SD 5.7] years, Female 54.4%, Black 25.4%), we assessed the association of BUN with incident HF. BUN levels (mg/dL) were divided by quartiles in the primary analysis, and the highest quartile was further divided into tertiles in the secondary analysis (Q121). We defined HF as hospitalization or death with HF diagnosis and estimated hazard ratios (HRs) using multivariable Cox regression models. Results: During a median follow-up of 26.2 years, 3,506 participants developed incident HF (incidence rate 10.7 per 1,000 person-year). When we adjusted for demographic variables, using the lowest quartile (Q1) as the reference, the top quartile (Q4) showed an HR of 1.18 (95% CI 1.08, 1.10) (Model 1 in Table ). When we subdivided Q4, Q4c showed the highest HR (1.40 [95% CI 1.21, 1.61]). The association was similar after further adjusting for lifestyle and other clinical factors (Model 2 in Table ). Further adjustment for estimated glomerular filtration rate modestly attenuated the association (Model 3 in Table ), but HRs remained significant for Q4 as a whole (1.11 [1.01, 1.22]) and Q4c (1.27 [1.09, 1.47]). In subgroup analysis, the association was stronger in Black participants than in White participants (p-for-interaction Conclusion: In this community-based cohort, higher BUN levels were significantly associated with incident HF. BUN levels are often measured as part of routine clinical care and thus may inform clinicians to identify individuals at risk of HF, particularly in resource-constrained settings with limited availability of measuring HF-specific markers such as natriuretic peptides.

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 (β 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 (β coefficient per SD decrease: −5.8; 95% CI: −9.1 to −2.5 m; p 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.

Background and aims Elevated serum calcium and phosphorus have been associated with increased risk of cardiovascular disorders. We evaluated whether abnormal calcium and high serum phosphorus are associated cross-sectionally with echocardiographic measures of left ventricular (LV) structure and function, as doing so may provide insight into the etiology of cardiac disorders. Methods and results Included in the analysis were 5213 Atherosclerosis Risk in Communities Study (ARIC) participants who in 2011–2013 had echocardiography and serum calcium and phosphorus measurements. We evaluated the association of serum calcium (corrected for albumin) and phosphorus quintiles with measures of LV structure and function, after adjusting for other cardiovascular risk factors. Participants were on average 75.3 years old; 59.1% were female and 19.8% were African American. Mean (±SD) concentrations of calcium and phosphorus were 9.33 ± 0.38 and 3.46 ± 0.45 mg/dL, respectively. Higher calcium was associated with lower LV end-diastolic diameter (LVEDD) but greater prevalence of concentric remodeling (p-trend: 0.005 and 0.004 respectively). We observed association between high phosphorus and high septal E/e’ (p-trend: 0.02). Likewise, higher serum phosphorus was associated with higher left atrial volume index (p-trend: 0.001) and LV hypertrophy prevalence (p-trend: 0.04). Conclusions In conclusion, higher calcium was associated with more concentric remodeling but lower LVEDD, suggesting complex associations between calcium and cardiac function. Serum phosphorus was related to worse indices of LV diastolic function and LV hypertrophy, but not to LV systolic function. However, the magnitudes of association were modest, so clinical implications of these findings may be limited.

Introduction: The AHA/ACC framework of valvular heart disease (VHD) stages emphasizes the progressive nature of VHD. Limited data exist regarding the association of VHD stages with prognostic cardiac biomarkers of myocardial stress (NT-proBNP) and injury (high sensitivity troponin-T [hs-TnT]). Methods: Among 6,078 participants in the community-based Atherosclerosis Risk in Communities (ARIC) who underwent echocardiography at the 5 th study visit (2011-2013) and were free of prior valve replacement, we classified VHD stages based on quantitative and qualitative assessments of mitral and aortic valve stenosis and regurgitation. Multivariable linear regression models were used to relate VHD stages to concentrations of NT-proBNP and hs-TnT at Visit 5. Biomarker values were log-transformed. Models were adjusted for age, sex, race, hypertension, diabetes, heart failure, prior myocardial infarction, body mass index, atrial fibrillation, study center, and systolic blood pressure at Visit 5. Results: The mean age was 76±5, 58% were women, 22% were Black. Stage A VHD was present in 2,362 participants (39%), Stage B in 1011 (17%), and Stage C or D in 65 (1%). In multivariable models, higher VHD stage was associated with a graded increase in NT-proBNP and hs-TnT concentrations (Figure) . Compared to participants free of VHD, even Stage A (‘at risk’) participants demonstrated higher concentrations of both NT-proBNP (p Conclusion: Worse VHD stages, even in the absence of severe stenosis or regurgitation, are associated with higher concentrations of markers of myocardial stress (NT-proBNP) and injury (hs-TnT) independent of traditional cardiovascular risk factors. Figure: Concentrations (median, IQR) of NT-proBNP and hs-TnT by VHD stage. *p

