Determinants of left ventricular hypertrophy and its regression in people of African ancestry in South Africa

ABSTRACT There is substantial evidence to suggest that independent of conventional BP, LV mass (LVM) is higher in African-Americans than in European-Americans a difference that may translate into a higher prevalence of cardiovascular diseases. In the present thesis I assessed whether LVM is similarly elevated in groups of African descent living in Africa, and subsequently whether 24-hour, day or night BP or indices of arterial stiffness could explain the variability in LVM beyond conventional BP in this population group. As there is considerable controversy as to whether 24-hour BP measurements are better predictors of the regression of LVH than conventional BP and whether antihypertensive agents that target the renin-angiotensin system (RAS) regress LV hypertrophy (LVH) independent of BP in groups of African descent, in the present thesis I therefore also assessed these questions. In 141 healthy adult participants obtained from a random sample of nuclear families (n=399) of African ancestry living in Soweto, I determined that LVM adjusted for body surface area to the first power was an appropriate allometric signal to account for growth effects on LVM. The allometric signals established in other populations considerably over-adjusted for LVM in the group that I studied with marked negative relations noted. After adjusting for body surface area I noted upper thresholds of LVM index (LVMI) of 134 g/m2 for men and 112 g/m2 for women. As compared to thresholds described for other population samples these thresholds were noted to be modestly higher. In 187 women from randomly recruited nuclear families of African ancestry, after appropriate adjustments, conventional BP was as closely associated with LVMI as 24- hour BP, and daytime BP was as closely associated with LVMI as night-time BP in women. However, in 110 men from randomly recruited nuclear families of African ancestry, after appropriate adjustments, only night-time BP was associated with LVMI, an effect that was independent of conventional BP (r=0.21, p<0.05). Indices of nocturnal decreases in BP were not associated with LVMI in either gender group. Furthermore, in randomly recruited nuclear families of African ancestry, after appropriate adjustments, including systolic BP or pulse pressure, pulse wave velocity (an index of arterial stiffness assessed using applanation tonometry) was independently associated with LVMI in women (n=204, r=0.25, p<0.0005), but not in men (n=123, r=-0.07). In 173 hypertensive patients of African descent of whom 64 were previously untreated and 109 were previously treated, I assessed whether ambulatory BP is a better predictor of on-treatment decreases in LVMI over a 4 month treatment period. In the previously untreated patients, the regression in LVMI correlated to a similar degree (p<0.09) with decreases in conventional (r=0.34; p<0.005) and 24-hour (r=0.26; p<0.04) systolic BP. In this same study sample followed prospectively for 25 months, accounting for effects on ambulatory BP at each time point, the use of the angiotensin-converting enzyme inhibitor, enalapril, was not associated with LVMI, whereas, on-treatment conventional systolic BP (p=0.01) and night-time systolic BP (p=0.01) were associated with LVMI. In a further study conducted in 87 patients of African ancestry with hypertension and LVH, I showed that changes in systolic ambulatory BP (daytime, r=0.46, p=0.006) were predictive of changes in LVMI after 2 months of treatment with an angiotensin II receptor blocker (candesartan), ACE-I (ramipril) and the diuretic agent, hydrochlorothiazide. Moreover, in a final study I showed that in hypertensive patients of African ancestry, initiating therapy with the diuretic, indapamide SR and then adding the ACE-I, perindopril 4 mg (n=42), was equally as effective as amlodipine (calcium channel blocker) (n=44) therapy at reducing ambulatory BP and LVMI. Thus, in conclusion, groups of African descent living in Africa have only marginally higher thresholds for LVM than other population groups. Moreover, in this population group, nocturnal BP has a conventional BP-independent effect on LVMI in men, but not in women, whereas arterial stiffness has a conventional BP-independent effect on LVMI in women, but not in men. Further, in this population, reductions in LVM produced by antihypertensive therapy appear to be equally as closely related to conventional as ambulatory BP and in contrast to findings in groups of European ancestry, where RAS blockers produce unique benefits on LVM beyond conventional BP reductions, in groups of African ancestry in Africa, RAS blockers produce no BPindependent reductions in LVM. Moreover, in this population, decreases in LVM in patients with LVH produced by RAS blockers are related to ambulatory BP changes and despite the ineffectiveness of RAS blockers on BP when used as monotherapy in this population, RAS blockers together with diuretics are equally as effective in decreasing BP and LVM as compared to a class of antihypertensive agents with established efficacy (calcium channel blockers). Hence when compelling indications for RAS blockade exist, RAS blocker-diuretic combinations are effective therapy in patients of African descent living in Africa

