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Background and Aims: Vitamin D counteracts the reduction in the peripheral conversion of tiroxine (T4) into triiodothyronine (T3), which is the mechanism of low T3 syndrome (LT3) in acute myocardial infarction (AMI). The aim of this study was to assess the relationship between LT3 and hypovitaminosis D in AMI patients. Methods and Results: One hundred and twenty-four AMI patients were enrolled. Blood samples were taken at admission, and at 3, 12, 24, 48, and 72 h after admission. LT3 was defined as a value of fT3 ≤ 2.2 pg/mL, occurring within 3 days of hospital admission. Levels were defined as follows: sufficiency as a value of ±30 ng/mL, vitamin D insufficiency as 25-hydroxyvitamin D (25(OH)D) between 21 and 29 ng/mL, deficiency in 25(OH)D as below 20 ng/mL, and severe deficiency as values under 10 ng/mL. The percentage of subjects with severe 25(OH)D deficiency was significantly higher in the LT3 group (33% vs. 13%, p &lt, 0.01). When LT3S was evaluated as a dependent variable, severe 25(OH)D deficiency (OR 2.6: 95%CI 1–6.7, p &lt, 0.05) remained as an independent determinant after logistic multivariate adjustment together with age (&gt, 69 yrs, 50th percentile, OR 3.4, 95% CI 1.3–8.3, p &lt, 0.01), but not female gender (OR 1.7, 95% CI 0.7–4.2, p = ns). Conclusions: This pilot study shows a relationship between hypovitaminosis D and LT3 in AMI patients. This association opens potential therapeutic challenges concerning the restoration of euthyroidism through vitamin D administration, together with the normalization of hypovitaminosis.

The role of thyroid hormones (THs) in the cardiovascular (CV) system, through several direct and indirect effects is recognized. Even very small modification in TH levels (as those observed in subclinical hypothyroidism or hyperthyroidism, and low triiodothyronine syndrome) may adversely affect the CV system, whereas thyroid hormones benefit the CV system and improve the prognosis. There is also evidence of vitamin D effects on cardiometabolic disease (e.g., through modulation of endothelial and smooth muscle cell activity, renin-angiotensin-aldosterone system, nitric oxide, oxidative stress, and inflammatory response), as well as an association between vitamin D [25(OH)D] deficiency and autoimmune thyroid diseases or cancer, and a relationship between vitamin D concentration and titers of antibodies and thyroid autoimmunity replacement. Interestingly, experimental data indicate a direct effect of vitamin D on Type 2 deiodinase expression causing subsequential peripheral conversion of T4 into T3. However, the functional links among THs, vitamin D and the cardiovascular system, and clinical effects of coexisting abnormalities in this new troublesome triad, have not yet been reviewed. The main aim of this review is to discuss pathophysiology of this relationship, proposing new mechanistic insights involving vitamin D in the modulation of cardiometabolic disease and thyroid profile.

Background: Prediabetes (preT2D) is considered a subtle adverse cardiovascular (CV) risk factor after acute myocardial infarction. Glycated hemoglobin (HbA1c) ranges to identify preT2D are different between ADA and WHO guidelines (5.7–6.4 vs. 6.0–6.4%, respectively). Aim: To evaluate the prognostic value of HbA1c different preT2D-ranges and their correlation with demographic, instrumental, and laboratory parameters in STEMI. Methods: A total of 1681 patients (mean age 67 ± 13 years, 1217 males) were enrolled. Admission HbA1c was used to identify patients with no-T2D (&lt, 5.7%), HbA1c 5.70–5.99%, and WHO-preT2D with HbA1c 6–6.49%, and T2D (HbA1c ≥ 6.5). Results: HbA1c 5.7–5.99, WHO-preT2D, and T2D progressively correlated with an increasing number of CV risk factors. However, only T2D, but not preT2D, was significantly associated with adverse prognosis (in-hospital and one-year death). Conclusions: PreT2D is correlated with CV risk factors, but not with adverse prognosis as compared to no-T2D. Nonetheless, routine HbA1c testing in the STEMI population and HbA1c-5.7–5.99 patient inclusion in the preT2D category may help to identify those who may benefit from intervention and lifestyle strategies to early prevent preT2D progression.

Background: Exercise may affect lipid profile which in turn is related to inflammation, although changes of ceramides, diacylglycerols-DAG and sphingomyelin-SM and their relationship with inflammatory parameters following a half-marathon have never been examined. Methods: Ceramides, DAG and SM, and markers of inflammation (soluble fractalkine-CX3CL1, vascular endothelial growth factor-VEGF, interleukin6-IL-6 and tumor necrosis factorα-TNFα) were evaluated in trained half-marathoners before, post-race (withdrawal within 20 min after the race end) and 24 h after. Results: IL-6 and CX3CL1 increased immediately after the race, returning to baseline after 24 h. Total ceramides and total DAG significantly decreased post-race. Several ceramide classes decreased after exercise, while only one of the DAG (36:3) changed significantly. Total SM and specific species did not significantly change. Conclusion: Some inflammatory parameters (IL-6 and CX3CL1) transiently increased after the race, and, being reversible, these changes might represent a physiological response to acute exercise rather than a damage-related response. The decrease of specific lipid classes, i.e., DAGs and ceramides, and the lack of their relationship with inflammatory parameters, suggest their involvement in beneficial training effects, opening promising research perspectives to identify additional mechanisms of aerobic exercise adaptation.

