Risk factors and clinical implications of thyroxine replacement therapy on major adverse cardiovascular events in type 2 diabetes: a retrospective cohort study.

After propensity score matching, 416 patients were in each of the MACE and non-MACE groups among diabetic patients receiving thyroxine replacement therapy.

• Retrospective cohort study using longitudinal claims data from 2008 to 2017 from the Chang Gung Research Database.
• Individuals with diabetes who used thyroxine were included.
• 1:1 group matching by propensity score between MACE and non-MACE groups was performed by sex, age, and interval of using thyroxine.
• The primary outcome was the occurrence of MACE.

Worse renal function (eGFR <45 ml/min/1.73 m²) was associated with a higher risk of experiencing MACE in diabetic patients receiving thyroxine.

• eGFR threshold used was <45 ml/min/1.73 m².
• This finding was identified through comparison between MACE and non-MACE groups after propensity score matching.
• End-stage renal disease (ESRD) was also independently identified as a risk factor for MACE.

Multiple comorbidities were associated with higher risk of MACE in diabetic patients on thyroxine replacement therapy.

• Conditions associated with higher MACE risk included hypertension, history of diabetic microvascular complications, ESRD, coronary heart disease (CHD), heart failure, cerebrovascular accident (CVA), and diabetic foot infection.
• Peripheral artery disease (PAD) was not a significant risk factor for MACE, distinguishing it from the other comorbidities examined.
• These associations were identified after 1:1 propensity score matching of 416 patients per group.

Free T4 had a weak positive correlation with HDL cholesterol.

• Correlation coefficient was 0.131 with a p-value of 0.022.
• The correlation was described as 'weak' by the authors.
• This suggests a modest association between higher free T4 levels and higher HDL levels in this population.

TSH had a weak positive correlation with LDL cholesterol and a weak negative correlation with HDL cholesterol.

• TSH positive correlation with LDL: correlation coefficient 0.124, p-value 0.016.
• TSH negative correlation with HDL: correlation coefficient -0.157, p-value 0.003.
• These correlations suggest that higher TSH levels are associated with less favorable lipid profiles in diabetic patients on thyroxine.

There were no optimal cutoff points identified by ROC curve analysis for TSH, free T4, or LDL in discriminating between patients who experienced MACE and those who did not.

• Receiver operating characteristic (ROC) curve analysis was performed for TSH, free T4, and LDL.
• No best discrimination point was identified for any of these three biomarkers with respect to MACE occurrence.
• This suggests that TSH, free T4, and LDL individually do not serve as reliable predictors of MACE in this population.

Even with normalized TSH levels from thyroxine replacement, LDL and total cholesterol levels remain higher than in people with normal thyroid function.

• This finding is cited from prior literature referenced in the study background.
• It highlights a residual lipid abnormality in treated hypothyroid diabetic patients despite biochemical euthyroidism.
• The authors used this as part of the rationale for investigating MACE risk in this population.