Nicolaas T. Malan

Coping with urbanization: A cardiometabolic risk? The THUSA study

An assessment of specific coping styles in rural-urban Africans is done to evaluate its contribution as cardiometabolic risk factor. In total, 608 apparently healthy Africans were included in a cross-sectional comparative study from the North-West Province in South Africa. The adapted and translated COPE Questionnaire classified participants according to their responses into active (AC) or passive (PC) copers. Fasting resting metabolic syndrome (MS) indicators using the WHO definition (glucose, high density lipoproteins, waist/hip ratio, hypertension prevalence, and triglyceride) and associated MS values, i.e. fibrinogen were obtained. The Finapres recorded resting blood pressure continuously. Co-variates for all statistical analyses included age, body mass index (BMI) and lifestyle factors (alcohol consumption, smoking habits and physical activity). The only MS values prevalent in urbanized participants were higher hypertension prevalence rates and fibrinogen (women only) compared to their rural counterparts. Adding coping styles, it was mainly the urbanized AC participants that indicated higher MS values (hypertension prevalence, glucose and fibrinogen) when compared to their rural and PC counterparts. In conclusion, urbanization is associated with enhanced blood pressure and fibrinogen (women) values only. Coping as cardiometabolic risk is accentuated in the urbanized AC group, especially the men. The urbanized AC group with their higher blood pressure values and more MS indicators appears to have behaviorally an AC style but physiologically a dissociated AC style.

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.

Conventional and behavioral risk factors explain differences in sub-clinical vascular disease between black and Caucasian South Africans: the SABPA study

OBJECTIVES There is an emerging burden of cardiovascular disease among urban black Africans in South Africa, which has been largely explained by the transition from traditional African lifestyles to more westernized behavior. We examined the role of health behaviors in explaining the excess burden of sub clinical vascular disease seen in black Africans compared to Caucasians. METHODS This was a cross-sectional study, comprising of urban African teachers (n=192 black, 206 Caucasian) working for one of the four Kenneth Kaunda Education districts in the North West Province, South Africa. Conventional cardiovascular risk factors, 24 h ambulatory blood pressure and objectively measured physical activity (Actical® accelerometers), smoking (confirmed by serum cotinine), and alcohol (serum gamma glutamyl transferase) were assessed. The main outcome was a marker of sub-clinical vascular disease, mean carotid intima media thickness (mCIMT), measured using high resolution ultrasound. RESULTS Compared with Caucasians, the black Africans demonstrated higher mCIMT (age and sex adjusted β=0.044, 95% CI, 0.024-0.064 mm). The blacks also had higher 24h systolic and diastolic blood pressure, triglycerides, adiposity, and C-reactive protein. In addition, blacks were less physically active (790.0 kcal/d vs 947.3 kcal/d, p<0.001), more likely to smoke (25% vs 16.3%, p=0.002), and demonstrated higher alcohol abuse (gamma glutamyl transferase, 66.6 μ/L vs 27.2 μ/L, p<0.001) compared with Caucasians. The difference in mCIMT between blacks and Caucasians was attenuated by 34% when conventional risk factors were added to the model and a further 18% when health behaviors were included. CONCLUSION There is an excess burden of sub clinical vascular disease seen in black Africans compared to Caucasians, which can be largely explained by health behaviors and conventional risk factors.

Arterial Stiffness Profiles: Investigating Various Sections of the Arterial Tree of African and Caucasian People

In Africans, arterial stiffness progression seems more pronounced compared to Caucasians. We compared the arterial stiffness profiles of different age groups and focused on muscular arteries and two more central arterial segments in African and Caucasian people from South Africa. In African (N = 374) and Caucasian (N = 376) participants (20–70 years), we measured carotid-radial (C-R) and carotid-dorsalis pedis (C-DP) pulse wave velocity (PWV) and aortic characteristic impedance (Zao). Major findings were that normotensive and high-normal/hypertensive (HT) Caucasians indicated increased trends of C-R PWV with aging (P = .029 and P = .067), not seen in the African groups (P = .122 and P = .526). Both ethnic groups showed significant increases of C-DP PWV and Zao with aging. High-normal/hypertensive Africans had significantly stiffer arteries than hypertensive Caucasians for almost all age groups, and for all stiffness measures. African C-R PWV correlated significantly with blood pressure (BP), but not with age. Opposite results were observed for Caucasians. In conclusion, the stiffness of muscular arteries is already elevated in young Africans, in both those with normal or elevated BP. This is possibly due to an earlier deterioration during childhood, or perhaps already present from birth. Also, in Caucasians stiffness seems more age-related, while in Africans it seems to be more pressure-related.

