Hendrik Stefanus Steyn

Cohort Profile: Sympathetic activity and Ambulatory Blood Pressure in Africans (SABPA) prospective cohort study

Adapting to an over-demanding stressful urban environment may exhaust the psychophysiological resources to cope with these demands, and lead to sympathetic nervous system dysfunction. The evidence that an urban-dwelling lifestyle may be detrimental to the cardiometabolic health of Africans motivated the design of the Sympathetic activity and Ambulatory Blood Pressure in African Prospective cohort study. We aimed to determine neural mechanistic pathways involved in emotional distress and vascular remodelling. The baseline sample included 409 teachers representing a bi-ethnic sex cohort from South Africa. The study was conducted in 2008-09 and repeated after 3-year follow-up in 2011-12, with an 87.8% successful follow-up rate. Seasonal changes were avoided and extensive clinical assessments were performed in a well-controlled setting. Data collection included sociodemographics, lifestyle habits, psychosocial battery and genetic analysis, mental stress responses mimicking daily life stress (blood pressure and haemostatic, cardiometabolic, endothelial and stress hormones). Target organ damage was assessed in the brain, heart, kidney, blood vessels and retina. A unique highly phenotyped cohort is presented that can address the role of a hyperactive sympathetic nervous system and neural response pathways contributing to the burden of cardiometabolic diseases in Africans.

Specific coping strategies of Africans during urbanization: Comparing cardiovascular responses and perception of health data

Specific coping mechanisms of Africans during urbanization were compared to and correlated with cardiovascular responses and perception of health data. Subjects included men (N=286) and women (N=360). The COPE questionnaire classified subjects as active (AC) or passive (PC) copers and the General Health Questionnaire measured subjective perception of health. The Finapres recorded blood pressure continuously before and during application of a handgrip test. Analyses adjusting for age, body mass index and resting cardiovascular data revealed that AC rural subjects showed predominantly cardiac responses and PC rural subjects predominantly vascular responses. All urbanized African men and women showed higher resting blood pressure, vascular responsiveness and hypertension prevalences than their rural counterparts. All rural AC subjects, especially women, and all urban PC subjects, especially men, reported a poorer perception of health. In conclusion, subjects with a PC style showed a predominantly vascular response in rural and urban areas whereas subjects with an AC style seem to shift from a predominant cardiac output response to a predominant vascular resistance response when moving from a rural to an urban area.

Hypnotherapeutic Ego Strengthening with Male South African Coronary Artery Bypass Patients

Abstract Morbidity (i.e., elevated anxiety and depression) is a common feature of coronary artery bypass surgery (CABS) patients, pre- and postoperatively. Since hypnotherapy can possibly reduce morbidity in CABS patients, the aim of this study was to determine the feasibility of hypnotherapeutic ego strengthening (HES) to facilitate patient coping with concomitant anxiety and depression. Fifty patients were randomly assigned to a non-intervention control group (n = 25) and an experimental group (n = 25) and exposed to a pre- and postoperative HES intervention. Anxiety and depression were assessed with the Beck Depression Inventory and Profile of Mood States, administered preoperatively, at discharge, and at 6-week follow-up. Findings confirmed large practical reductions of anxiety and depression in the experimental group and were maintained at follow-up, while a trend towards increased depression levels occurred in the control group. Although not generalizable, results suggest broadened applications of hypnotherapy with patients in cardiac centers.

Dual radiolabeling as a technique to track nanocarriers: the case of gold nanoparticles.

Gold nanoparticles (AuNPs) have shown great potential for use in nanomedicine and nanotechnologies due to their ease of synthesis and functionalization. However, their apparent biocompatibility and biodistribution is still a matter of intense debate due to the lack of clear safety data. To investigate the biodistribution of AuNPs, monodisperse 14-nm dual-radiolabeled [14C]citrate-coated [198Au]AuNPs were synthesized and their physico-chemical characteristics compared to those of non-radiolabeled AuNPs synthesized by the same method. The dual-radiolabeled AuNPs were administered to rats by oral or intravenous routes. After 24 h, the amounts of Au core and citrate surface coating were quantified using gamma spectroscopy for 198Au and liquid scintillation for the 14C. The Au core and citrate surface coating had different biodistribution profiles in the organs/tissues analyzed, and no oral absorption was observed. We conclude that the different components of the AuNPs system, in this case the Au core and citrate surface coating, did not remain intact, resulting in the different distribution profiles observed. A better understanding of the biodistribution profiles of other surface attachments or cargo of AuNPs in relation to the Au core is required to successfully use AuNPs as drug delivery vehicles.

The effect of the Pheroid delivery system on the in vitro metabolism and in vivo pharmacokinetics of artemisone.

