The chronic stress risk phenotype mirrored in the human retina as a neurodegenerative condition.

The brain is the key organ that orchestrates the stress response which translates to the retina. The retina is an extension of the brain and retinal symptoms in subjects with neurodegenerative diseases substantiated the eye as a window to the brain. The retina is used in this study to determine whether chronic stress reflects neurodegenerative signs indicative of neurodegenerative conditions. A three-year prospective cohort (n = 333; aged 46 ± 9 years) was stratified into stress-phenotype cases (n = 212) and controls (n = 121) by applying the Malan stress-phenotype index. Neurodegenerative risk markers included ischemia (astrocytic S100 calcium-binding protein B/S100B); 24-h blood pressure, proteomics; inflammation (tumor-necrosis-factor-α/TNF-α); neuronal damage (neuron-specific-enolase); anti-apoptosis of retinal-ganglion-cells (beta-nerve-growth-factor), astrocytic activity (glial-fibrillary-acidic-protein); hematocrit (viscosity) and retinal follow-up data [vessels; stress-optic-neuropathy]. Stress-optic-neuropathy risk was calculated from two indices: a newly derived diastolic-ocular-perfusion-pressure cut-point ≥68 mmHg relating to the stress-phenotype; combined with an established cup-to-disk ratio cut-point ≥0.3. Higher stress-optic-neuropathy (39% vs. 17%) and hypertension (73% vs. 16%) prevalence was observed in the stress-phenotype cases vs. controls. Elevated diastolic-ocular-perfusion-pressure, indicating hypoperfusion, was related to arterial narrowing and trend for ischemia increases in the stress-phenotype. Ischemia in the stress-phenotype at baseline, follow-up and three-year changes was related to consistent inflammation (TNF-α and cytokine-interleukin-17-receptor-A), neuron-specific-enolase increases, consistent apoptosis (chitinase-3-like protein 1, low beta-nerve-growth-factor), glial-fibrillary-acidic-protein decreases, elevated viscosity, vein widening as risk marker of endothelial dysfunction in the blood-retinal barrier, lower vein count, and elevated stress-optic-neuropathy. The stress-phenotype and related neurodegenerative signs of ongoing brain ischemia, apoptosis and endothelial dysfunction compromised blood-retinal barrier permeability and optic nerve integrity. In fact, the stress-phenotype could identify persons at high risk of neurodegeneration to indicate a neurodegenerative condition.

Attenuated Relationships Between Indexes of Volume Overload and Atrial Natriuretic Peptide in Uncontrolled, Sustained Volume-Dependent Primary Hypertension.

BACKGROUND: Whether systolic blood pressure (SBP) control in sustained volume-dependent primary hypertension is associated with blunted ANP (atrial natriuretic peptide) relationships with indexes of volume load is unknown. METHODS: Systemic hemodynamics (central pressure, echocardiographic aortic velocity and diameter measurements in the outflow tract), circulating ANP concentrations (ELISA assays) and glomerular and tubular function (24-hour urine collections [n=519]) were determined in a community of African ancestry (n=772). RESULTS: As compared with those with a controlled SBP, those with an uncontrolled SBP (n=198) showed lower ANP concentrations (P<0.005) despite higher stroke volume and cardiac output (P<0.0001) and renal differences consistent with enhanced fluid retention. In those with a controlled SBP, fractional Na+ excretion (FeNa+; P<0.0005) and creatinine clearance (glomerular filtration rate; P<0.005) were inversely associated with ANP concentrations independent of confounders. Moreover, in those with a controlled SBP, stroke volume and cardiac output (P<0.0001) were independently and positively associated with ANP concentrations. In addition, in those with a controlled SBP, ANP concentrations were independently and inversely associated with systemic vascular resistance (SVR; P<0.0001) and aortic characteristic impedance (Zc; P<0.005). By contrast, in those with uncontrolled SBP, no relationships between either stroke volume (P>0.25), cardiac output (P>0.29), FeNa+ (P>0.77), or glomerular filtration rate (P>0.47) and ANP concentrations were noted. Furthermore, in those with an uncontrolled SBP, no relationships between ANP concentrations and SVR or Zc were observed (P>0.34). CONCLUSIONS: In a population where primary hypertension is strongly volume-dependent, those with an uncontrolled SBP have an attenuated relationship between ANP and both renal and hemodynamic indexes of volume overload and the vascular effects of ANP.

