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


J Am Heart Assoc

Background Malaria exposure in childhood may contribute to high blood pressure ( BP ) in adults. We used sickle cell trait ( SCT ) and alpha(+)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 alpha(+)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.

Etyang, A. O., Kapesa, S., Odipo, E., Bauni, E., Kyobutungi, C., Abdalla, M., Muntner, P., Musani, S. K., Macharia, A., Williams, T. N., Cruickshank, J. K., Smeeth, L., Scott, J. A. G.

Pages:e011771, Volume:8, Edition:3/19/2019, Date,Mar-19

Link: https://www.ncbi.nlm.nih.gov/pubmed/30879408

Notes:Etyang, Anthony O|Kapesa, Sailoki|Odipo, Emily|Bauni, Evasius|Kyobutungi, Catherine|Abdalla, Marwah|Muntner, Paul|Musani, Solomon K|Macharia, Alex|Williams, Thomas N|Cruickshank, J Kennedy|Smeeth, Liam|Scott, J Anthony G|eng|HHSN268201300049C/HL/NHLBI NIH HHS/|HHSN268201300046C/HL/NHLBI NIH HHS/|R01 HL117323/HL/NHLBI NIH HHS/|HHSN268201300047C/HL/NHLBI NIH HHS/|HHSN268201300048C/HL/NHLBI NIH HHS/|WT_/Wellcome Trust/United Kingdom|HHSN268201300050C/HL/NHLBI NIH HHS/|Multicenter Study|Research Support, N.I.H., Extramural|Research Support, Non-U.S. Gov’t|England|2019/03/19 06:00|J Am Heart Assoc. 2019 Mar 19;8(6):e011771. doi: 10.1161/JAHA.118.011771.

ISBN: 2047-9980 (Electronic)|2047-9980 (Linking) Permanent ID: PMC6475058 Accession Number: 30879408

Author Address: 1 KEMRI-Wellcome Trust Research Programme Kilifi Kenya.|2 London School of Hygiene and Tropical Medicine London United Kingdom.|3 African Population and Health Research Centre Nairobi Kenya.|4 Columbia University Medical Center New York NY.|5 University of Alabama at Birmingham AL.|6 University of Mississippi Medical Center Jackson MS.|7 Imperial College London United Kingdom.|8 King’s College London United Kingdom.