Dataset Information

Relation of serum uric acid to asymptomatic proximal extracranial artery stenosis in a middle-aged Chinese population: a community-based cross-sectional study.

ABSTRACT: OBJECTIVE:Serum uric acid (SUA) has been associated with cardiovascular diseases, including atherosclerosis and carotid artery stenosis. However, data on the relationship between SUA level and proximal extracranial artery stenosis (PEAS) are limited. Therefore, this study investigates the association between SUA levels and the risk of PEAS in asymptomatic Chinese population. SETTING:This community-based cross-sectional study was conducted in Jidong Community Hospital, Tangshan, Hebei, China between July 2013 and August 2014. PARTICIPANTS:The study examined 3325 asymptomatic participants (40-60?years) to evaluate the risk of PEAS. RESULTS:For the participants stratified into quartiles based on gender-specific SUA levels, the prevalence of PEAS increased from Q1 to Q4 from 12.3% to 29.8% in the vertebral artery (VA), and from 2.8% to 5.8% in the common carotid artery. The proportion of PEAS relative to the detected number of arterial stenosis was lower in Q1 than in Q2-Q4. The multivariable ORs and 95% CI of PEAS in the second through fourth compared with the lowest quartiles for arterial stenosis were 1.278 (0.980 to 1.665), 1.117 (0.851 to 1.468) and 1.375 (1.033 to 1.830) (ptrend=0.0399); and for VA stenosis, 1.285 (0.966 to 1.709), 1.085 (0.808 to 1.457) and 1.439 (1.061 to 1.952) (ptrend=0.0235). CONCLUSION:Elevated SUA concentration is significantly associated with PEAS in an asymptomatic middle-aged Chinese population, and vertebral arteries appeared to be the most vulnerable vessels.

SUBMITTER: Yang X

PROVIDER: S-EPMC6112387 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Relation of serum uric acid to asymptomatic proximal extracranial artery stenosis in a middle-aged Chinese population: a community-based cross-sectional study.

Yang Xiaolei X Lv Haichen H Hidru Tesfaldet Habtemariam TH Wu Jing J Liu Henghui H Wang Youxin Y Liu Kejia K Xia Yunlong Y Zhou Yong Y Jiang Yinong Y

BMJ open 20180823 8

<h4>Objective</h4>Serum uric acid (SUA) has been associated with cardiovascular diseases, including atherosclerosis and carotid artery stenosis. However, data on the relationship between SUA level and proximal extracranial artery stenosis (PEAS) are limited. Therefore, this study investigates the association between SUA levels and the risk of PEAS in asymptomatic Chinese population.<h4>Setting</h4>This community-based cross-sectional study was conducted in Jidong Community Hospital, Tangshan, He ...[more]

