Genetic polymorphisms in emerging cardiovascular risk factors and response to statin therapy.
Current strategies for both the primary and secondary prevention of coronary heart disease (CHD) focus on the traditional risk factors, such as hypertension, smoking cessation, and cholesterol, as the primary determinants of the cardiac risk profile, with particular emphasis on the reduction of low-density lipoprotein cholesterol (LDL-C) to targeted goal levels as endorsed by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATPIII). Large primary and secondary prevention trials with the hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have demonstrated varying reductions in cardiovascular events associated with similar changes in LDL-C levels, suggesting statins may possess additional beneficial effects on other risk factors. Retrospective analyses of many statin trials have evaluated the association between several polymorphic candidate genes (apolipoprotein E, stromelysin-1, beta-fibrinogen, cholesteryl ester transfer protein, lipoprotein lipase, hepatic lipase, and platelet glycoprotein III) which have been identified as predictors of disease severity and both metabolic and clinical response to statin therapy. These results suggest that statin therapy improves plasma lipid profiles in all patients, but preferentially benefits individuals who carry a high risk, variant genotype for these risk factors as compared to individuals with the wild-type genotype. These observations suggest that determining individual patient genotype may be useful in optimizing the benefits of statin therapy. These hypothesis-generating data need to be prospectively evaluated in genotyped patients.
Dornbrook-Lavender
Kimberly A
KA
Department of Pharmacotherapy, University of North Carolina at Chapel Hill School of Pharmacy, Chapel Hill, NC 27599-7360, USA. kadlav@unc.edu
Pieper
John A
JA
D008078:Cholesterol, LDL / Q000097:blood; D002986:Clinical Trials as Topic; D003327:Coronary Disease / Q000235:genetics* / Q000517:prevention & control*; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000235:genetics; D011110:Polymorphism, Genetic; D012307:Risk Factors
D008078:Cholesterol, LDL; D005819:Genetic Markers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors