Browsing by Author "Rayner, Brian"

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    A multicentre cross-sectional descriptive study evaluating the cardiovascular risk profile of preoperatively identified patients with hypertension
    (2021) Govender, Sarisha; Rayner, Brian; Dyer, Robert
    Background. The prevalence of hypertension in adults in South Africa (SA) is 35%. Hypertension is the most important modifiable risk factor for cardiovascular (CV) and chronic kidney disease (CKD) in subSaharan Africa. However, 49% of people are unaware of their blood pressure status. Screening for hypertension prior to surgery provides a unique opportunity to diagnose and treat affected individuals. Furthermore, assessing overall CV risk identifies patients at highest risk for complications, and improves the utilisation of scarce resources. Objective. To evaluate the CV risk profile of hypertensive patients in the adult population of the Western Cape Province presenting for elective non-cardiac, non-obstetric surgery. Methods. This report documents the CV risk profile of patients recruited to the HASS-2 study (Hypertension and Surgery Study 2), which was undertaken in seven Western Cape hospitals. Patients were screened for hypertension and pharmacological treatment was initiated or adjusted in patients with stages 1 and 2 disease. Stage 3 patients were referred to a physician. In the present substudy, patients with stages 1 and 2 hypertension were assessed for associated CV risk factors, the presence of target organ damage, and documented CV or kidney disease; they received an overall risk stratification according to the 2018 European Society of Cardiology and the European Society of Hypertension Guidelines. Results. Sixty-one patients with stage 1 and 12 with stage 2 hypertension were analysed. Established CV disease was present in 13.7% of the study population, and CKD (eGFR <60 ml/min) in 10.8%. Seventy-one percent of the study group had a raised body mass index, and 55.9% underlying metabolic syndrome. Prediabetes and diabetes were present in 16.1% and 14.5% respectively. According to the 2018 European guidelines, 34.7% were at moderate, 33.3% at high and 16.7% at very high risk for a CV event in the following 10 years. Conclusions. The perioperative period is a critical time during which surgeons, nurses and anaesthetists can influence patients' CV risk of adverse events. This involves appropriate screening, education and treatment. In this study population, nearly 9 out of 10 elective surgical patients with stage 1 or 2 hypertension had CV risk factors placing them at moderate to very high risk. The simultaneous assessment of these additional CV risk parameters, in addition to diagnosis and management of hypertension, may further decrease the health and financial burden in resource-limited facilities in SA, and improve CV outcomes.
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    A quality improvement project evaluating the perioperative implementation of a hypertension management protocol by anaesthesiologists at seven government hospitals in the Western Cape. “a multi-center, cross-sectional quality improvement project: the peri-operative implementation of a hypertension protocol by anesthesiologists”
    (2021) Pfister, Claire-Louise; Biccard, Bruce; Dyer, Robert A; Rayner, Brian
    BACKGROUND: Hypertension is a common risk factor for cardiovascular morbidity and mortality, with a high prevalence in patients presenting for elective surgery. In limited resource environments, patients have poor access to primary care physicians, limiting the efficacy of life-style modification for the initial management of hypertension in the community. In these circumstances, the perioperative period presents a unique opportunity for diagnosis and initiation and/or modification of pharmacotherapy of hypertension. Anesthesiologists are ideally placed to lead this aspect of perioperative medicine. METHODS: In collaboration with expert physicians, we designed and implemented an algorithm for the diagnosis of hypertension and subsequent initiation or modification of anti-hypertensive therapy, or referral to a physician. The study was a multi-center, cross-sectional quality improvement project in seven hospitals in the Western Cape, South Africa. On the day before scheduled elective surgery, adult inpatients had two sets of blood pressure (BP) readings taken, one by nurses and the other by anesthesiologists, using a noninvasive automated blood pressure device. These were averaged on an electronic database, to diagnose hypertension. Patients with normal BP or well-controlled hypertension required no further management. Those with borderline BP received educational pamphlets. Patients with stage 1 or 2 hypertension were managed with medication according to the algorithm, starting 