Thyroid Function and the Risk of Atherosclerotic Cardiovascular Morbidity and Mortality: The Rotterdam Study
Rationale: Thyroid hormones have been linked with various proatherogenic and antiatherogenic processes. However, the relationship of thyroid function with manifestations of atherosclerosis remains unclear.
Objective: To investigate the association of thyroid function with atherosclerosis throughout its spectrum; i.e. subclinical atherosclerosis, incident atherosclerotic cardiovascular (ASCV) events and ASCV mortality.
Methods and Results: This population-based study was embedded within the Rotterdam Study. The risk of atherosclerosis was evaluated by measuring: 1. Presence of subclinical atherosclerosis, assessed by coronary artery calcification (CAC) score >100 AU; 2. ASCV events, defined as fatal and nonfatal myocardial infarction, other coronary heart disease (CHD) mortality or stroke; 3. ASCV mortality, defined as death due to CHD, cerebrovascular or other atherosclerotic diseases. Associations of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) with the outcomes were assessed through logistic regression and Cox proportional-hazard models, adjusted for potential confounders including cardiovascular risk factors. A total of 9420 community-dwelling participants (mean age±SD, 64.8±9.7 years) were included. During a median follow-up of 8.8 years (interquartile range:4.5-11.8 years), 934 incident ASCV events and 612 ASCV deaths occurred. FT4 levels were positively associated with high CAC score (odds ratio [OR]; 95% confidence interval [CI]: 2.28; 1.30-4.02) and incident ASCV events (hazard ratio [HR]; CI: 1.87; 1.34-2.59). The risk of ASCV mortality increased in a linear manner with higher FT4 levels (HR; CI: 2.41; 1.68-3.47 per 1 ng/dl) and lower TSH levels (HR; CI: 0.92; 0.84-1.00 per 1 logTSH). Results remained similar or became stronger among euthyroid participants.
Conclusions: FT4 levels in middle-aged and elderly subjects were positively associated with atherosclerosis throughout the whole disease spectrum, independently of cardiovascular risk factors.
- Received June 27, 2017.
- Revision received September 13, 2017.
- Accepted September 28, 2017.