Leoné Malan1, Mark Hamer2, Roland von Känel3, Konstantin Kotliar4, Roelof D van Wyk5, Gavin W Lambert6, Walthard Vilser7, Tjalf Ziemssen8, Markus P Schlaich9, Wayne Smith10, Martin Magnusson11, Annemarie Wentzel12, Carlien E Myburgh12, Hendrik S Steyn13, Nico T Malan12. 1. Hypertension in Africa Research Team (HART), North-West University, Potchefstroom, South Africa. Email: leone.malan@nwu.ac.za. 2. Division of Surgery & Interventional Science, Faculty of Medical Sciences, University College London, United Kingdom. 3. Hypertension in Africa Research Team (HART), North-West University, Potchefstroom, South Africa; Department of Consultation-Liaison Psychiatry and Psychosomatic Medicine, University Hospital Zurich 8091, Switzerland. 4. Department of Medical Engineering and Technomathematics, FH Aachen University of Applied Sciences, Jülich, Germany. 5. Surgical Ophthalmologist, Potchefstroom, South Africa. 6. Iverson Health Innovation Research Institute, Swinburne University of Technology, Hawthorn; Baker Heart & Diabetes Institute, Melbourne, Australia. 7. Imedos Systems GmbH, Jena, Germany. 8. Autonomic and Neuroendocrinological Laboratory Dresden, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany. 9. Dobney Hypertension Centre, School of Medicine, Royal Perth Hospital Unit, University Western Australia, Perth, Australia. 10. Hypertension in Africa Research Team (HART), North-West University, Potchefstroom, South Africa; Medical Research Council Research Unit: Hypertension and Cardiovascular Disease, North-West University, Potchefstroom, South Africa. 11. Department of Clinical Sciences, Malmö, Lund University; Wallenberg Centre for Molecular Medicine, Malmö, Lund University; Department of Cardiology, Malmö, Skåne University Hospital, Sweden. 12. Hypertension in Africa Research Team (HART), North-West University, Potchefstroom, South Africa. 13. Statistical Consultation Services, North-West University, Potchefstroom, South Africa.
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.
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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