Association Of Thyroid Function With White-coat,Masked And Sustained Hypertension

Background:There is a close and complicated connection between thyroid function and hypertension.Both overt hyperthyroidism and hypothyroidism can lead to elevated blood pressure.Whether subclinical hypothyroidism or subclinical hyperthyroidism can cause elevated blood pressure is still controversial despite several clinical explorations.Subclinical hypothyroidism has a higher incidence than subclinical hyperthyroidism,and has a more definite effect on cardiovascular damage,so the association between subclinical hypothyroidism and blood pressure is more important.In euthyroid subjects,there may also be a correlation between thyroid function and blood pressure level.There have been meta-analysis results showing that Thyroid stimulating hormone(TSH)is related to the elevated systolic and diastolic blood pressure,but the analysis results have high heterogeneity and cannot be explained.Recent large-scale clinical studies suggest that free triiodothyronine(FT3)and free thyroxine(FT4)are related to hypertension,but not TSH.This also makes the association between thyroid function and blood pressure controversial in euthyroid subjects.In fact,the above studies are only based on the clinic blood pressure and relying solely on the blood pressure in the clinic may not fully reflect the real correlation between thyroid function and blood pressure status.With the gradual popularization of ambulatory blood pressure monitoring and home self-test blood pressure,the medical profession found that there was inconsistency between the blood pressure in the clinic and the blood pressure outside the clinic.The blood pressure could be divided into four kinds of hypertension subtypes by combining the blood pressure in the clinic and the blood pressure outside the clinic,namely,normotension(NT),white-coat hypertension(WCH)with elevated blood pressure in the clinic alone,masked hypertension(MHT)with elevated blood pressure outside the clinic alone,and sustained hypertension(SHT)with elevated blood pressure inside and outside the clinic.The mechanism of hypertension subtypes such as WCH is still unclear.This study combines the clinic and 24-hour ambulatory blood pressure to divide WCH,MHT and SHT,and discusses the correlation between subclinical hypothyroidism and hypertension subtypes such as WCH,and analyzes the thyroid function characteristics of WCH,MHT and SHT in the euthyroid subjects.It is hoped that this can be used to understand the relationship between thyroid function and blood pressure more comprehensively,and try to explain the previous research disputes on blood pressure level in the clinic.Section ?Objective:To explore the association of subclinical hypothyroidism with WCH,MHT and SHT.Methods:This study is a cross-sectional observational study.From December 2017 to November 2019,a total of 3,078 adults volunteered to participate in this study.All participants had completed 24-hour ambulatory blood pressure monitoring.Continue to understand the participants' age,sex,smoking history,drinking history,history of illness,medication history through questionnaires.Height and weight were measured and body mass index(BMI)was calculated.The upper brachial artery blood pressure and heart rate of participants were measured in the clinic.The average value of blood pressure and heart rate for 3 times other than the same day was recorded as the intra-clinic blood pressure and intra-clinic heart rate.Blood lipid,fasting blood glucose,liver function,renal function,TSH,FT3 and FT4 of the participants were detected.After detailed understanding of the participants' medical history and examination results,1354 cases were excluded for antihypertensive drugs or drugs affecting thyroid function use according to the exclusion criteria,29 cases for congenital heart disease,cardiomyopathy and moderate or severe valvular heart diseases,17 cases for secondary hypertension,65 cases for subjects of liver and kidney insufficiency,182 cases for abnormal thyroid function other than subclinical hypothyroidism.A total of 104 cases of subclinical hypothyroidism group(S-HYPO group)and 1327 cases of euthyroid group(ET group)were included.The total age of the samples was 61.9 ± 11.7 years old,736 cases of males and 695 cases of females.NT,WCH,MHT and SHT were divided among participants according to the standards of the European Hypertension Practice Guide(2014)and the results of clinic blood pressure and ambulatory blood pressure.SPSS 22.0 software was used to analyze the distribution of WCH and other hypertension subtypes between the S-HYPO group and ET group.Results:1.The concentration of TSH in S-HYPO group was significantly higher than that in ET group,while the concentration of FT3 and FT4 in S-HYPO group was lower than that in ET group(P < 0.001,P=0.002,P < 0.001).2.There was no significant difference in clinic systolic and diastolic blood pressure between S-HYPO group and ET group(P > 0.05).The mean daytime systolic blood pressure,night systolic blood pressure,night diastolic blood pressure,24-h systolic blood pressure and 24-h diastolic blood pressure in S-HYPO group were significantly higher than those in ET group(P=0.048,P=0.002,P=0.007,P=0.014,P=0.046).3.The results of contingency table analysis suggested that there were statistical differences in the overall distribution of NT,WCH,MHT and SHT between S-HYPO group and ET group(P =0.002).After adjusting P value by Bonferroni method,the results showed that there were statistical differences in the distribution of subclinical hypothyroidism patients and euthyriod subjects between MHT and NT groups and between SHT and NT groups.4.Multivariate Logistic regression analysis showed that subclinical hypothyroidism was an independent risk factor for MHT and SHT after adjusting for the confounding factors of sex,age,body mass index,smoking history,drinking history,diabetes and hyperlipidemia(OR=2.197,95% CI: 1.298-3.719,P=0.003;OR=2.232,95% CI: 1.290-3.863,P=0.004).Conclusions:Subclinical hypothyroidism is associated with MHT and SHT,but not with WCH.Section ?Objective:To explore whether TSH,FT3,FT4 