Cardiovascular (CV) risk factors are strongly and similarly associated with incident heart failure (HF) in both sexes, highlighting the similar importance of risk factor control in reducing HF risk, explains Navin Suthahar, MD, MSc, PhD. “Sex-related differences in association with CV risk factors and biomarkers with HF are not only of great interest to the medical community, but also among the general public,” he says. “Interestingly, despite HF syndrome affecting a substantial number of women, it is often considered to be a ‘man’s disease.’”

Sex-related Differences in HF Pathogenesis Consistently Observed

For a study published in Journal of the American College of Cardiology, Dr. Suthahar, Jennifer E. Ho, MD, Rudolf A. de Boer, MD, PhD, and colleagues sought to understand whether CV disease risk factors and biomarkers associate differentially with HF risk in men and women. Sex-related differences in HF pathogenesis have consistently been observed, stresses Dr. de Boer. For instance, when subjected to CV stress, female hearts can experience left ventricular hypertrophy more readily than that of men. On the other hand, cardiomyocytes die more often in men than women. The exact mechanisms underlying these sex-related differences are incompletely understood, and sex-specific associations of CV biomarkers and risk factors with incident HF might provide insights into sex-specific pathophysiological mechanisms associated with HF.”

The purpose of studying sex-specific associations of CV risk factors with incident HF also directly relates to public health, Dr. Suthahar explains. “If a specific risk factor is known to be more prevalent in either sex or is more strongly associated with incident HF in either sex, public health policies could be designed, promoted, and implemented accordingly,” he says.

In this study, analysis was conducted using data from four community-based cohorts with 12.5 years of follow-up, according to Dr. Ho. The cohorts included Framingham Heart Study (FHS), Multi-Ethnic Study of Atherosclerosis (MESA), and Cardiovascular Health Study (CHS) from the United States, as well as Prevention of Renal and Vascular End-stage Disease (PREVEND) from The Netherlands. Between 1989 and 2002, 22,756 participants who were free of HF at baseline were recruited.

Men and Women Equal in HF Risk Prediction

Among total subjects, (mean age 60 years, 53% women), HF occurred in 2,095 (47% women). Age, smoking, type 2 diabetes, hypertension, BMI, atrial fibrillation, myocardial infarction, left ventricular hypertrophy, and left bundle branch block were strongly associated with HF in both sexes, and the combined clinical model had good discrimination in both men and women (Table). The majority of biomarkers were strongly and similarly associated with HF in both sexes.  “From a public health point of view, sex-related differences in prevalence of risk factors should also be taken into account,” Dr. Suthahar notes. “For example, atrial fibrillation and myocardial infarction, both precursors of HF, bear equal risk in both sexes but are more frequently observed in men than in women.”

Dr. de Boer notes two key findings from the investigation. “There may be important sex-related differences in HF incidence, presentation, and hospitalizations, but when it comes to HF risk prediction with commonly available tools, such as clinical risk factors and biomarkers, men and women are almost equal,” he says. “Surprisingly, our study demonstrated that major HF-related pathophysiological mechanisms sensed by biomarkers were, in fact, broadly similar in both women and men.”

Dr. de Boer stresses the importance of identifying both men and women with CV risk factors and treating them adequately. “A single biomarker measurement may not directly improve HF risk prediction, but it would definitely facilitate discussion with patients about how to prevent HF and may also motivate patients to initiate HF preventative strategies,” he says.

Universal Definition of HF Is Crucial

Future research should focus on three factors, according to Dr. Suthahar. “Biomarkers selected for this study were limited to those with a priori knowledge and were mostly circulating proteomic biomarkers,” he explains. “Subsequent studies should employ an unbiased biomarker approach, focusing on urinary biomarkers as well as non-protein biomarkers. Also, particularly for HF risk prediction, studies examining the value of serial biomarker measurements should be conducted, with a focus on sex-related differences. Perhaps most importantly, clinicians and researchers need to work together to create a universal definition of HF.”


Sex-Specific Associations of Cardiovascular Risk Factors and Biomarkers With Incident Heart Failure