Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: Consensus Statement of the European Atherosclerosis Society

Abstract

AimsThe first aim was to critically evaluate the extent to which familial hypercholesterolaemia (FH) is underdiagnosed and undertreated. The second aim was to provide guidance for screening and treatment of FH, in order to prevent coronary heart disease (CHD).Methods and resultsOf the theoretical estimated prevalence of 1/500 for heterozygous FH, <1% are diagnosed in most countries. Recently, direct screening in a Northern European general population diagnosed approximately 1/200 with heterozygous FH. All reported studies document failure to achieve recommended LDL cholesterol targets in a large proportion of individuals with FH, and up to 13-fold increased risk of CHD. Based on prevalences between 1/500 and 1/200, between 14 and 34 million individuals worldwide have FH. We recommend that children, adults, and families should be screened for FH if a person or family member presents with FH, a plasma cholesterol level in an adult ≥8 mmol/L(≥310 mg/dL) or a child ≥6 mmol/L(≥230 mg/dL), premature CHD, tendon xanthomas, or sudden premature cardiac death. In FH, low-density lipoprotein cholesterol targets are <3.5 mmol/L(<135 mg/dL) for children, <2.5 mmol/L(<100 mg/dL) for adults, and <1.8 mmol/L(<70 mg/dL) for adults with known CHD or diabetes. In addition to lifestyle and dietary counselling, treatment priorities are (i) in children, statins, ezetimibe, and bile acid binding resins, and (ii) in adults, maximal potent statin dose, ezetimibe, and bile acid binding resins. Lipoprotein apheresis can be offered in homozygotes and in treatment-resistant heterozygotes with CHD.ConclusionOwing to severe underdiagnosis and undertreatment of FH, there is an urgent worldwide need for diagnostic screening together with early and aggressive treatment of this extremely high-risk condition.

Putting Into Perspective the Hazards of Untreated Familial Hypercholesterolemia

“…New, objective screening projects in large US populations, with genetic testing done without regard to lipid levels, place the prevalence of FH mutation carriers (with mutations in LDLR , APOB , and PCSK9 ) in 3 different studies at 1 in 204,2 1 in 211,3 and 1 in 2224: more than double older estimates of 1 in 500. Similar estimates for prevalence of FH are reported for European populations 5, 6, 7, 8. Yet, FH remains seriously underdiagnosed and inadequately treated.…”

Interpretation of the evidence for the efficacy and safety of statin therapy

“…165,166 Genetic disorders in humans that cause large elevations of LDL cholesterol concentrations (in particular, LDL receptor mutations) are associated with substantially elevated rates of atherosclerotic disease. 167,168 Moreover, these disorders (i.e. familial hypercholesterolaemia) provide compelling evidence of "dose" effects, whereby individuals in Western populations who inherit the abnormal genetic variant from both parents typically have LDL cholesterol levels above 12 mmol/L and coronary events before the age of 20 years, 167 while those who inherit the abnormal variant from one parent typically have levels above 8 mmol/L and events in early middle-age.…”

Development of Aortic Valve Disease in Familial Hypercholesterolemic Swine: Implications for Elucidating Disease Etiology

“…FH is a disorder of lipoprotein metabolism often caused by mutations in the low‐density lipoprotein (LDL) receptor, leading to high circulating levels of LDL 2, 3, 4. Numerous studies have established a relationship between FH and a high risk of atherosclerosis at a young age 5, 6, 7…”