suPAR as a biomarker for cardiovascular disease

The suPAR level is elevated in patients with cardiovascular diseases compared to healthy individuals, and elevated suPAR level is associated with:

  • Atherosclerosis1
  • Ischemic heart disease2,13,21
  • Poor prognosis2,16,18,19
  • Venous thromboembolism20

As well as incidence of:

  • Cardiovascular diseases in the general population7-11

suPAR is a promising biomarker of cardiovascular diseases, as it reflects “low-grade inflammation” and is associated with lifestyle factors like smoking, alcohol, and an inactive lifestyle. Previous studies have shown, that the uPA/uPAR-system plays a key role in the pathogenesis of atherosclerosis1. Physiologically the system is involved in fibrinolysis, angiogenesis, and immune function, including leucocyte migration, proliferation, and degradation of matrix during tissue remodeling in the atherosclerotic plaque2. uPAR is expressed in various cells involved in the development of atherosclerosis, including macrophages, endothelial cells, and smooth muscle cells, and an accumulation of uPAR in the atheroma has been found3. uPAR plays a role in the coagulation cascade during plasminogen activation and fibrinolysis4. So far, no causal relationship between the uPAR system and atherosclerosis or cardiovascular diseases has been shown2. However, new data have demonstrated an association between suPAR and focal segmental glomerulosclerosis. The kidneys play a key role in blood pressure and fluid balance regulation, and therefore suPAR may be associated with heart failure and myocardial strain5,6. A similar suPAR-mediated effect on endothelial cells and platelets may potentially play a role in vascular inflammation and thrombosis5.

In five large studies, including a total of 4866 individuals7-11, suPAR is a predictor of cardiovascular morbidity and mortality in the general population even after adjustment for the well-validated Framingham risk score11 and taking into account well-known risk factors, CRP, and other biomarkers associated with cardiovascular diseases. In general, the prognostic value of baseline suPAR level appears to be strongest in the younger age groups and in males11.

In patients with ST-segment elevation myocardial infarction (STEMI) treated with primary PCI, the suPAR level is elevated the first 24 hours after admission. Following adjustment for traditional risk factors, age, sex, CRP, creatinine, troponin T, total cholesterol, diabetes, and hypertension, suPAR remains associated with mortality and a new myocardial infarction2. In non-survivors, baseline suPAR values are significantly higher than in survivors (4.9 ng/mL vs. 3.9 ng/mL), and all-cause mortality increases significantly with higher suPAR values2.

“suPAR is an early predictive marker for complications in type 1 diabetes … and is a potent risk factor in prediction of cardiovascular and renal diseases.”

Viktor Rotbain Curovic,
Dr. MD, Steno Diabetes Center Copenhagen, Denmark
suPAR News Vol. 2, Sept. 2019