The relationship between serum uric acid-creatinine ratio and risk factors of cerebral Hemodynamics and stroke in physical examination population

DOI: https://doi.org/10.21203/rs.3.rs-2825187/v1

Abstract

Background The serum uric acid to creatinine ratio (SUA/Cr) is important in cardiovascular diseases. The aim of this study was to investigate the correlation between SUA/Cr ratio and cerebral hemodynamics and to analyze the relationship between different levels of SUA/Cr ratio and risk factors associated with stroke.

Methods A population of 12,785 middle-aged and elderly medical checkups who completed CVHI testing at the First Affiliated Hospital of Xinjiang Medical University from June 2020 to May 2021 was selected for the study. The medical examination population was divided into Q1, Q2, Q3 and Q4 groups according to the quartiles of SUA/Cr ratio. The relationship between the SUA/Cr ratios and CVHI and stroke related risk factors in the middle-aged and elderly population was analyzed.

Results A total of 12785 cases were included in the study, with an age range of 35 to 91 years and a mean of (50.64 ± 10.12) years. In the SUA/Cr grouping, the differences in the composition ratios of the population by gender and age were significant (P < 0.05), and the composition ratios of the population with abnormal systolic blood pressure, diastolic blood pressure, BMI, and history of alcohol consumption, hypertension, diabetes mellitus, and hyperlipidemia in the SUA/Cr grouping showed statistical significance (P < 0.05). the composition ratios of the group with abnormal blood pressure, alcohol consumption, history of hypertension, history of diabetes mellitus, and hyperlipidemia in the Q4 group were significantly higher than those of the other groups (P < 0.05), The composition ratios of the group with abnormal blood pressure, alcohol consumption, history of hypertension, history of diabetes mellitus, and history of hyperlipidemia were all significantly higher than those of the other groups (P < 0.05). As the ratio of SUA/Cr increases, the CVHI integral value will show a corresponding decreasing trend.

Conclusions There is a correlation between SUA/Cr and CVHI, which should be given high priority.

Introduction

Stroke is characterized by neurological dysfunction caused by cerebrovascular[1]. It is one of the diseases that seriously threaten human health. Cerebral vascular hemodynamic index (CVHI) score values allow dynamic assessment of cerebrovascular health and have been used as an important test for primary prevention of cerebrovascular diseases [2]. With the advantages of easy access and low cost, blood biochemical indexes have been the focus of research on cardiovascular and cerebrovascular diseases. Several studies at home and abroad have shown that SUA/Cr ratio has good predictive value for the development of coronary heart disease [3], metabolic syndrome [4], diabetes [5] and chronic obstructive pulmonary disease [6]. However, studies on SUA/Crratio and CVHI score values and risk factors associated with stroke have rarely been addressed. The study population consisted of 12,785 medical checkups that included cerebrovascular hemodynamic testing at the health management center of the First Affiliated Hospital of Xinjiang Medical University from June 2020 to May 2021.

Methods

Research design and study subjects

12,785 physical examination professionals who passed the CVHI test at the Xinjiang Medical University's First Affiliated Hospital were chosen between June 2020 and May 2021. Inclusion criteria: (1) People under the age of 35; (2) Regular Urumqi inhabitants (less than six months); (3) Voluntary population screening for CVHI, serum uric acid, creatinine and related laboratory tests and questionnaires for people at high risk of stroke; Exclusion criteria: (1) Individuals having incomplete laboratory and demographic data; (2) Those who already have a clear clinical diagnosis: chronic kidney disease, malignant tumors, mental disorders and infectious diseases. (3) People with language communication disorder.

Demographic data

A cross-sectional study was carried out to collect general demographic data and medical history information, including age, sex, past history, smoking history and alcohol consumption history, by means of a questionnaire survey of the examined population. Height, weight, blood pressure, and body mass index are all measured and calculated.

