Differential management and associations of dyslipidaemia and hypertension by glycaemic status in urban South Africans.

BACKGROUND: Dyslipidaemia and hypertension care have not been reported in large samples of community-based participants with known diabetes (KD) nor compared with individuals at high risk for diabetes. OBJECTIVES: To describe the management and associations of dyslipidaemia and hypertension in adults with KD, newly diagnosed diabetes (NDD) and normoglycaemia. METHODS: This urban population-based cross-sectional study comprised participants with KD, NDD and normoglycaemia. Participants at high risk for diabetes but without KD underwent oral glucose tolerance tests; those who were subsequently classified as NDD or normoglycaemic were included in this study. Data collection comprised administered questionnaires, clinical measurements and biochemical analyses. Multivariable logistic regressions determined the associations with hypertension and dyslipidaemia management in separate models. RESULTS: Among 618 participants (82% women), aged median 58 years, there were 339 participants with KD, 70 with NDD and 209 with normoglycaemia. Prevalence of hypertension (BP ≥140/90 mmHg or on treatment) and dyslipidaemia (raised low-density lipoprotein cholesterol >3 mmol/L or on treatment) was highest in KD (89% and 83%) compared with NDD (64% and 74%) and normoglycaemia (66% for both) (p<0.001). Detected or known hypertension was highest in KD (97.4%), followed by NDD (88.9%) and normoglycaemia (80.3%). Among participants with known or detected hypertension, those with KD were most likely to be treated (90.2%) compared with NDD (77.5%) and normoglycaemia (74.5.%). Hypertension control among participants on treatment was highest in KD (69.5%) compared with NDD (51.6%) and normoglycaemia (61.0%). Participants with KD had significantly higher rates of previously detected dyslipidaemia (85.1%) compared with NDD (36.5%) and normoglycaemia (35.5%). KD participants were also more likely to be treated for their previously detected dyslipidaemia (85.4%) and to be controlled when on treatment (56.3%) compared with their counterparts (NDD: 63.2% and 33.3%, normoglycaemia: 61.2% and 43.3%, respectively). Diabetes control was poor; only 20% of those with KD had HbA1c <7%. In the regression models, compared with normoglycaemia, KD was associated with hypertension detection (odds ratio (OR) 6.91, 95% confidence interval (CI) 2.25 - 21.22) and control (OR 2.05, 95% CI 1.04 - 4.02). KD compared with normoglycaemia was associated with dyslipidaemia detection (OR 10.29, 95% CI 5.21 - 20.32) and treatment (OR 3.94, 95% CI 1.68 - 9.27). Sociodemographic and cardiovascular disease risk factors were generally not associated with hypertension or dyslipidaemia management. CONCLUSION: Albeit that diabetes control was poor and required better management, dyslipidaemia and hypertension prevalence were higher and better managed in KD than NDD and normoglycaemia. Different approaches are required to improve glucose control in KD, better identify NDD and monitor and prevent diabetes in high-risk individuals. Also important would be to improve care of hypertension and dyslipidaemia in those without KD.

Depression and post-traumatic stress symptoms two years post-rape and the role of early counselling: Rape Impact Cohort Evaluation (RICE) study.

Background: Survivors of sexual violence are at higher risk of adverse mental health outcomes compared to those exposed to other interpersonal traumas.Objective: To examine the trajectory of both post-traumatic stress disorder (PTSD) and depression as well as the role of early counselling over 24 months among rape survivors.Method: The South African Rape Impact Cohort Evaluation (RICE) study enrolled women aged 16-40 years attending post-rape care services within 20 days of a rape incident (n = 734), and a comparison group (n = 786) was recruited from primary health care. Women were followed for 24 months; the main study outcomes were depression and PTSD. Reports of early supportive counselling by the exposed group were also included. The analysis included an adjusted joint mixed model with linear splines to account for correlated observations between the outcomes.Results: At 24 months, 45.2% of the rape-exposed women met the cut-off for depression and 32.7% for PTSD. This was significantly higher than levels found among the unexposed. Although a decline in depression and PTSD was seen at 3 months among the women who reported a rape, mean scores remained stable thereafter. At 24 months mean depression scores remained above the depression cut-off (17.1) while mean PTSD scores declined below the PTSD cut-off (14.5). Early counselling was not associated with the trajectory of either depression or PTSD scores over the two years in rape-exposed women with both depression and PTSD persisting regardless of early counselling.Conclusion: The study findings highlight the importance to find and provide effective mental health interventions post-rape in South Africa.

Pathways to adverse pregnancy outcomes: exploring the mediating role of intimate partner violence and depression: results from a South African rape cohort study.

