ObjectivesHeterozygous familial hypercholesterolaemia (FH) confers a significant risk for premature cardiovascular disease (CVD). However, the estimated prevalence of FH varies substantially among studies. We aimed to provide a summary estimate of FH prevalence in the general population and assess variations in frequency across different sociodemographic characteristics.Setting, participants and outcome measuresWe searched MEDLINE, EMBASE, Global Health, the Cochrane Library, PsycINFO and PubMed for peer-reviewed literature using validated strategies. Results were limited to studies published in English between January 1990 and January 2017. Studies were eligible if they determined FH prevalence using clinical criteria or DNA-based analyses. We determined a pooled point prevalence of FH in adults and children and assessed the variation of the pooled frequency by age, sex, geographical location, diagnostic method, study quality and year of publication. Estimates were pooled using random-effects meta-analysis. Differences by study-level characteristics were investigated through subgroups, meta-regression and sensitivity analyses.ResultsThe pooled prevalence of FH from 19 studies including 2 458 456 unique individuals was 0.40% (95% CI 0.29% to 0.52%) which corresponds to a frequency of 1 in 250 individuals. FH prevalence was found to vary by age and geographical location but not by any other covariates. Results were consistent in sensitivity analyses.ConclusionsOur systematic review suggests that FH is a common disorder, affecting 1 in 250 individuals. These findings underscore the need for early detection and management to decrease CVD risk.

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Heterozygous familial hypercholesterolemia (HeFH) is a common genetic disorder predisposing affected individuals to lifelong low-density lipoprotein cholesterol (LDL-C) elevation and coronary heart disease. However, whether HeFH increases the risk of peripheral arterial disease (PAD) and ischemic stroke is undetermined. We examined associations between HeFH and these outcomes in a comprehensive systematic review and meta-analysis. We searched MEDLINE, EMBASE, Global Health, the Cochrane Library, and PubMed (for ahead-of-print publications) for relevant English-language studies. Maximally adjusted risk estimates were pooled under random- and fixed-effects meta-analysis to derive odds ratios (ORs) and 95% confidence intervals (CIs). We included 6 studies representing 183 388 participants. Heterozygnous familial hypercholesterolemia was associated with a higher risk of PAD (OR: 3.59 [95% CI: 1.30-9.89]). This trend was nonsignificantly preserved (OR: 2.96 [95% CI: 0.68-12.88]) in sensitivity analyses of genetically defined HeFH. Genetic HeFH was not associated with increased ischemic stroke risk (OR: 0.76 [95% CI: 0.37-1.58]) although possessing an LDL-C >4.9 mmol/L (190 mg/dL) was (OR: 1.42 [95% CI: 1.06-1.89]). We found clinical and genetic diagnoses of HeFH to be associated with increased PAD risk. Genetically confirmed HeFH may not confer an increased risk of ischemic stroke. Modest associations may exist between LDL-C and ischemic stroke risk in HeFH.