Independent relationships between renal mechanisms and systemic flow, but not resistance to flow in primary hypertension in Africa.

AIMS: Whether renal mechanisms of hypertension primarily translate into increases in systemic vascular resistance (SVR) in all populations is uncertain. We determined whether renal mechanisms associate with either increases in SVR (and impedance to flow) or systemic flow in a community of African ancestry. METHOD: In a South African community sampled across the full adult age range (n = 546), we assessed stroke volume (SV), peak aortic flow (Q), SVR, characteristic impedance (Zc) and total arterial compliance (TAC) from velocity and diameter measurements in the outflow tract (echocardiography) and central arterial pressures. Renal changes were determined from creatinine clearance (glomerular filtration rate, GFR) and fractional Na+ excretion (FeNa+) (derived from 24-h urine collections). RESULTS: Independent of confounders (including MAP and pressures generated by the product of Q and Zc), SV (and hence cardiac output) (P < 0.0001) and Q (P < 0.01), but not SVR, Zc or TAC (P = 0.09-0.20) were independently associated with decreases in both GFR (index of nephron number) and FeNa+. Through an interactive effect (P < 0.0001), the impact of GFR on SV or Q was strongly determined by FeNa+ and vice versa. The relationship between the GFR-FeNa+ interaction and either SV or Q was noted in those above or below 50 years of age, although neither GFR, FeNa+ nor the interaction were independently associated with SVR, Zc or TAC at any age. CONCLUSION: Across the full adult lifespan, in groups of African ancestry, renal mechanisms of hypertension translate into increases in systemic flow rather than into resistance or impedance to flow.

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.

Defensive coping and essential amino acid markers as possible predictors for structural vascular disease in an African and Caucasian male cohort: The SABPA study.

Defensive coping (DefS), oxidative stress, inflammation, and related amino acids (phenylalanine [Phe] and tyrosine [Tyr]) have been implicated in cardiovascular disease. This study assessed whether inflammation, oxidative stress, changes in essential amino acids, and altered coping strategies are correlated with subclinical vascular changes in African (n = 82) and Caucasian (n = 100) men from the Sympathetic Activity and Ambulatory Blood Pressure in Africans (SABPA) study. The Coping Strategy Indicator questionnaire identified DefS participants. Ambulatory blood pressure (BP) was monitored for 24 h, whereas carotid intima media thickness (CIMT) and cross-sectional wall area (CSWA) were determined ultrasonically. Essential amino acids were analyzed with a liquid chromatography tandem mass spectrometry method. Oxidative-inflammatory markers were measured by spectrophotometry. African men had poorer health than Caucasian men, including higher alcohol abuse, elevated BP, abdominal obesity, physical inactivity, and elevated inflammation. Phe (p < .001) and Phe/Tyr ratio (p = .006) as well as CIMT (p = .032) were higher in African men. DefS African men had higher levels of Phe (p = .002) and Phe/Tyr (p = .009) compared to DefS Caucasian men; these differences were not observed in non-DefS men. Systolic BP and inflammation (C-reactive protein) were positively associated with left (L-) CSWA, while Phe/Tyr was negatively associated with L-CSWA in DefS African men. African males presented with elevated Phe and Phe/Tyr ratio, catecholamine precursors, worsening during DefS-possibly driven by inflammation and BP contributing to structural vascular abnormalities.

Emotional Stress as a Risk for Hypertension in Sub-Saharan Africans: Are We Ignoring the Odds?

