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- Dieden, Anna, 1984-, et al.
(författare)
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Exploring biomarkers associated with deteriorating vascular health using a targeted proteomics chip : The SABPA study
- 2021
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Ingår i: Medicine. - : Lippincott Williams & Wilkins. - 0025-7974 .- 1536-5964. ; 100:20
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: In this observational study, by the use of a multiplex proteomic platform, we aimed to explore associations between 92 targeted proteins involved in cardiovascular disease and/or inflammation, and phenotypes of deteriorating vascular health, with regards to ethnicity.Proteomic profiling (92 proteins) was carried out in 362 participants from the Sympathetic activity and Ambulatory Blood Pressure in Africans (SABPA) study of black and white African school teachers (mean age 44.7 ± 9.9 years, 51.9% women, 44.5% Black Africans, 9.9% with known cardiovascular disease). Three proteins with <15% of samples below detectable limits were excluded from analyses. Associations between multiple proteins and prevalence of hypertension as well as vascular health [Carotid intima-media thickness (cIMT) and pulse wave velocity (PWV)] measures were explored using Bonferroni-corrected regression models.Bonferroni-corrected significant associations between 89 proteins and vascular health markers were further adjusted for clinically relevant co-variates. Hypertension was associated with growth differentiation factor 15 (GDF-15) and C-X-C motif chemokine 16 (CXCL16). cIMT was associated with carboxypeptidase A1 (CPA1), C-C motif chemokine 15 (CCL15), chitinase-3-like protein 1 (CHI3L1), scavenger receptor cysteine-rich type 1 protein M130 (CD163) and osteoprotegerin, whereas PWV was associated with GDF15, E-selectin, CPA1, fatty acid-binding protein 4 (FABP4), CXCL16, carboxypeptidase B (CPB1), and tissue-type plasminogen activator. Upon entering ethnicity into the models, the associations between PWV and CPA1, CPB1, GDF-15, FABP4, CXCL16, and between cIMT and CCL-15, remained significant.Using a multiplex proteomic approach, we linked phenotypes of vascular health with several proteins. Novel associations were found between hypertension, PWV or cIMT and proteins linked to inflammatory response, chemotaxis, coagulation or proteolysis. Further, we could reveal whether the associations were ethnicity-dependent or not.
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| 2. |
- Malan, Leoné, et al.
(författare)
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Delayed retinal vein recovery responses indicate both non-adaptation to stress as well as increased risk for stroke : the SABPA study
- 2021
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Ingår i: Cardiovascular Journal of Africa. - 1995-1892. ; 32:1, s. 7-18
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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