Adverse pregnancy outcomes (APOs) are common occurrences that contribute to negative maternal and child health outcomes. Our aim was to test the hypothesis that trauma exposure and depression are drivers of the better-recognised risk factors for miscarriage, abortion and stillbirths. Our comparative cohort study based in Durban, South Africa recruited women who reported a recent rape (n = 852) and those who had never experienced rape (n = 853), with follow-up for 36 months. We explored APOs (miscarriage, abortion or stillbirth) among those having a pregnancy during follow-up (n = 453). Potential mediators were baseline depression, post-traumatic stress symptoms, substance abuse, HbA1C, BMI, hypertension and smoking. A structural equation model (SEM) was used to determine direct and indirect paths to APO. Overall, 26.6% of the women had a pregnancy in the follow-up period and 29.4% ended in an APO, with miscarriage (19.9%) the most common outcome, followed by abortion (6.6%) and stillbirths (2.9%). The SEM showed two direct pathways from exposure to childhood trauma, rape and other trauma, to APO which were ultimately mediated by hypertension and/or BMI, but all paths to BMI were mediated by depression and IPV-mediated pathways from childhood and other trauma to hypertension. Food insecurity mediated a pathway from experiences of trauma in childhood to depression. Our study confirms the important role of trauma exposure, including rape, and depression on APOs, through their impact on hypertension and BMI. It is critical that violence against women and mental health are more systematically addressed in antenatal, pregnancy and postnatal care.

Leveraging the South African Diabetes Prevention Programme to screen for chronic kidney disease: an observational study.

OBJECTIVE: To evaluate the viability of leveraging an existing screening programme (the South African Diabetes Prevention Programme (SA-DPP)) to screen for chronic kidney disease (CKD), by assessing the yield of CKD cases among those participating in the programme. DESIGN: Observational study conducted between 2017 and 2019. SETTING: 16 resource-poor communities in Cape Town, South Africa. PARTICIPANTS: 690 participants, aged between 25 and 65 years, identified as at high risk for type 2 diabetes mellitus (T2DM) by the African Diabetes Risk Score. PRIMARY OUTCOME MEASURE: The prevalence of CKD among those participating in the SA-DPP. RESULTS: Of the 2173 individuals screened in the community, 690 participants underwent further testing. Of these participants, 9.6% (n=66) and 18.1% (n=125) had screen-detected T2DM and CKD (defined as an estimated glomerular filtration rate (eGFR) of<60 mL/min/1.73 m2 and/or albumin-to-creatinine ratio >3 mg/mmol), respectively. Of those with CKD, 73.6% (n=92), 17.6% (n=22) and 8.8% (n=11) presented with stages 1, 2 and 3, respectively. Of the participants with an eGFR <60 mL/min/1.73 m2, 36.4% had no albuminuria and of those with normal kidney function (eGFR ≥90 mL/min/1.73 m2), 10.2% and 3.8% had albuminuria stages 2 and 3, respectively. Of those with T2DM and hypertension, 22.7% and 19.8% had CKD, respectively. CONCLUSION: The fact that almost one in five participants identified as high risk for T2DM had CKD underscores the value of including markers of kidney function in an existing screening programme. By using an opportunistic approach to screen high-risk individuals, those with CKD can be identified and appropriately treated to reduce disease progression.

Estimating the changing burden of disease attributable to high fasting plasma glucose in South Africa for 2000, 2006 and 2012.

BACKGROUND: Worldwide, higher-than-optimal fasting plasma glucose (FPG) is among the leading modifiable risk factors associated with all- cause mortality and disability-adjusted life years (DALYs) due to the direct sequelae of diabetes and the increased risk for cardiovascular and chronic kidney disease. OBJECTIVES: To report deaths and DALYs of health outcomes attributable to high FPG by age and sex for South Africa (SA) for 2000, 2006 and 2012. METHODS: Comparative risk assessment methodology was used to estimate the burden attributable to high FPG. A meta-regression analysis was performed using data from national and small-area studies to estimate the population distribution of FPG and diabetes prevalence. Attributable fractions were calculated for selected health outcomes and applied to local burden estimates from the second South African National Burden of Disease Study (SANBD2). Age-standardised rates were calculated using World Health Organization world standard population weights. RESULTS: We estimated a 5% increase in mean FPG from 5.31 (95% confidence interval (CI) 5.18 - 5.43) mmol/L to 5.57 (95% CI 5.41 - 5.72) mmol/L and a 75% increase in diabetes prevalence from 7.3% (95% CI 6.7 - 8.3) to 12.8% (95% CI 11.9 - 14.0) between 2000 and 2012. The age-standardised attributable death rate increased from 153.7 (95% CI 126.9 - 192.7) per 100 000 population in 2000 to 203.5 (95% CI 172.2 - 240.8) per 100 000 population in 2012, i.e. a 32.4% increase. During the same period, age-standardised attributable DALY rates increased by 43.8%, from 3 000 (95% CI 2 564 - 3 602) per 100 000 population in 2000 to 4 312 (95% CI 3 798 - 4 916) per 100 000 population in 2012. In each year, females had similar attributable death rates to males but higher DALY rates. A notable exception was tuberculosis, with an age-standardised attributable death rate in males double that in females in 2000 (14.3 v. 7.0 per 100 000 population) and 2.2 times higher in 2012 (18.4 v. 8.5 per 100 000 population). Similarly, attributable DALY rates were higher in males, 1.7 times higher in 2000 (323 v. 186 per 100 000 population) and 1.6 times higher in 2012 (502 v. 321 per 100 000 population). Between 2000 and 2012, the age-standardised death rate for chronic kidney disease increased by 98.3% (from 11.7 to 23.1 per 100 000 population) and the DALY rate increased by 116.9% (from 266 to 578 per 100 000 population). CONCLUSION: High FPG is emerging as a public health crisis, with an attributable burden doubling between 2000 and 2012. The consequences are costly in terms of quality of life, ability to earn an income, and the economic and emotional burden on individuals and their families. Urgent action is needed to curb the increase and reduce the burden associated with this risk factor. National data on FPG distribution are scant, and efforts are warranted to ensure adequate monitoring of the effectiveness of the interventions.

