Prognostic value of subclinical myocardial necrosis using high-sensitivity cardiac troponin T in patients with prediabetes

Marco Witkowski, Yuping Wu, Stanley L Hazen, W H Wilson Tang, Marco Witkowski, Yuping Wu, Stanley L Hazen, W H Wilson Tang

Abstract

Background: Risk stratification of patients with prediabetes is an unmet clinical need. Here, we examine the utility of subclinical myocardial necrosis assessed by high-sensitivity cardiac troponin T (hs-cTnT) in predicting health outcomes in stable subjects with prediabetes.

Methods: hs-cTnT was analyzed by a high-sensitivity assay (Roche 5th generation) in 2631 stable subjects with prediabetes (HbA1c 5.7-6.4% or fasting glucose 100-125 mg/dL without previous diagnosis of diabetes or glucose-lowering therapy) who underwent elective coronary angiography for cardiac evaluation, and followed for major adverse cardiac events (MACE; death, myocardial infarction, stroke) over 3 years and all-cause mortality over 5 years.

Results: In our study cohort, hs-cTnT was highly prevalent with a median level of 13 ng/L (interquartile range 8.2-21.6 ng/L). Hs-cTnT was independently associated with incident MACE at 3 years (Q4 vs. Q1 adjusted hazard ratio (HR) 2.42 [95% CI 1.69-3.46], P < 0.001) and 5-year mortality (adjusted HR 3.8 [95% CI 2.55-5.67], P < 0.001). This association remained significant in all subsets after adjustment for traditional risk factors and multiple factors known to increase hs-cTnT levels. Moreover, hs-cTnT independently predicted event risk in primary prevention subjects (n = 557, HR 5.46 [95% CI 1.50-19.89), p < 0.01) for MACE; HR 9.53 [95% CI 2.08-43.73] for all-cause mortality) and secondary prevention subjects (n = 2074, HR 1.86 [95% CI 1.31-2.66], P < 0.001 for MACE; and 2.7 [95% CI 1.79-4.08), P < 0.001 for all-cause mortality).

Conclusions: In stable prediabetic subjects, the presence of subclinical myocardial necrosis as detected by hs-cTnT portends heightened long-term adverse cardiovascular event risk. Hs-cTnT levels may help to stratify risk and improve clinical decision making in patients with prediabetes. Trial registration ClinicalTrials.gov Identifier: NCT00590200.

Keywords: Cardiac troponin T; Prediabetes; Prognosis.

Conflict of interest statement

Dr. Hazen reports being named as co-inventor on pending and issued patents held by the Cleveland Clinic relating to cardiovascular diagnostics and therapeutics. Dr. Hazen also reports being a paid consultant for Procter & Gamble, having received research funds from Procter & Gamble, and Roche Diagnostics, and being eligible to receive royalty payments for inventions or discoveries related to cardiovascular diagnostics or therapeutics from Cleveland HeartLab, a fully owned subsidiary of Quest Diagnostics, and Procter & Gamble. Dr. Tang has served as a paid consultant for Sequana Medical AG, Owkin Inc, Relypsa Inc, Cardiol Therapeutics Inc, preCARDIA Inc, Genomics plc, and received honoraria from Springer Nature and American Board of Internal Medicine, all unrelated to the present topic. The other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Kaplan–Meier estimates and the risk of incident major adverse cardiac events (MACE, defined as myocardial infarction, stroke, or death) as well as all-cause mortality over follow-up periods of 3 and 5 years, respectively, stratified by quartile of hs-cTnT levels. Shown is the analysis for all patients (A, B), primary prevention subjects (C, D) and secondary prevention subjects (E, F)
Fig. 2
Fig. 2
Forest plots indicating the risks of incident MACE at 3 years and death after 5 years ranked by quartiles of hs-cTnT levels. The multivariable Cox model for hazard ratio included adjustments for age, sex, systolic blood pressure, low density lipoprotein cholesterol, high density lipoprotein cholesterol, smoking and estimated glomerular filtration rate. The 5–95% confidence interval is indicated by line length. Shown is the analysis for all patients (A, B), primary prevention subjects (C, D) and secondary prevention subjects (E, F)
Fig. 3
Fig. 3
Forest plot of the hazard ratio for A MACE in 3 years and B 5-year all-cause mortality risk comparing first and fourth quartiles of hs-cTnT levels in different groups as indicated. The 5–95% confidence interval is indicated by line length. P value for trend was calculated by Cochran–Armitage and Jonckheere–Terpstra tests of trend to compare baseline characteristics across increasing quartiles of hs-cTnT for categorical and continuous variables, respectively. CAD coronary artery disease, eGFR estimated glomerular filtration rate, LDL low density lipoprotein cholesterol, PAD peripheral artery disease, TRGs triglycerides
Fig. 4
Fig. 4
Cubic spline curves of the hazard ration (HR) for A major adverse cardiac events (MACE, death, nonfatal myocardial infarction, and stroke) at 3 years and B death at 5 years with hs-cTnT levels

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