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A study on the relationship between serum uric acid and the thickness of intima-mediated carotid

Ahmad Enhesari1, Manouchehr Khatami2, Mohammad Hossein Gozashti3*, Zohreh Safi3, Mehrdad Khatami4, 5

1Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran. 2Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran. 3Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran. 4Noncommunicable Research Center, Bam University of Medical Sciences, Bam, Iran. 5Cell Therapy and Regenerative Medicine Comprehensive Center, Kerman University of Medical Sciences, Kerman, Iran.

Correspondence: Mohammad Hosseini Gozashti, Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran. [email protected]; [email protected]


Levels of serum uric acid are associated with cardiovascular attacks and high blood pressure. Some researchers have suggested that the serum levels of uric acid may also be related to the thickness of the Intima-mediated carotid. The aim of this study was to evaluate the serum level of uric acid and its relationship with the thickness of Intima-mediated carotid in patients referred to Be’sat Clinic of Kerman. 180 patients, including 86 males and 94 females with an average age of 41.1 ± 3, were studied. In all patients, blood pressure and BMI were measured. Serum levels of uric acid, TG, cholesterol, HDL, LDL, and also the thickness of Intima-mediated carotid was measured and statistically analyzed.

The results of this study showed that the thickness of Intima-mediated carotid significantly correlated with serum uric acid (p = 0.02, r = 0.71). The results also showed that uric acid levels were related with higher BMI and higher levels of metabolic factors. The results of our study generally show that people with higher serum uric acid have a significantly higher thickness of the Intima-mediated carotid. People with high blood pressure also had higher carotid thickness compared to those with normal blood pressure. Other metabolic factors were higher in people with high serum uric acid than those that have levels of normal uric acid.

Keywords:  High blood pressure, Intima-mediated thickness of carotid artery, Serum uric acid, Cardiovascular, Metabolic factors


Stroke is one of the reasons for death and long-term disability around the world so that one person suffering from a stroke per second in the United States and every 1/3 minutes someone dies because of it [1, 2]. Every year, hundreds of people die due to brain stroke in Iran. The point is that the disease does not happen suddenly and doctors can identify those who are at risk of it.

Several factors contributing to stroke, such as blood pressure, etc., due to changes in lifestyles and poor eating habits, and the outcomes of all these changes will increase the stroke in the community. About 80% of ischemic stroke cases are due to ambulatory events or stenosis of the cerebellar arteries. In particular, atherosclerotic plaques and arterial stenosis are associated with about 20% to 30% of brain infarction [3, 4].

Atherosclerosis is characterized by an increase in the progressive thickness of the arteries wall. The risk factors for atherosclerosis are divided into two modifiable groups including hyperlipidemia, hyperuricemia, diabetes, smoking, hypertension, and non-modifiable groups including aging, male sex, family background, and genetic abnormalities [5, 6]. In humans, the final oxidative product of purine catabolism is known as Serum uric acid. Various studies indicate a strong association between atherosclerotic disease and serum uric acid [7-12]. Feng et al. (2018) [13] studied 564 people in China and suggested that serum uric acid levels are associated with the development and progression of atherosclerotic vascular changes. Serum uric acid contributes to the development of ATs, including endothelial damage, oxidative metabolism, and increased platelet aggregation and adhesion [14, 15]. In another study by Choi et al. (2018), the thickness of Intima-Media in patients with high uric acid levels was higher than those with normal uric acid levels. The study also suggested that renal dysfunction in patients with hyperuricemia is associated with an increase in CIMT [16].

Carotid ultrasonography is used as a non-invasive and effective diagnostic method for determining the early stages of atherosclerotic changes in the arterial wall. Intima-media thickness (IMT) measurements and plaque formation are used as early warning and early indicators for early diagnosis of atherosclerosis. For measuring IMT, a high-resolution B-mode ultrasound scanner is used [17, 18].

Since serum uric acid can be effective in developing atherosclerosis, calculating CIMT is an easy method for detecting the presence of atherosclerosis, so the purpose of this study was to determine the relationship between serum uric acid and CIMT.