Background Glycated haemoglobin (HbA1c) test, introduced for diagnosing prediabetes and diabetes by the American Diabetes Association for some years, is currently under extensive discussion for contradictory data on the concordance between this test and the oral glucose tolerance test (OGTT). Hypothesis To assess concordance between HbA1c and OGTT to diagnose prediabetes and diabetes in subjects with overweight or obesity, focusing on possible gender-related differences. Methods A total of 949 outpatients with overweight or obesity at risk for diabetes (mean age 50 ± 15 years; 660 F) were enrolled and underwent HbA1c test and OGTT. Results In both genders, HbA1c test identified more patients with prediabetes than OGTT (42% vs 22% in males, 40% vs 18% in females, respectively): a slight concordance between HbA1c and OGTT (60% of total tests in both genders). In subjects diagnosed by OGTT, post-OGTT insulin levels and HOMA INDEX were significantly higher than those found in HbA1c(+) cases. Instead, those diagnosed with HbA1c were significantly older and showed higher uric acid than those with both tests (-). Conclusions HbA1c test and OGTT did not reach full concordance for the diagnosis of diabetes and prediabetes in both genders. The two tests likely reflect different physiopathological aspects of dysglycaemia, suggesting that the 'diagnostic thresholds' could be reconsidered in light of the discordance observed.

BACKGROUND Modulation of oxidative stress/inflammation during exercise may have both positive and negative health effects, depending by a number of factors (e.g. training status, and exercise type, intensity and duration) and the oxidative stress or inflammation-related biomarkers considered, which may reflect different levels of the oxidative stress/inflammatory multi entities. The aim of this study was to evaluate oxidative stress and inflammatory multi-biomarker panel in response to a half-marathon during early and delayed recovery. METHODS Blood samples (baseline, postrace within 20 min after the race end, and 24 h and 48 h after the run) from runners (N.=31, 20 males, mean age 47±6 years) were assessed for reactive oxygen species (ROM assay) and total antioxidant capacity (OXY test), leukocyte telomere length (LTL), procoagulant activity of circulating microparticles (MP-PCA), inflammatory parameters obtained by hemocrome, and irisin. RESULTS A significant decrease for OXY (from 375±71 to 280±66, 239±54, 239±45 µmolHClO/mL) after the half-marathon and during recovery was observed. A reduction for ROMs was also evidenced respect to baseline (from 328±46 to 301±39, 290±56, 320±55 AU). Instead, MP-PCA increased after the race (from 6.2±6 to 10.5±6, 7±4.3 and 5.8±2.1 nmol/L), whereas the other biomarkers did not significantly change. CONCLUSIONS The oxidant counterpart did not increase in response to the half-marathon, likely counteracted by antioxidants, which appeared greatly worn out. MP-PCA and WBC increase, always within the normality range, may represent an adaptation to regular chronic endurance training. In any case, antioxidant supply could be considered and tailored for each athlete in this exercise setting.

Coronavirus disease 2019 (COVID-19) has quickly become a worldwide health crisis.Although respiratory disease remains the main cause of morbidity and mortality in COVID patients,myocardial damage is a common finding. Many possible biological pathways may explain therelationship between COVID-19 and acute myocardial infarction (AMI). Increased immune andinflammatory responses, and procoagulant profile have characterized COVID patients. All theseresponses may induce endothelial dysfunction, myocardial injury, plaque instability, and AMI.Disease severity and mortality are increased by cardiovascular comorbidities. Moreover, COVID-19has been associated with air pollution, which may also represent an AMI risk factor. Nonetheless,a significant reduction in patient admissions following containment initiatives has been observed,including for AMI. The reasons for this phenomenon are largely unknown, although a real decreasein the incidence of cardiac events seems highly improbable. Instead, patients likely may presentdelayed time from symptoms onset and subsequent referral to emergency departments because offear of possible in-hospital infection, and as such, may present more complications. Here, we aim todiscuss available evidence about all these factors in the complex relationship between COVID-19and AMI, with particular focus on psychological distress and the need to increase awareness ofischemic symptoms.

All the latest international guidelines recommend that cardiac troponin (cTn) I and T should be considered the preferred biomarkers for diagnosis of acute myocardial infarction. However, only in the last 5 years, a progressive improvement in analytical performance of immunometric assays has allowed the measurement of circulating levels of cTnI and cTnT in the large part of apparently healthy adult subjects. The routine use of these high-sensitivity methods for cardiac troponin (hs-cTn) assay has in a short time demonstrated that cardiac troponin concentrations frequently increase after strenuous prolonged exercise in healthy athletes. This acute response of hs-cTn assay following exercise was at first considered to be physiological and without long-term adverse consequences. More recent studies have suggested that exercise-induced increases in hs-cTn values may not be always a physiological response to exercise, but, conversely, it should sometimes be considered as an early cardiovascular risk marker. The aim of this review is to provide an overview of acute and chronic effects of strenuous physical exercise on hs-cTn circulating levels and also to discuss the potential pathophysiological and clinical implications of biomarker responses.

IntroductionEnvironmental pollution has been progressively becoming one of the main risk factors to human diseases. In particular, populations living in high-contaminated sites are particularly exposed to environmental toxicants, with consequent increased risks to human health. In Italy, there are currently ongoing three epidemiological etiological studies aimed at evaluating the association between exposure to inorganic and organic chemicals and presence of biological markers of early effects in population living in three National Priority Contaminated Sites (NPCSs). Specifically, the correlations concern preclinical indicators of liver disease in Priolo NPCS, thyroid diseases in Milazzo-Valle del Mela NPCS and cardiovascular risk and kidney damage in Crotone NPCS.Methods and analysisOverall, approximately 1300 subjects of both sexes will be enrolled in the three NPCSs according to specific inclusion criteria. For each subject, serum and urine specimens are collected, on which the determination of biological markers of exposure and early effects for the selected outcomes are performed. Individual information on environmental and occupational exposure, medical history, diet and life habits is obtained through questionnaires provided by web platform. In Milazzo-Valle del Mela and Crotone NPCSs, not invasive instrumental and imaging examinations are performed in order to evaluate further risk factors of thyroid carcinoma and cardiovascular disease, respectively.Ethics and disseminationThe protocol studies have been approved by the Ethics Committees responsible for the three involved NPCSs: the Ethics Committee ‘Catania 2’ for the NPCS of Priolo (21 July 2017, n. 500/2017/CECT2), the Ethics Committee of the University Hospitals of Messina for the NPCS of Milazzo-Valle del Mela (19 February 2018, n.2/2018); the Ethics Committee of the Region of Calabria for the NPCS of Crotone (20 July 2017, n. 174). Results will be disseminated among policy-makers, citizens, stakeholders and scientific community through the organisation of conferences and events, and the publication on international peer/reviewed journals.

