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The first documented case of SARS-CoV-2 infection was confirmed in South Africa (SA) in March 2020. The Western Cape (WC) province was the initial epicenter. The pandemic peaked in July 2020 when 76,851 cases were documented and 2,323 deaths reported. COVID-19 can have multisystem involvement. Acute kidney injury (AKI) is well-documented and associated with increased mortality. We report our experience as the pandemic evolved in the WC province, focusing on those patients with a SARS-CoV-2 positive test presenting with AKI. We also reviewed our chronic dialysis cohort and renal transplant recipients who tested positive to assess incidence and outcomes. All patients presenting to nephrology services at the four main public hospitals were included. Information regarding demographics, co-morbidities, medical care, laboratory data, and outcomes were recorded. There were 86 patients referred with AKI, 48 required dialysis, and 47 died. There were 52 patients admitted to the intensive care unit with AKI (37 received dialysis, 1 of whom survived). In those presenting with AKI, diabetes, obesity, hypertension, and HIV were the most common comorbidities. Of the 295 patients receiving chronic dialysis within our services, 31 tested positive for SARS-CoV-2, and 6 died. Of the 45 kidney transplant recipients who tested positive, 9 died. Only 3 required dialysis. In conclusion, we report a high rate of AKI and poor prognosis in those requiring kidney replacement therapy, a better prognosis than anticipated was found in our chronic dialysis cohort, and high numbers of admissions were required for renal transplant recipients.

Elevated blood pressure (BP) is a growing burden worldwide, leading to over 10 million deaths each year. May Measurement Month (MMM) is a global initiative of the International Society of Hypertension (ISH) aimed at raising awareness of high BP and acting as a temporary solution to the lack of screening programmes worldwide. As part of MMM, screening in South Africa in 2017 revealed that 24.5% of adults (mean age = 31 years) have hypertension and only half of those with hypertension had controlled BP. These data highlight the need for continued screening and awareness campaigns. An opportunistic cross-sectional survey of volunteers aged ≥18 years was carried out in May 2018. Blood pressure measurements, the definition of hypertension and statistical analyses followed the MMM protocol. The sites screened were general populations and university campuses in preference to hospitals and clinics, aiming to raise awareness and allow access to screening to those less likely to be aware of their BP. In total, 2965 individuals (age 40.5 ± 18.2 years) were screened. After multiple imputation for missing BP readings, 34.6% had hypertension, only 56.7% of those with hypertension were aware, 21.2% of those not receiving treatment for hypertension were hypertensive, and a large proportion (42.5%) of individuals receiving antihypertensive medication had uncontrolled BP. These results suggest that opportunistic screening campaigns can identify significant numbers with undiagnosed and uncontrolled hypertension. The high proportions of individuals with undiagnosed and treated uncontrolled hypertension highlight the need for hypertension awareness campaigns and more rigorous management of hypertension.

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.

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).

BACKGROUND The prevalence of hypertension among black African patients is high, and these patients usually need two or more medications for blood-pressure control. However, the most effective two-drug combination that is currently available for blood-pressure control in these patients has not been established. METHODS In this randomized, single-blind, three-group trial conducted in six countries in sub-Saharan Africa, we randomly assigned 728 black patients with uncontrolled hypertension (≥140/90 mm Hg while the patient was not being treated or was taking only one antihypertensive drug) to receive a daily regimen of 5 mg of amlodipine plus 12.5 mg of hydrochlorothiazide, 5 mg of amlodipine plus 4 mg of perindopril, or 4 mg of perindopril plus 12.5 mg of hydrochlorothiazide for 2 months. Doses were then doubled (10 and 25 mg, 10 and 8 mg, and 8 and 25 mg, respectively) for an additional 4 months. The primary end point was the change in the 24-hour ambulatory systolic blood pressure between baseline and 6 months. RESULTS The mean age of the patients was 51 years, and 63% were women. Among the 621 patients who underwent 24-hour blood-pressure monitoring at baseline and at 6 months, those receiving amlodipine plus hydrochlorothiazide and those receiving amlodipine plus perindopril had a lower 24-hour ambulatory systolic blood pressure than those receiving perindopril plus hydrochlorothiazide (between-group difference in the change from baseline, −3.14 mm Hg; 95% confidence interval [CI], −5.90 to −0.38; P=0.03; and −3.00 mm Hg; 95% CI, −5.8 to −0.20; P=0.04, respectively). The difference between the group receiving amlodipine plus hydrochlorothiazide and the group receiving amlodipine plus perindopril was −0.14 mm Hg (95% CI, −2.90 to 2.61; P=0.92). Similar differential effects on office and ambulatory diastolic blood pressures, along with blood-pressure control and response rates, were apparent among the three groups. CONCLUSIONS These findings suggest that in black patients in sub-Saharan Africa, amlodipine plus either hydrochlorothiazide or perindopril was more effective than perindopril plus hydrochlorothiazide at lowering blood pressure at 6 months. (Funded by GlaxoSmithKline Africa Noncommunicable Disease Open Lab; CREOLE ClinicalTrials.gov number, NCT02742467. opens in new tab.)

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 forgt; 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 analyzed 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. 17 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 brachial systolic BP and central systolic BP was 10.4 mmHg, 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.

