Thyroid Function and the Risk of Atherosclerotic Cardiovascular Morbidity and Mortality

Abstract

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; that is, 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 score >100 AU; (2) ASCV events, defined as fatal and nonfatal myocardial infarction, other coronary heart disease mortality, or stroke; (3) ASCV mortality, defined as death because of coronary heart disease and cerebrovascular or other atherosclerotic diseases. Associations of thyroid-stimulating hormone and free thyroxine 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. Free thyroxine levels were positively associated with high coronary artery calcification score (odds ratio, 2.28; 95% confidence interval, 1.30–4.02) and incident ASCV events (hazard ratio, 1.87; confidence interval, 1.34–2.59). The risk of ASCV mortality increased in a linear manner with higher free thyroxine levels (hazard ratio, 2.41; confidence interval, 1.68–3.47 per 1 ng/dL) and lower thyroid-stimulating hormone levels (hazard ratio, 0.92; confidence interval, 0.84–1.00 per 1 logTSH). Results remained similar or became stronger among euthyroid participants. Conclusions: Free thyroxine levels in middle-aged and elderly subjects were positively associated with atherosclerosis throughout the whole disease spectrum, independent of cardiovascular risk factors.

Thyroid Function and Cardiovascular Disease: The Mediating Role of Coagulation Factors

“…Cardiovascular mortality was defined as death due to CHD, cerebrovascular disease or other cardiovascular diseases, as previously described. (2,23) The ascertainment of cardiovascular mortality in the Rotterdam Study has been extensively described in a previous study. (23) In short, information on cardiovascular mortality is obtained from municipality records, general practitioners and reports of medical specialists.…”

“…(1) To date, population-based studies among middle-aged and older adults have shown that high and high-normal thyroid hormone levels are associated with an increased risk of cardiovascular disease and mortality, independent of traditional cardiovascular risk factors as hyperlipidemia, hypertension, diabetes, and obesity. (2)(3)(4) This points towards other factors that can mediate the increased cardiovascular risk in case of excess thyroid hormones. The identification of these mediating factors is essential to better understand the role of thyroid hormones in cardiovascular disease, as well as to identify potential targets for future preventive strategies.…”

Mendelian Randomization analyses reveal a causal effect of thyroid function on stroke via atrial fibrillation

“…Observational studies have shown that even thyroid hormone levels within the normal range are associated with subclinical atherosclerosis, as assessed by coronary artery calcification score and the overall risk of adverse atherosclerotic cardiovascular events, including fatal and nonfatal myocardial infarction, other CAD mortality and stroke (10). However, several large population-based studies investigated the association between variation in normal range thyroid function and the CAD risk only, and did not find an association (8, 45–47).…”

“…Whereas smoking, hypertension, diabetes, obesity and dyslipidaemia are the major modifiable cardiovascular risk factors(2), observational studies have demonstrated that also overt and subclinical thyroid dysfunction are associated with a higher risk of CVD(3–6). Moreover, even variation in thyroid function within the normal range has been associated with an increased risk of CVD, including atherosclerotic disease and stroke (7–10). This poses the question as to whether common forms of mild thyroid dysfunction (with a prevalence of 5-10 % in the general population) should be treated to prevent these complications.…”

Risk factors of concomitant pathology development in patients with climacteric syndrome with secondary to hypothyroidism

“…Як відомо, ССЗ і хвороби периферійних судин є причиною значно більш високої захворюваності і смертності в пацієнтів із гіпотиреозом, ніж класична тріада: нефропатія, нейропатія, ретинопатія, хоча небезпека цих захворювань також дуже висока. Тобто, наявність гіпотиреозу і асоційованих із ним клініко-метаболічних порушень істотно підвищує ризик серцево-судинних захворювань (ССЗ) [20]. Аналіз чинників ризику розвитку ССЗ у жінок із клімактеричним синдромом на тлі гіпотиреозу свідчить, що всі обстежені пацієнтки мали два і більше чинників ризику розвитку.…”