A Stress Syndrome Prototype Reflects Type 3 Diabetes and Ischemic Stroke Risk: The SABPA Study.

Type 3 diabetes (T3D) accurately reflects that dementia, e.g., Alzheimer's disease, represents insulin resistance and neurodegeneration in the brain. Similar retinal microvascular changes were observed in Alzheimer's and chronic stressed individuals. Hence, we aimed to show that chronic stress relates to T3D dementia signs and retinopathy, ultimately comprising a Stress syndrome prototype reflecting risk for T3D and stroke. A chronic stress and stroke risk phenotype (Stressed) score, independent of age, race or gender, was applied to stratify participants (N = 264; aged 44 ± 9 years) into high stress risk (Stressed, N = 159) and low stress risk (non-Stressed, N = 105) groups. We determined insulin resistance using the homeostatic model assessment (HOMA-IR), which is interchangeable with T3D, and dementia risk markers (cognitive executive functioning (cognitiveexe-func); telomere length; waist circumference (WC), neuronal glia injury; neuron-specific enolase/NSE, S100B). Retinopathy was determined in the mydriatic eye. The Stressed group had greater incidence of HOMA-IR in the upper quartile (≥5), larger WC, poorer cognitiveexe-func control, shorter telomeres, consistently raised neuronal glia injury, fewer retinal arteries, narrower arteries, wider veins and a larger optic cup/disc ratio (C/D) compared to the non-Stressed group. Furthermore, of the stroke risk markers, arterial narrowing was related to glaucoma risk with a greater C/D, whilst retinal vein widening was related to HOMA-IR, poor cognitiveexe-func control and neuronal glia injury (Adjusted R2 0.30; p ≤ 0.05). These associations were not evident in the non-Stressed group. Logistic regression associations between the Stressed phenotype and four dementia risk markers (cognitiveexe-func, telomere length, NSE and WC) comprised a Stress syndrome prototype (area under the curve 0.80; sensitivity/specificity 85%/58%; p ≤ 0.001). The Stress syndrome prototype reflected risk for HOMA-IR (odds ratio (OR) 7.72) and retinal glia ischemia (OR 1.27) and vein widening (OR 1.03). The Stressed phenotype was associated with neuronal glia injury and retinal ischemia, potentiating glaucoma risk. The detrimental effect of chronic stress exemplified a Stress syndrome prototype reflecting risk for type 3 diabetes, neurodegeneration and ischemic stroke.

Delayed retinal vein recovery responses indicate both non-adaptation to stress as well as increased risk for stroke: the SABPA study.

OBJECTIVES: Low or high sympatho-adrenal-medullary axis (SAM) and hypothalamic-pituitary-adrenal axis (HPA) dysregulation reflect chronic stress. Retinal vessel dynamics may relate to SAM, HPA activity and stroke risk. Our objectives were therefore to assess the relationships between retinal vessel, SAM and HPA responses, and to determine stroke risk. METHODS: A prospective bi-ethnic gender cohort (n = 275, 45 ± 9 years) was included. Urine/serum/saliva samples for SAM [norepinephrine:creatinine ratio (u-NE)] and HPA [adrenocorticotrophic hormone (ACTH), cortisol] were obtained at baseline, three-year follow up and upon flicker light-induced provocation. Diastolic ocular perfusion pressure was measured as a marker of hypo-perfusion. Retinal arterial narrowing and venous widening calibres were quantified from digital images in the mydriatic eye. A validated stress and stroke risk score was applied. RESULTS: An interaction term was fitted for venous dilation in u-NE tertiles (p ≤ 0.05) and not in u-NE median/quartiles/quintiles. Independent of race or gender, tertile 1 (low u-NE) had a 112% increase in u-NE, decreases in cortisol, and no changes in ACTH over three years (positive feedback). Tertile 3 (high u-NE) contradictorily had decreases in u-NE and cortisol, and increases in ACTH (negative feedback). In tertile 1, reduced arterial dilation, and faster arterial vasoconstriction and narrowing were related to higher SAM activity and hypo-perfusion (p ≤ 0.05), whereas delayed venous dilation, recovery and widening were related to cortisol hypo-secretion (p ≤ 0.05). In tertile 1, delayed venous recovery responses predicted stress and stroke risk [odds ratio 4.8 (1.2-19.6); p = 0.03]. These associations were not found in u-NE tertiles 2 and 3. CONCLUSIONS: In response to low norepinephrine, a reflex increase in SAM activity occurred, enhancing arterial vasoconstriction and hypo-perfusion. Concomitant HPA dysregulation attenuated retinal vein vasoactivity and tone, reflecting delayed vein recovery responses and non-adaptation to stress. These constrained vein recovery responses are indicative of increased chronic stress and stroke risk.

