Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Current Neurology and Neuroscience Reports
Published in: Current Neurology and Neuroscience Reports 11/2022

01-10-2022 | Stroke | Stroke (B. Ovbiagele, Section Editor)

Promise of Physiological Profiling to Prevent Stroke in People of African Ancestry: Prototyping Ghana

Authors: Fred Stephen Sarfo, Bruce Ovbiagele

Published in: Current Neurology and Neuroscience Reports | Issue 11/2022

Login to get access

Abstract

Purpose of Review

Worldwide, compared to other racial/ethnic groups, individuals of African ancestry have an excessively higher burden of hypertension-related morbidities, especially stroke. Identifying modifiable biological targets that contribute to these disparities could improve global stroke outcomes. In this scoping review, we discuss how pathological perturbations in the renin–angiotensin–aldosterone pathways could be harnessed via physiological profiling for the purposes of improving blood pressure control for stroke prevention among people of African ancestry.

Recent Findings

Transcontinental comparative data from the USA and Ghana show that the prevalence of treatment-resistant hypertension among stroke survivors is 42.7% among indigenous Africans, 16.1% among African Americans, and 6.9% among non-Hispanic Whites, p < 0.0001. A multicenter clinical trial of patients without stroke in 3 African countries (Nigeria, Kenya, and South Africa) demonstrated that physiological profiling using plasma renin activity and aldosterone to individualize selection of antihypertensive medications compared with usual care resulted in better blood pressure control with fewer medications over 12 months. Among Ghanaian ischemic stroke survivors treated without renin-aldosterone profiling data, an analysis revealed that those with low renin phenotypes did not achieve any meaningful reduction in blood pressure over 12 months on 3–4 antihypertensive medications despite excellent adherence.

