Nonthyroidal illness: a risk factor for coronary calcification and arterial stiffness in patients undergoing peritoneal dialysis?

Abstract

Objectives. Low triiodothyronine levels, as part of the nonthyroidal illness syndrome, are common in dialysis patients and have repeatedly been shown to be associated with increased (cardiovascular) mortality rates. We hypothesized that increased vascular calcification may mediate this relationship.Methods. A total of 84 patients from the Stockholm region receiving maintenance peritoneal dialysis were included in the study. Serum concentrations of free triiodothyronine (fT3), thyroxine and thyroidstimulating hormone were measured. Coronary artery calcium (CAC) scores were assessed by cardiac computed tomography scans. Surrogates of arterial stiffness included aortic diastolic and systolic blood pressures, pulse pressure, augmentation pressure and Buckberg's subendocardial viability ratio measured by pulse waveform analyses. Patients were subsequently followed, and events of death and censoring were recorded. Thyroid hormone concentrations were associated with CAC scores, measures of arterial stiffness and allcause mortality. The associations between CAC scores and arterial stiffness surrogates and mortality were also determined to evaluate a possible causal pathway.Results. Both CAC scores and arterial stiffness surrogates were substantially higher in individuals with low fT3 levels. These associations persisted in multivariate logistic and linear regression analyses. During a median (interquartile range) follow-up of 32 (22-42) months, 24 patients died. Both fT3 levels below the median value [HR crude 4.1, 95% confidence interval (CI) 1.4-12.6] and CAC scores above the median value (HR crude 5.8, 95% CI 1.7-20.1) were strongly associated with mortality.Conclusions. In patients undergoing peritoneal dialysis, fT3 levels were strongly associated with arterial stiffness, coronary artery calcification and mortality. We speculate that the association between nonthyroidal illness and mortality may be partly mediated by acceleration of vascular calcification.

Euthyroid Sick Syndrome

“…This is especially true in patients with renal disease, especially end-stage renal disease either on hemodialysis or peritoneal dialysis (32, 53) and cardiorenal syndrome (73). Increased mortality associated with low T3 levels is also correlated with increased cardiac risk factors, such as coronary calcification scores and arterial stiffness (72), lower left ventricular ejection fracture and higher mass index (63). Low free T3 and high rT3 levels have also been associated with increased risk for mortality in patients in the intensive care unit (ICU) (89,105), hospitalized cardiac patients (82), patients with congestive heart failure (CHF) (40,92) and patients with liver cirrhosis (34).…”

Thyroid Functional Disease and Mortality in a National Peritoneal Dialysis Cohort

“…However, when we examined finer gradations of TSH, we observed a potent association between TSH levels in the overt-hyperthyroid range and mortality, whereas the association between TSH levels in the subclinical-hyperthyroid range were attenuated to the null, which may have been due to lack of biological effect or limited power of the subclinical-hyperthyroid range category. Although a growing body of evidence suggests that thyroid hormone deficiency is linked with higher mortality in dialysis patients due to alterations in cardiovascular pathways, little is known about the mechanisms underlying thyroid hormone excess and death in kidney disease (33)(34)(35)(36)(37). In the general population, hyperthyroidism even in the subclinical range has been associated with conditions that are common and fatal in dialysis patients, including atrial fibrillation, coronary ischemia, CHF, and fracture risk (13,17,18,38).…”

Thyroid Hormone and Cardioprotection

“…Indeed, this was a primary incentive for including D-T4 in the Coronary Drug Project. Low TH levels have also been linked to increased vascular calcifications (113,153), even within the normal reference range (281). More long-term studies examining the potential of therapeutic, low doses of THs in patients with atherosclerosis are needed.…”