Assessment of causal direction between thyroid function and cardiometabolic health:a Mendelian randomization study

BACKGROUND 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 The Mendelian randomization(MR)was used to test genetic,potentially causal relationships between instrumental variables and cardiometabolic traits.Genetic variants of free thyroxine(FT4)and thyrotropin(TSH)levels within the reference range were used as instrumental variables.Data for genetic associations with cardiometabolic diseases were acquired from the genome-wide association studies of the FinnGen,CARDIoGRAM and CARDIoGRAMplusC4D,CHARGE,and MEGASTROKE.This study was conducted using summary statistic data from large,previously described cohorts.Association between thyroid function and 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 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).However,genetically predicted thyroid function traits were not associated with EHTN and MI.CONCLUSIONS Our study suggests FT4 and TSH are associated with cardiometabolic diseases,underscoring the importance of the pituitary-thyroid-cardiac axis in cardiometabolic health susceptibility.

Free triiodothyronine level correlates with statin responsiveness in acute myocardial infarction

Background Although thyroid hormone （TH） has important effects on lipid metabolism, the relationship between TH and statin responsiveness has never been investigated. We hypothesize that TH plays an important role in statin responsiveness in patients with acute myocardial infarction （AMI）. Methods Consecutive 1091 hospitalized AMI patients in Fuwai hospital （Beijing, China） were enrolled into this current study. The study population was divided into three groups based on the intensity of statin treatment： low-intensity （n = 221）, moderate-intensity （n = 712） and high-intensity （n = 158）. Lipid levels were measured after statin therapy lasting for 10-14 days. The association between TH, lipid profile levels and achievement of low-density lipoprotein cholesterol （LDL-C） lowering goals was explored in patients with AMI on statin therapy. Results By general linear analysis, a significant linear trend between free triiodothyronine （FT3） and LDL-C level （linear coefficient r = -0.082, P = 0.001） and FT3 and total cholesterol （TC） level （r = -0.105, P = 0.031） was observed in the moderate-intensity statin group. A more apparent linear trend was detected in the high-intensity statin group （for LDL-C： r = -0.113, P = 0.005; for TC： r = -0.172, P = 0.029, respectively）. However, no significant correlation was observed in the low-intensity statin group. Compared with the low-FT3 group （defined as FT3 〈 1.79 pg/mL）, the OR （95% CI） for attaining a LDL-C 〈 3.0mmol/L was found to be 2.217 （1.001–4.839） in the higher FT3 group （〉 2.95 pg/mL）. The OR （95% CI） for attaining the more intensive goal （LDL-C 〈 1.8mmol/L） was 2.836 （1.014–5.182）. Conclusions Our study reveals that variation in FT3 levels is related to the cholesterol-lowering responsiveness of statins in AMI patients. These findings suggest that low FT3 may be a factor responsible for lack of LDL-C goal attainment and patients’ poor responsiveness to statin treatment.

Development and validation of a nomogram predicting oneyear mortality in patients undergoing percutaneous coronary intervention

OBJECTIVE To formulate a nomogram to predict the risk of one-year mortality after percutaneous coronary intervention(PCI)based on a large-scale real-world Asian cohort.METHODS This study cohort included consecutive patients undergoing PCI in the National Center for Cardiovascular Diseases of China.The endpoint was all-cause mortality.Least absolute shrinkage and selection operator Cox regression and backward stepwise regression were used to select potential risk factors.A nomogram based on the predictors was accordingly constructed to predict one-year mortality.The performance of the nomogram was evaluated.Patients were stratified into low-,intermediate-and high-risk groups according to the tertile points in the nomogram and compared by the Kaplan-Meier analysis.RESULTS A total of 9603 individuals were included in this study and randomly divided into the derivation cohort(60%)and the validation cohort(40%).Six variables were selected to formulate the nomogram,including age,renal insufficiency,cardiac dysfunction,previous cerebrovascular disease,previous PCI,and TIMI 0–1 before PCI.The area under the curve of this nomogram regarding one-year mortality risks were 0.792 and 0.754 in the derivation cohort and validation cohort,respectively.Kaplan-Meier curve successfully stratified the patients according to three risk groups.This nomogram calibrated well and exhibited satisfactory clinical utility in the decision curve analysis.CONCLUSIONS This study developed and validated a simple-to-use nomogram predicting one-year mortality risk in Asian patients undergoing PCI and could help clinicians make risk-dependent decisions.

