Reduction in Mortality in Subjects With Homozygous Familial Hypercholesterolemia Associated With Advances in Lipid-Lowering Therapy

• Published in: Circulation (New York, N.Y.) Vol. 124; no. 20; pp. 2202 - 2207
• Main Authors: RAAL, Frederick J, PILCHER, Gillian J, PANZ, Vanessa R, VAN DEVENTER, Hendrick E, BRICE, Brigitte C, BLOM, Dirk J, MARAIS, A. David
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 15.11.2011
• Subjects: Adolescent; Adult; Biological and medical sciences; Blood and lymphatic vessels; Blood. Blood coagulation. Reticuloendothelial system; Cardiology. Vascular system; Child; Cholesterol, LDL - blood; Cholesterol, LDL - genetics; Cohort Studies; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Female; Homozygote; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Hyperlipoproteinemia Type II - blood; Hyperlipoproteinemia Type II - drug therapy; Hyperlipoproteinemia Type II - mortality; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Retrospective Studies; Young Adult; Human; Mortality; Metabolic diseases; Lipids; Cardiovascular disease; Hyperlipoproteinemia; Statin derivative; Lipoprotein; Homozygosity; Cholesterol; Genetic disease; familial; lipid-lowering therapy; Hypercholesterolemia; Treatment; statins; Dyslipemia; Antilipemic agent
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/CIRCULATIONAHA.111.042523

Homozygous familial hypercholesterolemia is an inherited disorder caused by mutations in both low-density lipoprotein receptor alleles, which results in extremely elevated plasma low-density lipoprotein cholesterol concentrations and very early morbidity and mortality due to cardiovascular disease. To evaluate the impact of advances in lipid-lowering (predominantly statin) therapy on cardiovascular disease morbidity and mortality in a large cohort of patients with homozygous familial hypercholesterolemia, the records of 149 patients (81 females, 68 males) from 2 specialized lipid clinics in South Africa were evaluated retrospectively. Homozygous familial hypercholesterolemia was diagnosed by confirmation of mutations in genes affecting low-density lipoprotein cholesterol or by clinical criteria. A Cox proportional hazard model with time-varying exposure was used to estimate the risk of death and major adverse cardiovascular events among statin-treated patients compared with statin-naive patients. The hazard ratio for benefit from lipid therapy, calculated with the Cox proportional hazards model for the end point of death, was 0.34 (95% confidence interval 0.14-0.86; P=0.02), and for the end point of major adverse cardiovascular events, it was 0.49 (95% confidence interval 0.22-1.07; P=0.07). This occurred despite a mean reduction in low-density lipoprotein cholesterol of only 26.4% (from 15.9±3.9 to 11.7±3.4 mmol/L; P<0.0001) with lipid-lowering therapy. Lipid-lowering therapy is associated with delayed cardiovascular events and prolonged survival in patients with homozygous familial hypercholesterolemia.