(VP100) SEX DIFFERENCES IN THE PRESENTATION,TREATMENT AND OUTCOMES OF PATIENTS WITH HOMOZYGOUS FAMILIAL HYPERCHOLESTEREMIA

Background: Homozygous familial hypercholesteremia (HoFH) is a rare, autosomal recessive lipid metabolism disorder characterized by high levels of LDL-C, and premature cardiovascular disease. HoFH affects equal numbers of female and male patients. Sex-related differences are well described in heterozygous FH, but whether there are sex-related differences in patients with HoFH is unknown.

The objective of this study was to investigate sex-related differences in the treatment and outcomes of patients with HoFH.

METHODS AND RESULTS: Data were extracted from the Canadian HoFH registry. The registry used an observational study design with 48 enrolled patients across 5 provinces.

Patient clinical and lipid characteristics, lipid-lowering therapies (LLTs), and cardiovascular events are presented using descriptive statistics, including median and interquartile range (IQR) and frequency with percentages. Major adverse cardiovascular events (MACE) was defined as the composite of cardiovascular death, non-fatal myocardial infarction, and stroke. Sex differences between continuous and categorical variables were analyzed using Mann-Whitney U-test and Fisher’s Exact test, respectively.

This study included 48 HoFH patients (27 (56%) female). The median age at diagnosis in females was 14 (IQR 9.0-30.0) and in males was 8 (IQR 2.0-23.0) (p=0.07). Baseline characteristics were comparable between females and males (BMI in females = 23.6 (IQR 21.5-31.1), males = 23.6 (IQR 21.0-26.9) (p=0.8); current smoker in females= 3 (11.1%), males = 3 (14.3%) (p=0.4); hypertension in females = 4 (14.8%), males = 4 (19.1% (p=0.7)). The median baseline LDL-C was 11.5 mmol/L (IQR 9.6-18.3) in females and 12.5 mmol/L (IQR 10.5-15.8) in males (p=0.51). The on-treatment LDL-C at follow up was 7.6 mmol/L (IQR 4.8-11.0) in females and 6.3 (IQR 4.6-7.5) in males (p=0.1). Most patients were taking 3 or more LLTs, including 20 (74%) females and 16 (76%) males (p=0.26), respectively. The use of lipoprotein apheresis was similar in females and males, 14 (51.8%) vs. 10 (47.6%), respectively (p=0.2). Over a mean of 10 years of follow-up, MACE occurred in 3 females (11.1%) and 4 males (19.1%) (p=0.2).

Conclusion: To our knowledge, this is the first study to examine sex-differences in HoFH. Females tend to be diagnosed later than males, although this difference was not statistically significant. Lipid levels and treatment were similar between sexes. MACE occurred in similar proportions between sexes, indicating that HoFH offsets the inherently lower cardiovascular risk in pre-menopausal females. Further investigation into sex-differences in HoFH in larger sample sizes is warranted.