Do Biomarkers, CV Risk Factors Determine Heart Failure Development in Women, Men?

Over a median 12.5 years of follow-up, close to 10% of participants in a study developed incident heart failure following investigation of possible differentiation of cardiovascular (CV) risk factors and biomarkers based on sex, according to the study results published in Journal of the American College of Cardiology.

“Circulating biomarkers reflect distinct pathophysiological processes, and elevated levels of HF-related biomarkers may indicate [CV] or systemic derangement early in the time course of disease progression,” the authors noted, but sex-related differences are not well understood.

Their study enrolled 22,756 participants, with a mean (SD) age of 60 (13) years, and most (53%) were women. All were recruited between 1989 and 2002 and did not have heart failure at baseline. Data were gathered from 4 community-based cohorts: the Framingham Heart Study, the Prevention of REnal and Vascular Endstage Disease trial, the Multi-Ethnic Study of Atherosclerosis, and the Cardiovascular Health Study.

The biomarkers measured were natriuretic peptides (NPs), cardiac troponins (cTns), plasminogen activator inhibitor-1 (PAI-1), D-dimer, fibrinogen, C-reactive protein (CRP), sST2, galectin-3, cystatin-C, and urinary albumin:creatinine ratio (UACR). A baseline exam following study enrollment also evaluated for several clinical factors: blood pressure, body mass index (BMI), diabetes status, left ventricular hypertrophy (LVH), and left bundle branch block (LBBB). In addition, first heart failure event was classified into heart failure with preserved ejection fraction (HFpEF; LV ejection fraction [LVEF] ≥ 50%) or heart failure with reduced ejection fraction (HFrEF; LVEF < 50%).

Results show that development of incident heart failure strongly correlated with age, smoking status, type 2 diabetes, hypertension, BMI, atrial fibrillation (afib), myocardial infarction (MI), LVH, and LBBB in both women and men (P < .001). In addition, good discrimination was demonstrated for both men (C-statistic = 0.80; 95% CI, 0.79-0.82) and women (C-statistic = 0.83; 95% CI, 0.82-0.84).

Per 1000 person-years, the overall incidence of heart failure was 25% lower among women than men: 7.1 (95% CI, 6.6-7.5) vs 9.5 (95% CI, 8.9-10.1). Women also had a lower overall risk of heart failure (multivariable-adjusted HR, 0.75; 95% CI, 0.68-0.82); a longer median time to diagnosis, at 8.2 (range, 4.8-10.8) vs 7.1 (range, 3.7-10.2) years; and an older mean (SD) age at diagnosis: 79.6 (8.3) vs 77.3 (8.9) years.

Additional analysis revealed:

• Heart failure risk was more than twice as high per 10 years of age among women (HR, 2.07; 95% CI, 1.89-2.28) vs 1.8 among men (HR, 1.8, 95% CI, 1.67-1.95)
• Hypertension meant a 98% greater risk of women developing heart failure compared with 67% among men
• BMI increasing by 4 kg/m² meant men had a 28% greater heart failure risk vs 18% for women
• Women had higher baseline NPs, D-dimer, fibrinogen, CRP, galectin-3, and UACR (P < .001)
• Men had higher baseline cTns, PAI-1, sST2, and cystatin-C (P < .001)
• Incident heart failure was strong for both women (HR, 1.47; 95% CI, 1.35-1.61) and men (HR, 1.57; 95% CI, 1.45-1.70) when accounting for overall NPs
• NPs, cTns, and UACR had a stronger correlation with HFrEF in men vs women
• cTns, CRP, and UACR had a stronger correlation with HFpEF in women vs men

Overall, despite certain correlations for both men and women, the investigators’ attempt to improve risk prediction for heart failure had limited success.

“CV risk factors are strongly and similarly associated with incident [heart failure] in both sexes, highlighting the similar importance of risk factor control in reducing [heart failure] risk in the community,” the authors concluded. “There are subtle sex-related differences in the predictive value of individual biomarkers, but the overall improvement in [heart failure] risk estimation when included in a clinical [heart failure] risk prediction model is limited in both sexes.”

Limitations to the study results include lack of a universal definition for heart failure, the 4 cohorts used for the study analysis did not contain the same biomarker data, biomarker measures were only taken once, and the LVEF cutoff of 50% that was used.

Reference

Suthahar N, Lau ES, Blaha MJ, et al. Sex-specific association of cardiovascular risk factors and biomarkers with incident heart failure. J Am Coll Cardiol. 2020;76(12):1455-1465. doi:10.1016/j.jacc.2020.07.044