Summary

For a polygenic condition such as hypertension, individualized therapy based on plasma renin-aldosterone-guided selection of therapy for uncontrolled BP following precision medicine principles may be a viable strategy for primary and secondary stroke prevention with the potential to reduce disparities in the poor outcomes of stroke disproportionately shared by individuals of African ancestry. A dedicated clinical trial to test this hypothesis is warranted.
Literature
1.
Owolabi M, Akarolo-Anthony S, Akinyemi R, Arnett D, Gebregziabher M, Jenkins C, et al. The burden of stroke in Africa: a glance at the present and a glimpse into the future. Cardiovasc J Afr. 2015;26(2 Suppl 1):S27-38.PubMedPubMedCentralCrossRef
2.
Ovbiagele B, Goldstein LB, Higashida RT, Howard VJ, Johnston SC, Khavjou OA, et al. American Heart Association Advocacy Coordinating Committee and Stroke Council. Forecasting the future of stroke in the United States: a policy statement from the American Heart Association and American Stroke Association. Stroke. 2013;44(8):2361–75. https://​doi.​org/​10.​1161/​STR.​0b013e31829734f2​.CrossRefPubMed
3.•
Howard VJ, Kleindorfer DO, Judd SE, McClure LA, Safford MM, Rhodes JD, et al. Disparities in stroke incidence contributing to disparities in stroke mortality. Ann Neurol. 2011;69:619–27. https://​doi.​org/​10.​1002/​ana.​22385. Compared to non-Hispanic Whites, African Americans (AA) have disproportionately higher stroke incidence and mortality rates largely due to differences in hypertension burden.CrossRefPubMedPubMedCentral
4.
Kissela B, Schneider A, Kleindorfer D, Khoury J, Miller R, Alwell K, et al. Stroke in a biracial population: the excess burden of stroke among blacks. Stroke. 2004;35:426–31.PubMedCrossRef
5.
Rosamond WD, Folsom AR, Chambless LE, Wang CH, McGovern PG, Howard G, et al. Stroke incidence and survival among middle-aged adults: 9-year follow-up of the Atherosclerosis Risk in Communities (ARIC) cohort. Stroke. 1999;30:736–43.PubMedCrossRef
6.
Walker R, Whiting D, Unwin N, Mugusi F, Swai M. Stroke incidence in rural and urban Tanzania: a prospective, community-based study. Lancet Neurol. 2010;9:786–92.PubMedCrossRef
7.
Ezejimofor MC, Uthman OA, Maduka O, et al. Stroke survivors in Nigeria: a door-to-door prevalence survey from the Niger Delta region. J Neurol Sci. 2017;15(372):262–9.CrossRef
8.
Sarfo FS, Awuah DO, Nkyi C, Akassi J, Opare-Sem OK, Ovbiagele B. Recent patterns and predictors of neurological mortality among hospitalized patients in Central Ghana. J Neurol Sci. 2016;363:217–24.PubMedCrossRef
9.
Sarfo FS, Akassi J, Awuah D, Adamu S, Nkyi C, Owolabi M, et al. Trends in stroke admission and mortality rates from 1983 to 2013 in central Ghana. J Neurol Sci. 2015;357(1–2):240–5.PubMedCrossRef
10.
Sarfo FS, Akassi J, Ofori E, Ovbiagele B. Long-term determinants of death after stroke in Ghana: analysis by stroke types and subtypes. J Stroke Cerebrovasc Dis. 2022;31(9): 106639.PubMedCrossRef
11.
Feigin VL, Roth GA, Naghavi M. Global burden of stroke and risk factors in 188 countries, during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2016;15:913–24.CrossRef
12.
Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, et al. Heart disease and stroke statistics—2014 update: a report from the american heart association. Circulation. 2014;129(3):e28–292.PubMed
13.
O’Donnell MJ, Xavier D, Liu L, et al. Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): a case-control study. Lancet. 2010;376:112–23.PubMedCrossRef
14.
Howard G, Prineas R, Moy C, Cushman M, Kellum M, Temple E, et al. Racial and geographic differences in awareness, treatment and control of hypertension: the Reasons for Geographic and Racial Differences in Stroke study. Stroke. 2006;37:1171–8.PubMedCrossRef
15.
Owolabi MO, Sarfo FS, Akinyemi R, Gebregziabher M, Akpa O, Akpalu A, et al. Dominant modifiable risk factors for stroke in Ghana and Nigeria (SIREN): a case-control study. Lancet Glob Health. 2018;6(4):e436–46.PubMedPubMedCentralCrossRef
16.
Kaze AD, Schutte AE, Erqou S, Kengne AP, Echouffo-Tcheugui JB. Prevalence of hypertension in older people in Africa: a systematic review and meta-analysis. J Hypertens. 2017;35:1345–52.PubMedCrossRef
