| Objectives:Recently,it has been found that a variety of vasoactive substances in the blood circulation,such as urotensin?(U?)and endothelin-1(ET-1),play an important role in the cardiovascular system.However,the association of U ? and ET-1 with hypertension and other cardiovascular diseases(CVDs)remains unclear with been poorly studied in humans,and the most of those published studies were case-control studies with small sample sizes,which were unconducive to elucidating the causal relationship between the levels of U ? /ET-1 and CVDs.Therefore,we conduct a prospective cohort study to explore the association of U? and ET-1 with the risk of CVDs,and to provide epidemiological evidence for the association of U? and ET-1and hypertension and other CVDs.Study methods1.Basiline survey: Baseline population for our study was from a population-based investigation of risk factors for CVDs,which was conducted in rural communities of Changshu,Jiangsu province of China from 2007 to 2008.A total of 20434 participants were enrolled in the investigation.Standard questionnaires regarding the data on demographic characteristics,lifestyle risk factors,medical histories,and so on,were completed face-to-face by trained staffs.Data on blood pressure,pulse,and anthropometric variables were also measured for all participants according to standard methods.Fasting blood samples were taken in the morning and separated into plasma and serum.Fasting plasma glucose(FPG),trigly ceride(TG),total cholesterol(TC)and high-density lipoprotein cholesterol(HDL-C)were tested in all participants.For the current study,we selected 1824 individuals over the age of 30 years among the baseline individuals who were free of hypertension,CVDs and any other severe diseases atbaseline.Furthermore,enzyme-linked immunosorbent assay(ELISA)was adopted to measure the levels of plasma U? and ET-1 of those participants involved in our study.2.Follow-up survey: All 20343 participants were followed up from October 2013,and follow-up questionnaires were same as that of the baseline survey.Our study focus on documenting records for newly occurring hypertension,coronary heart disease and stroke during the follow-up.Statistics analysis1.Analysis on baseline characteristics: The baseline characteristics of the general demographics,behavioral habits,family disease history,blood pressure,FPG,and blood lipids were described by groups of gender,quartiles of U? and quartiles of ET-1,and interpreted with median [inter quartile range(IQR)] or composition ratio,while the difference of baseline characteristics among those groups were compared by using Wilcoxon test and ?2test.The correlation between baseline U?/ET-1 and baseline BMI,blood pressure,FPG or Blood lipids was quantified by spearman partial rank correlation coefficients.2.Follow-up results: The cumulative incidence of CVDs was calculated by gender,quartiles of U? and quartiles of ET-1.The chi-square test or the Fisher exact test was used to compare the difference among groups.3.Association analysis between baseline levels of U ? /ET-1 and follow-up outcomes: With the lowest quartile(?QL)and the low-level group(?QU)of U?/ET-1 as a reference group,the relative risk(RR)and 95% confidence interval(CI)for risk of hypertension and other CVDs in each high-level groups of U?/ET-1 were estimated by using generalized linear regression model with log link and binomial error distribution.In addition,a subgroup analysis was performed according to traditional risk factors for CVDs to analyze the association of baseline levels of U ? /ET-1 with the risk of hypertension and other CVDs in different subgroups,and the results were showed with forest plots.Epidata3.1 software was used to establish a database,and all data was checked after data was entried for two times.All statistical analyses were conducted using SAS9.4 and Stata14.0 software.All p-values were obtained based on 2-sided tests and a statistical significance level was set at 0.05.Results1.During the follow-up period,among 1824 participants that were followed,there were a total of 1819 participants that were finally included in the analysis due to 5participants being lost to follow-up.Among the 1819 cases,there were 732 males and1087 females,and median of age was 51.7 years old(IQL,47.5-55.3 years old),baseline medians of SBP and DBP were 121.0mm Hg(IQL,113.0-129.0mm Hg)and76.3mm Hg(IQL,70.7-81.7mm Hg),respectively.At baseline,there were significant differences in SBP(P=0.013),FPG(P=0.006),and ET-1(P=0.001)among quartiles of U ?,as well as the significant differences in SBP(p=0.045),DBP(P=0.026)among quartiles of ET-1.2.After multiple adjustment,the baseline level of U? did not correlate with SBP,DBP,BMI,TC,TG,LDL-C and HDL_C(all P >0.05),while the spearman partial rank correlation analysis showed significant association between baseline U ? and FPG(rs' =-0.058,p=0.013).The correlation of ET-1 and baseline SBP,DBP,BMI,TC,TG,FPG,LDL-C and HDL_C was not statistically significant(all P > 0.05).3.The cases and cumulative incidence(%)of hypertension,stroke,coronary heart disease and composite outcome of cardiovascular events in five-year follow-up study were 722(39.69%),5(0.27%),9(0.49%)and 725(39.86%),respectively.There were no significant differences in the incidence of hypertension,stroke,coronary heart disease,and composite outcome of cardiovascular events among subjects with different levels of U?/ET-1(all P>0.05).4.In comparison to the lowest quartile(Q1)of U?,after adjusting the confounding factors related to CVDs,RR(95%CI)for the risk of hypertension in the Q2,Q3 and Q4 groups were 0.98(0.85-1.13),0.97(0.83-1.12)and 0.94(0.81-1.09),respectively(all p>0.05).RR(95% CI)for the risk of cardia-cerebrovascular disease(coronary heart disease and stroke)in Q2,Q3 and Q4 were 0.53(0.13-2.13),0.49(0.12-2.00)and0.18(0.02-1.50),respectively(all P>0.05).In addition,in comparation to the low-level of U ?,the association of high-level U ? with the risk of hypertension and cardia-cerebrovascular disease was not statistically significant(all P>0.05).5.With the Q1 of ET-1 as a reference group,after adjusting for confounding factors related to CVDs,RR(95%CI)for the risk of hypertension in Q2,Q3 and Q4 groups were 1.04(0.90-1.21),1.10(0.95-1.27)and 0.97(0.83-1.13),respectively(allP>0.05).RR(95%CI)for the risk of cardia-cerebrovascular disease(coronary heart disease and stroke)in Q2,Q3 and Q4 were 1.47(0.25-8.83),2.64(0.5-13.88)and 1.43(0.24-8.61),respectively(all P>0.05).The association of high-level ET-1 with hypertension and cardia-cerebrovascular disease were not statistically significant(all P>0.05),compared with the low-level of ET-1.6.Subgroup analysis did not find that the risk of hypertension and composite outcome of cardiovascular events in the high U? group was statistically significant higher than that in the low group.Compared with the low-level of ET-1,RR(95% CI)for the risk of hypertension and composite outcome of cardiovascular events in the high-level ET-1 among study participants without family history of CVDs were 0.83(0.69-1.00)and 0.82(0.68-0.99),the P-value were 0.050 and 0.036,respectively.While among other subgroup participants,the high-level ET-1 were not significantly associated with the risk of hypertension and composite outcome of cardiovascular events(all P > 0.05),compared with the low-level of ET-1.Conclusion1.Plasma U ? and ET-1 were not correlated with BMI,SBP,DBP,TC,TG,HDL-C,LDL-C and FPG among normotensive participants.2.High level of U? at baseline was not found to predict the 5-year cumulative incidence of hypertension and other CVDs in normotensive individuals.3.High level of ET-1 at baseline was not found to predict the 5-year cumulative incidence of hypertension and other CVDs in normotensive individuals.4.In the subgroup analysis according to traditional risk factors for CVDs,high-levels of U? or ET-1 were not associated with 5-year cumulative incidence of hypertension and other CVDs in normotensive individuals. |
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