Correction to: Heart rate variability, the dynamic nature of the retinal microvasculature and cardiac stress: providing insight into the brain-retina-heart link: the SABPA study.

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Ambulatory blood pressure monitoring and morning surge in blood pressure in adult black and white South Africans.

We examined whether there were differences in the circadian variation in blood pressure and the morning surge in blood pressure between black and white Africans. Clinic and ambulatory blood pressure data obtained from the Sympathetic Activity and Ambulatory Blood Pressure in Africans (SABPA) study was examined (n = 406; 49% black African). Ambulatory blood pressure readings were fitted to a six-parameter double logistic equation to determine the power and rate of the morning surge in blood pressure. Multiple linear regression analysis was used to examine differences in blood pressure between black and white participants. Clinic and ambulatory blood pressure were higher in black participants throughout the day and night. In those taking medications, blood pressure was less well controlled in black subjects. Despite the higher systolic blood pressure, the day-night difference estimated by the logistic function was similar in black and white participants. However, the rate of rise and power in the morning surge in blood pressure was lower in black participants. We conclude that black participants of the SABPA study present with higher blood pressure throughout the day and night but have a lower power of the morning surge in blood pressure due to a slower morning rate of increase. Moreover, they had an increased prevalence of undiagnosed hypertension and, in those taking medication, were less likely to have their blood pressure controlled than their white counterparts.

Heart rate variability, the dynamic nature of the retinal microvasculature and cardiac stress: providing insight into the brain-retina-heart link: the SABPA study.

BACKGROUND AND AIMS: Decreased heart-rate-variability (HRV) indicates increased sympathetic nervous system (SNS) activity and modulation with a shift in the sympatho-vagal balance towards SNS predominance. Increased SNS activity may precede volume-loading hypertension, contribute to increases in cardiac troponin T (cTnT), endothelial dysfunction and small vessel disease. Therefore, we investigated the retinal vasculature, HRV during flicker-light-induced-provocation (FLIP) and systemic cTnT, a marker of cardiac stress, to provide further evidence in support of the brain-retina-heart link. METHODS: Cross-sectional observations were obtained from a bi-ethnic cohort (N = 264), aged 23-68 years. Fasting serum samples for cTnT were obtained. Retinal vascular calibres were quantified from mydriatic eye fundus images and dynamic retinal vessel calibre responses were determined during FLIP. Time-and frequency domain parameters of HRV were calculated during FLIP for each participant. RESULTS: Africans had wider venules and attenuated time domain parameters during FLIP. In Africans, inverse associations emerged between arteriolar dilation and both cTnT and root-mean squared of the standard deviations of successive RR-intervals (rMSSD) (p = 0.030), and between arteriolar constriction and both low-frequency expressed in normalised units (LFnu) (p = 0.003) and high-frequency expressed in normalised units (p = 0.021). Wider venules inversely associated with standard deviation of the NN intervals (SDNN) as well as LFnu (p = 0.009) in Africans. An opposite profile was observed in Caucasians with both time-and frequency domain parameters of HRV in relation to retinal vessel structure and function. CONCLUSION: FLIP elicited increased SNS activity and modulation in this bi-ethnic cohort. In Africans, decreased HRV during FLIP accompanied arteriolar and venular responses and elevated systemic levels of cTnT, implying that the SNS exerted a significant effect on the smooth muscle tone of the retinal vasculature. Disrupted retinal autoregulation may imply general autonomic nervous system dysfunction; exemplifying central control by the brain on all systemic regulatory functions, across different vascular beds.

