Soluble urokinase plasminogen activator receptor: a risk factor for carotid plaque, stroke, and coronary artery disease

Stroke. 2014 Jan;45(1):18-23. doi: 10.1161/STROKEAHA.113.003305. Epub 2013 Nov 19.

Abstract

Background and purpose: Recent studies indicate that the urokinase system could have an important role in atherogenesis and plaque rupture. The relationships among the soluble urokinase plasminogen activator receptor (suPAR), carotid plaque, and incidence of ischemic stroke and coronary artery disease (CAD) events were studied in a prospective cohort.

Methods: Occurrence of carotid plaque and plasma levels of suPAR were assessed in 5166 men and women, aged 45 to 68 years, participating in the Malmö Diet and Cancer study. Incidences of ischemic stroke and CAD were monitored during a mean follow-up of 15 years.

Results: Subjects with carotid plaque had significantly higher levels of suPAR compared with those without carotid plaque. suPAR was associated with increased incidence of ischemic stroke (hazard ratio [HR] for third versus first tertile, 1.50; 95% confidence interval [CI], 1.06-2.11) and CAD (HR, 1.55; 95% CI, 1.13-2.13) after adjustment for risk factors. The risk factor-adjusted HR for ischemic stroke was 2.21 (95% CI, 1.52-3.22) in subjects with carotid plaque and high suPAR (ie, third tertile) and 1.51 (95% CI, 1.05-2.17) in subjects with carotid plaque and low suPAR compared with those without carotid plaque and low suPAR (reference). High levels of suPAR significantly increased the risk of ischemic stroke and CAD in subjects with carotid plaque.

Conclusions: suPAR is associated with increased occurrence of carotid plaque and increased incidence of ischemic stroke and CAD. Presence of both elevated levels of suPAR and carotid plaque increases the risk of ischemic stroke in an additive way.

Keywords: carotid artery plaque; coronary artery disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers
  • Brain Ischemia / epidemiology
  • Brain Ischemia / genetics
  • Brain Ischemia / metabolism
  • Carotid Artery Diseases / epidemiology*
  • Carotid Artery Diseases / genetics*
  • Carotid Artery Diseases / metabolism
  • Cohort Studies
  • Coronary Artery Disease / epidemiology*
  • Coronary Artery Disease / genetics*
  • Coronary Artery Disease / metabolism
  • Diabetes Mellitus, Type 2 / complications
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Plaque, Atherosclerotic / epidemiology*
  • Plaque, Atherosclerotic / genetics*
  • Plaque, Atherosclerotic / metabolism
  • Population
  • Prospective Studies
  • Receptors, Urokinase Plasminogen Activator / genetics*
  • Receptors, Urokinase Plasminogen Activator / metabolism*
  • Risk Factors
  • Stroke / epidemiology*
  • Stroke / genetics*
  • Stroke / metabolism
  • Survival Analysis

Substances

  • Biomarkers
  • Receptors, Urokinase Plasminogen Activator