Jeevarethinam, Anand; (2018) Cardiovascular risk stratification: Relationship between carotid atherosclerosis and coronary artery disease in asymptomatic diabetes. Doctoral thesis (M.D(Res)), UCL (University College London).

Abstract

Background: Carotid intima-media thickness (CIMT) measurement and carotid plaque detection by B-mode carotid ultrasound (CUS) are frequently used as surrogates to predict coronary artery disease (CAD). However, they are not routine clinical practice in the asymptomatic diabetic population. Objectives: The aims of this study were 1) evaluate the relationship between carotid disease assessed by Carotid US and CAD assessed by computed tomography coronary angiography (CTCA), which also included a coronary calcium (CAC) scan; 2) identify carotid parameters to predict the severity and extent of coronary atherosclerosis and cardiovascular events in patients with asymptomatic type 2 diabetes (T2DM); and 3) evaluate the relationship between endothelial dysfunction and carotid atherosclerosis in relation to risk factors. Research design and methods: A cohort of 262 asymptomatic T2DM patients were prospectively studied with carotid US to evaluate CIMT and carotid plaque, CTCA for coronary plaque and EndoPAT for endothelial function. Results: Two hundred (76%) patients had a CAC score >0, of whom 57 (22%) had severe coronary calcification (>400 Au). Carotid plaque was present in 40 (70%) patients with severe coronary artery calcification (p<0.001), 59/95 (74%) with >50% coronary stenosis (P<0.001) and 28/43 (65%) with >70% coronary stenosis. Carotid plaque was predictive of non-zero CAC score ( odds ratio 2.59 [CI 1.17–5.74]) even after adjustment and CIMT was borderline significant (p=0.05). Carotid plaque continued to be predictive of severe CAC burden (CAC >400 Au; odds ratio 3.26 [ CI 2.05–5.19]) on binary logistic regression analysis. Also carotid plaque was significantly associated with >50% coronary stenosis on logistic regression analysis [ odds ratio 2.57 ( CI 1.34, 4.92), P 0.004 ] after adjustment with traditional risk factors and risk score. Greater maximal IMT was associated with increased risk of coronary plaque >50% stenosis, (odds ratio 1.21 [95% CI 1.02, 1.44]; P=0.03) and >70% coronary plaque (odds ratio 1.23 [1.01, 1.50]; P=0.04) after adjusting for traditional risk factors and risk scores. At 34 months the estimated occurrence of any event (total MACE) was 7.1% in the whole population and significantly higher in patients with carotid plaque (P=0.005). Carotid plaque (regression co-efficient = 4.0 (2.3–5.7), P < 0.001) and CIMT (regression co-efficient = 0.8 (0.2–1.4), P < 0.007) were significant determinants of Framingham risk score (FRS) on multiple linear regression analysis but the association between endothelial function and FRS was not significant. Association between endothelial dysfunction and the carotid variable was not significant on univariable and multivariable analysis. Conclusion: Carotid plaque is an independent predictor of cardiovascular events and a prognostic marker in asymptomatic T2DM with CAD. Carotid plaque is a better predictor of underlying silent coronary atherosclerosis presence, severity and extent than CIMT. There was a significant association between CIMT/carotid plaque and FRS, but no correlation was found between endothelial dysfunction and CIMT/ carotid plaque.

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