Risks Associated with FH

Many articles have been published on this subject from various perspectives. Individual risk is a topic of discussion between practitioner and patient. Many (risk) factors play a role in this. For FH, it is important that LDL is elevated from an early age.

The large (meta) analysis below found that people with FH are 10 times more likely to develop cardiovascular disease and 20 times more likely to develop it prematurely. 

• Beheshti SO, Madsen CM, Varbo A, Nordestgaard BG. Worldwide Prevalence of Familial Hypercholesterolemia: Meta-Analyses of 11 Million Subjects. J Am Coll Cardiol. 2020 May 26;75(20):2553-2566. doi: 10.1016/j.jacc.2020.03.057. PMID: 32439005

Patients with FH have twice the risk of premature death and a significantly reduced life expectancy (at age 18, life expectancy is 15.9 years lower). 

• Ray KK, Pillas D, Hadjiphilippou S, Khunti K, Seshasai SRK, Vallejo-Vaz AJ, Neasham D, Addison J. Premature morbidity and mortality associated with potentially undiagnosed familial hypercholesterolemia in the general population. Am J Prev Cardiol. 2023 Sep 6;15:100580. doi: 10.1016/j.ajpc.2023.100580. PMID: 37727649; PMCID: PMC10506055.

Patients with FH are at increased risk because their LDL levels are elevated from an early age. This means you are exposed to higher LDL levels for longer (known as 'cumulative exposure'), which increases your risk of heart disease and other illnesses. The article below shows that this risk increases with additional risk factors (such as diabetes, high blood pressure, and smoking).

• Shirin Ibrahim, G Kees Hovingh, Barbara A Hutten, Erik S G Stroes, Laurens F Reeskamp, Impact of cumulative LDL cholesterol and other risk factors on coronary artery disease prevalence in patients with familial hypercholesterolaemia. European Journal of Preventive Cardiology, Volume 32, Issue 3, February 2025, Pages 262–265, https://doi.org/10.1093/eurjpc/zwae349

With equal LDL values (slightly to severely elevated), having a genetic FH variant results in a 2-3 times higher risk. See illustration B for an overview.

• Amit V. Khera, Hong-Hee Won, Gina M. Peloso, Kim S. Lawson, Traci M. Bartz, Xuan Deng, Elisabeth M. van Leeuwen, Pradeep Natarajan, Connor A. Emdin, Alexander G. Bick, Alanna C. Morrison, Jennifer A. Brody, Namrata Gupta, Akihiro Nomura, Thorsten Kessler, Stefano Duga, Joshua C. Bis, Cornelia M. van Duijn, L. Adrienne Cupples, Bruce Psaty, Daniel J. Rader, John Danesh, Heribert Schunkert, Ruth McPherson, Martin Farrall, Hugh Watkins, Eric Lander, James G. Wilson, Adolfo Correa, Eric Boerwinkle, Piera Angelica Merlini, Diego Ardissino, Danish Saleheen, Stacey Gabriel, Sekar Kathiresan. Diagnostic Yield and Clinical Utility of Sequencing Familial Hypercholesterolemia Genes in Patients With Severe Hypercholesterolemia,
  Journal of the American College of Cardiology, Volume 67, Issue 22, 2016, Pages 2578-2589, ISSN 0735-1097,
  https://doi.org/10.1016/j.jacc.2016.03.520.