17.
KuateDefo B, Mbanya JC, Tardif JC, et al. Diagnosis, prevalence, awareness, treatment, prevention, and control of hypertension in Cameroon: protocol for a systematic review and meta-analysis of clinic-based and community-based studies. JMIR Res Protoc. 2017;6:e102.CrossRef
18.
Opie LH, Seedat YK. Hypertension in sub-Saharan African populations. Circulation. 2005;112(23):3562–8.PubMedCrossRef
19.
Towfighi A, Markovic D, Ovbiagele B. Consistency of blood pressure control after ischemic stroke: prevalence and prognosis. Stroke J Cereb Circ. 2014;45:1313–7.CrossRef
20.
Sacco RL, Boden-Albala B, Gan R, et al. Stroke incidence among white, black, and Hispanic residents of an urban community: the Northern Manhattan Stroke Study. Am J Epidemiol. 1998;147:259–68.PubMedCrossRef
21.
Sarfo FS, Mobula LM, Plange-Rhule J, Ansong D, Ofori-Adjei D. Incident stroke among Ghanaians with hypertension and diabetes: a multicenter, prospective cohort study. J Neurol Sci. 2018;395:8–16.PubMedPubMedCentralCrossRef
22.
Ovbiagele B, Ernstrom K, Markovic D, Raman R. Trends in antihypertensive drug prescription patterns among ambulatory stroke patients in the United States, 2000–2009. J Stroke Cerebrovasc Dis Off J Natl Stroke Assoc. 2013;22:e568–75.CrossRef
23.•
Carey RM, Calhoun DA, Bakris GL, Brook RD, Daugherty SL, Dennison-Himmelfarb CR, et al. Resistant hypertension: detection, evaluation, and management. A scientific statement from the American Heart Association. Hypertens. 2018;72:e53–90. This study reported the burden of resistant hypertension among Americans and identified its risk factors.CrossRef
24.
Daugherty SL, Powers JD, Magid DJ, Tavel HM, Masoudi FA, Margolis KL, et al. Incidence and prognosis of resistant hypertension in hypertensive patients. Circ. 2012;125:1635–42.CrossRef
25.
Cuspidi C, Macca G, Sampieri L, Michev I, Salerno M, Fusi V, et al. High prevalence of cardiac and extracardiac target organ damage in refractory hypertension. J Hypertens. 2001;19:2063–70.PubMedCrossRef
26.
Carey RM, Sakhuja S, Calhoun DA, Whelton PK, Munter P. Prevalence of apparent treatment resistant hypertension in the United States. Comparison of the 2008 and 2018 American Heart Association Scientific statements on resistant hypertension. Hypertens. 2019;73:424–31.CrossRef
27.
Batuman J. Salt and hypertension: an evolutionary perspective. J Hypertens. 2012;1:e106.CrossRef
28.
Grim CE, Robinson M. Salt, slavery and survival-hypertension in African diaspora. Epidemiol. 2003;14:120–2.CrossRef
29.
Jones ES, Spence JD, Mcintyre AD, Nondi J, Gogo K, Akintunde A, et al. High frequency of variants of candidate genes in black Africans with low renin-resistant hypertension. Am J Hypertens. 2017;30:478–83.PubMed
30.
Bochud M, Staessen JA, Maillard M, Mazeko MJ, Kuznetsova T, Woodiwiss A, et al. Ethnic differences in proximal and distal tubular sodium reabsorption are heritable in black and white populations. J Hypertens. 2009;27:606–12.PubMedPubMedCentralCrossRef
31.
Tu W, Eckert GJ, Hannon TS, Liu H, Pratt LM, Wagner MA, et al. Racial differences in sensitivity of blood pressure to aldosterone. Hypertension. 2014;63:1212–8.PubMedCrossRef
32.
Thomas G, Xie D, Chen HY, Anderson AH, Appel LJ, Bodana S, et al. CRIC Study Investigators. Prevalence and prognostic significance of apparent treatment resistant hypertension in chronic kidney disease: report from the Chronic Renal Insufficiency Cohort Study. Hypertens. 2016;67:387–96.CrossRef
33.
Smith SM, Gong Y, Handberg E, Messerli FH, Bakris GL, Ahmed A, et al. Predictors and outcomes of resistant hypertension among patients with coronary artery disease and hypertension. J Hypertens. 2014;32:635–43.PubMedPubMedCentralCrossRef
34.
Smith SM, Huo T, Delia Johnson B, Bittner V, Kelsey SF, Vido Thompson D, et al. Cardiovascular and mortality risk of apparent resistant hypertension in women with suspected myocardial ischemic: a report from the NHLBI-sponsored WISE Study. J Am Heart Assoc. 2014;3:e000660.PubMedPubMedCentralCrossRef
35.