1 day postoperatively, and provided with educational pamphlets. Patients with stage 3 disease were referred to a physician. The primary outcome was adherence by the anesthesiologist to the algorithm, defined as initiation of the prescribed medication. An 80% adherence rate was considered successful implementation. The secondary outcome was the issue of the antihypertensive medication at discharge. RESULTS: Two hundred and ninety-eight patients were screened for hypertension. One hundred and six patients were eligible for the quality improvement project. Thirty-seven (34.9%) had borderline blood pressure readings, 43 (40.6%) had stage 1-, 22 (20.8%) stage 2-, and 4 (3.8%) stage 3 hypertension respectively. The adherence rate by the anesthesiologist was 84.0% (95% confidence interval (CI) 77.0% to 91.0%) for initiation of anti-hypertensive therapy. It was noted that 55.5% (95% CI 46.2% to 65.1%) received their medication upon discharge. CONCLUSIONS: Anesthesiologists successfully implemented a quality improvement project for diagnosis and management of hypertension in the perioperative period. This has the potential to reduce the public health burden of hypertension in limited resource environments. Successful ongoing prescription and follow-up requires cooperation within a multi-disciplinary team involving anesthesiologists, surgeons, nurses, pharmacists and physicians.
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    ASCOT-BPLA signals changes to hypertension guidelines
    (2005) Rayner, Brian
    The Anglo-Scandanavian Cardiac Outcomes Trial - Blood Pressure Lowering Arm (ASCOT-BPLA) was a multi-centre, prospective, randomised, controlled trial in 19 257 patients with hypertension, aged 40-79 years, with at least three other cardiovascular (CVS) risk factors. Patients were assigned to either arnlodipine (5-10 mg), adding perindopril (4-8 mg) as required (arnlodipine-based regimen, n = 9 639), or atenolol (50-100 mg), adding bendroflumethiazide (1.25-2.5 mg) and potassium as required (atenolol-based regimen, n = 9 618). The primary end-point was non-fatal myocardial infarction (MI) and fatal coronary heart disease (CHD). Although there was a non-significant 10% reduction in the primary end-point in favour of the arnlodipine-based regimen, the study was prematurely stopped after a median follow up of 5.5 years by the Data and Safety Monitoring Committee, because of clinically important reductions in secondary end-points (Table I).
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    Clinical lessons from an elderly man with amiodarone-induced interstitial lung disease
    (2007) Rayner, Brian
    An 82-year-old man was in relatively good health despite a background of hypertension, chronic kidney disease stage 4 (estimated glomerular filtration rate 15 – 30 ml/min) and extensive vascular disease requiring carotid endartectomy, coronary artery bypass grafting, repair of an abdominal aortic aneurysm, and stenting of both renal arteries. In May 2005 he developed rapid atrial flutter after an episode of acute coronary syndrome. He was successfully cardioverted to sinus rhythm. After a loading dose of amiodarone he continued on 200 mg daily, and remained in sinus rhythm.
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    Computational analysis of candidate disease genes and variants for salt-sensitive hypertension in indigenous Southern Africans
    (Public Library of Science, 2010) Tiffin, Nicki; Meintjes, Ayton; Ramesar, Rajkumar; Bajic, Vladimir B.; Rayner, Brian
    Multiple factors underlie susceptibility to essential hypertension, including a significant genetic and ethnic component, and environmental effects. Blood pressure response of hypertensive individuals to salt is heterogeneous, but salt sensitivity appears more prevalent in people of indigenous African origin. The underlying genetics of salt-sensitive hypertension, however, are poorly understood. In this study, computational methods including text- and data-mining have been used to select and prioritize candidate aetiological genes for salt-sensitive hypertension. Additionally, we have compared allele frequencies and copy number variation for single nucleotide polymorphisms in candidate genes between indigenous Southern African and Caucasian populations, with the aim of identifying candidate genes with significant variability between the population groups: identifying genetic variability between population groups can exploit ethnic differences in disease prevalence to aid with prioritisation of good candidate genes. Our top-ranking candidate genes include parathyroid hormone precursor ( PTH ) and type-1angiotensin II receptor ( AGTR1 ). We propose that the candidate genes identified in this study warrant further investigation as potential aetiological genes for salt-sensitive hypertension.
