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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

Malan, Leoné ; Hamer, Mark ; von Känel, Roland ; Kotliar, Konstantin ; van Wyk, Roelof D ; Lambert, Gavin W ; Vilser, Walthard ; Ziemssen, Tjalf ; Schlaich, Markus P and Smith, Wayne , et al. (2021) In Cardiovascular Journal of Africa 32(1). p.7-18
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... (More)

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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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cardiovascular Journal of Africa
volume
32
issue
1
pages
7 - 18
publisher
Clinics Cardive Publishing (pty) Ltd
external identifiers
  • pmid:33104153
  • scopus:85102536074
ISSN
1995-1892
DOI
10.5830/CVJA-2020-031
language
English
LU publication?
yes
id
2d04dcd5-1633-4ea9-892d-5ec14ae3a92f
alternative location
http://www.cvja.co.za/onlinefirst/DOI-10-5830-CVJA-2020-031.pdf
date added to LUP
2020-10-31 13:28:32
date last changed
2024-06-12 22:36:43
@article{2d04dcd5-1633-4ea9-892d-5ec14ae3a92f,
  abstract     = {{<p>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.</p><p>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.</p><p>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.</p><p>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.</p>}},
  author       = {{Malan, Leoné and Hamer, Mark and von Känel, Roland and Kotliar, Konstantin and van Wyk, Roelof D and Lambert, Gavin W and Vilser, Walthard and Ziemssen, Tjalf and Schlaich, Markus P and Smith, Wayne and Magnusson, Martin and Wentzel, Annemarie and Myburgh, Carlien E and Steyn, Hendrik S and Malan, Nico T}},
  issn         = {{1995-1892}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{7--18}},
  publisher    = {{Clinics Cardive Publishing (pty) Ltd}},
  series       = {{Cardiovascular Journal of Africa}},
  title        = {{Delayed retinal vein recovery responses indicate both non-adaptation to stress as well as increased risk for stroke : the SABPA study}},
  url          = {{http://dx.doi.org/10.5830/CVJA-2020-031}},
  doi          = {{10.5830/CVJA-2020-031}},
  volume       = {{32}},
  year         = {{2021}},
}