Cardiac Troponin, Natriuretic Peptide, and Incident PAD

Study Questions:

What is the association of high-sensitivity cardiac troponin T (hs-cTnT) with peripheral artery disease (PAD) incidence, and does natriuretic peptide (NT-proBNP) predict PAD risk?


The investigators quantified the associations of hs-cTnT and NT-proBNP with incident PAD (hospitalizations with PAD diagnosis or leg revascularization—cases with rest pain or tissue loss considered as critical limb ischemia [CLI]) among 12,288 middle-aged adults. Multivariable Cox regression models were used for analysis. 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 (HRs) were greater for CLI than for PAD (HR, 7.74; 95% confidence interval [CI], 4.43–13.55 vs. HR, 2.84; 95% CI, 2.02–4.00 for the highest vs. reference hs-cTnT category and HR, 4.63; 95% CI, 2.61–8.23 vs. HR, 3.16; 95% CI, 2.23–4.49 for the highest vs. reference NT-proBNP category). The addition of these cardiac markers improved c-statistics for CLI.


The authors concluded that hs-cTnT and NT-proBNP were independently associated with incident PAD.


This community-based study with over two decades of follow-up reports robust associations of both hs-cTnT and NT-proBNP with PAD risk. These associations were independent of each other and well-known risk factors for atherosclerotic disease. Furthermore, both cardiac markers, especially hs-cTnT, demonstrated stronger associations with CLI than overall PAD and improved risk discrimination of CLI beyond traditional risk factors. Additional studies are needed to confirm these findings and to investigate pathophysiological mechanisms behind the associations of these cardiac markers with incident PAD.

Clinical Topics: Anticoagulation Management, Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Prevention, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Cardiac Surgery and Arrhythmias, Interventions and Vascular Medicine

Keywords: Atherosclerosis, Biological Markers, Ischemia, Lower Extremity, Myocardial Revascularization, Natriuretic Peptide, Brain, Peptide Fragments, Peripheral Arterial Disease, Primary Prevention, Risk Factors, Troponin T, Vascular Diseases

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