Non-coronary atherosclerotic cardiovascular disease in patients with familial hypercholesterolaemia

Abstract

Objective: Familial hypercholesterolaemia (FH) is a common autosomal dominant inherited disease, affecting 1 in 200−500 individuals worldwide. FH is characterized by elevated circulating low-density lipoprotein cholesterol (LDL-C) concentrations. Its association with increased risk of coronary heart disease (CHD) (>10-fold, compared with patients without FH) is well documented. However, the association between FH and non-CHD atherosclerotic cardiovascular disease (ASCVD) risk has been poorly documented.

Methods: PubMed was searched for English language publications regarding the association between FH and carotid artery stenosis, stroke, peripheral artery disease (PAD; lower limbs and other arterial beds), aortic valve calcification (AoVC), aortic and renal artery disease, chronic kidney disease, atrial fibrillation and heart failure, from conception until 22 December 2019.

Results: Despite the small number of available studies, as well as their characteristics (sample size, diagnostic criteria used, retrospective or cross-sectional design), there is evidence for a positive association between FH and stroke, PAD or AoVC. More data are needed for definitive conclusions regarding aortic and renal artery disease, chronic kidney disease, atrial fibrillation and heart failure. There is paucity of data with respect to homozygous FH. Increased lipoprotein (a) concentrations, often seen in FH patients, may also contribute to this non-CHD atherosclerotic process. A key question is whether statins or other LDL-C-lowering therapies, provide an additional reduction in the risk of these less-recognized vascular and non-vascular complications in FH patients.

Conclusions: Heterozygous FH is associated with increased risk for stroke, PAD and AoVC. Clinicians should take these non-CHD ASCVD aspects into consideration for optimal management of FH patients.

Keywords:

• Familial hypercholesterolaemia
• non-cardiac atherosclerotic cardiovascular disease
• peripheral artery disease
• carotid artery disease
• stroke
• aortic valve calcification

Transparency

Declaration of funding

There is no funding to disclose.

Declaration of financial/other relationships

DPM has given talks and attended conferences sponsored by Amgen, AstraZeneca and Libytec. The authors and peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

PA designed the study, analysed and interpreted the data and contributed to the first draft of the paper. KV and GM searched the literature, analysed data and contributed to the first draft of the paper. DGG reviewed the manuscript and provided critical scientific input. DPM conceived the idea of the study, provided critical scientific input and had the primary responsibility for the paper’s final content. All authors approved the final version of the review.

Acknowledgements

None reported.