Overweight, obesity, and cardiovascular disease in heterozygous familial hypercholesterolaemia: the EAS FH Studies Collaboration registry
Authors: Elshorbagy Amany , Vallejo-Vaz Antonio J , Barkas Fotios , Lyons Alexander R M , Stevens Christophe A T , Dharmayat Kanika I , Catapano Alberico L , Freiberger Tomas , Hovingh G Kees , Mata Pedro , Raal Frederick J , Santos Raul D , Soran Handrean , Watts Gerald F , Abifadel Marianne , Aguilar-Salinas Carlos A , Alhabib Khalid F , Alkhnifsawi Mutaz , Almahmeed Wael , Alnouri Fahad , Alonso Rodrigo , Al-Rasadi Khalid , Al-Sarraf Ahmad , Arca Marcello , Ashavaid Tester F , Averna Maurizio , Banach Maciej , Becker Marianne , Binder Christoph J , Bourbon Mafalda , Brunham Liam R , Chlebus Krzysztof , Corral Pablo , Cruz Diogo , Davletov Kairat , Descamps Olivier S , Dwiputra Bambang , Ezhov Marat , Groselj Urh , Harada-Shiba Mariko , Holven Kirsten B , Humphries Steve E , Kayikcioglu Meral , Khovidhunkit Weerapan , Lalic Katarina , Latkovskis Gustavs , Laufs Ulrich , Liberopoulos Evangelos , Lima-Martinez Marcos M , Maher Vincent , Marais A David , März Winfried , Mirrakhimov Erkin , Miserez André R , Mitchenko Olena , Nawawi Hapizah , Nordestgaard Børge G , Panayiotou Andrie G , Paragh György , Petrulioniene Zaneta , Pojskic Belma , Postadzhiyan Arman , Reda Ashraf , Reiner Željko , Reyes Ximena , Sadiq Fouzia , Sadoh Wilson Ehidiamen , Schunkert Heribert , Shek Aleksandr B , Stroes Erik , Su Ta-Chen , Subramaniam Tavintharan , Susekov Andrey V , Tilney Myra , Tomlinson Brian , Truong Thanh Huong , Tselepis Alexandros D , Tybjærg-Hansen Anne , Vázquez-Cárdenas Alejandra , Viigimaa Margus , Vohnout Branislav , Yamashita Shizuya , Ray Kausik K 
Published: January 2025

Abstract

Background and Aims
Overweight and obesity are modifiable risk factors for atherosclerotic cardiovascular disease (ASCVD) in the general population, but their prevalence in individuals with heterozygous familial hypercholesterolaemia (HeFH) and whether they confer additional risk of ASCVD independent of LDL cholesterol (LDL-C) remains unclear.

Methods
Cross-sectional analysis was conducted in 35 540 patients with HeFH across 50 countries, in the EAS FH Studies Collaboration registry. Prevalence of World Health Organization–defined body mass index categories was investigated in adults (n = 29 265) and children/adolescents (n = 6275); and their association with prevalent ASCVD.

Results
Globally, 52% of adults and 27% of children with HeFH were overweight or obese, with the highest prevalence noted in Northern Africa/Western Asia. A higher overweight/obesity prevalence was found in non-high-income vs. high-income countries. Median age at familial hypercholesterolaemia diagnosis in adults with obesity was 9 years older than in normal weight adults. Obesity was associated with a more atherogenic lipid profile independent of lipid-lowering medication. Prevalence of coronary artery disease increased progressively across body mass index categories in both children and adults. Compared with normal weight, obesity was associated with higher odds of coronary artery disease in children (odds ratio 9.28, 95% confidence interval 1.77–48.77, adjusted for age, sex, lipids, and lipid-lowering medication) and coronary artery disease and stroke in adults (odds ratio 2.35, 95% confidence interval 2.10–2.63 and odds ratio 1.65, 95% confidence interval 1.27–2.14, respectively), but less consistently with peripheral artery disease. Adjusting for diabetes, hypertension and smoking modestly attenuated the associations.

Conclusions
Overweight and obesity are common in patients with HeFH and contribute to ASCVD risk from childhood, independent of LDL-C and lipid-lowering medication. Sustained body weight management is needed to reduce the risk of ASCVD in HeFH.