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

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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 32, No 1, January/February 2021 10 AFRICA
and included age, waist circumference (WC), cotinine smoking
status, γ-GT, HbA1c, HDL-C, hypertensive/diabetic retinopathy
and DOPP.4,18 An interaction term was fitted for retinal vein
dilation [F1, 254 = 4.34 ( p = 0.014)] in u-NE tertiles, and not in
median/quartiles or quintiles. Hence the cohort was stratified
into baseline norepinephrine:creatinine (u-NE in nmol/l:mmol/l)
ratio tertile groups supporting assessment for SAM activity/
adrenergic drive and potential monoamine depletion.33-36 The
Table 2. Comparing unadjusted stress hormones, HDL-C and retinal vessel calibres across norepinephrine:creatinine (u-NE nmol/l:mmol/l) tertile groups
Tertile 1 Tertile 2 Tertile 3 p-values
u-NE median
(min–max): 8.74
(1.05–14.77) (n = 93)
u-NE median
(min–max): 21.23
(15.05–28.62) (n = 9)
u-NE median
(min–max): 40.62
(28.69–113.63) ( n = 91)
u-NE
tertiles
1 vs 3
u-NE
tertiles
1 vs 2
u-NE
tertiles
2 vs 3
3-yr stress hormones changes
∆3yr u-NE (%) 111.6 (4.1, 207.4) –7.08 (–46.0, 53.4) –27.8 (–54.0, 21.1) 0.01 (0.01) 0.01 (0.01) 0.01 (0.04)
∆3yr ACTH (%) 2.5 (–30.1, 37.2) 16.1 (–20.6, 58.4) 26.2 (–15.8, 83.9) 0.02 (0.01) 0.25 (0.09) 0.91 (0.32)
∆3yr cortisol (%) –37.9 (–53.6, –17.7) –34.0 (–49.8, –13.0) –41.7 (–54.5, –19.3) 1.00 (0.59) 1.00 (0.32) 0.50 (0.19)
∆3yr HDL-C (%) –11.4 (–24.6, 0.81) –13.3 (–27.6, 1.67) –11.8 (–20.0, 4.88) 1.00 (0.63) 1.00 (0.79) 1.00 (0.48)
Saliva stress hormones prior to and upon FLIP
Pre-FLIP α-amylase (U/ml) 36.8 (20.4, 73.9) 39.7 (17.5, 72.0) 41.4 (26.0, 62.2) 1.00 (0.89) 1.00 (0.87) 1.00 (0.83)
∆FLIP α-amylase (U/ml) 38.3 (22.0, 64.3) 37.6 (19.3, 66.9) 38.8 (22.7, 68.4) 1.00 (0.89) 1.00 (0.89) 1.00 (0.76)
∆FLIP α-amylase (%) –9.79 (–35.3, 44.8) –5.6 (–48.4, 64.5) –4.30 (–36.7, 39.2) 1.00 (0.96) 1.00 (0.89) 1.00 (1.00)
Pre-FLIP cortisol (nmol/l) 5.5 (3.94, 8.05) 5.1 (3.55, 8.59) 5.1 (3.34, 7.04) 0.64 (0.21) 1.00 (0.50) 1.00 (0.59)
∆FLIP cortisol (nmol/l) 5.3 (3.79, 8.11) 4.87 (3.38, 7.39) 4.7 (3.20, 6.65) 0.37 (0.12) 0.69 (0.24) 1.00 (0.74)
∆FLIP cortisol (%) –0.2 (–9.12, 7.28) –8.2 (–14.9, 1.46) –5.2 (–11.4, 3.48) 1.00 (0.33) 0.05 (0.02) 0.39 (0.10)
Structure: retinal arteries and veins
Retinal artery (MU) 151.2 (143.1, 158.9) 152.1 (141.0, 160.0) 151.4 (141.7, 157.4) 1.00 (0.97) 1.00 (0.65) 1.00 (0.63)
Retinal vein (MU) 245.3 (231.9, 257.8) 243.1 (227.2, 261.0) 239.5 (226.7, 249.8) 0.17 (0.05) 1.00 (0.87) 0.29 (0.11)
Functionality: arteries
Mean maximal arterial dilation, (% baseline) 3.7 (2.3, 5.2) 3.9 (1.9, 5.6) 3.6 (1.9, 5.3) 1.00 (0.85) 1.00 (0.70) 1.00 (0.57)
Time of maximal arterial constriction (from
the start of flicker) (s)
44.5 (37.0, 56.5) 50.0 (43.0, 62.0) 48.0 (38.0, 68.0) 0.55 (0.24) 0.05 (0.01) 0.82 (0.35)
Functionality: veins
Mean maximal venous dilation (% baseline) 3.9 (3.0, 5.0) 4.4 (3.1, 5.9) 3.8 (2.8, 4.7) 0.80 (0.37) 0.89 (0.30) 0.01 (0.03)
Post-FLIP vein recovery (% of baseline) 100.6 (100.3, 101.0) 100.5 (100.2, 100.9) 100.4 (100.1, 100.7) 0.10 (0.03) 1.00 (0.52) 0.44 (0.16)
Diastolic ocular perfusion pressure (mmHg) 69.0 (64.0, 75.0) 69.0 (59.0, 77.0) 69.0 (63.0, 75.0) 1.00 (0.07) 1.00 (0.46) 1.00 (0.61)
Data are presented as median values (inter-quartile ranges) whereas significance is shown using p-values of non-parametric Kruskal–Wallis tests followed by multiple
comparison tests (uncorrected p-values of Mann–Whitney U-test).
