Hypertension treatment in sub-Saharan Africa: a systematic review.

Sub-Saharan Africa (SSA) faces the highest rate of hypertension worldwide. Blood pressure (BP) control rests on the association of lifestyle modification and antihypertensive medicines. We aimed to systematically review antihypertensive strategies implemented in SSA to achieve BP control. A systematic search beginning in 2003 was performed in MEDLINE, COCHRANE and EMBASE. We included only original and observational studies in SSA countries. Thirty studies were included from 11 countries. No study was multinational. The number of patients varied from 111 to 897 (median: 294; IQR: 192-478). Overall, 21% of patients received monotherapy, 42.6% two-drug and 26.6% three-drug combinations. Out of all the strategies, renin-angiotensin system (RAS) blockers were mostly prescribed, followed by diuretics and calcium channel blockers. In monotherapy, RAS blockers were the first to be prescribed. Only 10 articles described antihypertensive strategies beyond triple combinations. BP control was highly variable (range: 16.4 to 61.2%). Multicentre studies performed in several SSA countries are needed to ensure international guidelines actually do improve outcomes in SSA.

Time trends in infectious and chronic disease consultations in Dakar, Senegal: Impact of COVID-19 sanitary measures.

Background: The impact of COVID-19 sanitary measures on the time trends in infectious and chronic disease consultations in Sub-Saharan Africa remains unknown. Methods: We conducted a cohort study on all emergency medical consultations from January 2016 to July 2020, from SOS Medecins in Dakar, Senegal. The consultation records provided basic demographic information such as age, ethnicity (Senegalese or Caucasian), and sex as well as the principal diagnosis using an ICD-10 classification ("infectious", "chronic", and "other"). We first investigated how the pattern in emergency consultation differed from March to July 2020 compared to previous years. Then, we examined any potential racial/ethnic disparities in COVID-19 consultation. Results: We obtained data on emergency medical consultations from 53 583 patients of all ethnic origins. The mean age of patients was 37.0 (standard deviation (SD) = 25.2) and 30.3 (SD = 21.7) in 2016-2019 and 45.5 (SD = 24.7) and 39.5 (SD = 23.3) in 2020 for Senegalese and Caucasian patients, respectively. The type of consultations between January and July were similar from 2016 to 2019; however, in 2020, there was a drop in the number of infectious disease consultations, particularly from April to May 2020, when sanitary measures for COVID-19 were applied (average of 366.5 and 358.2 in 2016-1019 and 133.0 and 125.0 in 2020). The prevalence of chronic conditions remained steady during the same period (average of 381.0 and 394.7 in 2016-2019 and 373.0 and 367.0 in 2020). In a multivariate analysis adjusted for age and sex, infectious disease consultations were significantly more likely to occur in 2016-2019 compared to 2020 (2016 odds ratio (OR) = 2.39, 2017 OR = 2.74, 2018 OR = 2.39, 2019 OR = 2.01). Furthermore, the trend in the number of infectious and chronic consultations was similar among Senegalese and Caucasian groups, indicating no disparities among those seeking treatment. Conclusions: During the implementation of COVID-19 sanitary measures, infectious disease rates dropped as chronic disease rates remained stagnant in Dakar. We observed no racial/ethnic disparities among the infectious and chronic consultations.

Use of traditional medicine and control of hypertension in 12 African countries.

BACKGROUND: Use of traditional medicine (TM) is widespread in sub-Saharan Africa as a treatment option for a wide range of disease. We aimed to describe main characteristics of TM users and estimate the association of TM use with control of hypertension. METHODS: We used data on 2128 hypertensive patients of a cross-sectional study (convenience sampling), who attended cardiology departments of 12 sub-Saharan African countries (Benin, Cameroon, Congo, Democratic Republic of the Congo, Gabon, Guinea, Côte d'Ivoire, Mauritania, Mozambique, Niger, Senegal, Togo). To model association of TM use with odds of uncontrolled, severe and complicated hypertension, we used multivariable mixed logistic regressions, and to model the association with blood pressure (systolic (SBP) and diastolic (DBP)) we used mixed linear models. All models were adjusted for age, sex, wealth, adherence to hypertension conventional treatment and country (random effect). RESULTS: A total of 512 (24%) participants reported using TM, varying across countries from 10% in the Congo to 48% in Guinea. TM users were more likely to be men, living in rural area, poorly adhere to prescribed medication (frequently due to its cost). Use of TM was associated with a 3.87 (95% CI 1.52 to 6.22)/1.75 (0.34 to 3.16) mm Hg higher SBP/DBP compared with no use; and with greater odds of severe hypertension (OR=1.34; 95% CI 1.04 to 1.74) and of any hypertension complication (OR=1.27; 95% CI 1.01 to 1.60), mainly driven by renal complication (OR=1.57; 95% CI 1.07 to 2.29) after adjustment for measured confounders. CONCLUSIONS: The use of TM was associated with higher blood pressure, more severe hypertension and more complications in Sub-Saharan African countries. The widespread use of TM needs to be acknowledged and worked out to integrate TM safely within the conventional healthcare.

