Obesity and atherosclerotic cardiovascular disease in adults with heterozygous familial hypercholesterolemia: An analysis from HELLAS-FH registry.

ABSTRACT

BACKGROUND: Familial hypercholesterolemia (FH) and obesity are well-established risk factors of atherosclerotic cardiovascular disease (ASCVD). Despite high prevalence, their joint association with ASCVD remains largely unknown. OBJECTIVE: To investigate the association of obesity with prevalent ASCVD in individuals with heterozygous FH (HeFH) enrolled in the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH). METHODS: FH diagnosis was based on Dutch Lipid Clinic Network (DLCN) criteria. Adults with at least possible FH diagnosis (DLCN score ≥3) and available body mass index (BMI) values were included. Homozygous FH individuals were excluded. RESULTS: 1655 HeFH adults (mean age 51.0 ± 14.4 years, 48.6% female) were included; 378 (22.8%) and 430 (26.0%) were diagnosed with probable and definite FH, respectively. Furthermore, 371 participants (22.4%) had obesity and 761 (46.0%) were overweight. Prevalence of ASCVD risk factors increased progressively with BMI. Prevalence of coronary artery disease (CAD) was 23.4% (3.2% for stroke and 2.7% for peripheral artery disease [PAD]), and increased progressively across BMI groups. After adjusting for traditional ASCVD risk factors and lipid-lowering medication, individuals with obesity had higher odds of established CAD (OR 1.54, 95% CI 1.04-2.27, p = 0.036) as well as premature CAD (OR 1.74, 95% CI 1.17-2.60, p = 0.009) compared with those with normal BMI. No association was found with stroke or PAD. CONCLUSIONS: Over half of adults with HeFH have overweight or obesity. Obesity was independently associated with increased prevalence of CAD in this population.