This article is more than 5 years old. Information may no longer be current.
Women may particularly benefit from sex-specific HF prevention
Click Here to Manage Email Alerts
Sex-specific prevention strategies are critical in the presence of different HF risk factors and mechanisms in men and women, according to a review published in JACC: Heart Failure.
Melissa A. Daubert, MD, associate professor of medicine at Duke University School of Medicine, member of the Duke Clinical Research Institute and Cardiology Today Next Gen Innovator, and Pamela S. Douglas, MD, professor of medicine and Ursula Geller Professor for Research in Cardiovascular Disease at Duke University School of Medicine and member of the Duke Clinical Research Institute, analyzed data regarding sex differences for HF with preserved ejection fraction and HF with reduced ejection fraction.
Prevention of HFrEF
The most common etiology of HFrEF in women is CAD, although it affects a smaller proportion of women vs. men. The effective treatment of CAD risk factors should be a major component of primary prevention and includes hyperlipidemia, hypertension, obesity, diabetes and physical inactivity. There are some risk factors and mechanisms that are specific to women and include hormonal changes from menopause, pregnancy complications, psychosocial stress, autoimmune disease and cancer treatments.
Although hypertension has the highest attributable risk for HFrEF in women, they are less likely to control their BP compared with men. The number of women who adequately control their BP decreases with advancing age. Poor BP control may be explained through increased arterial stiffness, medication uptitration, hormonal influences, overactivation of the renin-angiotensin system, autonomic control, and salt and water regulation. Women typically require lower doses of medications such as beta-blockers, diuretics and ACE inhibitors because they have better responses to them vs. men. Even with these lower doses, women are more likely to have more adverse effects.
“Antihypertensive therapy needs to be individualized in women to ensure target blood pressure levels are achieved with medications that minimize side effects and maximize compliance,” Daubert and Douglas wrote.
Besides hypertension treatment, other coexisting CAD risk factors should also be treated for primary prevention of HF in women, including diabetes, which is the second highest risk factor for the development of HFrEF in women. Diabetes increases the risk for HF even in the absence of significant CAD. Early and aggressive treatment for women with diabetes is necessary for the prevention of macrovascular and microvascular coronary complications related to the development of HFrEF and may include SGLT2 inhibitors.
Physical inactivity is not only inversely associated with the incidence of HF, but it also contributes to a similar number of CV deaths as tobacco smoking. Current guidelines recommend 150 minutes of moderate activity per week for CVD prevention in women.
“Along with effective risk factor treatment, a critical component of preventing HFrEF in women is to prescribe regular physical activity, assess for compliance and encourage ongoing efforts,” Daubert and Douglas wrote.
Early indicators of increased CV risk in women are pregnancy complications, including premature birth, gestational diabetes and preeclampsia.
“This underscores the importance of obtaining a comprehensive reproductive history when evaluating cardiovascular risk in women,” Daubert and Douglas wrote. “Pregnancy complications can identify women at high risk who might benefit from the early application of preventive interventions and risk factor modification.”
Another significant contribution to the global burden of CVD is HFrEF caused by nonischemic dilated cardiomyopathy and may be related to sex differences in genetics and sex hormones. Peripartum cardiomyopathy may also have genetic underpinnings to HFrEF. Cardiotoxicity from cancer treatments is another cause of nonischemic cardiomyopathy, especially in women with breast cancer.
Women have been underrepresented in clinical trials focused on HFrEF, according to the review.
“Current HF treatment guidelines are not sex-specific due to underrepresentation of women and a lack of prospective, randomized data for sex-specific analyses of safety and treatment efficacy,” Daubert and Douglas wrote.
Women with HFpEF
HFpEF is more often seen in women compared with men, which may be a result of women living longer. There also may be underlying sex-specific pathophysiology that explains the disproportionate burden of HFpEF in women, according to the review.
Hypertension and obesity account for more than half of the attributable risk for HFpEF in women. The mechanisms behind obesity and incidence HFpEF may include insulin resistance, systemic inflammation, myocardial remodeling and fibrosis, and coronary microvascular dysfunction. Weight loss has been shown to reduce the effects of the inflammatory response.
Incident HFpEF in women can also be predicted by other factors of metabolic syndrome, including elevated HP, increased waist-to-hip ratio, higher fasting glucose and greater insulin resistance.
“Taken together, this suggests that the pathogenesis of HFpEF may be a complication of the metabolic syndrome, which is significantly more prevalent among women compared with men (35.6% vs. 30.3%; P < .001),” Daubert and Douglas wrote.
Statin therapy may also help to prevent HFpEF in women, according to the review. This therapy can go beyond its lipid-lowering properties by restoring nitric oxide bioavailability and improving endothelial redox balance.
“In HFpEF, because there are no proven therapies, identification and implementation of effective preventive strategies in women is particularly urgent,” Daubert and Douglas wrote. “In HFrEF, additional research is needed to generate evidence to support whether sex-specific primary and secondary treatment interventions are advantageous.” – by Darlene Dobkowski
Disclosures: Daubert and Douglas report no relevant financial disclosures.
Read more about
Click Here to Manage Email Alerts