Barriers to up-titrated antihypertensive strategies in 12 sub-Saharan African countries: the Multination Evaluation of hypertension in Sub-Saharan Africa Study.

BACKGROUND: Sub-Saharan Africa (SSA) faces the highest rate of hypertension worldwide. The high burden of elevated blood pressure (BP) in black people has been emphasized. Guidelines recommend two or more antihypertensive medications to achieve a BP control. We aimed to identify factors associated with prescription of up-titrated antihypertensive strategies in Africa. METHODS: We conducted a cross-sectional study on outpatient consultations for hypertension across 12 SSA countries. Collected data included socioeconomic status, antihypertensive drugs classes, BP measures, cardiovascular risk factors and complication of hypertension. We used ordinal logistic regression to assess factors associated with prescription of up-titrated strategies. RESULTS: The study involved 2123 treated patients with hypertension. Patients received monotherapy in 36.3 vs. 25.9%, two-drug in 42.2 vs. 45% and three and more drugs strategies in 21.5 vs. 29.1% in low (LIC) and middle (MIC) income countries, respectively. Patients with sedentary lifestyle [OR 1.4 (1.11-1.77)], complication of hypertension [OR 2.4 (1.89-3.03)], former hypertension [OR 3.12 (2.3-4.26)], good adherence [OR 1.98 (1.47-2.66)], from MIC [OR 1.38 (1.10-1.74)] and living in urban areas [OR 1.52 (1.16-1.99)] were more likely to be treated with up-titrated strategies. Stratified analysis shows that in LIC, up-titrated strategies were less frequent in rural than in urban patients (P for trend <0.01) whereas such difference was not observed in MIC. CONCLUSION: In this African setting, in addition to expected factors, up-titrated drug strategies were associated with country-level income, patient location and finally, the interplay between both in LIC. These results highlight the importance of developing policies that seek to make multiple drug classes accessible particularly in rural and LIC.

Blood pressure-lowering medicines implemented in 12 African countries: the cross-sectional multination EIGHT study.

OBJECTIVE: In Africa, the number of patients with hypertension is expected to reach 216.8 million by 2030. Large-scale data on antihypertensive medications used in Sub-Saharan Africa (SSA) are scarce.Here, we describe antihypertensive drug strategies and identify treatment factors associated with blood pressure (BP) control in 12 Sub-Saharan countries. SETTING: Outpatient consultations for hypertension in urban tertiary cardiology centres of 29 hospitals from 17 cities across 12 SSA countries between January 2014 and November 2015. PARTICIPANTS: Patients ≥18 years of age with hypertension were enrolled at any visit during outpatient consultations in the cardiology departments MAIN OUTCOME MEASURE: We collected BP levels, demographic characteristics and antihypertensive treatment use (including traditional medicine) of patients with hypertension attending outpatient visits. BP control was defined as seated office BP <140/90 mm Hg. We used logistic regression with a random effect on countries to assess factors of BP control. RESULTS: Overall, 2198 hypertensive patients were included and a total of 96.6% (n=2123) were on antihypertensive medications. Among treated patients, 653 (30.8%) patients received a monotherapy by calcium channel blocker (n=324, 49.6%), renin-angiotensin system blocker (RAS) (n=126, 19.3%) or diuretic (n=122, 18.7%). Two-drug strategies were prescribed in 927 (43.6%) patients including mainly diuretics and RAS (n=327, 42% of two-drug strategies). Prescriptions of three-drugs or more were used in 543 (25.6%) patients. Overall, among treated patients, 1630 (76.7%) had uncontrolled BP, of whom 462 (28.3%) had BP levels ≥180/110 mm Hg, mainly in those on monotherapy. After adjustment for sociodemographic factors, the use of traditional medicine was the only factor significantly associated with uncontrolled BP (OR 1.72 (1.19 to 2.49) p<0.01). CONCLUSION: Our study provided large-scale data on antihypertensive prescriptions in the African continent. Among patients declared adherent to drugs, poor BP control was significantly associated with the use of traditional medicine.

Epidemiological transition in morbidity: 10-year data from emergency consultations in Dakar, Senegal.

