Effect of Previous Exposure to Malaria on Blood Pressure in Kilifi, Kenya: A Mendelian Randomization Study

Background Malaria exposure in childhood may contribute to high blood pressure ( BP ) in adults. We used sickle cell trait ( SCT ) and α⁺thalassemia, genetic variants conferring partial protection against malaria, as tools to test this hypothesis. Methods and Results Study sites were Kilifi, Kenya, which has malaria transmission, and Nairobi, Kenya, and Jackson, Mississippi, where there is no malaria transmission. The primary outcome was 24-hour systolic BP. Prevalent hypertension, diagnosed using European Society of Hypertension thresholds was a secondary outcome. We performed regression analyses adjusting for age, sex, and estimated glomerular filtration rate. We studied 1127 participants in Kilifi, 516 in Nairobi, and 651 in Jackson. SCT frequency was 21% in Kilifi, 16% in Nairobi, and 9% in Jackson. SCT was associated with -2.4 (95% CI , -4.7 to -0.2) mm Hg lower 24-hour systolic BP in Kilifi but had no effect in Nairobi/Jackson. The effect of SCT in Kilifi was limited to 30- to 59-year-old participants, among whom it was associated with -6.1 mm Hg ( CI , -10.5 to -1.8) lower 24-hour systolic BP. In pooled analysis allowing interaction by site, the effect of SCT on 24-hour systolic BP in Kilifi was -3.5 mm Hg ( CI , -6.9 to -0.1), increasing to -5.2 mm Hg ( CI , -9.5 to -0.9) when replacing estimated glomerular filtration rate with urine albumin to creatinine ratio as a covariate. In Kilifi, the prevalence ratio for hypertension was 0.86 ( CI , 0.76-0.98) for SCT and 0.89 ( CI , 0.80-0.99) for α⁺thalassemia. Conclusions Lifelong malaria protection is associated with lower BP in Kilifi. Confirmation of this finding at other sites and elucidating the mechanisms involved may yield new preventive and therapeutic targets.