Prognostic impact of subclinical thyroid dysfunction in heart failure

Background

Therapeutic and prognostic implications of subclinical thyroid dysfunction in patients with heart failure (HF) are unclear. We compared the prognostic impact of euthyroidism, subclinical thyroid dysfunction, and euthyroid sick syndrome (ESS) in systolic HF.

Methods

We included 1032 patients hospitalized for systolic HF (left ventricular ejection fraction [LVEF] ≤ 40%) who participated in a randomized trial assessing the effects of a HF disease management program. Patients with incomplete thyroid function tests or thyrotropic medication were excluded. In the remaining 758 subjects, the risk of all-cause death was estimated based on TSH only, or full thyroid function profile. Changes of thyroid function after six months were assessed in 451 subjects.

Results

Subclinical thyroid dysfunction was present in 103 patients at baseline (14%). No differences were found between groups regarding NYHA class (P = 0.29), and LVEF (P = 0.60). After a median follow-up of three years patients with ESS (n = 13) had a 3-fold age-adjusted increased risk of death compared to euthyroid patients (P = 0.001). However, neither subclinical hyperthyroidism (HR 1.18, 95%CI:0.82–1.70) nor hypothyroidism (HR 1.07, 95%CI:0.58–1.98) were associated with increased age-adjusted mortality risk. Subclinical thyroid dysfunction had normalized spontaneously at follow-up in 77% of patients. However, persistent subclinical thyroid dysfunction was also not associated with worse outcome.

Conclusions

In this large well-characterized HF cohort, subclinical thyroid dysfunction did not predict an increased mortality risk. Thus, in patients with moderate to severe HF, further diagnostic and therapeutic procedures for subclinical thyroid dysfunction appear dispensable. ESS was an infrequent but important indicator of a poor prognosis in HF.

Clinical trial registration

URL: http://www.controlled-trials.com. Unique identifier: ISRCTN23325295.     

Elevated levels of Factor XI are associated with cardiovascular disease in women

Coronary artery disease (CAD) continues to be the most frequent cause of death among women in the United States. Although elevated levels of clotting factors have been associated with CAD, few of these studies have been performed in women. Elevated levels of Factor XI have previously been associated with venous thrombosis, but little is known about its effect on arterial thrombosis. We selected women referred for cardiac catheterization who were found to have either normal coronaries or evidence of severe CAD and compared levels of homocysteine, anticardiolipin IgG/IgM antibodies, fibrinogen, platelet count, Factor VII, Factor VIII and Factor XI. Women with severe CAD had significantly higher levels of Factor XI than those without CAD (128% vs. 82%, p<0.04). Statistical adjustment for age, diabetes, hypertension, total cholesterol (TC), current smoking, or BMI had no effect on the independent association between CAD status and Factor XI. Factor XI was higher in women with total cholesterol levels >6.18 mmol/l (>239 mg/dl) compared with normocholesteremic women and was also higher in the upper tertile of age, but even when adjusted for these, the association remained significant. This initial study suggests that Factor XI may be an important parameter in arterial as well as venous thrombosis.     

Community notification: Neither a panacea nor a calamity

Community notification of the release of sex offenders has provoked opposition from offender treatment providers who fear that it does not enhance community safety and is a short-sighted response to the problem of sex offending. Many of the arguments opposing community notification misunderstand its role, are based on speculation and might jeopardize the justifications for treatment alternatives. Sex offender treatment providers take risks when they denigrate or oppose the wishes of the community.     

Small skin blood vessel occlusions by cryoglobulin aggregates in ulcerative lesions in IgM-IgG cryglobulinemia

The skin biopsy specimens from six patients with primary mixed IgM-IgG cryoglo-bulinemia were examined by immunofluorescence, light and electron microscopy. The biopsy taken from the involved skin of one patient with leg ulcers revealed small blood vessel occlusions by cryoglobulin aggregates. Since a similar finding was not observed in the biopsy material taken from the other five patients who had no ulcerative skin lesions, it seems that the cryoglobulin aggregates play a role in the development of the skin ulcerations in primary mixed IgM-IgG cryoglobulinemia.     

Characterization of NADPH-cytochrome P-450 reductase in a mouse hepatoma cell line

NADPH-cytochrome c reductase in Hepa-1 cells was induced 2-fold by phenobarbital, but was not induced by benz[a]anthracene or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The apparent K_m of the enzyme for NADPH was 0.57 μM; the activity was inhibitable by NADP; and segregated primarily to the microsomal fraction. Cytoplasm of Hepa-1 cells bound antibody to rabbit cytochrome P-450 reductase. 3T3 cells, which possessed one sixth of the cytochrome c reductase activity of Hepa-1 cells, bound correspondingly less cytochrome P-450 reductase antibody. This supports the notion that cytochrome P-450 reductase was responsible for the cytochrome c reductase activity that was measured.