Introduction: The incidence and prevalence of both frailty and heart failure (HF) are greatest in late life, and both have been associated with inflammation and markers of myocardial injury. While frailty is cross-sectionally associated with HF, the association of frailty with incident HF, and HF with preserved (HFpEF) or reduced ejection fraction (HFrEF) is unclear. Methods: Among 5,517 participants in the Atherosclerosis Risk in Communities study with frailty assessment and free of HF at Visit 5 (2011-2013), frailty was ascertained using information on weight loss, low grip strength, exhaustion, low energy expenditure and slow gait. Frail was defined as the presence of > 3 frailty components, pre-frail as 1-2 components, and robust as 0 components. HF was ascertained through adjudication of hospitalizations with related ICD codes. Multivariable Cox proportional hazard models were used to evaluate the association of frailty status at Visit 5 with incident HF overall, HFpEF (LVEF ≥50%), and HFrEF (LVEF Results: Mean age was 75 +/- 5 years, 58% were female, and 22% were Black. Forty-six percent were classified as robust, 48% as pre-frail, and 6% frail. Frail participants were older and had a higher prevalence of cardiovascular co-morbidities. Over a median follow-up of 7.1 (IQR 5.5-7.8) years, 525 participants developed incident HF (249 HFpEF, 209 HFrEF, 67 HF with unknown LVEF). Both pre-frailty and frailty were associated with heightened risk of incident HF compared to robust participants (Figure). The magnitude of risk associated with frailty status was similar for both HFpEF and HFrEF. Conclusions: Pre-frailty and frailty are both associated with heightened risk of incident HF in late life, independent of traditional cardiovascular risk factors. These associations are similar in magnitude for HFpEF and HFrEF.

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.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.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.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.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.

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 structure and function with 6MWD are unclear, and may provide insight regarding the risk of incident HF. OBJECTIVES: To understand the relationships between cardiac function and exercise capacity. METHODS: We evaluated the associations of cardiac mechanics with 6MWD in the 6(th) exam of the Multi-Ethnic Study of Atherosclerosis. Two-dimensional, Doppler and speckle-tracking echocardiography 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, 48% male, 58% non-White), individuals with lower (worse) left atrial (LA) reservoir strain were older and had higher blood pressure. Lower resting LA reservoir strain (β coefficient per SD decrease: −5.0, 95% CI: −8.8, −1.3 meters; P=0.009), inability to augment LA reservoir strain after passive leg raise (β coefficient per SD decrease: −5.8, 95% CI: −9.1, −2.5 meters; P

Key Points Question Is sickle cell trait associated with increased risk of myocardial infarction and coronary heart disease among African American individuals? Findings In this cohort study of 23 197 African American individuals in 5 cardiovascular epidemiologic studies, sickle cell trait was not associated with increased risk of myocardial infarction or coronary heart disease among African American individuals. Meaning In this study, sickle cell trait was not associated with increased risk of fatal and nonfatal myocardial infarction or coronary heart disease, suggesting that these disorders may not be associated with sickle cell trait–related sudden death., 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., This cohort study evaluates whether African American individuals with sickle cell trait have a higher incidence of myocardial infarction or composite coronary heart disease outcomes compared with those without sickle cell trait.

Introduction: While the prognostic implications of higher pulmonary artery systolic pressure (PASP) are well established, few data exist regarding longitudinal change in pulmonary pressure in the community. We characterized longitudinal changes in PASP over ~6.5 years in late life, and identified predictors of this change. Methods: We studied 1,426 elderly participants in the prospective, community-based Atherosclerosis Risk in Communities (ARIC) study who underwent protocol echocardiography and had assessable tricuspid regurgitation spectral Doppler at 5 th (2011-2013) and 7 th (2018-2019) study visits. We used multivariable linear regression to identify clinical, echocardiographic and biomarker predictors of change in PASP. Results: Mean age was 74±5 years at Visit 5, 32% were men, 24% black, and mean PASP was 27.5±5.0 mmHg. Over a median of 6.5±3.0 years, PASP increased by 5.2±7.7 mmHg on average, with no significant differences by race (white 5.0±7.6, black 5.8±7.9; p=0.40) or sex (women 5.2±7.7, men 5.1±7.8; p=0.95). In models adjusted for heart rate and blood pressure at both visits, and for PASP, clinical and echocardiographic measures at Visit 5, independent predictors of longitudinal increase in PASP at Visit 5 were higher NT-proBNP (p=0.005), larger left atrial volume index (p=0.045), and lower forced expiratory volume at 1 second (p=0.019). Longitudinal increase in PASP was associated with concomitant increases in LAVi, E/e’ ratio, and LV mass index ( Figure ; all p Conclusions: PASP increased by 5±8 mmHg over 6.5±3.0 years in late life, with greater increases associated with higher filling pressure and worse pulmonary function. Increases in PASP are accompanied by longitudinal worsening in LV diastolic - but not systolic - measures.