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    Efficacy of a text messaging (SMS) based intervention for adults with hypertension: protocol for the StAR (SMS Text-message Adherence suppoRt trial) randomised controlled trial
    (2014-01-11) Bobrow, Kirsty; Brennan, Thomas; Springer, David; Levitt, Naomi S; Rayner, Brian; Namane, Mosedi; Yu, Ly-Mee; Tarassenko, Lionel; Farmer, Andrew
    Abstract Background Interventions to support people with hypertension in attending clinics and taking their medication have potential to improve outcomes, but delivery on a wide scale and at low cost is challenging. Some trials evaluating clinical interventions using short message service (SMS) text-messaging systems have shown important outcomes, although evidence is limited. We have developed a novel SMS system integrated with clinical care for use by people with hypertension in a low-resource setting. We aim to test the efficacy of the system in improving blood pressure control and treatment adherence compared to usual care. Methods/design The SMS Text-message Adherence suppoRt trial (StAR) is a pragmatic individually randomised three-arm parallel group trial in adults treated for hypertension at a single primary care centre in Cape Town, South Africa. The intervention is a structured programme of clinic appointment, medication pick-up reminders, medication adherence support and hypertension-related education delivered remotely using an automated system with either informational or interactive SMS text-messages. Usual care is supplemented by infrequent non-hypertension related SMS text-messages. Participants are 1:1:1 individually randomised, to usual care or to one of the two active interventions using minimisation to dynamically adjust for gender, age, baseline systolic blood pressure, years with hypertension, and previous clinic attendance. The primary outcome is the change in mean systolic blood pressure at 12-month follow-up from baseline measured with research staff blinded to trial allocation. Secondary outcomes include the proportion of patients with 80% or more of days medication available, proportion of participants achieving a systolic blood pressure less than 140 mmHg and a diastolic blood pressure less than 90 mmHg, hospital admissions, health status, retention in clinical care, satisfaction with treatment and care, and patient related quality of life. Anonymised demographic data are collected on non-participants. Discussion The StAR trial uses a novel, low cost system based on widely available mobile phone technology to deliver the SMS-based intervention, manage communication with patients, and measure clinically relevant outcomes. The results will inform implementation and wider use of mobile phone based interventions for health care delivery in a low-resource setting. Trial registration NCT02019823
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    Investigating kidney disease clinical epidemiology using routinely collected administrative data and proteomics
    (2024) Aylward, Ryan Edward; Rayner, Brian
    Data collected routinely during healthcare visits and additional biospecimens collected as part of cohort study activities are invaluable to better understand kidney disease epidemiology. This thesis explores the detection and characterization of acute kidney injury (AKI), chronic kidney disease (CKD), acute-on-chronic kidney disease (A-on-CKD) and kidney disease progression using rule-based laboratory- and database-embedded algorithms and proteomic analysis. The research includes three components. Firstly, an internal validation of the National Health Services England (NHSE) AKI detection algorithm-generated alerts received by the United Kingdom Renal Registry. Secondly, a description of the clinical epidemiology of AKI, CKD and A-on-CKD in Cape Town, South Africa, within the Provincial Health Data Centre, a health information exchange that houses administrative and clinical data about clients accessing public healthcare in the province. Lastly, proteins and biological pathways in association with CKD progression in older European adults were investigated (European Quality Study). The implementation of the NHSE AKI detection algorithm in English laboratories was largely successful, though further investigation is required for alerts in people with CKD and alerts from a few outlying laboratories. Overall, the epidemiological findings in Cape Town shed light on the burden and characteristics of AKI, CKD and A-on-CKD in the region and challenges to research with routinely collected data in complex health systems like South Africa. In the EQUAL study, three proteins were associated with eGFR decline, potentially serving as markers of CKD progression and targets for treatment. In conclusion, the digitome (administrative data) and proteome provided unique opportunities for detecting and understanding kidney disease, but limitations such as misclassification, missing data and inability to establish causal relationships were identified, requiring future refinements.
