Log in to MyACC
Sex-Specific Associations of CV Risk Factors and Biomarkers With Incident HF
Quick Takes
- There are no major sex-related differences in the association between CV risk factors, biomarkers, and the risk of incident HF.
- Clinical risk factors combined capture the bulk of HF risk, with biomarkers (including natriuretic peptides) adding little to improving HF risk prediction.
Study Questions:
Does the association between cardiovascular (CV) risk factors and biomarkers with incident heart failure (HF) differ between men and women?
Methods:
The authors pooled data from four cohorts, generating a sample of 22,756 participants, ages >30 years, without known HF. The four cohorts included the FHS (Framingham Heart Study), PREVEND (Prevention of Renal and Vascular End-stage Disease), the MESA (Multi-Ethnic Study of Atherosclerosis), and the CHS (Cardiovascular Health Study). They examined sex-specific associations between CV risk factors, electrocardiogram findings, a panel of biomarkers (natriuretic peptides [NPs], high-sensitivity troponin, D-dimer, C-reactive protein [CRP], cystatin-C, urinary albumin-to-creatinine ratio [UACR], galectin-3, soluble ST-2, plasminogen activator inhibitor [PAI], and fibrinogen), with incident HF. The incremental predictive value of the selected biomarkers of the clinical HF model was examined in men and women separately.
Results:
Of 22,756 participants (mean age 60 years, 53.1% women, 75% white), 989 women (8.1%) and 1,106 men (10.4%) developed HF at a median follow-up of 12 years. Amongst clinical risk factors, the age and hypertension-related increase in risk of HF was higher in women than in men, while body mass index was more strongly associated with HF risk in men than in women. Amongst biomarkers, NPs, D-dimer, fibrinogen, CRP, galectin-3, and UACR levels were higher in women, while troponin, PAI-1, soluble ST2, and cystatin-C levels were higher in men. None of the biomarkers showed a significant interaction with sex for incident HF. After adjustment for NPs, only troponin, CRP, and UACR were associated with incident HF in the overall population. In men, only troponin was associated with incident HF, while in women, all three aforementioned markers were associated with incident HF. The addition of individual biomarkers (i.e., NPs, cardiac troponins, and CRP) to a clinical model did not appreciably improve model discrimination in both sexes.
Conclusions:
Biomarkers (NPs, troponin, CRP, and UACR) were similarly associated with incident HF in both sexes and did not significantly improve overall risk prediction of HF.
Perspective:
This pooled analysis represents one of the largest biomarker studies to date. While the focus of the study was on sex differences—which were minimal, there are other important findings that warrant highlighting: clinical risk factors combined capture the bulk of HF risk, with biomarkers (including NPs) adding little to improving HF risk prediction. Overall, these findings argue against systematic incorporation of biomarker testing in establishing risk of incident HF—whether in men or women. However, the study design—pooling multiple different cohorts together with varying definitions—has numerous limitations and does not address the clinical utility of measuring biomarkers to identify patients who would benefit from preventive therapies, establishing risk in specific patient populations such as those with diabetes, or determine which pathologic pathways are involved in specific forms of HF; a highly heterogeneous disease. Much work remains to be done to fulfill the promise of biomarkers in assessing risk and personalizing therapies.
Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Hypertension
Keywords: Biomarkers, Body Mass Index, C-Reactive Protein, Creatinine, Cystatin C, Electrocardiography, Fibrinogen, Galectin 3, Heart Failure, Hypertension, Natriuretic Peptides, Plasminogen Activator Inhibitor 1, Risk Factors, Secondary Prevention, Troponin
< Back to Listings
