Overweight and obesity are common in patients with heterozygous familial hypercholesterolemia (HeFH) and are associated with a greater risk of atherosclerotic cardiovascular disease (ASCVD) starting in childhood and regardless of LDL-C level and lipid-lowering medication, according to a cross-sectional analysis published Jan. 13 in the European Heart Journal.

Amany Elshorbagy, MD, et al., examined the prevalence of overweight and obesity, as defined by World Health Organization body mass cut-offs, and its association with prevalent ASCVD among 29,265 adults and 6,275 children with HeFH from 50 countries across six continents in the EAS FH Studies Collaboration registry.

Results showed that 36% of adults were overweight and 16% were obese. In children, 18% were overweight and 9% were obese. More men (42%) than women (30%) were overweight, whereas more women (17%) than men (15%) were obese. The highest prevalence was in Northern Africa/Western Asia. In children, both overweight and obesity were slightly more prevalent in boys than girls. Only 2% of children and 4% of adults were underweight and were included in the normal weight group. Additionally, more adults were overweight or obese (63%) in non–high-income countries compared with high-income countries (50%).

Notably, the median age at HeFH diagnosis in adults with obesity was nine years older than in those with normal weight.

Among all patients with HeFH, overweight and obesity were associated with a more atherogenic lipid profile and with higher odds of ASCVD, independent of age, sex, lipid profile and use of lipid-lowering medication. Of note, there was a progressive increase in the prevalence of coronary artery disease (CAD) across BMI categories.

Obesity compared with normal weight was associated with higher risk of CAD in children (odds ratio [OR], 9.28; 95% CI, 1.77-48.77), and CAD and stroke in adults (OR, 2.35; 95% CI, 2.10-2.63 and OR, 1.65; 95% CI, 1.27-2.14, respectively).

The authors write that obesity in patients with HeFH is associated with a more severe hyperlipidemia phenotype and greater likelihood of ASCVD from childhood. Thus, the authors recommend intensive lifestyle management starting as soon as HeFH is diagnosed. "A holistic approach, integrating body weight management with LDL-C-lowering treatments, should be used to improve cardiovascular outcomes in people with FH."