Background
Cardiovascular disease (CVD) remains a serious complication in individuals with type 2 diabetes (T2D), accounting for greater than 60% of all-cause mortality. However, not all individuals with T2D experience the same risk for macrovascular disease and other complications; this variable risk likely reflects different underlying environmental and inherited risk factors, diabetes duration, extent of subclinical CVD, and clinical management. As such, risk stratification remains an important priority in the prevention of T2D-associated morbidity and mortality.
The Diabetes Heart Study (DHS) is a family-based study enriched for T2D affected individuals. Recent findings from the DHS have shown that coronary artery calcified plaque (CAC) determined by non-invasive, non-contrast computed tomography (CT) scanning and accepted as reflecting subclinical CVD, is an independent predictor of both all-cause mortality and CVD-mortality. Observed odds ratios for CAC scores exceeding 1000 were 6.7–11.2. In an effort to further refine these models, we have investigated whether other non-invasive clinical measures were independent predictors of mortality in T2D-affected individuals after accounting for CAC.
Reduction in kidney function (or estimated glomerular filtration rate; eGFR) is an established risk factor for adverse CVD outcomes in a range of settings, including acute coronary syndrome, heart failure and acute myocardial infarction. However, uncertainty remains as to direct causality and the mechanisms underpinning relationships between kidney function and CVD. In addition, although a range of renal function indices are associated with CVD-mortality in both population-based studies and T2D-affected cohorts, adjustment for underlying vascular disease burden is frequently overlooked. We have previously reported strong independent associations between albuminuria and CAC in the DHS. Likewise, microalbuminuria has also been associated with increased presence and progression of CAC in the Multi-Ethnic Study of Atherosclerosis as well as with increased carotid intima-media thickness, another measure of subclinical CVD. Given the potential interplay between kidney function, endothelial dysfunction, atherosclerotic plaque formation and CVD outcomes, this investigation examined whether measures of kidney function and albuminuria were predictive of mortality in European Americans (EAs) with T2D, independent of CAC.