Groote Schuur Hospital in Cape Town, South Africa, offers a PD-First policy as a result of haemodialysis (HD) restrictions and resource limitations. This study aimed to compare health-related quality of life (HRQOL) between HD and peritoneal dialysis (PD) patients, given the lack of autonomy in modality choice and the socio-economic challenges. This single-centre, cross-sectional study was performed between July 2015 and December 2016. Demographic, socio-economic variables and perceptions of safety were collected. HRQOL was assessed using the Kidney Disease Quality of Life-Short Form (KDQOL-SFTM) version 1.3. All data were compared between the two dialysis modalities; 77 HD and 33 PD patients were included in the study and there were no significant differences in demographics. Median age was 42.5 years (IQR: 32.4–48.6) and 57.3% were female. HD patients had less pain (P = 0.036), better emotional well-being (P = 0.020) and a better energy/fatigue score (P = 0.015). Both cohorts experienced role-limitations due to physical health with PD being more affected overall (P = 0.05). The only significant symptom in the kidney domain was that PD patients experienced more shortness of breath (P < 0.001). Patients in both groups had very poor socio-economic circumstances, and safety within their communities was a major concern. The patients in our dialysis service have very challenging social circumstances. Those on PD scored worse in four HRQOL domains, possibly due to a lack of autonomy in dialysis modality choice and less frequent contact with dialysis staff. Additional psychological and social support needs to be instituted to help improve our patients’ well-being on PD.

Human immunodeficiency virus (HIV) affects over 36 million people worldwide. Antiretroviral therapy (ART) is expanding and improving HIV viral suppression, resulting in increasing exposure to drugs and drug interactions. Polypharmacy is a common complication as people are living longer on ART, increasing the risk of drug toxicities. Polypharmacy is related not only to ART exposure and medication for opportunistic infections, but also to treatment of chronic lifestyle diseases. Acute kidney injury (AKI) is frequent in HIV and is commonly the result of sepsis, dehydration and drug toxicities. Furthermore, HIV itself increases the risk of chronic kidney disease (CKD). Drug treatment is often complicated in people living with HIV because of a greater incidence of AKI and/or CKD compared to the HIV-negative population. Impaired renal function affects drug interactions, drug toxicities and importantly drug dosing, requiring dose adjustment. This review discusses ART and its nephrotoxic effects, including drug-drug interactions. It aims to guide the clinician on dose adjustment in the setting of renal impairment and dialysis, for the commonly used drugs in patients with HIV.

OBJECTIVES African and African American hypertensives tend to retain salt and water, with lower levels of plasma renin and more resistant hypertension. We tested the hypothesis that physiological phenotyping with plasma renin and aldosterone would improve blood pressure control in uncontrolled hypertensives in Africa. METHODS Patients at hypertension clinics in Nigeria, Kenya, and South Africa with a systolic blood pressure >140 mm Hg or diastolic pressure > 90 mm Hg despite treatment were allocated to usual care (UC) vs. physiologically individualized care (PhysRx). Plasma renin activity and aldosterone were measured using ELISA kits. Patients were followed for 1 year; the primary outcome was the percentage of patients achieving blood pressure RESULTS Results are presented for the 94/105 participants who completed the study (42 UC, 52 PhysRx). Control of both systolic and diastolic pressures was obtained in 11.1% of UC vs. 50.0% of PhysRx (P = 0.0001). Systolic control was achieved in 13.9% of UC vs. 60.3% of PhysRx (P = 0.0001); diastolic control in 36.1% of UC vs. 67.2% of PhysRx, vs. (P = 0.003). Number of visits and total number of medications were not significantly different between treatment groups, but there were differences across the sites. There were important differences in prescription of amiloride as specified in the PhysRx algorithm. CONCLUSIONS Physiologically individualized therapy based on renin/aldosterone phenotyping significantly improved blood pressure control in a sample of African patients with uncontrolled hypertension. This approach should be tested in African American and other patients with resistant hypertension. Registered as ISRCTN69440037

Hypertension is highly prevalent in Black Africans and has been found to be associated with worse blood pressure (BP) control and more cardiovascular disease. Black Africans are more salt sensitive with low renin and aldosterone levels. This can be explained in part by variants in the epithelial sodium channel (ENaC) causing an increase in channel activity resulting in sodium and water retention. These variants in the ENaC are increased in the Black African populations presumably due to selective pressure for sodium retention in traditionally low-salt diets. Furthermore, increased endothelial sodium channel activity contributes to the risk of vascular stiffness, which may also result in more difficult to control hypertension. Patients with increased activity of the ENaC are more likely to respond to amiloride (a selective sodium channel antagonist), which has implications for the management of severe and resistant hypertension in Black Africans. A large-scale controlled trial on the use of amiloride compared to usual care is warranted in Blacks with severe or resistant hypertension.