Laboratory examination

All study individuals received venous blood tests after fasting for at least 8 hours. Total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglyceride (TG), blood glucose (fasting blood glucose (FBG), serum uric acid (SUA), creatinine (Cr), and glycosylatedhemoglobin (HbA1c), urea and other laboratory indicators. The above blood biochemical index tests were done by the Laboratory Department of Xinjiang Medical University's First Affiliated Hospital.

Cerebral hemodynamics testing

The cerebrovascular function testing instrument (GT-300) was used with a probe frequency of 5 MHz, and the subject was placed in a supine position to fully expose the neck. The test indexes included right and left side mean blood flow Qmean/(cm/m3), maximum flow velocity Vmax/(cm/s), minimum flow velocity Vmin/(cm/s), mean flow velocity Vmean/(cm/s), peripheral resistance (Rv), characteristic impedance (Zcv), pulse wave velocity (Wv), dynamic resistance (DR), critical pressure level (Cp), diastolic pressure and The difference between diastolic and critical pressure (Dp) and other 10 pairs of indicators [7]. A person is considered to be at high risk of stroke if their CVHI score is below 75, which is the recommended cutoff point.

SUA/Cr levels were stratified

The study subjects were divided into groups Q1 to Q4 according to their quartiles: SUA/Cr ≤ 3.92 (3196 cases, Q1 group), 3.93 ≤ SUA/Scr ≤ 4.68 (3196 cases, Q2 group), 4.69 ≤ SUA/Scr ≤ 5.54 (3197 cases, Q3 group), SUA/Cr ≥ 5.55 (3196 cases, Q4 group ).

Statistical data analysis

All data were statistically processed using SPSS(version26.0)software. Mean and standard deviation were used to represent measurement data that followed a normal distribution, express measurement data that did not follow a normal distribution, median and interquartile spacing were used. and composition ratio was used to describe count data.ANOVA was used to compare multiple groups; the chi-square test was used to compare categorical variables.The CVHI integral value was used as the dependent variable in the logistic regression model, and SUA/Cr and stroke-related risk factors were included as independent variables in the regression equation. The difference was considered significant at P < 0.05.

Results

General characteristics of study subjects

There are a total of 12785 subjects of medical examiners were incorporated into the research, with an age range of 35 to 91 years and a mean of (50.64 ± 10.12) years. Among them, 7892 were males with an average age of (50.16 ± 10.18) years and there were 4893 females with an average age of (51.42 ± 10.17). The abnormal group of CVHI score values in the SUA/Cr subgroup showed a rising trend as their subgroup levels are increased. Age, ethnicity, smoking, alcohol consumption, lack of exercise, hypertension history, hyperlipidemia history, diabetes mellitus history, stroke family history, BMI, SUA/Cr, triglycerides, glucose, urea, uric acid, creatinine, and glycosylated hemoglobin showed statistically considerable differences (all P < 0.05), as shown in Table 1.

Table 1

The basic condition of normal and abnormal CVHI group

Variables

N

CVHI

χ2/t

P

Normal groups(≥75)

Abnormal group(<75)

Age/yrs

12785

49.30 ± 9.103

58.49 ± 12.460

30.49

<0.001

Gender

Males

7892

6775(61.7%)

1117(62.2%)

0.164

0.685

Females

4893

4213(38.3%)

680(37.8%)

Nationality

Han

9656

8357(76.1%)

2631(23.9%)

11.87

0.001

Other

3129

1299(72.3%)            498(27.7%)

History of smoking

Yes

3768

3343(88.7%)

425(11.3%)

34.09

<0.001

No

9017

7645(84.8%)

1372(15.2%)

History of drinking

Yes

5380

4753(88.3%)

627(11.7%)

44.34

<0.001

No

7405

6235(84.2%)

1170(15.8%)

History of hypertension

Yes

4716

4163(88.3%)

553(11.7%)

33.57

<0.001

No

8069

6825(84.6%)

1244(15.4%)

History of hyperlipidemia

Yes

3655

3044(83.3%)

611(16.7%)

