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(Circulation. 1995;92:698-699.)
© 1995 American Heart Association, Inc.

Articles

Lipid Lowering and Enhancement of Fibrinolysis With Niacin

Paul Holvoet; Désiré Collen

From the Center for Molecular and Vascular Biology, University of Leuven, Campus Gasthuisberg, O&N, Leuven, Belgium.

Correspondence to Désiré Collen, Center for Molecular and Vascular Biology, University of Leuven, Campus Gasthuisberg, O&N, Herestraat 49, B-3000, Leuven, Belgium. E-mail Desire.Collen@med.kuleuven.ac.bc.

Key Words: fibrinolysis • editorials • lipids

	Introduction

 
Several controlled trials in patients with atherosclerotic heart disease have demonstrated that a 30% to 40% reduction in low-density lipoprotein (LDL) cholesterol levels is associated not only with a moderate reduction of angiographic progression but, importantly, also with an impressive reduction of ischemic clinical events,¹ suggesting that intensive lipid lowering may stabilize existing lesions. Atherosclerotic plaque rupture occurs primarily at the site of unstable, lipid-rich areas² where infiltrated macrophages facilitate matrix degradation,³ activate the extrinsic pathway of blood coagulation through tissue factor expression, and inhibit fibrinolysis via increased plasminogen activator inhibitor type 1 (PAI-1) synthesis.⁴

LDL cholesterol levels are, however, only weak predictors of the progression of atherosclerotic disease.⁵ Their inherent susceptibility to oxidative modification may constitute a more important pathogenic mechanism.⁶ Oxidized LDL may facilitate atherogenesis by enhancing monocyte/macrophage adhesion and foam cell generation; inducing smooth muscle cell migration, proliferation, and foam cell generation; enhancing platelet adhesion and aggregation; initiating thrombosis; and impairing vasodilation (reviewed in Reference 7). Patients with hypertension, obesity, hypertriglyceridemia, depressed high-density lipoprotein (HDL) cholesterol levels and insulin resistance, for example, have increased levels of small, dense LDL particles with a pronounced predisposition to oxidative modification,⁸ whereas elevated levels of oxidatively modified LDL have also been demonstrated in the plasma of patients with acute myocardial infarction.⁹

Deficient fibrinolytic capacity, eg, due to increased PAI-1 levels or reduced levels of tissue-type plasminogen activator (TPA), predisposes patients to thrombotic events.¹⁰ Ischemic heart disease, angina pectoris, and recurrent myocardial infarction are indeed associated with increased levels of PAI-1.¹¹ Oxidized . . . [Full Text of this Article]