Increasing blood pressure: could malaria have a role?

About one in ten adolescents in sub-Saharan Africa1Chen A Waite L Mocumbi AO et al.Elevated blood pressure among adolescents in sub-Saharan Africa: a systematic review and meta-analysis.Lancet Glob Health. 2023; 11: e1238-e1248Summary Full Text Full Text PDF PubMed Scopus (2) Google Scholar and one in three adults in India2Anjana RM Unnikrishnan R Deepa M et al.Metabolic non-communicable disease health report of India: the ICMR-INDIAB national cross-sectional study (ICMR-INDIAB-17).Lancet Diabetes Endocrinol. 2023; 11: 474-489Summary Full Text Full Text PDF PubMed Scopus (11) Google Scholar have hypertension. Between 2009 and 2019, an 100% increase in the number of individuals with hypertension was reported globally; this change is estimated to be due to an increased prevalence of hypertension in low-income and middle-income countries.3NCD Risk Factor Collaboration (NCD-RisC)Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants.Lancet. 2021; 398: 957-980Summary Full Text Full Text PDF PubMed Scopus (972) Google Scholar Many biological, sociocultural, economic, environmental, and nutritional risk factors have been scrutinised and traditionally attributed to this burgeoning increase in hypertension. However, infectious diseases, such as malaria, have not been sufficiently investigated as risk factors for elevated blood pressure and other cardiovascular diseases. Studying the effect of infectious diseases on cardiovascular outcomes could be particularly relevant in populations in rural areas and low-income and middle-income countries, in whom lifestyle, sociocultural, and economic changes could have a lesser effect on blood-pressure elevation than in high-income countries.2Anjana RM Unnikrishnan R Deepa M et al.Metabolic non-communicable disease health report of India: the ICMR-INDIAB national cross-sectional study (ICMR-INDIAB-17).Lancet Diabetes Endocrinol. 2023; 11: 474-489Summary Full Text Full Text PDF PubMed Scopus (11) Google Scholar, 4India State-Level Disease Burden Initiative CVD CollaboratorsThe changing patterns of cardiovascular diseases and their risk factors in the states of India: the global burden of disease study 1990–2016.Lancet Glob Health. 2018; 6: e1339-e1351Summary Full Text Full Text PDF PubMed Scopus (276) Google Scholar This risk-factor profile could be the case for some African and Indian populations where malaria has been endemic for many decades. Malaria exposure, particularly repeated malaria episodes and severe malaria in childhood, has been reported to be a contributing risk factor for the development of hypertension and other cardiovascular diseases.5Holm AE Gomes LC Marinho CRF et al.Prevalence of cardiovascular complications in malaria: a systematic review and meta-analysis.Am J Trop Med Hyg. 2021; 104: 1643-1650Crossref PubMed Scopus (14) Google Scholar Malaria exposure has direct effects on blood pressure elevation6Etyang AO Kapesa S Odipo E et al.Effect of previous exposure to malaria on blood pressure in Kilifi, Kenya: a mendelian randomization study.J Am Heart Assoc. 2019; 8e011771Crossref PubMed Scopus (13) Google Scholar and has also been hypothesised to have indirectly modulated evolutionary selection in malaria-endemic areas.7Gallego-Delgado J Walther T Rodriguez A The high blood pressure–malaria protection hypothesis.Circ Res. 2016; 119: 1071-1075Crossref PubMed Scopus (27) Google Scholar As a direct effect, malaria exposure has been shown to result in extended elevation of pro-inflammatory cytokines, which have a negative effect on cardiovascular health and lead to cardiovascular diseases.5Holm AE Gomes LC Marinho CRF et al.Prevalence of cardiovascular complications in malaria: a systematic review and meta-analysis.Am J Trop Med Hyg. 2021; 104: 1643-1650Crossref PubMed Scopus (14) Google Scholar, 6Etyang AO Kapesa S Odipo E et al.Effect of previous exposure to malaria on blood pressure in Kilifi, Kenya: a mendelian randomization study.J Am Heart Assoc. 2019; 8e011771Crossref PubMed Scopus (13) Google Scholar In addition, malaria exposure has had an indirect effect on genetic selection. Specific mutations in the two pivotal enzymes (ACE mutation rs4646994 and ACE2 mutation rs2106809) of the human renin angiotensin system, which maintain the circulating concentration of plasma angiotensin II, have been implicated in protection from severe malaria, particularly in childhood. This protection, which is thought to be due to resultant elevated plasma angiotensin II concentrations,8Gallego-Delgado J Baravian C Edagha I et al.Angiotensin II moderately decreases plasmodium infection and experimental cerebral malaria in mice.PLoS One. 2015; 10e0138191Crossref PubMed Scopus (19) Google Scholar has been hypothesised to predispose individuals to hypertension in adulthood.7Gallego-Delgado J Walther T Rodriguez A The high blood pressure–malaria protection hypothesis.Circ Res. 2016; 119: 1071-1075Crossref PubMed Scopus (27) Google Scholar, 9De A Tiwari A Pande V Sinha A Evolutionary trilogy of malaria, angiotensin II and hypertension: deeper insights and the way forward.J Hum Hypertens. 2022; 36: 344-351Crossref PubMed Scopus (6) Google Scholar This hypothesis has only been evaluated in hospitalised severe malaria patients.10Dhangadamajhi G Mohapatra BN Kar SK Ranjit M Gene polymorphisms in angiotensin I converting enzyme (ACE I/D) and angiotensin II converting enzyme (ACE2 C–>T) protect against cerebral malaria in Indian adults.Infect Genet Evol. 2010; 10: 337-341Crossref PubMed Scopus (39) Google Scholar More robust population-wide research should be funded and conducted to ascertain both the direct and the indirect (ie, evolutionary) roles of malaria exposure in predisposing individuals to hypertension and other cardiovascular diseases, particularly in malaria-endemic areas. These research efforts would provide insight into the inter-pathogenesis between malaria and hypertension, which are, at present, two apparently distinct pathologies. This research would also help to delve deeper into the causes of pathogenesis for many non-communicable diseases that might be driven, at least partly, by various communicable diseases, particularly in low-income and middle-income countries. We declare no competing interests. Elevated blood pressure among adolescents in sub-Saharan Africa: a systematic review and meta-analysisTo our knowledge, this systematic review and meta-analysis is the first systematic synthesis of blood pressure data specifically derived from adolescents in sub-Saharan Africa. Although many low-income countries were not represented in our study, our findings suggest that approximately one in ten adolescents have elevated blood pressure across sub-Saharan Africa. Accordingly, there is an urgent need to improve preventive heart-health programmes in the region.