BDNF increases associated with constant troponin T levels and may protect against poor cognitive interference control: The SABPA prospective study.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) modulates brain health and cognition, which can interfere with executive cognitive function. BDNF was implicated with microcirculatory ischaemia and may reflect cardiomyocyte injury. We aimed to determine whether prospective changes (%Δ) in BDNF and cardiac troponin T (cTnT) will be associated with executive cognitive function in a bi-ethnic cohort. DESIGN: A prospective investigation was conducted over a three-year period in a bi-ethnic sex cohort (N = 338; aged 20-65 years) from South Africa. Fasting serum samples for BDNF and cTnT were obtained. The STROOP-color-word conflict test (CWT) was applied to assess executive cognitive function at baseline. RESULTS: In Blacks, BDNF (P < 0.001) increased over the three-year period while cTnT did not change. In contrast, in Whites, BDNF and cTnT decreased over three years. In Black men, no change in cTnT was associated with increased ΔBDNF (ß = 0.25; 95% CI 0.05-0.45; P = 0.02). In the Black men, constant cTnT levels were inversely associated with executive cognitive function (ß = -0.33; 95% CI -0.53 to -0.12; P = 0.003). Three-year increases in BDNF increased the likelihood for chronic lower cTnT levels at a pre-established cut-point of <4.2 ng/L [OR = 2.35 (1.12-4.94), P = 0.02]. The above associations were not found in the White sex groups. CONCLUSIONS: Central neural control mechanisms may have upregulated BDNF in Black men as a way to protect against myocardial stress progression and to possibly improve processes related to cognitive interference control. High-sensitive cTnT levels may act as an early predictor of disturbed neural control mechanisms.

Ethnicity-Specific Changes in Cardiac Troponin T in Response to Acute Mental Stress and Ethnicity-Specific Cutpoints for the R Wave of the aVL Lead.

Acute mental stressor-induced cardiac stress responses might contribute to excessive myocardial strain and resultant cardiovascular episode risk. We assessed ethnicity-specific acute cardiac stress (by measuring cardiac troponin T (cTnT) and N-terminal prohormone of brain natriuretic peptide) related to hemodynamic activity. The prospective Sympathetic Activity and Ambulatory Blood Pressure in Africans (SABPA) study was conducted during 2007-2008 in South Africa. In the cross-sectional phase of the SABPA study, 388 black and white participants underwent a 1-minute acute mental stressor, during which blood pressure was continuously measured. Fasting blood samples for cardiac stress markers were obtained before and 10 minutes after stress (% change). Resting 10-lead electrocardiogram measured the R wave of the aVL lead (RaVL). Black participants exhibited greater cardiac stress responses (P < 0.001), diastolic blood pressure, total peripheral resistance, and stroke volume compared with white participants, who displayed decreases in cardiac stress and increases in cardiac output. Prestress and stressor cTnT cutpoints of 4.2 pg/mL predicted 24-hour, daytime, and nighttime diastolic hypertension in black participants (P < 0.001). These cTnT cutpoints were associated with an ethnicity-specific RaVL cutpoint of 0.28 mV (odds ratio = 3.49, 95% confidence interval: 2.18, 5.83; P = 0.021). Acute mental stress elicited an α-adrenergic activation pattern and cardiac stress hyperreactivity only in black participants. Mental stress might increase the black population's risk for ischemic episodes and heart disease.

Longitudinal changes of cardiac troponin and inflammation reflect progressive myocyte stretch and likelihood for hypertension in a Black male cohort: The SABPA study.

Inflammation was cross-sectionally associated with subclinical wall remodeling and hypertension. Whether longitudinal changes (∆) in inflammation, myocyte injury (troponin T), and stretch (N-terminal-pro-B-type natriuretic peptide) are associated with hypertension and ECG left ventricular hypertrophy (ECG-LVH) is unclear. The first prospective analysis in Africa assessing these associations included a cohort of Black and White teachers (N = 338; aged 20-63 years). Fasting blood samples were obtained to measure tumor necrosis factor-alpha (TNF-α), cardiac troponin T (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Ambulatory blood pressure, 2-lead ECG and resting 10-lead ECG values were obtained. A higher mean hypertensive status (62%) was evident in Blacks compared to Whites (44%, p < 0.001). Over 3-years, NT-proBNP increased in both ethnic groups. No associations were evident in women or in White men. In Black men, ECG-LVH at follow-up was positively associated with baseline cTnT (Adj R2 0.43; ß = 0.48; 95% CI 0.28-0.68, p < 0.001) and baseline SBP (Adj R2 0.43; ß = 0.29; 95% CI 0.09-0.49, p = 0.006). In Black men, baseline TNF-α (OR = 1.49, 95% CI 1.05-2.14, p = 0.03) and decreased ΔTNF-α (OR = 2.07, 95% CI 1.26-3.40, p = 0.004) increased the likelihood for cTnT levels ≥ 4.2 ng/L. Here, baseline NT-proBNP (OR = 1.12, 95% CI 1.01-1.23, p = 0.03) and ΔNT-proBNP progression (OR = 1.09, 95% CI 1.00-1.81, p = 0.04) increased the likelihood for 24-h hypertension. In conclusion, chronically increased levels of markers of myocyte injury accompanied by progressive myocardial stretch, reflective of cardiac metabolic overdemand, may ultimately increase hypertension and ischemic heart disease risk in a cohort of Black males.

