Traditional cardiovascular risk factors and their association with atherosclerotic cardiovascular disease in homozygous familial hypercholesterolemia: A cross-sectional analysis from the HICC registry.

BACKGROUND AND AIMS: As survival improves in patients with homozygous familial hypercholesterolemia (HoFH), exposure to traditional cardiovascular risk factors may increasingly influence outcomes. This study aimed to determine the prevalence of traditional coronary artery disease (CAD) risk factors-hypertension, diabetes, smoking, and obesity-and their associations with CAD in HoFH.

METHODS

We performed a cross-sectional analysis of patients enrolled in the HoFH International Clinical Collaborators (HICC) registry (NCT04815005) between February 2016 and December 2024. Logistic regression was used to estimate the association between risk factors and CAD in risk factor propensity score-matched subgroups. Analyses were stratified by sex, on-treatment LDL-C tertiles, and country-income status.

RESULTS

Among 912 patients with HoFH (53.3% female; median age 33.0 years), the prevalence of hypertension was 16.5%, diabetes 3.8%, smoking 8.2%, overweight 25.4%, and obesity 17.6%. Cardiovascular risk factors were more frequent in older patients (e.g., hypertension: 25.7% ≥ 30 years vs. 4.3% < 30 years; p < 0.001), in those from high-income countries (17.8% vs. 14.9%; p = 0.011), and in those achieving lower LDL-C levels (24.1% in the lowest vs. 14.6% in the highest LDL-C tertile; p = 0.004). After propensity score matching, hypertension was significantly associated with CAD (OR 1.85; 95%CI 1.11-3.08, p = 0.02), while diabetes, smoking, and obesity were not associated.

CONCLUSIONS

Despite the dominant role of cumulative LDL-C burden in the development of CAD, our findings indicate an association between hypertension and CAD in HoFH. Although causal inference is limited by the cross-sectional design, these results highlight the importance of proactive identification and management of hypertension in HoFH alongside intensive lipid-lowering therapy.