Premature Heart Attacks: Bad Lifestyle, Bad Luck, or Bad Genes?

Abstract

Homozygous familial hypercholesterolaemia (HoFH), a rare inherited lipid disorder usually caused by bi-allelic defects in the LDLR gene, is characterised by marked elevation in low-density lipoprotein -cholesterol (LDL-C). Aggressive, early intervention with lipid-lowering therapy is warranted in patients with HoFH, and the recent introduction of new drug treatments including lomitapide and mipomersen has enabled physicians and their patients to achieve lower LDL-C levels than previously possible in this hard- to-treat condition. Understanding the overall impact of new interventions in HoFH requires a correct assessment of the true prevalence of the disease. Although it is rare, emerging studies suggest that HoFH may be more common than previously thought. We have reviewed data on the epidemiology and management of HoFH, with a focus on raising awareness on this condition so that clinicians can be made aware of the potential for genetic causes for presentation with premature cardiovascular disease. As classic clinical characteristics may be absent in HoFH patients, genetic status and/or family history should be part of the assessment of patients with significantly elevated LDL-C and premature atherosclerosis with a premature heart attack or clinical complications. As direct outcomes data for new treatments for HoFH are not yet available, intermediate phenotypes of arterial structure and function are being studied as endpoints in clinical trials. Novel therapies which enable lowering of LDL-C to levels that were, until recently, unachievable, have the potential to alter cardiovascular morbidity and mortality in this high-risk group of patients.