Low Triiodothyronine Syndrome and Long-Term Cardiovascular Outcome in Incident Peritoneal Dialysis Patients

Abstract

Background and objectives A direct association between low triiodothyronine (T3) syndrome and cardiovascular (CV) mortality has been reported in hemodialysis patients. However, the implications of this syndrome in peritoneal dialysis (PD) patients have not been properly investigated. This study examined the association between low T3 syndrome and CV mortality including sudden death in a large cohort of incident PD patients.Design, setting, participants, & measurements This prospective observational study included 447 euthyroid patients who started PD between January 2000 and December 2009. Measurement of thyroid hormones was performed at baseline. All-cause and cause-specific deaths were registered during the median 46 months of follow-up. The survival rate was compared among three groups based on tertile of T3 levels.Results In Kaplan-Meyer analysis, patients with the lowest tertile were significantly associated with higher risk of all-cause and CV mortality including sudden death (P,0.001 for trend). In Cox analyses, T3 level was a significant predictor of all-cause mortality (per 10-unit increase, adjusted hazard ratio [HR], 0.86; 95% confidence interval [95% CI], 0.78 to 0.94; P=0.002), CV death (per 10-unit increase, adjusted HR, 0.84; 95% CI, 0.75 to 0.98; P=0.01), and sudden death (per 10-unit increase, adjusted HR, 0.69; 95% CI, 0.56 to 0.86; P=0.001) after adjusting for well known risk factors including inflammation and malnutrition. The higher T3 level was also independently associated with lower risk for sudden death (per 10-unit increase, adjusted HR, 0.71; 95% CI, 0.56 to 0.90; P=0.01) even when accounting for competing risks of death from other causes.Conclusions T3 level at the initiation of PD was a strong independent predictor of long-term CV mortality, particularly sudden death, even after adjusting well known risk factors. Low T3 syndrome might represent a factor directly implicated in cardiac complications in PD patients.

Low-T3 Syndrome in Peritoneal Dialysis

“…This study provides important contributions to the existing body of literature by (1) corroborating that thyroid hormone deficiency may be a novel cardiovascular risk factor in patients with CKD and (2) adding incremental knowledge to our understanding of the mechanistic pathways underlying the low T3-mortality association in CKD (14). This is the first study showing an association between low T3 and cardiovascular mortality in patients on PD (14), and it is the first time that the low-T3 syndrome has been shown to predict sudden death in patients with CKD, the leading cause of cardiovascular mortality in this population (1).…”

“…In contrast to previously published reports, TSH and free T4 levels were not associated with all-cause or cardiovascular death (15,16). However, this study excluded patients whose thyroid functional tests showed overt hypothyroidism (i.e., high TSH and low free T4) or hyperthyroidism (i.e., low TSH) as well as those with known hypo-and hyperthyroidism, which may have restricted the range of observed TSH and free T4 values in this study population (14).…”

“…In this issue of CJASN, Chang et al (14) examined the association between circulating T3 levels and mortality among a prospective cohort of 447 patients who initiated PD over the period of 2000-2007. Thyroid functional tests were measured at baseline as a proxy of long-term exposure-mortality associations.…”

“…The outcomes of interest were all-cause death as well as several cause-specific mortality end points, including sudden death and combined cardiovascular death. After a median follow-up of 46 months, Chang et al (14) found that a 10-ng/dl higher T3 level was associated with a 14% and a 16% lower risk of all-cause death and combined cardiovascular death, respectively, independent of comorbidities and markers of nutrition and inflammation. Chang et al (14) also observed that a 10-ng/dl higher T3 level was associated with a 31% lower risk of sudden death, and this association was robust in analyses that accounted for competing risks.…”

“…After a median follow-up of 46 months, Chang et al (14) found that a 10-ng/dl higher T3 level was associated with a 14% and a 16% lower risk of all-cause death and combined cardiovascular death, respectively, independent of comorbidities and markers of nutrition and inflammation. Chang et al (14) also observed that a 10-ng/dl higher T3 level was associated with a 31% lower risk of sudden death, and this association was robust in analyses that accounted for competing risks. In contrast to previously published reports, TSH and free T4 levels were not associated with all-cause or cardiovascular death (15,16).…”