Pasteur\u27s legacy featured at UM shows, lecture

AIMS: Left atrial (LA) volume is an important predictor of morbidity and mortality in cardiovascular disease. Left atrial strain is a feasible technique for assessing LA function. The EchoNoRMAL study recently highlighted the possibility that ethnic-based differences may exist in LA size. There is a paucity of data regarding LA parameters in an African population. We sought to establish normative values for LA volumetric and strain parameters in a black population. METHODS AND RESULTS: This cross-sectional study comprised 120 individuals between 18 and 70 years of age. Left atrial volumes were measured by biplane Simpson\u27s method, and strain parameters were measured using Philips QLAB 9 (Amsterdam, The Netherlands) speckle-tracking software. The mean age was 38.7 ± 12.8 years (50% male). Maximum LA volume indexed (LAVi), pre-atrial LAVi, and minimum LAVi were 19.7 ± 5.9, 12.2 ± 4.4, and 7.7 ± 3.2 mL/m(2), respectively. Females had a higher LAVi compared with males (20.9 ± 6.3 vs. 18.6 ± 5.3 mL/m(2), P = 0.04). Peak global longitudinal strain in the reservoir phase (ɛR) was 39.0 ± 8.3%, and the peak LA strain in the contractile phase (ɛCT) was -2.7 ± 2.5%. No gender differences were noted in ɛR. Body surface area, age, and weight were the main determinants of ɛR on multivariate linear regression analysis. CONCLUSION: The data reported in this study establish the normal reference values for phasic LA volumes and strain in a normal black population and serve as a platform for future studies

The relationship between the nitric oxide synthase gene and the risk of hypertension defi ned according to ambulatory blood pressures

Although nitric oxide (NO) plays an important role in blood pressure (BP) control, whether variation of genes involved in regulating the synthesis of NO infl uences BP is uncertain. As the heritability of BP is stronger for ambulatory than it is for conventional BP, we assessed the independent association of the well described functional exon 7 Glu298Asp variant of the eNOS gene with the presence of hypertension in 511 randomly selected normotensive control participants and 503 hypertensives with a diagnosis of hypertension confi rmed with 24-hour ambulatory BP profiles whilst off therapy. We also assessed the relationship between eNOS genotype and 24 hour ambulatory BP. Comparisons of genotype and allele frequencies indicated a lack of association of the exon 7 Glu298Asp gene variant with hypertension (Odds ratio of genotype predicting the presence of hypertension=0.97, confidence interval=0.70-1.30, p=0.92). However, patients with the Glu/Glu genotype of the Glu298Asp variant (n=424) had increased 24-hour systolic and diastolic blood pressures (152±1/97±1 mm Hg) in comparison to patients heterozygous for the Glu298Asp variant or homozygous for the 298Asp allele (n=79) (145±1/94±1 mm Hg, p‹0.005 for systolic BP and p‹0.001 for diastolic BP after multiple adjustments including age, gender, body mass index and the presence of diabetes mellitus). Differences in systolic and diastolic BP between genotype groups were noted during the day as well as at night. The association of eNOS genotype with ambulatory BP translated into an increased risk of more severe grades of hypertension in patients with the Glu/Glu genotype (grade II and III vs. grade I, Odds ratio=2.20, confidence interval=1.34-3.59, p‹0.0002). In conclusion, a functional gene variant (Glu298Asp) at the eNOS locus contributes ~1.4-2.5% to the variation in ambulatory blood pressure within hypertensives, but is not associated with the presence of hypertension in patients in whom the diagnosis has been confirmed by 24-hour ambulatory BP values. The relationship between eNOS genotype and 24-hour ambulatory BP and the severity of hypertension warrants further study

Relationships between plasma amino acid concentrations and blood pressure in South Africans of African descent

Oral supplementation with the amino acid arginine, the precursor of the vasodilator nitric oxide (NO), is associated with a reduction in blood pressure (BP). However, it is uncertain whether a decreased plasma arginine concentration predicts increases in BP. We assessed the relationship between fasting plasma arginine or other amino acid concentrations and 24 hour ambulatory BP in 75 nevertreated participants recruited from the Johannesburg area, 55 of whom were male. Plasma amino acid concentrations were measured with high performance liquid chromatography-mass-spectrometry. Plasma arginine concentrations were not inversely correlated with ambulatory BP. However, plasma arginine concentrations were increased in 36 participants with a mean daytime systolic BP &gt;140 mm Hg (61 ± 17 μmol/L) as compared to the remaining participants (54 ± 15 μmol/L, p‹0.05). Moreover, plasma arginine concentrations were positively correlated with 24-hour diastolic BP (r=0.26, p‹0.05). In males with a BMI‹30kg/m2, plasma arginine concentrations were positively correlated with both night diastolic (r=0.46, p‹0.005) and systolic (r=0.42, p‹0.005) BP. In a multivariate model with adjustments for age gender, body mass index, and other amino acid concentrations, plasma arginine concentrations were independently and positively associated with night diastolic BP (p‹0.05). In conclusion plasma arginine concentrations are positively associated with ambulatory BP in a group of participants of African descent in South Africa. These data do not support the notion that deficiencies of arginine, the amino acid substrate for NO, are related to increases in BP in groups of African ancestry living in South Africa. However, as with other ethnic groups, the positive relationship between plasma arginine concentrations and BP suggests a reduced capacity to utilise the amino acid substrate for NO synthesis