Increased or reduced action of thyroid hormones (THs), both hyper- and hypothyroidism, may have relevant cardiovascular effects, which include regulation of cardiac contractility and heart rate, diastolic function, and systemic vascular resistance, thus affecting the onset and development of heart failure (HF). Many of these actions are determined by thyroid-induced oxidative stress modulation, for example, through the direct production of hydrogen peroxide (H2O2) during the synthesis of THs. Oxidative stress alteration, as both increased oxidative stress and reduced availability of antioxidants, exacerbated oxidation of low density lipoproteins, modulated nitric oxide bioavailability, and increased inflammation. These events have been clearly involved in any phase of HF development and extent. The present review aims to discuss oxidative stress status under altered thyroid states in HF pathology.

Aim: to evaluate the relationship between uric acid (UA), hepatic and cardiac iron overload (T2*-MRI), ferritin, endocrinological diseases and cardiac complications in a large thalassemia major (TM) cohort. Methods: A total of 369 TM patients (187 men; 33 ± 6 years) were retrospectively studied, from the myocardial iron overload in thalassemia (MIOT) electronic databank. Results: Multiple regression model identified male sex (p 3 mg/g/dw), heart failure, endocrinopathies, ferritin (>2000 ng/l), alanine transaminase (>40 UI/l) and/or aspartate transaminase (>35 UI/l) and/or glutamyl transferase (>64 UI/l). Discussion: UA appears directly associated to T2* and inversely with derivatives of reactive oxygen species, and as such reduced according to increased oxidative stress and cardiac iron overload in TM patients.

Background Sarcopenia is the progressive loss of muscle mass and strength that occurs with advancing age and plays a pivotal role in the causal pathway leading to frailty, disability and, eventually, to death among older persons. As oxidative damage of muscle proteins has been shown to be a relevant contributory factor, in this study we hypothesized that uric acid (UA), a powerful endogenous antioxidant, might exert a protective effect on muscle function in the oldest old and we tested our hypothesis in a group of nonagenarians who participated in the Mugello Study. Methods 239 subjects, 73 men and 166 women, mean age 92.8 years ± SD 3.1, underwent the assessment of UA serum level and isometric handgrip strength, a widely used clinical measure of sarcopenia. Results Mean UA serum level was 5.69 mg/dL ± SD 1.70 and mean handgrip strength was 15.0 kg ± SD 6.9. After adjusting for relevant confounders, higher UA serum levels remained independent positive predictors of isometric handgrip strength (β 1.24 ± SE(β) 0.43, p = 0.005). Conclusion Our results show that higher UA serum levels are associated with better muscle function in the oldest old and, accordingly, might slow down the progression of sarcopenia.

Evaluation of calcium status is important in the osteoporotic risk assessment. Although guidelines indicate total calcium (tCa) as first-line measurement, directly measured ionized calcium (m-iCa), considered as the gold standard, is more and more often required. Aim of this study is to evaluate the agreement between m-iCa, tCa and iCa calculated from a formula based on total calcium and albumin (c-iCa) in osteopenic/osteoporotic postmenopausal outpatients.A total of 140 postmenopausal outpatients, 41 osteopenic (OPN) and 99 osteoporotic (OP) were enrolled. Levels of tCa, m-iCa, c-iCa, total protein and albumin, vitamin D (25-OHD), parathyroid hormone 1-84 (PTH), bone alkaline phosphatase, osteocalcin and serum collagen type 1 cross-linked C-telopeptide (CTX) were also measured.There were no statistically significant differences between OPN and OP groups regarding values of tCa, m-iCa, and c-iCa, 25-OHD and PTH. However, OP women had lower levels of CTX (p 0.05). A significant direct correlation between m-iCa and tCa (r = 0.60, p 0.001) and c-iCa (r = 0.61, p 0.001) was found. Women with isolated hyper-m-iCa had similar DEXA parameter levels respect to the other patients. However, one patient with confirmed primary hyperparathyroidism presented hyper-m-iCa versus normal tCa and c-iCa values.The use of tCa could be sufficient to characterize the calcium status in postmenopausal outpatients, but reflexive calcium testing strategy for m-iCa test is necessary to women presenting the low or high extremes of tCa levels, or in women with suspected PHPT.

Vascular calcification (VC) represents a recognized adverse predictor for cardiovascular morbidity and mortality. Previously considered passive and degenerative, VC is now recognized as an active process that resembles bone formation, and shares a number of histopathological features, mineral composition, and initiation mechanisms with bone development and metabolism. Oxidative stress and inflammation are key factors in both VC and osteoporosis (OP). Biochemical factors known to be primarily involved in the healthy bone metabolism also regulate VC. These biomarkers include vitamin D, osteoprotegerin, osteopontin, matrix Gla protein, cathepsin K, fibroblast growth factor-23, and fetuin-A. A better understanding of this highly controlled regulatory network, with multiple, nested feedback loops and cross talk between organs, may help to decrease the growing prevalence of calcific vasculopathy as well as OP in the aging population, and to advance in common preventive and therapeutic interventions targeted at both conditions.

The aim of the study was to investigate whether TH replacement therapy is safe and impact infarct size, left ventricular (LV) volumes and function in patients with acute myocardial infarction (AMI) and low T3 syndrome (LT3S). Thirty-seven AMI/LT3S patients were randomly treated or untreated with liothyronine (T3) therapy (maximum dosage 15 mcg/m2/die) in addition to standardized treatment (T3-treated group, n = 19; untreated group, n = 18). TH and thyroxine (TSH) during hospital stay and at 1-month and 6 months were evaluated. At discharge and at 6 months LV volumes, ejection fraction, wall motion score index (WMSI) and infarct extent were measured by cardiac MR. T3-treated patients had a significant increase in fT3 (p = 0.003 and p

The process of atherosclerosis may begin early in lifetime and develop for decades, until leading to manifest cardiovascular disease (CVD).