Objectives: The objectives were to determine the pharmacokinetics (PK) of artemisone and artemisone formulated in the Pheroid® drug delivery system in primates and to establish whether the formulation affects the in vitro metabolism of artemisone in human and monkey liver and intestinal microsomes. Methods: For the PK study, a single oral dose of artemisone was administered to vervet monkeys using a crossover design. Plasma samples were analyzed by means of liquid chromatography-tandem mass spectrometry. For the in vitro metabolism study, clearance was determined using microsomes and recombinant CYP3A4 enzymes, and samples were analyzed by means of ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry. Results: Artemisone and M1 plasma levels were unexpectedly low compared to those previously recorded in rodents and humans. The in vitro intrinsic clearance (CLint) of the reference formulation with monkey liver microsomes was much higher (1359.33 ± 103.24 vs 178.86 ± 23.42) than that of human liver microsomes. The in vitro data suggest that microsomal metabolism of artemisone is inhibited by the Pheroid delivery system. Conclusions: The in vivo results obtained in this study indicate that the Pheroid delivery system improves the PK profile of artemisone. The in vitro results indicate that microsomal metabolism of artemisone is inhibited by the Pheroid delivery system.

Cardiometabolic markers to identify cardiovascular disease risk in HIV-infected black South Africans

BACKGROUND The prevalence of HIV is the highest in sub-Saharan Africa; South Africa (SA) is one of the most affected countries with the highest number of adults living with HIV infection in the world. Besides the traditional risk factors for cardiovascular disease (CVD) in the general population, in people living with HIV there are specific factors - chronic inflammation, metabolic changes associated with the infection, therapy, and lipodystrophy - that potentially increase the risk for developing CVD. OBJECTIVE This study proposes a screening discriminant model to identify the most important risk factors for the development of CVD in a cohort of 140 HIV-infected black Africans from the North West Province, SA. METHODS Anthropometric measures, systolic blood pressure, diastolic blood pressure and the carotid-dorsalis pedis pulse wave velocity were determined. Blood was analysed to determine the levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, triglycerides (TGs) and glucose. Partial least squares discriminant analysis was performed as a supervised pattern recognition method. Independent Students t-tests were further employed to compare the means of risk factors on interval scales; for comparison of categorical risk factors between groups, chi2 tests were used. RESULTS A TG:HDL-C ratio > or = 1.49, TC:HDL-C ratio > or = 5.4 and an HDL-C level < or = 0.76 mmol/l indicated CVD risk in this cohort of patients living with HIV. CONCLUSION The results have important health implications for black Africans living with HIV as these lipid levels may be a useful indicator of the risk for CVD.

Low testosterone and hyperkinetic blood pressure responses in a cohort of South African men: the SABPA study

Hypertension (HT) and the metabolic syndrome are major problems in Africa. The role of sex hormones in the cardiovascular profile of black Africans in South Africa has not been studied. Our objective was to study the association between the sex hormones and ambulatory blood pressure and the heart rate (HR) in black and white South Africans. The 24-hour ambulatory blood pressure measurements were performed and the blood samples were taken between 07:00 and 09:00 hours. A total of 80 black and 98 white South African teachers between 25 and 65 years of age from similar socioeconomic backgrounds from the Sympathetic Activity and Ambulatory Blood Pressure in Africans (SABPA) study were included. As a result, a more vulnerable cardiovascular profile was observed in Africans compared with Caucasians. In the African group, low testosterone (T) explained 19%–36% of the variance in systolic blood pressure (SBP), diastolic blood pressure (DBP), and HR, whereas in the Caucasian group non-sex-hormone-binding globulin (non-SHBG)-bound T explained 27% of the variance in HR. In the African males, inverse associations between blood pressure and T (SBP: P = .08; DBP: P = .02) and non-SHBG-bound T (SBP: P < .001; DBP: P < .01) and HR (P < 0.01) were observed. Ambulatory HR predicted a prediabetic state in Africans. In conclusion, low T levels may predispose or result in impaired cardiovascular function in African men. The possibility exists that a prediabetic state, vagal-impaired HR, and hyperkinetic blood pressure responses may predispose or result in low T levels in African men.

Chronic defensiveness and neuroendocrine dysfunction reflect a novel cardiac troponin T cut point : the SABPA study

