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
Keywords: cerebral vascular disease; familial hypercholesterolemia; meta-analysis; peripheral artery disease; stroke; systematic review.