Cardiovascular Journal of Africa: Vol 31 No 6 (November/December 2020)

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 31, No 6, November/December 2020

AFRICA

301

stroke risk, with ORs of 2.48 and 4.48 for all participants

and females. Combinations UA

Hcy

LDL-C- and

Hcy

LDL-C

were significantly associated with

stroke risk, with ORs of 7.85 and 3.04 for females but not for all

participants. All other combinations were non-significant.

Discussion

We observed a significant association between UA level and

stroke risk in females but not in males. The combinations of

Hcy

TG-TC-LDL-C-, UA

Hcy

LDL-C- and

Hcy

LDL-C

could significantly increase the risk

of stroke.

We observed significant associations between UA level and

stroke risk for females and all participants, which was consistent

with the Rotterdam study,

but differed from the study of elderly

patients with isolated systolic hypertension

and a Chinese

hypertensive cohort study.

In the general population, two systematic reviews across

countries identified consistently significant associations between

UA level and stroke for men and women.

31,32

The inconsistent

associations between UA level and stroke risk may be explained

by the dual characteristics of UA.

UA can exert neuroprotective effects by acting as a free radical

scavenger,

therefore, UA may reduce the risk of neurological

disease, especially vascular and non-vascular dementia.

However, as a molecule generated locally in the vessel wall, UA

stimulates vascular smooth cell proliferation, which may directly

lead to the development of microvascular disease and afferent

arteriolopathy. UA also has a pro-inflammatory effect on the

vascular cell, with activation of P38, MAPK, NF-KB and AP-1,

and increased expression of cyclooxygenase-2 (COX-2) and

monocyte chemo-attractant protein-1 (MCP-1).

We identified a significant dose–response relationship

between UA level and stroke in female hypertensive patients,

which was consistent with the AMORIS study.

The gender-

specific difference in the association between UA level and stroke

may be due to differences in their endocrine profile, because sex

steroids play a significant role in UA regulation in biological

fluids.

Besides, high levels of UA were associated with silent

brain infarction, which strongly increased the risk of stroke in

females.

38,39

The menopause status in women may also explain

the gender-specific difference. UA levels are known to increase in

postmenopausal women because oestrogen can increase the renal

excretion rate of urate.

40,41

In the subgroup analyses stratified by stroke subtypes

comparing HU with normo-uricaemia, we observed significant

associations only between HU and IS. The small sample size of

HS and the different pathogenesis of IS and HS may explain

the non-significant association between HU and HS because

UA could stimulate vascular smooth muscle cell (VSMC)

proliferation and oxidative stress

and induce IS.

Previous prospective studies focused on the relationship

between UA level and stroke in various populations such as in

an older general population,

and hypertensive participants with

different diagnosis criteria.

16,17

Our study was consistent with two

studies conducted in China and Australia,

16,36

and was at variance

with one study conducted in China.

Table 3.The association between UA level and IS risk

Variables

UA (μmol/l)

-value

Q1 (UA ≤ 273)

Q2 (273 < UA ≤ 332)

Q3 (332 < UA ≤ 396)

Q4 (UA > 396)

Male (stroke/non-stroke)

18/261

24/469

46/663

49/805

0.74 (0.40–1.39)

1.01 (0.57–1.77)

0.88 (0.51–1.54)

0.6649

0.78 (0.41–1.47)

1.04 (0.59–1.84)

0.92 (0.53–1.61)

0.7239

0.77 (0.40–1.48)

1.16 (0.63–2.12)

1.22 (0.65–2.30)

0.3946

Female

39/851

33/644

34/429

29/281

1.12 (0.70–1.80)

1.73 (1.08–2.78)

2.25 (1.37–3.71)

0.0043

1.07 (0.66–1.72)

1.53 (0.94–2.46)

1.91 (1.15–3.17)

0.0428

1.25 (0.76–2.06)

2.06 (1.22–3.47)

3.19 (1.74–5.85)

0.0007

Total

57/1112

57/1113

80/1092

78/1086

1.00 (0.69–1.46)

1.43 (1.01–2.03)

1.40 (0.99–1.99)

0.0558

0.99 (0.67–1.44)

1.37 (0.95–1.97)

1.36 (0.93–1.97)

0.1339

1.11 (0.75–1.64)

1.69 (1.15–2.50)

1.99 (1.29–3.06)

0.0033

M0: crude model not adjusted, M1: model 1 adjusted by age and gender, M2: model 2 adjusted by age, gender, BMI, TG, TC, LDL-C, Cr, glucose, Hcy, heart ratio,

SBP, DBP, drinking, smoking, sport, heart failure, kidney disease, hypertensive retinopathy, diabetes, family history of stroke and hypertension years, Q: quartile.

Table 4.The relationships between different combinations

of UA, Hcy,TG,TC and LDL and stroke

Combinations

Number (non-

stroke/stroke) OR 95% CI

-value

Female

UA-Hcy-TG-TC-LDL-C-

455/29

Hcy-TG-TC-LDL-C-

63/7

1.74 0.73–4.15 0.2087

Hcy

TG-TC-LDL-C-

21/6

4.48 1.68–11.97 0.0027

Hcy

TC-LDL-C-

25/2

1.26 0.28–5.56 0.7647

Hcy

LDL-C-

4/2

7.85 1.38–44.63 0.0202

Hcy

LDL-C

31/6

3.04 1.17–7.86 0.0221

Male

UA-Hcy-TG-TC-LDL-C-

332/26

Hcy-TG-TC-LDL-C-

60/6

1.28 0.50–3.23 0.6062

Hcy

TG-TC-LDL-C-

83/12

1.85 0.89–3.81 0.0975

Hcy

TC-LDL-C-

88/6

0.87 0.35–2.18 0.7675

Hcy

LDL-C-

26/3

1.47 0.42–5.19 0.5466

Hcy

LDL-C

66/5

0.97 0.36–2.61 0.9478

Total

UA-Hcy-TG-TC-LDL-C-

787/55

Hcy-TG-TC-LDL-C-

123/13

1.51 0.80–2.85 0.2007

Hcy

TG-TC-LDL-C-

104/18

2.48 1.40–4.38 0.0018

Hcy

TC-LDL-C-

113/8

1.01 0.47–2.18 0.9736

Hcy

LDL-C-

30/5

2.39 0.89–6.39 0.0838

Hcy

LDL-C

97/11

1.62 0.82–3.21 0.1635

Reference: UA-Hcy-TG-TC-LDL-C-