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    Kidney tissue characterization using magnetic resonance in HIV infected individuals undergoing kidney biopsy
    (2024) Banda, Tayanjana; Rayner, Brian; Wearne, Nicola; Ntusi, Ntobeko
    BACKGROUND: Kidney disease is a common complication of human immunodeficiency virus (HIV) infection. Kidney biopsy is the gold standard for assessing causation, but being invasive, it carries increased risk in advanced chronic kidney disease (CKD). Magnetic resonance imaging (MRI) is noninvasive and may serve as an alternative to kidney biopsy in a subset of patients. OBJECTIVES: The primary aim of this study was to compare the kidney biopsy Sethi chronicity score and MRI findings. METHODS: This was a prospective pilot study, conducted at Groote Schuur Hospital, Cape Town and the Cape Universities Body Imaging Centre (CUBIC). People with HIV (PWH) >18 years with a clinical indication for kidney biopsy were included. Demographics and other clinical data were documented. Uncontrasted MRI scans were performed between 1-7 days prior to kidney biopsy that included diffusion tensor imaging (DTI), and proton (H1) spectroscopy. The kidney biopsy Sethi chronicity score was compared to MRI-DTI using linear regression modeling as well as with H1 spectroscopy. RESULTS: Sixteen participants were included in the study. Thirty-one percent were female, 47% hypertensive, 6% diabetic, 44% had current tuberculosis, and 56 % were receiving antiretroviral therapy {ART). The most common histology observed on kidney biopsy were granulomatous interstitial nephritis (31%}, hypertensive changes (31%) and HIV associated nephropathy (HIVAN) (25%). Mixed pathology was observed in 25% of participants. There was significant negative correlation with Sethi chronicity score and MRI-DTI findings. Spectroscopy showed an element of cell degradation and inflammation in all participants with highest lipid peaks in participants with HIVAN, and pauci-immune crescentic glomeru!onephritis. CONCLUSION: In this small pilot study Sethi chronicity scores negatively correlated with MRI-DTI findings suggesting that this may potentially be a useful tool to assess chronicity. Further research ls required to corroborate these findings and include BOLD sequence and Tl and T2 parametric mapping.
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    Life-threatening angio-oedema and death associated with the ACE inhibitor enalapril
    (2007) Cupido, Clint; Rayner, Brian
    Angiotensin-converting enzyme (ACE) inhibitors are widely used and effective drugs in the treatment of a broad range of cardiovascular and renal disorders. The recent death of a patient as a result of angio-oedema related to enalapril use prompted us to review all admission records of the intensive care units (ICUs) of Victoria, G F Jooste, New Somerset and Groote Schuur hospitals.
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    Potential renoprotective effects of the angiotensin receptor blocker eprosartan: A review of preliminary renal studies
    (2004) Rayner, Brian; Jaeger, Bodo; Verboom, Cees-Nico; Pascoe, Michael
    The importance of the renin-angiotensin-aldosterone system (RAAS) in the pathogenesis of hypertension and in renal disease, particularly in patients with diabetes, has become increasingly evident. Pharmacological blockade of the RAAS offers potential for the therapeutic management of these pathologies. Angiotensin converting enzyme (ACE) inhibitors and angiotensin II (AII) receptor blockers have been shown to exhibit effectiveness in the treatment of hypertension. AII receptor blockers have a renal protective effect owing to their ability to reduce systemic blood and intraglomerular pressures. Eprosartan is a chemically distinct AII blocker, which displays a dual mode of action whereby it blocks both pre- and postsynaptic AT1 receptors, potentially benefiting patients with hypertension and renal disease. In addition, evidence suggests that eprosartan is well tolerated by both healthy subjects and patients with varying degrees of renal impairment, such that the dose does not need to be - modified in patients with mild to moderate renal impairment.