Background. Hypertension in pregnancy is a risk factor for end-stage chronic kidney disease (ESKD) and is particularly common in South Africa (SA). There are no data for the risk of developing chronic kidney disease (CKD). Objectives. To conduct a study of all female patients who presented to the renal replacement programme at Groote Schuur Hospital, Cape Town, SA. Methods. This was a retrospective study of female patients with ESKD who were presented to renal replacement meetings between 2007 and 2017. For each patient who was assessed, there was a comprehensive letter detailing patient demographics, as well as psychosocial and medical history, which served as the source data. Patients with a history of hypertension in pregnancy were identified as the case group and those without the condition were the control group. Patient demographics, causes of CKD, kidney function and outcome of the meeting were documented. Results. Of the 415 female patients with ESKD, 70 (16.9%) had a history of hypertension in pregnancy. The ethnic breakdown was as follows: 132 (42.44%) black, 172 (55.3%) mixed ancestry and 7 (2.25%) white. Compared with the control group, the patients were younger, with a median age of 33 v. 41 years ( p

ObjectivesThe 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.SettingA questionnaire was emailed to facilities, where renal replacement therapy is available; to determine type of services available; quality of care and identify clinicians involved.ParticipantsClinicians and administrators involved in the care of patients with acute kidney injury (AKI) completed the questionnaire.ResultsCompleted 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.ConclusionIn 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.

In late 2017, the publication of the new American College of Cardiology (ACC)/American Heart Association (AHA) hypertension guidelines created considerable controversy. The threshold for hypertension was redefined as > 130/80 mmHg and target blood pressure < 130/80 mmHg. The purpose of this commentary is to give clarity on the position of the Southern African Hypertension Society (SAHS). In South Africa more than 90% of hypertensives are not controlled at < 140/90 mmHg. Furthermore, by redefining hypertension to a level of 130/80 mmHg, this will significantly increase the prevalence of hypertension by 43%. The new targets will necessitate greater use of health services for increased health visits to monitor patients, greater use of antihypertensives to achieve the lower target, and increased use of laboratory services to monitor for adverse effects. It is the position of SAHS that the new definition and targets are not relevant to low- and middle-income countries such as South Africa, the threshold for hypertension remains at 140/90 mmHg, and a universal target is < 140/90 mmHg for all categories of hypertension.

South Africa continues to be burdened by human immunodeficiency virus (HIV) and tuberculosis (TB). In Cape Town, the epidemic of HIV-TB co-infection is as high as 70%. Granulomatous interstitial nephritis (GIN) has increased in frequency on renal biopsy. This study aimed to determine GIN prevalence and causes in HIV-positive patients as well as renal outcomes, patient survival and associated factors. This observational cohort study reviewed HIV-positive renal biopsies for GIN from 2005 to 2012. Causes of GIN (medications, TB, fungal and other), and baseline characteristics were analysed. A comparison of baseline data, renal function and survival was made between GIN and non-GIN cohorts. There were 45/316 biopsies demonstrating GIN. TB was the likely cause of GIN in 27 (60%) and 9 (20%) were due to a drug. Low estimated glomerular filtration rate was a statistically significant factor associated with mortality in both GIN (P = 0.045) and non-GIN cohorts (P < 0.000). In the GIN group, there were 12 (26.7%) deaths. Mortality for all patients was greatest in the first 6 months (P = 0.057). TB co-infection in both cohorts was associated with a higher mortality. The multivariate logistic regression demonstrated that a higher urine protein/creatinine ratio (uPCR) and lower estimated glomerular filtration rate were statistically associated with death. GIN is common in HIV-positive renal biopsies in Cape Town. TB-GIN was the commonest cause and associated with a high early mortality. GIN should be considered in HIV-positive patients with acute kidney injury, its presence conveys a survival benefit. There is a need for improved diagnostic accuracy and treatment strategies of TB-GIN.

Introduction Access to dialysis and transplantation in the developing world remains limited. Therefore, optimising renal allograft survival is essential. This study aimed to evaluate clinical outcomes and identify poor prognostic factors in the renal transplant programme at Groote Schuur Hospital [GSH], Cape Town. . Method Data were collected on all patients who underwent a kidney transplant at GSH from 1st July 2010 to the 30 June 2015. Analyses were performed to assess baseline characteristics, graft and patient survival, as well as predictors of poor outcome. . Results 198 patients were transplanted. The mean age was 38 +/- 10.5 years, 127 (64.1%) were male, and 86 (43.4%) were of African ethnicity. Deceased donor organs were used for 130 (66.7%) patients and living donors for 65 (33.3%). There were > 5 HLA mismatches in 58.9% of transplants. Sepsis was the commonest cause of death and delayed graft function [DGF] occurred in 41 (21.4%) recipients. Patient survival was 90.4% at 1 year and 83.1% at 5 years. Graft survival was 89.4% at 1 year and 80.0% at 5 years. DGF (HR 2.83 (1.12-7.19), p value = 0.028) and recipient age > 40 years (HR 3.12 (1.26-7.77), p value = 0.014) were predictors of death. Conclusion Despite the high infectious burden, stratified immunosuppression and limited tissue typing this study reports encouraging results from a resource constrained transplant programme in South Africa. Renal transplantation is critical to improve access to treatment of end stage kidney disease where access to dialysis is limited.

