Global prevalence of overweight and obesity among paediatric and adult patients with homozygous or heterozygous familial hypercholesterolaemia, and association with coronary artery disease

Background and Aims: Overweight and obesity are modifiable risk factors for coronary artery disease (CAD) in the general population, but their prevalence in patients with familial hypercholesterolaemia (FH) and whether they confer additional risk of CAD independent of LDL-cholesterol in FH is largely unknown. Methods: Cross-sectional analysis on 35,919 patients across 46 countries, included in the EAS FH Studies Collaboration (FHSC) Registry. We assessed body mass index distribution (adults: underweight:<18.5, normal weight:18.5-<25.0, overweight:25.0-<30.0, obesity:≥30 kg/m2; children: z-scores) in patients with homozygous (HoFH; n=57 children/adolescents [<18 years], n=325 adults) or heterozygous FH (HeFH; n=6275 children/adolescents, n=29,262 adults), overall and by geographic region, and whether obesity was independently associated with CAD independent of LDL-cholesterol levels. Results: Among patients with HoFH, 55% of adults and 25% of children were overweight or obese; corresponding proportions for HeFH were 52% and 27%; Figure-top. By region, prevalence of overweight/obesity was highest in Northern-Africa/Western-Asia. In HeFH and HoFH, CAD was more prevalent in patients with vs. without obesity; Figure-middle. After adjusting for age, sex, LDL-cholesterol and lipid-lowering medication, being obese vs. non-obese was associated with higher odds of CAD in patients with HeFH (OR, adults: 2.16 [95%CI: 1.97,2.36]; children/adolescents: 6.87 [1.55,30.46]), but not in patients with HoFH; Figure-bottom. Results remained similar after further adjustment for diabetes. Conclusions: Obesity is independently associated with the presence of CAD in adults and children with HeFH, with similar trends in HoFH. In addition to LDL-cholesterol control, preventing and treating obesity are required to reduce the risk of CAD among those with FH.