PMID: 30139894

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Project description:ObjectiveWe have shown that almost 50% of patients with asymptomatic carotid stenosis (ACS) will demonstrate cognitive impairment. Recent evidence has suggested that cerebral hypoperfusion is an important cause of cognitive impairment. Carotid stenosis can restrict blood flow to the brain, with consequent cerebral hypoperfusion. In contrast, cross-hemispheric collateral compensation through the Circle of Willis, and cerebrovascular vasodilation can also mitigate the effects of flow restriction. It is, therefore, critical to develop a clinically relevant measure of net brain perfusion in patients with ACS that could help in risk stratification and in determining the appropriate treatment. To determine whether ACS results in cerebral hypoperfusion, we developed a novel approach to quantify interhemispheric cerebral perfusion differences, measured as the time to peak (TTP) and mean transit time (MTT) delays using perfusion-weighted magnetic resonance imaging (PWI) of the whole brain. To evaluate the utility of using clinical duplex ultrasonography (DUS) to infer brain perfusion, we also assessed the relationship between the PWI findings and ultrasound-based peak systolic velocity (PSV).MethodsStructural and PWI of the brain and magnetic resonance angiography of the carotid arteries were performed in 20 patients with ≥70% ACS. DUS provided the PSV, and magnetic resonance angiography provided plaque geometric measures at the stenosis. Volumetric perfusion maps of the entire brain from PWI were analyzed to obtain the mean interhemispheric differences for the TTP and MTT delays. In addition, the proportion of brain volume that demonstrated a delay in TTP and MTT was also measured. These proportions were measured for increasing severity of perfusion delays (0.5, 1.0, and 2.0 seconds). Finally, perfusion asymmetries on PWI were correlated with the PSV and stenosis features on DUS using Pearson's correlation coefficients.ResultsOf the 20 patients, 18 had unilateral stenosis (8 right and 10 left) and 2 had bilateral stenoses. The interhemispheric (left-right) TTP delays measured for the whole brain volume identified impaired perfusion in the hemisphere ipsilateral to the stenosis in 16 of the 18 patients. More than 45% of the patients had had ischemia in at least one half of their brain volume, with a TTP delay >0.5 second. The TTP and MTT delays showed strong correlations with PSV. In contrast, the correlations with the percentage of stenosis were weaker. The correlations for the PSV were strongest with the perfusion deficits (TTP and MTT delays) measured for the whole brain using our proposed algorithm (r = 0.80 and r = 0.74, respectively) rather than when measured on a single magnetic resonance angiography slice as performed in current clinical protocols (r = 0.31 and r = 0.58, respectively).ConclusionsInterhemispheric TTP and MTT delay measured for the whole brain using PWI has provided a new tool for assessing cerebral perfusion deficits in patients with ACS. Carotid stenosis was associated with a detectable reduction in ipsilateral brain perfusion compared with the opposite hemisphere in >80% of patients. The PSV measured at the carotid stenosis using ultrasonography correlated with TTP and MTT delays and might serve as a clinically useful surrogate to brain hypoperfusion in these patients.

Project description:Serum uric acid (SUA), as the end product of purine metabolism, has proven emerging roles in human disorders. Here based on a sample of 379 middle and old-aged Chinese twin pairs, we aimed to explore the magnitude of genetic impact on SUA variation by performing sex-limitation twin modeling analyses and further detect specific genetic variants related to SUA by conducting a genome-wide association study. Monozygotic (MZ) twin correlation for SUA level (rMZ = 0.56) was larger than for dizygotic (DZ) twin correlation (rDZ = 0.39). The common effects sex-limitation model provided the best fit with additive genetic parameter (A) accounting for 46.3%, common or shared environmental parameter (C) accounting for 26.3% and unique/nonshared environmental parameter (E) accounting for 27.5% for females and 29.9, 33.1, and 37.0% for males, respectively. Although no SUA-related genetic variants reached genome-wide significance level, 25 SNPs were suggestive of association (P < 1 × 10-5). Most of the SNPs were located in an intronic region and detected to have regulatory effects on gene transcription. The cell-type specific enhancer of skeletal muscle was detected which has been reported to implicate SUA. Two promising genetic regions on chromosome 17 around rs2253277 and chromosome 14 around rs11621523 were found. Gene-based analysis found 167 genes nominally associated with SUA level (P < 0.05), including PTGR2, ENTPD5, well-known SLC2A9, etc. Enrichment analysis identified one pathway of transmembrane transport of small molecules and 20 GO gene sets involving in ion transport, transmembrane transporter activity, hydrolase activity acting on acid anhydrides, etc. In conclusion, SUA shows moderate heritability in women and low heritability in men in the Chinese population and genetic variations are significantly involved in functional genes and regulatory domains that mediate SUA level. Our findings provide clues to further elucidate molecular physiology of SUA homeostasis and identify new diagnostic biomarkers and therapeutic targets for hyperuricemia and gout.

Dataset Information

Relation of serum uric acid to asymptomatic proximal extracranial artery stenosis in a middle-aged Chinese population: a community-based cross-sectional study.

Publications

Relation of serum uric acid to asymptomatic proximal extracranial artery stenosis in a middle-aged Chinese population: a community-based cross-sectional study.

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