Retinal-glia ischemia and inflammation induced by chronic stress: The SABPA study.

Background: Psychobiological processes linking stress and vascular diseases remain poorly understood. The retina and the brain share a common embryonic-diencephalon origin and blood-barrier physiology e.g. ongoing ischemia facilitates S100B release with astrocytic activity and glial-fibrillary-acidic-protein expression (GFAP). However, GFAP decreases revealed astrocyte pathology in the prefrontal cortex of depression/suicide cases; and might be a key mechanism in stress - disease pathways. Methods: A chronic emotional stress phenotype independent of age, ethnicity or sex was used to stratify the current prospective cohort (N â€‹= â€‹359; aged 46 â€‹± â€‹9 years) into Stress (N â€‹= â€‹236) and no-Stress groups (N â€‹= â€‹123). Prospective data for glia ischemia risk markers were obtained, including 24 â€‹h BP, fasting S100B, GFAP, HbA1C and tumor-necrosis-factor-α (TNF-α). At 3-yr follow-up: diastolic-ocular-perfusion-pressure (indicating hypo-perfusion risk) was measured and retinal vessel calibers were quantified from digital images in the mydriatic eye. Results: Higher hypertension (75% vs. 16%), diabetes (13% vs. 0%) and retinopathy (57% vs. 45%) prevalence was observed in Stress compared to no-Stress individuals. Stressed individuals had consistently raised S100B, TNF-α, HbA1C and higher diastolic-ocular-perfusion-pressure, but decreases in GFAP and GFAP:S100B. Furthermore stroke risk markers, arterial narrowing and venous widening were associated with consistently raised S100B, GFAP:S100B (p â€‹= â€‹0.060), TNF-α and higher diastolic-ocular-perfusion-pressure [Adj. R2 0.39-0.41, p â€‹≤ â€‹0.05]. No retinal-glia associations were evident in the no-Stress group. Conclusions: Retinal-glia ischemia and inflammation was induced by chronic stress. Persistent higher inflammation and S100B with GFAP decreases further reflected stress-induced astrocyte pathology in the human retina. It is recommended to increase awareness on chronic stress and susceptibility for brain ischemia.

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.

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.

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 (ß=0.33, p<0.001) and DBP (ß=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.

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.

The effect of hypnotherapeutic ego strengthening with female spouses of South African coronary artery bypass surgery patients.

In addition to exacerbating morbidity in male coronary artery bypass surgery (CABS) patients, their plight can also impose considerable strain on their female spouses' mood states, resulting in compromised quality of life. The current study was aimed at determining the impact of pre postoperative hypnotherapeutic ego strengthening (HES) on anxiety and depression in female spouses. It was conducted simultaneously with a recently published study of their CABS husbands' response to HES. Spouses whose husbands had been randomly assigned to an experimental group, were designated the experimental spouse group (n = 25) and spouses whose husbands constituted the control group, likewise comprised the control spouse group (n = 25). Assessment occurred preoperatively, on the day of discharge and at six week follow-up. Spouses in the experimental group (n = 25) were introduced to hypnotherapeutic ego strengthening (HES), pre and postoperatively. In the postoperative assessment experimental female spouses showed significantly reduced morbidity levels, which were maintained at follow-up. In contrast, females in the control group (n = 25) showed no change. The results supported the value of brief hypnotherapy as a means of psychologically empowering spouses whose husbands' were undergoing CABS.

Hypnotherapeutic ego strengthening with male South African coronary artery bypass patients.

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.

Cardiovascular reactivity patterns elicited by the cold pressor test as a function of aging.

BACKGROUND AND AIMS: The cold pressor test has been widely used in previous cardiovascular reactivity studies as a predictor of hypertension. However, the influence of the physical adaptations of the arterial wall with increasing age on reactivity has not been delineated. METHODS: 64 men divided into 5 different age groups participated in a laboratory protocol consisting of submerging one hand in ice water for one minute while changes in blood pressure were continuously measured. RESULTS: The results indicated that with increasing age, the systolic blood pressure change, especially the rate of change (slope) is more pronounced than changes in diastolic blood pressure. CONCLUSIONS: With increasing age, there is a shift from a diastolic blood pressure reactivity pattern to a more systolic blood pressure reactivity pattern during application of the cold pressor test. This could be ascribed to a decrease in arterial compliance.