Low Elastin Content of Carotid Plaques Is Associated With Increased Risk of Ipsilateral Stroke

PLoS One. 2015 Mar 24;10(3):e0121086. doi: 10.1371/journal.pone.0121086. eCollection 2015.

Abstract

Objectives: Atherosclerotic plaques with a low content of connective tissue proteins are believed to have an increased risk of rupture and to give rise to clinical events. The aim of the present study was to investigate if the content of elastin, collagen and of the matrix metalloproteinase (MMP) -1, -3, -9 and -12 in plaques removed at surgery can be associated with the occurrence of ipsilateral symptoms.

Methods: The atherosclerotic plaques of 221 patients undergoing carotid endarterectomy were analyzed and their composition was related to the incidence of preoperative, intraoperative and postoperative neurological events.

Results: Elastin, collagen and MMP-12 contents were lower in males and diabetic patients. Elastin (P .010), MMP-3 (P .008) and MMP-9 (P < .0001) were lower, while MMP-1 (P .004) and MMP-9 (P .002) were higher in plaques of patients with preoperative symptoms, even after correction for the time between the occurrence of symptoms and surgery. Elastin and MMP-12 decreased (r = -0.17, P .009 and r = -.288, P <.0001 respectively) while MMP-1 (r = 0.17, P .012) and MMP-9 (r = .21 P <.0001) increased with age. After a mean follow-up time of 39.6 ± 16.6 months, 7.7% of patients had suffered one or multiple ipsilateral neurological events. Patients with plaque elastin levels lower than the median (52 mg/g) had increased post-operative incidence of ipsilateral stroke (P for trend 0.009 using Log Rank Chi-square test). This finding was confirmed when controlling for age, gender, hypertension, diabetes, smoking, pre-operative symptoms and statin usage in a Cox Proportional Hazard model (hazard ratio 7.38, 95% C.I. 1.50-36.31).

Conclusions: These observations support the concept that elastin may be important for plaque stability, and suggest that a low plaque content of elastin is associated with a higher risk for ipsilateral stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carotid Artery Diseases / complications*
  • Carotid Artery Diseases / epidemiology
  • Carotid Artery Diseases / metabolism*
  • Carotid Artery Diseases / surgery
  • Collagen / metabolism
  • Comorbidity
  • Elastin / metabolism*
  • Endarterectomy, Carotid
  • Female
  • Humans
  • Incidence
  • Male
  • Matrix Metalloproteinases / metabolism
  • Plaque, Atherosclerotic / complications*
  • Plaque, Atherosclerotic / epidemiology
  • Plaque, Atherosclerotic / metabolism*
  • Plaque, Atherosclerotic / surgery
  • Risk Factors
  • Stroke / complications*
  • Stroke / epidemiology

Substances

  • Collagen
  • Elastin
  • Matrix Metalloproteinases

Grant support

This work was supported by the Swedish Research Council (JN, IG) (2010–2932 http://www.vr.se/), the Marianne and Marcus Wallenberg Foundation (JN, IG) (MMW 2010.0040 https://www.wallenberg.com/mmw/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.—The Swedish Heart and Lung Foundation (JN, IG) 20110355 http://hjart-lungfonden.se/—The Swedish Foundation for Strategic Research (JN) RBa08-0075 http://www.stratresearch.se/