Building knowledge, optimising physical and mental health and setting up healthier life trajectories in South African women (Bukhali): a preconception randomised control trial part of the Healthy Life Trajectories Initiative (HeLTI).

INTRODUCTION: South Africa's evolving burden of disease is challenging due to a persistent infectious disease, burgeoning obesity, most notably among women and rising rates of non-communicable diseases (NCDs). With two thirds of women presenting at their first antenatal visit either overweight or obese in urban South Africa (SA), the preconception period is an opportunity to optimise health and offset transgenerational risk of both obesity and NCDs. METHODS AND ANALYSIS: Bukhali is the first individual randomised controlled trial in Africa to test the efficacy of a complex continuum of care intervention and forms part of the Healthy Life Trajectories Initiative (HeLTI) consortium implementing harmonised trials in Canada, China, India and SA. Starting preconception and continuing through pregnancy, infancy and childhood, the intervention is designed to improve nutrition, physical and mental health and health behaviours of South African women to offset obesity-risk (adiposity) in their offspring. Women aged 18-28 years (n=6800) will be recruited from Soweto, an urban-poor area of Johannesburg. The primary outcome is dual-energy X-ray absorptiometry derived fat mass index (fat mass divided by height2) in the offspring at age 5 years. Community health workers will deliver the intervention randomly to half the cohort by providing health literacy material, dispensing a multimicronutrient supplement, providing health services and feedback, and facilitating behaviour change support sessions to optimise: (1) nutrition, (2) physical and mental health and (3) lay the foundations for healthier pregnancies and early child development. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Human Ethics Research Committee University of the Witwatersrand, Johannesburg, South Africa (M1811111), the University of Toronto, Canada (19-0066-E) and the WHO Ethics Committee (ERC.0003328). Data and biological sample sharing policies are consistent with the governance policy of the HeLTI Consortium (https://helti.org) and South African government legislation (POPIA). The recruitment and research team will obtain informed consent. TRIAL REGISTRATION: This trial is registered with the Pan African Clinical Trials Registry (https://pactr.samrc.ac.za) on 25 March 2019 (identifier: PACTR201903750173871). PROTOCOL VERSION: 20 March 2022 (version #4). Any protocol amendments will be communicated to investigators, Institutional Review Board (IRB)s, trial participants and trial registries.

MicroRNAs associated with chronic kidney disease in the general population and high-risk subgroups: protocol for a systematic review and meta-analysis.

INTRODUCTION: Chronic kidney disease (CKD) is a significant health and economic burden, owing to its ever-increasing global prevalence. Due to the limitations in the current diagnostic methods, CKD is frequently diagnosed at advanced stages, where there is an increased risk of cardiovascular complications and end-stage kidney disease. As such, there has been considerable interest in microRNAs (miRNAs) as potential markers for CKD detection. This review seeks to identify all miRNAs associated with CKD and/or markers of kidney function or kidney damage in the general population and high-risk subgroups, and explore their expression profiles in these populations. METHODS AND ANALYSIS: A systematic search of published literature will be conducted for observational studies that report on miRNAs associated with CKD or kidney function or kidney damage markers (serum creatinine and cystatin C, estimated glomerular filtration rate and urinary albumin excretion) in adult humans. The electronic database search will be restricted to English and French publications up to 31 October 2021. Two investigators will independently screen and identify studies for inclusion, as well as extract data from eligible studies. Risk-of-bias and methodological quality will be assessed by the Newcastle-Ottawa Quality Assessment Scale for observational studies and Grading of Recommendations Assessment, Development and Evaluation tools. Appropriate meta-analytic techniques will be used to pool estimates from studies with similar miRNAs, overall and by major characteristics, including by country or region, sample size, gender and risk-of-bias score. Heterogeneity of the estimates across studies will be quantified and publication bias investigated. This protocol is reported according to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 guidelines. ETHICS AND DISSEMINATION: This study design does not require formal ethical clearance and findings will be published in a peer-reviewed journal. CONCLUSION: This review will provide the expression pattern of miRNAs associated with CKD. This will allow for further research into the identified miRNAs, which could later be used as biomarkers for prediction and early detection of CKD, monitoring of disease progression to advanced stages and as potential therapeutic targets. PROSPERO REGISTRATION NUMBER: CRD42021270028.

