The kidney, subclinical thyroid disease and cardiovascular outcomes in older patients

Abstract

Objective Thyroid hormones have been implicated to play a role in cardiovascular disease, along with studies linking thyroid hormone to kidney function. The aim of this study is to investigate whether kidney function modifies the association of subclinical thyroid dysfunction and the risk of cardiovascular outcomes. Methods In total, 5804 patients were included in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). For the current analysis, 426 were excluded because of overt thyroid disease at baseline or 6 months, 266 because of inconsistent thyroid function at baseline and 6 months, 294 because of medication use that could influence thyroid function, and 16 because of missing kidney or thyroid values. Participants with normal fT4 were classified, based on TSH both at inclusion and 6 months, into three groups: subclinical hypothyroidism (TSH >4.5 mIU/L); euthyroidism (TSH = 0.45–4.5 mIU/L); and subclinical hyperthyroidism (TSH <0.45 mIU/L). Strata of kidney function were made based on estimated glomerular filtration rate into three clinically relevant groups: <45, 45–60, and >60 mL/min/1.73 m2. The primary endpoint consists of death from coronary heart disease, non-fatal myocardial infarction and (non)fatal stroke. Results Mean age was 75.3 years, and 49.0% patients were male. Mean follow-up was 3.2 years. Of all participants, 109 subjects (2.2%) had subclinical hypothyroidism, 4573 (94.0%) had euthyroidism, and 182 (3.7%) subclinical hyperthyroidism. For patients with subclinical hypothyroidism, euthyroidism, and subclinical hyperthyroidism, primary outcome occurred in 9 (8.3%), 712 (15.6%), and 23 (12.6%) patients, respectively. No statistically significant relationship was found between subclinical thyroid dysfunction and primary endpoint with adjusted hazard ratios of 0.51 (0.24–1.07) comparing subclinical hyperthyroidism and 0.90 (0.58–1.39) comparing subclinical hypothyroidism with euthyroidism. Neither was this relationship present in any of the strata of kidney function, nor did kidney function interact with subclinical thyroid dysfunction in the association with primary endpoint (P interaction = 0.602 for subclinical hyperthyroidism and 0.388 for subclinical hypothyroidism). Conclusions In this secondary analysis from PROSPER, we found no evidence that the potential association between thyroid hormones and cardiovascular disease is modified by kidney function in older patients with subclinical thyroid dysfunction.

Cardiovascular outcomes in subclinical thyroid disease: an update

“…Other recent studies have explored the association between SCH and cardiovascular event risk in the presence of other comorbidities, including rheumatoid arthritis [23], diabetes [24], chronic kidney disease [25], atrial fibrillation [26], and heart failure [27][28][29]. Overall, the results of these studies are mixed, with SCH portending increased risk of cardiovascular events in patients with rheumatoid arthritis and heart failure but not in the other patient populations.…”

Renal function changes in patients with subclinical hyperthyroidism: a novel postulated mechanism

“…This ultimately results in renal vasodysfunction, defined as impaired renal vasodilation and abnormally increased renal vascular resistance in response to increased salt retention which is involved in the initiation of salt-induced hypertension [ 10 ]. Regarding the effect of subclinical hyperthyroidism (SCH) on kidney function, data are still limited and controversial [ 7 , 11 , 12 ].…”