30.01

<0.001

No

9130

7944(87.0%)

1186(13.0%)

History of diabetes

Yes

1781

1604( 90.1%)

177(9.9%)

29.04

<0.001

No

11004

9384(85.3%)

1620(14.7%)

Lack of movement

         

Yes

6610

5877(88.9%)

733(11.1%)

99.68

<0.001

No

6175

5111(82.8%)

1064(17.2%)

Family history of stroke

Yes

443

284(64.1%)

159(35.9%)

181.1

<0.001

No

12342

10704(86.7%)

1638(13.3%)

BMI (kg/m)2 )

25.22 ± 3.29

27.49 ± 3.57

-25.3

<0.001

SUA/Cr ratio

 

Q1

3196

2797(25.5%)

399(22.2%)

39.42

<0.001

Q2

3196

2795(25.4%)

401(22.3%)

Q3

3197

2751(25.0%)

446(24.8%)

Q4

3196

2645(24.1%)

551(30.7%)

TC (mmol/L)

5.02 ± 2.00

5.13 ± 2.50

-1.76

0.079

TG (mmol/L)

2.14 ± 2.42

2.47 ± 2.80

-4.72

<0.001

LDL (mmol/L)

3.42 ± 2.03

3.52 ± 2.43

-1.5

0.135

HDL-c (mmol/L)

1.46 ± 1.80

1.51 ± 2.25

-0.96

0.336

FBG (mmol/L)

6.31 ± 3.21

5.38 ± 2.27

11.85

<0.001

HbA1c(mmol/L)

0.10 ± 0.52

0.07 ± 0.33

2.517

<0.001

Urea(mmol/L)

5.30 ± 2.29

5.70 ± 2.78

-5.83

<0.001

SUA(umol/L)

330.30 ± 87.32

349.42 ± 88.94

-8.59

<0.001

Cr(umol/L)

72.12 ± 25.56

76.10 ± 43.71

-3.72

<0.001

 

Comparison of brain Hemodynamics in different SUA/Cr groups

The maximum flow velocity (Vmax), minimum flow velocity (Vmin) and mean flow velocity (Vmean) of bilateral carotid arteries decreased with increasing SUA/Cr ratio and the difference was statistically meaningful (P < 0.001), while peripheral resistance (Rv), characteristic impedance (Zcv), pulse wave velocity (Wv), dynamic resistance (DR), critical pressure (CP) and difference (DP) increased with increasing SUA/Cr ratio, and the difference was Statistically significant (P < 0.001), see Table 2.

Table 2

Comparison of Hemodynamics in different groups with different levels of SUA/Cr

Index

Left side

Q1 group

Q2 group

Q3 group

Q4 group

F

P

Vmax (cm/s)

42.08 ± 7.21

41.49 ± 6.96

41.32 ± 6.92

40.53 ± 7.01

26.4

<0.001

Vmin(cm/s)

10.03 ± 2.46

9.92 ± 2.27

9.91 ± 2.21

9.68 ± 2.26

12.34

<0.001

Vmean (cm/s)

20.68 ± 4.12

20.27 ± 3.85

20.16 ± 3.82

19.67 ± 3.87

34.81

<0.001

Rv (kPa·s m)

66.00 ± 21.73

68.45 ± 21.97

69.51 ± 21.49

72.41 ± 22.70

46.67

<0.001

Zcv (kPa·s/m)

15.57 ± 6.54

15.90 ± 6.62

15.91 ± 6.46

16.69 ± 7.02

15.46

<0.001

WV(m/s)

14.82 ± 6.23

15.14 ± 6.31

15.15 ± 6.16

15.90 ± 6.69

15.46

<0.001

DR(kPa·s/m)

34.64 ± 15.31

35.84 ± 15.55

36.58 ± 16.34

38.66 ± 16.78

34.92

<0.001

CP (kPa)

6.39 ± 1.94

6.50 ± 2.05

6.50 ± 2.05

6.54 ± 2.04

4.37

0.004

DP (kPa)