Insufficient iodine nutrition status and the risk of pre-eclampsia: a systemic review and meta-analysis.

BACKGROUND: Although subclinical hypothyroidism in pregnancy is one of the established risk factors for pre-eclampsia, the link between iodine deficiency, the main cause of hypothyroidism, and pre-eclampsia remains uncertain. We conducted a systematic review to determine the iodine nutrition status of pregnant women with and without pre-eclampsia and the risk of pre-eclampsia due to iodine deficiency. METHODS: MEDLINE, EMBASE, Google Scholar, Scopus and Africa-Wide Information were searched up to 30th June 2020. Random-effect model meta-analysis was used to pool mean difference in urinary iodine concentration (UIC) between pre-eclamptic and normotensive controls and pool ORs and incidence rates of pre-eclampsia among women with UIC <150 µg/L. RESULTS: Five eligible studies were included in the meta-analysis. There was a significant difference in the pooled mean UIC of 254 pre-eclamptic women and 210 normotensive controls enrolled in three eligible case-control studies (mean UIC 164.4 µg/L (95% CI 45.1 to 283.6, p<0.01, I2 >50)). The overall proportions of pre-eclampsia among women with UIC <150 µg/L and UIC >150 µg/L in two cross-sectional studies were 203/214 and 67/247, respectively, with a pooled OR of 0.01 (95% CI 0 to 4.23, p=0.14, I2 >50) for pre-eclampsia among women with UIC >150 µg/L. The overall incidence of pre-eclampsia among women with UIC <150 µg/L and UIC >150 µg/L in two cohort studies was 6/1411 and 3/2478, respectively, with a pooled risk ratio of 2.85 (95% CI 0.42 to 20.05, p=0.09, I2 <25). CONCLUSION: Although pre-eclamptic women seem to have lower UIC than normotensive pregnant women, the available data are insufficient to provide a conclusive answer on association of iodine deficiency with pre-eclampsia risk. PROSPERO REGISTRATION NUMBER: CRD42018099427.

Oral Microbiome Signatures in Diabetes Mellitus and Periodontal Disease.

Disturbances in the oral microbiome are associated with periodontal disease initiation and progression and diabetes mellitus (DM), but how this contributes to the cause-and-effect relationship between periodontal disease and DM is poorly understood. We examined the bacterial composition in plaque samples from 128 South Africans with periodontal disease across glycemic statuses using 16S rDNA sequencing of regions 2, 3, 4, 6-7, 8, and 9. Of the 9 phyla identified, Firmicutes, Proteobacteria, Bacteroidetes, Fusobacteria, and Actinobacteria made up >98%. Fusobacteria and Actinobacteria were significantly more abundant in subjects with diabetes, while Proteobacteria were less abundant. However, in the presence of gingival bleeding and DM, as compared with DM without gingival bleeding, Actinobacteria were markedly reduced while Bacteroidetes were more abundant. In contrast, no differences in Actinobacteria or Bacteroidetes abundance were observed between DM with and without pocket depth (PD) ≥4 mm. At the genus level, similar changes in relative abundance were observed in the presence of DM and periodontal disease. Our findings remained in conditional logistic regression models adjusted for age, sex, waist circumference, and the 5 most dominant phyla. For example, Actinobacteria significantly increased the odds of diabetes by 10% in subjects with gingival bleeding, while Fusobacteria increased this odd by 14%; yet, among subjects with PD ≥4 mm, Fusobacteria decreased the odds of DM by 47%. Our findings have confirmed the alterations in the composition of the oral microbiota across glycemic statuses as well as different stages of periodontal disease. However, it is not clear whether these differences were the consequence of hyperglycemia or the presence of periodontal diseases. Therefore, we recommend further investigations in a longitudinal study design.

Prevalence of overweight and obesity among African primary school learners: a systematic review and meta-analysis.