The heart is one of the principal targets of thyroid hormones (TH) action, affecting cardiac contractility, heart rate, and diastolic function. Oxidative damage is pivotal for onset and development of cardiovascular disease (CVD) and heart failure. Specifically, free radical generation is associated to hyper-metabolic state in hyperthyroidism, whereas hypo-metabolic state induced by hypothyroidism leads to a decrease of oxidative stress. In the present review, the role of oxidative damage in CVD and failing heart-TH interplay will be considered. The main oxidative events leading to cardiac dysfunction and TH cardiac regulation at genomic and non-genomic levels will be discussed, as well as role of TH in cardioprotection and reversion of cardiac remodeling.

Aim: To assess gender differences in uric acid (UA) as predictor for hard events (HE, mortality and nonfatal myocardial infarction) in a large cohort of patients referred for coronary angiography. Design & patients: 3020 inpatients (2177 males, age: 68 ± 9 years, mean ± SD) were retrospectively studied, collecting data from the Institute electronic databank which included demographic, clinical, instrumental and follow-up data. Results: Although the Kaplan–Meier survival estimates showed a significantly worst outcome in female patients, high UA did not remained a significant predictor for HE after adjustment. Moreover, UA correlated with antioxidant capacity in both sexes. Conclusion: Hyperuricemia was not an independent risk for HE, and being correlated with antioxidant capacity, its elevation appears more likely compensatory than causative for HE.

International audience; Extrahepatic manifestations of chronic HCV infection include cardiovascular diseases and an increase in cardiovascular mortality. The pathogenic mechanisms by which HCV contributes to cardiovascular disease are not well defined, however, it is likely that systemic inflammation, and the promotion of other metabolic diseases are involved. In this Review, the evidence for HCV infection as a non-traditional risk factor for cardiovascular disease is evaluated. Furthermore, practical advice to evaluate cardiovascular disease risk and disease in chronic hepatitis C patients are included for help in daily clinical practice. Despite the advances in therapies for the treatment of HCV, there remains a need for increased awareness among specialists so that patients are more likely to obtain the treatment required to mitigate disease progression.

We read with interest the manuscript by Lee et al. [(1)][1], which reports statin use impact on coronary plaque features. Statins increase coronary artery calcification, reducing local inflammation, changing phenotypic plaque composition, and lowering the high-risk plaques, as also observed in

Purpose/Introduction: Osteoporosis (OP) and cardiovascular (CV) disease emerge as closely related conditions, showing common risk factors and/or pathophysiological mechanisms. The aim of this study was to evaluate the association between bone health markers (BHM) and individual CV risk factors and overall CV risk (FRAMINGHAM-FRS, and PROCAM scores) in a general adult population. Methods: In 103 subjects (21 males; age: 56 ± 12 years), vitamin D (25(OH)D), osteocalcin (OC), bone alkaline phospatase (BALP), procollagen I aminoterminal propeptide (P1NP), CTx-telopeptide, as well clinical history and life style were evaluated. Results: Aging (p < 0.001) and glycemia (p < 0.05) emerged as independent 25(OH)D predictors. Aging (p < 0.001), male sex (p < 0.05), and obesity (p < 0.05) represented independent OC determinants. Aging (p < 0.05) was the only independent BALP determinant. After multivariate adjustment, low 25(OH)D (75th percentile-16.6 ng/mL) (6.7 (1.9–23.8) p < 0.01) were found to be significant FRS predictors, while subjects with elevated OC and/or BALP (>75th percentile-9.8 μg/L) showed a higher CV risk as estimated by PROCAM (3.6 (1.2–10.7) p < 0.05). CTx and P1NP did not significantly correlate with CV risk factors or scores. Conclusion: As we go further into bone and CV physiology, it is evident that a close relationship exists between these diseases. Further studies are needed to investigate mechanisms by which bone turnover markers are related to metabolic risk and could modulate CV risk. This knowledge may help to develop possible multiple-purpose strategies for both CV disease and OP prevention and treatment.

Cardiac Troponins (cTnI, cTnT), NT-proBNP, and galectin-3 (GAL-3) mirror cardiomyocyte injury, stretch, and fibrosis. However, although these biomarkers has been thoroughly studied in marathon or ultramarathon, the effects occurring running shorter distances, as half-marathon, are less known and data are generally limited to immediately post-race evaluation. Moreover, significant variation of alpha-1 antitrypsin (AAT), an anti-protease factor with anti-inflammatory properties, has been recently observed in heart failure, but not investigated in paraphysiological settings. The aim of the study was to evaluate these biomarkers concentration and trends in trained runners before half-marathon run and during a 48-h recovery period. In 18 half-marathon runners (15 males, 46 ± 6 years), cTnI, GAL-3 (Architect, Abbott), cTnT, NT-proBNP (Cobas e411, Roche), and AAT (Abcam, Cambridge, UK) were evaluated at rest, immediately post-run, and at 24 and 48-h recovery period. cTnT, NT-proBNP, and GAL-3 transiently increased after post-race, but normalized at 24 h (GAL-3 p

Aims: We assessed the inter-relationship that exists between variations of different biochemical and hematological parameters following strenuous endurance exercise in Ironmen by using multiple factor analysis (MFA). MFA was used to estimate the associations among groups of parameters in order to identify concurrent changes in many different biochemical variables. Materials & methods: In total, 14 Ironman athletes were followed before and early after a race. MFA was applied to the parameters that showed a significant variation after the race, as we previously described in detail. Specifically, MFA standardizes data in each group and calculates the global axes (GAs), which are the linear combination of original parameters that maximize the global data variance. Results: MFA identified three global axes (GAs) as significant, explaining approximately 62% of the global data variance. The first GA contained NT-proBNP, IL-1ra, IL-6, IL-8 and the oxidative index. The second and third GAs included calcium, creatinine, potassium, uric acid, hemoglobin, hematocrit and glucose. Analysis of the first two GAs showed that changes in the oxidative index were associated with variations in IL-8 and NT-proBNP. Conclusion: Among all the variables considered, MFA evidenced a close relationship between variations in oxidative stress, IL-8 and NT-proBNP, which may have a meaning in the mechanisms related to the physiological response after strenuous acute exercise.

