| BackgroundHypertension is the leading risk factor of many highly fatal cardiovascular and cerebrovascular diseases,affecting approximately 1.4 billion people worldwide.Until 2018,the prevalence of hypertension among adults over 18 years old in China is 23.20%,and the prevalence among adults aged 35-75 years is as high as 37.20%,which has caused a heavy burden of disease for individuals,families,and the whole society.Extensive research evidence confirms that hypertension is closely related to liver fat accumulation and the abnormal serum lipoprotein metabolism which was caused by abnormal liver metabolism.However,the association between serum alanine aminotransferase(ALT)level,the most sensitive indicator of liver fat accumulation,and hypertension is still controversial.This study used two study designs,including a cross-sectional study and a prospective cohort study,to explore the association between serum ALT levels and hypertension as well as blood pressure among adults.Furthermore,the additive interactions for common hypertension risk factors on the association between serum ALT levels and hypertension were analyzed.Finally,the impact of serum ALT decreasing on the risk of hypertension was explored.MethodsPart ?.Association between serum alanine aminotransferase levels and blood pressures as well as the prevalence of hypertension:a cross-sectional studyA population-based cross-sectional study was conducted based on the registration data from National Free Preconception Checkups Project(NFPCP)in 2016-2017.Eligible participants were enrolled from 2907 counties(districts/cities)of 31 provinces including autonomous regions and municipalities across China.During the preconception checkups,a conventional automatic biochemical analyzer was used,and then appropriate kits were selected according to the instrument to continuously monitor the decreasing rate of the absorbance in the serum samples at a wavelength of 340nm and calculate the activity unit of serum ALT.The validated upper arm medical electronic blood pressure monitor was used to measure the upper arm blood pressure in a sitting state.In our study,serum ALT levels were divided into 3 groups.Group I includes normal ALT level(ALT ?40U/L)and elevated ALT level(ALT>40U/L):Group? contains 5 levels,from the lowest serum ALT level(?20 U/L)to the highest ALT level(>80 U/L)L)for each layer increasing by 20 U/L in turn;Group III includes quartile ALT levels,namely Q1:?14U/L,Q2:14.01-20 U/L,Q3:20.01-30 U/L and Q4:>30 U/L.According to the diagnostic criteria of the World Health Organization(WHO).hypertension was defined as SBP? 140 mmHg and/or DBP? 90 mmHg.Multivariable logistic regression models were used to assess the association between serum ALT levels and hypertension among total and subgroup populations.and the strength of association including odds ratio(OR)and its 95%confidence intervals(95%CI).Multivariable linear regression models were used to assess the association between serum ALT levels and systolic blood pressures(SBP)as well as diastolic blood pressures(DBP).The Least-squares means(LS-means)method was used to estimate the average blood pressure levels corresponding to different ALT levels after adjusting for gender and age.Restricted cubic spline function was used to fit the dose-response relationship between serum ALT concentrations and the odds of hypertension.Stratified analyses were used to evaluate the additive interactions of overweight/obesity,alcohol consumption,smoking,fasting blood glucose(FBG)?6.1 mmol/L,and positive hepatitis B surface antigen(HBsAg)on the association between serum ALT levels and hypertension.Finally,sensitivity analyses were used to evaluate the robustness of observed association between serum ALT levels and hypertension.Part ?.Association between serum alanine aminotransferase levels and blood pressures as well as the risk of hypertension:a prospective cohort studyA prospective cohort study was conducted based on the Kailuan cohort study.Data were collected from in-service and retired employees who had undergone health check-ups in 11 hospitals of the Kailuan Group.Eligible participants who took