INTRODUCTION: The increasing trend in the global prevalence of childhood overweight and obesity presents a major public health challenge. This study reports the results of a systematic review and meta-analysis to estimate the prevalence of overweight and obesity among primary school learners residing in Africa according to the different body mass index criteria and population level characteristics. METHODS: A search of multiple databases was conducted to identify relevant research articles published between January 1980 and February 2017. Random effects models were used to pool prevalence data within and across population level characteristics after variance stabilization through arcsine transformation (PROSPERO registration number CRD42016035248). RESULTS: Data from 45 studies across 15 African countries, and comprising 92,379 and 89,468 participants for overweight and obesity estimates were included. Estimated overweight and obesity prevalence differed significantly across criteria: 10.5% [95% confidence interval, CI: 7.1-14.3] and 6.1% [3.4-9.7] by World Health Organization; 9.5% [6.5-13.0] and 4.0% [2.5-5.9] by International Obesity Task Force; and 11.5% [9.6-13.4] and 6.9% [5.0-9.0] by Centre for Diseases Control, respectively (p = 0.0027 for overweight; p < 0.0001 for obesity). Estimates were mostly higher in urban, and private schools, but generally similar by gender, major geographic regions, publication year and sample size. Substantial heterogeneity in the estimates across and within criteria were not always explained by major study characteristics. CONCLUSION: Overweight and obesity are prevalent among African primary school learners, particularly those attending urban, and private schools. The results from this meta-analysis could be helpful in making informed decisions on childhood obesity prevention efforts in African countries.

Measured Versus Calculated Small Dense LDL-Cholesterol and Cardiometabolic Traits in a South African Population.

Small-dense low density lipoprotein (sdLDL) is increasingly viewed as a marker for evaluating atherogenic risk, however its clinical uptake is hampered by the cumbersomeness of available methods. Consequently, a number of alternative methods for the estimation of sdLDL have been developed and none have been tested in a population from Africa. We evaluated an equation to estimate sdLDL-C from classic lipid parameters in South Africans. This is a cross-sectional study involving 1550 participants in which direct measurement of sdLDL in 237 participants was performed using a homogeneous enzymatic assay. Their mean age (standard deviation, SD) was 54.2 (14.7) years. 156 (65.8%) were normotolerant, 29 (12.2%) prediabetes, 17 (7.2%) screen detected diabetes and 35 (14.8%) known diabetes. Measured sdLDL values ranged from 0.17 to 3.39 versus-1.85 to 2.52 mmol/L calculated sdLDL. There was a significant positive correlation between the two measurements with a Pearson correlation coefficient of 0.659 (95%CI: 0.581-0.726). In a regression model, the adjusted R2 was 0.440 after adding age, 0.441 after further adding gender, then 0.443 with dysglycemia and lastly 0.447 upon adding body mass index. With the exception of HDL-cholesterol levels that decreased across increasing quintiles of calculated sdLDL, our data showed significant correlations between sdLDL and cardiometabolic risk factors, all p values < 0.0001. In conclusion, this study has shown that calculated sdLDL can be efficiently used to approximate population levels of sdLDL; however the modest correlation indicate that at the individual level, it will poorly approximate true sdLDL levels, with possible implications for risk stratification.

Increase in blood pressure over a 7-year period in a mixed-ancestry South African population.

BACKGROUND: An increase in the prevalence of high blood pressure (BP) has been reported globally and in the South African (SA) population. OBJECTIVES: To investigate temporal changes in absolute BP levels and hypertension prevalence in the mixed-ancestry South Africans. METHODS: Participants were from two independent cross-sectional surveys conducted during 2008/09 (N=928) and 2014/16 (N=1 969) in Bellville South, Cape Town, SA. Participants' eligibility was based on several criteria, including age >20 years and neither bedridden nor pregnant. Data were obtained by administered questionnaires, clinical measurements (BP and anthropometry) and biochemical assessments (oral glucose tolerance tests and cotinine levels). Known hypertension was based on a self-reported history of doctor-diagnosed hypertension and ongoing treatment. Comparison across years was based on the crude prevalence of hypertension as well as direct age-standardised prevalence, based on the SA 2011 mixed-ancestry population distribution, in 10-year age increments. RESULTS: In all, 708 participants (76.3%) in 2008/09 and 1 488 (75.6%) in 2014/16 were female. Between 2008/09 and 2014/16, mean systolic BP increased from 124 to 136 mmHg (absolute mean difference 15 mmHg) and mean diastolic BP from 75 to 85 mmHg (absolute mean difference 9 mmHg) in the overall sample. The prevalence of screen-detected hypertension increased from 11.6% to 24.8%, with a similar increase in males and females, while the prevalence of known cases remained stable. These changes remained significant after adjustment for age and gender. CONCLUSIONS: A rightward shift in absolute BP translated into a significant increase in the prevalence of hypertension over time in this population. The predominant increases in screen-detected hypertension suggest that the deteriorating profile was not matched by efforts to detect and manage individuals with higher-than-optimal BP levels.