3.27 ± 1.13

3.38 ± 1.21

3.46 ± 1.26

3.55 ± 1.27

32.22

<0.001

 

Index

Right side

Q1 group

Q2 group

Q3 group

Q4 group

F

P

Vmax(cm/s)

40.78 ± 7.37

40.33 ± 7.16

40.04 ± 7.04

39.11 ± 7.10

31.02

<0.001

Vmin(cm/s)

9.56 ± 2.43

9.52 ± 2.20

9.49 ± 2.20

9.21 ± 2.21

16.02

<0.001

Vmean (cm/s)

19.43 ± 4.15

19.15 ± 3.84

19.04 ± 3.82

18.47 ± 3.83

33.61

<0.001

Rv(kPa·s/m)

70.83 ± 24.39

72.83 ± 24.26

74.02 ± 23.39

77.61 ± 25.13

42.07

<0.001

Zcv (kPa·s m)

16.06 ± 6.93

16.26 ± 6.98

16.46 ± 6.83

17.16 ± 7.35

13.99

<0.001

WV(m/s)

15.30 ± 6.60

15.49 ± 6.65

15.67 ± 6.50

16.34 ± 7.00

13.99

<0.001

DR(kPa·s/ m)

37.85 ± 17.13

38.89 ± 17.01

39.63 ± 17.01

42.21 ± 18.66

33.80

<0.001

CP(kPa)

6.24 ± 1.98

6.35 ± 2.02

6.41 ± 2.02

6.39 ± 2.11

4.95

0.002

DP(kPa)

3.39 ± 1.21

3.51 ± 1.21

3.57 ± 1.24

3.68 ± 1.34

28.03

<0.001

 

Comparison of CVHI score and abnormal rate between groups with different levels of SUA/Cr

The results of different SUA/Cr levels and CVHI integral values and comparisons showed that the mean CVHI of group Q1, group Q2, group Q3 and group Q4 were (89.48 ± 16.75), (89.04 ± 16.21), (88.37 ± 16.28) and (85.66 ± 18.42), respectively, which showed a decreasing trend in order.The abnormal CVHI score value (< 75 points) showed an increasing trend in the four groups level. The differences in the CVHI score values and the incidence of abnormalities and the differences between the groups were statistically meaningful (P < 0.001), as shown in Table 3.

Table 3

Comparison of CVHI scores with different levels of SUA/Cr

Groups

N

CVHI integral

≥ 75 point

<75 point

Q1

3196

89.48 ± 16.75

2786(87.2%)

410(12.8%)

Q2

3196

89.04 ± 16.21

2775(86.8%)

421(13.2%)

Q3

3197

88.37 ± 16.28

2738(85.6%)

459(14.4%)

Q4

3196

85.66 ± 18.42

2621(82.0%)

575(18.0%)

F/χ2

/

29.38

42.925

P

/

<0.001

<0.001

 

Logistic regression analysis of factors influencing CVHI integral values

As dependent variables, the CVHI score values 75 and 75 were used,and equations for logistic regression were fitted based on the factors that were statistically significant in the univariate analysis described above as independent variables. The results showed that SUA/Cr, smoking, alcohol consumption, history of hyperlipidemia, hypertension history, diabetes mellitus history, stroke family history, GLU, uric acid, and triglycerides were directly associated with abnormal CVHI score (< 75), and the distinctions were statistically significant (P < 0.05), see the Table 4.

Table 4

Binary logistic regression research of SUA/CR, CVHI score and stroke related risk factors.

