The purpose of this study is to investigate the relationship between exposure to malaria and the risk of developing subclinical and manifest cardiovascular disease. The study is conducted in the high endemic malaria zone pertaining to the city of Cruzeiro do Sul, located in the state of Acre, Brazil. The city is considered a part of the Amazon basin.

By invitation of a random sample of patients with a history of malaria, controls with no history of malaria, and symptomatic patients with ongoing malaria infection, the aim is to elucidate potential pathways linking malaria to cardiovascular disease.

Aim 1: Determine whether prior exposure to malaria is associated with myocardial dysfunction. We hypothesize that adults with a history of treated malaria (cases) will have worse left ventricular (LV) diastolic function and systolic strain compared to age- and sex-matched controls without a history of malaria infection. We will recruit 500 cases and 500 controls from Cruzeiro-do-Sul, Brazil. State-of-the-art ultrasonographic examinations will be used to asses novel imaging metrics of cardiac function.

Aim 2: Define the extent to which proinflammatory factors (such as Ang-2, CRP, VEGF) are associated with cardiac dysfunction in subjects with a history of malaria. We hypothesize that proinflammatory biomarkers will be higher in cases compared to controls, and that higher concentrations of inflammatory markers will associate with worse LV diastolic function and strain. We will measure inflammatory biomarkers, determine the association with cardiac dysfunction, and test whether history of malaria modifies this association.

Aim 3: Determine if echocardiographic parameters of systolic and diastolic function and cardiac biomarkers are significantly elevated in patients with symptomatic malaria (N=200).

Upon conclusion of this study, we will better understand the relationship of malaria with subclinical cardiac dysfunction. This will allow us to develop the scientific foundation and necessary infrastructure to expand this project to a longitudinal study to prospectively assess associations with relevant clinical outcomes.