Plasma Urokinase Plasminogen Activator and Pro-Adrenomedullin as Biomarkers in Hypertensive Individuals with Malaria Co-Infection at Nauth, Nnewi, Nigeria

Background:Hypertension (HTN) and malaria remain major causes of comorbidity and mortality in low- and middle-income countries (LMICs), including Nigeria. The coexistence of these conditions poses a significant double disease burden. Malaria infection may influence hypertension progression, possibly through inflammatory and endothelial pathways. This study aimed to evaluate plasma levels of urokinase plasminogen activator (uPA), a serine protease involved in fibrinolysis and tissue remodeling, and pro-adrenomedullin (Pro-ADM), a precursor of a vasoactive peptide associated with endothelial function, in hypertensive individuals with and without malaria infection. Methods:This cross-sectional study was conducted at NAUTH, Nnewi, Nigeria, and included 90 participants aged 22–79 years. Participants were grouped into 30 hypertensive individuals with confirmed Plasmodium falciparum malaria infection, 30 hypertensive individuals without malaria, and 30 apparently healthy controls (46 females and 44 males). Five milliliters of venous blood was collected from each participant. Malaria diagnosis was performed using Giemsa-stained thick and thin blood smears. Plasma uPA and Pro-ADM levels were measured using Enzyme-Linked Immunosorbent Assay (ELISA). Exclusion criteria included HIV infection, diabetes mellitus, chronic kidney or liver disease, pregnancy, or other acute infections. Results:Hypertensive individuals with malaria infection had significantly higher mean plasma levels of uPA (7.02±3.57 ng/mL) and Pro-ADM (52.02±27.23 pg/mL) than hypertensive individuals without malaria (2.14±0.52 ng/mL, 20.39±2.34 pg/mL) and healthy controls (2.39±2.48 ng/mL, 21.23±2.51 pg/mL) (p = 0.000 respectively). A significant positive correlation (r = 0.640, p = 0.000) was observed between uPA and Pro-ADM levels in the malaria-infected hypertensive group. Conclusion:The concurrent elevation of uPA and Pro-ADM in hypertensive individuals with Plasmodium falciparum infection may suggest a combined response to endothelial dysfunction and inflammatory stress. These findings point to a potential pathophysiological link between infectious and cardiovascular diseases. However, given the cross-sectional design, causality cannot be established. Further longitudinal studies are warranted to explore these biomarker relationships and their clinical implications in malaria-endemic settings.