Spectrum of cardiac disease in maternity in a low-resource cohort in South Africa

Background: Lack of evidence-based data on the spectrum of cardiovascular disease (CVD) in pregnancy or in the postpartum period, as well as on maternal and fetal outcome, provides challenges for treating physicians, particularly in areas of low resources. The objectives of this study were to investigate the spectrum of disease, mode of presentation and maternal and fetal outcome of patients referred to a dedicated Cardiac Disease and Maternity Clinic (CDM). Methods: The prospective cohort study was conducted at a single tertiary care centre in South Africa. Two hundred and twenty-five women presenting with CVD in pregnancy, or within 6 months postpartum, were studied over a period of 2 years. Clinical assessment, echocardiography and laboratory tests were performed at baseline and follow-up visits. Prepartum, peripartum and postpartum complications were grouped into cardiac, neonatal and obstetric events. Results: Ethnicity was black African (45%), mixed ethnicity (32%), white (15%), Indian/others (8%) and 12% were HIV positive. Of the 225 consecutive women (mean age 28.8±6.4), 196 (86.7%) presented prepartum and 73 in modified WHO class I. The 152 women presenting in a higher risk group (modified WHO class II-IV) were offered close follow-up at the CDM clinic and were diagnosed with congenital heart disease (32%, 15 operated previously), valvular heart disease (26%, 15 operated previously), cardiomyopathy (27%) and other (15%). Women presenting with symptoms of CVD or heart failure postpartum (n=30) presented in a higher New York Heart Association, had higher heart rates (p42 days postpartum. Perinatal death occurred in 1/152 (0.7%) - translating to a perinatal mortality rate of 7/1000 live births. Conclusions: Disease patterns were markedly different to that seen in the developed world. However, joint obstetric-cardiac care in the low-resource cohort was associated with excellent survival outcome rates of pregnant mothers (even with complex diseases) and their offspring and was similar to that seen in the western world. Mortality typically occurred in the postpartum period, beyond the standard date of recording maternal death

Antiphospholipid antibodies in black south africans with hiv and acute coronary syndromes: prevalence and clinical correlates

<p>Abstract</p> <p>Background</p> <p>HIV infection is associated with a high prevalence of antiphospholipid antibodies (aPL) and increased thrombotic events but the aetiopathogenic link between the two is unclear.</p> <p>Findings</p> <p>Prospective single centre study from Soweto, South Africa, comparing the prevalence of aPL in highly active anti-retroviral therapy (HAART) naïve HIV positive and negative patients presenting with Acute Coronary Syndromes (ACS). Between March 2004 and February 2008, 30 consecutive black South African HIV patients with ACS were compared to 30 black HIV negative patients with ACS. The HIV patients were younger (43 ± 7 vs. 54 ± 13, p = 0.004) and besides smoking (73% vs. 33%, p = 0.002) and lower HDL levels (0.8 ± 0.3 vs. 1.1 ± 0.4, p = 0.001) had fewer risk factors than the control group. HIV patients had a higher prevalence of anticardiolipin (aCL) IgG (47% vs. 10%, p = 0.003) and anti-prothrombin (aPT) IgG antibodies (87% vs. 21%, p < 0.001) but there was no difference in the prevalence of the antiphospholipid syndrome (44% vs. 24%, p = N/S) and aPL were not predictive of clinical or angiographic outcomes.</p> <p>Conclusions</p> <p>Treatment naïve black South African HIV patients with ACS are younger with fewer traditional coronary risk factors than HIV negative patients but have a higher prevalence and different expression of aPL which is likely to be an epiphenomenon of the HIV infection rather than causally linked to thrombosis and the pathogenesis of ACS.</p

Closing the barrier between disease and health outcomes in Africa through research and capacity development

Background: While the burden of disease in Africa is high, health research emanating from the continent is low. Building human capacity and research infrastructure to close the gap between research and disease is thus of great imporatance. Objective: In order to improve research outputs and postgraduate training in the Faculty of Health Sciences, University of the Witwatersrand, the Health Sciences Research Office put in place a series of strategic initiatives over time. Methods: A range of strategic activities, for both postgraduate students and academic staff, were developed in parallel and sequentially over a period of approximately nine years (2008–2016). The latter years were a time of consolidation of the programmes. Outcomes of these activities were ‘measured’ by increases in publications, decreases in time to graduation and enrichment of the research environment. Results: A doubling of research publications and an increase in citations occurred over the period under review. In addition, there was a decrease in the time postgraduate students took to graduate. Conclusions: A varied, but structured research management plan may be of value in African and other developing health sciences institutions to enable the increase in research outputs and capacity development, desperately needed to close the barrier between disease and health

