Arterial stiffness and atherosclerosis and incident cardiovascular events and all-cause mortality in individuals with manifest cardiovascular disease with and without type 2 diabetes

Background: It is unclear if arterial stiffness and atherosclerosis are differentially related to cardiovascular events and mortality in individuals with manifest cardiovascular disease with and without type 2 diabetes (T2DM) and to what extent they mediate the relation between T2DM and these outcomes. Methods: Prospective data were used from the UCC-SMART cohort, including individuals with manifest cardiovascular disease (n = 9465). Arterial stiffness (brachial pulse pressure and carotid artery distensibility coefficient (DC)) and atherosclerosis (presence of carotid plaque and ankle-brachial index <0.9) were determined. Cardiovascular events included non-fatal stroke, non-fatal myocardial infarction and cardiovascular death. Cox regression and structural equation models were used with adjustment for confounders. Results: Over a median follow-up of 10.3 years, 2087 cardiovascular events and 2808 deaths occurred. Higher brachial pulse pressure was related to cardiovascular events and mortality in individuals with T2DM and without T2DM (HRs ≥ 1.09; 95% confidence intervals (CIs) between 1.03 and 1.30). Lower carotid artery DC was related to mortality in individuals with T2DM and without T2DM (hazard ratios (HRs) ≥ 1.20; 95% CI between 1.00 and 1.48), but only related to cardiovascular events in individuals without T2DM (HR 1.34; 95% CI between 1.20 and 1.49). Carotid and lower extremity atherosclerosis were both related to cardiovascular events and mortality in individuals with T2DM and without T2DM (HRs ≥ 1.52; 95% CI between 1.27 and 2.21). Up to 8.1% and 16.3% of the relation between T2DM and outcomes was mediated through arterial stiffness and atherosclerosis, respectively. Conclusion: Arterial stiffness and atherosclerosis are independently, but not differentially, related to cardiovascular events and mortality in individuals with manifest cardiovascular disease with and without T2DM. Atherosclerosis explained a larger proportion of the relation between T2DM and outcomes.