Prevalence, Neurohormonal Correlates, and Prognosis of Heart Failure Stages in the Community

The purpose of this study was to describe the prevalence and prognosis of HF stages in the community; to evaluate if preclinical HF stages are characterized by elevation of pro-inflammatory (C-reactive protein), neurohormonal activation (B-type natriuretic peptide, renin and aldosterone), and cardiac stress biomarkers (high-sensitivity troponin I, ST-2, and growth differentiation factor-15).

The American Heart Association/American College of Cardiology heart failure (HF) classification has 3 stages. Knowledge regarding the community burden of HF stages is limited, and data on the biomarker profile associated with HF stages are scarce, although higher concentrations of certain biomarkers are associated with preclinical HF.

We evaluated 6,770 participants (mean age 51 years; 54% women) from the Framingham Study, defining 4 stages: 1) healthy: no risk factors; 2) stage A: presence of HF risk factors (hypertension, diabetes, obesity, coronary artery disease), no cardiac structural/functional abnormality; 3) stage B: presence of prior myocardial infarction, valvular disease, left ventricular (LV) systolic dysfunction, LV hypertrophy, regional wall motion abnormality, or LV enlargement; 4) stage C/D: prevalent HF.

The prevalence of HF stages A and B were 36.5% and 24.2%, respectively, rising with age (odds ratio: 1.70 [95% confidence interval: 1.64 to 1.77] per decade increment). In age- and sex-adjusted models, we observed a gradient of increasing biomarker levels across HF stages (p < 0.05; n = 3,416). Adjusting for age and sex, mortality rose across HF stages (232 deaths, mean follow-up 7 years), with 2- and 8-fold mortality risks for stages B and C/D, respectively, compared with healthy.

Approximately 60% of our sample has preclinical HF, and those in stage B had higher concentrations of HF biomarkers and experienced a substantial mortality risk.