Prospective associations between cardiac stress, glucose dysregulation and executive cognitive function in Black men: The Sympathetic activity and Ambulatory Blood Pressure in Africans study.

OBJECTIVE: Glucose dysregulation is an independent risk factor for cardiovascular and neurodegenerative disease development through synaptic dysfunction resulting in cognitive decline. The aim of this study was to study the interplay between impaired glycaemic metabolism (hyperglycaemia and insulin resistance), cardiac stress (cardiac troponin T and N-terminal brain natriuretic peptide) and executive cognitive function prospectively, in a bi-ethnic sex cohort. METHODS: Black and White teachers (N = 338, aged 20-63 years) from the Sympathetic activity and Ambulatory Blood Pressure in Africans study were monitored over a 3-year period. Fasting blood samples were obtained for cardiac troponin T, N-terminal brain natriuretic peptide, glycated haemoglobin and the homeostatic model assessment-insulin resistance for insulin resistance. The Stroop colour-word conflict test was applied to assess executive cognitive function at baseline. RESULTS: Over the 3-year period, Black men revealed constant high levels of cardiac troponin T (⩾4.2 ng/L), pre-diabetes (glycated haemoglobin > 5.7%) and insulin resistance (homeostatic model assessment-insulin resistance >3). %Δ Glycated haemoglobin was associated with %Δ insulin resistance (p < 0.001) and increases in %ΔN-terminal brain natriuretic peptide (p = 0.02) in Black men only. In the latter, baseline Stroop colour-word conflict test was inversely associated with %Δ cardiac troponin T (p = 0.001) and %Δ insulin resistance levels (p = 0.01). CONCLUSION: Progressive myocyte stretch and chronic myocyte injury, coupled with glucose dysregulation, may interfere with processes related to interference control in Black men.

Retinal Vasculature Reactivity During Flicker Light Provocation, Cardiac Stress and Stroke Risk in Africans: The SABPA Study.

Structural and functional similarities exist between the retinal, cerebral and, as previously suggested, the coronary microvasculature. Retinal microvascular structure and functionality (in response to flicker-light-induced-provocation (FLIP)) may relate to coronary artery disease risk and possible stroke risk. We investigated associations between retinal vessel structure, functionality and cardiac stress markers (cardiac troponin T [cTnT], amino-terminal B-type natriuretic peptide [NT-proBNP]) to translate these retina-heart relationships to stroke risk. We included 317 African and Caucasian teachers' (aged 23-68 years), who participated in the Sympathetic Activity and Ambulatory Blood Pressure in Africans (SABPA) study. Fasting plasma and serum samples for cTnT and NT-proBNP were collected. Retinal vascular calibres were quantified from fundus images and dynamic retinal vessel calibre responses during FLIP. The University of California stroke risk score was applied to assess sub-clinical 10-year stroke risk. cTnT levels were similar in Africans and Caucasians, whereas NT-proBNP levels were lower in Africans. In Africans, a reduced arteriolar calibre and attenuated arteriolar dilation during FLIP was associated with higher cTnT (p < 0.01). Their larger retinal-venular calibre (p < 0.02) and attenuated arteriolar dilation during FLIP (p < 0.05) were associated with lower NT-proBNP. Again, exclusively in Africans, increased cardiac stress, wider venular calibres and retinal arteriovenous nicking predicted an increased 10-year stroke risk with odds ratios of 1.57 (95% CI, 1.34; 1.68, p = 0.031), 1.51 (95% CI, 1.26; 1.59, p = 0.002), 1.10 (95% CI, 0.94; 2.85, p = 0.002) and 1.06 (95% CI 0.83; 1.56, p = 0.052), respectively. None of these associations were evident in the Caucasian group. Investigating the retinal vasculature may serve as a tool to approximate sub-clinical coronary and cerebral microvasculature damage or dysfunction. These cardiac stress-retinal associations additionally predicted a greater stroke risk in the SABPA African cohort. Observable changes in the retinal vasculature may serve as markers for the identification and prediction of cardio-systemic and cerebral vascular morbidities and risks, thereby establishing a brain-heart link. Graphical Abstract Proposed series of events during which sustained high pressure and increased cardiac stress may alter retinal reactivity and link to increased stroke risk.