participate in health check-ups in 2006 were included as the research object and then followed up by health check-ups every two years.Until December 31,2017,a total of 6 follow-ups have been conducted,forming a prospective cohort with substantial and complete datasets.During the physical examination,a standard automatic biochemical analyzer and a unified brand kit are used to measure serum ALT levels.All operations are strictly performed in accordance with the requirements of the using instructions.A calibrated mercury sphygmomanometer was used to measure the right side of the seat Brachial artery blood pressure,and then the averaged value of 3 consecutive measurements was obtained.In our study,serum ALT levels were divided into 3 groups.Group I includes normal ALT level(ALT ?40U/L)and abnormal ALT level(ALT>40U/L);Group II includes quartile ALT levels,namely Q1:?12 U/L,Q2:12.01-17 U/L,Q3:17.01-24 U/L and Q4:>24 U/L;Group III contains 5 levels,from the lowest level of serum ALT in the normal range(? 10 U/L)to the abnormal ALT(>40 U/L)for each layer increasing by 10 U/L.The endpoint of follow-up was defined as hypertension at least 2 times during the 5 follow-ups.Hypertension at each follow-up was defined as SBP? 140 mmHg and/or DBP? 90 mmHg and/or taking any antihypertensive medicine.Multivariable Cox regression models were used to assess the association between baseline serum ALT levels and the risk of hypertension[Hazard ratio(HR)and 95%CI].Considering that the multivariable Cox regression may not meet the Equal-proportional hypothesis,the multivariable weighted Cox regression models were used to re-assess the association between baseline serum ALT levels and the risk of hypertension as well as the strength of association in different subgroups[Average hazard ratio(AHR)and 95%CI].Multivariable linear regression models were used to assess the association between baseline serum ALT levels and SBP as well as DBP at the last follow-up,and to estimate the LS-means of blood pressures corresponding to different baseline ALT levels after adjusted by gender and age.Restricted cubic spline function was used to fit the dose-response relationship between baseline serum ALT concentrations and the AHR of hypertension.Stratified analyses were used to evaluate the additive interactions of baseline overweight/obesity,alcohol consumption,smoking,high salt intake,fatty liver,and high triglycerides on the association between serum ALT levels and the risk of hypertension.Sensitivity analyses were used to evaluate the robustness of observed association between baseline serum ALT levels and the risk of hypertension.Finally,the impact of changes in serum ALT levels(whether back to normal)on the risk of hypertension was also assessed.ResultsPart I.Association between serum alanine aminotransferase levels and blood pressures as well as the prevalence of hypertension:a cross-sectional studyFinally,21,103,790 subjects were included in the population-based cross-sectional study,including 10,095,225(47.84%)males and 11,008,565(52.16%)females,with an average age of 29.55 years.The abnormal serum ALT(>40 U/L)rate in eligible participants was 11.67%,and the prevalence of hypertension(SBP?140 mmHg|DBP?90 mmHg)was 4.21%.After multivariable adjustment,the OR for hypertension showed a monotonous upward trend with the increasing of ALT concentrations;compared with the normal ALT group,the OR for hypertension in the abnormal ALT group was 1.53(95%CI:1.53-1.54);Compared with the 0-20U/L level,the ORs for hypertension was increased by 22%,65%,76%.and 90%(OR,1.22,95%CI:1.21-1.22;OR,1.65,95%CI:1.64-1.66;OR,1.76,95%CI:1.64-1.66;OR,1.90,95%CI:1.88-1.92)(P for trend<0.001)in higher ALT level within normal range(20.01-40 U/L).slightly increased ALT level(40.01-60 U/L).moderately increased ALT level(60.01-80 U/L),and severely increased ALT level(>80 U/L).respectively.In group ?,with the increasing of serum ALT levels,the ORs of hypertension were increased linearly(P for trend<0.001).The association between serum ALT levels and hypertension was consistent in all subgroups.After multivariable adjustment.ALT concentration was linearly