To audit the young patients referred to the Hypertension Clinic at Groote Schuur Hospital that predominately serves the underprivileged communities of Cape Town. Folders of patients between the ages of 15 and 30 years over a 2 year period were reviewed. The data collected included demographic, clinical and laboratory data, investigations, causes of hypertension, and presence of hypertensive organ damage. Of the 110 patients reviewed, 61 (55.5%) were females, 22 (20%) Black African, and 88 (80%) of Mixed Ancestry. Eight (7.3%) were found to be normotensive, 16 (14.5%) had a secondary cause and 86 (78.2%) had essential hypertension. Thirty five (31.8%) were current or previous smokers, and 11 (10%) admitted to current or prior use of metamphetamines. A family history of hypertension in a first degree relative was present in 80 (72.7%) patients. Comorbidities present were diabetes in 7 (6.4%) patients, metabolic syndrome in 13 (11.8%), and obesity in 26 (23.6%), but 42.6% had a body mass index (BMI)

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

BACKGROUND: The utility of exercise‐induced ST‐segment depression for diagnosing ischemic heart disease (IHD) in women is unclear. HYPOTHESIS: Based on evidence that IHD pathophysiology in women involves coronary vascular dysfunction, we hypothesized that coronary vascular dysfunction contributes to exercise electrocardiography (Ex‐ECG) ST‐depression in the absence of obstructive coronary artery disease, so‐called false positive results. We tested our hypothesis in a pilot study evaluating the relationship between peripheral vascular endothelial function and Ex‐ECG. METHODS: Twenty‐nine asymptomatic women without cardiac risk factors underwent maximal Bruce protocol exercise treadmill testing and peripheral endothelial function assessment using peripheral arterial tonometry (Itamar EndoPAT 2000) to measure reactive hyperemia index (RHI). The relationship between RHI and Ex‐ECG ST‐segment depression was evaluated using logistic regression and differences in subgroups using 2‐tailed t tests. RESULTS: Mean age was 54 ± 7 years, body mass index 25 ± 4 kg/m(2), and RHI 2.51 ± 0.66. Three women (10%) had RHI 0.05). RHI did not predict ST‐segment depression. CONCLUSIONS: Our pilot study demonstrates high prevalence of exercise‐induced ST‐segment depression in asymptomatic, middle‐aged, overweight women. Peripheral vascular endothelial dysfunction did not predict Ex‐ECG ST‐segment depression. Further work is needed to investigate the utility of vascular endothelial testing and Ex‐ECG for IHD diagnostic and management purposes in women.

Precordial pain is the primary cardiac-related complaint in 7%–24% of general population. Women represent a special segment in which evaluation of precordial pain is particularly challenging. In the absence of significant coronary stenosis, they have been classified as cardiac syndrome X. Availability of more sophisticated techniques to investigate coronary circulation, such radioisotopes and endothelial analysis by coronary flow measurements are changing this scenario. Angina due to coronary microvascular dysfunction (CMD) is now recognized in women with chest pain and normal coronaries at the classical angiogram and cardiac syndrome x terminology is no longer used. Thus CMV is defined based on: (1) presence of myocardial ischemia; and (2) presence of my coronary vascular dysfunction in macro- and microvascular beds. An abnormal response to intracoronary acetylcholine predicts future cardiovascular events such as angina, myocardial infarction heart failure, need for revascularization, and death. Cardiac events have been noted only in patients with severe endothelial dysfunction and not only mild dysfunction. In addition, the worst prognosis is observed when a significant atheroma burden coincides with severe endothelial dysfunction. A reduction in coronary flow reserve, an imbalance between NO bioavailability and endothelin-1, and slow coronary blood flow are also possible underlying mechanisms. Insulin resistance, increased sodium/potassium exchange in red blood cells, hyperglycemia, inflammation, and smooth muscle abnormalities (both vascular and nonvascular) may be additional mechanisms. These findings establish a new paradigm in the pathophysiology of angina with normal coronary arteries specifically for women.

Background. Non-adherence to antihypertensives is a cause of ‘pseudo-treatment-resistant’ hypertension. Objective. To determine whether monitoring plasma amlodipine concentrations and inhibition of angiotensin-converting enzyme (ACE) can be adjunct adherence tools. Methods. Patients with hypertension who were prescribed enalapril and amlodipine were enrolled. Blood pressures (BPs) were monitored and an adherence questionnaire was completed. Steady-state amlodipine was assayed using liquid chromatography-mass spectrometry and degree of ACE inhibition using the Z-FHL/HHL (z-phenylalanine-histidine-leucine/hippuryl-histidine-leucine) ratio. Results. One hundred patients (mean (standard deviation) age 50.5 (12) years, 46% male) were enrolled. Based on plasma assays, 26/97 patients (26.8%) were unsuppressed by enalapril and 20/100 (20%) were sub-therapeutic for amlodipine. There were significant BP differences based on plasma levels of the medication: 21/20 mmHg lower in the group with suppressed ACE and 26/20 mmHg in the group with steady-state amlodipine concentrations. Conclusions. Monitoring antihypertensive adherence by assaying plasma medication concentrations is a feasible option for evaluating true v. pseudo-resistant hypertension.S Afr Med J 2017;107(10):887-891