BACKGROUND Sympatho-adrenal responses are activated as an innate defense coping (DefS) mechanism during emotional stress. Whether these sympatho-adrenal responses drive cardiac troponin T (cTnT) increases are unknown. Therefore, associations between cTnT and sympatho-adrenal responses were assessed. METHODS A prospective bi-ethnic cohort, excluding atrial fibrillation, myocardial infarction and stroke cases, was followed for 3 years (N=342; 45.6±9.0years). We obtained serum high-sensitive cTnT and exposure measures [Coping-Strategy-Indicator, depression/Patient-Health-Questionnarie-9, 24h BP, 24h heart-rate-variability (HRV) and 24h urinary catecholamines]. RESULTS Blacks showed moderate depression (45% vs. 16%) and 24h hypertension (67% vs. 42%) prevalence compared to Whites. A receiver-operating-characteristics cTnT cut-point 4.2ng/L predicting hypertension in Blacks was used as binary outcome measure in relation to exposure measures [AUC 0.68 (95% CI 0.60-0.76); sensitivity/specificity 63/70%; P≤0.001]. Bi-ethnic cTnT-incidence was similar (Blacks=27%, Whites=25%) with cTnT-recovery better in Blacks (9%) compared to Whites (5%), P=0.001. In cross-sectional analyses, elevated cTnT was related to DefS [OR 1.08 (95% CI 0.99-1.16); P=0.06]; 24h BP [OR 1.03-1.04 (95% CI 1.01-1.08); P≤0.02] and depressed HRV [OR 2.19 (95% CI 1.09-4.41); P=0.03] in Blacks, but not in Whites. At 3year follow-up, elevated cTnT was related to attenuated urine norepinephrine:creatinine ratio in Blacks [OR 1.46 (95% CI 1.01-2.10); P=0.04]. In Whites, a cut point of 5.6ng/L cTnT predicting hypertension was not associated with exposure measures. CONCLUSION Central neural control systems exemplified a brain-heart stress pathway. Desensitization of sympatho-adrenal responses occurred with initial neural- (HRV) followed by neuroendocrine dysfunction (norepinephrine:creatinine) in relation to elevated cTnT. Chronic defensiveness may thus drive the desensitization or physiological depression, reflecting ischemic heart disease risk at a novel 4.2ng/L cTnT cut-point in Blacks.

The protective role of oestradiol against silent myocardial ischemia and hypertension risk in South African men: The SABPA study

BACKGROUND Oestradiol has a protective effect on coronary artery health in women but the effect it has on men, is controversial. A translational approach was followed to assess whether sex hormone levels are associated with silent myocardial ischemia (SMI) and hypertension risk over a 3year period. METHODS Participants included 89 Black and 91 White men (aged 21-63years) participating in both phases of the Sympathetic activity and Ambulatory Blood Pressure in Africans prospective study. Fasting blood samples, ambulatory blood pressure and 2-lead ECG recordings were obtained. RESULTS No difference in the levels of the various baseline serum T fractions between the two ethnic groups occurred. Oestradiol of the Black men increased by 54.2% compared to a decrease of 24.1% in the White men. Changes in total oestradiol (adjusted R2=0.33, β=-0.31, p=0.023) and free oestradiol (adjusted R2=0.34, β=-0.33, p=0.019) were inversely associated with changes in SMI in the Black men but not in White men. Baseline serum nitric oxide metabolites were inversely associated with ΔSMI in the Blacks only (adjusted R2=0.33, β=-0.28, p=0.047). Chronic SMI was associated with 24h hypertension in Blacks [cut point 1.5 events: Area under the curve 0.71 (95% CI: 0.60, 0.82); p=0.006; with sensitivity/specificity 44%/94%]. CONCLUSIONS Chronic SMI events facilitated future ischemic heart disease in Black men. Up-regulated free oestradiol seems to be involved in the protection of the heart against SMI and hypertension risk in Black but not in White men. A similar protective role for testosterone could however not be shown.

Nocturnal blood pressure, 3–methoxy–4–hydroxyphenylglycol and carotid intima–media thickness: the SABPA study

BACKGROUND Research demonstrated a significant relationship between elevated nocturnal blood pressure and sympathetic hyperactivity. The study aimed to investigate possible associations between norepinephrine metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), nocturnal BP and carotid intima-media thickness (CIMT) in urban African and Caucasian men. METHODS The study included 82 African and 100 Caucasian male teachers, aged 33-56 years, recruited in the North-West Province, South Africa. Ambulatory BP and fasting saliva and blood samples were collected. B-mode ultrasound images were obtained to determine CIMT. RESULTS Despite higher usage of anti-hypertensive medication usage (p=0.039), a large number of the African men were nocturnal hypertensives (75, 61%). The nocturnal systolic blood pressure (SBP) (p<0.001), diastolic blood pressure (DBP) (p<0.001) and heart rate (p<0.001) of the African men were higher. After stratifying groups into only nocturnal hypertensives the trend was the same (SBP p<0.001; DBP p<0.001; heart rate p=0.058). In the African and Caucasian men, CIMT was linearly predicted by SBP (β=0.33, p<0.001) and DBP (β=0.24, p=0.016) respectively, but not MHPG. CONCLUSION No associations were firstly demonstrated between MHPG as sympathetic activity marker and CIMT or secondly, between MHPG and nocturnal blood pressure. Novel findings of elevated nocturnal BP evidently seem to promote structural vascular disease in urban African and Caucasian men.