Chronic depression symptoms desensitize renin activity to protect against volume-loading hypertension in Blacks: The SABPA study.

BACKGROUND: Low-renin levels in Blacks have been associated with volume-loading hypertension (HT). Depression symptoms, frequently co-occurring with vascular dysregulation, might reflect a disturbed renin-angiotensin-aldosterone-system (RAAS). We aimed to assess prospective changes (∆) in depression symptoms, RAAS (renin, aldosterone), diastolic blood pressure (DBP), and estimated glomerular filtration rate (eGFR) in a bi-ethnic sex cohort. METHODS: We included 195 Black and White teachers (43.7 ±â€¯9 years) from a South African 3-year prospective study. Hypertension medication users, diabetics and human immunodeficiency virus infected individuals were excluded. Depression symptoms (Patient-Health-Questionnaire-9/PHQ-9), 24 h blood pressure measurements and fasting blood samples were obtained. RESULTS: Blacks had lower renin but higher DBP and eGFR levels at baseline (p ≤ .01) when compared to Whites. Blacks and Whites with depression (PHQ-9 ≥ 10) at baseline developed co-morbidity for having both depression plus DBP-HT at follow-up (Blacks, 49.1%; Whites, 13.1%). At 3-year follow-up, chronic depression symptoms were related to chronic lower renin in Blacks [Adjusted R2 0.20; ß -0.37 (-0.66, -0.08), p = .02]. Chronic depression symptoms also predicted DBP hypertension in Blacks [ROC AUC = 0.61 (0.48-0.75); sensitivity/specificity 78.1/46.3%]. No prospective associations existed between depression symptoms, aldosterone and eGFR. CONCLUSION: Chronic depression symptoms in Blacks activated the RAAS system activity with apparent desensitization of renin activity. Chronic depression could be causal to hypertension and in turn, lowers renin activity as a protective mechanism against volume-loading. These findings emphasize the potential impact of depression on the low renin-hypertension phenotype in Blacks in terms of diagnosis and treatment.

QTc prolongation, increased NT-proBNP and pre-clinical myocardial wall remodeling in excessive alcohol consumers: The SABPA study.

Alcohol contributes greatly to vascular and structural modifications. Due to differences in the metabolism and tolerance of alcohol between ethnic groups, the manner of these modifications may differ. We investigated the association between alcohol consumption - measured via ethnic-specific gamma glutamyl transferase (γ-GT) cut-points - and markers of cardiac perfusion, electrical activity, and pre-clinical structural alterations. A South African target population study was performed in a bi-ethnic cohort (n = 405). Alcohol consumption was determined according to previously defined ethnic-specific γ-GT cut-points, where γ-GT ≥ 19.5 U/L and γ-GT ≥ 55 U/L indicated excessive alcohol consumption in Caucasians and Africans, respectively. Ambulatory 24-h blood pressure and electrocardiograms (ECG), 10-lead ECG left ventricular hypertrophy (LVH), ischemic events, N-terminal pro-brain natriuretic peptide (NT-proBNP), and QTc prolongation were assessed. Fasting blood samples were obtained. A poorer cardio-metabolic profile and mean 24-h hypertensive and ECG-LVH values were evident in high γ-GT groups of both ethnicities, when compared to their low counterparts. The African high γ-GT group reported a higher intake of alcohol and presented significant increases in NT-proBNP (p < 0.001), QTc prolongation (p = 0.008), and ischemic events (p = 0.013). Regression analyses revealed associations between ECG-LVH and NT-proBNP, QTc prolongation, ischemic events, and SBP, in the African high γ-GT group exclusively. High alcohol consumers presented delayed electrical conduction in the heart accompanied by ECG-LVH, ischemic events, and increased vaso-responsiveness, predominantly in Africans. Ultimately, increased left ventricular distension on a pre-clinical level may elevate the risk for future cardiovascular events in this population.

