Impaired endothelial function in patients with undifferentiated connective tissue disease: a follow-up study

Rheumatology (Oxford). 2014 Nov;53(11):2035-43. doi: 10.1093/rheumatology/keu236. Epub 2014 Jun 10.

Abstract

Objective: In this study the alteration of endothelial function, arterial stiffness and autoantibodies was investigated in patients with UCTD.

Methods: Thirty-one patients with UCTD were included in this prospective study. All the patients remained in the UCTD stage during the average 3.8 years follow-up period. The onset of UCTD was denoted as UCTD1, while the end of the follow-up period was called UCTD2. Flow-mediated vasodilation (FMD), carotid intima-media thickness (IMT), autoantibodies [such as anti-SSA, anti-SSB, anti-DNA, anti-RNP, anti-CCP, aCL, anti-oxidized low-density lipoprotein (oxLDL) and AECA], von Willebrand factor antigen, thrombomodulin (TM), endothelin 1 (ET-1) and lipid parameters were measured.

Results: In the UCTD1 stage, high-sensitivity CRP (hsCRP) and endothelial cell activation and/or damage markers such as TM, ET-1 and AECA levels were significantly higher compared with controls (controls vs UCTD1: hsCRP, P < 0.0001; TM, P = 0.001; ET-1, P < 0.0001). In the UCTD2 stage, the carotid IMT increased (UCTD1 vs UCTD2, P = 0.01) and FMD further deteriorated (UCTD1 and UCTD2, P = 0.001). In UCTD2 there was a close correlation between the carotid IMT, and duration of the disease (r = 0.612, P < 0.001), the level of TM (r = 0.673, P < 0.001) and anti-oxLDL (r = 0.800, P < 0.001).

Conclusion: Our data suggest that the presence of inflammation and autoantibodies provoke endothelial cell activation and/or injury in UCTD patients. The persistent endothelial dysfunction may provoke the development of atherosclerosis. FMD was found to be the most sensitive marker for arterial stiffness, and the increase of IMT clearly indicated the existence of preclinical atherosclerosis in UCTD patients.

Keywords: accelerated atherosclerosis; endothelial cell markers; endothelial dysfunction; flow-mediated vasodilation; undifferentiated connective tissue disease.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Brachial Artery / diagnostic imaging*
  • Brachial Artery / physiopathology
  • Carotid Arteries / diagnostic imaging*
  • Carotid Arteries / physiopathology
  • Carotid Intima-Media Thickness
  • Endothelium, Vascular / physiopathology*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Mixed Connective Tissue Disease / diagnosis
  • Mixed Connective Tissue Disease / physiopathology*
  • Prognosis
  • Prospective Studies
  • Time Factors
  • Vasodilation / physiology*
  • Young Adult