Evaluation of Differences in Coronary Plaque Mechanical Behavior in Individuals With and Without Type 2 Diabetes Mellitus
Diabetes mellitus is a major risk factor for the development of atherosclerosis.1 Although there has been a significant amount of work examining histological factors which predispose to plaque rupture and subsequent acute coronary syndromes,2 less is known about the role of plaque and vessel biomechanical properties. We have previously shown using intravascular ultrasound (IVUS), that there is a significant change in coronary plaque area between systole and diastole, and this is a major determinant of coronary compliance.3 In the current study we used IVUS to assess coronary plaque characteristics in individuals with and without type 2 diabetes mellitus.
All patients scheduled for percutaneous coronary intervention of lesions in the circumflex or left anterior descending (LAD) arteries were considered eligible for inclusion, other than those undergoing emergent revascularization for acute myocardial infarction. Diabetic patients were identified as those who had their diabetes diagnosed in adult life with biochemical confirmation including a fasting glucose >7.0 mmol/L. The study was approved by the Human Ethics Committee of the Alfred Hospital.
Collection of IVUS images, pressure recordings, and analysis were performed as in our previous study.3 Assessment was undertaken in the proximal left anterior descending artery (LAD) at a site remote from any hemodynamically significant stenosis or site of intervention and with no more than a 20% angiographic stenosis
Group data are presented as mean±SEM. Comparisons between groups were made by t test or Wilcoxon signed rank test in the case of a nonnormal distribution. Categorical variables were compared using the χ2 test. A probability value of <0.05 was considered significant.
A total of 53 patients with an average age 59±10 years (mean±SD) were studied. Of the 18 patients with diabetes, 2 were insulin requiring, 14 took oral hypoglycaemic agents, and 2 were diet controlled. They were compared with 35 nondiabetic subjects. Fifty six percent of the diabetic subjects had presented with an unstable coronary event, in comparison with 26% of the nondiabetic population (P<0.05).
Patient characteristics including baseline hemodynamic characteristics are presented in supplemental Table I (available online at http://atvb.ahajournals.org).
Thirteen of the diabetic subjects had stents placed in their LAD with an average preintervention angiographic stenosis in the LAD of 85%. Of the 35 nondiabetics, 19 patients had stents in their LAD with an average angiographic stenosis of 80%.
The vessel characteristics in the LAD for the 2 groups are shown in supplemental Table II. The difference in cross-sectional plaque (intima plus media) area (Figure) between systole and diastole (ΔIM) was significantly higher in the diabetic subjects (1.3±0.4 versus 0.2±0.2 mm2 P<0.05). In a multiple regression analysis we examined the impact of diabetes and presentation with stable and unstable symptoms on change in plaque area, the only significant factor was the presence or absence of diabetes(P<0.05).
The major finding of this study is that the change in cross-sectional coronary plaque area between diastole and systole is significantly greater in diabetic patients than in those without diabetes. As noted, diabetic subjects had more frequent presentation with unstable symptoms however change in plaque area was not greater in those with unstable symptoms.
The mechanism underlying the reduction in plaque cross-sectional area during systole is undetermined. It may occur either as a result of a change in plaque mass or result from plaque being redistributed along the vessel wall with such redistribution being greater in diabetic subjects, perhaps as a result of increased lipid content. Redistribution may result from vessel lengthening. However, previous experiments on other conduit arteries have suggested that lengthening during systole in vivo is very small. Patel et al found that the thoracic aorta lengthens 0.011% per mm Hg.4 A second possibility is that not only plaque cross-sectional area but also volume diminishes during systole.
The most likely explanation for a reduction in plaque mass is that material such as fluid is extruded from the plaque during systole. The importance of plaque vascularization in both the development of atherosclerosis and in the pathophysiology of plaque stability has recently become clear.5–7 Thus it is possible that compression of these vascular spaces in systole leads to blood leaving the plaque and results in the reduction in cross-sectional area as seen in this study.
In conclusion, this study shows that diabetic individuals have a more marked change in plaque cross-sectional area during the cardiac cycle than a well matched group of patients without diabetes. It is postulated that this greater “compressibility” is attributable to the presence of more vascularity in the diabetic plaque.
Sources of Funding
This work was supported by an NH&MRC program grant to the Baker Heart Research Institute and a Center for Clinical Excellence grant to the Alfred and Baker Medical Unit. Prof Dart and Associate Prof Kingwell are both National Health and Medical Research Council Fellows. Dr Duffy is supported by a National Health and Medical Research Council of Australia Career Development Award (No. 182830). Dr Anthony White is supported by an Australian National Heart Foundation post graduate medical scholarship.
Davies MJ, Thomas AC. Plaque fissuring—the cause of acute myocardial infarction, sudden ischaemic death, and crescendo angina. Br Heart J. 1985; 53: 363–373.
Patel DJ, Mallos AJ, Fry DL. Aortic mechanics in the living dog. J Appl Physiol. 1961; 16: 293–299.
Moreno PR, Purushothaman KR, Fuster V, Echeverri D, Truszczynska H, Sharma SK, Badimon JJ, O’Connor WN. Plaque neovascularization is increased in ruptured atherosclerotic lesions of human aorta: implications for plaque vulnerability. Circulation. 2004; 110: 2032–2038.