Background: Oxidative stress is crucial in the pathogenesis of atherosclerosis and acute myocardial infarction (AMI). Under the generic terms &ldquo, oxidative stress&rdquo, (OS), many biomarkers belonging to different pathways have been proposed. Aim: To compare the levels of recently proposed OS-related parameters in acute coronary syndromes (ACS) and stable coronary artery disease (CAD), to evaluate their effectiveness as additive risk or illness indicators of stable and acute ischemic events, and their response over time during the course of AMI. Methods: 76 ACS, 77 CAD patients, and 63 controls were enrolled in the study. Different OS-related biomarkers, including reactive oxygen metabolites (ROM), the total antioxidant capacity (OXY), nitrite/nitrate (final nitric oxide products, NOx), and Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), were evaluated. Moreover, time response during AMI course (admission, and 6, 12, 18, 24, 36, and 48 hours after, T0-T6, respectively) and correlation with traditional cardiovascular (CV) risk factors (age, gender, hypertension, diabetes mellitus, dyslipidemia, smoking habit) were also assessed. Results: Over time, ROM progressively increased while OXY and NOx decreased. Kinetics of LOX-1 during AMI shows that this biomarker boosts early during the acute event (T1 and T2) and then progressively decreases, being significantly lower from T0 to T6. Different OS-related biomarkers were differentially associated with CV risk factors and CAD or ACS presence. Conclusion: Differences in OS-related biomarkers (between groups, according to the response over time during AMI, and to the presence of CV risk factors) confirmed OS involvement in the transition from healthy status to stable CAD and ACS, although evidencing the heterogeneous nature of redox processes. In future, a multi-marker panel including different biomarkers and pathways of oxidative stress could be evaluated as an additive tool to be used in the CV prevention, diagnosis, patient stratification, and treatment.

Aims/hypothesis: Cardiac steatosis and myocardial insulin resistance elevate the risk of cardiac complications in obesity and diabetes. We aimed to disentangle the effects of circulating glucose, insulin and NEFA on myocardial triacylglycerol (TG) content and myocardial glucose uptake. Methods: Twenty-two pigs were stratified according to four protocols: low NEFA + low insulin (nicotinic acid), high NEFA + low insulin (fasting) and high insulin + low NEFA ± high glucose (hyperinsulinaemia-hyperglycaemia or hyperinsulinaemia- euglycaemia). Positron emission tomography, [U-13C]palmitate enrichment techniques and tissue biopsies were used to assess myocardial metabolism. Heart rate and rate-pressure product (RPP) were monitored. Results: Myocardial glucose extraction was increased by NEFA suppression and was similar in the hyperinsulinaemia-hypergylcaemia, hyperinsulinaemia-euglycaemia and nicotinic acid groups. Hyperglycaemia enhanced myocardial glucose uptake due to a mass action. Myocardial TG content was greatest in the fasting group, whereas hyperinsulinaemia had a mild effect. Heart rate and RPP increased in hyperinsulinaemia-euglycaemia, in which cardiac glycogen content was reduced. Heart rate correlated with myocardial TG and glycogen content. Conclusions/interpretation: Elevated NEFA levels represent a powerful, self-sufficient promoter of cardiac TG accumulation and are a downregulator of myocardial glucose uptake, indicating that the focus of treatment should be to 'normalise' adipose tissue function to lower the risk of cardiac TG accumulation and myocardial insulin resistance. The observation that hyperinsulinaemia and nicotinic acid led to myocardial fuel deprivation provides a potential explanation for the cardiovascular outcomes reported in recent intensive glucose-lowering and NEFA-lowering clinical trials. © 2014 Springer-Verlag Berlin Heidelberg.

Background Although magnesium (Mg) has recognized cardioprotective properties and hypomagnesemia is common in patients with acute myocardial infarction (AMI), data regarding the role of Mg as prognostic factor for adverse events are scarce, as well as there are conflicting results on the use of Mg as adjuvant therapy in AMI. Aim To evaluate the role of Mg as predictor for hard events (HE, all cause death, and nonfatal myocardial infarction) in AMI patients. Design and patients We studied 406 AMI patients (306 males, age: 67 ± 12 years, mean ± SD). Patient data were collected from the Institute electronic databank which saves demographic, clinical, instrumental, therapeutical and follow-up data of all patients admitted to our Coronary Unit. Results During a mean follow-up period of 21 ± 18 months, the combined endpoint accounted for 63 HE, 44 (11%) deaths (35 cardiac deaths), 19 (5%) nonfatal MI. The multiple regression model identified glycemia as the only independent determinant of Mg in AMI pts. (T value = − 2.8, standard coefficient = − 0.15, p 67 years—50th percentile), and ejection fraction (, Graphical abstract Image 1, Highlights • It has been hypothesized that Mg may play a key role in ischemic heart disease. • Mg role as predictor for HE-death, nonfatal myocardial infarction-in AMI was studied. • Our results do not give support for a role of hypomagnesia as HE predictor in AMI.

Cardiovascular disease (CVD) is the leading determinant of mortality and morbidity in women. However, a full understanding of the basic and clinical aspects of CVD in women is far from being accomplished. Sexual dimorphism in CVD has been reported both in humans and experimental animals. Menopause is a risk factor for CVD due to the reduction of endogenous estrogen, although the mechanisms underlying are poorly understood. Estrogens act through binding to vascular estrogen receptors and by non-genomic mechanisms. Advances in this field are essential to improve CVD diagnostic and clinical strategies in women, and to develop sex-specific prevention plans as much as female-oriented treatment algorithms. This paper reviews pathophysiology of CVD in women and its potential clinical implications. Particular emphasis is given to biochemical markers and to indicators of cardiovascular dysfunction and damage. Estimation of these parameters, central to cardiovascular pathophysiology, could represent a particularly relevant tool in female patients. More research is needed to identify women who will profit most of early intervention.

