Recent Studies Identify Pair of Biomarkers in Peripheral Artery Disease

Published on: 

Two studies, including one that examined patient data from a well-known diabetes trial, confirmed the value of 2 cardiovascular biomarkers in predicting mortality in peripheral artery disease.

A pair of recent studies with different designs tested the same 2 cardiovascular biomarkers and concluded they could be used to identify patients at risk of future peripheral artery disease (PAD).

Both studies examined the predicative value of high-sensitivity cardiac troponin T (hs-CTnT) and natriuretic peptide (NT-proBNP), which are strongly associated with coronary heart disease, heart failure, and shortened life expectancy in population-based studies.

The first study, presented earlier this month at the 79th Scientific Sessions of the American Diabetes Association (ADA) in San Francisco, California,1 examined whether patients who took part in the ADVANCE trial and had elevated levels of the biomarkers at baseline were more likely to develop PAD after 5 years. The ADVANCE trial, which published results in 2007, tested the effect of a fixed dose of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes (T2D).


Patients who had ≥ 14 ng/L hs-cTnT and ≥ 200 pg/mL NT-proBNP were studied using Cox models. Even after adjusting for cardiovascular risk factors, PAD risk was higher among participants with at least 1 elevated biomarker, and highest among those with both biomarkers elevated:

  • elevated hs-CTnT (hazard ratio [HR] 1.35 95% CI, 1.07-1.70).
  • elevated NT-proBNP (HR 1.44, 95% CI, 1.15-1.81).
  • both biomarkers (HR 1.85, 95% CI, 1.38-2.49).

The authors concluded the 2 biomarkers may be useful in predicting which patients with T2D are likely to develop PAD.

A second study, published online in April and appearing in the current issue of Clinica Chimica Acta,2 also confirmed the predictive value of hs-cTnT and NT-proBNP. A total of 95 PAD patients were enrolled; their mean age was 68 years, and 73 were men. In addition to the first 2 biomarkers, investigators measured carotid intima-media thickness (cIMT) and ankle brachial index (ABI).

After a median follow-up period of 9.5 years, results were as follows:

  • 44 patients died and 51 survived
  • A Kaplan-Meier analysis showed hs-CTnT and NT-proBNP above the median but not the other 2 markers.
  • After adjustments for age, gender, prior cerebral artery disease and diabetes, the significant associations that remained were for hs-cTnT and mortality; the combination of hs-cTnT and NT-proBNP and both biomarkers were both superior to cIMT and ABI in assessing risk for mortality.

The researchers concluded that both hs-cTnT and NT-proBNP “should be taken into account for prognosis of patients with PAD.”


  1. Hicks CW, Wang D, Matsushita K, Chalmers J, Woodward M, Selvin E. Cardiac biomarkers and incident peripheral arterial disease (PAD) in patients with type 2 diabetes in the ADVANCE trial. Diabetes. Presented at: 79th Scientific Sessions of the American Diabetes Association; San Francisco, California; June 7-11, 2019; Abstract 409-P.
  2. Clemens Rk, Annema W, Baumann F, et al. Cardiac biomarkers but not measures of vascular atherosclerosis predict mortality of patients with peripheral artery disease. Clin Chim Acta. 2019;495:215-220.doi:10.1016/j.cca.2019.04.061.