A Study Of The Correlation Between Autonomic Function And Cardiometabolism

Part ?:Conventional and bi-directional genetic evidence on resting heart rate and cardiometabolic traits:results from 1 million British and Chinese participants in two biobanks.Background and Objectives:Resting heart rate(RHR),as a sensitive indicator of automatic nervous tone,reflecting a balance of sympathetic and parasympathetic inputs.Accumulating evidence has suggested elevated RHR might play a critical role in increased risk of cardiometabolic diseases.To examine the direction,strength and causality of the associations of RHR with cardiometabolic traits.Methods:We assessed the strength of associations between measured RHR and cardiometabolic traits in 506,211 participants from the China Kadoorie Bi-obank(CKB)and 372,452 participants from the UK Biobank(UKB).Mendelian randomization(MR)analysis was used to make causal inference in 99,228 participants from CKB and 371,508 participants from UKB.Results:We identified significant observational associations between RHR and higher level of total cholesterol(TC),triglycerides(TG),low-density lipoprotein(LDL),C-reactive protein(CRP),glucose,body mass index(BMI),waist-hip ratio(WHR),systolic blood pressure(SBP)and diastolic blood pressure(DBP)after the Bonferroni correction.MR analysis showed that 10 beat/min higher genetically-predicted RHR was trans-ethically associated with a higher DBP(beta 2.059[95%CI 1.544,2.574]mmHg in CKB;2.037[1.845,2.229]mmHg in UKB),higher CRP(0.180[0.057,0.303]log mg/L in CKB;0.154[0.134,0.174]log mg/L in UKB),higher TG(0.052[-0.009,0.113]log mmol/L in CKB;0.020[0.010,0.030]log mmol/L in UKB)and higherWHR(0.218[-0.033,0.469]%in CKB;0.225[0.111,0.339]%in UKB).Conclusions:Our large-scale analyses provide causal evidence between RHR and cardiometabolic traits,highlighting the importance of monitoring heat rate as a means of alleviating the adverse effect of metabolic disorders.Part ?:Evaluation of the Risk Index for Predicting Short-term and Long-term Outcomes in Patients with ST-elevation Myocardial InfarctionBackground and Objectives:Admission Risk Index(RI)was developed as a simple tool in predicting risk of death in STEMI patients.The performance in predicting short-term and long-term risk of death in patients receiving PCI and conservative treatment remain unclear.This study aimed to evaluate the usefulness of RI for predicting the short-term and long-term outcomes in a broader population with ST-elevation Myocardial Infarction(STEMI)by using data from Chinese Acute Myocardial Infarction(CAMI)Registry.Methods:Heart rate(HR),systolic blood pressure(SBP)and age were used to calculate RI:(HR ×[age/10]2)/SBP.We assessed the prediction tool for predicting mortality over 12 months.Results:The C-index of admission RI for predicting in-hospital,1-month,6-month and 12-month mortality were 0.78,0.78,0.78 and 0.77,respectively,compared with 0.75 from the Global Registry in Acute Coronary Events score.Based on the receiver operating characteristic curve analysis,RI was categorized into quintiles for convenient clinical use,and it revealed a nearly 15-fold gradient of increasing mortality from 2.29 to 32.5%(p<0.0001)while RI>34 had the highest mortality.By categorized into 5 different risk groups,the short-term and long-term mortality of patients receiving different treatments could be distinguished.Conclusions:RI based on three routine variables easily calculated by any medical practitioners is useful for predicting in-hospital and long-term mortality in patients with STEMI at first medical contact.Part ?:Assessment of causal direction between thyroid hormone and cardiometabolic health:a mendelian randomization studyBackground and Objectives:Growing evidence have demonstrated that thyroid hormones have been involved in the processes of cardiovascular metabolism.However,the causal relationship of thyroid function and cardiometabolic health remains partly unknown.Methods:Genetic variants of free thyroxine(FT4)and thyrotropin(TSH)levels within the reference range were used as instrumental variables.This study was conducted using summary statistic data from genome-wide association studies of large,previously described cohorts.Association between thyroid function and resting heart rate(RHR),total cholesterol(TC),triglycerides(TG),low-density lipoprotein(LDL),high-density lipoprotein(HDL),essential hypertension(EHTN),secondary hypertension(SHTN),hyperlipidemia(HPL),type 2 diabetes mellitus(T2DM),ischemic heart disease(IHD),myocardial infarction(MI),heart failure(HF),pulmonary heart disease(PHD),stroke,and non-rheumatic valve disease(NRVD)were examined.Results:Genetically predicted FT4 levels were associated with SHTN(odds ratio=0.48;95%CI=0.04-0.82,p=0.027),HPL(odds ratio=0.67;95%CI=0.18-0.88,p=0.023),T2DM(odds ratio=0.80;95%CI=0.42-0.86,p=0.005),IHD(odds ratio=0.85;95%CI=0.49-0.98,p=0.039),NRVD(odds ratio=0.75;95%CI=0.27-0.97,p=0.039).Additionally,genetically predicted TSH levels were associated with RHR(beta=0.42;95%CI=1.194-1.954,p=0.001),TC levels(beta:0.051;95%CI:1.035-1.088,p=0.002),LDL levels(beta:0.041;95%CI:1.024-1.079,p=0.018),HF(odds ratio=0.82;95%CI=0.68-0.99,p=0.042),PHD(odds ratio=0.75;95%CI=0.32-0.82,p=0.006),stroke(odds ratio=0.95;95%CI=0.81-0.97,p=0.007).Conclusions:Our study suggests positive associations of thyroid function with cardiometabolic health,underscoring the importance of the pituitary-thyroid-cardiac axis in cardiometabolic health susceptibility.