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Low serum iron levels and risk of cardiovascular disease in high risk elderly population: Nested case-control study in the PREvención con DIeta MEDiterránea (PREDIMED) trial.
Gutierrez-Bedmar, M, Olmedo, P, Gil, F, Ruiz-Canela, M, Martínez-González, MA, Salas-Salvadó, J, Babio, N, Fito, M, Del Val, JL, Corella, D, et al
Clinical nutrition (Edinburgh, Scotland). 2021;(2):496-504
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Abstract
BACKGROUND & AIMS Epidemiological data on iron status and cardiovascular disease (CVD) are still controversial. The aim of this study was to determine whether low serum iron (SI) levels are associated with an increased odds of first CVD event in a population at high cardiovascular risk. METHODS Case-control study design nested within the "PREvención con DIeta MEDiterránea" (PREDIMED) trial. A total of 207 participants diagnosed with CVD (myocardial infarction, stroke or cardiovascular death) during follow-up period (2003-2010) were matched by sex, age and intervention group to 436 controls by incidence density sampling. Median time between serum sample collection and subsequent CVD event occurrence was 0.94 years. Inductively coupled plasma mass spectrometry analysis was used to determine SI levels. In-person interviews, medical record reviews, and validated questionnaires were used to assess covariates. Multivariable-adjusted odds ratios (ORs) of CVD were calculated with conditional logistic regression. RESULTS Mean SI levels were higher in men than in women (1224.0 μg/L vs. 1093.8 μg/L; p < 0.001). Among women, but not in men, the mean SI concentration was lower in cases than in controls (1008.5 μg/L vs. 1132.9 μg/L; p = 0.030). There was a gradual decrease in the multivariable-adjusted ORs of CVD with increasing SI levels (highest vs. lowest quartile: OR = 0.55, 95% CI: 0.32-0.93; ptrend = 0.020). This inverse relationship was more pronounced among women (highest vs. lowest quartile: OR = 0.15, 95% CI: 0.03-0.69; ptrend = 0.011). CONCLUSIONS The present findings are consistent with previously reported inverse associations between SI and CVD. SI levels as an independent marker of short-term cardiovascular risk may be useful for risk assessment in older populations. TRIAL REGISTRATION www.controlled-trials.com; International Standard Randomized Controlled Trial Number (ISRCTN): 35,739,639. Registered 5 October 2005. Retrospectively registered.
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Association between serum ferritin and osteocalcin as a potential mechanism explaining the iron-induced insulin resistance.
Juanola-Falgarona, M, Cándido-Fernández, J, Salas-Salvadó, J, Martínez-González, MA, Estruch, R, Fiol, M, Arija-Val, V, , , ,
PloS one. 2013;(10):e76433
Abstract
BACKGROUND Increased iron stores are associated with increased risk of type 2 diabetes, however, the mechanisms underlying these associations are poorly understood. Because a reduction of circulating osteocalcin levels after iron overload have been demonstrated in cell cultures, and osteocalcin is related to glucose and insulin metabolism, the iron-induced osteocalcin reductions could contribute to explain the role of iron metabolism in the development of type 2 diabetes mellitus. OBJECTIVE To analyzed the associations between serum total and uncarboxylated osteocalcin and adiponectin concentrations with serum ferritin and soluble transferrin receptor (sTfR) in elderly subjects. DESIGN We evaluated a total of 423 subjects from the PREDIMED cohort in a population-based cross-sectional analysis. Extensive clinical, nutritional and laboratory measurements, including total and uncarboxylated osteocalcin, adiponectin, ferritin and sTfR were recorded. RESULTS Serum ferritin was positively correlated with increased glucose and insulin circulating levels but also with HOMA-IR, and was inversely associated with total osteocalcin and adiponectin. A regression analysis revealed that serum ferritin and transferrin receptor levels were significantly associated with a decrease in total and uncarboxylated osteocalcin. Serum sTfR levels were associated with lower uncarboxylated osteocalcin levels in the whole-study subjects and remained significant only in the IFG (impaired fasting glucose) individuals. CONCLUSIONS We described, for the first time, an inverse association between serum ferritin and sTfR with osteocalcin and extend previous results on adiponectin, thus supporting that factors related to iron metabolism could contribute to the insulin resistance and the development of type 2 diabetes mellitus. TRIAL REGISTRATION Controlled-Trials.com ISRCTN35739639 .