Does Hyperglycemia Contribute to Subclinical Myocardial Damage?

It is well known that diabetes increases the risk of clinical cardiovascular events. We also know that persons who have hyperglycemia below the threshold for a diagnosis of diabetes (often called “prediabetes”) also have an elevated risk of cardiovascular disease. Much less is known about how pre-diabetes and diabetes may relate to asymptomatic heart muscle damage (also known as subclinical myocardial damage).

Troponin is a highly specific cardiac biomarker, and recent developments have led to progressively more sensitive tests. The most recent crop of highly sensitive troponin assays can detect troponin in 50-90% of middle-aged ambulatory populations. Studies of these assays in community-based populations have shown that troponin strongly predicts of future cardiovascular events, particularly heart failure and death. Indeed, the relationship of troponin with future cardiovascular risk appears along a continuum with no clear threshold. It is increasingly recognized that troponin detected with these novel highly sensitive assays may reflect chronic asymptomatic subclinical myocardial damage (as opposed to an acute symptomatic event).

We undertook a study to examine the association of pre-diabetes and diabetes with future elevations in high-sensitivity cardiac troponin T (hs-cTnT ; “new” myocardial injury). Our study included over 9,000 participants from the Atherosclerosis Risk in Communities (ARIC) Study with no history of cardiovascular disease who had two measurements of hs-cTnT conducted approximately 6 years apart.

We found that persons with pre-diabetes or diabetes had an approximate 2-fold increased risk of developing incident myocardial damage, as assessed by elevated hs-cTnT at the 6 year follow-up visit. This elevated risk remained, even after adjustment for traditional cardiovascular risk factors. Our study also confirms previous evidence that hs-cTnT is strongly associated with diabetes and hypertension, but not associated with cholesterol levels. We further found that those persons with incident subclinical myocardial damage were also at the highest risk of clinical events, particularly heart failure and death. Taken as a whole, our findings suggest that hyperglycemia may have a deleterious effect on the myocardium, independent of other cardiac risk factors (including elevated cholesterol). It is possible that myocardial damage contributes to the elevated cardiovascular risk--especially heart failure--in persons with diabetes and pre-diabetes?

The growing dual epidemics of obesity and diabetes threaten the gains we have made in reducing morbidity and mortality from cardiovascular disease over the past two decades.  Our findings underscore the need for effective prevention but also suggest that interventions to reduce myocardial damage may reduce the cardiovascular risk associated with diabetes.  How can the clinical laboratory assist in reducing cardiovascular risk related to prediabetes?