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, ß=-0.31, p=0.023) and free oestradiol (adjusted R2=0.34, ß=-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, ß=-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.

Hypothalamic-pituitary-adrenal-axis dysregulation and double product increases potentiate ischemic heart disease risk in a Black male cohort: the SABPA study.

Emotional distress has been associated with a poorer prognosis in myocardial infarction patients. Elevated adrenocorticotrophic hormone (ACTH), lower cortisol, dehydroepiandrosterone sulfate (DHEAS) and cortisol:DHEAS, as measures of emotional distress, might correlate with silent myocardial ischemia (SMI) and workload. Thus, we assessed the relationship between emotional distress, SMI and double product (systolic blood pressure (SBP) × heart rate). Cross-sectional South African biethnic single-set cohorts (N=378), aged 44.7±9.52 years, were investigated. Depressive symptoms (Patient Health Questionnaire-9), anthropometric, fasting blood, 24-h double product and 24-h 2-lead electrocardiogram (ST-segment depression) values were obtained. Blacks, mostly men, had increased depressive symptoms, hyperglycemia, SMI, double product, SBP hypertension and ACTH but lower cortisol, DHEAS and cortisol:DHEAS than their White counterparts. Black men had the highest combined SBP hypertension and below-median cortisol prevalence, 38%, compared with 5.9-13.8% in the other groups. Their SMI was associated with ACTH and cortisol:DHEAS (adj. R2 0.29; ß 0.27-0.31 (0.12-0.64); P⩽0.05), double product (adj. R2 0.29; ß 0.38 (0.18-0.57); P=0.050) and SBP hypertension (area under the curve: 0.68 (95% CI: 0.56, 0.80); P=0.042; sensitivity/specificity 49/85%). Double product was positively associated with central obesity in all sex groups and with cortisol in the Black men (P<0.05). A dysregulated hypothalamic-pituitary-adrenal-axis (HPAA) showed signs of a hyporesponsive adrenal cortex, suggesting chronic emotional stress in the Black male cohort. In this cohort, HPAA dysregulation and compensatory increases in double product occur as a potential defense mechanism to alleviate perfusion deficits, thereby potentiating ischemic heart disease risk.

Depression Symptoms Facilitated Fibrinolytic Dysregulation and Future Coronary Artery Disease Risk in a Black Male Cohort: The Sympathetic Activity and Ambulatory Blood Pressure in Africans Study.

BACKGROUND: Hypercoagulation is associated with coronary artery disease (CAD). Whether depression symptoms dysregulate inflammatory and hemostatic markers in an African cohort is not known; therefore, we assessed the relationship between depressive symptoms and inflammatory and hemostatic markers as potential CAD risk markers in an African sex cohort. MATERIAL AND METHODS: We included 181 black African urban-dwelling teachers (88 men, 93 women; aged 25-60 years) from the Sympathetic Activity and Ambulatory Blood Pressure in Africans Study. The Patient Health Questionnaire was used to assess depressive symptoms. Fasting plasma concentrations of C-reactive protein, fibrinogen, D-dimer, plasminogen activator inhibitor-1 (PAI-1) and 24-hour blood pressure measures were obtained. RESULTS: Moderately severe depression symptom status was similar in the black sex groups. Both sex groups showed a mean hypertensive state and low-grade inflammation (C-reactive protein > 3 mg/L). Levels of PAI-1 were higher in depressed men, whereas D-dimer levels were lower in depressed women when considering concomitant confounders. In black men only, depressive symptoms were associated with levels of PAI-1 (adj. R = 0.12; ß = .22 [95% confidence interval, .0-.44]; P = .04) and D-dimer (adj. R = 0.12; ß = .28 [95% confidence interval, .08-.48]; P = .01), independent of confounders. CONCLUSION: In black men, depression symptoms accompanied by a mean hypertensive status may up-regulate inflammatory and thrombotic processes. Depression symptoms in black men facilitated hypercoagulation or fibrinolytic dysregulation and potentially increased their CAD risk. Early screening of fibrinolytic markers and for the presence of depressive symptoms is recommended.