correlated with SBP and DBP(P<0.001,P<0.001).Compared with the normal serum ALT level,the SBP and DBP of the abnormal ALT level were increased by 4.16 mmHg and 2.63 mmHg on average,after adjustment for age and gender.For every 20 U/L increase in serum ALT concentrations,the SBP and DBP after adjustment for age and gender were increased by 1.83 mmHg and 1.20 mmHg on average.For each quartile increase in serum ALT levels,the averaged SBP and DBP after adjustment for age and gender were increased by 1.50 mmHg and 1.00 mmHg,respectively.Body mass index(BMI)?24 kg/m2,drinking and fasting blood glucose(FBG)?6.1 mmol/L have a synergistic effect on the association between serum ALT levels and hypertension(P<0.001);smoking and positive HBsAg status have an antagonistic effect on the association between serum ALT levels and hypertension(P<0.001).Part ?.Association between serum alanine aminotransferase levels and blood pressures as well as the risk of hypertension:a prospective cohort studyFinally,47,396 subjects were included in the prospective population-based cohort study,including 35,525(74.95%)men and 11,871(25.05%)women,with an average age of 47.69 years.The rate of abnormal baseline serum ALT(>40 U/L)in the eligible participants was 6.04%,the average follow-up time was about 9.23 years,and the cumulative incidence of hypertension(SBP?140 mmHg |DBP?90 mmHg)was 28.05%.After multivariable adjustment,the HR of hypertension showed a monotonous upward trend with the increase of baseline serum ALT concentrations.Compared with the normal ALT level,the AHR of abnormal ALT level at baseline was 1.14(95%CI:1.07-1.22).In group ?,with the increasing of serum ALT levels,the AHRs for hypertension were increased linearly(P for trend<0.001).Besides,compared with 0-10 U/L within the normal range in group ?,the AHRs for hypertension were increased by 10%,19%,34%,and 31%,respectively(AHR,1.10,95%CI:1.04-1.17;AHR,1.19,95%CI:1.12-1.27;AHR,1.34,95%CI:1.23-1.44;AHR,1.31,95%CI:1.21-1.43)(P for trend<0.001)in ALT levels with 10.01-20 U/L,20.01-30 U/L,30.01-40 U/L,and>40 U/L groups,respectively.The association between baseline serum ALT levels and the risk of hypertension was consistent in all subgroups.After multivariable adjustment,the baseline ALT level was linearly correlated with SBP and DBP(P<0.001,P<0.001).Compared with the normal ALT level,the SBP and DBP of the abnormal baseline ALT level were increased by 5.02 mmHg and 3.03 mmHg on average after adjustment for age and gender.For each quartile increase in serum ALT levels at baseline,the averaged SBP and DBP after adjustment for age and gender were increased by 1.63 mmHg and 0.48 mmHg,respectively.For every 10 U/L increase in serum ALT level within the normal range of baseline,the SBP and DBP after adjustment for age and gender were increased by 2.00 mmHg and 0.82 mmHg on average.BMI?24 kg/m2,drinking,fatty liver,and TG?2.26 mmol/L at baseline have a stronger effect on the risk of hypertension than that of abnormal serum ALT levels at baseline(P<0.001);smoking and higher salt intake have no additive interactions on the association between baseline serum ALT levels and the risk of hypertension.Compared with those who had abnormal serum ALT levels during baseline and follow-up,people with abnormal baseline serum ALT levels and normal serum ALT levels at follow-up had a 34%reduction in AHR for hypertension,with AHRs of 1.45(95%CI:1.27-1.65)and 1.11(95%CI:1.02-1.22).ConclusionsOur study found that serum ALT levels were not only related to their current blood pressures and the prevalence of hypertension,but also affected their long-term blood pressures and the risk of hypertension.Meanwhile,serum ALT levels were positively linear with the current and long-term blood pressures.Many common risk factors had an additive interaction on the association between serum ALT levels and hypertension.Moreover,for people with abnormal serum ALT levels,returning to normal serum ALT levels may reduce their risks of hypertension.Our results support that maintaining a healthy liver is help for reducing their risk for hypertension. |
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