Background “Sex and Gender Medicine” is a novel medical discipline that takes into account the effects of sex and gender on the health of women and men. The Institute of Medicine in the USA declared in its 2001 and 2010 statements that being a woman or a man significantly impacts the course of diseases, and therefore, this fact must be considered in diagnosis and therapy. We evaluated the representation of Sex and Gender Medicine in clinical training at Cedars-Sinai Medical Center, a large, tertiary, non-profit, academic medical training center in the Western United States. Methods Post-graduate physician trainees (residents and fellows) in all medical and surgical departments (medicine, surgery, OB-GYN, pediatrics, anesthesiology, pathology, urology, electrophysiology, pulmonary critical care, cardiology, women’s heart, medical genetics, radiology, neurosurgery, and radiation oncology) were surveyed online; 80 (55 and 45 % female and male residents, respectively) out of 890 physicians (9 % response rate) responded to questions regarding sex and gender-based medicine. Results Seventy percent of post-graduate physician trainees indicated that gender medicine concepts are never or only sometimes discussed/presented in their training program. Slightly greater than 70 % of the trainees indicated that gender concepts are never or only sometimes incorporated into didactic lectures or clinical teaching. However, more than 65 % felt that gender medicine concepts are important, and 60 % agreed that gender medicine curriculum should be implemented and taught in their clinical program. Conclusions Current physician trainees endorse both a current lack of and need for Sex and Gender Medicine clinical training. Electronic supplementary material The online version of this article (doi:10.1186/s13293-016-0096-4) contains supplementary material, which is available to authorized users.

Background Women with signs and symptoms of ischemia, no obstructive coronary artery disease, and preserved left ventricular ejection fraction enrolled in the National Heart Lung and Blood Institute (NHLBI) sponsored Women's Ischemia Syndrome Evaluation (WISE) study have an unexpectedly high rate of subsequent heart failure (HF) hospitalization. We sought to verify and characterize the HF hospitalizations. Methods A retrospective chart review was performed on 223 women with signs and symptoms of ischemia, undergoing coronary angiography for suspected coronary artery disease followed for 6±2.6years. Data were collected from a single site in the WISE study. Results At the time of study enrollment, the women were 57±11years of age, all had preserved left ventricular ejection fraction, and 81 (36%) had obstructive CAD (defined as >50% stenosis in at least one epicardial artery). Among the 223 patients, 25 (11%) reported HF hospitalizations, of which 14/25 (56%) had recurrent HF hospitalizations (>2 hospitalizations). Medical records were available in 13/25 (52%) women. Left ventricular ejection fraction was measured in all verified cases and was found to be preserved in 12/13 (92%). HF hospitalization was not related to obstructive CAD. Conclusion Among women with signs and symptoms of ischemia undergoing coronary angiography for suspected obstructive CAD, HF hospitalization at 6-year follow-up was predominantly characterized by a preserved ejection fraction and not associated with obstructive CAD.

Background: Women frequently present with non-typical angina (NTA) making ischemia diagnosis and treatment challenging. We hypothesized that mortality would be higher in women with obstructive coronary artery disease (CAD) and NTA vs typical angina (TA). Methods: We studied 364 Women’s Ischemia Syndrome Evaluation (WISE) participants with signs and symptoms of ischemia and obstructive CAD, defined as ≥50% stenosis by WISE angiography core laboratory. TA was defined as sub-sternal chest pain precipitated by physical exertion or emotional stress and relieved with rest or nitroglycerin, while NTA was defined as symptoms not meeting criteria for TA. Death was confirmed by National Death Index. Time to death was analyzed and plotted using Kaplan-Meier survival analyses. The analyses were adjusted by age using a Cox Proportional Hazards regression, and reported with a hazard ratio (HR) and 95% confidence interval (CI). Results: Overall, 249 (68%) NTA and 115 (32%) TA women had a mean age of 63 ± 12yrs and 21% were non-white. Women with NTA were more hypertensive (72% vs. 60%, p=0.03) and more often on angiotensin-converting enzyme inhibitor (37% vs 25%, p= 0.03) than women with TA. There was no difference in mean cholesterol level, CAD severity or body mass index between the two groups. Over a median of 8.8 years, 122 (34%) women died including 92 NTA and 30 TA (HR 1.5, 95% CI 1.006, 2.30) (Figure). Conclusions: Among WISE women with signs and symptoms of ischemia and obstructive CAD, NTA has a higher mortality compared to TA. These findings extend prior evidence that chest pain, including NTA, identifies higher risk in women with obstructive CAD. These data support intensive management and clinical follow up of women with obstructive CAD and NTA. Further evaluation regarding ischemic burden and treatment is ongoing to further understand the elevated NTA mortality.

Cardiovascular disease is a leading cause of death in women and significant gender differences remain. Women have higher rates of post-procedural complications and worse outcomes compared to male counterparts following percutaneous coronary intervention (PCI). The aim of this analysis was to

Background: A high prevalence of the R563Q mutation of the epithelial sodium channel β-subunit has been reported in South African hypertensives compared with unrelated normotensive controls. To delineate the effects of this mutation against a more uniform genetic background, this study investigated the association of the mutation with hypertension within affected kindreds. Methods: Forty-five index patients and members of their kindreds were studied. Blood pressure, serum potassium and the presence of the R563Q mutation were determined. Results: Of the 136 individuals studied, 89 were heterozygous for the R563Q mutation and 47 homozygous RR. The mean arterial pressure was significantly higher in the R563Q heterozygous group (p = 0.005) after adjusting for gender, race, age and kindred membership. Of the R563Q heterozygous subjects, 71 (80%) had hypertension, while 17 (36%) of the R563Q homozygous RR subjects were hypertensive. Six R563Q heterozygous subjects had hypokalaemia and one R563Q homozygous RR subject had hypokalaemia, but the difference was not statistically significant. Two heterozygous patients had Liddle's syndrome, both occurring during pregnancy. Conclusion: The R563Q mutation of β-ENaC is associated with hypertension within affected kindreds, but does not usually cause the full Liddle's syndrome phenotype.

