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CLINICAL RESEARCH: CORONARY ARTERY DISEASE

Effect of Diabetes on Progression of Coronary Atherosclerosis and Arterial Remodeling

A Pooled Analysis of 5 Intravascular Ultrasound Trials

Stephen J. Nicholls, MBBS, PhD^_*,,_*, E. Murat Tuzcu, MD^_*, Srinivasa Kalidindi, MD, MPH^_*, Kathy Wolski, MPH^_*, Keon-W. Moon, MD^_*, Ilke Sipahi, MD^_*, Paul Schoenhagen, MD^_* and Steven E. Nissen, MD^_*

^_* Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio
Department of Cell Biology, Cleveland Clinic, Cleveland, Ohio.

Manuscript received December 13, 2007; revised manuscript received March 7, 2008, accepted March 11, 2008.

^_* Reprint requests and correspondence: Dr. Stephen J. Nicholls, Department of Cardiovascular Medicine, Mail Code JJ-65, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195. (Email: nichols1{at}ccf.org).

Objectives: Our goal was to characterize coronary atherosclerosis progression and arterial remodeling in diabetic patients.

Background: The mechanisms that underlie adverse cardiovascular outcomes in diabetic patients have not been well characterized.

Methods: A systematic analysis was performed in 2,237 subjects in randomized controlled studies of atherosclerosis progression. The pattern of arterial remodeling, extent of coronary atherosclerosis, and disease progression was compared in subjects with and without diabetes.

Results: In association with more risk factors, diabetic patients demonstrated a greater percent atheroma volume (PAV) (40.2 ± 0.9% vs. 37.5 ± 0.8%, p < 0.0001) and total atheroma volume (TAV) (199.4 ± 7.9 mm³ vs. 189.4 ± 7.1 mm³, p = 0.03) on multivariate analysis. A stronger correlation was observed between PAV and glycated hemoglobin (r = 0.22, p = 0.0003) than fasting glucose (r = 0.09, p < 0.0001), although the difference just failed to meet statistical significance after controlling for study. Diabetic patients exhibited a smaller lumen (291.1 ± 104.8 mm³ vs. 306.5 ± 108.2 mm³, p = 0.005) but no difference in external elastic membrane (494.9 ± 166.9 mm³ vs. 498.8 ± 167.2 mm³, p = 0.61) volumes. More rapid progression of PAV (0.6 ± 0.4% vs. 0.05 ± 0.3%, p = 0.0001) and TAV (–0.6 ± 2.5 mm³ vs. –2.7 ± 2.4 mm³, p = 0.03) was observed in diabetic patients on multivariate analysis. Smaller external elastic membrane (482.5 ± 160.7 mm³ vs. 519.9 ± 166.9 mm³, p = 0.03) and lumen (276.0 ± 100.3 mm³ vs. 310.1 ± 105.6 mm³, p = 0.001) volumes were observed in diabetic patients treated with insulin despite the presence of a similar TAV (206.5 ± 88.6 mm³ vs. 209.9 ± 90.2 mm³, p = 0.84). Intensive low-density lipoprotein cholesterol lowering in patients improved the rate of plaque progression, but only to the level observed in nondiabetic patients with suboptimal lipid control.

Conclusions: Diabetes is accompanied by more extensive atherosclerosis and inadequate compensatory remodeling. Accelerated plaque progression, despite use of medical therapies, supports the need to develop new antiatherosclerotic strategies in diabetic patients.

Key Words: diabetes • atherosclerosis • intravascular ultrasound • coronary artery disease • risk factors

Abbreviations and Acronyms   CRP = C-reactive protein   EEM = external elastic membrane   HDL = high-density lipoprotein   IVUS = intravascular ultrasound   LDL = low-density lipoprotein   PAV = percent atheroma volume   TAV = total atheroma volume

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