Facilitated defensive coping, silent ischaemia and ECG left-ventricular hypertrophy: the SABPA study.

Background: Defensive active coping responses (being-in-control, acceptance of the stressor as reality) have been associated with vascular hyper-responsiveness in urban Africans. However, the association between active coping responses, blood pressure (BP), and ECG-derived left-ventricular hypertrophy (LVH) responses is unknown. Objectives and methods: Associations between BP, silent ischaemia and ECG Cornell product LVH were assessed in 161 African and Caucasian men with active coping responses identified by the Amirkhan Coping Strategy Indicator. BP, ECG and silent ischaemia data were obtained from 24-h ambulatory monitoring. Beat-to-beat BP was continuously recorded during stress testing and fasting resting blood samples obtained for biochemical analyses. Results: Enhanced ß-adrenergic central cardiac responses were evident in active coping Caucasians as opposed to a predomination of &agr;-adrenergic vascular responses in active coping Africans. Active coping African men displayed higher 24-h BP and prevalence of silent ischaemia events compared to the Caucasian men. Regression analyses revealed that &agr;-adrenergic responses were associated with silent ischaemic events, adjusted R2 0.21 [ß 1.07, 95% confidence interval (CI) 0.29–1.85] and that ischaemic events predicted LVH in active coping Africans (adjusted R2 0.12, ß 0.35, 95% CI 0.11–0.59). Receiver-operated characteristic (ROC) analyses indicated a defensive pathway cut point of 16 in Africans as opposed to 32 in Caucasians predicting silent ischaemia with sensitivity/specificity 100/96%. Conclusions: A defensive pathway revealed disturbed vascular function showing dissociation between behavioural and physiological ß-adrenergic active coping responses in Africans. Vascular responsiveness facilitated silent ischaemia events and structural LVH changes which potentially explain the increased risk for incident ischaemic stroke in black 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.

Blood glutathione and subclinical atherosclerosis in African men: the SABPA study

BACKGROUND Sub-Saharan Africans face an increasing burden of hypertension and related cardiac and cerebrovascular morbidity and mortality, making the identification of factors leading to early vascular abnormalities imperative. METHODS We investigated the possible influence of the antioxidant glutathione (GSH) on early subclinical atherosclerosis in 63 hypertensive (aged 45.2 years) and 34 normotensive (aged 38.9 years; P < 0.001) nondiabetic African men. We measured ambulatory daytime systolic and diastolic blood pressure (SBP, DBP) as well as daytime mean arterial pressure (MAP), carotid intima-media thickness (CIMT), and calculated the cross-sectional wall area. We determined the reduced form of GSH in whole blood and blood glucose in serum. RESULTS Blood glucose (110 vs. 92 mg/dl; P < 0.001) and CIMT (0.75 vs. 0.61 mm; P < 0.001) were higher in hypertensives compared to normotensives. No significant difference existed for GSH. Associations in normotensives suggested the hypotensive effect of GSH after single (SBP: r = -0.35, P < or = 0.05; DBP: r = -0.37, P < or = 0.05; MAP: r = -0.38, P < or = 0.05) and multiple (SBP: B = -0.015, P < 0.05; DBP: B = -0.011, P < 0.05; MAP: B = -0.012, P < 0.05) regression analyses. In hypertensives, CIMT (B = -0.00027, P < 0.01) and cross-sectional wall area (CSWA) (B = -0.0066, P < 0.05) correlated negatively with GSH. These findings were consistent after excluding 10 human immunodeficiency virus (HIV)-positive hypertensive subjects. CONCLUSIONS In hypertensive African men, CIMT is negatively associated with GSH, suggesting a possible contributory role of attenuated GSH levels in the development of subclinical atherosclerosis.

