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In Africa, the burden of hypertension has been rising at an alarming rate for the last two decades and is a major cause for cardiovascular disease (CVD) mortality and morbidity. Hypertension is characterised by elevated blood pressure (BP) ≥ 140/90 mmHg. Current hypertension guidelines recommend the use of antihypertensives belonging to the following classes: calcium channel blockers (CCB), angiotensin converting inhibitors (ACEI), angiotensin receptor blockers (ARB), diuretics, β-blockers, and mineralocorticoid receptor antagonists (MRAs), to manage hypertension. Still, a considerable number of hypertensives in Africa have their BP uncontrolled due to poor drug response and remain at the risk of CVD events. Genetic factors are a major contributing factor, accounting for 20% to 80% of individual variability in therapy and poor response. Poor response to antihypertensive drug therapy is characterised by elevated BPs and occurrence of adverse drug reactions (ADRs). As a result, there have been numerous studies which have examined the role of genetic variation and its influence on antihypertensive drug response. These studies are predominantly carried out in non-African populations, including Europeans and Asians, with few or no Africans participating. It is important to note that the greatest genetic diversity is observed in African populations as well as the highest prevalence of hypertension. As a result, this warrants a need to focus on how genetic variation affects response to therapeutic interventions used to manage hypertension in African populations. In this paper, we discuss the implications of genetic diversity in CYP11B2, GRK4, NEDD4L, NPPA, SCNN1B, UMOD, CYP411, WNK, CYP3A4/5, ACE, ADBR1/2, GNB3, NOS3, B2, BEST3, SLC25A31, LRRC15 genes, and chromosome 12q loci on hypertension susceptibility and response to antihypertensive therapy. We show that African populations are poorly explored genetically, and for the few characterised genes, they exhibit qualitative and quantitative differences in the profile of pharmacogene variants when compared to other ethnic groups. We conclude by proposing prioritization of pharmacogenetics research in Africa and possible adoption of pharmacogenetic-guided therapies for hypertension in African patients. Finally, we outline the implications, challenges, and opportunities these studies present for populations of non-European descent.

Abstract Background Dipping of blood pressure (BP) at night is a normal physiological phenomenon. However, a non-dipping pattern is associated with hypertension mediated organ damage, secondary forms of hypertension and poorer long-term outcome. Identifying a non-dipping pattern may be useful in assessing risk, aiding the decision to investigate for secondary causes, initiating treatment, assisting decisions on choice and timing of antihypertensive therapy, and intensifying salt restriction. Objectives To estimate the prevalence and factors associated with non-dipping pattern and determine the effect of 6 months of three antihypertensive regimens on the dipping pattern among Black African hypertensive patients. Methods This was a secondary analysis of the CREOLE Study which was a randomized, single blind, three-group trial conducted in 10 sites in 6 Sub-Saharan African countries. The participants were 721 Black African patients, aged between 30 and 79 years, with uncontrolled hypertension and a baseline 24-h ambulatory blood pressure monitoring (ABPM). Dipping was calculated from the average day and average night systolic blood pressure measures. Results The prevalence of non-dipping pattern was 78% (564 of 721). Factors that were independently associated with non-dipping were: serum sodium > 140 mmol/l (OR = 1.72, 95% CI 1.17–2.51, p-value 0.005), a higher office systolic BP (OR = 1.03, 95% CI 1.01–1.05, p-value 0.003) and a lower office diastolic BP (OR = 0.97, 95% CI 0.95–0.99, p-value 0.03). Treatment allocation did not change dipping status at 6 months (McNemar’s Chi2 0.71, p-value 0.40). Conclusion There was a high prevalence of non-dipping among Black Africans with uncontrolled hypertension. ABPM should be considered more routinely in Black Africans with uncontrolled hypertension, if resources permit, to help personalise therapy. Further research is needed to understand the mechanisms and causes of non-dipping pattern and if targeting night-time BP improves clinical outcomes. Trial registration ClinicalTrials.gov (NCT02742467).

Abstract Catastrophic antiphospholipid antibody syndrome (CAPS) is a rare form of antiphospholipid syndrome, an autoimmune condition characterized by vascular thromboses, pregnancy loss, and antiphospholipid (aPL) antibodies. Diagnosis of CAPS relies on thrombosis of at least three different organs systems over 1 week, histopathological evidence of small vessel occlusion, and high aPL antibody titers. In a subset of precipitating circumstances, activation or disruption of endothelial cells in the microvasculature may occur along with cardiomyopathy. We present two cases of CAPS‐associated dilated cardiomyopathy at our institution, focusing on disease management, pathophysiology, and treatment. These patients were of Southeastern Asian descent, raising the possibility of genetic polymorphisms contributing to the development of cardiomyopathy. Both met CAPS criteria and both demonstrated clinicopathologic thrombotic microangiopathy (TMA) and complement activation and developed severe dilated cardiomyopathy with shock. Complement activation plays an important role in the development of CAPS and may be important in the pathogenesis of CAPS‐associated cardiomyopathy. Clinical suspicion for TMA as a pathophysiologic mechanism of unexplained heart failure in CAPS is important and increased awareness of cardiac side effects is necessary so that early treatment can be initiated to halt further cardiac and systemic complications.

