High Level of Serum Uric Acid induced Monocyte Inflammation is Related to Coronary Calcium Deposition in the Middle-Aged and Elder Population of China: A five-year Prospective Cohort Study

Figures & data

Table 1 Matrix of Outcome Measures and Assessments

	Baseline	1 Year	2 Years	3 Years	4 Years	5 Years
Baseline characteristics (Age, Gender, BMI, Smoke status, Alcoholic intake, Complications)	P
Serum uric acid	P
CACS	P	P	P	P	P	P
Blood glucose	P	P	P	P	P	P
Liver function test	P
Renal function test	P

Abbreviations: BMI, body mass index; CACS, coronary artery calcium score.

Table 2 Univariate and Multivariate Logistic Regression Between CACS and Hemogram Indices

Model	Mean±SD	Univariate Regression			Multivariate Regression
		OR	95% CI.	P-value	OR	95% CI.	P-value
Age	62.17±7.00	1.043	1.009–1.078	0.013	1.046	1.001–1.093	0.043
BMI	24.67±2.75	1.136	1.042–1.238	0.004	1.074	0.966–1.195	0.184
Gender	210(62.42)	5.670	3.092–10.399	<0.001	3.945	1.298–13.343	0.022
Smoke Status				-
Non-smoker	281 (86.2)	Reference	-	-	-	-	-
Ex-smoker	37 (11.35)	2.011	1.007–4.015	0.048	-	-	-
Smoker	8 (2.45)	1.273	0.298–5.445	0.744	-	-	-
Alcoholic Intake	26 (7.98)	2.442	1.088–5.478	0.030	1.353	0.520–3.523	0.536
HBP	33 (10.12)	0.965	0.450–2.070	0.927	-	-	-
Diabetes	18 (5.52)	0.733	0.254–2.111	0.565		-	-
SUA	349.80±69.75	1.016	1.012–1.021	<0.001	1.014	1.009–1.019	<0.001
eGFR	86.58±14.88	0.991	0.976–1.007	0.288	-	-	-
Scr	74.92±12.19	1.037	1.016–1.059	<0.001	1.011	0.984–1.038	0.431
HBAC1	5.57±0.77	2.378	1.552–3.644	<0.001	1.208	0.720–2.027	0.474
TC	4.17±4.77	0.999	0.951–1.048	0.954	-	-	-
TG	2.21±1.35	0.733	0.606–0.886	0.001	0.931	0.656–1.321	0.688
HDL	3.88±4.77	0.881	0.827–0.938	<0.001	1.132	0.990–1.293	0.070
LDL	2.26±0.71	1.392	1.012–1.915	0.042	0.994	0.642–1.539	0.978
FBG	5.68±0.85	1.966	1.405–2.752	<0.001	1.317	0.869–1.995	0.194
ALP	67.55±19.68	0.980	0.966–0.993	0.004	0.977	0.961–0.993	0.006

Abbreviations: SE, standard error; OR, odds ratio;95% CI,95% confidence interval; BMI, body mass index; HBP, high blood pressure; Scr, serum creatinine; eGFR, estimated glomerular filtration rate; ALP, alkaline phosphatase; TC, total cholesterol; TG, triglycerides; HDL, high-density lipoprotein; LDL, low-density lipoprotein; HBA1C, hemoglobin A1C. The P value in red means that the p value <0.05 and is considered to be significantly important.

Figure 1 Analysis of the predictive effect of different clinical indicators and scores on CAC score. (A) Representative examples of CAC in four patients. (B) ROC shows the predictive ability of SUA in asymptomatic participants. (C) The column diagram shows the correlation between four items in CACS and SUA. (D) ROC shows the predictive ability of the Framingham risk score in asymptomatic participants; (E) ROC shows the predictive ability of ESR in asymptomatic participants.

Abbreviations: CAC, coronary artery calcification; LAD, left anterior descending coronary artery; LCX, left circumflex coronary artery; LMCA, left main coronary artery; RCA, right coronary artery; SUA, serum uric acid. (****, P<0.0001).

Figure 2 A total of 326 asymptomatic middle-aged and elderly patients with 5-year clinical follow-up analysis. (A) Survival curve in 326 asymptomatic middle-aged and elderly patients over five years. K-M analysis demonstrated that SUA level was associated with CACS. P<0.05 means statistically significance between two groups. (B) Binary cox regression analysis for CACS within 5 years. Forest plot showed the result of cox regression analysis.

Abbreviations: HR, hazard ratio; CI, confidence interval; BMI, body mass index; HBP, high blood pressure; Scr, serum creatinine; eGFR, estimated glomerular filtration rate; TC, total cholesterol; TG, triglycerides; FBG, fasting blood-glucose; ALP, Alkaline phosphatase; HDL, high-density lipoprotein; LDL, low-density lipoprotein; HBA1C, hemoglobin A1C.

Figure 3 Potential pathogenesis of hyperuricemia on coronary atherosclerosis. (A) The Venn diagram of both hyperuricemia targets and coronary atherosclerosis targets. (B) Bubble chart of the top 9 signaling pathways screened by using the KEGG enrichment analysis. (C) Protein-protein interaction and gene co-expression network. (D) Hub genes were determined using the STRING and Cytoscape software. (E) Venn diagram showing the overlap genes between three types of pathways. (F) Protein-protein interaction and gene co-expression network.

Abbreviations: IL-6, interleukin (IL)-6; CXCL8, cysteine X chemokine ligand (CXCL) 8; TNF, tumor necrosis factor-α (TNF-α); Caspase3, CASP3; STAT3, signal transducer and activator of transcription-3.

Figure 4 An observational study on 104 asymptomatic middle-aged and elderly patients. (A-F) Density distribution of SUA, SCR, BUN, eGFR, TC and TG value in four groups. (G) Column plot shows the mRNA level of five genes (IL-6, CXCL8, TNF, Caspase3, STAT3) between four groups. (H) The correlation analysis between clinical indexes and relative gene expression in patients. (I) Expression profile cluster analysis of five genes from PBMCs involved in four groups patients.

Abbreviations: SCR, serum uric acid; SCR, serum creatinine; BUN, blood urea nitrogen; eGFR, estimated glomerular filtration rate; TC, total cholesterol; TG, triglycerides; IL-6, interleukin (IL)-6; CXCL8, cysteine X chemokine ligand (CXCL) 8; TNF, tumor necrosis factor-α (TNF-α); Caspase3, CASP3; STAT3, signal transducer and activator of transcription-3; NC, normal control; HUA, hyperuricemia; CAC, coronary calcium deposition. * Represents the statistic difference between the normal control group and all other groups. (**, adjusted P<0.01; ****, adjusted P<0.0001).