| dc.description.abstract | MOTIVATION - Myocardial infarction, stroke and hypertension (HT) prevalence have escalated in urban Africans. Psychosocial stress and behavioural defensive coping (DefS) have been depicted as important contributory factors in cardiovascular disease (CVD) risk, particularly in urban
African men. The specific mechanism by which neuro-endocrine coping responses impact on CVD risk is however, uncertain. Furthermore, studies on the neuro-endocrine stress mediators, cortisol and norepinephrine (NE), have shown variance in affecting cardiovascular health. Conversely, estradiol (E2) has attracted minimal attention in stress and coping research, but is deemed a coping response modulator and may be
cardioprotective. However, it is still debatable whether E2 is cardioprotective in men and it is controversial whether reduced or excessive E2 may be beneficial. It is therefore evident that more research is needed to clarify the roles of E2, NE and cortisol in neuro-endocrine coping responses, especially in DefS Africans with elevated CVD risk. AIMS - The primary aim of this study was to assess the influence of neuro-endocrine coping responses on CVD risk, in an urban South African cohort. The impacts of the neuroendocrine stress mediators (NE and cortisol) on subclinical vascular and renovascular disease risk, respectively, were to be determined. Additionally, E2 was studied to determine
its effects on neuro-endocrine coping responses and CVD risk. Furthermore, the effects of particularly DefS utilisation as regards to the aforementioned were to be determined. METHODOLOGY - This study is embedded in the SABPA (Sympathetic activity and Ambulatory Blood Pressure
in Africans) study. Recruited participants included n=200 African and n=209 Caucasian
teachers from the North-West Province (Dr Kenneth Kaunda Education District), South
Africa, of a similar socioeconomic status. From these participants, n=19 HIV positive, n=12 clinically confirmed diabetic, and n=1 renal impairment cases were excluded from analyses. Additionally, cortisone users (n=2) were excluded from Manuscripts 2 and 3, due to its effects on the cortisol values studied. The final participant group consisted of n=168 Africans and n=207 Caucasians. Groups were stratified according to sex, ethnicity and/or coping style, and according to statistical significant interactions between major variables. The Coping Strategy indicator questionnaire was used to assess preferred coping responses of each participant; their stress experience was indicated on the ambulatory diary cards.
Neuro-endocrine variables included MHPG (3-methoxy-4-hydroxyphenolglycol), cortisol, E2 and the original cortisol-to-E2 ratio. Cardiometabolic variables included waist circumference, cholesterol, glycated haemoglobin, C-reactive protein and blood pressure (BP), while carotid intima-media thickness of the far wall (CIMTf), the albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) indicated target organ damage. Statistical analysis comprised receiver operating characteristics (ROC), which determined a cut point for exacerbated CVD risk. Means and proportions were determined with standard
T-tests, analysis of covariance and Chi-squares. Multiple univariate and multivariate linear regression analyses calculated independent relationships between major variables while odds ratios (OR) determined probability, independent of covariates.
RESULTS AND CONCLUSIONS - The results and conclusions of the three manuscripts prepared for this thesis are as follows: 1. Defensive coping and subclinical vascular disease risk - Associations with autonomic exhaustion in Africans and Caucasians: The SABPA study. In the first manuscript, the impact of NE (MHPG) levels on subclinical vascular disease risk in Africans and Caucasians utilising DefS was determined. Main findings revealed high self-reported stress and DefS scores in urban Africans. In African women this was found in co-occurrence with decreased MHPG levels and increased subclinical vascular disease risk (CIMTf). Lower or possibly down-regulated MHPG also predicted increased CIMTf in African men. African men and women also displayed low-grade inflammation (C-reactive protein >3 mg/l) and a pre-diabetic state (glycated haemoglobin >5.7%). Therefore, the urban Africans presented with higher subclinical vascular disease risk, especially when defensive coping “fails” and sympathetic activity diminishes (possible
autonomic exhaustion), probably ensuing sympathetic hyperactivity, NE overload and
highly stimulated 1-adrenergic activity; predisposing to pathology risk. 2. Defensive coping and renovascular disease risk - Adrenal fatigue in a cohort of Africans and Caucasians: The SABPA study. The second manuscript explored the association between urinary cortisol levels and
renovascular disease risk in Africans and Caucasians, and the impact of DefS on this
risk. Results demonstrated that high cortisol Caucasians were more vulnerable to
renovascular disease than their low cortisol counterparts. Conversely, more Africans
reported severe stress but displayed lower cortisol concentrations. Increased ACR and
decreased eGFR were shown in co-occurence with this decreased cortisol in Africans,
especially in the DefS users. Therefore, sustained uncontrollable stress may drain coping abilities and resources in DefS Africans, giving rise to HPA dysfunction and/or adrenal fatigue with subsequently decreased cortisol. Nevertheless, possibly preceding hypercortisolism levels may have facilitated permanent physiological damage; this may contribute to persistent renovascular disease risk in low cortisol DefS Africans. 3. Defensive coping and estradiol - Unravelling neuro-endocrine dysfunction and augmented hypertension risk in Africans compared to Caucasians: The SABPA study
The final manuscript investigated whether urban Africans with higher self-reported stress than Caucasians, would present with increased E2 levels. Furthermore, we aimed to determine whether increased E2 would be associated with HPA hypoactivity and an
augmented risk of HT in urban DefS Africans, particularly in men. The main findings
revealed increased stress experience, E2 levels and HT risk in Africans compared to
Caucasians. The original cortisol-to-E2 ratio was decreased in Africans, particularly in
men, and was associated with augmented BP. These findings indicate that HT risk in
DefS African men coincides with neuro-endocrine dysfunction and possibly highly
stimulated 1-adrenergic vasoconstrictory responsiveness. In sustained stress, increased E2 may contribute to cardiovascular risk rather than accommodating cardioprotection,
particularly in urban DefS African men.
GENERAL CONCLUSION - Neuro-endocrine dysfunction was evident in urban Africans, particularly in men who reported severe stress. Nonetheless, the Africans’ coping resources (stress mediators) were inadequate for effective coping. In sustained stress, neuro-endocrine stress mediators
(vasoconstrictory properties) may be down-regulated while E2 as coping modulator is upregulated to enhance its vasodilatory and cardioprotective effects. Nevertheless, excessive E2 may also be detrimental and exacerbates CVD risk, particularly in men. Coping ability may further be impaired with sympatho-adrenal-medullary and HPA suppression, negatively influencing future coping responses of already severely stressed Africans. Increased E2 may therefore augment CVD risk in especially DefS African men, possibly through highly
stimulated 1-adrenergic vasoconstrictive activity. In fact, the observed increase in E2 and decrease in neuro-endocrine stress mediators were respectively associated with increased risk of HT, subclinical vascular and renovascular disease in urban DefS Africans. | en_US |