Globally most interventions focus on improving lifestyle habits and treatment regimens to combat hypertension as a non-communicable disease (NCD). However, despite these interventions and improved medical treatments, blood pressure (BP) values are still on the rise and poorly controlled in sub-Saharan Africa (SSA). Other factors contributing to hypertension prevalence, such as chronic emotional stress, might provide some insight for future health policy approaches.Currently, Hypertension Society guidelines do not mention emotional stress as a probable cause for hypertension. Recently the 2014 World Global Health reports, suggested that African governments should consider using World Health Organization hypertension data as a proxy indicator for social well-being. However, the possibility that a stressful life and taxing environmental factors might disturb central neural control of BP regulation has largely been ignored in SSA.Linking emotional stress to vascular dysregulation is therefore one way to investigate increased cardiometabolic challenges, neurotransmitter depletion and disturbed hemodynamics. Disruption of stress response pathways and subsequent changes in lifestyle habits as ways of coping with a stressful life, and as probable cause for hypertension prevalence in SSA, may be included in future preventive measures. We will provide an overview on emotional stress and central neural control of BP and will include also implications thereof for clinical practice in SSA cohorts.

Myocardial Perfusion SPECT Imaging in Dextrocardia with Situs Inversus: A Case Report.

Dextrocardia is a cardiac positional anomaly in which the heart is located in the right hemithorax with its base-to-apex axis directed to the right and caudad. Situs inversus is an autosomal recessive disorder that causes organs in the chest and abdomen to be positioned in a mirror image from their normal position. Dextrocardia may occur in isolation or as part of situs inversus. Similarly, situs inversus may occur with or without dextrocardia. Situs inversus accompanied with dextrocardia (situs inversus totalis) is a rare congenital abnormality occurring in 0.01% of live births. Herein, we present the case of a 35-year-old man with previously diagnosed situs inversus totalis with mirror-image dextrocardia, referred to our facility for diagnosis of coronary artery disease (CAD). The incidence and presentation of CAD in patients with dextrocardia are similar to the normal population. However, considerable attention should be paid to the acquisition of myocardial perfusion scintigraphy and data processing/analysis in this group of patients. The present case highlights the distinctive applications and potential pitfalls of myocardial perfusion single-photon emission computed tomography (SPECT) imaging in patients with dextrocardia.

Chronic depression symptoms and salivary NOx are associated with retinal vascular dysregulation: The SABPA study.

BACKGROUND: Depression has been associated with impaired nitric oxide (NO)-mediated vasodilation and vascular dysregulation (VD). Whether depression and NO levels will disturb retinal haemodynamics is not clear. OBJECTIVES AND METHODS: Associations between the retinal vasculature, diastolic ocular perfusion pressure (DOPP) as measure of hypoperfusion, NO metabolites (NOx) and depression symptoms were assessed. Chronic VD risk markers [depression symptoms (Patient Health Questionnaire/PHQ-9 ≥ 10) and 24 h pulse pressure] were determined in a bi-ethnic cohort (n = 313; 48.6 ± 9 years; 53.9% men). At 3 year follow-up, retinal vessel calibre and retinopathy signs were quantified from digital images. Salivary NOx was obtained pre- and post-flicker light-induced provocation (FLIP). DOPP was defined as diastolic blood pressure minus intraocular pressure. RESULTS: Chronic VD risk was evident in Blacks opposed to acute risk in Whites (P < 0.05). At follow-up, retinopathy (Blacks 60.4%/Whites 39.6%), lower pre-FLIP (µM) and higher post-FLIP NOx (changes from baseline, %), arteriolar narrowing and wider venular calibre values were evident in Blacks compared to Whites, independent of confounders. A wider venular calibre, an index of stroke risk, was associated with chronic depression symptoms [cut point 248 MU: Area under the curve 0.61 (95% CI: 0.51, 0.72); 71% sensitivity; 55% specificity] as well as with hypoperfusion in the Blacks. In this group, arteriolar narrowing was associated with hypoperfusion; and attenuated arteriolar dilation with increased post-FLIP NOx responses. CONCLUSIONS: Chronic depression symptoms may alter NO regulation and facilitate VD. NO-mediated vasoconstriction presumably impeded perfusion, retinal haemodynamics and -remodelling; potentiating stroke risk in Blacks.