Bangalore S, Fayyad R, Laskey R, Demicco DA, Deedwania P, Kostis JB, et al. Treating to new targets steering committee and investigators. Prevalence, predictors and outcomes in treatment-resistant hypertension in patients with coronary. Am J Med. 2014;127:71–81.PubMedCrossRef
36.
37.
Laffer CL, Elijovich F, Eckert GJ, Tu W, Pratt JH, Brown NJ. Genetic variation in CYP4A11 and blood pressure response to mineralocorticoid receptor antagonism or ENaC inhibition: an exploratory pilot study in African Americans. J Am Soc Hypertens. 2014;8:475–80.PubMedPubMedCentralCrossRef
38.
Michel FS, Norton GR, Majane OHI, et al. Contribution of circulating angiotensinogen concentrations to variations in aldosterone and blood pressure in a group of African ancestry depends on salt intake. Hypertension. 2012;59:62–9.PubMedCrossRef
39.•
Rayner BL, Spence JD. Hypertension in Blacks: insights from Africa. J Hypertens. 2017;35(2):234–9. This study highlighted that blacks have a greater propensity to salt sensitivity and suppressed plasma renin suggesting a predisposition to sodium retention. Target organ damage is more frequent and blood pressure is more difficult to control.PubMedCrossRef
40.
Grim CE, Robinson M. Salt, slavery and survival: hypertension in the African diaspora. Epidemiol. 2003;14:120–2.CrossRef
41.
Spence JD. The current epidemic of primary aldosteronism: causes and consequences. J Hypertens. 2009;22:2038–9.CrossRef
42.
Spence JD. Lessons from Africa: the importance of measuring plasma renin and aldosterone in resistant hypertension. Can J Cardiol. 2012;28:254–7.PubMedCrossRef
43.
Calhoun DA, Jones D, Textor S, et al. Resistant hypertension: diagnosis, evaluation, and treatment. A scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Hypertens. 2008;51:1403–19.CrossRef
44.
Russell RP, Masi AT. The prevalence of adrenal cortical hyperplasia at autopsy and its association with hypertension. Ann Intern Med. 1970;73:195–205.PubMedCrossRef
45.
Kidambi S, Kotchen JM, Grim CE, et al. Association of adrenal steroids with hypertension and the metabolic syndrome in blacks. Hypertens. 2007;49:704–11.CrossRef
46.
Joseph JJ, Echouffo-Tcheugui JB, Kalyani RR, Yeh HS, Bertoni AG, Effoe VS, et al. Aldosterone, renin, cardiovascular events, and all-cause mortality among African Americans. The Jackson Heart Study. J Am Coll Cardiol HF. 2017; 5:642–51.
47.
Brown NJ. Aldosterone and vascular inflammation. Hypertens. 2008;51:161–7.CrossRef
48.
Neves MF, Amiri F, Virdis A, Diep QN, Schiffrin EL. Role of aldosterone in angiotensin II- induced cardiac and aortic inflammation. Can J Physiol Pharmacol. 2005;83:999–1006.PubMedCrossRef
49.
Pitt B. “Escape” of aldosterone production in patients with left ventricular dysfunction treated with an angiotensin converting enzyme inhibitor: implications for therapy. Cardiovasc Drugs Ther. 1995;9:145–9.PubMedCrossRef
50.
Athyros VG, Mikhailidis DP, Kakafika AI, Tziomalos K, Karagiannis A. Angiotensin II reactivation and aldosterone escape phenomenon in renin-angiotensin-aldosterone system blockade: is oral renin inhibition the solution? Expert Opin Pharmcother. 2007;8:529–35.CrossRef
51.
Laragh JH, Baer L, Brunner HR, Buhler FR, Sealey JE, Vaughan ED Jr. Renin, angiotensin and aldosterone system in pathogenesis and management of hypertensive vascular disease. Am J Med. 1972;52:633–52.PubMedCrossRef
52.
Spence JD. Physiologic tailoring of therapy for resistant hypertension: 20 years’ experience with stimulated renin profiling. Am J Hypertens. 1999;12(11 pt 1):1077–83.PubMedCrossRef
53.
54.
55.
Spence JD. Rational medical therapy is the key to effective cardiovascular disease prevention. Can J Cardiol. 2017;33:626–34.PubMedCrossRef
56.
Egan BM, Basile JN, Rehman SU, Davis PB, Grob CH 3rd, Riehle JF, et al. Plasma renin test-guided drug treatment algorithm for correcting patients with treated but uncontrolled hypertension: a randomized controlled trial. Am J Hypertens. 2009;22:792–801.PubMedCrossRef
57.•
Akintunde A, Nondi J, Gogo K, Jones ESW, Rayner BL, Hackmam DG, Spence JD. Physiological phenotyping for personalized therapy of uncontrolled hypertension in Africa. Am J Hypertens. 2017;30:923–30. This is the first-of-its-kind randomized controlled trial which demonstrated the efficacy of physiologic profiling with renin-aldosterone to improve blood pressure control compared with usual care across 3 African countries .PubMedCrossRef
