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

A pilot investigation of the association between HIV-1 Vpr amino acid sequence diversity and the tryptophan-kynurenine pathway as a potential mechanism for neurocognitive impairment

Abstract HIV infection compromises both the peripheral and central immune systems due to its pathogenic and neuropathogenic features. The mechanisms driving HIV-1 pathogenesis and neuropathogenesis involve a series of events, including metabolic dysregulation. Furthermore, HIV-subtype-specific variations, particularly alterations in the amino acid sequences of key viral proteins, are known to influence the severity of clinical outcomes in people living with HIV. However, the impact of amino acid sequence variations in specific viral proteins, such as Viral protein R (Vpr), on metabolites within the Tryptophan (Trp)-kynurenine (Kyn) pathway in people living with HIV remains unclear. Our research aimed to explore the relationship between variations in the Vpr amino acid sequence (specifically at positions 22, 41, 45, and 55, as these have been previously linked to neurocognitive function) and peripheral Trp-Kyn metabolites. Additionally, we sought to clarify the systems biology of Vpr sequence variation by examining the link between Trp-Kyn metabolism and peripheral inflammation, as a neuropathogenic mechanism. In this preliminary study, we analyzed a unique cohort of thirty-two (n = 32) South African cART naïve people living with HIV. We employed Sanger sequencing to ascertain blood-derived Vpr amino acid sequence variations and a targeted LC-MS/MS metabolomics platform to assess Trp-Kyn metabolites, such as Trp, Kyn, kynurenic acid (KA), and quinolinic acid (QUIN). Particle-enhanced turbidimetric assay and Enzyme-linked immunosorbent assays were used to measure immune markers, hsCRP, IL-6, suPAR, NGAL and sCD163. After applying Bonferroni corrections (p =.05/3) and adjusting for covariates (age and sex), only the Vpr G41 and A55 groups was nearing significance for higher levels of QUIN compared to the Vpr S41 and T55 groups, respectively (all p =.023). Multiple regression results revealed that Vpr amino acid variations at position 41 (adj R2 = 0.049, β = 0.505; p =.023), and 55 (adj R2 = 0.126, β = 0.444; p =.023) displayed significant associations with QUIN after adjusting for age and sex. Lastly, the higher QUIN levels observed in the Vpr G41 group were found to be correlated with suPAR (r =.588, p =.005). These results collectively underscore the importance of specific Vpr amino acid substitutions in influencing QUIN and inflammation (specifically suPAR levels), potentially contributing to our understanding of their roles in the pathogenesis and neuropathogenesis of HIV-1

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

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 ischemia 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 colour-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 whilst 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 (β=0.25; 95% CI 0.05 to 0.45; p=0.02). In the Black men, constant cTnT levels were inversely associated with executive cognitive function (β= -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 to 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. This article is protected by copyright. All rights reserved

Additional file 1 of A pilot investigation of the association between HIV-1 Vpr amino acid sequence diversity and the tryptophan-kynurenine pathway as a potential mechanism for neurocognitive impairment

Supplementary Material 1: LC-MS/MS MRM parameter setu

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; β = 0.48; 95% CI 0.28-0.68, p < 0.001) and baseline SBP (Adj R2 0.43; β = 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

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 R2=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