Cardiovascular Journal of Africa: Vol 32 No 1 (JANUARY/FEBRUARY 2021)

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 32, No 1, January/February 2021

AFRICA

Cardiovascular Topics

Delayed retinal vein recovery responses indicate both

non-adaptation to stress as well as increased risk for

stroke: the SABPA study

Leoné Malan, Mark Hamer, Roland von Känel, Konstantin Kotliar, Roelof D van Wyk, Gavin W

Lambert, Walthard Vilser, Tjalf Ziemssen, Markus P Schlaich, Wayne Smith, Martin Magnusson,

Annemarie Wentzel, Carlien E Myburgh, Hendrik S Steyn, Nico T Malan

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 objec-

tives 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 (

= 275, 45

± 9 years) was included. Urine/serum/saliva samples for SAM

[norepinephrine:creatinine ratio (u-NE)] and HPA [adreno-

corticotrophic hormone (ACTH), cortisol] were obtained at

baseline, three-year follow up and upon flicker light-induced

provocation. Diastolic ocular perfusion pressure was meas-

ured as a marker of hypo-perfusion. Retinal arterial narrow-

ing 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 (

≤ 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 vasoconstric-

tion and narrowing were related to higher SAM activity and

hypo-perfusion (

≤ 0.05), whereas delayed venous dilation,

recovery and widening were related to cortisol hypo-secretion

(

≤ 0.05). In tertile 1, delayed venous recovery responses

predicted stress and stroke risk [odds ratio 4.8 (1.2–19.6);

= 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 vaso-

constriction and hypo-perfusion. Concomitant HPA dysregu-

Hypertension in Africa Research Team (HART), North-West

University, Potchefstroom, South Africa

Leoné Malan, RN, PhD,

leone.malan@nwu.ac.za

Roland von Känel, MD

Wayne Smith, PhD

Annemarie Wentzel, PhD

Carlien E Myburgh, MSc

Nico T Malan, DSc

Division of Surgery & Interventional Science, Faculty of

Medical Sciences, University College London, United Kingdom

Mark Hamer, PhD

Department of Consultation-Liaison Psychiatry and Psycho-

somatic Medicine, University Hospital Zurich 8091, Switzerland

Roland von Känel, MD

Department of Medical Engineering and

Technomathematics, FH Aachen University of Applied

Sciences, Jülich, Germany

Konstantin Kotliar, Dr-Ing, PhD

Surgical Ophthalmologist, Potchefstroom, South Africa

Roelof D van Wyk, MD

Iverson Health Innovation Research Institute, Swinburne

University of Technology, Hawthorn; Baker Heart &

Diabetes Institute, Melbourne, Australia

Gavin W Lambert, PhD

Imedos Systems GmbH, Jena, Germany

Walthard Vilser, Dr-Ing

Autonomic and Neuroendocrinological Laboratory

Dresden, University Hospital Carl Gustav Carus,

Technische Universität Dresden, Germany

Tjalf Ziemssen, PhD, MD

Dobney Hypertension Centre, School of Medicine, Royal

Perth Hospital Unit, University Western Australia, Perth,

Australia

Markus P Schlaich, PhD, MD

Medical Research Council Research Unit: Hypertension

and Cardiovascular Disease, North-West University,

Potchefstroom, South Africa

Wayne Smith, PhD

Department of Clinical Sciences, Malmö, Lund University;

Wallenberg Centre for Molecular Medicine, Malmö, Lund

University; Department of Cardiology, Malmö, Skåne

University Hospital, Sweden

Martin Magnusson, PhD, MD

Statistical Consultation Services, North-West University,

Potchefstroom, South Africa

Hendrik S Steyn, DSc