Sex differences and gender-related factors in the management and perception of LDL-cholesterol in ASCVD: Real-Life evidence from the EPHESUS registry in cardiology practice

Abstract

Aims

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality globally. While it impacts both sexes, women are frequently underdiagnosed and undertreated, particularly in lipid management. This study aimed to evaluate sex differences, and the gender-related factors potentially underlying them, in lipid control, the utilization of lipid-lowering therapy (LLT), and related perceptions within a large real-world cohort.

Methods

We analyzed 1482 patients with established ASCVD from the nationwide, multicenter EPHESUS registry, conducted in 40 cardiology outpatient clinics across Turkey. Differences between women and men in risk profiles, LLT use, low density lipoprotein-cholesterol (LDL-C) goal attainment, and perceptions from both patients and physicians were assessed. Women and men were compared before and after 1:1 propensity score matching for age and education; covariate balance was quantified with standardized mean differences (SMD).

Results

Women showed a greater burden of cardiometabolic conditions such as hypertension, diabetes, and obesity, yet were less often prescribed statins. Total cholesterol, HDL-C, non-HDL-C and on-treatment LDL-C were higher in women than in men, whereas triglycerides were similar between the sexes; on-treatment LDL-C was significantly higher in women (115 mg/dL vs. 100 mg/dL, p < 0.001). Women also met LDL-C targets less frequently according to the 2016 ESC/EAS guidelines (14.9% vs. 19.6%, p = 0.017), while the difference for the 2019 target was not significant (6.3% vs. 8.3%, p = 0.186). After matching, 924 patients (462 women and 462 men) remained; age and education were well balanced (SMD < 0.05), whereas cardiometabolic covariates remained imbalanced by design. Differences in lipid levels were no longer apparent, and among patients receiving high-intensity statins women more frequently achieved the 2016 LDL-C target (26.0% vs. 13.6%, p = 0.017), whereas the corresponding difference for the 2019 target did not reach statistical significance (10.7% vs. 4.5%, p = 0.072). Media influence was the most common physician-reported reason for LLT cessation; side effects and physician-advised discontinuation were reported more often for women, although these differences were not statistically significant.

Conclusion

Age and education accounted for a substantial part of the observed differences between women and men in ASCVD care, whereas lower statin prescription in women persisted after matching. Studies addressing sex differences should incorporate gender-related demographic factors into their design and analysis.