Background: Aortic stenosis (AS) is a growing health problem within the aging population. We aimed to quantify longitudinal changes in aortic valve hemodynamics in late life. Methods: We studied 2,512 community-based elderly participants in the Atherosclerosis Risk in Communities (ARIC) study who underwent uniform echocardiographic imaging at study visits 5 (2011-2013) and 7 (2018-2019). Peak aortic valve (AV) velocity was assessed by continuous wave spectral Doppler from the apical 5 chamber view. Participants with heart failure or in atrial fibrillation at either echocardiographic examination were excluded. Results: Mean age at Visit 5 was 74 ± 4 years, 41% were male, 24% black, and the mean AV velocity at Visit 5 was 1.27 ± 0.28 m/s. Over median 6.6 [IQR: 6.1-7.0] years, AV velocity increased by 0.15 ± 0.32 m/s and the mean velocity at Visit 7 was 1.43 ± 0.43 m/s. Of 2,454 participants with peak AV velocity < 2.0 m/s at Visit 5, 123 (5%) developed a peak AV velocity > 2.0 m/s at Visit 7 (mean 2.45 ± 0.46 m/s). In models accounting for blood pressure and heart rate at both study visits, Visit 5 predictors of transitioning to a peak AV velocity > 2.0 m/s included age, male sex, white race, BMI, higher NT-proBNP and hs-troponin T, and greater LA volume index and E/e’ ratio ( Table ). Conclusions: Peak AV velocity increases over 6 years in late life, with ~5% developing a peak velocity > 2.0 m/s. Demographics, higher cardiac biomarkers, and worse diastolic function predict increases in peak AV velocity in late life. These data have important implications for the development of age-related aortic stenosis.

Introduction: Older adults are at heightened risk for both kidney disease and heart failure, but there is limited data regarding the associations of kidney damage and dysfunction with incident heart failure with reduced (HFrEF) and preserved (HFpEF) ejection fraction in late life. Hypothesis: Kidney dysfunction, as assessed by lower estimated glomerular filtration rate (eGFR), and kidney damage, as assessed by higher urine albumin-to-creatinine ratio (UACR), are each independently associated with incident HFrEF and HFpEF in late life. Methods: We studied 4,563 elderly participants in the community-based, prospective ARIC study who were free of HF at study Visit 5 (2011-2013) at which time they had UACR measured and Cystatin-C-based eGFR estimated using the CKD-EPI formula. We estimated the association of Visit 5 eGFR and UACR with post-Visit 5 incident HF overall, HFrEF, and HFpEF using multivariable Cox proportional hazards regression models adjusted for demographics, diabetes, hypertension, coronary artery disease, atrial fibrillation, body mass index, pulse pressure, and either eGFR or UACR. Results: The mean age at Visit 5 was 75±5 years, 57% were female, 21% were black. Mean Visit 5 eGFR was 67±18 mL/min per 1.73 m 2 and median UACR was 10.2 [6.2 to 21.4] mg-g. Lower eGFR and higher UACR each associated with older age, wider pulse pressure and higher prevalence of diabetes, hypertension, coronary disease and atrial fibrillation (all pFigure ). Conclusions: Lower eGFR and higher UACR are independently and additively associated with both incident HFrEF and incident HFpEF in late life.

Introduction: Diastolic dysfunction is a potent risk factor for heart failure (HF). However, there is limited data regarding longitudinal changes of diastolic function in the very old, who are at the highest risk for HF. Methods: We studied 2,559 community-based elderly participants in the prospective ARIC study who underwent protocol echocardiography, were in sinus rhythm at study Visits 5 (2011-2013) and 7 (2018-2019), and did not have an interval myocardial infarction. The primary diastolic measures were Tissue Doppler e’, E/e’ ratio, and left atrial volume index (LAVi). Results: Mean age at Visit 5 was 74±4 years, 59% were women, and 25% black. At Visit 5, mean e’ was 5.8±1.4 cm/s, E/e’ 11.8±3.6, and LAVi 24.3±6.7 ml/m 2 . Over a mean of 6.5±3.1 years, e’ decreased by 0.6±1.4 cm/s, E/e’ increased by 3.1±4.5, and LAVi increased by 1.4±7.7 ml/m 2 . Using validated ARIC-based cut-points, there was significant increase in the proportion of participants with abnormal e’ (18% at Visit 5 to 34 % at Visit 7), E/e’ (20% vs 46%), LAVi (17% vs 25%; all pFigure ). Compared to participants free of cardiovascular (CV) risk factors or CV diseases (n=237), those with CV risk factors or diseases at Visit 5 (n=2,210) demonstrated greater increases in E/e’ (2.3±3.9 vs 3.1±4.5 respectively; p=0.006) and LAVi (0.0±7.0 vs 1.5±7.7 ml/m 2 ; p=0.008) while increases in E/e’ (5.0±5.1; p2 ; p Conclusions: Diastolic function progressively worsens over 6.5 years in late life, particularly among persons with CV risk factors. Further studies are necessary to determine if risk factor prevention or control will mitigate these changes.