Materials and Methods

This is a cross-sectional study in which 180 people who participated in Kerman's Coronary Artery disease study II (KERC AD SII) were randomly selected. After obtaining the informed consent of the people, demographic data including age, sex, weight, and blood samples were taken after 14-12 hours of fasting and were kept at room temperature. Then, the blood glucose tests, serum lipids (including HDL triglycerides and cholesterol) were measured by the enzymatic method.
Patients with intracranial hemorrhage, subarachnoid hemorrhage, and those with a background of cerebrovascular accident and cardiovascular disease, and uncontrolled blood pressure were excluded. Before completing the questionnaire and sonography, the purpose of the study was completely explained to all participants accurately.

Carotid sonography

Individuals were studied by carotid Doppler sonography at referring time and the thickness of the Intima-Media layer (IMT) was measured using the Philips IU22 ultrasound scanner. During the sonography, a high-resolution B-mode ultrasound scanner was used to measure IMT. In this method, a common carotid artery, carbohydrate Biloba, and internal carotid artery on both sides of the neck were examined for determining the thickest part of the Intima-Media carotid. The sonography scan was done accurately and IMT is defined based on the distance between the edge of the intima lumens from the edge of the advantis media (The distance between the two ecognic lines observed in the B-mode ultrasound) and the mean of the CIMT was calculated through the total thickness of both sides divided by two, and were used in the study, which is briefly described here as CIMT. It should be noted that hyperuricemia is defined by the levels of serum uric acid above 7 mg/dl in men and above 5.7-6 mg/dl in women.

Data analysis

After collecting data, it was analyzed by SPSS version 20 and then statistically analyzed. Descriptive tests were used to analyze the descriptive data and Pearson correlation coefficient analysis was used to analyze the variables related to IMT.

Results and Discussion

180 patients were evaluated totally. Based on the cut-off point, uric acid was considered to be 5.7 for men and 7.7 for men. 22 people had high uric acid and 158 normal serum uric acid. The mean uric acid in the studied patients was 6.0 ± 0.9 (Table 1).

Table 1. Demographic and clinical characteristics of persons in the study






0.53 ± 0.12

c-IMT mm, mean (range)


41.1 ± 3.1

Age, years (mean)


28.7 ± 2.1

Body mass index (kg/m2(


85.6 ± 11.9

Fasting plasma glucose (mg/dL)


186.9 ± 28.8

Cholesterol (mg/dL)


41.9 ± 8.7

HDL (mg/dL)


118.0 ± 25.4

LDL (mg/dL)


154.9 ± 89.4

TG (mg/dL)


160.1 ± 3.1

Systolic blood pressure


87.1 ± 3.1

Diastolic blood pressure


6.02 ± 0.9

Uric acid (m mol/L)


Plasma measurements are reported as means ± SD. *P o 0.05 by unpaired t-test. HDL: high-density lipoprotein; c-IMT: carotid intima-media thickness; LDL: low-density lipoprotein.

The gender abundance of the persons is described by 86 men (47.7%) and 94 women (52.3%). The mean of intima-media thickness of the carotid artery in studied persons was 0.12 ± 0.53.
The results of the statistical analysis showed a positive linear relationship between serum uric acid and carotid artery thickness (p = 0.02, r = 0.71) (Figure 1).

Figure 1. Relationship between Intima Thickness - Carotid Artery media with Serum Uric Acid

The results of the study also suggest that the intima-media thickness of the carotid artery separately and independently has a meaningful linear relationship with BMI, TG, HDL, cholesterol, diastolic blood pressure, Systolic blood pressure, and fasting plasma glucose (Tables 1 and 2, Figures 2-4).


Table 2. Multiple linear regression between various parameters and c-IMT







Body mass index




Fasting plasma glucose




















Blood pressure




Uric acid



The regression coefcient (B) represent data and. *P ˂ 0.05. Each parameter was adjusted against all the other parameters presented in this table. LDL: low-density lipoprotein; c-IMT: carotid intima-media- thickness; HDL: high-density lipoprotein.


