Eaton, Charles B.

Background: Heart failure (HF), a leading cause of morbidity and mortality in women, continues to disproportionately affect African-American (AA) women compared to women of other races/ethnicities. In a large cohort of post-menopausal women, we investigated if AA women progress through HF stages and coronary heart disease (CHD) death more rapidly than Caucasian (Cau) or Hispanic/Latina (HL) women. Methods: We assessed the American College of Cardiology/American Heart Association (ACC/AHA) HF stage A upon enrollment into the Women’s Health Initiative (1993-1998) and the progression from Stage A to Stage C, Stage C to CHD death, up to the last date of follow-up (2010). Cox proportional hazard regressions models were used to assess disease progression risk. We adjusted for age, baseline comorbidities, duration of comorbidities, interval development of myocardial infarction, ejection fraction at HF diagnosis, socioeconomic factors, and sex specific variables. Results: At baseline, AA women were younger and had a higher percentage of Stage A HF (76%) than Cau (54%) and HL (55%) women. Overall, AA and HL women had significantly lower risk of progressing from Stage A to Stage C compared to Cau women [AA vs. Cau adjusted Hazard Ratio (HR) 0.77 (95% Confidence Interval (CI) 0.64 -0.93) p = 0.0055; HL vs. Cau HR 0.54 (95% CI 0.40 -0.71) p < 0.0001]. After stratifying by age groups(<65, 65-69, >70 years), AA women had a similar risk of progression from stage A to C compared to Cau women. When compared to Cau women, AA had an insignificant increased risk of progressing from Stage C to CHD death [adjusted HR 1.29 (95% CI 0.72 -2.32) p = 0.3883)]. Conclusions: Cau women were at higher risk for HF progression from Stage A to Stage C compared to HL women, but at similar risk as AA women. AA women had an insignificant but increased risk of progression from Stage C to CHD death compared to Cau women.

Background: The relationship between obstructive sleep apnea (OSA) and heart failure (HF) has been under-researched especially in postmenopausal women. We therefore evaluated relationship between OSA risk factors and HFpEF and HFrEF in post-menopausal women. Methods: We performed a prospective analysis of a subset of participants who had adjudicated heart failure outcomes (n=42,362) in the Women Health Initiative Observational, Clinical Trial, and Extension Studies (1998-Present). The cohort was followed over an average of 13.4 years. Inverse probability weighting was employed to account for potential selection bias. Cox proportional hazards regression was used to examine the association between OSA risk factors and time to first hospitalized HF. Type of heart failure was determined using the ejection fraction (EF) obtained from 2D echocardiography. EF of ≥45% was categorized as HFpEF, and EF of < 45% was categorized as HFrEF. Models were adjusted for age, race/ethnicity, education, income, marital status, systolic blood pressure, waist-to-hip ratio, diabetes, coronary heart disease, atrial fibrillation, use of hormone replacement therapy, use of sleep medications, modified Charlson comorbidity index, smoking, alcohol consumption, physical activity, and hysterectomy. We also created an OSA summary score (obesity, snoring, poor sleep quality, sleep fragmentation, daytime sleepiness, and hypertension) based on the Berlin questionnaire, which reliably predicts OSA, to examine its relationship with HF. Results: Of the 42,362 women, 1,054 (2.49%) had preserved EF, and 631 (1.49%) had reduced EF. Four of the 6 risk factors (obesity (HR=1.51, 95% CI 1.29-1.76), snoring (HR=1.23, 95% CI 1.04-1.45), sleep fragmentation (HR=1.15, 95% CI 1.01-1.31), and hypertension (HR=1.46, 95% CI 1.31-1.62)) were associated HFpEF after adjusting for confounders. Each additional OSA risk factor in an OSA summary score compared to no risk factors significantly increased the risk of HFpEF in a dose-response fashion (HR=1.36, 1.61, 2.01, 1.97, 2.02, and 2.74 for scores of 1-6, respectively; P trend <0.001) and not HFrEF (P trend =0.26). Only hypertension was associated with HFrEF (HR=1.39, 95% CI 1.22-1.60). Conclusion: Having more OSA risk factors increases the risk of HFpEF but not HFrEF in postmenopausal women. Early recognition and management of OSA risk factors may play an important role in reducing risk of HFpEF in this population.

Background Classification of risk of ischemic stroke is important for medical care and public health reasons. Whether addition of biomarkers adds to predictive power of the Framingham Stroke Risk or other traditional risk factors has not been studied in older women. Methods The Hormones and Biomarkers Predicting Stroke Study is a case-control study of blood biomarkers assayed in 972 ischemic stroke cases and 972 controls, nested in the Women's Health Initiative Observational Study of 93 676 postmenopausal women followed for an average of eight-years. We evaluated additive predictive value of two commercially available biomarkers: C-reactive protein and lipoprotein-associated phospholipase A 2 to determine if they added to risk prediction by the Framingham Stroke Risk Score or by traditional risk factors, which included lipids and other variables not included in the Framingham Stroke Risk Score. As measures of additive predictive value, we used the C-statistic, net reclassification improvement, category-less net reclassification improvement, and integrated discrimination improvement index. Results Addition of C-reactive protein to Framingham risk models or additional traditional risk factors overall modestly improved prediction of ischemic stroke and resulted in overall net reclassification improvement of 6·3%, (case net reclassification improvement = 3·9%, control net reclassification improvement = 2·4%). In particular, high-sensitivity C-reactive protein was useful in prediction of cardioembolic strokes (net reclassification improvement = 12·0%; 95% confidence interval 4·3–19·6%) and in strokes occurring in less than three-years (net reclassification improvement = 7·9%, 95% confidence interval 0·8–14·9%). Lipoprotein-associated phospholipase A 2 was useful in risk prediction of large artery strokes (net reclassification improvement = 19·8%, 95% confidence interval 7·4–32·1%) and in early strokes (net reclassification improvement = 5·8%, 95% confidence interval 0·4–11·2%). Conclusions C-reactive protein and lipoprotein-associated phospholipase A 2 can improve prediction of certain subtypes of ischemic stroke in older women, over the Framingham stroke risk model and traditional risk factors, and may help to guide surveillance and treatment of women at risk.