Introduction: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high sensitivity cardiac troponin T (hs-cTnT) improve prediction of incident heart failure (HF) and are cross-sectionally associated with left ventricular (LV) remodeling, but their associations with changes in cardiac structure and function are unclear. Hypothesis: Concentrations of NT-proBNP and hs-cTnT associate with 6-year change in cardiac structure in older adults. Methods: We studied 1,916 participants aged 67-88 in the ARIC Study free of overt cardiovascular disease at baseline (study Visit 5; 2011-13). We quantified the associations of baseline NT-proBNP and hs-cTnT with subsequent changes in LV structure and systolic and diastolic function assessed by echocardiography over a median of 6.6 (IQR 6.1-7.0) years using multivariable linear regression and restricted cubic spline models. Models adjusted for demographics, systolic blood pressure, heart rate, body mass index, diabetes, hypertension, kidney function, and the baseline echocardiographic value of interest at Visit 5. Results: Mean age was 75±4 years, 60% were female, 23% were black, median hs-cTnT was 9 (IQR 6-13) ng/L and NT-proBNP was 88 (50-157) ng/L at Visit 5. In adjusted models, higher hs-cTnT was modestly associated with 6-year increase in LV wall thickness (p=0.02) but not with changes in LV function. In contrast, higher NT-proBNP at Visit 5 was associated with 6-year increase in LV mass, decline in LV systolic function (ejection fraction, longitudinal and circumferential strain), and worsening of diastolic function (left atrium volume, E/e’, tricuspid regurgitation peak velocity) (all pFigure ). These associations were non-linear. Conclusions: Higher NT-proBNP, but not hs-cTnT, concentrations are associated with greater declines in LV systolic and diastolic function over ~6 years in late life.

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.

There is a growing body of evidence that suggests cancer and cardiovascular disease have a shared biological mechanism. Although there are several shared risk factors for both diseases, including advancing age, gender, obesity, diabetes, physical activity, tobacco use, and diet, inflammation and biomarkers, such as insulinlike growth factor 1, leptin, estrogen, and adiponectin, may also play a role in the biology of these diseases. This article provides an overview of the shared biological mechanism between cancer and cardiovascular disease.

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., We describe the co‐occurrence of cancer and heart failure (HF), their potential shared risk factors, and their pathophysiological mechanisms. We advocate intense interaction between cardiologists and oncologists to achieve unifying hypotheses and collaborative pre‐clinical and clinical studies.

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/m 2 . AF was ascertained using study ECG s 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.

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.

Imaging modalities play an important role in the diagnosis and management of cardiotoxicity and cardiac tumors. In this review, we provide an overview of the imaging modalities that are relevant to the field of cardio-oncology. Cardiac magnetic resonance provides comprehensive tissue characterization in the assessment of cardiac tumors and cardiomyopathy. The combination of positron emission tomography/computed tomography offers improved localization of lesions, staging, targeting of biopsy and therapy, and greater confidence in interpretation. Overall, cardiac imaging plays a critical role in the assessment and management of cardiac tumors either for surgical planning or for initiation of appropriate cancer therapies. For certain higher risk cancer patients and survivors, routine surveillance with cardiac imaging may be warranted so appropriate interventions can be instituted to stabilize or even improve the cardiac dysfunction.

BACKGROUNDThe role of alcohol in the development of subclinical cardiovascular disease is unclear. We examined the association between alcohol consumption and markers of subclinical cardiac damage and wall stress.METHODSWe studied the cross-sectional and prospective associations of alcohol consumption with high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro B-type natriuretic peptide (NT-proBNP) measured at 2 time points, 6 years apart (baseline, 1990–1992; follow-up, 1996–1998), in over 11000 participants of the Atherosclerosis Risk in Communities (ARIC) Study with no history of cardiovascular disease. Alcohol consumption was categorized as follows: never, former, current: ≤1, 2–7, 8–14, and ≥15 drinks/week.RESULTSCompared to never drinkers, persons who consumed 2–7 drinks per week were less likely to have increased hs-cTnT (≥14 ng/L) at baseline (odds ratio = 0.67, 95% CI, 0.46–0.96), and had a lower risk of incident increases in hs-cTnT at follow-up (relative risk = 0.70, 95% CI, 0.49–1.00). Conversely, there was a positive association between alcohol intake and NT-proBNP concentrations at baseline. Consumption of ≥15 drinks/week was positively associated with incident increases in NT-proBNP (≥300 pg/mL) at the 6-year follow-up visit (relative risk = 2.38, 95% CI, 1.43–3.96).CONCLUSIONSIn this community-based study of middle-aged adults without a history of cardiovascular disease, moderate drinking was associated with lower concentrations of hs-cTnT, a marker of chronic subclinical myocardial damage, and positively associated with NT-proBNP, a biomarker of cardiac wall stress. Our results suggest that the cardiac effects of alcohol are complex. Cardiac biomarkers may help improve our understanding of the full cardiovascular effects of alcohol consumption.

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.

