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CLINICAL RESEARCH: ATHEROSCLEROSIS

Low Levels of Low-Density Lipoprotein Cholesterol and Blood Pressure and Progression of Coronary Atherosclerosis

Adnan K. Chhatriwalla, MD^_*, Stephen J. Nicholls, MBBS, PhD^_*,,,_*, Thomas H. Wang, MD^_*, Kathy Wolski, MPH^_*, Ilke Sipahi, MD^_*, Tim Crowe, BS^_*, Paul Schoenhagen, MD^_*,, Samir Kapadia, MD^_*, E. Murat Tuzcu, MD^_* and Steven E. Nissen, MD^_*

^_* Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio
Department of Cell Biology, Cleveland Clinic, Cleveland, Ohio
Department of Radiology, Cleveland Clinic, Cleveland, Ohio
Center for Cardiovascular Diagnostics and Prevention, Cleveland Clinic, Cleveland, Ohio

Manuscript received July 3, 2008; revised manuscript received September 16, 2008, accepted September 22, 2008.

^_* Reprint requests and correspondence: Dr. Stephen J. Nicholls, Cleveland Clinic, Cardiovascular Medicine, 9500 Euclid Avenue, Mail Code JJ65, Cleveland, Ohio 44195 (Email: nichols1{at}ccf.org).

Objectives: We investigated coronary atheroma progression in patients with low levels of low-density lipoprotein cholesterol (LDL-C) and systolic blood pressure (SBP).

Background: Low LDL-C and SBP beneficially impact coronary atherosclerosis. However, the association between intensive control of both risk factors and coronary plaque progression remains unclear.

Methods: Changes in atheroma burden monitored by intravascular ultrasound were studied in 3,437 patients with coronary artery disease (CAD) who were stratified according to on-treatment LDL-C and SBP.

Results: Patients with very low LDL-C (70 mg/dl) and normal SBP (120 mm Hg) had less progression in percent atheroma volume (PAV) (p < 0.001) and total atheroma volume (TAV) (p < 0.001), more frequent plaque regression (p = 0.01), and less frequent plaque progression (p < 0.001). In patients with SBP >120 mm Hg, very low LDL-C was associated with less progression of PAV (+0.30%, 95% confidence interval [CI]: –0.17% to 0.77% vs. +0.61%, 95% CI: 0.17% to 1.05%, p = 0.01) and TAV (–3.9 mm³, 95% CI: –7.24 to –0.63 mm³ vs. –1.2 mm³, 95% CI: –4.31 to 1.92 mm³, p = 0.001). In patients with LDL-C >70 mg/dl, normal SBP was not associated with less progression of PAV (+0.51%, 95% CI: 0.04% to 0.99% vs. +0.61%, 95% CI: 0.17% to 1.05%, p = 0.159) or TAV (–2.3 mm³, 95% CI: –5.59 to 1.05 mm³ vs. –1.2 mm³, 95% CI: –4.31 to 1.92 mm³, p = 0.617).

Conclusions: Very low LDL-C and normal SBP are associated with the slowest progression of coronary atherosclerosis. Although a greater beneficial association is observed in patients with very low LDL-C, these findings suggest the need for intensive control of global risk in patients with CAD.

Key Words: coronary artery disease • atherosclerosis • cholesterol • LDL-C • hypertension • blood pressure • intravascular ultrasound

Abbreviations and Acronyms   BP = blood pressure   CAD = coronary artery disease   CI = confidence interval   IVUS = intravascular ultrasound   JNC-7 = Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure   LDL-C = low-density lipoprotein cholesterol   NCEP = National Cholesterol Education Panel   PAV = percent atheroma volume   SBP = systolic blood pressure   TAV = total atheroma volume

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