Insufficient iodine nutrition status and the risk of pre-eclampsia: a protocol for systematic review and meta-analysis.

INTRODUCTION: Pre-eclampsia is one of the leading causes of maternal and perinatal morbidity and mortality worldwide. Although subclinical hypothyroidism (SCH) in pregnancy is one of the established risk factors for pre-eclampsia, the link between iodine deficiency, the main cause of hypothyroidism and pre-eclampsia remains uncertain. About two billion people live in areas with iodine insufficiency. The increased renal blood flow during pregnancy leading to increased renal iodine clearance together with the increased placental transfer of iodine to the fetus leads to further iodine deficiency in pregnancy. Iodine is one of the most potent exogenous antioxidants whose deficiency is associated with oxidant imbalance and endothelial dysfunction, one of the mechanisms associated with increased risk of pre-eclampsia. METHODS AND ANALYSIS: A systematic search of published literature will be conducted for case-control studies that directly determined the iodine nutrition status of women with pre-eclampsia and appropriate normotensive controls. A similar search will be conducted for cohort studies in which the incidence of pre-eclampsia among pregnant women with adequate and inadequate iodine nutrition status was reported. Databases including MEDLINE, EMBASE, Google Scholar, SCOPUS and Africa Wide Information will be searched up to 31 December 2018. Screening of identified articles and data extraction will be conducted independently by two investigators. Risk of bias of the included studies will be assessed using a Newcastle-Ottawa Scale. Appropriate meta-analytic techniques will be used to pool prevalence and incidence rates, odds and relative risk of pre-eclampsia from studies with similar features, overall and by geographical regions. Heterogeneity of the estimates across studies will be assessed and quantified and publication bias investigated. This protocol is reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis protocols (PRISMA-P) 2015 guidelines. ETHICS AND DISSEMINATION: Since the proposed study will use published data, there is no requirement for ethical approval. This review seeks to identify the risk of pre-eclampsia associated with insufficient iodine nutrition in pregnancy. This will help to ascertain whether insufficient iodine intake may be an independent risk factor for pre-eclampsia. This will advise policy makers on the possibility of maximising iodine nutrition in pregnancy and reproductive age as one of the remedies for prevention of pre-eclampsia among populations at risk of inadequate iodine intake. This review is part of the thesis that will be submitted for the award of a PhD in Medicine to the Faculty of Health Sciences of the University of Cape Town. In addition the results will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42018099427.

Prevalence of type 2 diabetes mellitus in women of childbearing age in Africa during 2000-2016: a systematic review and meta-analysis.

OBJECTIVES: The aim of this research was to estimate the prevalence of type 2 diabetes mellitus (T2DM), impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), in African women of childbearing age. STUDY DESIGN: Systematic review and meta-analysis of relevant African studies published from January 2000 to December 2016. DATA SOURCES: We searched several databases, including EMBASE, MEDLINE, CINAHL, grey literature and references of included studies. SETTING: Studies carried out in African communities or any population-based studies were included. PARTICIPANTS: We included studies, carried out in Africa, with non-pregnant women of childbearing age. Studies must have been published between the years 2000 and 2016. OUTCOMES: The primary outcome was prevalent T2DM. The secondary outcomes were IFG and IGT. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data and, using the adapted Hoy risk of bias tool, independently assessed for risk of bias. We used random-effects meta-analysis models to pool prevalence estimates across studies. We used Cochran's Q statistic and the I2 statistic to assess heterogeneity. RESULTS: A total of 39 studies from 27 countries were included, totaling 52 075 participants, of which 3813 had T2DM. The pooled prevalence of T2DM was 7.2% (95% CI 5.6% to 8.9%) overall and increased with age. The pooled prevalence was 6.0% (95% CI 4.2% to 8.2%) for impaired fasting glycemia while the prevalence of IGT ranged from 0.9% to 37.0% in women aged 15-24 and 45-54 years, respectively. Substantial heterogeneity across studies was not explained by major studies characteristics such as period of publication, rural/urban setting or whether a study was nationally representative or not. CONCLUSION: This review highlights the need for interventions to prevent and control diabetes in African women of childbearing age, in view of the significant prevalence of T2DM and prediabetes. PROSPERO REGISTRATION NUMBER: CRD42015027635.

Knowledge generation via publications on hypertension prevalence in population-based studies conducted in sub-Saharan Africa over 30 years: 1990 - 2019.