Background The relationship between ideal cardiovascular health reflected in the cardiovascular health score ( CVHS ) and valvular heart disease is not known. The purpose of this study was to determine the association of CVHS attainment through midlife to late life with aortic stenosis prevalence and severity in late life. Methods and Results The following 6 ideal cardiovascular health metrics were assessed in ARIC (Atherosclerosis Risk in Communities) Study participants at 5 examination visits between 1987 and 2013 (visits 1–4 in 1987–1998 and visit 5 in 2011–2013): smoking, body mass index, total cholesterol, blood pressure, physical activity, and blood glucose. Percentage attained CVHS was calculated in 6034 participants as the sum of CVHS at each visit/the maximum possible score. Aortic stenosis was assessed by echocardiography at visit 5 on the basis of the peak aortic valve velocity. Aortic stenosis was categorized sclerosis, mild stenosis, and moderate‐to‐severe stenosis. Mean age was 76±5 years, 42% were men, and 22% were black. Mean percentage attained CVHS was 63±14%, and the prevalence of aortic stenosis stages were 15.9% for sclerosis, 4.3% for mild stenosis, and 0.7% for moderate‐to‐severe stenosis. Worse percentage attained CVHS was associated with higher prevalence of aortic sclerosis ( P P P =0.002), adjusting for age, sex, and race. Conclusions Greater attainment of ideal cardiovascular health in midlife to late life is associated with a lower prevalence of aortic sclerosis and stenosis in late life in a large cohort of older adults.

Patients with cancer are subject to short-term and long-term adverse cardiovascular outcomes from cancer therapies. It is important to identify patients at risk for cardiotoxicity so that appropriate therapy can be instituted early. Cardiovascular magnetic resonance (MR) imaging is emerging as a promising imaging modality with unique applications beyond standard left-ventricular systolic function assessment. It can provide comprehensive evaluation of most cardiac structures in one setting. This article provides an overview of cardiac MR imaging in cardio-oncology.

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. 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. 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. 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.

Background Antibodies against human epidermal growth factor receptor 2 (HER2) affect metastatic breast cancer cells and cardiac myocytes. Guidelines recommend evaluation of cardiac ejection fraction (EF) every 3 months despite little supporting evidence for this need. We assessed the impact of EF screening on clinical practice. Patients and methods We carried out retrospective analysis of patients with HER2-positive metastatic breast cancer receiving HER2-directed therapy to assess the impact of aggressive cardiac screening on management decisions. Results Data for 128 patients were analyzed. The median number of EF screenings in the first year of therapy was 3 (range=1-8). A total of 29 patients had an asymptomatic decrease in EF. These patients had more EF screenings, more exposure to anthracyclines or left-sided radiation, were more likely to receive a cardiology consult and have an angiotensin converting enzyme inhibitor added to their therapy. Ninety patients underwent aggressive screening; this was not associated with cessation of HER2 therapy (p=0.92). Conclusion Routine EF screening did not have an impact on decisions regarding HER2 therapy in patients with metastatic breast cancer. Given the known benefit of HER2 treatment, reducing the frequency of cardiac screening may be reasonable.

Lipoprotein(a) [Lp(a)] is a proatherogenic lipoprotein associated with coronary heart disease, ischemic stroke, and more recently aortic stenosis and heart failure (HF). We examined the association of Lp(a) levels with incident HF hospitalization in the Atherosclerosis Risk in Communities (ARIC) study. We also assessed the relationship between Lp(a) levels and arterial stiffness as a potential mechanism for development of HF.Lp(a) was measured in 14,154 ARIC participants without prevalent HF at ARIC visit 1 (1987-1989). The association of Lp(a) quintiles with incident HF hospitalization was assessed using Cox proportional-hazards models. Arterial stiffness parameters were stratified based on Lp(a) quintiles, and p-trend was calculated across ordered groups.At a median follow-up of 23.4 years, there were 2605 incident HF hospitalizations. Lp(a) levels were directly associated with incident HF hospitalization in models adjusted for age, race, gender, systolic blood pressure, history of hypertension, diabetes, smoking status, body mass index, heart rate, and high-density lipoprotein cholesterol (quintile 5 vs. quintile 1: hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.09-1.41; p-trend across increasing quintiles0.01), but not after excluding prevalent and incident myocardial infarction cases (HR 1.07, 95% CI 0.91-1.27; p-trend = 0.70). When adjusted for age, gender, and race, Lp(a) quintiles were not significantly associated with arterial stiffness parameters.Increased Lp(a) levels were associated with increased risk of incident HF hospitalization. After excluding prevalent and incident myocardial infarction, the association was no longer significant. Lp(a) levels were not associated with arterial stiffness parameters.

