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 Ballew, Yingying Sang, Ron C. Hoogeveen, Bernard Jaar, Elizabeth Selvin, Christie M. Ballantyne, A. Richey Sharrett, Aaron R. Folsom, Gerardo Heiss, Josef Coresh, Alan T. Hirsch

Research output: Contribution to journalArticle

Abstract

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
Volume39
Issue number25
DOIs
StatePublished - Jul 1 2018

Fingerprint

Natriuretic Peptides
Troponin
Peripheral Arterial Disease
Lower Extremity
Atherosclerosis
Ischemia
Extremities
Troponin T
Nociceptive Pain
Amputation
Proportional Hazards Models
Leg
Hospitalization
Confidence Intervals

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

High-sensitivity cardiac troponin and natriuretic peptide with risk of lower-extremity peripheral artery disease : the Atherosclerosis Risk in Communities (ARIC) Study. / Matsushita, Kunihiro; Kwak, Lucia; Yang, Chao; Pang, Yuanjie; Ballew, Shoshana; Sang, Yingying; Hoogeveen, Ron C.; Jaar, Bernard; Selvin, Elizabeth; Ballantyne, Christie M.; Sharrett, A. Richey; Folsom, Aaron R.; Heiss, Gerardo; Coresh, Josef; Hirsch, Alan T.

In: European Heart Journal, Vol. 39, No. 25, 01.07.2018, p. 2412-2419.

Research output: Contribution to journalArticle

Matsushita, Kunihiro ; Kwak, Lucia ; Yang, Chao ; Pang, Yuanjie ; Ballew, Shoshana ; Sang, Yingying ; Hoogeveen, Ron C. ; Jaar, Bernard ; Selvin, Elizabeth ; Ballantyne, Christie M. ; Sharrett, A. Richey ; Folsom, Aaron R. ; Heiss, Gerardo ; Coresh, Josef ; Hirsch, Alan T. / High-sensitivity cardiac troponin and natriuretic peptide with risk of lower-extremity peripheral artery disease : the Atherosclerosis Risk in Communities (ARIC) Study. In: European Heart Journal. 2018 ; Vol. 39, No. 25. pp. 2412-2419.
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abstract = "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.",
keywords = "Cardiac troponin T, Critical limb ischaemia, Epidemiology, Natriuretic peptide, Peripheral artery disease, Risk prediction",
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T1 - High-sensitivity cardiac troponin and natriuretic peptide with risk of lower-extremity peripheral artery disease

T2 - the Atherosclerosis Risk in Communities (ARIC) Study

AU - Matsushita, Kunihiro

AU - Kwak, Lucia

AU - Yang, Chao

AU - Pang, Yuanjie

AU - Ballew, Shoshana

AU - Sang, Yingying

AU - Hoogeveen, Ron C.

AU - Jaar, Bernard

AU - Selvin, Elizabeth

AU - Ballantyne, Christie M.

AU - Sharrett, A. Richey

AU - Folsom, Aaron R.

AU - Heiss, Gerardo

AU - Coresh, Josef

AU - Hirsch, Alan T.

PY - 2018/7/1

Y1 - 2018/7/1

N2 - 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.

AB - 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.

KW - Cardiac troponin T

KW - Critical limb ischaemia

KW - Epidemiology

KW - Natriuretic peptide

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