Vessel Shrinkage as a Sign of Atherosclerosis Progression in Type 2 Diabetes

Abstract

OBJECTIVE-The aim of this study was to determine the natural history of vascular remodeling of atherosclerotic plaques in patients with type 2 diabetes and the predictors of vessel shrinkage.RESEARCH DESIGN AND METHODS-In this serial intracoronary ultrasound (IVUS) study, 237 coronary segments from 45 patients enrolled in the DIABETES I, II, and III trials were included. Quantitative volumetric IVUS analyses (motorized pullbacks at 0.5 mm/s) were performed in the same coronary segment after the index procedure and at the 9-month follow-up. Nontreated mild lesions (angiographic stenosis Ͻ25%) with Ն0.5 mm plaque thickening and length of Ն5 mm assessed by IVUS were included. Vessel shrinkage was defined as a ⌬external elastic membrane area/⌬plaque area Ͻ 0. Statistical adjustment by multiple segments and multiple lesions per patient was performed.RESULTS-Vessel shrinkage was identified in 37.1% of segments and was associated with a significant decrease in lumen area at 9 months (vessel shrinkage, 10 Ϯ 4 mm 2 vs. non-vessel shrinkage, 11 Ϯ 4 mm 2 ; P ϭ 0.04). Independent predictors of vessel shrinkage were insulin requirements (odds ratio 4.6 [95% CI 1.40 -15.10]; P ϭ 0.01), glycated hemoglobin (1.5 [1.05-2.10]; P ϭ 0.02), apolipoprotein B (0.96 [0.94 -0.98]; P Ͻ 0.001), hypertension (3.7 [1.40 -10.30]; P ϭ 0.009), number of diseased vessels (5.6 [2.50 -12.50]; P Ͻ 0.001), and prior revascularization (17.5 [6.50 -46.90]; P Ͻ 0.001).CONCLUSIONS-This serial IVUS study suggests that progression of coronary artery disease in patients with type 2 diabetes may be mainly attributed to vessel shrinkage. Besides, vessel shrinkage is influenced by insulin requirements and metabolic control and is associated with more advanced coronary atherosclerosis. Diabetes 58:209-214, 2009 C oronary artery remodeling is a phenomenon by which vessel dimension changes in response to atherosclerotic plaque accumulation. This concept was initially described by Glagov et al. (1) in a postmortem, histopathological study and confirmed by in vivo studies using intracoronary ultrasound (IVUS) analysis (2-7). Two different patterns of coronary remodeling have been described: a compensatory enlargement of the vessel in response to an increase of atherosclerotic plaque (positive remodeling) and a failure to enlarge or even vessel shrinkage (negative remodeling). The latter is a common finding in coronary stenosis of diabetic patients (8,9). In cross-sectional studies, negative remodeling has been associated with coronary risk factors, such as hypertension (5) and smoking (4), with the type of plaque (2,7) (calcified, hard plaques), and with metabolic control in diabetic patients (10 -12). In most studies, remodeling has been evaluated only at a single time point. Therefore, the natural history of this process has not been properly addressed. In addition, remodeling index has been assessed by comparing vessel dimension at target site and that at the most normal-looking cross-section within 10 mm from the lesion taken as reference segment (2-7). Howev...

Quantitative Proteome Analysis Reveals Increased Content of Basement Membrane Proteins in Arteries From Patients With Type 2 Diabetes Mellitus and Lower Levels Among Metformin Users

“…41 Thus, variations in α-1 and α-2 chains of type IV collagen regulate the capacity of arterial remodeling and determine stiffness, aneurysm formation, etc. This knowledge in combination with our observation of increased amounts of these collagen chains in T2DM therefore fits well with the novel idea that basement membrane accumulation may constitute at least part of the molecular background for increased arterial stiffness, 11 dysfunctional remodeling, 12,13 and increased protection against abdominal aneurysms, 14,15 which prevails in DM. Another striking observation in the present study is the reduced levels of many of the upregulated basement membrane proteins in the subgroup of type 2 diabetic patients treated with metformin.…”

“…7,8 Moreover, in a study based on RNA-microarray examinations of nonatherosclerotic arterial tissue from T2DM patients, we found altered expression of a matrix-related pathway 9 and increased expression of the basement membrane protein fibulin-1, both at the mRNA and protein level, in arterial samples from patients with T2DM. 10 Alterations in the arterial matrix could be involved in the increased arterial stiffness, 11 in the dysfunctional remodeling (shrinkage instead of compensatory enlargement of damaged arteries), 12,13 and in the paradoxically decreased risk of abdominal aortic aneurysms described among patients with T2DM. 14,15 Likewise, altered arterial matrix influence atherogenesis 16 and alter responses to injury.…”

Vascular Responses in Patients With and Without Diabetes Mellitus After Everolimus-Eluting Stent Implantation

“…Interestingly, previous investigators have consistently reported an association between greater residual plaque burden at reference vessel segments and edge stenosis in the cohorts of sirolimuseluting, paclitaxel-eluting, and bare metal stent implantation. 24, 25 Coupled with the rapid progression of remote or other atherosclerotic lesions and higher incidence of comorbidities in patients with DM, these factors may explain to some degree the higher incidence of future clinical events, even in the DES era, as described by others. 23 In this study, despite achieving a similar lumen area, lesions in patients with DM showed significantly greater asymmetric stent expansion than non-DM lesions and there was a significant relationship between SEI and NUS in the overall population.…”

Impact of Diabetes Mellitus on Vessel Response in the Drug-Eluting Stent Era

“…23 Additionally, DM patients more often have smaller reference vessels because of diffuse atherosclerosis and inadequate compensatory remodeling. [24][25][26] These plaque characteristics, coupled with smaller, less compliant reference vessels may be responsible for the smaller lumen area at postprocedure in DM patients. In this study, mechanical factors, such as lumen area at postprocedure, maximum balloon diameter, and maximum balloon pressure were independently associated with in-stent follow-up lumen, and the association of lumen area at postprocedure with the follow-up lumen in both in-stent and reference segments seemed to be the strongest, as assessed from the t statistic value in the multiple regression analysis.…”