Selenoprotein P deficiency is associated with higher risk of incident heart failure.

INTRODUCTION: Selenium deficiency has been associated with mortality, cardiovascular disease and worsened prognosis in heart failure (HF). In a recent population-based study, high selenium levels were shown to be associated with reduced mortality and reduced incidence of HF, but only in non-smokers. Here, we aimed to examine if selenoprotein P (SELENOP), a main selenium carrier protein, is associated with incident HF. MATERIALS AND METHODS: SELENOP concentrations were measured in plasma of 5060 randomly selected subjects from the population-based prospective cohort "Malmö Preventive Project" (n = 18240) using an ELISA approach. Exclusion of subjects with prevalent HF (n = 230) and subjects with missing data on co-variates included in the regression analysis (n = 27) resulted in complete data for 4803 subjects (29.1% women, mean age 69.6 ± 6.2 years, 19.7% smokers). Cox regression models adjusted for traditional risk factors were used to analyse SELENOP's association with incident HF. Further, subjects within the quintile with the lowest SELENOP concentrations were compared to subjects in the remaining quintiles. RESULTS: Each 1 standard deviation increment in SELENOP levels was associated with lower risk of incident HF (n = 436) during a median follow-up period of 14.7 years (hazard ratio (HR) 0.90; CI95% 0.82-0.99; p = 0.043). Further analyses showed that subjects in the lowest SELENOP quintile were at the highest risk of incident HF when compared to quintiles 2-5 (HR 1.52; CI95% 1.21-1.89; p = 2.5 × 10-4). CONCLUSION: Low selenoprotein P levels are associated with a higher risk of incident HF in a general population. Further studies are warranted.

Iron deficiency predicts impaired exercise capacity in patients with systolic chronic heart failure.

BACKGROUND: Iron is an indispensable element of hemoglobin, myoglobin, and cytochromes, and, beyond erythropoiesis, is involved in oxidative metabolism and cellular energetics. Hence, iron deficiency (ID) is anticipated to limit exercise capacity. We investigated whether ID predicted exercise intolerance in patients with systolic chronic heart failure (CHF). METHODS AND RESULTS: We prospectively studied 443 patients with stable systolic CHF (age 54 ± 10 years, males 90%, ejection fraction 26 ± 7%, New York Heart Association Class I/II/III/IV 49/188/180/26). ID was defined as: serum ferritin <100 µg/L or serum ferritin 100-300 µg/L with serum transferrin saturation <20%. Exercise capacity was expressed as peak oxygen consumption (VO(2)) and ventilatory response to exercise (VE-VCO(2) slope). ID was present in 35 ± 4% (±95% confidence interval) of patients with systolic CHF. Those with ID had reduced peak VO(2) and increased VE-VCO(2) slope as compared to subjects without ID (peak VO(2): 13.3 ± 4.0 versus 15.3 ± 4.5 mL•min•kg, VE-VCO(2) slope: 50.9 ± 15.8 versus 43.1 ± 11.1, respectively, both P < .001, P < .05). In multivariable models, the presence of ID was associated with reduced peak VO(2) (ß = -0.14, P < .01 P < .05) and higher VE-VCO(2) slope (ß = 0.14, P < .01 P < .05), adjusted for demographics and clinical variables. Analogous associations were found between serum ferritin, and both peak VO(2) and VE-VCO(2) slope (P < .05). CONCLUSIONS: ID independently predicts exercise intolerance in patients with systolic CHF, but the strength of these associations is relatively weak. Whether iron supplementation would improve exercise capacity in iron-deficient subjects requires further studies.

Iron deficiency: an ominous sign in patients with systolic chronic heart failure.

AIMS: Beyond erythropoiesis, iron is involved in numerous biological processes crucial for maintenance of homeostasis. Patients with chronic heart failure (CHF) are prone to develop iron deficiency (ID), and iron supplementation improves their functional status and quality of life. We sought to examine the relationship between ID and survival in patients with systolic CHF. METHODS AND RESULTS: In a prospective observational study, we evaluated 546 patients with stable systolic CHF [age: 55 +/- 11 (mean +/- standard deviation) years, males: 88%, left ventricular ejection fraction: 26 +/- 7%, New York Heart Association (NYHA) class (I/II/III/IV): 57/221/226/42]. Iron deficiency was defined as: ferritin <100 microg/L, or 100-300 microg/L with transferrin saturation <20%. The prevalence of ID was 37 +/- 4% [+/-95% confidence intervals (CI)] in the entire CHF population (32 +/- 4 vs. 57 +/- 10%-in subjects without vs. with anaemia defined as haemoglobin level <12 g/dL in women and <13 g/dL in men, P < 0.001). In a multiple logistic model, ID was more prevalent in women, those in the advanced NYHA class, with higher plasma N-terminal pro-type B natriuretic peptide and higher serum high-sensitivity C-reactive protein (all P < 0.05). At the end of follow-up (mean duration: 731 +/- 350 days), there were 153 (28%) deaths and 30 (6%) heart transplantations (HTX). In multivariable models, ID (but not anaemia) was related to an increased risk of death or HTX (adjusted hazard ratio 1.58, 95% CI 1.14-2.17, P < 0.01). CONCLUSION: In patients with systolic CHF, ID is common and constitutes a strong, independent predictor of unfavourable outcome. Iron supplementation may be considered as a therapeutic approach in these patients to improve prognosis.