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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:1851.)
© 2008 American Heart Association, Inc.

Clinical and Population Studies

Lipoprotein(a) Is Associated Differentially With Carotid Stenosis, Occlusion, and Total Plaque Area

Jonathan H. Klein; Robert A. Hegele; Daniel G. Hackam; Marlys L. Koschinsky; Murray W. Huff; J. David Spence

From the Schulich School of Medicine and Dentistry (J.H.K., R.A.H., D.G.H., M.W.H., J.D.S.), University of Western Ontario, London, Canada; the Vascular Biology Group (R.A.H., M.W.H.), Robarts Research Institute, London, Ontario, Canada; the Department of Biochemistry (M.L.K.), Queen’s University, Kingston, Ontario, Canada; and the Stroke Prevention and Atherosclerosis Research Centre (D.G.H., J.D.S.), Robarts Research Institute, London, Canada.

Correspondence to Dr David Spence, Stroke Prevention & Atherosclerosis Research Centre, Robarts Research Institute, 1400 Western Road, London, Ontario, Canada N6G 2V2. E-mail dspence{at}robarts.ca

Background— Lipoprotein(a) [Lp(a)] is a putative risk factor for myocardial infarction and stroke and is related to thrombosis and impaired fibrinolysis. We studied relationships of Lp(a) with carotid stenosis, occlusion, and total plaque area, distinct phenotypes of atherosclerosis that may be differentially affected by cardiovascular risk factors.

Methods and Results— Multivariable linear regression analysis was used to study relationships of Lp(a) to phenotypes of carotid atherosclerosis among 876 consecutive patients from an atherosclerosis prevention clinic with complete data for all variables used in the model. Occlusion of an internal carotid artery was present in 22 (2.5%) patients (one with bilateral occlusions). Risk factors predicted carotid plaque area, stenosis, and occlusion differently. Lp(a) was a significant independent predictor of baseline stenosis (P<0.0001) but not of plaque area (P=0.13); in logistic regression, Lp(a) significantly predicted occlusion (P=0.001). Patients with occlusion had significantly higher levels of Lp(a): 0.27±0.25 g/L versus 0.17±0.18 g/L without occlusion; P=0.007.

Conclusion— Lp(a) was a significant independent predictor of carotid stenosis and occlusion, but not of carotid plaque area, supporting the hypothesis that the effect of Lp(a) on atherogenesis and cardiovascular risk is largely related to thrombosis and impaired fibrinolysis. Stenosis and occlusion may not be attributable to plaque progression, but to plaque rupture and thrombosis; this relationship may also apply to other arterial beds.

We investigated the effect of lipoprotein(a) and traditional risk factors on carotid ultrasound phenotypes. Lipoprotein(a) significantly predicted baseline stenosis and occlusion, but not baseline plaque area, and traditional risk factors predicted these 3 phenotypes differently, supporting the concept that stenosis and plaque are fundamentally different processes. Much of the effect of Lp(a) was related to occlusion, suggesting that its effect on atherogenesis is largely attributable to thrombosis and impaired fibrinolysis.

Key Words: lipoprotein(a) • carotid • atherosclerosis • stenosis • plaque

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