Independent variable

β

SE值

Wald χ2

OR值(95% CI)

P

SUA/Cr

0.088

0.030

8.642

1.092(1.030~1.158)

0.003

Smoking

0.185

0.072

6.550

1.203(1.044~1.386)

0.010

Alcohol

0.304

0.066

21.413

1.355(1.192~1.542)

<0.001

History of hyperlipidemia

-0.318

0.073

19.171

0.727(0.631~0.839)

<0.001

History of hypertension

0.168

0.057

8.628

1.183(1.058~1.324)

0.003

History of diabetes

0.409

0.087

21.982

1.505(1.269~1.786)

<0.001

Family history of stroke

-1.153

0.106

117.586

0.316(0.256~0.389)

<0.001

FBG (mmol/L)

0.185

0.013

204.893

1.204(1.174~1.235)

<0.001

Urea(mmol/L)

0.009

0.018

0.257

1.009(0.975~1.044)

0.612

Cr(umol/L)

0.001

0.001

0.149

1.001(0.998~1.003)

0.699

SUA(umol/L)

0.002

0.000

24.316

1.002(1.001~1.003)

<0.001

TG (mmol/L)

-0.131

0.020

43.860

0.878(0.844~0.912)

<0.001

HbA1c(mmol/L)

-0.121

0.072

2.880

0.886(0.770~1.019)

0.090

Discussion

Globally, the prevalence of stroke has shown an increasing trend due to the aging of the population, further population growth, and the increasing prevalence of risk factors [8]. CVHI score values from cerebrovascular hemodynamic testing are used for early assessment and management of people at risk for stroke, facilitating early detection of subjects who can be prevented. SUA has been extensively evaluated and has been proved to be an unrelated predictor not only of cardiovascular death, but also of stroke [9]. Elevated Cr is linked to an increase in patient mortality with myocardial infarction or stroke in cardiovascular disease, and therefore Cr concentration has been suggested by scholars as a possible marker of increased stroke risk [10]. Studies have pointed out that SUA/Cr in normalized renal function has become a new kind of biomarker [11]. In this study, the relationship between the SUA/Cr ratio and the CVHI score was investigated based on a population with a healthy physical examination and selected for noninvasive cerebral hemodynamic testing.

According to the findings of this study, Vmax, Vmin and Vmean were gradually decreased in Q1, Q2, Q3 and Q4 groups when comparing different SUA/Cr level groups with cerebral hemodynamic testing indexes, where the lower Vmax and minimum flow velocity Vmin were relatively higher risk of stroke, which was similar to the findings of Lina Zhang [12]. Rv, Zcv, WV, DR, CP, and DP showed a tendency to increase in the Q1, Q2, Q3, and Q4 groups, with statistically significant differences (P < 0. 001). It was shown that peripheral resistance Rv, pulse wave velocity WV and and characteristic impedance Zcv exhibit elevated changes when cerebrovascular damage occurs, and the abnormal changes in these values can be used to explain the poor blood supply status of cerebral vessels or the decrease in cerebrovascular elasticity [7]. Rv values may reflect individual risk indicators for cerebral hemorrhage, and elevated CP values may indicate cerebrovascular microcirculatory disorders [13] This suggests that abnormalities in cerebral hemodynamic parameters may be suggested by different SUA/Cr ratio levels, especially when the SUA/Cr ratio is ≥ 5.55.

In the present study, the percentage of cerebral hemodynamic scores less than 75 was 12.8%, 13.2%, 14.4%, and 18.0% (P < 0.001) in Q1, Q2, Q3, and Q4 groups, which demonstrated that the increase of SUA/Cr may lead to the slowing down of carotid blood flow, and the lower value of CVHI score indicates the corresponding impairment of cerebrovascular function. The lower the CVHI score, the lower the cerebrovascular function. The increase in SUA/Cr levels was associated with a corresponding change in CVHI values. SUA has been found to have strong antioxidant properties, it is an excellent antioxidant for the brain. [14]. Therefore, scholars have found that a lower SUA/Cr ratio when a patient is at the beginning of a stroke implies a lower antioxidant capacity, that leads to neuronal damage and can eventually impair their neurological function [11]. In contrast, the outcomes of the current study were contrary to this, so the ratio could be focused on in physical examinations and in clinical settings in the future.