Mycobacterium tuberculosis (MTB) is an under-recognised cause of genitourinary disease. IgA nephropathy (IgAN), a leading cause of glomerulonephritis worldwide, has been described as a rare consequence of disseminated MTB infection. In this case report, we present the first case of MTB associated IgAN in Africa. Finding IgAN on kidney biopsy in an MTB endemic area should prompt a thorough investigation for MTB to increase the chance of remission of IgAN and prevent inappropriate use of immunosuppression.

Background: Women frequently present with symptoms not typical of angina (NTA) making ischemic heart disease recognition, diagnosis and treatment challenging. We compared mortality in women with obstructive coronary artery disease (CAD) with NTA vs typical angina (TA). Methods: We studied 326 Women’s Ischemia Syndrome Evaluation (WISE) participants undergoing coronary angiography for suspected myocardial ischemia with core-lab measured obstructive CAD. TA was defined as sub-sternal chest pain precipitated by physical exertion or emotional stress and relieved with rest or nitroglycerin; NTA did not meet criteria for TA. The women were followed for non-fatal events and death for a median of 5.9 and 9.6 years respectively. Multivariate cox proportional hazards regression determined relations to events. Results: Overall, 115 (35%) of the women had TA. Baseline demographics, risk factors or additional symptom characteristics were similar between the two angina groups. Non-fatal events did not differ between groups. Women with NTA had a higher mortality compared to TA women (36% vs 26%, respectively, p = 0.047). Despite adjustment for additional major risk variables, NTA was an independent predictor of mortality compared to TA with a hazard ratio of 1.73 (95% Confidence interval: 1.04, 2.89). Conclusions: Among women with suspected ischemia undergoing coronary angiography with obstructive CAD, NTA was more common than TA, and predicted a higher longer-term mortality. Further investigation is needed to confirm these results, and investigate potential explanations for the higher mortality observed in women with NTA women, including lower recognition or action in the setting of obstructive CAD. Keywords: Angina, Coronary artery disease, Mortality

BackgroundWomen with symptoms and signs of ischemia, preserved left ventricular ejection fraction (LVEF), and no obstructive coronary artery disease (CAD), often have coronary microvascular dysfunction (CMD), and are at risk of future heart failure with preserved ejection fraction (HFpEF). N-terminal pro-B-type natriuretic peptide (NT-proBNP) is used to evaluate HF and myocardial ischemia. Relationships between NT-proBNP and CMD are not well defined in this population.MethodsWe evaluated resting NT-proBNP levels in 208 women with symptoms and signs of ischemic heart disease, preserved LVEF and no obstructive CAD undergoing clinically indicated invasive coronary flow reserve (CFR) as a measure of CMD-related ischemia and resting left ventricular end-diastolic pressure (LVEDP). Chi-square testing was used for categorical variables and ANOVA or Kruskal-Wallis tests were used for continuous variables.ResultsOverall, 79% had an elevated resting LVEDP, and mean NT-proBNP was 115 ± 158 pg/mL. NT-proBNP levels correlated directly with age (r = 0.28, p = ConclusionAmong women with symptoms and signs of ischemia, preserved LVEF, no obstructive CAD, and undergoing clinically indicated functional coronary angiography (FCA) for suspected CMD, while a majority had elevated resting LVEDP, we failed to find an independent association between CFR and NT-proBNP, although stratified clinical thresholds may relate to lower CFR. Further work is needed to investigate if these findings support the hypothesis that CMD-related ischemia may be a precursor to HFpEF.

Objectives The International Society of Nephrology (ISN) has called for zero deaths by 2025. This survey aimed to determine the preparedness of Southern African Development Community (SADC) countries and Nigeria to heed this call.Setting A questionnaire was emailed to facilities, where renal replacement therapy is available; to determine type of services available; quality of care and identify clinicians involved.Participants Clinicians and administrators involved in the care of patients with acute kidney injury (AKI) completed the questionnaire.Results Completed questionnaires were received from 12 of the 15 SADC countries and Nigeria, covering 48 service providers. The government provided partial funding for dialysis in 41.7% of services. There was no funding for acute dialysis in two countries. Interdisciplinary teams in 72.9% of hospitals covered the intensive care units (ICUs), which included at least one nephrologist in 75%. Only 77% were able to provide dialysis in ICU. Intermittent haemodialysis was the most common modality available (91.7% of facilities), sustained low-efficiency dialysis in 50%, continuous therapies in 35% and peritoneal dialysis in 33.3%. Almost half (47.9%) of the sites were limited to one mode of dialysis and unable to care for severely ill patients. The clinical status was used to initiate and monitor dialysis, with very few sites having clear written standard operating procedures.Conclusion In the 16 countries surveyed, the majority had limited ability to provide comprehensive dialysis programmes for patients with AKI due to lack of facilities and government funding. Additionally, nephrologists are scarce; modes of dialysis are limited; as is the care for severely ill patients and lack of standard operating procedures. Resources, training and funding need to be made available to create universal coverage of dialysis for AKI. The ISN goal of providing renal replacement therapy to all by 2025 is unlikely to be achieved in SADC and Nigeria.