Association of Biomarkers With Heart Failure With Preserved, Reduced Ejection Fraction

There is a lack of recognized novel biomarkers of the risk of heart failure with preserved ejection fraction (HFpEF), underscoring limitations in understanding factors causing the development of HFpEF, according to a study published in JAMA Cardiology.

With heart failure occurring in 20% of men and women, there is a desire among clinicians to improve methods to identify people who are at an increased risk for heart failure and to implement preventive measures.

“Several previous studies have demonstrated the utility of targeting heart failure prevention efforts to high-risk individuals who were identified by single biomarker assessments,” wrote the authors of the study. “Individual assessment of heart failure risk, however, is still in its infancy, and the clinical applicability of existing models of assessment of heart failure is limited. Furthermore, half of patients presenting with heart failure are classified as HFpEF versus HFrEF.”

The study included 22,756 participants from 4 prospective, observational community-based cohorts: the Cardiovascular Health Study (1989-1990; 1992-1993 for supplemental African-American cohort); the Framingham Heart Study (1995-1998); the Multi-Ethnic Study of Atherosclerosis (2000-2002); and the Prevention of Renal and Vascular End-stage Disease study (1997-1998).

Statistical analysis was performed from June 25, 2015 through November 9, 2017. Medical history was documented, and physical examinations, fasting blood draws, and electrocardiography were performed at baseline examinations.

The following biomarkers were examined: N-terminal pro B-type natriuretic peptide or brain natriuretic peptide, high-sensitivity troponin T or I, C-reactive protein (CRP), UACR, renin to aldosterone ratio, D-dimer, fibrinogen, soluble suppressor of tumorigenicity, galectin-3, cystatin C, plasminogen activator inhibitor 1, and interleukin 6.

During a median follow-up of 12 years, 633 participants developed incident HFpEF, and 841 developed HFrEF. UACR (HR, 1.33; 95% CI, 1.20-1.48; P&thinsp; <&thinsp;.001) and natriuretic peptides (HR, 1.27; 95% CI, 1.16-1.40; P &thinsp;<&thinsp;.001) were significantly associated with incident HFpEF. Meanwhile, high-sensitivity troponin (HR, 1.11; 95% CI, 1.03-1.19; P&thinsp;=&thinsp;.008), plasminogen activator inhibitor 1 (HR, 1.22; 95% CI, 1.03-1.45; P &thinsp;=&thinsp;.02), and fibrinogen (HR, 1.12; 95% CI, 1.03-1.22; P&thinsp;=&thinsp;.01) had suggestive associations with incident HFpEF.

In contrast, 6 biomarkers were associated with incident HFrEF: natriuretic peptides (HR, 1.54; 95% CI, 1.41-1.68; P&thinsp; <&thinsp;.001), UACR (HR, 1.21; 95% CI, 1.11-1.32; P&thinsp; <&thinsp;.001), high-sensitivity troponin (HR, 1.37; 95% CI, 1.29-1.46; P&thinsp; <&thinsp;.001), cystatin C (HR, 1.19; 95% CI, 1.11-1.27; P&thinsp; <&thinsp;.001), D-dimer (HR, 1.22; 95% CI, 1.11-1.35; P&thinsp; <&thinsp;.001), and CRP (HR, 1.19; 95% CI, 1.11-1.28; P&thinsp; <&thinsp;.001).

“In general, biomarkers modestly improved risk estimation, and discrimination metrics overall were lower for HFpEF models, highlighting current limitations in our understanding of factors underlying the development of HFpEF,” concluded the authors. “Although some studies demonstrate the potential utility of biomarker-guided prevention strategies, nuances in antecedent factors differentiating HFpEF and HFrEF highlight the need for future studies to examine the role of biomarkers in heart failure subtype-specific risk estimation.”