To our knowledge, atypical Hemolytic Uremic Syndrome (aHUS) causing myocarditis in adults has not been previously reported. A 33 year-old female with a history of Kikuchi disease and immune thrombocytopenia was admitted for cholangitis. A CT Abdomen showed biliary ductal dilation as well as a small

To evaluate the safety and efficiency of a protocol for glycemic control in intensive care unit (ICU) patients with neurovascular or head injury.Two cohorts of 50 consecutive patients admitted to the ICU with an admission diagnosis of neurovascular or head injury before and after protocol implementation were evaluated. All patients in the interventional cohort received insulin using a standardized intravenous insulin infusion protocol targeting blood glucose levels of 7-9 mmol/l. Efficiency (time to reach and time within target range), safety (hypoglycemia), and nursing compliance (protocol violations) were evaluated.The median time to reach the target blood glucose range was shorter in the interventional cohort than the conventional cohort (5.0 h [0.5-20.5 h] vs. 12.9 h [1.3-90.3 h]; P0.001). More time was spent within target range in the interventional cohort than in the conventional cohort (36.4 +/- 16.3% vs. 27.1 +/- 19.0%; P0.001). The median prevalence of mild (4.9 mmol/l) hypoglycemia (0 [0-1.11]% vs. 0.58 [0-2.79]%; P0.001) and moderate (3.9) hypoglycemia (0[0-0.55]% vs. 0 [1-1.25]%; p0.001) was significantly lower in the interventional cohort.The intravenous insulin infusion protocol improved the safety and efficiency of glycemic control for ICU patients with neurovascular or head injury.

Background: Methamphetamine abuse has risen dramatically in South Africa. The chronic effects of abuse on the kidneys and blood pressure have not been documented. This study reviewed patients referred for evaluation of kidney disease and/or hypertension, who had been abusing methamphetamines. Methods: The records of patients referred to the renal unit between 2005 and 2013 who had been using methamphetamines were retrospectively reviewed. Patient demographics, biophysical parameters, blood pressure, renal function, renal ultrasound and biopsy findings, complications of chronic kidney disease and comorbidities were recorded. Results: Forty-seven patients were included in the study. Their mean age was 29 years. Hypertension was present in 42 (89.4%) of patients, with malignant hypertension in 21 (44.7%). Forty-five (95.7%) had chronic kidney disease (CKD), and 26 (55.3%) had end-stage renal disease. Renal biopsies were performed in 24 patients. Twelve (50.0%) of the biopsies showed hypertensive changes and 14 (58.3%) mesangiocapillary glomerulonephritis type 1, with deposition of IgM and C3 complement. Conclusion: Methamphetamine use is associated with severe hypertension, mesangiocapillary glomerulonephritis and CKD.

Background: Current guidelines do not endorse exercise electrocardiography (Ex-ECG) screening in asymptomatic adults due to poor diagnostic accuracy for clinical coronary artery disease (CAD), however Ex-ECG combined with other variables paradoxically has strong prognostic accuracy for cardiovascular mortality. Ex-ECG ST segment depression “false positive” results are common in women, who have higher rates of vascular dysfunction such as Raynaud’s and migraines compared to men. We hypothesized that ST segment depression indicates endothelial vascular dysfunction, which is known to predict an adverse prognosis. To test this hypothesis, we evaluated the relationship between Ex-ECG and peripheral endothelial vascular function in asymptomatic women. Methods: Asymptomatic women with no cardiac risk factors and normal resting ECG underwent maximal Bruce protocol Ex-ECG testing (GE Healthcare). Computer-generated Ex-ECG ST segment values were independently verified by 2 cardiologists. Based on established methods, endothelial vascular function was assessed by calculating reactive hyperemia index (RHI) using peripheral vascular testing (Endopat, Itamar). As established previously, RHI Results: Among 35 women, mean age 54±8 years and BMI 24±4, there were 5 (14%) women with abnormal RHI. Women with abnormal RHI had a greater (more abnormal) ST/HR slope, a trend toward greater peak ST depression, and achieved lower METs than women with normal RHI (Table 1). Conclusion: Among asymptomatic women, endothelial vascular dysfunction was associated with abnormal Ex-ECG results characterized by greater ST/HR slope, greater ST depression, and lower exercise capacity. These findings suggest that “false positive” ST-segment depression in the absence of clinical CAD in women may be explained by endothelial vascular dysfunction. Our study further suggests that endothelial vascular dysfunction may explain the Ex-ECG diagnostic/prognostic paradox.