Latent autoimmune diabetes in adults (LADA) is a subtype of autoimmune diabetes, which shares characteristics of both Type 1 and 2 diabetes (T1D and T2D), and for this reason, it is often confused with other types of diabetes, misdiagnosed, and inappropriately treated. Two cases were presented (41-year-old and 50-year-old females), one occasionally diagnosed during routine health checkup, the other one identified as having T2D, and as far as misclassified and not optimally treated. Now, after approximately 9 months of LADA diagnosis, the first patient has an optimal metabolic control while maintaining the values of glycated hemoglobin to around 7% with small doses of analogue insulin (lispro 4-6 UI) before meals and long acting insulin (glargine 4-6 UI) at bedtime. The second patient, after approximately 2 years from the LADA diagnosis, has an optimal metabolic control, with maintenance of glycated hemoglobin to around 6.5%, and stable C-peptide level (around 1.5 ng/mL), only with dietary and exercise habits. To avoid misclassification, any patient who does not fit the typical T2D profile, or with poor glycemic control, and who does not follow the expected clinical course, as become insulin dependent sooner than expected, should be investigated to exclude LADA. To define the best therapeutic approach, each patient must be evaluated and therapy tailored on his/her specific profile, considering as very low insulin doses may be effective to maintain a successful metabolic control and the only dietary approach may be sufficient until the insulin-secretory capacity remains good.

Cardiovascular disease is the leading cause of death in women in Western countries. Despite preventive strategies, in the past decades the incidence of cardiovascular events has shown a decline in men but a rise in women, matching the growth of the population of postmenopausal women. Several epidemiological findings suggest the causative pathophysiological role of ovarian hormone deficiency in the development of cardiovascular disease in women. Observational and randomized studies have suggested that hormone replacement therapy in early postmenopause could be beneficial from a cardiovascular point of view. Conversely, aging, time since menopause and presence of cardiovascular risk factors or cardiovascular disease may decrease its efficacy and increase the risk of cardiovascular events. It is plausible that the unfavorable effects of the estrogen/progestin combination used in the randomized studies are not related to the hormone preparation per se but rather to the use of hormones in the less receptive group of women, older and with cardiovascular risk factors. Clinical judgment, choice of the right dose and estrogen/progestin combination are of pivotal importance to maximize the beneficial effect of estrogen replacement therapy/hormone replacement therapy, especially if given within a reasonable time after the menopause to women who need the therapy for the relief of menopausal symptoms.

Background: Genetic variants related to the natriuretic peptide (NP) system [ScaI mutated allele (A1) of the atrial NP (ANP) gene and the C variant of the natriuretic peptide clearance receptor (NPRC) gene] have been identified as independent risk factors for cardiovascular morbidity and mortality. Despite the importance of NPs in heart failure (HF), the role of these polymorphisms in HF has not been evaluated.Methods: We screened 124 HF patients [mean (SD), age 66 (12) years, 100 men, ejection fraction 32% (10%), New York Heart Association (NYHA) class I–II 65, III–IV 59] for NP concentrations [ANP, brain NP (BNP) and amino-terminal pro-BNP (NT-proBNP)] and for the ScaI and NPRC variants.Results: ScaI polymorphism had no effect on NP concentration in the NYHA I–II subgroup. Conversely, in severe HF, A1 carriers had higher ANP (P ≤0.05), BNP (P Conclusions: The ScaI polymorphism of the ANP gene might be an important additive genetic factor influencing neurohormonal activation and disease progression in severe HF. The NPRC polymorphism is not an independent determinant of NP concentration in HF.

International audience; AIMS:Refractory hyperaldosteronism is frequently observed in heart failure patients on up-to-date treatment, and holds prognostic value. Our aim was to identify which factors, either genetic or nongenetic, are associated with refractory hyperaldosteronism.METHODS:We enrolled 109 consecutive patients with left ventricular systolic dysfunction [left ventricular ejection fraction (LVEF) 32 ± 10%; 86% males; age 65 ± 13 years (mean ± standard deviation)] on optimized adrenergic and renin-angiotensin-aldosterone system (RAAS) antagonism, undergoing clinical and neuroendocrine characterization, and genotyping for six polymorphisms in key RAAS-regulating genes [angiotensinogen (AGT M235T), angiotensin-converting enzyme (ACE-240A>T and I/D), angiotensin II type I receptor (AGTR1 1166A>C), aldosterone synthase (CYP11B2-344C>T) and renin (REN rs7539596)].RESULTS:Patients with refractory hyperaldosteronism (n = 41, 38%, with plasma concentration >180 ng/l, URL, median 283 ng/l, interquartile range 218-433), when compared with those without (106 ng/l, 74-144; P

To evaluate whether the route of estrogen therapy (ET) may affect the levels of different vasoactive factors in healthy recent post-menopausal women.We conducted a cross-over study in 20 healthy nonsmoking women in recent postmenopause (1.8+/-0.1 years). Women received either 1-month oral-ET (O-ET, 2 mg oral micronized 17beta estradiol daily) or transdermal-ET regimen (T-ET, 17beta estradiol 1.5 mg gel daily) with a 1-month wash-out interval. Blood pressure, plasma levels of endothelin-1 (ET), 6-ketoPGF1a (6-ketoPG, prostacyclin metabolite), nitrite/nitrate (NOx), epinephrine (E) and norepinephrine (NE) and lipid profile were measured at baseline and after each treatment.Both regimens significantly reduced E (p0.01) and NE levels (p0.05). O-ET reduced low-density lipoproteins (LDL) levels (p0.05) and increased NOx values (p0.01). Neither regimen caused significant changes of ET or 6-ketoPG.Our results, obtained in healthy women in recent menopause, indicate that the ratio between vasodilator (NOx and prostacyclin) and vasoconstrictor (ET) bioavailability shifted towards the previous ones after O-ET, while it remained unchanged after T-ET; moreover, catecholamines levels were reduced by both treatments already from 1 month of therapy. These changes might represent very early beneficial effects evoked by ET on the cardiovascular system.

