Sex-Based Differences for Heart Failure Risk Need More Attention, Research

The new data should encourage future investigation of specific prevention efforts to target specific populations, the study author says.

Sex-Based Differences for Heart Failure Risk Need More Attention, Research

Women are generally at lower risk for heart failure than men, but most heart failure can be traced back to the same cardiovascular risk factors in both sexes, according to new data. Experts say this information should encourage prevention efforts across the spectrum of patients vulnerable to developing heart failure.

“Modifiable risk factors . . . account for about 60% of the predictable risk, so if you would succeed in reducing these risk factors, we would be able to reduce the heart failure risk tremendously,” lead study author Christina Magnussen, MD (University Heart Center Hamburg, Germany), told TCTMD. “We have to address blood pressure, we have to modify the lifestyle of our patients so that we are able to prevent overweight and obesity, and perhaps if so we can prevent a large amount of incident heart failure in these patients.”

For the study, Magnussen and colleagues followed 78,657 individuals from European community-based studies in the BiomarCaRE consortium for a median of 12.7 years. Overall, heart failure was less common in women (5.9%) than in men (7.3%). Yet, while the incidence of heart failure increased for both sexes after age 60, there was a more rapid rise among men; heart failure incidence in women only exceeded that in men after age 85.

Additionally, incident heart failure increased the risk of death in both sexes by more than fivefold, but men were at even higher risk than women in multiple models.

With the exception of total cholesterol in men, all classic cardiovascular risk factors, history of MI and stroke, as well as C-reactive protein (CRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were associated with new onset heart failure in both sexes. However, the relationship between systolic BP, heart rate, CRP, and NT-proBNP with incident heart failure was less strong in women compared with men.

Risk Factors for Incident Heart Failure by Sex




P for Interaction


95% CI


95% CI

Systolic BP






Heart Rate





< 0.001













Lastly, the overall rate of population-attributable risk of all risk factors combined—including body mass index, systolic BP, total cholesterol, daily smoking, diabetes, history of MI, and stroke—was 59% for women and 62.9% for men. Obesity and systolic blood pressure were the most frequent modifiable risk factors observed in both men and women, and researchers labeled obese women and hypertensive men to be at the highest attributable risk.

The findings were published this week in a special issue of JACC: Heart Failure, which also looked at differences in heart failure drug efficacy and adverse reactions between men and women.

Focus on Modifying Obesity, Hypertension

In an editorial accompanying the study, Martin R. Cowie, MD, and Rosita Zakeri, MBChB, PhD (Royal Brompton Hospital, Imperial College London, England), write that the study “provides valuable insights into what causative factors are likely driving the development of heart failure in these European populations.” They caution, however, that because the study cohort is “almost exclusively Caucasian,” the findings may not be totally applicable to more diverse populations.

Still, the researchers show that “the two most important risk factors that contribute to the development of heart failure is being overweight and obese and [having] hypertension,” Cowie and Zakeri say. While these have both been shown to have substantial implications for a wide variety of heart diseases in the past, the editorialists argue that the public health message should be a continuation of what has already been started.

Initiatives to design cities that encourage physical activity, improved food labeling legislation, and even the institution of sugar taxes “should pay dividends not only in terms of a reduction in obesity and being overweight and diabetes, but also in a reduction in hypertension and coronary heart disease and the prevention (or at least a delay the onset) of heart failure,” they write.

Even though the study identifies sex-based differences in heart failure risk, Cowie and Zakeri argue that prevention efforts should be made for all. “Although sex does modify the impact of individual risk favors and their overall contribution to the burden of numbers of heart failures, the overall message for prevention is not sex-specific,” they write. “Prevention is surely better than cure for everyone, and the same advice can be given (or applied) to both men and women.”

Magnussen agreed, but noted that a reduction in smoking and hypertension may lower the risk of heart failure more proportionally in men than in women, for example, “because they had a higher degree of attributable risk in these two risk factors.”

At this point, “we now need further studies that highlight or investigate specific prevention strategies,” she said. Additionally, Magnussen called for more research to identify the cause of heart failure in the approximately 40% of patients in whom it remains unknown.

  • The BiomarCaRE Project was funded by European Union Seventh Framework Programme award.
  • Magnussen, Cowie, and Zakeri report no relevant conflicts of interest.