Leoné Malan

Psychophysiological risk markers of cardiovascular disease

Acute psychophysiological stress testing, involving measurement of cardiovascular and biological responses to laboratory-induced mental stress, is an important tool to investigate mechanisms that might account for the association between psychosocial stress and cardiovascular diseases (CVD). Accumulating evidence has demonstrated associations of disturbed psychophysiological responses with sub-clinical measures of atherosclerosis, hypertension, and metabolic risk. The complex pattern of stress responding is influenced by individual differences, such as coping style, race and ethnicity, genetics, background stress, and lifestyle habits, which should be taken into account when interpreting results. For example, an unique interplay between cardiac and vascular responses in black Africans and African Americans is thought to contribute towards a heightened risk of hypertension in this group. Whether or not psychophysiological risk markers provide prognostic information over and above that of established risk markers is not clear. In summary, controlled trials that examine if the modification of psychophysiological responses through lifestyle and psychosocial interventions can reduce the risk of CVD outcomes are needed to establish causality. Further work is also required that examines the associations of ambulatory responses to real life stress in relation to risk of CVD.

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.

Inflammation, obesity and cardiovascular function in African and Caucasian women from South Africa: the POWIRS study

The integrated relationship between inflammation, obesity and cardiovascular disease is currently a subject of much research interest. These specific relationships, however, have not been studied in-depth in South African population groups in order to determine the role of ethnicity. It is known that Africans, compared to Caucasians, suffer from a high prevalence of hypertension. It was therefore hypothesized that the levels of inflammatory markers (high-sensitivity C-reactive protein (hsCRP), fibrinogen and leptin) are higher in Africans compared to Caucasians and are notably associated with cardiovascular dysfunction in Africans. Apparently healthy African (N=102) and Caucasian (N=115) women, matched for age and body mass index (BMI), were recruited. Leptin, hsCRP, fibrinogen and lipid levels, waist circumference (WC), BMI, systolic and diastolic blood pressure, cardiac output (CO), total peripheral resistance (TPR) and Windkessel compliance were measured. Results showed that the levels of leptin, hsCRP and fibrinogen were significantly higher (P<0.05) in the African women. The inflammatory markers correlated strongly with cardiovascular parameters, age and obesity (BMI, WC) in both groups, but after adjusting for age and obesity, none of the correlations were significant anymore. Multiple regression analyses (with leptin, hsCRP or fibrinogen as dependent variable) showed that only leptin levels of African women were explained by cardiovascular parameters (BP, TPR and CO). In conclusion, even though African women had significantly higher leptin, hsCRP, fibrinogen and blood pressure levels than Caucasian women, no cardiovascular parameters explained the variation in the inflammatory markers (except for leptin levels of African women).

Comparison of central pressure estimates obtained from SphygmoCor, Omron HEM-9000AI and carotid applanation tonometry

Background The Omron HEM-9000AI is the first automated tonometer to provide an estimate of central SBP (cSBP), which is considered to be more predictive of cardiovascular events than brachial pressure. However, considerable differences between the cSBP estimate of Omron and that of SphygmoCor have been reported, but not explained. This study assesses the sources of differences between both cSBP estimates and provides a handle on which estimate is closest to reality. Method For this purpose, aortic cSBP derived from calibrated carotid SBP was used as device- and algorithm-independent reference. Radial, brachial and carotid applanation tonometry were performed in 143 black South Africans, aged 39–91 years. Each individual was measured with an Omron HEM-9000AI and a SphygmoCor. Results When using both devices as advocated by their manufacturers, the corresponding cSBP estimates correlated strongly (r = 0.99, P < 0.001), but the Omron estimate was 18.8 (4.3) mmHg higher than the SphygmoCor estimate. Aortic SBP was in between both estimates: 11.7 (5.5) mmHg lower than cSBP-Omron and 7.1 (5.0) mmHg higher than cSBP-SphygmoCor. Alternative calibration of the radial SphygmoCor-curves with radial instead of brachial pressures yielded a cSBP that was 3.0 (4.2) mmHg lower than aortic SBP. The shape of the recorded pressure waves was similar in both devices: less than 5% of the observed cSBP difference was caused by differences in wave shape. Conclusion The results from this study demonstrate that the considerable difference between the central pressure estimates of Omron HEM-9000AI and SphygmoCor is due to algorithm differences, and suggest that the overestimation by Omron HEM-9000AI is larger than the underestimation by SphygmoCor.

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.

Should obesity be blamed for the high prevalence rates of hypertension in black South African women

Hypertension is highly prevalent in South Africa, resulting in high stroke mortality rates. Since obesity is very common among South African women, it is likely that obesity contributes to the hypertension prevalence. The aims were to determine whether black African women have higher blood pressures (BPs) than Caucasian women, and whether obesity is related to their cardiovascular risk. African (N=102) and Caucasian (N=115) women, matched for age and body mass index, were included. Correlations between obesity (total body fat, abdominal obesity and peripheral fat) and cardiovascular risk markers (haemodynamic parameters, lipids, inflammatory markers, prothrombotic factors, adipokines, HOMA-IR (homoeostasis model assessment insulin resistance)) were compared between the ethnic groups (adjusted for age, smoking, alcohol and physical activity). Comparisons between low- and high-BP groups were also made for each ethnic group. Results showed that African women had higher BP (P<0.01) with increased peripheral vascular resistance. Surprisingly, African women showed significantly weaker correlations between obesity measures and cardiovascular risk markers when compared to Caucasian women (specifically systolic BP, arterial resistance, cardiac output, fibrinogen, plasminogen activator inhibitor-1, leptin and resistin). Interestingly, the latter risk markers were also not significantly different between low- and high-BP African groups. African women, however, presented significant correlations of obesity with triglycerides, C-reactive protein and HOMA that were comparable to the Caucasian women. Although urban African women have higher BP than Caucasians, their obesity levels are weakly related to traditional cardiovascular risk factors compared to Caucasian women. The results, however, suggest a link with the development of insulin resistance.

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.