Beyond Cholesterol: Why Weight Matters Even with Genetic High Cholesterol

Today, on March 4, World Obesity Day, we explore an important health connection that affects millions worldwide. For those living with familial hypercholesterolaemia (FH) – a genetic condition causing high LDL cholesterol – emerging research offers new insights into how weight affects their heart health. 

People with FH often focus primarily on their LDL cholesterol levels and medication. However, recent research suggests that weight may play a more significant role in their cardiovascular outcomes than previously understood. 

What the Research Shows 

Dr. Amany Elshorbagy, Cardiovascular Epidemiologist at the Imperial Centre for Cardiovascular Disease Prevention, and the FH Studies Collaboration (FHSC) Investigators, examined over 35,000 patients with FH across 50 countries in the FHSC registry. Their findings, published this year in the European Heart Journal, reveal interesting patterns (see figure): 

• More than half of adults and over a quarter of children with FH were overweight or obese, similar to rates in the general population. 
• Among participants with FH, those with obesity showed higher rates of coronary artery disease and stroke. 
• These associations persisted even when accounting for cholesterol levels and medication use. 
• Obesity was linked to a more atherogenic lipid profile (a pattern of blood fats more likely to cause artery blockages), regardless of medication use. 

Read here the accompanying editorial highlighting these findings as a testament to the power of global registry data in advancing clinical care and policy, and advocating a more comprehensive approach to FH management—extending beyond cholesterol medication to personalised management of body weight and lifestyle. The findings are explained in a podcast by Medical Digest, and in a press article by Medscape, with commentary from other experts in the field.  

What this might mean for individuals with FH  

These findings suggest that for people with FH, factors beyond their genetically high LDL cholesterol may influence heart health outcomes. While cholesterol remains the primary risk driver, weight appears to be another key factor. The research indicates that when both genetic cholesterol issues and excess weight are present, they may create compounding effects on heart health. 

A holistic perspective 

World Obesity Day offers an opportunity to consider how weight and lifestyle interact with genetic conditions like FH. Healthcare approaches for FH have traditionally focused on cholesterol-lowering medication to prevent heart disease, but this research highlights how multiple factors might work together to determine heart disease risk in individuals with FH. This evolving understanding may lead to more personalised approaches to care. 

By sharing this research, we hope to contribute to a fuller understanding of the relationship between weight and genetic cholesterol disorders. As research advances, patients and healthcare providers can have more informed conversations about the various factors influencing heart health in the context of FH. 

Prepared by: Dr. Amany Elshorbagy, Cardiovascular Epidemiologist
Imperial Centre for Cardiovascular Disease Prevention,
FH Studies Collaboration (FHSC) Investigators  

Would you be interested in getting healthy weight loss support information? At FH Europe Foundation, we are currently assessing the needs and opportunities to support people living with familial hyperlipidaemias healthy weight loss and management advice. Interested? Contact us: info@fheurope.org