Previous studies have also investigated the association of SUA/Cr ratio with clinical outcomes in certain diseases. The SUA/Cr ratio is strongly linked to the risk of metabolic syndrome and may serve as an independent predictor. [15]. Another multifactorial logistic regression outcome study of nonalcoholic fatty liver disease showed that SUA/Cr ratio was an independent risk factor [16]. The SUA/Cr ratio was significantly and positively associated with total adult mortality and cardiovascular disease mortality, according to data from the United States National Health and Nutrition Examination Survey. [17]. In this study's logit regression analysis, SUA/Cr was identified as a potential factor influencing CVHI integral value. SUA/Cr is an indirect important indicator for predicting and assessing high-risk groups for stroke because it serves as an independent risk factor for decreased CVHI score in high-risk groups for stroke (P 0.05). This study indicates that the risk of stroke may increase in high-risk groups for stroke with increased SUA/Cr levels.

Limitation

Some findings suggest that inflammatory factors such as BMI, TG, TC, DBP, and FBG maybe play an important role in mediating the relationship between SUA/Cr and stroke [18], but further research is needed to investigate the main reasons for this variation. This study only explored the physical examination population, so the findings of this study cannot be directly used to guide the prevention of stroke in high-risk groups, and further expansion of the population is still needed to explore the relationship between the two.

Conclusions

In summary, this study investigated the correlation between SUA/Cr and CVHI scores and risk factors associated with stroke. We found that the highest quartile of SUA/Cr was associated with an elevated risk of stroke relative to the lowest quartile of SUA/Cr. The potential role of the SUA/Cr ratio could be extended to another area in the future, and people with high SUA/Cr ratios should be particularly alert to CVHI integral values and should be closely followed for functional outcomes. In future studies scholars may focus on SUA/Cr levels, which may provide new ideas to improve primary prevention of stroke.

Abbreviations

SUA/Cr serum uric acid/creatinine

BP blood pressure

BMI body mass index

TC total cholesterol,

LDL-C low density lipoprotein cholesterol

HDL-C high density lipoprotein cholesterol

TG triglyceride

FBG fasting blood glucose

SUA serum uric acid

Cr creatinine

HbA1c glycosylatedhemoglobin

CVHI cerebral vascular hemodynamic index

Declarations

All study subjects enrolled had signed the informed consent form after being well informed of the study contents.

All data and material were available.

The authors declare that they have no conflicts of interest in the manuscript.

Ethics approval and consent to participate

All procedures for the study subjects were approved by Medical Ethics committee of the First Affiliated Hospital of Xinjiang Medical University. This study was approved by the Ethics Committee of the First Affiliated Hospital of Xinjiang Medical University(approval number:No.20160317-02), Patients were consented by an informed consent process that was reviewed by the Ethics Committee of the First Affiliated Hospital of Xinjiang Medical University and certify that the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki.

Consent to publish

The article has not been previously published in any journal and we would not consider publishing it elsewhere, if possible . The publication of the article has been approved by all co-authors; the publication of the work therein has been approved (tacitly or explicitly) by the competent authorities of the institution where the work is published. The authors agree to publish the article in this journal and agree to publish the article in English in the corresponding English-language journal.

Competing interests

The authors declare that they have no competing interests.

Acknowledgment

We wish to thanks Xinjiang Medical University and other institutions for its approval and assistance.

Authors' contributions

Dongxia Liu was responsible for data acquisition and paper writing; Xunan Dong was responsible for data management ;Yan Jiang was responsible for statistical analysis, Yu Zhu was responsible for data review and statistical analysis; Yu-Shan Wang was responsible for paper review.All the authors read and approved the final manuscript.

Funding

This project was funded by the Xinjiang Uygur Autonomous Region Natural Science Foundation (No. 2016D01C330) and Chinese Medical Association Health Management Branch Doctoral Consortium Project, 2020BSLM16.

Availability of data and materials

The datasets used and/or analyzed during the current study can be made available by the corresponding author on reasonable request.

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