    Results from preliminary studies demonstrate that eprosartan doses well below those required for blood pressure control have a pronounced effect on the kidney and do not compromise renal autoregulatory mechanisms. Therefore, eprosartan may have a benefit in the prevention or delay of renal damage in hypertensive patients with renal impairment, although this remains to be determined in a clinical setting.
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    A survey of hypertensive practices at two community health centres in Cape Town
    (Health and Medical Publishing Group, 2007) Rayner, Brian; Blockman, Marc; Baines, Donette; Trinder, Trinder
    Background: Control of hypertension remains an elusive goal, but doctors' non-compliance with guidelines, patient attitudes and adherence to treatment, and poor delivery of care at clinics are important contributing factors. Objectives: To determine the overall quality of hypertensive care, and compliance with current hypertension guidelines at community health centres (CHCs) in the Western Cape. Methods. Consecutive patients attending hypertension clinics at two CHCs were selected to participate. A questionnaire was designed to determine patient demographics, doctors' compliance with hypertension guidelines, factors leading to treatment non-adherence, and delivery of care. Accuracy of blood pressure (BP) recording was evaluated by comparing the clinic BP with that measured using an approved manometer. Results: One hundred and sixty-one patients were evaluated, 100 from CHC 1 and 61 from CHC 2. There was no difference in both control systolic and diastolic BP measured by the hypertension nurse (147.9 v. 144.8 mmHg, p = 0.45, and 89.3 v. 85.6 mmHg, p = 0.14) respectively. All clinic BP readings were recorded to the nearest 10 mmHg mercury. The difference in both systolic and diastolic BP > 10 mmHg between the clinic and control BP was significantly greater at CHC 2 than CHC 1 (28% v. 56%, p = 0.005, and 43% v. 64%, p = 0.007) respectively. Overall, 39.8% of patients had a systolic and diastolic BP < 140 and < 90 mmHg. The mean number of antihypertensive drugs was 2.4 per patient. The use of non-steroidal antiinflammatory drugs (NSAIDs) and tricyclic antidepressants was high at both centres, and few patients underwent basic investigations, lifestyle interventions, risk stratification or global cardiovascular risk reduction. Conclusions: 39.8% of patients achieved a BP < 140/90 mmHg. There is significant scope for improvement in prescription of medication, application of uniform lifestyle changes, and avoidance of NSAIDs and tricyclic antidepressants. Major deficiencies were identified in BP measurement, assessment of target organ damage, risk stratification and the reduction of overall cardiovascular risk.
