Enzymes Show Early Heart Damage in Diabetes

Elizabeth Selvin, PhD, MPH, from the Johns Hopkins Bloomberg School of Public Health, and colleagues reported that, baseline levels of HbA1c were linearly associated with results of a high-sensitivity cardiac troponin-T (hs-cTnT) test.

Compared with normal levels of HbA1c (<5.7%), those in the pre-diabetic range (5.7% to 6.4%) had hs-cTnT values about 25% higher, while those with HbA1c levels equal to or greater than 6.5% had hs-cTnT values about 70% higher, according to the study.

The use of these high-sensitivity troponin assays has shown promise in predicting cardiovascular events and death in patients with congestive heart failure and coronary heart disease, Selvin and colleagues noted.

Since hyperglycemia is associated with coronary heart disease, diabetes, and death, various researchers have hypothesized that subclinical heart damage associated with hyperglycemia might be an early biomarker that could influence treatment.

In the current study, the authors enrolled 9,661 participants from the Atherosclerosis Risk in Communities (ARIC) study. The researchers defined elevated levels of hs-cTnT as those above the previously reported 99^th percentile value (14 ng/L) in healthy people. In this cohort, 7.3% had elevated enzymes.

The mean age of the population was 56 and nearly 60% were women. Those with higher HbA1c levels were more likely to be African American and hypertensive and have higher body mass index and higher LDL cholesterol, as well as lower HDL cholesterol.

When researchers fully adjusted for covariates, they found that every 1% increase in HbA1c was associated with a 0.7 ng/L bump in hs-cTnT (P<0.001).

When adjusted for age, sex, and race, those with pre-diabetic levels of HbA1c were 51% more likely to have elevated hs-cTnT values (OR 1.51, 95% CI 1.23 to 1.85). Similarly, those with diabetic HbA1c levels were four times more likely to have elevated troponin (OR 4.09, 95% CI 3.25 to 5.15). Adjusting for cardiovascular risk factors and then for fasting glucose did not significantly change the risk.

A fasting glucose level higher than 100 mg/dL was associated with elevated hs-cTnT, but only in the analysis that adjusted for age, sex, and race. That HbA1c is a better marker of subclinical myocardial damage is consistent with other studies, researchers wrote.

"Our data support new recommendations for the use of HbA1c for the diagnosis of diabetes and identification of persons at high risk for development of complications," they concluded.

"Before troponin levels can be considered a validated intermediate phenotype in the pathway to heart failure, additional studies are needed linking changes in troponins with cardiovascular and noncardiovascular outcomes, and investigating the role of specific therapies on troponin release and subsequent events," they wrote. "These studies should be a high priority as they have the potential to facilitate earlier interventions to prevent heart failure."

Selvin and colleagues noted the study is limited because the HbA1c and hs-cTnT values were not obtained at the same visit so it cannot be ruled out that some participants might have had elevated troponin levels at the baseline visit. There is also a selection bias concern because those who died prior to the last visit were excluded. Although they did adjust for confounders, there may still be some residual in this observational study.

• The study found an association between low levels of troponin and HbA1c in individuals free of evident coronary heart disease and heart failure.
• New, extremely sensitive assays for circulating troponin levels allow detection of low levels which may reflect chronic sources of myocardial injury and may predict long-term heart failure.

Rubin J, et al "Chronic hyperglycemia and subclinical myocardial injury" J Am Coll Cardiol 2012; 59; 484-489.