Masked hypertension and its associated cardiovascular risk in young individuals: the African-PREDICT study.

Hypertension prevalence is increasing globally, yet little is known about the occurrence of masked hypertension (MHT) in young, sub-Saharan African adults, and how it relates to elevated cardiovascular risk. The African-PREDICT study (recruitment based on normotensive clinic blood pressure (BP)) determined the frequency of MHT and its relationship with arterial stiffness and biochemical markers of inflammation and endothelial activation. We included men and women (n=352), 20-30 years, screened for normotensive clinic BP (54% white, 40% men). Clinic BP, ambulatory blood pressure monitoring (ABPM), central systolic pressure, aortic pulse wave velocity (aPWV), augmentation index, anthropometry, physical activity and biochemical markers of cardiovascular risk were assessed (lipids, glucose, insulin, markers of endothelial activation and inflammation). Eighteen percent of the study population had MHT (60% white, 68% men). Those with MHT had increased adiposity, clinic-, ABPM- (24-h, day and night) and central-BP (within normal ranges), heart rate, aPWV and biochemical markers of cardiovascular risk, compared with normotensives (all P<0.05). Using multivariable adjusted odds ratios, we found that MHT was associated with increased likelihood for higher aPWV (odds ratio (OR)=1.567, P=0.010), insulin (OR=1.499, P=0.049), monocyte chemoattractant protein-1 (OR=1.499, P=0.026), vascular cellular adhesion molecule (OR=1.409, P=0.042) and C-reactive protein (OR=1.440, P=0.044). In a young adult (supposedly healthy) cohort, the occurrence of MHT is alarming, especially since MHT further demonstrated elevated cardiovascular risk via increased adiposity, arterial stiffness, endothelial activation and inflammation. Detection of MHT is crucial to increase awareness of elevated cardiovascular risk, and to ensure the required lifestyle and/or pharmaceutical interventions.

Three-year changes of prothrombotic factors in a cohort of South Africans with a high clinical suspicion of obstructive sleep apnea.

A hypercoagulable state might be one important mechanism linking obstructive sleep apnea (OSA) with incident myocardial infarction and stroke. However, previous studies on prothrombotic factors in OSA are not uniform and cross-sectional. We longitudinally studied prothrombotic factors in relation to OSA risk, adjusting for baseline levels of prothrombotic factors, demographics, metabolic parameters, aspirin use, and life style factors. The Berlin Questionnaire and/or neck circumference were used to define high OSA risk in 329 South African teachers (48.0% male, 44.6% black) at baseline and at three-year follow-up. Von Willebrand factor (VWF), fibrinogen, D-dimer, plasminogen activator inhibitor-1, clot lysis time (CLT), and soluble urokinase-type plasminogen activator receptor (suPAR) were measured in plasma. At baseline 35.7% of participants had a high risk of OSA. At follow-up, persistently high OSA risk, persistently low OSA risk, OSA risk remission, and new-onset OSA risk were present in 26.1%, 53.2%, 9.4%, and 11.3% of participants, respectively. New-onset OSA risk was associated with a significant and longitudinal increase in VWF, fibrinogen, CLT, and suPAR relative to persistently low OSA risk; in VWF, fibrinogen, and suPAR relative to remitted OSA risk; and in VWF relative to persistently high OSA risk. Persistently high OSA risk was associated with an increase in CLT and suPAR relative to persistently low OSA risk and in D-dimer relative to remitted OSA risk. Remitted OSA risk was associated with D-dimer decrease relative to persistently low OSA risk. In OSA, hypercoagulability is a dynamic process with a most prominent three-year increase in individuals with new-onset OSA risk.