The risk of cardiovascular disease significantly increases after menopause. Accordingly, many evidences suggest that estrogens may positively affect the production of different vasoactive factors, such as nitric oxide, prostacyclin, endothelin-1 and catecholamines and induce favourable changes in lipid profile. However, although observational data indicate that hormone replacement therapy (HRT) reduces significantly the cardiovascular risk, recent results have added controversial data to the institution of HRT in postmenopausal women. These last studies present numerous bias, related to inclusion of a single combination HRT regimen, recruitment women of older age groups who began treatment years after menopause and generally with pre-existing coronary artery disease. In fact, it is known that aging and atherosclerotic injury may induce estrogen receptors depletion, endothelial dysfunction and thrombosis, thus potentially decreasing HRT efficacy. Therefore, particular attention must be paid to the age of the woman and the complexity of atheroscleriotic lesions as determinants of the response to HRT for each patient. Moreover, the maintenance of an healthy and normal functioning endothelium after menopause emerges as a major target to retain maximal cardiovascular benefit from this treatment.

Background and aim The effect of low-density lipoproteins (LDLs) on endothelial nitric oxide synthase (eNOS) is debated. By coupling in viva and in vitro experiments we evaluated the role of oxidized lipid substrates in the modulation of eNOS activity by LDLs. Materials and methods Plasma lipids, nitrite/nitrates (NO 2 /NO 3 ), and malondialdehyde (MDA) were measured in 14 controls, and in 13 patients with familial hypercholesterolemia (FH) before and after 12 weeks of treatment with atorvastatin (20 mg u.i.d.). Nitric oxide synthase in cell lysate and NO 2 /NO 3 into the medium were measured in human microvascular (HMEC-1) and umbilical vein (HUVEC) endothelial cells after 24 h of incubation with increasing concentrations of mildly oxidized LDLs with and without atorvastatin and in HMEC-1 with and without vitamin C. In HMEC-1, NO 2 /NO 3 was also determined after exposure to more intensively oxidized LDLs. Results At baseline, plasma NO 2 /NO 3 (56 ± 7 vs. 35 ± 3 μM) and MDA (5.6 ± 0.7 vs. 2.9 ± 0.3 μM), were significantly (P < 0.02 for both) higher in the FH patients. In the whole study group, NO 2 /NO 3 was more strongly correlated with plasma MDA (Rho = 0.70) than LDL-cholesterol (Rho = 0.57). In the FH patients, atorvastatin induced a significant decline in plasma total and LDL-cholesterol (-3.1 ± 0.5 and -2.9 ± 0.5 mM, respectively), NO 2 / NO 3 (-35 ± 8 μM) and MDA (-3.4 ± 0.7 μM) (P < 0.001 for all). Changes in plasma NO 2 / NO 3 were related to the concomitant changes in plasma MDA (Rho = 0.79, P < 0.006) and not to changes in LDL-cholesterol. In HMEC-1 and in HUVEC, mildly oxidized LDLs stimulated both e-NOS and NO 2 /NO 3 accumulation; the effect on e-NOS was potentiated by vitamin C in HMEC-1. Atorvastatin had no effect in HMEC-1 while it stimulated eNOS but not NO 2 /NO 3 in HUVEC. The accumulation of NO 2 /NO 3 in HMEC exposed to increasing concentrations of more intensively oxidized-LDLs showed a nonlinear dose-response curve. Conclusions In uncomplicated patients with FH, plasma NO 2 /NO 3 concentrations are elevated; the cross-sectional data, intervention study and in vitro experiments indicate that oxidized lipids exert a tonic stimulatory action on e-NOS and NO 2 /NO 3 generation not mediated through superoxide anion formation. Atorvastatin amplify this eNOS response in HUVEC, but not in HMEC, and this effect is not associated with a parallel increased NO 2 / NO 3 generation.

Nitric oxide (NO) and cyclooxygenase (COX) derived prostaglandins (PGs) are involved in vascular homeostasis. Contradictory results have been obtained in previous studies on the putative ‘cross-talk’ between these two pathways. Our aim was to evaluate the interaction between NO and PG release in human microvascular endothelial cells (HMEC-1) and in umbilical vein endothelial cells (HUVEC). Methods: Medium samples were assayed for nitrite/nitrate (NOx) and L-citrulline levels while lysed cells were assayed for endothelial NO synthase (eNOS), as markers of NO production. Prostaglandin E2 (PGE2) and 6-keto-prostaglandin F1α (6-keto-PGF1α) were assessed as indicators of COX activity. Results: The NO donor sodium nitroprusside and L-arginine increased PGs levels in both cell types. NG-monomethyl-L-arginine (L-NMMA) significantly inhibited 6-keto-PGF1α release without significantly reducing PGE2 levels. Indomethacin increased both NOx, eNOS and L-citrulline levels. PGE2 treatment did not modify NOx values. Conclusion: The stimulation of PGs by NO may represent an additional pathway used by exogenous nitrovasodilators to elicit vasodilation. Reduction of PGs by inhibition of COX was compensated by enhanced NO. Conversely, PGsdid not compensatedecreased NO following L-NMMA treatment. Treatment with the vasodilatator prostaglandin E2 did not modifyNOx levels.

Somatic DNA damage has been suggested to contribute to the pathogenesis of atherosclerosis. However, little is known about the role of oxidative DNA damage in patients with coronary artery disease (CAD).In this study, we used the comet assay to measure oxidative DNA damage (DNA strand breaks and enzyme-sensitive sites) in peripheral blood lymphocytes from 13 patients with angiographically documented CAD and 11 age- and sex-matched control participants.Mean values of DNA strand breaks, oxidized pyrimidines and altered purines were significantly higher in CAD patients than in the control group (11.9 +/- 1.4, 18.0 +/- 2.7 and 18.1 +/- 3.1 compared with 3.3 +/- 0.2, 2.7 +/- 0.5 and 4.5 +/- 1.1; P0.0001, P0.0001 and P = 0.0009, respectively). Moreover, oxidized purines (for example, 8-oxo-guanine) increased with the number of affected vessels and positively correlated with the extent of CAD measured by means of the number of the coronary lesions (P = 0.76, P = 0.003) and the Duke scoring system (P = 0.66, P = 0.01). Diabetic patients showed higher levels of oxidized pyrimidines (31.3 +/- 5.5 compared with 14.1 +/- 2.7; P = 0.013), while patients with dyslipidemia had elevated altered purines compared with normal patients (20.4 +/- 2.6 compared with 4.9 +/- 3.1; P = 0.03).These data indicate an overall elevation of oxidative DNA damage in CAD patients correlated with the severity of the disease and some atherogenic risk factors, suggesting a possible role of oxidative genetic damage in the pathogenesis of atherosclerosis.