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    The prevalence of microalbuminuria and ECG left ventricular hypertrophy in hypertensive patients in private practices in South Africa
    (2006) Rayner, Brian; Becker, Piet
    Introduction: In South Africa a cluster of cardiovascular diseases accounts for 17% of all deaths. It is also predicted that South Africa will face an epidemic of chronic kidney disease due to obesity, type 2 diabetes and hypertension. It is important to estimate the burden of underlying cardiovascular and renal disease in South Africa. Objectives: The primary objective of the study was to establish the prevalence of left ventricular hypertrophy by ECG criteria, and micro- and macroalbuminuria in mild, moderate and severe hypertensive groups. The secondary objective was to establish the prevalence of left ventricular hypertrophy and micro- and macroalbuminuria in hypertensive patients with underlying type 2 diabetes. Methods: Patients ≥ 35 years with essential hypertension with or without type 2 diabetes were recruited from 100 general practices throughout South Africa. BP, weight, height, waist circumference and urinary albumin/creatinine ratio were measured, and an ECG was performed. The Sokolow-Lyon and Cornell criteria were used for estimation of left ventricular hypertrophy. An overall prevalence rate was determined using weights from the severity category distribution inside the study population. Results: One thousand and ninety-one patients were available for analysis. There were 530 (48.5%) males and 561 (51.5%) females, 691 (63.3%) whites, 162 (14.8%) blacks, 150 (13.7%) Asians and 88 (8.1%) Coloureds. Of the patients, 10.9% had newly diagnosed hypertension, 20% had type 2 diabetes, and 38.1% mild, 32.1% moderate and 30.6% severe hypertension. The prevalence of left ventricular hypertrophy in the sample weighted to the hypertensive population over the age of 35 years with access to medical aids was 18.9%. Relative to white ethnicity, black ethnicity (OR 2, p 5 0.03), and relative to mild hypertension, moderate (OR 2.2, p 5 0.05) and severe hypertension (OR 4.9, p < 0.0001) were independent predictors of left ventricular hypertrophy. The overall prevalence of micro- and macroalbuminuria in the weighted sample was 21.3 and 4.1%, respectively. In the diabetics the prevalence of microalbuminuria was 32.3% and macroalbuminuria 10.4%, respectively. The independent predictors of microalbuminuria or worse were severe hypertension (OR 2.9, p < 0.0001), type 2 diabetes (OR 2.5, p < 0.002), and Asian ethnic group (OR 2, p 5 0.02). Conclusions: The study, based on a convenience sample of hypertensives from private practices in South Africa showed that the prevalence of left ventricular hypertrophy and microalbuminuria or worse was 18.9 and 25.4%, respectively.
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    The relevance of performing 24-hour ambulatory blood pressure And pulse wave analysis in kidney transplant recipients
    (2021) Mzingeli, Luvuyo; Rayner, Brian
    Hypertension guidelines recommend out of office blood pressure (BP) measurement especially 24- hour ambulatory measurement (ABPM), to diagnose and manage hypertension but this is not routinely performed in kidney transplant units. This study was to determine if 24-hour ABPM, compared with office BP in kidney transplant recipients, would be more informative regarding BP management, and if pulse wave analysis (PWA) would assist in risk stratification. This study included patients older than 18 years, with working graft kidney for >12 months, and without problems affecting BP measurement and interpretation. After performing office BP measurements, a 24-hour ABPM with additional capability of calculating pulse wave velocity (PWV),augmentation index and central BP was undertaken. Patients were assessed for controlled hypertension, uncontrolled hypertension, masked hypertension, nocturnal hypertension, white coat hypertension, and dipping BP status. Data were analysed using standard statistical tests. Of 30 patients, 15 were Black Africans and 15 were of Mixed Ancestry with a mean age of 48.9 years. Seventeen patients were males and 36.7% had controlled hypertension, 30% uncontrolled hypertension, 6.7% white coat hypertension and 33.3% masked hypertension, of whom 70% had isolated nocturnal hypertension. 70% had a non-dipping, 26.7% a reverse dipping and only 3.3% had a normal dipping BP pattern. The mean difference between brachia! systolic BP and central systolic BP was 10.4 mm Hg, whereas PWV and augmentation index were similar to healthy populations. CONCLUSION: In kidney transplant recipients, 24-hour ABPM was superior to office BP in defining hypertensive status that qualified for modification of therapy but PWA did not contribute to risk assessment.