Introduction Coronary artery disease (CAD) is a potent risk factor for heart failure with reduced ejection fraction (HFrEF), and is a common comorbidity in HF with preserved EF (HFpEF). However, data regarding the association of incident CAD with subsequent HFpEF independent of shared comorbidities are limited. Hypothesis Incident CAD is a risk factor for incident HFpEF independent of common shared comorbidities. Methods We evaluated 9,902 CAD-free and HF-free participants in the Atherosclerosis Risk in Communities (ARIC) cohort and followed them from 2005 to 2017. Multivariable Cox proportional hazard models were used to assess the association of incident CAD (defined as adjudicated MI or revascularization) with subsequent adjudicated hospitalization for incident HFpEF (EF ≥50%) or incident HF with mid-range or reduced EF (HFmrEF/HFrEF; EF 1 year after CAD diagnosis. Results The average age as of 2005 was 70 ± 6, 61% were female, and 26% were black. During median follow-up of 13 years, incident CAD occurred in 892 participants who subsequently experienced 71 incident HFpEF events and 86 HFmrEF/HFrEF events. Risk of both incident HFpEF and HFmrEF/HFrEF was greatest early following CAD diagnosis. Incident CAD remained predictive of both incident HFpEF (HR 1.9 [1.4 - 2.6]) and HFmrEF/HFrEF (HR 2.8 [2.0 - 3.8]) at >1 year following the CAD event, with no detected effect modification by sex or race (Figure). Similar risks for HFpEF were observed at >1 year following incident MI or following incident revascularization alone. At >1 year after incident CAD, the adjusted incidence rates of HFpEF and HFmrEF/HFrEF were similar (1.10 [95% CI 0.77 - 1.43] and 1.10 [95% CI 0.77 - 1.44] per 100 person-years respectively). Conclusions Incident CAD is an independent risk factor for subsequent incident HFpEF. At >1 year after incident CAD, incidence of HFpEF is similar to HFmrEF/HFrEF. These findings argue for an important, and potentially under-recognized, role of CAD in the development of HFpEF.

Background— Heart failure is an important public health concern, particularly among persons >65 years of age. Women and blacks are critically understudied populations that carry a sizeable portion of the heart failure burden. Limited normative and prognostic data exist on measures of cardiac structure, diastolic function, and novel measures of systolic deformation in older adults living in the community. Methods and Results— The Atherosclerosis Risk in Communities (ARIC) study is a large, predominantly biracial, National Heart, Lung, and Blood Institute–sponsored epidemiological cohort study. Between 2011 and 2013, ≈6000 surviving participants, now in their seventh to ninth decade of life, are expected to return for a fifth study visit during which comprehensive 2-dimensional, Doppler, tissue Doppler, and speckle-tracking echocardiography will be performed uniformly in all cohort clinic visit participants. The following objectives will be addressed: (1) to characterize cardiac structural and functional abnormalities among the elderly and to determine how they differ by sex and race/ethnicity, (2) to determine the relationship between ventricular and vascular abnormalities, and (3) to prospectively examine the extent to which these noninvasive measures associate with incident heart failure. Conclusions— We describe the design, imaging acquisition and analysis methods, and quality assurance metrics for echocardiography in visit 5 of the ARIC cohort. A better understanding of the differences in cardiac structure and function through the spectrum of heart failure stages in elderly persons generally, and between sexes and racial/ethnic groups specifically, will deepen our understanding of the pathophysiology driving heart failure progression in these at-risk populations and may inform novel prevention or therapeutic strategies.

Cardiovascular disease is the leading noncancer cause of death among survivors of childhood cancer. Ejection fraction (EF) and fractional shortening (FS) are common echocardiographic measures of cardiac function, but newer imaging modalities may provide additional information about preclinical disease. This study aimed to evaluate these modalities in detection of anthracycline-induced cardiac toxicity.We compared mean radial displacement, EF, and FS among 17 adult survivors of childhood cancer exposed to ≥ 300 mg/m(2) of anthracyclines to 17 age- and sex-matched healthy controls. Survivors with a history of cardiac-directed radiation, diabetes, or heart disease were excluded.Survivors (35% male), mostly with history of treatment for a solid tumor, had a median age at diagnosis of 15 years (1-20) and 27 years (18-50) at evaluation. Median anthracycline exposure was 440 (range 300-645) mg/m(2). FS (35.5 vs. 39.6%, p 0.01) and radial displacement (5.6 vs. 6.7 mm, p = 0.02) were significantly lower in survivors compared to controls, respectively. Although the mean EF was lower in survivors versus controls (55.4 vs. 59.7%), it was not statistically significant (p = 0.057). All echocardiographic measures were inversely associated with anthracycline dose, though radial displacement was no longer significantly correlated with anthracycline dose after controlling for survival time (p = 0.07), while EF remained correlated (p = 0.003).Radial displacement, EF, and FS are lower in childhood cancer survivors compared to controls. In this study, radial displacement added no new information beyond the traditional measures, but clinical utility remains undetermined and requires further longitudinal study.

Publisher's Note: There is an Inside Blood Commentary on this article in this issue.

Background: Although age-associated changes in left ventricular diastolic function are well recognized, limited data exist characterizing measures of diastolic function in older adults, including both reference ranges reflecting the older adult population and prognostically relevant values for incident heart failure (HF), as well as their associations with circulating biomarkers of HF risk. Methods: Among 5801 elderly participants in the ARIC study (Atherosclerosis Risk in Communities; age range, 67–90 years; mean age, 76±5 years; 42% male; 21% black), we determined the continuous association of diastolic measures (tissue Doppler imaging [TDI] e’, E/e’, and left atrial size) with concomitant N-terminal pro-brain natriuretic peptide and subsequent HF hospitalization or death. We also determined sex-specific 10th and 90th percentile limits for these measures using quantile regression in 401 participants free of prevalent cardiovascular disease and risk factors. Results: Each measure of diastolic function was robustly associated with N-terminal pro-brain natriuretic peptide and incident HF or death. ARIC-based reference limits for TDI e’ (4.6 and 5.2 cm/s for septal and lateral TDI e’, respectively) were substantially lower than guideline cut points (7 and 10 cm/s, respectively), whereas E/e’ and left atrial size demonstrated good agreement with guideline cut points. TDI e’ was nonlinearly associated with incident HF or death, with inflection points for risk supportive of ARIC-based limits. ARIC-based limits for diastolic function improved risk discrimination over guideline-based cut points based on the integrated discrimination improvement ( P P Conclusions: Our findings suggest that left ventricular longitudinal relaxation velocity declines as a part of healthy aging and is largely prognostically benign. The use of age-based normative values when considering an elderly population improves the risk discrimination of diastolic measures for incident HF or death.