BACKGROUND: It is thought that low-income countries are undergoing an epidemiological transition from infectious to non-communicable diseases; however, this phenomenon is yet to be examined with long-term data on morbidity. METHODS: We performed a prospective evaluation of all emergency medical consultations at a major emergency service provider in Dakar, Senegal from 2005 to 2014. Using standardised definitions, the primary diagnosis for each consultation was classified using the International Classification of Diseases-10 and then broadly categorised as 'infectious', 'non-communicable' and 'other' diseases. Morbidity rates for each year in the 10-year observation period were plotted to depict the epidemiological transition over time. To quantify the yearly rate ratios of non-communicable over infectious diagnosis, we used a generalised Poisson mixed model. RESULTS: Complete data were obtained from 49 702 visits by African patients. The mean age was 36.5±23.2 and 34.8±24.3 years for women and men, respectively. Overall, infections accounted for 46.3% and 42.9% and non-communicable conditions 32.2% and 40.1% of consultations in women and men, respectively. Consultation for non-communicable compared with infectious conditions increased by 7% every year (95% CI: 5% to 9%; p<0.0001) over the 10 years. Consultations for non-communicable condition were more likely in women compared with men (RR=1.29, 95% CI: 1.18, 1.40) and at older ages (RR=1.27; 95% CI 1.25, 1.29 for 10-year increase in age). CONCLUSION: Using high-quality disease morbidity data over a decade, we provide novel data showing the epidemiological transition of diseases as manifested in emergency service consultations in a large Sub-Saharan African city. These results can help reorientation of healthcare policy in Sub-Saharan Africa.

Factors associated with poor adherence to medication among hypertensive patients in twelve low and middle income Sub-Saharan countries.

INTRODUCTION: Over the past few decades, the prevalence of hypertension has dramatically increased in Sub-Saharan Africa. Poor adherence has been identified as a major cause of failure to control hypertension. Scarce data are available in Africa. AIMS: We assessed adherence to medication and identified socioeconomics, clinical and treatment factors associated with low adherence among hypertensive patients in 12 sub-Saharan African countries. METHOD: We conducted a cross-sectional survey in urban clinics of both low and middle income countries. Data were collected by physicians on demographics, treatment and clinical data among hypertensive patients attending the clinics. Adherence was assessed by questionnaires completed by the patients. Factors associated with low adherence were investigated using logistic regression with a random effect on countries. RESULTS: There were 2198 individuals from 12 countries enrolled in the study. Overall, 678 (30.8%), 738 (33.6%), 782 (35.6%) participants had respectively low, medium and high adherence to antihypertensive medication. Multivariate analysis showed that the use of traditional medicine (OR: 2.28, 95%CI [1.79-2.90]) and individual wealth index (low vs. high wealth: OR: 1.86, 95%CI [1.35-2.56] and middle vs. high wealth: OR: 1.42, 95%CI [1.11-1.81]) were significantly and independently associated with poor adherence to medication. In stratified analysis, these differences in adherence to medication according to individual wealth index were observed in low-income countries (p<0.001) but not in middle-income countries (p = 0.17). In addition, 26.5% of the patients admitted having stopped their treatment due to financial reasons and this proportion was 4 fold higher in the lowest than highest wealth group (47.8% vs 11.4%) (p<0.001). CONCLUSION: This study revealed the high frequency of poor adherence in African patients and the associated factors. These findings should be useful for tailoring future programs to tackle hypertension in low income countries that are better adapted to patients, with a potential associated enhancement of their effectiveness.

Subclinical Cardiac Dysfunction Is Associated With Extracardiac Organ Damages.

Background: Several studies conducted in America or Europe have described major cardiac remodeling and diastolic dysfunction in patients with sickle cell disease (SCD). We aimed at assessing cardiac involvement in SCD in sub-Saharan Africa where SCD is the most prevalent. Methods: In Cameroon, Mali and Senegal, SCD patients and healthy controls of the CADRE study underwent transthoracic echocardiography if aged ≥10 years. The comparison of clinical and echocardiographic features between patients and controls, and the associations between echocardiographic features and the vascular complications of SCD were assessed. Results: 612 SCD patients (483 SS or Sß0, 99 SC, and 19 Sß+) and 149 controls were included. The prevalence of dyspnea and congestive heart failure was low and did not differ significantly between patients and controls. While left ventricular ejection fraction did not differ between controls and patients, left and right cardiac chambers were homogeneously more dilated and hypertrophic in patients compared to controls and systemic vascular resistances were lower (p < 0.001 for all comparisons). Three hundred and forty nine SCD patients had extra-cardiac organ damages (stroke, leg ulcer, priapism, microalbuminuria or osteonecrosis). Increased left ventricular mass index, cardiac dilatation, cardiac output, and decreased systemic vascular resistances were associated with a history of at least one SCD-related organ damage after adjustment for confounders. Conclusions: Cardiac dilatation, cardiac output, left ventricular hypertrophy, and systemic vascular resistance are associated with extracardiac SCD complications in patients from sub-Saharan Africa despite a low prevalence of clinical heart failure. The prognostic value of cardiac subclinical involvement in SCD patients deserves further studies.

