High-sensitivity troponins and mortality in the general population

Abstract

Aims: Cardiac troponin T and I can be measured using a number of high-sensitivity (hs) assays. This study aimed to characterize correlations between four such assays and test their comparative associations with mortality.

Methods and results: Among adults without cardiovascular disease in the 1999-2004 National Health and Nutrition Examination Survey, hs-troponin T was measured using one assay (Roche) and hs-troponin I using three assays (Abbott, Siemens, and Ortho). Cox regression was used to estimate associations with all-cause and cardiovascular mortality. Pearson's correlation coefficients comparing concentrations from each assay ranged from 0.53 to 0.77. There were 2188 deaths (488 cardiovascular) among 9810 participants. Each hs-troponin assay [log-transformed, per 1 standard deviation (SD)] was independently associated with all-cause mortality: hazard ratio (HR) 1.20 [95% confidence interval (CI) 1.13-1.28] for Abbott hs-troponin I; HR 1.10 (95% CI 1.02-1.18) for Siemens hs-troponin I; HR 1.23 (95% CI 1.14-1.33) for Ortho hs-troponin I; and HR 1.31 (95% CI 1.21-1.42) for Roche hs-troponin T. Each hs-troponin assay was also independently associated with cardiovascular mortality (HR 1.44 to 1.65 per 1 SD). Associations of hs-troponin T and all-cause and cardiovascular mortality remained significant after adjusting for hs-troponin I. Furthermore, associations of hs-troponin I remained significant after mutually adjusting for hs-troponin I from the other individual assays: e.g. cardiovascular mortality HR 1.46 (95% CI 1.19-1.79) for Abbott after adjustment for the Siemens assay and HR 1.29 (95% CI 1.09-1.53) for Abbott after adjustment for the Ortho assay.

Conclusion: This study demonstrates only modest correlations between hs-troponin T and three hs-troponin I assays and that hs-troponin I assays can provide distinct risk information for mortality in the general population.

Keywords: All-cause mortality; Cardiovascular mortality; High-sensitivity cardiac troponin; NHANES.

Structured Graphical Abstract

CVD, cardiovascular disease; F/U, follow-up; NHANES, National Health and Nutrition Examination Survey; yr, year.

Figure 1

Hazard ratios (95% confidence intervals) for four high-sensitivity troponin assays with all-cause mortality (panel A, high-sensitivity troponin T, Roche; panel B, high-sensitivity troponin I, Siemens; panel C, high-sensitivity troponin I, Abbott; panel D, high-sensitivity troponin I, Ortho) and cardiovascular disease mortality (panel E, high-sensitivity troponin T, Roche; panel F, high-sensitivity troponin I, Siemens; panel G, high-sensitivity troponin I, Abbott; panel H, high-sensitivity troponin I, Ortho) among US adults without a history of cardiovascular disease, NHANES 1999–2004. High-sensitivity troponin was log-transformed and modeled as a restricted cubic spline (solid line). Knots were placed at 5th, 35th, 65th, 95th, percentiles. The shaded areas on each side of the regression line are the 95% confidence intervals. The background shaded area is the distribution (histogram) of each high-sensitivity troponin assay in the population. The models were adjusted for age, sex, race/ethnicity, total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure, cigarette smoking status, diabetes mellitus, family history of cardiovascular disease, body mass index, use of blood pressure medications, use of cholesterol-lowering medications, and estimated glomerular filtration ratio. CI, confidence interval; CVD, cardiovascular disease; Tn, troponin.

Figure 2

Unweighted pairwise correlations between log-transformed high-sensitivity troponin assays among primary prevention US adults aged 18 or older with concentrations above the assay limit of blank, NHANES 1999–2004. Unweighted Scatterplots. Non-linear dashed line, locally weighted scatterplot smoothing; straight unbroken line, linear regression; horizontal and vertical intersecting dashed lines, 99th percentile of troponin in the analytic sample. Participants with high-sensitivity troponin concentrations below the limit of blank for each assay were excluded from correlation analyses. RMSE, root mean square error; NRMSE, normalized root mean square error.