Uric acid is associated with cardiac death in patients with hypertrophic obstructive cardiomyopathy

BACKGROUND The role of uric acid(UA) in survival of patients with hypertrophic obstructive cardiomyopathy(HOCM) has not been fully evaluated. This study aimed to determine whether UA could be an independent risk factor of cardiac death in patients with HOCM.METHODS A total of 317 patients with HOCM, who were receiving conservative treatment in Fuwai Hospital from October2009 to December 2014, all of them completed UA evaluations, were analyzed. Patients were divided into three groups according to the UA levels: Tertile 1(≤ 318 μmol/L, n = 106), Tertile 2(319 to 397 μmol/L, n = 105), and Tertile 3(≥ 398 μmol/L, n = 106).RESULTS During a median follow-up of 45 months, 29 cardiac deaths(9.1%) occurred, including 6 sudden cardiac deaths and23 heart failure-related deaths. Cardiac death in Tertile 3(n = 16, 55.2%) was significantly higher than in Tertile 1(n = 6, 20.7%)and Tertile 2(n = 7, 24.1%). In univariate model, UA level(continuous value) showed predictive value of cardiac death [hazard ratio(HR) = 1.006, 95% CI: 1.003-1.009, P = 0.009]. Univariate Cox survival analysis had shown a significant higher property of cardiac death in patients of Tertile 3 when compared with those of Tertile 1, but cardiac death in patients of Tertile 2 did not show significant prognositic value compared with those of Tertile 1(HR = 3.927, 95% CI: 0.666-23.162, P = 0.131). UA was found to be an independent risk factor(HR = 1.005, 95% CI: 1.001-1.009, P = 0.009) of cardiac death in the multivariate regression analysis after the adjustment for age, body mass index, atrial fibrillation, hemoglobin, creatinine, high-sensitivity C-reactive protein, interventricular septum/left ventricular posterior wall ratio, left ventricular outflow tract and left ventricular ejection fraction.CONCLUSIONS UA concentration was found to be independently associated with cardiac death in HOCM patients receiving conservative treatment. Randomized trials of UA-lowering agents for HOCM patients are warranted.

Assessment of causal association between thyroid function and lipid metabolism:a Mendelian randomization study

Background:Thyroid dysfunction is associated with cardiovascular diseases.However,the role of thyroid function in lipid metabolism remains partly unknown.The present study aimed to investigate the causal association between thyroid function and serum lipid metabolism via a genetic analysis termed Mendelian randomization(MR).Methods:The MR approach uses a genetic variant as the instrumental variable in epidemiological studies to mimic a randomized controlled trial.A two-sample MR was performed to assess the causal association,using summary statistics from the Atrial Fibrillation Genetics Consortium(n=537,409)and the Global Lipids Genetics Consortium(n=188,577).The clinical measures of thyroid function include thyrotropin(TSH),free triiodothyronine(FT3)and free thyroxine(FT4)levels,FT3:FT4 ratio and concentration of thyroid peroxidase antibodies(TPOAb).The serum lipid metabolism traits include total cholesterol(TC)and triglycerides,high-density lipoprotein,and low-density lipoprotein(LDL)levels.The MR estimate and MR inverse variance-weighted method were used to assess the association between thyroid function and serum lipid metabolism.Results:The results demonstrated that increased TSH levels were significantly associated with higher TC(β=0.052,P=0.002)and LDL(β=0.041,P=0.018)levels.In addition,the FT3:FT4 ratio was significantly associated with TC(β=0.240,P=0.033)and LDL(β=0.025,P=0.027)levels.However,no significant differences were observed between genetically predicted FT4 and TPOAb and serum lipids.Conclusion:Taken together,the results of the present study suggest an association between thyroid function and serum lipid metabolism,highlighting the importance of the pituitary-thyroid-cardiac axis in dyslipidemia susceptibility.