P631Sex-related differences in clinical characteristics, low-density lipoprotein cholesterol control and cardiovascular outcomes in familial hypercholesterolemia

Abstract

Background: Heterozygous familial hypercholesterolemia (HeFH) is a metabolic disorder associated with very high low-density lipoprotein cholesterol (LDL-C) and premature atherosclerotic coronary artery disease. While gender has been already shown to contribute to differences in clinical presentation, atherosclerosis and cardiovascular events, it remains to be fully elucidated whether gender differences in HeFH patients exist. Purpose: The aim of this study was to compare clinical characteristics, lipid profile, and the occurrence of cardiovascular events between men and women with HeFH. Methods: We evaluated 271 HeFH who did not receive any lipid lowering therapy (LLT) at their first visit to our institution. LLT including a statin was commenced in all subjects after their first visit. HeFH was diagnosed according to the following Japanese HeFH guidelines: the presence of two or more factors including LDL-C ≥4.7 mmol/l (180 mg/l), tendon/skin xanthomas, and a familial history of HeFH or premature coronary artery disease within second degree of kinship. The clinical characteristics, change in LDL-C under LLT and the occurrence of major adverse cardiac events (MACE: cardiac death, non-fatal myocardial infarction and any revascularization) were evaluated. Results: The proportion of women and men with HeFH was similar (49% vs. 51%). The average age of women and men was 44±16 vs. 43±16 years (p=0.53), respectively. 4% of women and 11% of men already had premature coronary artery disease prior to their first visit (p=0.01). Female patients were less likely to be obese (21±3 vs. 24±5 kg/m2 p<0.01), smokers (13 vs. 70%, p<0.01) and to have a history of hypertension (15 vs. 33%, p<0.01). LDL-C level prior to LLT were significantly higher in women (5.9±0.1 vs. 5.5±0.1 mmol/l, p=0.03). Highintensity statin (35 vs. 49%, p=0.02) and probucol (3 vs. 8%) were less frequently used in women although the latter comparison failed to meet statistical significance (p=0.07). However, percent change in LDL-C level was similar in both genders (41±23 vs. 43±21%, p=0.54), resulting in its higher on-treatment level in women (3.3±0.1 vs. 3.0±0.1 mmol/l, p=0.02) (Table 1). Despite less favourable control of LDL-C in women, a less likelihood of experiencing a MACE was observed in women compared to men (1.4 vs. 9.1%, log-rank test p<0.01, Figure 1). Conclusions: Female subjects with HeFH harborued less atherogenic risks. While women with HeFH received less intensive management of lipid profiles and achieved less favourable control of LDL-C, their cardiovascular risk was still low compared to men. These observations suggest sex-related differences in lipid profiles, response to a statin and cardiovascular event rates of HeFH patients. In addition to classical coronary risk factors, sex hormone might affect cardioprotective effect for women even in HeFH. (Table Presented).