Background: Although heart failure (HF) disproportionately affects older adults, little data exist regarding the prevalence of American College of Cardiology/American Heart Association HF stages among older individuals in the community. Additionally, the role of contemporary measures of longitudinal strain and diastolic dysfunction in defining HF stages is unclear. Methods: HF stages were classified in 6118 participants in the Atherosclerosis Risk in Communities study (67–91 years of age) at the fifth study visit as follows: A (asymptomatic with HF risk factors but no cardiac structural or functional abnormalities), B (asymptomatic with structural abnormalities, defined as left ventricular hypertrophy, dilation or dysfunction, or significant valvular disease), C1 (clinical HF without prior hospitalization), and C2 (clinical HF with earlier hospitalization). Results: Using the traditional definitions of HF stages, only 5% of examined participants were free of HF risk factors or structural heart disease (Stage 0), 52% were categorized as Stage A, 30% Stage B, 7% Stage C1, and 6% Stage C2. Worse HF stage was associated with a greater risk of incident HF hospitalization or death at a median follow-up of 608 days. Left ventricular (LV) ejection fraction was preserved in 77% and 65% in Stages C1 and C2, respectively. Incorporation of longitudinal strain and diastolic dysfunction into the Stage B definition reclassified 14% of the sample from Stage A to B and improved the net reclassification index ( P =0.028) and integrated discrimination index ( P =0.016). Abnormal LV structure, systolic function (based on LV ejection fraction and longitudinal strain), and diastolic function (based on e’, E/e’, and left atrial volume index) were each independently and additively associated with risk of incident HF hospitalization or death in Stage A and B participants. Conclusions: The majority of older adults in the community are at risk for HF (Stages A or B), appreciably more compared with previous reports in younger community-based samples. LV ejection fraction is robustly preserved in at least two-thirds of older adults with prevalent HF (Stage C), highlighting the burden of HF with preserved LV ejection fraction in the elderly. LV diastolic function and longitudinal strain provide incremental prognostic value beyond conventional measures of LV structure and LV ejection fraction in identifying persons at risk for HF hospitalization or death.

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 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.

Opinion statement Survivors of hematopoietic stem cell transplant (HSCT) are at significant risk for cardiac disease and cardiac complications. While there may be cardiac complications during the acute period of HSCT, long-term survivors remain at risk for cardiovascular disease at a rate at least fourfold higher than the general population. Aggressive screening for cardiac risk factors such as diabetes, hypertension, and arrhythmias is warranted pretransplant. For those with risk factors, particularly a history of cardiovascular disease or atrial fibrillation, cardiology consultation is warranted in the pretransplantation period. Aggressive screening for cardiac risk factors such as diabetes, hypertension, and hyperlipidemia is warranted in HSCT survivors as well; early and aggressive treatment of left ventricular dysfunction is warranted. Collaboration between hematology/oncology and cardiology through a cardio-oncology clinic is an optimal way to help manage these patients.

Background— Several cardiovascular risk factors have been associated with the risk of atrial fibrillation (AF). Limited and inconsistent evidence exists on the association of blood lipid levels and lipid-lowering medication use with AF risk. Methods and Results— We analyzed 13 969 participants (25% African American, 45% men) free of AF at baseline from the Atherosclerosis Risk in Communities study. Fasting high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), triglycerides, and total cholesterol were measured at baseline (1987–1989) and each of 3 follow-up visits. The incidence of AF was ascertained through 2007. The association of the use of statins and other lipid-lowering medications with AF was estimated in 13 044 Atherosclerosis Risk in Communities participants attending visit 2 (1990–1992), adjusting for covariates from the previous visit. During a median follow-up of 18.7 years, there were 1433 incident AF cases. Multivariable hazard ratios (HRs) and 95% CIs of AF associated with a 1-SD increase in lipid levels were as follows: HDLc, 0.97 (0.91–1.04); LDLc, 0.90 (0.85–0.96); total cholesterol, 0.89 (0.84–0.95); and triglycerides, 1.00 (0.96–1.04). Participants taking lipid-lowering medications had an adjusted HR (95% CI) of AF of 0.96 (0.82–1.13) compared with those not taking medications, whereas those taking statins had an adjusted HR of 0.91 (0.66–1.25) compared with those taking other lipid-lowering medications. Conclusions— Higher levels of LDLc and total cholesterol were associated with a lower incidence of AF. However, HDLc and triglycerides were not independently associated with AF incidence. No association was found between the use of lipid-lowering medications and incident AF.

