CLINICAL RESEARCH: CORONARY ARTERY DISEASE
Effect of Diabetes on Progression of Coronary Atherosclerosis and Arterial RemodelingA 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
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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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