Low serum testosterone and increased diastolic ocular perfusion pressure: a risk for retinal microvasculature.

BACKGROUND: Low levels of testosterone in men and changes in retinal microvascular calibre are both associated with hypertension and cardiovascular disease risk. Sex hormones are also associated with blood flow in microvascular beds which might be a key intermediate mechanism in the development of hypertension. Whether a direct association between endogenous testosterone and retinal microvascular calibre exists is currently unknown. We aimed to determine whether testosterone is independently associated with ocular perfusion via a possible association with retinal vascular calibre or whether it plays only a secondary role via its effect on blood pressure in a bi-ethnic male cohort. PROBANDS AND METHODS: A total of 72 black and 81 white men (28-68 years of age) from the follow-up phase of the Sympathetic activity and Ambulatory Blood Pressure in Africans (SABPA) study were included in this sub-study. Ambulatory pulse pressure and intraocular perfusion pressures were obtained, while metabolic variables and testosterone were measured from fasting venous blood samples. Retinal vascular calibre was quantified from digital photographs using standardised protocols. RESULTS: The black men revealed a poorer cardiometabolic profile and higher pulsatile pressure (>50 mm Hg), intraocular pressure and diastolic ocular perfusion pressure than the white men (p≤0.05). Only in the white men was free testosterone positively associated with retinal calibre, i.e. arterio-venular ratio and central retinal arterial calibre and inversely with central retinal venular calibre. These associations were not found in the black men, independent of whether pulse pressure and ocular perfusion pressure were part of the model. CONCLUSIONS: These results suggest an independent, protective effect of testosterone on the retinal vasculature where an apparent vasodilatory response in the retinal resistance microvessels was observed in white men.

Defensive coping and renovascular disease risk - Adrenal fatigue in a cohort of Africans and Caucasians: The SABPA study.

BACKGROUND: Defensive coping is an established cardiovascular risk factor in Africans. Additionally, chronic, excessive or inadequate hypothalamic-pituitary-adrenal axis (HPAA) stress responses could either increase or decrease cortisol responses, which may relate to renal impairment. We scrutinised the relationship between urinary cortisol levels and renovascular disease risk in Africans and Caucasians utilising defensive coping. METHODS: Africans (n=168) and Caucasians (n=207) from the SABPA (Sympathetic activity and Ambulatory Blood Pressure in Africans) study were included in our analyses, excluding HIV positive, diabetic, renal impairment, and cortisone users. The Coping Strategy Indicator questionnaire assessed preferred coping responses. Ambulatory blood pressure was recorded together with 8h fasting blood and urine sampling. Renovascular disease risk markers included the albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). RESULTS: The main findings revealed that Caucasians with high cortisol showed augmented renovascular disease risk. Conversely, Africans revealed low cortisol levels whilst 21.84% reported experience of severe stress, possibly depicting HPAA hypoactivity. Additionally, these Africans with low cortisol revealed increased ACR and decreased eGFR, which was further enhanced by defensive coping. CONCLUSIONS: Defensive coping enhanced renovascular risk in Africans, especially in those with lower cortisol, which may be due to HPAA dysfunction and/or adrenal fatigue.

Comparison of telomere length in black and white teachers from South Africa: the sympathetic activity and ambulatory blood pressure in Africans study.

