Thrombospondin-4 increases with the severity of peripheral arterial disease and is associated with diabetes - PubMed (original) (raw)

Thrombospondin-4 increases with the severity of peripheral arterial disease and is associated with diabetes

Bernhard Zierfuss et al. Heart Vessels. 2020 Jan.

Abstract

Thrombospondin-4 (TSP-4) is an extracellular matrix protein of the vessel wall. Despite bench evidence, its significance in the clinical setting of atherosclerosis is missing. TSP-4 (ng/ml) was measured in 365 PAD patientsusing a commercially available ELISA. PAD was diagnosed by the ankle-brachial index (ABI) and clinically graded using the Fontaine classification. TSP-4 levels were significantly higher in Fontaine II vs. Fontaine I (4.78 ± 0. 42, 4.69 ± 0.42, p = 0.043). TSP-4 significantly correlated with ABI (r = - 0.141, p = 0.023, n = 259) after the exclusion of mediasclerotic patients. Binary logistic regression analysis for Fontaine I vs. II showed an OR of 1.70 (1.02-2.82) in a multivariable model adjusted for traditional risk factors. Interestingly, TSP-4 levels were higher in patients with type 2 diabetes mellitus or prediabetes (DGT) compared with normal glucose tolerance (NGT) (4.76 ± 0.42 vs. 4.66 ± 0.41, p = 0.035). ANOVA for PAD and diabetes subgroups showed a linear increase with disease burden with the highest difference between Fontaine I-NGT and Fontaine II-DGT (4.59 ± 0.40, 4.79 ± 0.43, p = 0.015). TSP-4 levels increased with PAD severity and showed a former unknown association with diabetes. Thus, TSP-4 could be a novel marker of atherosclerotic activity, especially in the major subgroup of patients with concomitant diabetes.

Keywords: Atherosclerosis; Biomarker; Diabetes; Extracellular matrix protein; Lower extremity arterial disease; Peripheral arterial disease.

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Conflict of interest statement

There are no potential conflicts of interest to declare. This research received no specific Grant from any funding agency in the public, commercial, or not-for-profit sectors.

Figures

Fig. 1

Fig. 1

Boxplot for PAD I vs. II shows a significant difference in means (4.78 ± 0.42, 4.69 ± 0.42, p = 0.043)

Fig. 2

Fig. 2

Boxplot for different PAD and glucose metabolism stages. *The overall model shows a significant difference in means (p = 0.03). #Post hoc analysis shows a significant difference in means between PAD I-NGT (n = 55) vs. PAD II-DGT (n = 134) (4.59 ± 0.40, 4.79 ± 0.43, p = 0.015)

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