Circulating biomarkers in the early detection of hypertensive heart disease: usefulness in the developing world

Although the varying phenotypic spectra of hypertensive heart disease (HHD) can be assessed by electrocardiography (ECG), echocardiography and cardiovascular magnetic resonance (CMR), ECG criteria for left ventricular hypertrophy (LVH) are insensitive, while echocardiography and CMR are expensive, less readily available and often lack requisite expertise. Consequently, the use of circulating biomarkers in the diagnosis and prognostication of HHD beyond the traditional N-terminal pro- b-type natriuretic peptide (NT-proBNP) and B-type natriuretic peptide (BNP) have become an attractive alternative. We carried out a PubMed and Google Scholar databases’ search of original articles on circulating biomarkers used in the diagnosis of the different spectrum of HHD over the last 10 years [2005–2015] in humans. Fourteen studies met the inclusion criteria with NT-pro BNP being the most studied circulating biomarker in HHD followed by soluble ST2 (sST2). There is a lack of data on the use of circulating biomarkers in HHD. There is a need to explore further this area of investigative cardiology

Progress in transforming a health sciences postgraduate cohort in a south african research-intensive institution, 2008–2017

Abstract Background Equity redress in the higher education and health sectors is a global discourse that seeks to address the inequalities caused by past discrimination practices. The apartheid regime in South Africa fragmented both the higher education and the health sectors, creating White and male dominated systems. Consequently, Black Africans and females were under-represented in these sectors. Furthermore, the provision of higher education including medical training was unequal between the different populations. As democracy was established in South Africa in 1994, it is necessary to assess whether transformation in population affinity and sex of postgraduate students in the higher education and health sector has occurred, as these individuals are crucial for providing the future academic workforce and also healthcare to the public. Methods The demographic profile of postgraduate students graduating in a health sciences facility in South Africa over the period 2008–2017 was retrospectively assessed. Survival analysis models were used to investigate the time taken to graduate. Log-rank tests were used to compare the completion rates. Results More females (53.3%) than males (41.9%) completed their postgraduate degree over the period 2008–2017 (p˂0.0001). In relation to population affinity, more White students (56.4%) than Black African students (40.8%) completed their degrees overall (p˂0.0001). Conclusion While transformation occurred in the sex of graduating students over the ten year period, the same change has not occurred with regards to population affinity. The under-representation of Black African graduates is a major setback for efforts to diversify the South African higher education and health sectors. Transformation of the demographic profile of postgraduate students at South African institutions is vital for developing individuals who will contribute to equitable redress of academic staff in the higher education sector and also of the healthcare workforce. Diversified health personnel including highly skilled clinician scientists will aid in improving the provision of health care to communities particularly the underpriviledged rural areas, and also assist in training the next generation of healthcare staff. The challenges identified in this study may assist other countries where adequate transformation of the education and health sectors has not occurred

Population-Based Temporal Trends and Ethnic Disparity in Cervical Cancer Mortality in South Africa (1999–2018): A Join Point and Age–Period–Cohort Regression Analyses

Cervical cancer is one of the leading causes of cancer deaths among women in low- and middle-income countries such as South Africa. The current impact of national cervical cancer control and sexual and reproductive health interventions in South Africa reduce its burden. The aim of this study was to assess the trends in cervical cancer mortality and its relation to breast and gynaecological cancers in South Africa from 1999 to 2018. We conducted joinpoint regression analyses of the trends in crude and age-standardised mortality rates (ASMR) for cervical cancer mortality in South Africa from 1999 to 2018. An age–period–cohort regression analysis was also conducted to determine the impact of age, period, and cohort on cervical cancer mortality trends. Analyses were stratified by ethnicity. Cervical cancer (n = 59,190, 43.92%, 95% CI: 43.65–44.18%) was responsible for about 43.9% of breast and gynecological cancer deaths. The mortality rate of cervical cancer (from 11.7 to 14.08 per 100,000) increased at about 0.9% per annum (Average Annual Percent Change (AAPC): 0.9% (AAPC: 0.9%, p-value p-value < 0.001) had increased rates. The risk of cervical cancer mortality increased among successive birth cohorts. In 2018, cervical cancer mortality rate among Blacks (16.74 per 100,000 women) was about twice the rates among Coloureds (8.53 deaths per 100,000 women) and approximately four-fold among Indians/Asians (4.16 deaths per 100,000 women), and Whites (3.06 deaths per 100,000 women). Cervical cancer control efforts should be enhanced in South Africa and targeted at ethnic difference, age, period, and cohort effects