Estimating the prevalence of heterozygous familial hypercholesterolaemia: a systematic review and meta-analysis

Abstract

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.

The familial hypercholesterolaemia phenotype: Monogenic familial hypercholesterolaemia, polygenic hypercholesterolaemia and other causes

“…Familial hypercholesterolaemia (FH) is an autosomal dominant condition characterised by substantially increased plasma concentrations of low‐density lipoprotein cholesterol (LDL‐C) from birth, leading to premature atherosclerosis . FH is one of the most common inherited disorders associated with premature coronary heart disease, with a frequency around 1:250 in most populations …”

“…1 FH is one of the most common inherited disorders associated with premature coronary heart disease, with a frequency around 1:250 in most populations. 2 The genetic causes of FH are pathogenic variants mainly in the LDL receptor gene (LDLR) 1 or apolipoprotein B gene (APOB), [3][4][5] and gain-of-function mutations in the proprotein convertase subtilisin/ kesin type 9 gene (PCSK9). 6 However, an increasing number of FH phenocopies are being identified and a few individuals with a clinical diagnosis of FH have been found to have rare variants in other genes, such as apolipoprotein E (APOE), 7 ATP-binding cassette sub-family G member 5 or 8 (ABCG5/8) 8 or lysosomal acid lipase (LIPA).…”

Molecular Screening of Familial Hypercholesterolemia in the Icelandic Population

“…Early diagnosis and treatment with statins is essential to reduce the risk of coronary heart disease (8,27), therefore effective screening strategies should be available. FH increases in prevalence with age, peaking between ages 60 and 69 and declining thereafter (5). This suggests errors in diagnosis and insufficient dyslipidemia screening in children and adolescents, which was apparent for the two Icelandic children of FH families diagnosed free of the disease and marked as negative controls.…”

“…Identification of subjects before the onset of overt cardiovascular disease provides an opportunity to initiate preventive statin therapy (3,4). However, FH is grossly underdiagnosed and undertreated worldwide (2), and it is estimated that in the US alone one million people remain undiagnosed (5,6).…”

Prediction of Familial Hypercholesterolemia in Patients at High Atherosclerotic Cardiovascular Disease Risk Using a Recently Validated Algorithm

“…The prevalence of heterozygous FH is estimated at 1 of 250 in the general population and approximately 1 of 125 in patients with ASCVD. [4][5][6] Despite FH being the most common monogenic disorder encountered in clinical practice, it is often not recognized clinically. The reasons for this are complex and may relate to the difficulty for clinicians in applying the current definitions.…”