No abstract

Background Cardiovascular health (CVH) has been defined by the American Heart Association (AHA) as the presence of the “Life’s Simple 7” ideal lifestyle and clinical factors. CVH is known to predict longevity and freedom from cardiovascular disease, the leading cause of death for women in the United States. DNA methylation markers of aging have been aggregated into a composite epigenetic age score, which is associated with cardiovascular morbidity and mortality. However, it is unknown whether poor CVH is associated with acceleration of aging as measured by DNA methylation markers in epigenetic age. Methods and results We performed a cross-sectional analysis of racially/ethnically diverse post-menopausal women enrolled in the Women’s Health Initiative cohort recruited between 1993 and 1998. Epigenetic age acceleration (EAA) was calculated using DNA methylation data on a subset of participants and the published Horvath and Hannum methods for intrinsic and extrinsic EAA. CVH was calculated using the AHA measures of CVH contributing to a 7-point score. We examined the association between CVH score and EAA using linear regression modeling adjusting for self-reported race/ethnicity and education. Among the 2,170 participants analyzed, 50% were white and mean age was 64 (7 SD) years. Higher or more favorable CVH scores were associated with lower extrinsic EAA (~ 6 months younger age per 1 point higher CVH score, p < 0.0001), and lower intrinsic EAA (3 months younger age per 1 point higher CVH score, p < 0.028). Conclusions These cross-sectional observations suggest a possible mechanism by which ideal CVH is associated with greater longevity.

No abstract

Optimal therapy for diastolic heart failure (DHF), the most common form of heart failure in older persons, is unclear. To determine the effect of aldosterone antagonism in DHF, we conducted an open-label preliminary trial of spironolactone 25mg/day in 11 women with DHF. Cardiopulmonary exercise testing, Doppler-echocardiography, and a quality of life (QOL) survey were administered at baseline and after 4-months. Peak exercise VO 2 increased by 8.3% (p=0.001), the ratio of Doppler diastolic early filling velocity to mitral annulus velocity decreased by 25% (p=0.02), QOL score improved by 21% (p=0.16 for trend), and median NYHA class improved from class III to class II (p=0.004). Findings from this preliminary study confirm the role of aldosterone in the pathophysiology of DHF and suggest that aldosterone antagonism may benefit such patients. These hypotheses are currently being tested in two separated NIH-funded, randomized trials, the Spironolactone For Failure in the Elderly (SPIFFIE) and the Treatment Of Preserved Cardiac Function Heart Failure with an Aldosterone antagonist (TOPCAT) trials.

Background There is limited data on electrocardiographic (ECG) abnormalities and their prognostic significance in women with peripartum cardiomyopathy (PPCM). We sought to characterize ECG findings in PPCM and explore the association of ECG findings with myocardial recovery and clinical outcomes. Hypothesis We hypothesized that ECG indicators of myocardial remodeling would portend worse systolic function and outcomes. Methods Standard 12‐lead ECGs were obtained at enrollment in the Investigations of Pregnancy‐Associated Cardiomyopathy study and analyzed for 88 women. Left ventricular ejection fraction (LVEF) was measured by echocardiography at baseline, 6 months, and 12 months. Women were followed for clinical events (death, mechanical circulatory support, and/or cardiac transplantation) until 1 year. Results Half of women had an “abnormal” ECG, defined as atrial abnormality, ventricular hypertrophy, ST‐segment deviation, and/or bundle branch block. Women with left atrial abnormality (LAA) had lower LVEF at 6 months (44% vs 52%, P = 0.02) and 12 months (46% vs 54%, P = 0.03). LAA also predicted decreased event‐free survival at 1 year (76% vs 97%, P = 0.008). Neither left ventricular hypertrophy by ECG nor T‐wave abnormalities predicted outcomes. A normal ECG was associated with recovery in LVEF to ≥50% (84% vs 49%, P = 0.001) and event‐free survival at 1 year (100% vs 85%, P = 0.01). Conclusions ECG abnormalities are common in women with PPCM, but a normal ECG does not rule out the presence of PPCM. LAA predicted lower likelihood of myocardial recovery and event‐free survival, and a normal ECG predicted favorable event‐free survival.