Estimating the Prevalence of Familial Hypercholesterolemia in Acute Coronary Syndrome: A Systematic Review and Meta-analysis

Abstract

Background: Heterozygous familial hypercholesterolemia (FH) is one of the most common monogenic conditions but remains substantially underdiagnosed. One method for increasing the diagnosis is via opportunistic screening of individuals presenting with acute coronary syndrome (ACS). The prevalence of FH in the ACS population has been assessed in numerous studies using various diagnostic criteria, resulting in wide variability of prevalence estimates. The purpose of this study was to perform a systematic review and meta-analysis to provide a more robust estimate.

Methods: We searched MEDLINE, EMBASE, Pubmed, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews to identify peer-reviewed articles reporting the prevalence of FH in ACS. We calculated pooled prevalence using a random-effects model. When multiple diagnostic criteria were used in a single study, we gave priority to DNA-based criteria, followed by Dutch Lipid Clinic Network (DLCN) criteria. We also investigated the prevalence in subanalyses according to age and diagnostic criteria.

Results: The overall pooled prevalence of FH in ACS, derived from 22 studies, was 4.7% (95% confidence interval [CI], 3.0-7.3). DNA-based criteria and DLCN criteria provided similar estimates of 5.0% (95% CI, 2.6-9.3) and 5.5% (95% CI, 3.0-10.0), respectively. The prevalence was 7.3% (95% CI, 5.3-10.0) for patients aged ≤ 60 years and increased to 13.7% (95% CI, 8.2-22.1) for those aged ≤45 years.

Conclusions: Approximately 1 in 21 patients with ACS has FH, and this increases to 1 in 7 among those ≤45 years. These results reinforce the importance of screening for FH in the ACS population.