Socioeconomic Status and Hypertension Control in Sub-Saharan Africa: The Multination EIGHT Study (Evaluation of Hypertension in Sub-Saharan Africa).

Systemic hypertension is a rapidly growing epidemic in Africa. The role of socioeconomic status on blood pressure control has not been well studied in this part of the world. We, therefore, aimed to quantify the association of socioeconomic status both at the individual and at the country level with blood pressure control in Sub-Saharan Africa. We conducted a cross-sectional survey in urban clinics of 12 countries, both low income and middle income, in Sub-Saharan Africa. Standardized blood pressure measures were made among the hypertensive patients attending the clinics. Blood pressure control was defined as blood pressure <140/90 mm Hg, and hypertension grades were defined according to the European Society of Cardiology guidelines. A total of 2198 hypertensive patients (58.4±11.8 years; 39.9% men) were included. Uncontrolled hypertension was present in 1692 patients (77.4%), including 1044 (47.7%) with ≥grade 2 hypertension. The proportion of uncontrolled hypertension progressively increased with decreasing level of patient individual wealth, respectively, 72.8%, 79.3%, and 81.8% (P for trend, <0.01). Stratified analysis shows that these differences of uncontrolled hypertension according to individual wealth index were observed in low-income countries (P for trend, 0.03) and not in middle-income countries (P for trend, 0.26). In low-income countries, the odds of uncontrolled hypertension increased 1.37-fold (odds ratio, 1.37 [0.99-1.90]) and 1.88-fold (odds ratio, 1.88 [1.10-3.21]) in patients with middle and low individual wealth as compared with high individual wealth. Similarly, the grade of hypertension increased progressively with decreasing level of individual patient wealth (P for trend, <0.01). Strategies for hypertension control in Sub-Saharan Africa should especially focus on people in the lowest individual wealth groups who also reside in low-income countries.

Degree of anemia, indirect markers of hemolysis, and vascular complications of sickle cell disease in Africa.

The hyperhemolysis paradigm that describes overlapping "hyperhemolytic-endothelial dysfunction" and "high hemoglobin-hyperviscous" subphenotypes of sickle cell disease (SCD) patients is based on North American studies. We performed a transversal study nested in the CADRE cohort to analyze the association between steady-state hemolysis and vascular complications of SCD among sub-Saharan African patients. In Mali, Cameroon, and Ivory Coast, 2407 SCD patients (1751 SS or sickle ß-zero-thalassemia [Sß0], 495 SC, and 161 sickle ß+-thalassemia [Sß+]), aged 3 years old and over, were included at steady state. Relative hemolytic intensity was estimated from a composite index derived from principal component analysis, which included bilirubin levels or clinical icterus, and lactate dehydrogenase levels. We assessed vascular complications (elevated tricuspid regurgitant jet velocity [TRV], microalbuminuria, leg ulcers, priapism, stroke, and osteonecrosis) by clinical examination, laboratory tests, and echocardiography. After adjustment for age, sex, country, and SCD phenotype, a low hemoglobin level was significantly associated with TRV and microalbuminuria in the whole population and with leg ulcers in SS-Sß0 adults. A high hemolysis index was associated with microalbuminuria in the whole population and with elevated TRV, microalbuminuria, and leg ulcers in SS-Sß0 adults, but these associations were no longer significant after adjustment for hemoglobin level. In conclusion, severe anemia at steady state in SCD patients living in West and Central Africa is associated with elevated TRV, microalbuminuria, and leg ulcers, but these vascular complications are not independently associated with indirect markers of increased hemolysis. Other mechanisms leading to anemia, including malnutrition and infectious diseases, may also play a role in the development of SCD vasculopathy.

Arterial Stiffness Impairment in Sickle Cell Disease Associated With Chronic Vascular Complications: The Multinational African CADRE Study.