58.
59.
Sarfo FS, Akassi J, Adamu S, Obese V, Agbenorku M, Ovbiagele B. Frequency and factors linked to refractory hypertension among stroke survivors in Ghana. J Neurol Sci. 2020;415:116976.PubMedPubMedCentralCrossRef
60.•
Sarfo FS, Olasoji E, Banfill GP, Ovbiagele B, Simpkins AN. Apparent treatment resistant hypertension among stroke survivors: a transcontinental study assessing impact of race and geography. Am J Hypertens. 2022;35(8):715–22. This transcontinental study highlighted a high burden of resistant hypertension among stroke survivors particularly among individuals of Africans ancestry compared with non-hispanic Caucasians.PubMedCrossRef
61.
Sarfo FS, Ovbiagele B. Key determinants of long-term post-stroke mortality in Ghana. J Neurol Sci. 2022;434:120123.PubMedCrossRef
62.
White H, Boden-Albala B, Wang C, Elkind MS, Rundek T, Wright CB, et al. Ischemic stroke subtype incidence among whites, blacks, and Hispanics: the Northern Manhattan Study. Circulation. 2005;111:1327–31.PubMedCrossRef
63.
Markus HS, Khan U, Birns J, Evans A, Kalra L, Rudd AG, et al. Differences in stroke subtypes between black and white patients with stroke: the South London Ethnicity and Stroke Study. Circulation. 2007;116:2157–64.PubMedCrossRef
64.
Flaherty ML, Woo D, Haverbusch M, Sekar P, Khoury J, Sauerbeck L, et al. Racial variations in location and risk of intracerebral hemorrhage. Stroke. 2005;36:934–7.PubMedCrossRef
65.
Sarfo FS, Sarfo-Kantanka O, Adamu S, Obese V, Voeks J, Tagge R, et al. Stroke Minimization through Additive Anti-atherosclerotic Agents in Routine Treatment (SMAART): study protocol for a randomized controlled trial. Trials. 2018;19(1):181.PubMedPubMedCentralCrossRef
66.
Howard VJ, Tanner RM, Anderson A, Irvin MR, Calhoun DA, Lackland DT, et al. Apparent treatment-resistant hypertension among individuals with history of stroke or transient ischemic attack. Am J Med. 2015;128(7):707-14.e2.PubMedPubMedCentralCrossRef
67.
Sim JJ, Bhandari SK, Shi J, et al. Characteristics of resistant hypertension in a large, ethnically diverse hypertension population of an integrated health system. Mayo Clin proc. 2013;88(10):1099–107.PubMedCrossRef
68.
Nansseu JR, Noubiap JJ, Mengnjo MK, et al. The highly neglected burden of resistant hypertension in Africa: a systematic review and meta-analysis. BMJ Open. 2016;6:e011452.PubMedPubMedCentralCrossRef
69.
Sarfo FS, Kyem G, Ovbiagele B, Akassi J, Sarfo-Kantanka O, Agyei M, et al. One-year rates and determinants of post-stroke systolic blood pressure control among Ghanaians. J Stroke Cerebrovasc Dis. 2017;26(1):78–86.PubMedCrossRef
70.
Sarfo FS, Ovbiagele B. Utilizing implementation science to bridge cerebrovascular health disparities: a local to global perspective. Curr Neurol Neurosci Rep. 2022;22(5):293–303.PubMedCrossRef
Metadata
Title
Promise of Physiological Profiling to Prevent Stroke in People of African Ancestry: Prototyping Ghana
Authors
Fred Stephen Sarfo
Bruce Ovbiagele
Publication date
01-10-2022
Publisher
Springer US
Published in
Current Neurology and Neuroscience Reports / Issue 11/2022
Print ISSN: 1528-4042
Electronic ISSN: 1534-6293
DOI
https://doi.org/10.1007/s11910-022-01239-x

Other articles of this Issue 11/2022

Current Neurology and Neuroscience Reports 11/2022 Go to the issue

Stroke (B. Ovbiagele, Section Editor)

Sleep and Stroke: Opening Our Eyes to Current Knowledge of a Key Relationship

Stroke (B. Ovbiagele, Section Editor)

Navigating Antiplatelet Treatment Options for Stroke: Evidence-Based and Pragmatic Strategies

Stroke (B. Ovbiagele, Section Editor)

Cerebrovascular Disease, Cardiovascular Disease, and Chronic Kidney Disease: Interplays and Influences

Demyelinating Disorders (J. Bernard and M. Cameron, Section Editors)

Bruton’s Tyrosine Kinase Inhibition in Multiple Sclerosis

Dementia (K.S. Marder, Section Editor)

Cognitive and Neuropsychiatric Impairment in Dystonia

Dementia (K.S. Marder, Section Editor)

Vascular Considerations for Amyloid Immunotherapy