Hypertension prevalence in sub-Saharan Africa (SSA) is high, is rising and has emerged as the most prevalent cardiovascular disease risk factor. Research is required to provide evidence-based findings to prioritise hypertension prevention and control. This systematic review aims to describe the distribution of and trends in scientific outputs on hypertension prevalence in population-based studies in SSA over the last three decades. Relevant English-language articles documenting hypertension prevalence in population-based studies in SSA, published between 1 January 1990 and 25 April 2019, were identified through a comprehensive electronic search of MEDLINE. Of the 3 795 citations retrieved, 414 fulfilled the inclusion criteria. Scientific outputs increased incrementally per 10-year period: 1990 - 1999: n=32; 2000 - 2009: n=65; and 2010 - 2019: n=317. The greatest number of scientific outputs over the 30-year period originated from South Africa (n=81) and Nigeria (n=74). Increasing scientific outputs on hypertension prevalence in SSA have not translated into optimal hypertension management, which remains inadequate.

The association between dietary inflammatory properties and bone mineral density and risk of fracture in US adults.

BACKGROUND/OBJECTIVES: To examine the associations of dietary inflammatory index (DII) with bone mineral density (BMD) and fracture risk in adult Americans.Subjects/Method:The United States National Health and Nutrition Examination Survey participants during 2005-2010 were included if they had measured data on dietary intake and BMD. DII scores were calculated from estimated micro- and macronutrients from a single 24-h dietary recall. BMD was measured using dual-energy X-ray absorptiometry densitometers. Risk of fractures was obtained from participant self-report (ever) based on doctor information. Analyze of covariance and χ2-tests were employed, while accounting for the complex survey design. RESULTS: A total of 18 318 participants were included, with 51.3% (9397) being men. Age, sex, race, physical activity, smoking, C-reactive protein and body mass index-adjusted mean BMD (g/cm2) in different bodily sites significantly decreased across increasing quarters of the DII (all P<0.001). After further adjustment for calcium intake, the trend in BMD across DII quarters remained significant for total femur, femoral neck, trochanter and intertrochanter BMD (all P<0.001). Across increasing quarters of the DII, the proportion of fractures ranged from 1.1 to 1.5% for hip fracture (P=0.02), from 7.9 to 10.5% for wrist fracture (P<0.001) and from 2.2 to 2.7% for spine fracture (P=0.002. Prevalent wrist fractures significantly differed across DII quarters (P<0.0001), driven by high prevalence in the top quarter, while hip and spine fractures' prevalence did not vary significantly. CONCLUSIONS: The current study provides evidence suggesting a potential adverse effect of pro-inflammatory diet on bone health; which may have implications for dietary approaches for those with history of abnormal bone health complications.

Gender disparities in pulmonary hypertension at a tertiary centre in Cameroon.

BACKGROUND: Pulmonary hypertension (PH) is a potent cause of heart failure and has been little investigated in the African setting. OBJECTIVE: To investigate the effects of gender on the clinical presentation, echocardiographic features and outcomes of patients with PH in Douala, Cameroon. METHODS: A prospective cohort study was conducted from March 2012 to December 2013 as part of the Pan African Pulmonary Hypertension Cohort study. PH was diagnosed by echocardiography and defined as a right ventricular systolic pressure >35 mmHg in the absence of acute right heart failure. Patients were followed up for a maximum of 12 months for primary endpoint mortality. RESULTS: In total, 130 patients with PH were recruited; 71 (54.6%) were women. The median age was 59.2 years for men and 58.3 years for women (p=0.76). Active smoking and alcohol use were more frequent in men than women (both p<0.001), but women had greater exposure to indoor cooking fumes than men (p<0.001). Previous tuberculosis infection (11.3% v. 1.7%) and S3 gallop rhythm (30.9% v. 11.9%) were more common in women (both p<0.03). Women had a significantly higher mean systolic blood pressure (134 mmHg v. 125 mmHg; p=0.04) and pulse pressure (53.8 mmHg v. 44.9 mmHg; p=0.01) and a lower mean haemoglobin concentration (10.4 g/dL v. 12.4 g/dL; p<0.05) compared with men. Echocardiographic left ventricular (LV) systolic dysfunction was more frequent in men: mean LV ejection fraction 42.6% v. 51.5% (p=0.01) and mean fractional shortening 21.4% v. 28.6% (p=0.01). The overall mortality rate was 20.3%, and rates were similar in the two groups (Kaplan-Meier log rank 1.1; p=0.30). CONCLUSIONS: Despite differences in baseline characteristics including cardiovascular risk factors, mortality rates on follow-up were similar in men and women in this study. However, these different baseline characteristics probably suggest differences in the pathogenesis of PH in men and women in our setting that need further investigation.

The association between seven-day objectively measured habitual physical activity and 24 h ambulatory blood pressure: the SABPA study.