Atrial fibrillation (AF) is one of the most clinically diagnosed cardiac disturbances but little is known about its risk factors. Previous epidemiological studies have reported on the association between diabetes mellitus (DM) and subsequent risk of AF with inconsistent results. The aim of this study was to conduct a meta-analysis of published studies to reliably determine the direction and magnitude of any association between DM and AF. A systematic review and meta-analysis was conducted. PUBMED and EMBASE were searched to identify prospective cohort and case-control studies that had reported on the association between DM and other measures of glucose homeostasis with incident AF by April 2010. Studies conducted in primarily high-risk populations and participants in randomized controlled trials were excluded. Seven prospective cohort studies and four case-control studies with information on 108,703 cases of AF among 1,686,097 individuals contributed to this analysis. The summary estimate indicated that individuals with DM had an approximate 40% greater risk of AF compared with unaffected individuals: RR 1.39 (95% Confidence Intervals: 1.10 – 1.75; p for heterogeneity

Tako-tsubo syndrome appears to be an apparently reversible form of the cardiomyopathy, but little is known about the long term risk even with normalization of ventricular function. The incidence of ventricular arrhythmias after resolution of cardiomyopathy is not known. We present a unique case of tako-tsubo syndrome in a 71-year-old woman who developed symptomatic ventricular arrhythmias after complete resolution of cardiomyopathy.

Background: The new 2013 ACC/AHA cholesterol guidelines recommend statin therapy to reduce atherosclerotic cardiovascular disease. Statins inhibit cholesterol biosynthesis which may impair gonadal steroidogenesis. Higher levels of estradiol (E2) and lower levels of sex hormone binding globulin (SHBG) are associated with greater central obesity, metabolic syndrome and diabetes in both men and postmenopausal women. There is however limited information regarding the impact of statins on endogenous sex hormones in large population studies. Methods: We included 3163 men and 1977 women from the baseline examination of the MESA study who had measurement of serum sex hormones: total and bioavailable testosterone (T), E2, dehydroepiandrosterone (DHEA) and SHBG, and excluded those on hormone replacement therapy and non-statin lipid medications. Results: Of the 5140 individuals examined, statin users (n=812) were 67 + 9 years old, 57% males, 41% Whites, 29% Blacks, 11% Chinese and 19% Hispanics. After adjustment for age, gender and race, total cholesterol, HDL-c and BMI, compared to non-users of statins, statin users had significantly lower SHBG by 4.5 nmol/L (95% CI; -6.1, -2.9) and DHEAS by 0.9 nmol/L (95% CI; -1.4, -0.4). No significant gender interaction with statin was seen. No association was noted between statin use and E2, total and bioavailable T. Conclusion: Statin use is associated inversely with serum SHBG and DHEA levels. This is particularly interesting in light of the association of statin use and diabetes, raising the possibility of mediation by endogenous hormones.

Introduction: Understanding population-based trends in heart failure incidence is important to evaluation and planning of prevention and treatment strategies. Hypothesis: Community trends of acute decompensated heart failure (ADHF) in racially diverse populations may differ by race and sex. Methods: The Atherosclerosis Risk in Communities (ARIC) Study conducted continuous and comprehensive surveillance of hospitalized ADHF events (age ≥55 years) in four US communities between 2005-2012 and estimated hospitalized ADHF incidence and survival by race and sex. 17,651 hospitalizations for ADHF were identified by ICD-9-CM codes, then validated by standardized physician review of hospital records, yielding a weighted sample of 31,006 hospitalizations after accounting for sampling design. HF with reduced EF (HFrEF) was defined as EF Results: Of the ADHF hospitalizations, 16259 (52.4%) were HFrEF, 11835 (38.2%) were HF with preserved EF (HFpEF), and 2912 (9.4%) were HF with unknown EF. HFrEF (both incident and recurrent ADHF) was more common in men (black men 70.4%, white men 61.4%), whereas HFpEF was more common in women (white women 50.0%, black women 39.5%). Compared to whites, blacks were younger, with less coronary heart disease and atrial arrhythmias, and more hypertension, diabetes, and chronic kidney disease. Between 2005-2012, the incidence of hospitalized ADHF increased, which mostly reflected the increase in rates of HFpEF (average annual percent change of incident HFpEF: black women 16.6%, black men 13.2%, white women 8.0%, white men 8.3%), with higher age-adjusted average incident HFpEF rates in women (black women 6.2 per 1000 persons, white women 5.9/1000, black men 4.6/1000, white men 4.2/1000). Changes in HFrEF incidence and changes in 28-day and 1-year case fatality for HFpEF and HFrEF were modest and generally not statistically significant. Age-adjusted 1-year case fatality was similar across all race-sex groups (~30% after any incident ADHF). Similar trends were seen for recurrent ADHF (HFpEF and HFrEF). Conclusions: Incident ADHF rates increased between 2005 and 2012 in the ARIC Study communities, primarily because of incident HFpEF in women and blacks. Further study is needed to understand the differences by race and sex.