Cortisol:brain-derived neurotrophic factor ratio associated with silent ischaemia in a black male cohort: the SA BPA study.

AIM: Emotional distress has been associated with cardiovascular disease (CVD) in Africans. Cortisol and brain-derived neurotrophic factor (BDNF), as markers of emotional distress, increase cardiometabolic risk. We therefore aimed to investigate associations between cardiometabolic risk markers and the cortisol-to-BDNF ratio (cortisol:BDNF). METHODS: A cross-sectional study included a bi-ethnic gender cohort (n = 406) aged 44.7 ± 9.52 years. Ambulatory blood pressure (ABPM), ECG, fasting serum cortisol and BDNF levels and cardiometabolic risk markers were obtained. RESULTS: Africans had increased incidence of hyperglycaemia and 24-hour silent ischaemic events, and elevated 24-hour blood pressure (BP) and cortisol:BDNF ratios compared to Caucasians. Forward stepwise linear regression analysis underscored a similar trend with associations between hyperglycaemia, 24-hour BP [Adj R2 0.21-0.29; ß 0.23 (0.1-0.4); p = 0.01], silent ischaemia [Adj R2 0.22; ß 0.40 (0.2-0.6); p < 0.01] and cortisol:BDNF levels in Africans, mostly in the men. CONCLUSION: Attenuated cortisol levels in this group may be indicative of emotional distress and if chronic, drive the cortisol:BDNF ratio to desensitise BDNF. Desensitised cortisol:BDNF may sustain cardiometabolic risk and induce neurodegeneration in African men via silent ischaemia. Compensatory increases in blood pressure to increase perfusion and maintain homeostasis may increase coronary artery disease risk.

Fibrosis and coronary perfusion - a cardiovascular disease risk in an African male cohort: The SABPA study.

Low-grade inflammation has been correlated with risk factors of cardiovascular diseases (CVD). Whether the pro-inflammatory and thrombotic ratio (fibrosis) may contribute to CVD is not known. We therefore aimed to assess whether Cornell Product left ventricular hypertrophy (LVH) is associated with fibrosis and coronary perfusion (silent ischemia) in a bi-ethnic male cohort from South Africa. A cross sectional study was conducted including 165 African and Caucasian men between the ages of 20-65. Fasting blood samples were obtained to measure fibrinogen, C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor (TNF-α). Ambulatory blood pressure, ECG and 12 lead ECG measures were obtained to determine silent ischemic events (ST events) and LVH, respectively. Africans revealed more silent ischemia, higher 24 h blood pressure, inflammatory, coagulation as well as fibrosis levels than Caucasians. In a low-grade inflammatory state (CRP > 3 mg/l), Africans revealed higher fibrosis (p ≤ 0.01) values, but lower IL-6 and TNF-α values than Caucasians. Linear regression analyses in several models demonstrated positive associations between silent ischemia and fibrosis [Adj. R(2) 0.23; ß 0.35 (95% CI 0.13, 0.58), p ≤ 0.01]. In a low-grade inflammatory state (CRP>3mg/l), fibrinogen predicted AV-block in African men [OR 3.38 (95% CI 2.24, 4.53); p = 0.04]. Low-grade inflammation may induce AV-block through mechanisms involving fibrosis and ischemia to increase the burden on the heart in African men.

The defense response and alcohol intake: A coronary artery disease risk? The SABPA Study.