Defensive coping facilitates higher blood pressure and early sub–clinical structural vascular disease via alterations in heart rate variability: The SABPA study

OBJECTIVES Defensive coping (AC) responses in urban African males have been associated with vascular responsiveness, partly explaining autonomic nervous system dysfunction. We therefore aimed to assess whether AC responses facilitate higher blood pressure and early sub-clinical structural vascular disease via alterations in frequency- and time-domain heart rate variability (HRV) responses. METHODS We included 355 African and Caucasian men and women without pre-existing atrial fibrillation, aged 45 ± 9 years. Significant interaction on main effects (coping × ethnicity × gender) for left carotid intima media thickness far wall (L-CIMTf) and cross sectional wall area values necessitated selection of AC responders above mean via the Coping Strategy Indicator. We collected B-mode ultrasound L-CIMTf, ambulatory BP and-HRV data. Overnight fasting blood was obtained. RESULTS Overall, Africans and AC Africans, mostly men, revealed a poorer lifestyle profile, higher prevalence of hypertensive status, disturbed sympathovagal balance and depressed HRV temporal and geometric patterns compared to the Caucasians (P ≤ 0.05). Moderately depressed non-linear and time-domain HRV (SDNN <100 ms) was prevalent in 28% of Africans compared to 11% of Caucasians. A similar trend was shown for the AC African participants (32%) compared to Caucasians (16%). Only depressed HRV time-domain (SDNN: adj. R(2) = 0.34; β = -0.24; p = 0.08) and vagal-impaired heart rate responses (RMSSD: adj. R(2) = 0.28; β = -0.28; p < 0.05) were associated with higher blood pressure and early structural vascular changes in AC African men. CONCLUSION Defensive coping facilitated autonomic nervous system dysfunction, which was associated with higher blood pressure and sub-clinical structural vascular disease in an African male cohort.

Blood pressure variability is significantly associated with ECG left ventricular mass in normotensive Africans: The SABPA Study

The prognostic significance of blood pressure (BP) variability has lately enjoyed considerable attention. The need for early markers of cardiovascular dysfunction is imperative in black South Africans who have a significant risk for cardiovascular disease. We therefore compared 24-h BP variability with various traditional and advanced BP measurements, regarding their association with sub-clinical organ damage in black and white South Africans. The study included 409 African and Caucasian teachers aged 25–60 yrs. We measured office BP, 1-min continuous (finger) BP, ambulatory BP, BP reactivity and determined weighted 24-h BP variability. Albumin-to-creatinine ratio, Cornell product and carotid cross-sectional wall area (CSWA) were measures of organ damage. Africans had higher 24-h BP, BP variability, BP reactivity and sub-clinical organ damage (P<0.001). Correlations of BP variability with organ damage were overall weak when compared with other BP measurements. In normotensive groups, we found an independent association of 24-h systolic BP (SBP) variability with Cornell product only in Africans (r=0.37; P=0.01), confirmed in multiple regression models, with 24-h SBP included in the model. Only in hypertensive Caucasians, a significant correlation between CSWA and 24-h SBP variability was evident (r=0.30; P=0.01), although CSWA indicated stronger correlations with office or 24-h SBP than 24-h SBP variability. To conclude, 24-h SBP variability could potentially be an effective measure for the early detection of normotensive Africans at increased risk for the development of cardiovascular complications. Its usefulness based on associations with target organ damage in hypertensive groups seems to be less than traditional office or 24-h BP measurements.

Greater cardiovascular reactivity to a cold stimulus is due to higher cold pain perception in black Africans: the sympathetic activity and ambulatory blood pressure in Africans (SABPA) study

Objective: To evaluate the role of pain perception and pain stimulus components for blood pressure responses to stress in the black and the white African population with hypertension. Basic methods: Cardiovascular regulation in response to a cold pressor stimulus was studied in hypertensive black (n = 110) and white (n = 95) Africans. Perception of stressfulness of the task was assessed on a seven-point Likert scale. Chronic stress levels were evaluated by the General Health Questionnaire and the Coping Strategy Indicator was used to assess individual coping behavior. Autonomic and baroreflex function was evaluated by spectral analysis. Main results: The cold pressor test elicited significant blood pressure elevations with higher relative increases in the black Africans. The higher blood pressure reactivity in black Africans was accompanied by a substantially greater cardiac response and lower parasympathetic outflow as compared with white Africans. Black Africans also reported higher chronic stress levels and rated the stimulus as more painful than their white counterparts. A significant interaction was observed for cardiovascular responses with pain perception but not with chronic stress. Individuals with high pain perception exhibited less dampening of autonomic cardiac exertion than those with low or moderate pain perception. Principal conclusion: Black Africans display a more pronounced cold pressor test-induced rise in heart rate and blood pressure, which may be explained by greater pain-related increments in blood pressure. A higher cognitive appraisal of pain and a blunted baroreflex-mediated dampening of autonomic structures may contribute to the exaggerated blood pressure reactivity in black Africans.