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    The spectrum of HIV-related kidney disease in South Africa
    (2025) Dave, Nicola; Post, Frank; Rayner, Brian
    The spectrum of HIV-related kidney disease in South Africa Associate Professor Nicola Wearne Background: HIV is associated with a spectrum of kidney diseases, including HIV-associated nephropathy (HIVAN), opportunistic infections, including tuberculosis (TB), and adverse effects of drugs and immune activation/viral replication. This thesis explores the evolving landscape of HIV-related kidney disease in a setting where antiretroviral therapy (ART) has been progressively rolled out to all. Methods: This PhD comprises four studies: 1. A longitudinal study describing the relationship between HIV immune-virological status, ART usage, and kidney pathology. 2. A study of corticosteroids for the treatment of patients with HIVAN. 3. A descriptive analysis of kidney disease in the setting of HIV/TB coinfection. 4. A descriptive analysis of kidney pathology in biopsies from HIV-positive donors transplanted into HIV-positive recipients. Results: 1. Among 671 participants, an increase in ART usage was associated with a reduction in the proportion of biopsies showing HIVAN. In contrast, an increase in tubulointerstitial disease was associated with exposure to tenofovir disoproxil containing ART and likely TB. 2. We included 38 ART-naïve individuals with HIVAN, 21 of whom were randomly assigned to receive six months of prednisone. While adjunctive prednisone was associated with slightly more significant improvements in eGFR, mortality was increased in this group. 3. A high prevalence of acute and chronic kidney disease (CKD) in African people with HIV/TB was observed across three cohorts. TB affected the kidneys in 60% at post-mortem, and 8% had severe CKD with multiple aetiologies, including HIVAN, identified on kidney biopsy. 8 4. Based on 179 allograft biopsies from 50 recipients, we report a high cumulative incidence of rejection episodes, with 36% showing T-cell-mediated rejection or antibody-mediated rejection (ABMR). Non-rejection findings included fibrosis, pyelonephritis, and calcineurin toxicity. Features of HIVAN were identified in nine patients. ABMR significantly impacted kidney function and contributed to graft failure over 14 years. Conclusion: The studies document a shift in kidney pathologies among people with HIV in Cape Town, which was temporarily associated with the progressive rollout of tenofovir based ART. Corticosteroids cannot be recommended to improve kidney outcomes in patients with HIVAN. Kidney disease is a significant complication of HIV/TB. While HIV+ to HIV+ kidney transplantation is feasible, high rates of allograft rejection and infection suggest a need for carefully balanced immunosuppression.
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    Towards Evidence-Based Implementation of Pharmacogenomics in Southern Africa: Comorbidities and Polypharmacy Profiles across Diseases
    (Multidisciplinary Digital Publishing Institute, 2023-07-26) Soko, Nyarai Desiree; Muyambo, Sarudzai; Dandara, Michelle T. L.; Kampira, Elizabeth; Blom, Dirk; Jones, Erika S. W.; Rayner, Brian; Shamley, Delva; Sinxadi, Phumla; Dandara, Collet
    Pharmacogenomics may improve patient care by guiding drug selection and dosing; however, this requires prior knowledge of the pharmacogenomics of drugs commonly used in a specific setting. The aim of this study was to identify a preliminary set of pharmacogenetic variants important in Southern Africa. We describe comorbidities in 3997 patients from Malawi, South Africa, and Zimbabwe. These patient cohorts were included in pharmacogenomic studies of anticoagulation, dyslipidemia, hypertension, HIV and breast cancer. The 20 topmost prescribed drugs in this population were identified. Using the literature, a list of pharmacogenes vital in the response to the top 20 drugs was constructed leading to drug–gene pairs potentially informative in translation of pharmacogenomics. The most reported morbidity was hypertension (58.4%), making antihypertensives the most prescribed drugs, particularly amlodipine. Dyslipidemia occurred in 31.5% of the participants, and statins were the most frequently prescribed as cholesterol-lowering drugs. HIV was reported in 20.3% of the study participants, with lamivudine/stavudine/efavirenz being the most prescribed antiretroviral combination. Based on these data, pharmacogenes of immediate interest in Southern African populations include ABCB1, CYP2B6, CYP2C9, CYP2C19, CYP2D6 CYP3A4, CYP3A5, SLC22A1, SLCO1B1 and UGT1A1. Variants in these genes are a good starting point for pharmacogenomic translation programs in Southern Africa.