Association of Thyroid Function With Life Expectancy With and Without Cardiovascular Disease

Abstract

IMPORTANCEVariations in thyroid function within reference ranges are associated with an increased risk of cardiovascular disease (CVD) and mortality. However, the impact of thyroid function on life expectancy (LE) and the number of years lived with and without CVD remains unknown.OBJECTIVE To investigate the association of thyroid function with total LE and LE with and without CVD among euthyroid individuals. DESIGN, SETTING, AND PARTICIPANTSThe Rotterdam Study, a population-based, prospective cohort study. We included participants without known thyroid disease and with thyrotropin and free thyroxine (FT 4 ) levels within the reference ranges. MAIN OUTCOMES AND MEASURESMultistate life tables were used to calculate total LE and LE with and without CVD among thyrotropin and FT 4 tertiles. Life expectancy estimates in men and women aged 50 years and older were obtained using prevalence, incidence rates, and hazard ratios for 3 transitions (healthy to CVD, healthy to death, and CVD to death), adjusting for sociodemographic and cardiovascular risk factors. RESULTSThe mean (SD) age of the 7785 participants was 64.7 (9.8) years, and 52.5% were women. Over a median follow-up of 8.1 (interquartile range, 2.7-9.9) years, we observed 789 incident CVD events and 1357 deaths. Compared with those in the lowest tertile, men and women in the highest thyrotropin tertile lived 2.0 (95% CI, 1.0 to 2.8) and 1.4 (95% CI, 0.2 to 2.4) years longer, respectively, of which, 1.5 (95% CI, 0.2 to 2.6) and 0.9 (95% CI, −0.2 to 2.0) years longer without CVD. Compared with those in the lowest tertile, the difference in life expectancy for men and women in the highest FT 4 tertile was −3.2 (95% CI, −5.0 to −1.4) and −3.5 (95% CI, −5.6 to −1.5) years, respectively, of which, −3.1 (95% CI, −4.9 to −1.4) and −2.5 (95% CI, −4.4 to −0.7) years without CVD.CONCLUSIONS AND RELEVANCE At the age of 50 years, participants with low-normal thyroid function live up to 3.5 years longer overall and up to 3.1 years longer without CVD than participants with high-normal thyroid function. These findings provide supporting evidence for a reevaluation of the current reference ranges of thyroid function and can help inform preventive and clinical care.

Adipose TSHB in Humans and Serum TSH in Hypothyroid Rats Inform About Cellular Senescence

“…These data agree with the positive association between serum TSH levels and longevity reported in rodents [1][2][3] and euthyroid humans [3][4][5][6][7][8][9]. In line with these observations, rhTSH administration in human visceral adipocytes during 7 days, but not In parallel with these findings, a recent publication demonstrated that TSH administration (48h) in fully differentiated human adipocytes resulted in a significant improvement of mitochondrial biogenesis and function, increasing basal respiration, ATP production and spare respiratory capacity in parallel to increased SIRT1 and mitochondrial biogenesisrelated gene markers [22].…”

“…Euthyroid 50 year-old participants with increased levels of TSH had a longer life expectancy than participants with decreased serum TSH levels [4]. Increased TSH levels were also associated with lower mortality in participants between ages 85 and 90 [5] and in their offspring [6], and even in centenarians [7,8].…”

“…In humans, the relationship between hypothyroidism and increased life expectancy has also been observed [4][5][6][7][8][9]. Euthyroid 50 year-old participants with increased levels of TSH had a longer life expectancy than participants with decreased serum TSH levels [4].…”

“…A causal relationship between thyroid function and longevity was further demonstrated by experimental induction of hypothyroidism in rats, which resulted in extended life span. Conversely, inducing hyperthyroidism resulted in significantly shorter life span [4][5][6].…”

Association between Thyroid-Stimulating Hormone Levels and Non-Alcoholic Fatty Liver Disease Is Not Independent from Metabolic Syndrome Criteria

“…Indeed, it may often be recognized as one of the metabolic syndrome features. Also, TSH levels have been associated with increased body fat and BMI, as well as increased cardiovascular risk [35], although the studies are still controversial [36,37]. Within the reference range, it was already acknowledged that TSH levels seem to increase the BMI proportionally [38].…”