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Inconsistencies in the genetic prediction of HDL cholesterol versus atherosclerosis

Carlquist, John; Anderson, Jeffrey L

Current Opinion in Cardiology: July 2007 - Volume 22 - Issue 4 - p 352–358
doi: 10.1097/HCO.0b013e3281bd881e
HDL cholesterol

Purpose of review High-density lipoprotein (HDL) is generally perceived as having a protective role with respect to cardiovascular disease. The metabolism of HDL is mediated through a complex network of apoproteins, enzymes and transfer proteins. Genetic variants within this network can increase plasma HDL, but not with uniformly beneficial clinical outcomes. The purpose of this review is to explore and propose mechanisms for these discrepant observations.

Recent findings Recent developments in this area include new observations of genetic variants that paradoxically increase both HDL and cardiovascular risk. Also discussed are newly observed, function-altering modifications of the HDL particle. Proposed explanations include the segregation of the genetic variants associated with the respective endpoints of plasma HDL and cardiovascular risk. Functionally impaired but quantitatively robust plasma HDL and the emerging understanding of proinflammatory HDL also may contribute to our understanding of discordant observations.

Summary Enhanced understanding of these relationships may allow a more accurate assessment of clinical risk based on plasma HDL and help explain why HDL may, in some circumstances, be an inappropriate therapeutic target.

Department of Internal Medicine, Division of Cardiology, University of Utah School of Medicine, Cardiovascular Department, LDS Hospital, Intermountain Healthcare, Salt Lake City, Utah, USA

Correspondence to John Carlquist, PhD, Cardiovascular Department, LDS Hospital, Salt Lake City, UT 84143, USA Tel: +1 801 408 1028; fax: +801 408 5655; e-mail:

© 2007 Lippincott Williams & Wilkins, Inc.