The behavioral defense coping response (DefS) as a measure of coping with emotional stress may increase alcohol intake (gamma glutamyl transferase (γGT)), the risk for coronary artery disease (CAD) and insulin sensitivity (homeostasis model assessment, HOMA). We assessed associations between coping and cardiometabolic risk markers in a bi-ethnic cohort (N = 390) from South Africa. Ambulatory blood pressure (BP) and ECG, fasting blood and coping scores were obtained. Africans, and mostly when utilizing DefS, showed higher 24h BP, a low-grade inflammatory state, central obesity, increased HOMA [4.07 (3.66, 4.47)] and more ST events compared to their Caucasian counterparts. ROC γ-GT analyses predicting 24-h ambulatory hypertension showed a higher γ-GT cut-point in Africans (55.4 U/l) than in Caucasians (19.5 U/l). Odds ratios (ORs) of γ-GT cut-points predicting 24-h ambulatory hypertension was evident in DefS African men [OR: 7.37 (95% CI: 6.71-8.05), p = 0.003] and in DefS Caucasians, albeit at a lower γ-GT cut-point (19.5 U/l). Higher γ-GT cut-points in DefS Africans or Caucasians were not associated with HOMA > 3. DefS accompanied by alcohol abuse in taxing emotional situations, if no social support is forthcoming, underscores a profile of reduced coronary perfusion. It may enhance vasoconstriction of the coronary arteries, with compensatory increases in BP, and induce a risk for future coronary artery disease.

Retinal vessel caliber and its relationship with nocturnal blood pressure dipping status: the SABPA study.

Adverse changes in retinal microvasculature caliber are associated with incident hypertension, coronary heart disease and stroke. The absence of a nocturnal dipping in arterial pressure may induce changes throughout the vascular tree, including the retinal microvasculature, but the later link is not sufficiently studied. We explored the relationship between retinal vessel caliber and dipping status in a group of black and white teachers. The study included black (n=68) and white (n=81) men (24-66 years) from the SABPA study. We measured 24 h ambulatory blood pressure and the percentage mean arterial pressure dipping(%MAPdip) was calculated as (diurnal MAP-nocturnal MAP)/diurnal MAP × 100. Retinal images were captured and the central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) calculated. Black men demonstrated higher diurnal and nocturnal MAP (P⩽0.001) and a lesser %MAPdip compared with white men (P=0.047). When stratified by dipping status, black non-dippers (n=33) revealed an increased CRVE (P<0.001) compared with their dipper counterparts (n=35). In black men, CRVE was negatively (R2=0.38, ß=-0.47, P<0.001) associated with %MAPdip independent of 24 h MAP or nocturnal MAP. CRVE also associated negatively with dipping status as a dichotomized variable (R2=0.29, ß=-0.32, P=0.006), independent of 24 h MAP. These associations were absent in the white men. In conclusion, in this group of black men, a non-dipping blood pressure profile was associated with a larger CRVE, suggesting microvascular deterioration due to the absence of nocturnal dipping in blood pressure. This may add to our understanding of the stroke risk in black populations.

Hyperpulsatile pressure, systemic inflammation and cardiac stress are associated with cardiac wall remodeling in an African male cohort: the SABPA study.

Inflammation may contribute to an increase in cardiac wall stress through pathways related to cardiac remodeling. Cardiac remodeling is characterized by myocyte hypertrophy, myocyte death and modifications of the extracellular matrix. We sought to explore associations among cardiac remodeling, inflammation and myocardial cell injury in a bi-ethnic cohort of South African men and women. We included 165 men (76 African and 89 Caucasian) and 174 women (80 African and 94 Caucasian) between 20 and 65 years of age. Inflammatory markers used were C-reactive protein (CRP), interleukin-6 and tumor necrosis factor-alpha (TNF-α), whereas troponin T (Trop T) and the N-terminal of pro B-type natriuretic peptide (NT-proBNP) were used as cardiac markers. The frequency of ischemic events (ST segment depression) and left ventricular strain (left ventricular hypertrophy: LVH) were monitored by a 24-h recording of ambulatory blood pressure (BP), ECG and 12-lead standard ECG. Hypertension diagnosed with ambulatory monitoring was more frequent in Africans (53.85 vs. 24.59%; P<0.001), as was the number of ischemic events (6±15 (1; 5) vs. 3±6 (0; 3)). Inflammatory markers (CRP, IL-6 and TNF-α) and the degree of LVH were all significantly higher in Africans (P<0.05). BP was associated (P<0.05) with Trop T in men across ethnic groups. In African men, cardiac stress (NT-proBNP) was associated with TNF-alpha (P<0.001), Trop T (P<0.001) and pulse pressure (P=0.048; adjusted R(2)=0.45). The susceptibility for cardiac wall remodeling appears to increase with hyperpulsatile pressure, low-grade systemic inflammation and ventricular stress, and may lead to the development of future cardiovascular events in African men.