Regional and National Familial Hypercholesterolemia Registries: Present International Application, Importance, and Needs for Canada

Abstract

Cardiovascular disease (CVD) is the leading cause of death in the Western world. Atherosclerosis is the most common pathological vascular change underlying CVD with hypercholesterolemia constituting a major risk factor. Heterozygous familial hypercholesterolemia (FH) is a common autosomal dominant disease with a prevalence of 1:500 in the general population. Thus, approximately 13 million people worldwide and 68,000 in Canada are carriers of an FH gene. FH is caused by loss-offunction mutations in the low-density lipoprotein (LDL) receptor or apolipoprotein B-100 gene, or gain-of-function mutations in proprotein convertase subtilisin/kexin type 9, resulting in very high blood cholesterol levels and premature CVD. It is clinically characterized by arcus cornealis and tendon xanthomas, more common among people of French Canadian, Christian Lebanese, and Afrikaner descent. If undiagnosed and untreated, the cumulative risk of coronary artery disease by age 60 is more than 60% among men and 30% among women. In contrast to many other genetic diseases, treatment in the form of lifestyle management and lipid-lowering medications is highly effective in preventing not only CVD but also total morbidity and mortality. Not infrequently, FH is diagnosed only after a major cardiovascular event; therefore implementation of nationwide screening is warranted to allow early diagnosis and treatment. Despite an international effort to improve the identification and management of FH patients, only a few countries (The Netherlands, Spain, and Wales) have large-scale programs to systematically determine the FH status of relatives of FH patients. Although FH is more common than type 1 diabetes mellitus, both lay people and health professionals lack awareness of FH, its diagnostic features, and consequences. Framingham-based cardiovascular risk assessment should not be used in individuals with extreme hypercholesterolemia, but health professionals may still reassure FH patients