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

Anthony O. Etyang; Sailoki Kapesa; Emily Odipo; Evasius Bauni; Catherine Kyobutungi; Marwah Abdalla; Paul Muntner; Solomon K. Musani; Alex Macharia; Thomas N. Williams; J. Kennedy Cruickshank; Liam Smeeth; J. Anthony G. Scott

doi:10.1161/JAHA.118.011771

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

Anthony O. Etyang^*, Sailoki Kapesa, Emily Odipo, Evasius Bauni, Catherine Kyobutungi, Marwah Abdalla, Paul Muntner, Solomon K. Musani, Alex Macharia, Thomas N. Williams, J. Kennedy Cruickshank, Liam Smeeth, J. Anthony G. Scott

^*Corresponding author for this work

Diabetes

Research output: Contribution to journal › Article › peer-review

17 Citations (Scopus)

Abstract

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.

Original language	English
Article number	e011771
Journal	Journal of the American Heart Association
Volume	8
Issue number	6
DOIs	https://doi.org/10.1161/JAHA.118.011771
Publication status	Published - 19 Mar 2019

Keywords

ambulatory blood pressure monitoring
high blood pressure
hypertension
malaria
Mendelian randomization
sickle cell disease
sickle cell trait
thalassemia

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1161/JAHA.118.011771

Cite this

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. (2019). Effect of Previous Exposure to Malaria on Blood Pressure in Kilifi, Kenya: A Mendelian Randomization Study. Journal of the American Heart Association, 8(6), Article e011771. https://doi.org/10.1161/JAHA.118.011771

@article{9d20e02e5f20475bab7c263d32af54ac,

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

abstract = "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.",

keywords = "ambulatory blood pressure monitoring, high blood pressure, hypertension, malaria, Mendelian randomization, sickle cell disease, sickle cell trait, thalassemia",

author = "Etyang, {Anthony O.} and Sailoki Kapesa and Emily Odipo and Evasius Bauni and Catherine Kyobutungi and Marwah Abdalla and Paul Muntner and Musani, {Solomon K.} and Alex Macharia and Williams, {Thomas N.} and Cruickshank, {J. Kennedy} and Liam Smeeth and Scott, {J. Anthony G.}",

year = "2019",

month = mar,

day = "19",

doi = "10.1161/JAHA.118.011771",

language = "English",

volume = "8",

journal = "Journal of the American Heart Association",

issn = "2047-9980",

publisher = "American Heart Association, Inc.",

number = "6",

}

Etyang, AO, Kapesa, S, Odipo, E, Bauni, E, Kyobutungi, C, Abdalla, M, Muntner, P, Musani, SK, Macharia, A, Williams, TN, Cruickshank, JK, Smeeth, L & Scott, JAG 2019, 'Effect of Previous Exposure to Malaria on Blood Pressure in Kilifi, Kenya: A Mendelian Randomization Study', Journal of the American Heart Association, vol. 8, no. 6, e011771. https://doi.org/10.1161/JAHA.118.011771

TY - JOUR

T1 - Effect of Previous Exposure to Malaria on Blood Pressure in Kilifi, Kenya

T2 - A Mendelian Randomization Study

AU - Etyang, Anthony O.

AU - Kapesa, Sailoki

AU - Odipo, Emily

AU - Bauni, Evasius

AU - Kyobutungi, Catherine

AU - Abdalla, Marwah

AU - Muntner, Paul

AU - Musani, Solomon K.

AU - Macharia, Alex

AU - Williams, Thomas N.

AU - Cruickshank, J. Kennedy

AU - Smeeth, Liam

AU - Scott, J. Anthony G.

PY - 2019/3/19

Y1 - 2019/3/19

N2 - 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.

AB - 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.

KW - ambulatory blood pressure monitoring

KW - high blood pressure

KW - hypertension

KW - malaria

KW - Mendelian randomization

KW - sickle cell disease

KW - sickle cell trait

KW - thalassemia

UR - http://www.scopus.com/inward/record.url?scp=85063268524&partnerID=8YFLogxK

U2 - 10.1161/JAHA.118.011771

DO - 10.1161/JAHA.118.011771

M3 - Article

C2 - 30879408

AN - SCOPUS:85063268524

SN - 2047-9980

VL - 8

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

IS - 6

M1 - e011771

ER -

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

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this