Moderated Poster ContributionsStable Ischemic Heart Disease Moderated Poster Theater, Poster Hall B1Sunday, March 15, 2015, 10:00 a.m.-10:10 a.m.Session Title: Ischemia in Women without Obstructive Coronary Artery DiseaseAbstract Category: 26. Stable Ischemic Heart Disease: ClinicalPresentation Number: 1205M-05Authors: May Bakir, Janet Wei, Louise Thomson, John Petersen, Quanlin Li, Erika Jones, Puja Mehta, Chrisandra Shufelt, Daniel Berman, Eileen Handberg, Sheryl Kelsey, George Sopko, Carl Pepine, C. Noel Bairey Merz, Cedars-Sinai Medical Center, Los Angeles, CA, USABackground: Women with signs and symptoms of ischemia and no obstructive coronary artery disease (CAD) have an elevated major adverse cardiac event rate. We evaluated the presence, extent and distribution of scar using cardiac magnetic resonance imaging (CMRI) late gadolinium enhancement (LGE) in the Women’s Ischemia Syndrome Evaluation.methods: Women (n=344) with signs and symptoms of ischemia and no obstructive CAD underwent 1.5T CMRI LGE. Scans were read blindly for presence and segmental distribution of LGE. Scar size was quantified using Pie Medical Imaging software. LGE type was defined as ischemic when subendocardial or transmural and localized to a coronary artery distribution, and non-ischemic when mid-myocardial or epicardial. Fisher’s exact and two sample t-tests were used for statistical analysis.results: LGE was present in 20 (5.8%) women, including 15 (75%) with ischemic LGE. Women with non-ischemic LGE (n=5) had larger scar size compared to women with ischemic LGE (Table). There were no significant differences in cardiac risk factors among women with no LGE, ischemic LGE, or non-ischemic LGE, and there was no significant correlation between LGE presence and cardiac risk factors.Conclusion: Women with signs and symptoms of ischemia and no obstructive CAD have a 5.8% prevalence of myocardial scar detected by CMRI, with a predominant ischemic LGE pattern. These findings demonstrate that these women can develop irreversible myocardial injury, which may be clinically under-diagnosed.No LGE(n=324)Ischemic LGE(n=15)Non-ischemic LGE(n=5)Age 54 ± 11 years 55 ± 8 years 37 ± 15 yearsBody Mass Index 30 ± 8 32 ± 11 35 ± 7Hypertension 40% 31% 75%Diabetes 11% 14% 50%Dyslipidemia 20% 10% 33%Family History of Coronary Artery Disease 48% 21% 50%Scar pattern n/a4 LAD6 LCX4 RCA1 LAD and RCA3 patchy epicardial1 midmyocardial ASH1 RV insertion pointsScar size n/a 4.83 ± 3.12g* 9.57 ± 6.10g*ASH= asymmetric septal hypertrophy, LAD= left anterior descending artery, LCX= left circumflex artery, LGE= late gadolinium enhancement, RCA= right coronary artery, RV= right ventricular*p=0.0034

End Stage Kidney Disease (ESKD) is a public health problem with an enormous economic burden. In resource limited settings management of ESKD is often rationed. Racial and socio-economic inequalities in selecting candidates have been previously documented in South Africa. New guidelines for dialysis developed in the Western Cape have focused on prioritizing treatment. With this in mind we aimed at exploring whether the new guidelines would improve inequalities previously documented. A retrospective study of patients presented to the selection committee was conducted at Groote Schuur Hospital. A total of 564 ESKD patients presented between 1 January 2008 and 31 December 2012 were assessed. Half of the patients came from low socioeconomic areas, and presentation was late with either overt uremia (n = 181, 44·4%) or fluid overload (n = 179, 43·9%). More than half (53·9%) of the patients were not selected for the program. Predictors of non-acceptance onto the program included age above 50 years (OR 0·3, p = 0·001), unemployment (OR 0·3, p

Objectives Black subjects tend to retain salt and water, be more sensitive to aldosterone, and have suppression of plasma renin activity. Variants of the renal sodium channel (ENaC, SCNN1B) account for approximately 6% of resistant hypertension (RHT) in Blacks; other candidate genes may be important. Methods Six candidate genes associated with low renin-resistant hypertension were sequenced in Black Africans from clinics in Kenya and South Africa. CYP11B2 was sequenced if the aldosterone level was high (primary aldosteronism phenotype); SCNN1B, NEDD4L, GRK4, UMOD, and NPPA genes were sequenced if the aldosterone level was low (Liddle phenotype). Results There were 14 nonsynonymous variants (NSVs) of CYP11B2: 3 previously described and associated with alterations in aldosterone synthase production (R87G, V386A, and G435S). Out of 14, 9 variants were found in all 9 patients sequenced. There were 4 NSV of GRK4 (R65L, A116T, A142V, V486A): at least one was found in all 9 patients; 3 were previously described and associated with hypertension. There were 3 NSV of SCNN1B (R206Q, G442V, and R563Q); 2 previously described and 1 associated with hypertension. NPPA was found to have 1 NSV (V32M), not previously described and NEDD4L did not have any variants. UMOD had 3 NSV: D25G, L180V, and T585I. Conclusions A phenotypic approach to investigating the genetic architecture of RHT uncovered a surprisingly high yield of variants in candidate genes. These preliminary findings suggest that this novel approach may assist in understanding the genetic architecture of RHT in Blacks and explain their two fold risk of stroke.