OBJECTIVE: Telomere length is a marker of biological aging that has been linked to cardiovascular disease risk. The black South African population is witnessing a tremendous increase in the prevalence of cardiovascular disease, part of which might be explained through urbanization. We compared telomere length between black South Africans and white South Africans and examined which biological and psychosocial variables played a role in ethnic difference in telomere length. METHODS: We measured leukocyte telomere length in 161 black South African teachers and 180 white South African teachers aged 23 to 66 years without a history of atherothrombotic vascular disease. Age, sex, years having lived in the area, human immunodeficiency virus (HIV) infection, hypertension, body mass index, dyslipidemia, hemoglobin A1c, C-reactive protein, smoking, physical activity, alcohol abuse, depressive symptoms, psychological distress, and work stress were considered as covariates. RESULTS: Black participants had shorter (median, interquartile range) relative telomere length (0.79, 0.70-0.95) than did white participants (1.06, 0.87-1.21; p < .001), and this difference changed very little after adjusting for covariates. In fully adjusted models, age (p < .001), male sex (p = .011), and HIV positive status (p = .023) were associated with shorter telomere length. Ethnicity did not significantly interact with any covariates in determining telomere length, including psychosocial characteristics. CONCLUSIONS: Black South Africans showed markedly shorter telomeres than did white South African counterparts. Age, male sex, and HIV status were associated with shorter telomere length. No interactions between ethnicity and biomedical or psychosocial factors were found. Ethnic difference in telomere length might primarily be explained by genetic factors.

Appropriate indications for positron emission tomography/computed tomography, 2015.

These recommendations are intended to serve an important and relevant role in advising referring physicians on the appropriate use of 18F-fluorodeoxyglucose (18F-FDG) and non-18F-FDG positron emission tomography/computed tomography (PET/CT), which can be a powerful tool in patient management in oncology, cardiology, neurology and infection/inflammation. PET is a non-invasive molecular imaging tool that provides tomographic images and quantitative parameters of perfusion, cell viability, proliferation and/or metabolic activity of tissues. These images result from the use of different substances of biological interest (sugars, amino acids, metabolic precursors, hormones) labelled with positron-emitting radionuclides (PET radiopharmaceuticals). Fusion of the aforementioned important functional information with the morphological detail provided by CT as PET/CT provides clinicians with a sensitive and accurate one-step whole-body diagnostic and prognostic tool, which directs and changes patient management. Hence PET/CT is currently the most widely used molecular imaging technology for a patient-tailored treatment approach. In these recommendations we outline which oncological and non-oncological indications are appropriate for PET/CT. Once each combination of pathology and clinical indication is defined, a recommendation is given as: 1. Recommended; 2. Recommended in select cases; 3. May be considered; or 4. Not recommended.

Progression of cardiovascular risk factors in black Africans: 3 year follow up of the SABPA cohort study.

Recent work identified a high prevalence of modifiable risk factors for cardiovascular disease (CVD) among urban black South Africans. The aim was to track the progression of CVD risk factors in a multi-ethnic sample of South Africans. Participants were 173 black (aged 47.5 ± 7.8 yrs) and 186 white teachers (aged 49.6 ± 9.9 yrs) that were examined at baseline and 3 years follow-up. Blacks demonstrated a substantially higher prevalence of composite CVD burden (defined as history of physician diagnosed heart disease, use of anti-hypertensives, anti-diabetic, or statin medications at either time point) compared to whites (49.1 vs. 32.0%, p = 0.012) respectively. After controlling for baseline, the black participants demonstrated greater increases in 24 h systolic and diastolic blood pressure, total cholesterol, fasting glucose, fibrinogen, D-dimer, and waist circumference in comparison with whites. In summary, an adverse progression of CVD risk factors was observed in the whole sample, although to a larger degree in black participants. Aggressive treatment strategies for controlling risk factors in black Africans are needed to reduce the increasing burden of CVD in South Africa.

Sex hormones associated with subclinical kidney damage and atherosclerosis in South African men: the SABPA study.