∆3yr, three-year changes; FLIP, flicker light-induced provocation; ∆FLIP, changes during FLIP; ACTH, adrenocorticotrophic hormone; HDL-C, high-density lipopro-
tein cholesterol.
Table 3. Forward stepwise linear regression analyses depicting
associations between retinal vessel calibres, stress hormones and risk
markers in norepinephrine:creatinine (u-NE nmol/l:mmol/l) tertile 1
u-NE tertile 1 median (min–max):
8.74 (1.05–4.77) (n = 92)
∆3yr stress hormones (%) Arteries (MU) Veins (MU)
Adjusted R2 0.32 0.38
β (95% CI) β (95% CI)
∆3yr u-NE (%) – –
∆3yr cortisol (%) – –
Baseline HDL-C (mmol/l) –0.20 (–0.38, –0.02),
p = 0.040
–
Stress hormone levels prior to FLIP
Adjusted R2 0.26 0.33
β (95% CI) β (95% CI)
Saliva α-amylase (U/ml) –0.28 (–0.50, –0.06),
p = 0.010
-
Saliva cortisol (nmol/l) – –0.33 (–0.53, –0.13),
p = 0.002
Diastolic ocular perfusion pres-
sure (mmHg)
–0.24 (–0.46, –0.02),
p = 0.024
–
∆3yr; three-year stress hormone changes (%); Prior to FLIP, saliva stress
hormone levels prior to FLIP. ∆, changes; FLIP, flicker light-induced provoca-
tion; HDL-C, high-density lipoprotein cholesterol.
Additional covariates included age, waist circumference, cotinine smoking
status, log-normalised gamma-glutamyl transferase, glycated haemoglobin,
hypertensive/diabetic retinopathy, diastolic ocular perfusion pressure and the
respective retinal artery/vein diameter.
Table 4. Ocular media and fundus assessment at three-year follow up
across norepinephrine:creatinine (u-NE nmol/l:mmol/l) tertiles
Count, prevalence (%)
u-NE
tertile 1
(n = 93)
u-NE
tertile 2
(n = 91)
u-NE
tertile 3
(n = 91)
Referred to opthalmologist 6 (6.7) 7 (7.8) 11 (12.5)
Hypertensive/diabetic retinopathy 41 (44.6) 47 (51.7) 54 (59.3)*
Retinopathy included, n (%)
Intra-ocular pressure < 11 mmHg 12 (13.3) 8 (8.9) 9 (10.2)
Optic head (cup:disc ratio > 0.50) 17 (18.9) 12 (13.5) 21 (24.1)
Optic nerve head damage† 8 (8.9) 9 (10.2) 6 (6.7)
Acute anterior glaucoma risk 1 (1.1) 6 (6.7) 8 (9.1)
Retinal atrophy 2 (2.2) 0 (0.00) 0 (0.0)
Drusen 0 (0.0) 1 (1.1) 0 (0.0)
Ciliary blood vessels 1 (1.1) 0.(0.0) 0 (0.0)
Exudates 0 (0.0) 1 (1.1) 0 (0.0)
Haemorrhaging 4 (4.44) 1 (1.1) 1 (1.1)
Arteriovenous nicking 31 (33.7) 38 (41.8) 39 (42.9)
Neovascularisation 1 (1.1) 0 (0.0) 0 (0.0)
Cotton wool ischaemia 0 (0.0) 0 (0.0) 0 (0.0)
Focal narrowing 1 (1.1) 2 (2.2) 1 (1.1)
Macula scarring 1 (1.1) 0 (0.0) 0 (0.0)
Chi-squared statistics were used to determine prevalence in u-NE tertile 1 vs
u-NE tertile 3 [u-NE tertile 1, median (min–max): 8.74 (1.05–14.77); u-NE
tertile 2, median (min–max): 21.23 (15.05–28.62); u-NE tertile 3, median (min–
max): 40.62 (28.69–113.63)].
†Optic nerve head damage, cup-to-disc ratio ≥ 0.3 plus intra-ocular pressure ≥ 21
mmHg. *p ≤ 0.05.