Few studies have examined objective physical activity in relation to 24 h ambulatory blood pressure (BP). We aimed to assess the association of 7-day objectively measured habitual physical activity with ambulatory BP in a sample of African and Caucasian school teachers (n=216, age 49.7 years) from the sympathetic activity and blood pressure in Africans prospective cohort study. Hypertension (ambulatory systolic BP⩾130 and/or diastolic BP⩾80 mm Hg) was prevalent in 53.2% of the sample, particularly in black Africans. The hypertensive group spent significantly more awake time in sedentary activity (51.5% vs 40.8% of waking hours, P=0.001), as well as doing less light- (34.1% vs 38.9%, P=0.043) and moderate-intensity (14.0% vs 19.7%, P=0.032) activities compared with normotensives, respectively. In covariate adjusted models, light-intensity activity time was associated with lower 24 h and daytime ambulatory systolic BP (ß=-0.15, 95% confidence interval (CI): -0.26, -0.05, P=0.004; ß=-0.14, CI: -0.24, -0.03, P=0.011) and diastolic BP (ß=-0.14, CI: -0.25, -0.03, P=0.015; ß=-0.13, CI: -0.24, -0.01, P=0.030), as well as resting systolic BP (ß=-0.13, CI: -0.24, -0.01, P=0.028). Sedentary time was associated only with 24 h systolic BP (ß=0.12; CI: 0.01, 0.22), which was largely driven by night-time recordings. Participants in the upper sedentary tertile were more likely to be 'non-dippers' (odds ratio=2.11, 95% CI: 0.99, 4.46, P=0.052) compared with the lowest sedentary tertile. There were no associations between moderate to vigorous activity and BP. In conclusion, objectively assessed daily light physical activity was associated with ambulatory BP in a mixed ethnic sample.

VEGF, the underlying factor for metabolic syndrome; fact or fiction?

Metabolic syndrome (MetS) is currently diagnosed by the co-presence of at least three of the five following abnormalities: abdominal obesity, dysglycaemia, elevated serum triglycerides, low high-density cholesterol (HDL) and finally elevated blood pressure. Metabolic syndrome increases the risk of developing cardiovascular disease and diabetes. This review is on the associations between MetS and vascular endothelial growth factor (VEGF). VEGF induces migration and proliferation of endothelial cells (ECs), increases vascular permeability and has a role in tumor growth, adipose tissue expansion, age-related macular degeneration and diabetic retinopathy. Circulating levels of VEGFs are elevated in obese individuals and it has also been suggested that VEGF is secreted from adipose tissues, especially from intra-abdominal adipose tissue. There is abundant evidence to support that poor glycemic control in diabetic patients is associated with increased plasma VEGF, which in turn may cause hypertension and several vascular complications in diabetic patients. Circulating VEGF levels are increased in children and young adults with type 1 diabetes mellitus and middle-aged diabetic patients with proliferative retinopathy. It has been revealed that plasma VEGF increases in patients with hyperlipidemia and may trigger the development of atherosclerosis. It can be concluded that there is a positive association between VEGF and components of MetS. Because of the importance of this relationship, more investigations are needed in this field.

Gender disparities in pulmonary hypertension at a tertiary centre in Cameroon

Background. Pulmonary hypertension (PH) is a potent cause of heart failure and has been little investigated in the African setting.Objective. To investigate the effects of gender on the clinical presentation, echocardiographic features and outcomes of patients with PH in Douala, Cameroon.Methods. A prospective cohort study was conducted from March 2012 to December 2013 as part of the Pan African Pulmonary Hypertension Cohort study. PH was diagnosed by echocardiography and defined as a right ventricular systolic pressure >35 mmHg in the absence of acute right heart failure. Patients were followed up for a maximum of 12 months for primary endpoint mortality.Results. In total, 130 patients with PH were recruited; 71 (54.6%) were women. The median age was 59.2 years for men and 58.3 years for women (p=0.76). Active smoking and alcohol use were more frequent in men than women (both p<0.001), but women had greater exposure to indoor cooking fumes than men (p<0.001). Previous tuberculosis infection (11.3% v. 1.7%) and S3 gallop rhythm (30.9% v. 11.9%) were more common in women (both p<0.03). Women had a significantly higher mean systolic blood pressure (134 mmHg v. 125 mmHg; p=0.04) and pulse pressure (53.8 mmHg v. 44.9 mmHg; p=0.01) and a lower mean haemoglobin concentration (10.4 g/dL v. 12.4 g/dL; p<0.05) compared with men. Echocardiographic left ventricular (LV) systolic dysfunction was more frequent in men: mean LV ejection fraction 42.6% v. 51.5% (p=0.01) and mean fractional shortening 21.4% v. 28.6% (p=0.01). The overall mortality rate was 20.3%, and rates were similar in the two groups (Kaplan-Meier log rank 1.1; p=0.30).Conclusions. Despite differences in baseline characteristics including cardiovascular risk factors, mortality rates on follow-up were similar in men and women in this study. However, these different baseline characteristics probably suggest differences in the pathogenesis of PH in men and women in our setting that need further investigation