BACKGROUND: Hypertension and increased blood glucose are associated with subclinical kidney damage, atherosclerosis and with low testosterone values. Low testosterone in men is often accompanied by increased levels of estradiol. OBJECTIVES AND METHODS: In this study, the association between estradiol, subclinical kidney damage and atherosclerosis in African and white men in a South African cohort was investigated. Cardiovascular variables were studied by means of B-mode ultrasound and ambulatory blood pressure (BP) monitoring. The sex hormones and other biochemical values were measured from fasting venous blood and overnight urine samples. The ethnic groups were stratified into low and high testosterone groups by means of median split. RESULTS: The low testosterone African group demonstrated a higher cardiovascular risk compared with the low testosterone white men with 91% being hypertensive and having increased albumin-to-creatinine ratio (ACR), left carotid intima-media thickness (L-CIMTf) and estradiol-to-testosterone ratio. In the low-testosterone African men, estradiol explained 33% of the variance in ACR, whereas the estradiol-to-testosterone ratio explained 22% of the variance in L-CIMTf, respectively. Estradiol-to-testosterone ratio was positively associated with ACR in the low testosterone whites. CONCLUSION: We conclude that increased levels of estradiol may play a role in the development of subclinical kidney damage in both African and white men as well as atherosclerosis in low-testosterone African men.

Are behavioural risk factors to be blamed for the conversion from optimal blood pressure to hypertensive status in Black South Africans? A 5-year prospective study.

BACKGROUND: Longitudinal cohort studies in sub-Saharan Africa are urgently needed to understand cardiovascular disease development. We, therefore, explored health behaviours and conventional risk factors of African individuals with optimal blood pressure (BP) (≤ 120/80 mm Hg), and their 5-year prediction for the development of hypertension. METHODS: The Prospective Urban Rural Epidemiology study in the North West Province, South Africa, started in 2005 and included African volunteers (n = 1994; aged > 30 years) from a sample of 6000 randomly selected households in rural and urban areas. RESULTS: At baseline, 48% of the participants were hypertensive (≥ 140/90 mmHg). Those with optimal BP (n = 478) were followed at a success rate of 70% for 5 years (213 normotensive, 68 hypertensive, 57 deceased). Africans that became hypertensive smoked more than the normotensive individuals (68.2% vs 49.8%), and they also had a greater waist circumference [ratio of geometric means of 0.94 cm (95% CI: 0.86-0.99)] and greater amount of γ-glutamyltransferase [0.74 U/l (95% CI: 0.62-0.88)] at baseline. The 5-year change in BP was independently explained by baseline γ-glutamyltransferase [R(2) = 0.23, ß = 0.13 U/l (95% CI: 0.01-0.19)]. Alcohol intake also predicted central systolic BP and carotid cross-sectional wall area (CSWA) at follow-up. Waist circumference was another predictor of BP changes [ß = 0.18 cm (95% CI: 0.05-0.24)] and CSWA. HIV infection was inversely associated with increased BP. CONCLUSIONS: During the 5 years, 24% of Africans with optimal BP developed hypertension. The surge in hypertension in Africa is largely explained by modifiable risk factors. Public health strategies should focus aggressively on lifestyle to prevent a catastrophic burden on the national health system.

Defensive coping, urbanization, and neuroendocrine function in Black Africans: the THUSA study.

Dissociation between ß-adrenergic behavioral and physiological defensive active coping (AC) responses was associated with cardiometabolic risk in urban but not rural African males. Whether this is partly driven by underlying neuroendocrine dysfunction is not certain. We aimed to assess the association between coping style, urbanization, and neuroendocrine function. Blood pressure (BP) and serum stress hormones were assessed across levels of urbanization (rural vs. urban) and coping style (active vs. passive) in 178 Black African men. Urban men demonstrated increased hypertension prevalence, α-adrenergic hemodynamic pattern, lower testosterone levels, and a larger cortisol:testosterone ratio (Cort:Test) compared to their rural counterparts. This was particularly evident in urban AC men where cortisol and Cort:Test explained 36-40% of the variance in BP. Dissociation between behavioral and physiological ß-adrenergic neuroendocrine responses in urban AC African men was shown. A stressful urban environment might induce an apparent loss of physiological control, thereby facilitating disturbed neuroendocrine AC responses, which could increase cardiovascular disease risk.