Mechanistic Investigation of the Relationship Between Chronic Malaria Exposure and Accelerated Cardiovascular Ageing in Adults in Malaria-Endemic Regions of North East Nigeria

Cumulative malaria exposure across the life course may drive premature cardiovascular ageing through chronic systemic inflammation, endothelial dysfunction, and autonomic dysregulation, yet this mechanistic pathway has never been prospectively investigated in a Nigerian adult cohort. This study mechanistically investigates the relationship between chronic Plasmodium falciparum malaria exposure and accelerated cardiovascular ageing in adults in malaria-endemic communities of Borno and Adamawa States, North East Nigeria. A cross-sectional study with longitudinal biomarker follow-up is applied to 1,000 adult participants aged 25 to 60 years stratified by lifetime malaria exposure estimated through retrospective malaria history, current antibody titres to Plasmodium falciparum antigens (anti-PfMSP1, anti-PfAMA1), and remotely sensed malaria endemicity at place of residence. Cardiovascular ageing biomarkers include carotid intima-media thickness by ultrasound, pulse wave velocity, epigenetic clock acceleration (PhenoAge), telomere length in leukocytes by qPCR, and plasma biomarkers of endothelial activation (ICAM-1, VCAM-1, von Willebrand factor). Mediation analysis in R tests inflammatory cytokine profiles as mechanistic mediators. The Allostatic Load Theory and Plasmodium-Cardiovascular Interaction Model provide the theoretical basis. Original contributions include the first mechanistic data linking chronic malaria exposure to cardiovascular ageing biomarkers in a Nigerian adult population, establishing a novel research pathway with implications for malaria elimination strategy. Keywords: malaria, cardiovascular ageing, epigenetic clock, endothelial dysfunction, North East Nigeria.