Cardiovascular Biomarkers and Incident Heart Failure

Study Questions:

What are the associations of 12 cardiovascular biomarkers with heart failure with preserved ejection fraction (HFpEF) versus HF with reduced EF (HFrEF)?

Methods:

This study included four longitudinal community-based cohorts that had prospective ascertainment of incident HFpEF (left ventricular EF [LVEF] ≥50%) and HFrEF (LVEF <50%). These included 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). The authors performed a data analysis from June 25, 2015, to November 9, 2017. Biomarkers included were N-terminal pro–B-type natriuretic peptide or brain natriuretic peptide, high-sensitivity troponin (hs-Tn) T or I, C-reactive protein (CRP), urinary albumin-to-creatinine ratio (UACR), renin-to-aldosterone ratio, D-dimer, fibrinogen, soluble suppressor of tumorigenicity, galectin-3, cystatin C, plasminogen activator inhibitor-1 (PAI-1), and interleukin-6. The main outcome measures included development of incident HFpEF and incident HFrEF. They assessed the incremental effect of each biomarker on its association with HFpEF and HFrEF. They compared C-statistics between models with clinical covariates alone (based on a previously validated prediction model) and models including both clinical covariates and the given biomarker.

Results:

In the final study cohort of 22,756 participants (12,087 women and 10,669 men; mean [SD] age, 60 [13] years) with a median follow-up period of 12 years, 633 participants developed incident HFpEF, and 841 developed HFrEF. The investigators, using models adjusted for clinical risk factors of HF (such as age, sex, race/ethnicity, systolic blood pressure, hypertension treatment, body mass index, diabetes, smoking status, presence of LV hypertrophy, and left bundle branch block), found that two biomarkers were significantly associated with incident HFpEF: UACR (hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.20-1.48; p < 0.001) and natriuretic peptides (HR, 1.27; 95% CI, 1.16-1.40; p < 0.001), with suggestive associations for hs-Tn (HR, 1.11; 95% CI, 1.03-1.19; p = 0.008), PAI-1 (HR, 1.22; 95% CI, 1.03-1.45; p = 0.02), and fibrinogen (HR, 1.12; 95% CI, 1.03-1.22; p = 0.01). Six biomarkers were associated with incident HFrEF: natriuretic peptides (HR, 1.54; 95% CI, 1.41-1.68; p < 0.001), UACR (HR, 1.21; 95% CI, 1.11-1.32; p < 0.001), hs-Tn (HR, 1.37; 95% CI, 1.29-1.46; p < 0.001), cystatin C (HR, 1.19; 95% CI, 1.11-1.27; p < 0.001), D-dimer (HR, 1.22; 95% CI, 1.11-1.35; p < 0.001), and CRP (HR, 1.19; 95% CI, 1.11-1.28; p < 0.001). The study authors reported that natriuretic peptides and hs-Tn were more strongly associated with HFrEF compared with HFpEF. Specifically, a 1-SD increase in log-transformed natriuretic peptides was associated with a 1.5-fold increased risk of future HFrEF (95% CI, 1.41-1.68) compared with a 1.3-fold increased risk of HFpEF (95% CI, 1.16-1.40; p = 0.005 for difference). Similarly, a 1-SD increase in hs-Tn was associated with a 1.4-fold increased risk of HFrEF (95% CI, 1.29-1.46), whereas hs-Tn was more weakly associated with HFpEF (HR, 1.11; 95% CI, 1.03-1.19; p = 0.008; p < 0.001 for difference).

Conclusions:

The study authors concluded that biomarkers of renal dysfunction, endothelial dysfunction, and inflammation were associated with incident HFrEF, whereas only natriuretic peptides and UACR were associated with HFpEF.

Perspective:

This study of ‘big data’ suggests that using a panel of biomarkers may be a better tool for management of HF. Prospective studies are needed to confirm these findings and the potential clinical utility of a multimarker strategy of managing HF patients.

Clinical Topics: Anticoagulation Management, Dyslipidemia, Heart Failure and Cardiomyopathies, Lipid Metabolism, Novel Agents, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Aldosterone, Biological Markers, C-Reactive Protein, Creatinine, Cystatin C, Fibrin Fibrinogen Degradation Products, Fibrinogen, Galectin 3, Heart Failure, Inflammation, Interleukin-6, Natriuretic Peptide, Brain, Natriuretic Peptides, Outcome Assessment (Health Care), Peptide Fragments, Plasminogen Activator Inhibitor 1, Protein C Inhibitor, Renin, Salivary Cystatins, Stroke Volume, Troponin T, Troponin I


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