Figure 2. Investigating the relationship between BMI and intima-media thickness


Figure 3. Relationship of Medium Blood Pressure with Intima Thickness and Carotid Artery


Figure 4. Investigating the relationship between metabolic factors and intima-media thickness of the carotid artery


The results of the study generally indicate that there is a significant relationship between serum uric acid and carotid thickness. According to Santa et al. (2018), there is a significant relationship between serum uric acid level and CIMT, which is not dependent on age, the traditional risk (LDL/HDL ratio), and nontraditional risk (inflammation, circumference, and inflammatory factors).

Other studies examine the relationship between the thickness of the intima-media of the carotid artery and the serum uric acid levels. A study by Choi et al. (2018), suggested that the thickness of the intima-media in patients with high uric acid is significantly higher than those with normal levels of uric acid. This study also suggested that hyperuricemia is associated with impaired renal function and causes a further increase in CIMT [19]. Nguyen TBT et al. (2009) investigated the association between carotid hyperuricemia and cartilage IMT in patients with and without hypertension; cartilage IMT in hypertensive and high uric acid serum had an increased intima-mediated thickness [20]. In another study by Caliskan M et al., the level of uric acid and cartilage IMT hyperuricemia in patients with Masked Hypertension was evaluated and it was found that uric acid levels and carotenoid IMT in these patients were higher than the control group and the higher level of uric acid increases with the increase of carotid IMT [21]. In another study by Li Q et al. (2010), the relationship between the prevalence of atherosclerotic plaques and serum uric acid was investigated and it was found that independent higher levels of uric acid with other risk factors of atherosclerotic are inconsistency with an increase in the prevalence of atherosclerotic plaque [22]. The results of all these studies were consistent with this study.

Blood pressure testing revealed that Intima-Media Carotid thickness was significantly higher in people with high blood pressure than in people with normal blood pressure. Also, there was a significant relationship between the thickness of the intima-media of the carotid artery and BMI, FBS, TG, CHOLESTEROL, HDL, and LDL.

However, studies have shown that high levels of uric acid can contradict the role of neuroprotective role in brain damage. Logaloo et al. found that serum concentration at the time of admission had a positive correlation with the clinical improvement of patients with stroke [23]. Seet et al. showed that serum urate concentrations had a U-shaped relationship with a poor prognostic factor in acute stroke, whereas no significant correlation was found with the vascular outcome. They stated that uric acid, depending on its serum level, could play both useful and harmful roles in the prognosis of stroke [24]. In a study by Chamaru, it was also investigated that there is an inverse association between neurological deficits in stroke patients with serum uric acid serum levels [23]. Studies reject the association between the levels of serum uric acid and CIMT, including a study by Delhin et al. (2018), who suggested that high levels of serum uric acid are associated with calcification in coronary arteries and there is no significant relationship with CIMT [19].

The present study generally indicates more metabolic factors in people with higher concentrations of serum uric acid. In epidemiological studies, the importance of LDL-C as a marker of CHD (cardiovascular disease) has been proven. Although half of the patients with normal CHD have LDLC, and the Tanaka study showed that the LDLC / HDLC ratio was able to predict myocardial infarction and sudden death when LDL is less than 120 mg/dl [25], and there is a significant relationship between CMIT and LDL in many studies [26], but in some studies, this relationship has not been seen [27] and it has more relationship with The lower HDL [27]. Lopes et al. (2018) studied 55 patients with an average age of 11.9 years, suggesting a significant correlation with CIMT increase in chronic kidney disease and blood pressure as an independent factor [28].

However, the present study and most of the studies that have been done so far have been confronted with limitations, including the effects of genetic and nutritional differences between individuals, coincident diseases, methodological considerations, outcome measures, time of interventions, etc.


This study generally indicates that people with higher serum uric acid have significantly higher carotid artery intimal-mediated thickness. People with high blood pressure also had higher carotid thickness compared to those with normal blood pressure. Other metabolic factors were higher in patients with high serum uric acid than those with normal uric acid levels.

Acknowledgments: Appreciate all individuals, institutions, and organizations that have helped either in the project process or financially.

Conflict of interest: None

Financial support: Kerman University of Medical Sciences with number: IR.KMU.AH.REC.1397.2607.

Ethics statement: Taken from Ethic committee of Kerman University of Medical Sciences with number: IR.KMU.AH.REC.1397.2607


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