HYPONATREMIA, OFTEN DEFINED AS SERUM SODIUM LESS THAN 130 mmol/L, is the most common electrolyte disturbance among hospitalized patients. A complication of a variety of diseases, surgical treatments, or drugs, it may be hypertonic, hypotonic, or isotonic in nature. Antidiuretic hormone (ADH) is also known as arginine vasopressin (AVP). Produced in the posterior pituitary gland in response to an increased plasma sodium concentration, it induces water retention. It increases cellular permeability to water in the distal tubule and collecting duct of the nephron, leading to increased water resorption by the kidney. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is characterized by either the sustained release of ADH in the absence of stimuli, or by the enhanced action of ADH on the kidneys. Increased ADH activity impairs the kidney’s ability to dilute urine, resulting in decreased excretion of ingested water and a highly concentrated and decreased volume of urine. If fluid intake is not sufficiently reduced in the setting of increased ADH activity, serum hypotonicity and hyponatremia will occur. Patients with SIADH will present with normal volume status (euvolemic) because the excess water distributes evenly throughout the body’s fluid compartments. Causes of SIADH include malignant diseases (e.g., carcinoma, lymphomas, sarcomas), pulmonary disorders (e.g., pneumonia, asthma), central nervous system disorders (e.g., meningitis, stroke, head trauma), and a number of medications.

Background The kidney is one of the major target organs affected by systemic lupus erythematosus. Although proliferative forms of lupus nephritis (LN) occur more frequently than membranous LN (MLN), the latter appears to have a more favourable outcome. Only a few studies have reported the outcome of patients with MLN. Methods A retrospective analysis of patients with biopsy-confirmed MLN from a single centre in South Africa treated from 1st January 2000 to 31st December 2009. Results The mean age of the patients (n = 42) at onset of LN was 35.0 ± 12.8 years with 73.8% of the patients being of mixed ancestry (coloureds). Eleven patients (26.2%) reached the composite end point of death or end-stage renal disease or persistent doubling of serum creatinine. The overall median survival and median renal survival times were 82.3 ± 15.5 months (95% confidence interval 52.0-112.6) and 84.5 ± 15.0 months (55.1-113.8), respectively. Also, 5-year event-free survival and renal survival were 64 and 71%, respectively. On multivariate analysis, systolic blood pressure (BP) during follow-up (P = 0.029), diastolic BP during follow-up (P = 0.020) and attainment of complete remission at 6 months (P = 0.033) were factors associated with the composite end points. Although treatment with chloroquine was not significantly associated with the composite end points (P = 0.05), we found that patients who received chloroquine had better renal survival compared with those who did not (P = 0.007). Conclusions The outcome of patients with MLN in Cape Town is poorer than for similar patients reported from other centres across the world. Better BP control may significantly influence outcome of disease in these patients.

Women with cardiac chest pain indicated by signs and symptoms of myocardial ischemia in the absence of obstructive CAD are often labelled as cardiac syndrome X (CSX). A subset of patients with CSX may have symptoms of ischemia due to microvascular dysfunction. Angina due to microvascular coronary dysfunction (MCD) is an etiologic mechanism in women with vascular dysfunction. New data provide improve understanding of coronary vascular dysfunction and resultant myocardial ischemia that characterize MCD among patients with cardiac syndrome X. MCD has an adverse prognosis and health care cost expenditure comparable to obstructive CAD. The high prevalence of this condition, particularly in women, adverse prognosis and substantial health care costs, coupled with a lack of evidence regarding treatment strategies, places MCD as a research priority area.

Background A robust human challenge model for Campylobacter jejuni is an important tool for the evaluation of candidate vaccines. The previously established model conveys a potential risk of Guillain-Barre syndrome attributable to lipooligosaccharide ganglioside mimicry. This work establishes a new C. jejuni human challenge model that uses a strain (CG8421) without ganglioside mimicry and that applies Campylobacter-specific cellular immunity screening to achieve high attack rates at lower inoculum doses. Methods Healthy Campylobacter-naive adults participated in an open-label challenge trial. Participants were dosed with C. jejuni CG8421 and followed as inpatients. Pattern of illness, bacterial shedding, and immunologic responses were determined. Results Following screening, 23 subjects received 1 X 10(6) or 1 X 10(5) colony-forming units of C. jejuni, with attack rates (percentage of patients who became ill) of 100% (1 X 10(6) colony-forming units) or 93% (1 X 10(5) colony-forming units). Every subject shed CG8421; the median time to diarrhea onset was 72.3 h (interquartile range, 53.9-99.9 h). Symptoms included abdominal cramps (74%), nausea (65%), and fever (39%). No major safety concerns occurred, including bacteremia, hypotension, or postinfectious sequelae. Unexpectedly, recrudescent infection occurred in 2 subjects (1 subject without Campylobacter-specific adaptive immune responses and 1 with azithromycin resistance acquired in vivo); both infections cleared after receipt of additional antibiotics. Cumulative Campylobacter-specific immune responses were as follows: serologic response occurred in 87% (immunoglobulin [Ig] A) and 48% (IgG) of subjects, in vitro interferon-gamma production occurred in 91% of subjects, and 96% of subjects had IgA antibody-secreting cells and fecal IgA detected. Conclusions The C. jejuni CG8421 challenge model provides a safe and effective tool, without the risk of Guillain-Barre syndrome. The model demonstrates high attack rates after lower doses of challenge inoculum, provides further understanding of immunologic responses, and permits future investigation of candidate Campylobacter vaccines.