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Vincent M. G. Maher, MD, MRCPI; B. Greg Brown, MD, PhD; Santica M. Marcovina, PhD; Lynn A. Hillger, PhD; Xue-Qiao Zhao, MD; John J. Albers, PhD

JAMA. 1995;274(22):1771-1774.

Abstract
Objective.
—To determine if lowering elevated low-density lipoprotein cholesterol (LDL-C) levels offsets the adverse effect of raised lipoprotein(a) (Lp[a]) levels on coronary artery disease (CAD) in men.

Design.
—Randomized, double-blind, placebo-controlled trial of lipid lowering for CAD.

Setting.
—Post hoc analysis of the Familial Atherosclerosis Treatment Study.

Participants.
—A total of 146 men aged 62 years or younger with CAD and apolipoprotein B levels of at least 125 mg/dL.

Intervention.
—Patients received a Step II Diet and lovastatin (40 mg daily) plus colestipol (30 g daily), niacin (4 g daily) plus colestipol, or placebo (plus colestipol if LDL-C >90th percentile) for 2.5 years. They were grouped by their LDL-C responses: "minimal" if LDL-C decreased by 10% or less from baseline (mean [SD] change, +6% [13%]) and "substantial" if LDL-C decreased more than 10% (mean [SD] change, —40% [16%]).

Main Outcome Measure.
—Impact of lowering elevated LDL-C on the cardiac event rate (death, myocardial infarction, and revascularization for refractory ischemia) and CAD change associated with elevated Lp(a).

Results.
—In multivariate analyses, the best correlate of baseline CAD severity was Lp(a) (r=0.30; P<.001). For 36 patients with minimal LDL-C reduction, CAD progression correlated only with in-treatment Lp(a) levels (r=0.45; P<.01), but for 84 patients with substantial LDL-C reduction, disease regressed and its change correlated with in-treatment LDL-C (r=0.24; P<.05) but not with Lp(a) (r=—0.05). Lipoprotein(a) levels were not significantly altered in either group. For 40 patients with Lp(a) at the 90th percentile or higher, events were frequent (39%) if reduction of LDL-C was minimal, but were few (9%) if reduction was substantial (relative risk, 0.23; 95% confidence interval, 0.06 to 0.99).

Conclusions.
—In men with CAD and elevated LDL-C, Lp(a) levels were dominant correlates of baseline disease severity, its progression, and event rate over 2.5 years. However, with substantial LDL-C reductions, persistent elevations of Lp(a) were no longer atherogenic or clinically threatening. This provides a possible direction for treatment in such patients with elevated Lp(a) and LDL-C.

(JAMA. 1995;274:1771-1774)

Author Affiliations
From the Department of Medicine, Cardiology Division, and the Division of Metabolism, Endocrinology, and Nutrition, University of Washington School of Medicine, Seattle.

Footnotes
Reprint requests to the Cardiology Division, RG-22, University of Washington, Seattle, WA 98195 (Dr Maher).

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