Chaitman, Bernard

Background: In spite of aggressive preventive therapy, patients with type 2 diabetes (T2D) and stable ischemic heart disease (SIHD) remain at high risk for major cardiovascular events and death. Understanding the pathophysiologic determinants of that residual risk could help identify effective preventive therapies. Methods and Results: In this Ancillary Study of the BARI 2D trial, we examined the predictive value of biomarkers from 6 distinct pathophysiologic pathways in 2285 men and women with T2D and SIHD who were followed for a median (IQR) of 5.0 (4.1-6.0) years. The endpoint for this Ancillary Study was a composite of myocardial infarction, stroke, heart failure, or all-cause mortality. The 5-year Kaplan-Meier event rate was 31%. The pathophysiologic processes evaluated included dysglycemia (HbA1c), dyslipidemia (LDL-C), myocardial strain (NT-proBNP), myocardial injury (high-sensitivity cardiac troponin T [hsTnT]), subclinical inflammation (high-sensitivity C-reactive protein [hsCRP]), and nephropathy (presence/absence of macroalbuminuria). In Cox proportional hazards models adjusted for baseline risk factors, angiographic severity of disease, and ejection fraction, each marker except LDL-C was a significant predictor of outcome (Figure) in this population with 74% baseline statin use. After mutual adjustment for all 6 markers and baseline risk factors, the hazard ratio (95% CI) per 1-SD of natural logarithm transformed concentration was largest for NT-proBNP [1.29 (1.17, 1.42)], followed by hsTnT [1.16 (1.07, 1.26)], HbA1c [1.12 (1.03, 1.21)], and hsCRP [1.11 (1.03, 1.20). Macroalbuminuria was not a significant predictor after adjustment for the other markers (Figure). Conclusions: In this high-risk population of patients with type 2 diabetes and stable ischemic heart disease, strategies to target myocardial strain, myocardial injury, and subclinical inflammation may lead to improvements in cardiovascular outcome.