Sensitive Cardiac Troponin T Assay and the Risk of Incident Cardiovascular Disease in Women With and Without Diabetes Mellitus

Abstract

Background Very low levels of cardiac troponin T associate with increased risk of cardiovascular death in patients with stable chronic coronary disease. Whether high-sensitivity cardiac troponin T (hsTnT) levels associate with adverse cardiovascular outcomes in individuals without cardiovascular disease (CVD) has not been well studied. Methods and Results Utilizing two complementary study designs, we evaluated the relationship between baseline cardiac troponin and incident CVD events among diabetic and non-diabetic participants in the Women’s Health Study (median follow-up 12.3 years). All diabetic women with blood specimens were included in a cohort study (n=512 diabetic women, n=65 events) and non-diabetic women were sampled for inclusion in a case-cohort analysis (n=564 comprising the subcohort, n=479 events). HsTnT was detectable (≥0.003 μg/L) in 45.5% of diabetic women and 30.3% of non-diabetic women (P<0.0001). In models adjusted for traditional risk factors and hemoglobin A1c, detectable hsTnT was associated with subsequent CVD (myocardial infarction, stroke, cardiovascular death) in diabetic women (adjusted HR 1.79, 95% CI 1.04-3.07, P=0.036), but not non-diabetic women (adjusted HR 1.13, 95% CI 0.82-1.55, P=0.46). Further adjustment for NT-proBNP and estimated renal function did not substantially alter this relationship among diabetic women (HR 1.76, 95% CI 1.00-3.08, P=0.0499), which appeared to be driven by a threefold increase in CVD death that was not observed in non-diabetic women. Conclusions Very low but detectable levels of cardiac troponin T associate with total CVD and CVD death in women with diabetes. Among healthy non-diabetic women, detectable compared to undetectable troponin was not associated with CVD events.

Randomized Trial of the Effects of Insulin and Metformin on Myocardial Injury and Stress in Diabetes Mellitus: A Post Hoc Exploratory Analysis

“…Higher proportions have been reported in other cohorts (eg, 39% in the BARI 2D [Bypass Angioplasty Revascularization Investigation 2 Diabetes] trial) 10. In patients with diabetes mellitus with and without established cardiovascular disease, cardiac troponin concentrations are a significant predictor of myocardial infarction, stroke, heart failure, and cardiovascular death 9, 10, 23, 24. As a result, there is considerable interest in identifying treatment strategies that might modify troponin concentrations and thus confer cardiovascular benefit.…”

“…Although a reduction in cardiovascular morbidity and mortality has been a major goal of therapy in patients with T2DM, therapeutic strategies focused on intensive glycemic control in these patients have largely failed to show a substantial impact on cardiovascular morbidity and mortality, at least in the short term 5, 6, 7, 8. Circulating concentrations of cardiac troponin, a marker of myocardial injury, and natriuretic peptides (NPs), markers of myocardial stress, have emerged as powerful predictors of cardiovascular risk in stable patients with and without T2DM 9, 10, 11, 12, 13. Both markers have also been associated with abnormalities in glucose metabolism.…”

“…Both markers have also been associated with abnormalities in glucose metabolism. For example, minor elevations in glycated hemoglobin (HbA1c) in the prediabetic range are associated with elevations in cardiac troponin 9, 14. In contrast, observational and Mendelian randomization studies suggest modest elevations in NPs protect against the development of T2DM 15, 16.…”

Cardiac troponins: State of the (He)Art

“…However, the increase in sensitivity due to lower cut-off values came at the expense of a decreased specificity 12 : Elevations of cardiac troponin levels turned out not to be specific for acute myocardial infarction, but were also associated with several other acute and chronic conditions like myocarditis, heart failure, pulmonary embolism, stroke, stable coronary artery disease, type 2 diabetes mellitus, decreased renal function and as the result of prolonged exercise 32,[71][72][73][74][75][76][77][78][79][80] . Since the cut-off values of the current diagnostic algorithms are specifically aimed at not missing subjects with acute myocardial infarction (thus the sensitivity is rather high), this may lead to an overdiagnosis or even an overtreatment of patients with persistently elevated cardiac troponin concentrations 81,82 .…”

“…Several of these studies showed that (slightly, even below the 99the percentile) elevated cardiac troponin concentrations reflect future or (sub)clinical disease, and are associated with an unfavorable prognosis, an increased risk for cardiovascular disease and mortality 77,78,[83][84][85][86][87] . These findings indicate a potential role of cardiac troponins in secondary prevention.…”