medwireNews: The risk for atherosclerotic cardiovascular disease (ASCVD) is lower in women with familial hypercholesterolemia than in their male counterparts, the SAFEHEART study indicates.
While women tended to receive less intensive treatment than men and have similar levels of low-density lipoprotein (LDL)-cholesterol, they were around 10 years older than men when they experienced their first ASCVD event, report the researchers. Such events included myocardial infarction, nonfatal ischemic stroke, percutaneous or surgical coronary revascularization, peripheral artery revascularization, and aortic valve replacement.
“These findings might help inform and implement clinical and public health strategies and underscore the need to account for sex when developing risk stratification and personalized care for patients with heterozygous familial hypercholesterolaemia,” write Leopoldo Pérez de Isla (Universidad Complutense, Madrid, Spain) and colleagues in The Lancet Diabetes & Endocrinology.
There is a lot of heterogeneity in the onset and severity of ASCVD among patients with familial hypercholesterolemia, write the authors, and until now, there has been no consensus on the effect of sex on this population.
The researchers assessed data from 5262 participants of the ongoing SAFEHEART study who were 18 years and older with genetically confirmed familial hypercholesterolemia. They tracked the participants’ cardiovascular health at enrolment and over a median follow-up of 10.3 years.
The patients had a mean age of 46.1 years, 54.1% were women, and all were White. Women in the study were 2.2 years older than men, on average (mean 47.1 vs 44.9 years), while men were more often former or current smokers (60.6 vs 41.7%) and had a higher BMI (27.1 vs 26.0 kg/m2).
A total of 82.3% of the participants were taking lipid-lowering medication at the start of the study. By the end of the follow-up, the mean LDL-cholesterol level was similar for women and men, at 3.1 mmol/L and 3.0 mmol/L, respectively. Both groups also experienced a mean 1.39 mmol/L drop in LDL-cholesterol over time.
Pérez de Isla and colleagues found that, at enrolment, 6.8% of women had ASCVD, significantly fewer than the 18.9% of men, and the most common type was coronary artery disease.
First ASCVD events occurred significantly later in women, at a median age of 61.6 years, compared with 50.6 years for men, and significantly fewer women than men had ASCVD events during follow-up, at 7.1% versus 13.8%.
After adjusting for medication use, cardiovascular risk, and other confounding factors, men were 90% more likely than women to experience an ASCVD event and 74% more likely to die from cardiovascular causes.
Women also lived for longer without major adverse cardiovascular disease events (MACE), amounting to a median of 90.1 years in women and 71.0 years in men and a hazard ratio of 3.52. Overall, 25% of women had MACE by 74.9 years of age compared with 55.5 years of age in men.
“ASCVD is the leading cause of morbidity and mortality in females, but risk in females is frequently under-recognized,” write the investigators, adding that “[w]omen have been traditionally under-represented in cardiovascular clinical trials, limiting the ability to develop sex-specific strategies and their implementation in clinical guidelines.”
In an editorial related to the study, Xavier Rossello and Francisca Caimari, both from Hospital Universitari Son Espases in Palma, Spain, said that the consistent sex difference in fatal and nonfatal cardiovascular events among the study participants with familial hypercholesterolemia was “striking.”
They add: “Females have already been described as being frequently underdiagnosed and undertreated relative to males, although this is usually associated with a higher risk of cardiovascular events in females. This report shows a paradoxical lower risk for female participants.”
Pérez de Isla and team suggest that, in addition to sex disparities in disease management, the difference in ASCVD risk between women and men could be due to sex-specific biological differences, such as hormonal effects on metabolism and endothelial function, and higher high-density lipoprotein cholesterol in women.
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group
Lancet Diabetes Endocrinol 2024; doi: 10.1016/S2213-8587(24)00192-X
Lancet Diabetes Endocrinol 2024; doi: 10.1016/S2213-8587(24)00236-5