BACKGROUND: Although a blood genetic disease, sickle cell disease (SCD) leads to a chronic vasculopathy with multiple organ involvement. We assessed arterial stiffness in SCD patients and looked for associations between arterial stiffness and SCD-related vascular complications. METHODS: The CADRE (Coeur Artères et Drepanocytose, ie, Heart Arteries and Sickle Cell Disease) study prospectively recruited pediatric and adult SCD patients and healthy controls in Cameroon, Ivory Coast, Gabon, Mali, and Senegal. Patients underwent clinical examination, routine laboratory tests (complete blood count, serum creatinine level), urine albumin/creatinine ratio measure, and a measure of carotid-femoral pulse wave velocity (cf-PWV) and augmentation index (AI) at a steady state. The clinical and biological correlates of cf-PWV and AI were investigated by using a multivariable multilevel linear regression analysis with individuals nested in families further nested in countries. RESULTS: Included were 3627 patients with SCD and 943 controls. Mean cf-PWV was lower in SCD patients (7.5±2.0 m/s) than in controls (9.1±2.4 m/s, P<0.0001), and lower in SS-Sß(0) than in SC-Sß(+) phenotypes. AI, corrected for heart rate, increased more rapidly with age in SCD patients and was higher in SCD than in control adults. cf-PWV and AI were independently associated with age, sex, height, heart rate, mean blood pressure, hemoglobin level, country, and hemoglobin phenotype. After adjustment for these correlates, cf-PWV and AI were associated with the glomerular filtration rate and osteonecrosis. AI was also associated with stroke, pulmonary hypertension, and priapism, and cf-PWV was associated with microalbuminuria. CONCLUSIONS: PWV and AI are deeply modified in SCD patients in comparison with healthy controls. These changes are independently associated with a lower blood pressure and a higher heart rate but also with the hemoglobin phenotype. Moreover, PWV and AI are associated with several SCD clinical complications. Their prognostic value will be assessed at follow-up of the patients.

Early renal damage in patients with sickle cell disease in sub-Saharan Africa: a multinational, prospective, cross-sectional study.

BACKGROUND: Chronic kidney disease is one of the leading causes of mortality in patients with sickle cell disease. However, it has been almost exclusively studied in patients with the SS phenotype and in high-income countries, despite more than 80% of patients living in Africa. We looked for the determinants of glomerulopathy in a multinational cohort of patients with sickle cell disease of different phenotypes in sub-Saharan Africa. METHODS: In the CADRE cohort, we prospectively included patients 3 years and older with sickle cell disease of all haemoglobin phenotypes in Cameroon, Côte d'Ivoire, Mali, and Senegal. All individuals were assessed at steady state. The main outcome of interest was albuminuria defined as a urine albumin-to-creatinine ratio of greater than 30 mg/g. We investigated the clinical and biological determinants (including haemolysis markers) of albuminuria in two main phenotype groups (SS and Sß(0); SC and Sß(+)) with further stratification by age and country. FINDINGS: The study is ongoing because of follow-up. 2582 patients with sickle cell disease were included (1776 SS, 136 Sß(0), 511 SC, and 159 Sß(+)). 644 patients with the SS and Sß(0) phenotypes (33·7%, 95% CI 31·6-35·8) and 110 with the SC and Sß(+) phenotypes (16·4%, 13·6-19·2) had albuminuria. In the SS and Sß(0) group, albuminuria was detected in 144 (27%) of 527 children younger than 10 years and its frequency increased with age (29 [48%] of 60 patients aged >40 years). Multivariable analysis showed that albuminuria was associated with age (odds ratio 1·43, 95% CI 1·20-1·71; p<0·0001), female sex (1·35, 1·02-1·82; p=0·045), low haemoglobin (0·79, 0·66-0·93; p=0·006), high lactate dehydrogenase concentrations (1·33, 1·14-1·58; p=0·0009), and, using Côte d'Ivoire as the reference, Mali (2·49, 1·64-3·79; p=0·042) and Cameroon (1·59, 1·01-2·51; p=0·0007) in patients with the SS and Sß(0) phenotypes. The magnitude of the association of albuminuria with haemoglobin and lactate dehydrogenase concentrations increased with age. In the SC and Sß(+) patients, only low haemoglobin (0·69, 0·48-0·97; p=0·029), high blood pressure (1·63, 1·17-2·27; p=0·0017), and Mali (3·75, 1·75-8·04; p<0·0001) were associated with albuminuria. INTERPRETATION: Hyperhaemolysis is associated with albuminuria, with an age-dependent effect, in the SS and Sß(0) phenotypes only, suggesting a different pathological mechanism for glomerular disease in the patients with SC and Sß(+) phenotypes. However, both phenotypes are associated with a high prevalence of albuminuria in childhood. Therefore, screening for albuminuria is advised in African children with sickle cell disease to detect early renal damage. FUNDING: Paris Cité Sorbonne University (GrEX project) and Cardiology and Development.