Soluble urokinase plasminogen activator receptor (suPAR) is a novel, independent predictive marker of myocardial infarction in HIV‐1‐infected patients: a nested case‐control study

Abstract

ObjectivesPatients infected with HIV are at increased risk of myocardial infarction (MI). Increased plasma levels of the inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) have been associated with increased risk of cardiovascular diseases (CVD), including MI in the general population. We tested suPAR as a predictive biomarker of MI in HIV‐1‐infected individuals.MethodssuPAR levels were investigated in a nested case‐control study of 55 HIV‐1‐infected cases with verified first‐time MI and 182 HIV‐1‐infected controls with no known CVD. Controls were matched for age, gender, duration of antiretroviral therapy (ART), smoking and no known CVD. suPAR was measured in the four plasma samples available for each patient at different time‐points; 1, Before initiation of ART; 2, 3 months after initiation of ART; 3, 1 year before the case's MI; and 4, The last sample available before the case's MI.ResultsIn unadjusted conditional regression analysis, higher levels of suPAR were associated with a significant increase in risk of MI at all time‐points. Patients in the third and fourth suPAR quartiles had a three‐ to 10‐fold higher risk of MI compared to patients in the lowest suPAR quartile at all time‐points. suPAR remained a strong significant predictor of MI, when adjusting for HIV‐1 RNA, total cholesterol, triglycerides and high‐density lipoprotein.ConclusionElevated suPAR levels were associated with increased risk of MI in HIV‐infected patients, suggesting that suPAR could be a useful biomarker for prediction of first‐time MI in this patient group, even years before the event.

Mechanisms underlying the J-curve for diastolic blood pressure: Subclinical myocardial injury and immune activation

“…Furthermore, in patients with known atherosclerosis, elevated suPAR may additionally represent significant endothelial dysfunction associated with CAD, thus providing a more specific marker that incorporates several disease pathways, as opposed to hsCRP [9]. While elevations in suPAR have been associated with adverse outcomes in a wide variety of disease processes [11,13,[32][33][34], it has more recently shown promise as a predictor of incident cardiovascular events [10,15,35]. Both serum and intraplaque levels of suPAR were elevated in patients with symptomatic carotid atherosclerosis, suggesting its potential utility in identifying a vulnerable plaque phenotype [36].…”

Serum suPAR and syndecan-4 levels predict severity of community-acquired pneumonia: a prospective, multi-centre study

“…suPAR has been widely studied in a variety of infectious diseases, including sepsis [ 23 ], tuberculosis [ 24 ], and HIV infection [ 25 ]. Savva et al demonstrated that suPAR is a reliable predictor of severity of sepsis and can independently predict unfavourable outcomes in both ventilator-associated pneumonia and sepsis [ 26 ].…”

Risk of Cardiovascular Disease in an Aging HIV Population: Where Are We Now?

“…Elevated soluble urokinase-type plasminogen activator receptor (suPAR) is an inflammation marker and has recently been identified as a predictor of MI in HIVinfected patients [93].…”