Prognostic Impact of Aortic Stiffness in High-Risk Type 2 Diabetic Patients: The Rio de Janeiro Type 2 Diabetes Cohort Study

OBJECTIVE

The prognostic importance of carotid-femoral pulse wave velocity (PWV), the gold standard measure of aortic stiffness, has been scarcely investigated in type 2 diabetes and never after full adjustment for potential confounders. The aim was to evaluate the prognostic impact of carotid-femoral PWV for cardiovascular morbidity and all-cause mortality in a cohort of 565 high-risk type 2 diabetic patients.

RESEARCH DESIGN AND METHODS

Clinical, laboratory, ambulatory blood pressure (BP) monitoring, and carotid-femoral PWV data were obtained at baseline. The primary end points were a composite of fatal and nonfatal cardiovascular events and all-cause mortality. Multiple Cox survival analysis was used to assess the associations between carotid-femoral PWV, as a continuous variable and categorized at 10 m/s, and the end points.

RESULTS

After a median follow-up of 5.75 years, 88 total cardiovascular events and 72 all-cause deaths occurred. After adjustments for potential cardiovascular risk factors, including micro- and macrovascular complications, ambulatory BP, and metabolic control, carotid-femoral PWV was predictive of the composite end point but not of all-cause mortality both as a continuous variable (hazard ratio 1.13 95% CI 1.03–1.23], P = 0.009 for increments of 1 m/s) and as categorized at 10 m/s (1.92 1.16–3.18], P = 0.012). On sensitivity analysis, carotid-femoral PWV was a better predictor of cardiovascular events in younger patients (<65 years), in those with microvascular complications, and in those with poorer glycemic control (HbA_1c ≥7.5% 58.5 mmol/mol]).

CONCLUSIONS

Carotid-femoral PWV provides cardiovascular risk prediction independent of standard risk factors, glycemic control, and ambulatory BPs and improves cardiovascular risk stratification in high-risk type 2 diabetes.In the past decade, knowledge of the importance of arterial stiffness in the pathogenesis of cardiovascular diseases grew (1,2). Arterial stiffness depends on the structural and geometric properties of the arterial wall and on the distending pressure, and aging and blood pressure (BP) are its main determinants (1,2). The measurement of carotid-femoral pulse wave velocity (PWV) is considered the gold standard evaluation of central aortic stiffness (1). Furthermore, aortic stiffness has been demonstrated to predict cardiovascular morbidity and mortality above and beyond other traditional cardiovascular risk factors in patients with end-stage renal disease (3) and hypertension (4), elderly individuals (5), and general population-based samples (6,7). This prognostic importance has also been recently confirmed in a meta-analysis (8).Type 2 diabetic patients have increased arterial stiffness (9–11) and are at particular risk for augmented cardiovascular morbidity and mortality. This high cardiovascular risk is not completely explained by clustering of traditional risk factors, and increased arterial stiffness may be one pathophysiological mechanism that links diabetes to increased cardiovascular morbidity and mortality (12). Nevertheless, only one previous study investigated the prognostic impact of increased aortic stiffness for cardiovascular outcomes in type 2 diabetes (13), but because of a smaller sample size (397 diabetic individuals), the study could not completely adjust for traditional cardiovascular risk factors, chronic diabetes complications, or metabolic control parameters. Therefore, we aimed to investigate in a prospective follow-up cohort of high-risk type 2 diabetic patients the prognostic impact of increased aortic stiffness for cardiovascular morbidity and mortality and for all-cause mortality. In particular, we evaluated whether aortic stiffness was able to add prognostic information beyond traditional cardiovascular risk markers and whether there were interactions between aortic stiffness and other important covariates, such as age, sex, presence of diabetes complications, and glycemic control.