are consistent with the association of blood pressure inside and outside the clinic in the euthyroid subjects,and to analyze the thyroid function characteristics of WCH,MHT and SHT in the euthyroid subjects.Methods:There were 1327 euthyroid participants included in the first section,with an average age of 61.6 years,including 700 males and 627 females.According to the European Hypertension Practice Guidelines(2014),SHT is defined as the group with both elevated clinic blood pressure and ambulatory blood pressure.WCH is defined as the group with normal ambulatory blood pressure and elevated clinic blood pressure.MHT is defined as the group with normal clinic blood pressure and elevated ambulatory blood pressure.NT group is defined as the group with normal clinic blood pressure and ambulatory blood pressure,and the combination of NT group and MHT group is called as the group with normal clinic blood pressure(NT + MHT group),the combination of WCH group and SHT group is called as the group with elevated clinic blood pressure(WCH + SHT group),the combination of NT group and WCH group is called as the group with normal ambulatory blood pressure(NT + WCH group),and the combination of MHT group and SHT is called as the group with elevated ambulatory blood pressure(MHT + SHT group).There were 489 cases in WCH+SHT group,838 cases in NT+MHT group,598 cases in MHT+SHT group,729 cases in NT+WCH group,544 cases in NT group,185 cases in WCH group,294 cases in MHT group and 304 cases in SHT group.SPSS 22.0 software was used to compare the concentrations of TSH,FT3 and FT4 among the groups.Results:1.The concentrations of FT3 and FT4 in WCH+SHT group were higher than those in NT+MHT group(P<0.001,P=0.003),but there was no statistical difference in TSH concentration between groups(P=0.148).The levels of TSH and FT3 in MHT +SHT group were higher than those in NT+WCH group(P=0.023,P=0.007),but there was no statistical difference in FT4 level between groups(P=0.975).2.The concentration of TSH in SHT group was higher than that in NT group and WCH group(P=0.011,P=0.018),and the concentration of FT3 in SHT group was higher than that in NT group and MHT group(P < 0.001,P=0.002).3.The concentration of FT4 in WCH group was significantly higher than that in NT group,MHT group and SHT group(P < 0.001,P=0.002,P=0.001).4.The above difference results were adjusted for age,sex,body mass index,smoking history,drinking history,diabetes and hyperlipidemia confounding factors by multivariate unconditional Logistic regression analysis,and the above difference was still significant(P < 0.05).5.When distinguishing between WCH and SHT,the area under the curve(AUC)of TSH was 0.561(95% CI:0.508-0.614,P=0.023)and that of FT4 was 0.594(95% CI:0.542-0.646,P < 0.001)Conclusions:The association between TSH,FT3,FT4 and clinic blood pressure is not consistent with that between TSH,FT3,FT4 and ambulatory blood pressure.SHT is characterized by elevated TSH and FT3,while WCH is characterized by elevated FT4.Section ?Objective:The results of the second section suggest that TSH and FT4 have statistical differences between WCH and SHT groups,but their discrimination between WCH and SHT is poor.Therefore,further attempts are made to establish a differential diagnosis model between WCH and SHT by combining other indexes other than thyroid function.Methods:Based on the clinical information of patients with elevated clinic blood pressure in the euthyroid participants,a differential diagnosis model of WCH was established.A total of 185 WCH patients and 304 SHT patients were included.The differential diagnosis model of WCH was established by dividing training set and verification set,Lasso regression screening variables,Logistic regression modeling and drawing nomogram,discrimination degree and calibration degree test using RStudio software version 1.2.1335.The European Guidelines for Hypertension Practice point out that ambulatory blood pressure examination should be carried out for patients with hypertension grade 1 to determine whether WCH exists.This method is regarded as hypertension grading method.In this model,non-low-risk patients(disease risk ? 30%)are listed as ambulatory blood pressure monitoring objects,and the corresponding methods are regarded as differential diagnosis model methods.Chi-square test was used to compare the statistical differences of participation rate and missed diagnosis rate of WCH between hypertension classification method and differential diagnosis model method.Results:1.Participants were randomly divided to training sets and verification sets through RStudio software,and 346 training sets and 143 verification sets obtained.There were 139 WCH patients and 207 SHT patients in the training concentration,46 WCH patients and 97 SHT patients in the verification concentration.There was no statistical difference in the proportion of WCH between the groups(P=0.097).2.Lasso regression and single-factor Logistic regression jointly determine the parameter model variables.The parameters selected in the model were Isolated systolic hypertension(ISH),clinic systolic and diastolic blood pressure,TSH,FT4 and serum creatinine.Multivariate Logistic Regression Modeling and Drawing nomogram.3.The discrimination degree of the differential diagnosis model in the training set and the verification set is relatively close(AUC=0.725,95% CI: 0.671-0.778;AUC=0.692,95% CI: 0.604-0.780).The calibration test shows that the differential diagnosis model has good calibration degree in both training set and verification set(MAE=0.017,MSE=0.00038;MAE=0.023,MSE=0.00097).4.The participation rate of hypertension grading method was 75.7%,and that of differential diagnosis model method was 68.1%.Differential diagnosis model method could significantly reduce the participation rate(P=0.008).However,the missed detection rate of WCH by hypertension classification was 14.1%.The rate of missed diagnosis was 16.8% by differential model method,but there was no statistical difference between the two methods(P=0.471).Conclusions:A stable WCH differential diagnosis model could be established in euthyroid subjects and showed a certain degree of discrimination.