Leveraging ongoing research to evaluate the health impacts of South Africa's salt reduction strategy: a prospective nested cohort within the WHO-SAGE multicountry, longitudinal study.

INTRODUCTION: Attempting to curb the rising epidemic of hypertension, South Africa implemented legislation in June 2016 mandating maximum sodium levels in a range of manufactured foods that contribute significantly to population salt intake. This natural experiment, comparing two African countries with and without salt legislation, will provide timely information on the impact of legislative approaches addressing the food supply to improve blood pressure in African populations. This article outlines the design of this ongoing prospective nested cohort study. METHODS AND ANALYSIS: Baseline sodium intake was assessed in a nested cohort of the WHO Study on global AGEing and adult health (WHO-SAGE) wave 2 (2014-2015), a multinational longitudinal study on the health and well-being of adults and the ageing process. The South African cohort consisted of randomly selected households (n=4030) across the country. Spot and 24-hour urine samples are collected in a random subsample (n=1200) and sodium, potassium, creatinine and iodine analysed. Salt behaviour and sociodemographic data are captured using face-to-face interviews, alongside blood pressure and anthropometric measures. Ghana, the selected control country with no formal salt policy, provided a nested subsample (n=1200) contributing spot and 24-hour urine samples from the SAGE Ghana cohort (n=5000). Follow-up interviews and urine collection (wave 3) in both countries will take place in 2017 (postlegislation) to assess change in population-level sodium intake and blood pressure. ETHICS AND DISSEMINATION: SAGE was approved by the WHO Ethics Review Committee (reference number RPC149) with local approval from the North-West University Human Research Ethics Committee and University of the Witwatersrand Human Research Ethics Committee (South Africa), and University of Ghana Medical School Ethics and Protocol Review Committee (Ghana). The results of the study will be published in peer-reviewed international journals, presented at national and international conferences, and summarised as research and policy briefs.

Leptin links with plasminogen activator inhibitor-1 in human obesity: the SABPA study.

The relationship between obesity and the development of cardiovascular disease is well established. However, the underlying mechanisms contributing to vascular disease and increased cardiovascular risk in the obese remain largely unexplored. Since leptin exerts direct vascular effects, we investigated leptin and the relationship thereof with circulating markers of vascular damage, namely plasminogen activator inhibitor-1 antigen (PAI-1(ag)), von Willebrand factor antigen (vWF(ag)) and urinary albumin-to-creatinine ratio (ACR). The study included a bi-ethnic population of 409 African and Caucasian teachers who were stratified into lean (<0.5) and obese (⩾0.5) groups according to waist-to-height ratio. We obtained ambulatory blood pressure measurements and determined serum leptin levels, PAI-1(ag), vWF(ag) and ACR, as markers of vascular damage. The obese group had higher leptin (P<0.001) and PAI-1(ag) (P<0.001) levels and a tendency existed for higher vWF(ag) (P=0.068). ACR did not differ between the two groups (P=0.21). In single regression analyses positive associations existed between leptin and all markers of vascular damage (all P<0.001) only in the obese group. After adjusting for covariates and confounders in multiple regression analyses, only the association between leptin and PAI-1(ag) remained (R(2)=0.440; ß=0.293; P=0.0021). After adjusting for gender, ethnicity and age, additional analyses indicated that leptin also associated with fibrinogen and clot lysis time in both lean and obese groups, which in turn is associated with 24- h blood pressure and pulse pressure. This result provides evidence that elevated circulating leptin may directly contribute to vascular damage, possibly through mechanism related to thrombotic vascular disease.

Autonomic activity and leptin in Africans and whites: the SABPA study.

OBJECTIVES: Evidence exists that leptin enhances sympathetic activity and may thereby contribute to the development of obesity-related hypertension. Sympathetic activation also seems more prominent in Africans than whites. We compared leptin levels, and different markers of autonomic activity between Africans and whites, and determined whether a relationship exists between leptin and autonomic activity. METHODS: The study included 409 African and white school teachers (aged, 44.6 ±â€Š9.6 years). We determined leptin in serum and measured ambulatory blood pressure. Markers reflecting autonomic activity included renin, cortisol, baroreflex sensitivity, ambulatory heart rate and heart rate variability (HRV) components (assessed by 24-h ECG recordings in the frequency and geometric domain). RESULTS: Africans had higher leptin levels, BMI, blood pressure and heart rate (all P < 0.001) as well as lower HRV triangular index and HRV total power (P < 0.001). After also adjusting for BMI in multivariate regression analyses, in African men, renin (ß = 0.228; P = 0.033), night-time heart rate (ß = 0.184; P = 0.034), HRV triangular index (ß = -0.230; P = 0.010) and HRV total power (ß = -0.214; P = 0.046) associated with leptin. In white men, leptin associated with 24-h heart rate (ß = 0.376; P < 0.001), as well as day and night-time heart rate (both P < 0.01), HRV triangular index (ß = -0.335; P < 0.001) and HRV total power (ß = -0.403; P < 0.001). In African women, we observed an association of leptin with the total power component of HRV (ß = -0.221; P = 0.015) and a borderline association with renin (ß = 0.219; P = 0.057). No significant associations were apparent in the white women. CONCLUSION: We found that leptin is independently associated with different markers of autonomic activity, especially in men.

Carotid cross-sectional wall area is significantly associated with serum leptin levels, independent of body mass index: the SABPA study.

Hypertension and obesity are serious health burdens in sub-Saharan Africa. Urbanized Africans seem to be more susceptible to the development of these diseases than Caucasians. Current research suggests that leptin may be an important contributor to the development of hypertension and atherosclerosis. The aim of this study was to investigate leptin levels and their associations with cardiovascular function in urbanized Africans and Caucasians. Serum leptin, ambulatory blood pressure and carotid intima-media thickness were measured, and the cross-sectional wall area (CSWA) was calculated. The results showed that Africans had higher leptin levels (P<0.001), ambulatory blood pressure (P<0.001), carotid intima-media thickness (P<0.01) and CSWA (P<0.01) than Caucasians. As we found no interaction between ethnicity and gender for the association between leptin and the cardiovascular variables, we focused mainly on the total group of Africans and Caucasians. In single, partial and multiple regression analyses, positive associations of ambulatory systolic blood pressure (ß=0.256; P<0.001), diastolic blood pressure (ß=0.143; P=0.012), pulse pressure (ß=0.327; P<0.001) and CSWA (ß=0.107; P=0.038) with leptin were observed. Even after adjusting for body mass index (BMI), the association between CSWA (ß=0.107; P=0.038) and leptin remained. Our findings therefore suggest that leptin may contribute to the development of atherosclerosis, independent of BMI.