Outcomes for heart failure (HF) patients remain suboptimal. No known therapy improves mortality in acute HF and HF with preserved ejection fraction; the most recent HF trial results have been negative or neutral. Improvement in surrogate markers has not necessarily translated into better outcomes. To translate breakthroughs with potential therapies into clinical benefit, a better understanding of the pathophysiology establishing the foundation of benefit is necessary. Vascular function plays a central role in the development and progression of HF. Endothelial function and nitric oxide availability affect myocardial function, systemic and pulmonary hemodynamics, and coronary and renal circulation. Arterial stiffness modulates ventricular loading conditions and diastolic function, key components of HF with preserved ejection. Endothelial function and arterial stiffness may therefore serve as important physiological targets for new HF therapies and facilitate patient selection for improved application of existing agents.

for the Health ABC Study Background-Despite the rising heart failure (HF) incidence and aging United States population, there are no validated prediction models for incident HF in the elderly. We sought to develop a new prediction model for 5-year risk of incident HF among older persons. Methods and Results-Proportional hazards models were used to assess independent predictors of incident HF, defined as hospitalization for new-onset HF, in 2935 elderly participants without baseline HF enrolled in the Health ABC study (age, 73.6Ϯ2.9 years, 47.9% males, 58.6% whites). A prediction equation was developed and internally validated by bootstrapping, allowing the development of a 5-year risk score. Incident HF developed in 258 (8.8%) participants during 6.5Ϯ1.8 years of follow-up. Independent predictors of incident HF included age, history of coronary disease and smoking, baseline systolic blood pressure and heart rate, serum glucose, creatinine, and albumin levels, and left ventricular hypertrophy. The Health ABC HF model had a c-statistic of 0.73 in the derivation dataset, 0.72 by internal validation (optimism-corrected), and good calibration (goodness-of-fit 2 6.24, Pϭ0.621). A simple point score was created to predict incident HF risk into 4 risk groups corresponding to Ͻ5%, 5% to 10%, 10% to 20%, and Ͼ20% 5-year risk. The actual 5-year incident HF rates in these groups were 2.9%, 5.7%, 13.3%, and 36.8%, respectively. Conclusion-The