Effect of diabetes on progression of coronary atherosclerosis and arterial remodeling: a pooled analysis of 5 intravascular ultrasound trials.
OBJECTIVE
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 mm(3) vs. 189.4 +/- 7.1 mm(3), 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 mm(3) vs. 306.5 +/- 108.2 mm(3), p = 0.005) but no difference in external elastic membrane (494.9 +/- 166.9 mm(3) vs. 498.8 +/- 167.2 mm(3), 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 mm(3) vs. -2.7 +/- 2.4 mm(3), p = 0.03) was observed in diabetic patients on multivariate analysis. Smaller external elastic membrane (482.5 +/- 160.7 mm(3) vs. 519.9 +/- 166.9 mm(3), p = 0.03) and lumen (276.0 +/- 100.3 mm(3) vs. 310.1 +/- 105.6 mm(3), p = 0.001) volumes were observed in diabetic patients treated with insulin despite the presence of a similar TAV (206.5 +/- 88.6 mm(3) vs. 209.9 +/- 90.2 mm(3), 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.
Nicholls
Stephen J
SJ
Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio 44195, USA. nichols1@ccf.org
Tuzcu
E Murat
EM
Kalidindi
Srinivasa
S
Wolski
Kathy
K
Moon
Keon-W
KW
Sipahi
Ilke
I
Schoenhagen
Paul
P
Nissen
Steven E
SE
D003324:Coronary Artery Disease / Q000000981:diagnostic imaging* / Q000503:physiopathology / Q000628:therapy*; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000473:pathology*; D003920:Diabetes Mellitus / Q000503:physiopathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D018084:Ultrasonography, Interventional