High-sensitivity cardiac troponin and natriuretic peptide with risk of lower-extremity peripheral artery disease: the Atherosclerosis Risk in Communities (ARIC) Study

Kunihiro Matsushita, Lucia Kwak, Chao Yang, Yuanjie Pang, Shoshana H. Ballew, Yingying Sang, Ron C. Hoogeveen, Bernard G. Jaar, Elizabeth Selvin, Christie M. Ballantyne, A. Richey Sharrett, Aaron R. Folsom, Gerardo Heiss, Josef Coresh, Alan T. Hirsch

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Aims Cardiac troponin T (cTnT) is suggested as a predictor of amputation in patients with peripheral artery disease (PAD). However, cTnT-PAD association has not been systematically studied in a large study. This study evaluated the association of high-sensitivity cTnT (hs-cTnT) with PAD incidence and also explored whether natriuretic peptide (NT-proBNP), another representative cardiac marker, predicts PAD risk. Methods Among 12 288 middle-aged adults, the associations of hs-cTnT and NT-proBNP with incident PAD (hospitalizations and results with PAD diagnosis or leg revascularization [cases with rest pain or tissue loss considered as critical limb ischaemia (CLI)]) were quantified with multivariable Cox regression models. The risk discrimination was assessed by c-statistic. During a follow-up over 22 years, 454 participants developed PAD (164 CLI cases). In demographically adjusted models, the highest category of hs-cTnT (>_14 vs. <3 ng/L) and NT-proBNP (>_258.3 vs. <51.5 pg/mL) showed 8- and 10–20-fold higher risk of PAD and CLI, respectively. Even after adjusting for potential confounders and each other, hazard ratios were greater for CLI than for PAD (7.74 95% confidence interval [95% CI 4.43–13.55] vs. 2.84 [2.02–4.00] for the highest vs. reference hs-cTnT category and 4.63 [2.61–8.23] vs. 3.16 [2.23–4.49] for the highest vs. reference NT-proBNP category). The addition of these cardiac markers improved c-statistics for CLI.Conclusion High-sensitivity cTnT and NT-proBNP were independently associated with incident PAD, particularly its severe form, CLI. Although future studies are warranted to investigate pathophysiological mechanisms behind these associations, our study suggests the usefulness of cardiac markers to identify individuals at high risk of CLI.

Original languageEnglish (US)
Pages (from-to)2412-2419
Number of pages8
JournalEuropean heart journal
Issue number25
StatePublished - Jul 1 2018

Bibliographical note

Funding Information:
The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN2682 01100007C, HHSN268201100008C, HHSN-268201100009C, HHSN 268201100010C, HHSN268201100011C, and HHSN268201100012C). This study is supported by a grant from the American Heart Association (#14CRP20380886) and a grant from the National Heart, Lung, And Blood Institute (R21HL133694) to K.M. Reagents for the hsc-TnT and NT-proBNP assays were donated by Roche Diagnostics.

Publisher Copyright:
© The Author(s)2018 All rights reserved.


  • Cardiac troponin T
  • Critical limb ischaemia
  • Epidemiology
  • Natriuretic peptide
  • Peripheral artery disease
  • Risk prediction


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