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.

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 (ß = 0.052, P = 0.002) and LDL (ß = 0.041, P = 0.018) levels. In addition, the FT3:FT4 ratio was significantly associated with TC (ß = 0.240, P = 0.033) and LDL (ß = 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.

Evaluation of a risk index for predicting short-term and long-term outcomes in patients with ST-elevation myocardial infarction.

OBJECTIVE: This study aimed to evaluate the usefulness of the admission risk index (RI) to predict short-term and long-term outcomes in a broad population with ST-elevation myocardial infarction (STEMI) using data from the Chinese Acute Myocardial Infarction Registry. BACKGROUND: The RI was developed as a simple tool to predict risk of death in STEMI patients. The performance in predicting short-term and long-term risk of death in Chinese patients receiving percutaneous coronary intervention and conservative treatment for STEMI remains unclear. METHODS: Age, heart rate (HR), and systolic blood pressure (SBP) were used to calculate RI using (HR×[age/10]2 )/SBP. We used the prediction tool to predict mortality over 12 months. RESULTS: The C-index of the admission RI for predicting in-hospital, 1-, 6-, and 12-months mortality were 0.78, 0.78, 0.78, and 0.77, respectively, compared with 0.75 of the Global Registry in Acute Coronary Events score. Based on the receiver operating characteristic curve analysis, the 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 < .0001) while RI >34 had the highest mortality. By categorizing into five 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 and easily calculated by any medical practitioner is useful for predicting in-hospital and long-term mortality in patients with STEMI at the initial consultation with clinicians.