Objective To evaluate whether obesity and smoking habit may accelerate the age-related increase of oxidative stress. Methods The Oxidative-INDEX, a score reflecting both oxidative and antioxidant counterparts, was estimated in 179 subjects (50 males, aged 16–79 years). Results Oxidative stress results were elevated in obese and smoker subjects. Adjusted logistic regression analysis indicated obesity and smoking as independent variables for elevated Oxidative-INDEX (odds ratio = 4.8 and 3.1, respectively). Oxidative-INDEX steadily rises at a mean rate of 5.3% (0.017 AU) per year in the overall population, showing twice and three times higher annual rate increase in smokers and obese subjects. Conclusion Our results suggest the pro-ageing effects of cigarette smoking and obesity by a more rapid and sharp elevation of the oxidative stress status.

Background: Results collected from the 2010–2012 cycles of the ‘Immunocheck’ external quality assessment scheme for 25-hydroxyvitamin D, conducted by QualiMedLab CNR (Italy) and ProBioQual (France; 250 among Italian and French laboratories) are presented in this article. Methods: Details of how QualiMedLab operates can be found in QualiMedLab website. Results: Interlaboratory imprecision was 19 (2010), 15 (2011) and 13% (2012). The LIAISON® analyzer (DiaSorin, Italy) was the most utilized, followed by Roche (UK), ImmunoDiagnostic Systems methods (UK), ARCHITECT (Abbott, IL, USA), radioimmunoassay (DiaSorin) and others. The within-method variability between laboratories (percentage coefficient of variation) were 15, 12.7 versus 9.8% for LIAISON, 27.8, 16.5 versus 11.7% for Roche, 15, 12 versus 17% for ImmunoDiagnostic Systems and 17.4, 18.6 versus 17.5% for radioimmunoassay in the 2010, 2011 versus 2012 cycles, and 15 versus 8.9% for ARCHITECT in the 2011 versus 2012, respectively. Conclusion: Significant differences in specific samples and discrepancies between laboratories and methods still exist, making the actuation of appropriate external quality assessment schemes mandatory.

Background: Oxidative stress has been postulated as an additive factor linking obesity to cardiovascular disease. Materials & methods: Derivatives of reactive oxygen species metabolites (d-ROMs) were measured in 136 obese (42 males, 94 females; mean age: 47 ± 12 years; BMI: 36 ± 5 kg/m2) and in 306 over- and normal-weight subjects (112 males, 194 females; age: 47 ± 12 years; BMI: 24 ± 3 kg/m2). Results: d-ROMs levels were higher in obese than in over- and normal-weight subjects (395 ± 104 vs 362 ± 102 and 351 ± 84 arbitrary units (AU); p < 0.001), in women than males (390 ± 104 vs 327 ± 68 AU; p < 0.001), in subjects with than those without hypertension (390 ± 103 vs 360 ± 95 AU; p < 0.01) and in smokers than former and nonsmokers (380 ± 97 vs 358 ± 97 AU; p < 0.05). A positive correlation was found between d-ROMs and BMI (r = 0.25; p < 0.001) and age (r = 0.13; p < 0.01). Levels of d-ROM (>75th percentile: 420 AU) remained as an independent obesity predictor (odds ratio: 2.5; p < 0.001) in women. Continuous variables are reported as mean ± standard deviation. Conclusion: d-ROMs are a powerful obesity predictor, and could represent a reliable tool in obesity and cardiovascular risk evaluation, especially in women.

OBJECTIVE To evaluate the predictive value of resting heart rate (RHR) for cardiac and total mortality in a large population of patients referred for coronary angiography with an extended follow-up, stratified in four subpopulations according to gender and age (50th percentile corresponding to 67 years).We studied 3559 subjects (2603 males, age: 66 ± 11 years, mean ± SD), obtaining patient data from the Institute electronic databank which saves demographic, clinical, instrumental and follow-up data of patients admitted to our department.During a mean follow-up period of 35 ± 25 months, 296 (8%) patients died; there were 173 (5%) cardiac deaths. In female patients irrespective of age, RHR (≥ 76 bpm, 75th percentile) did not appear predictive for cardiac death. In females, RHR was predictive for overall mortality after multivariate adjustment only in those aged ≥ 67 years (hazard ratio (HR) 1.7, 95% confidence interval (CI) 1-2.8, p ≤ 0.05). In male patients aged67 years, RHR remained as an independent predictive factor for overall mortality at the multivariate analysis (HR 2.5, 95% CI 1.5-4.2, p0.001), and as an independent predictor for both cardiac mortality (HR 1.8, 95% CI 1.2-2.7, p0.01) and total mortality (HR 1.6, 95% CI 1.2-2.3, p0.01) in male patients over 67 years.The current study suggests that the prognostic importance of RHR may differ according to the patient's gender and age, suggesting significant differences in cardiovascular physiopathology between female and male patients.

Myocardial tissue perfusion is not currently quantified in the clinical setting. Thus the aim of this paper is to review the quantitative information on myocardial perfusion provided by contrast echocardiography. In a circulatory model-without the capillary network interposed between injection and sampling point of contrast-the transit time of microbubbles (source of the echo contrast effect) is inversely related to absolute flow, thus providing accurate quantitation. A similar situation is represented by blood flow inside a vessel or a cardiac cavity, where, if the prerequisites for quantitation are respected, it is possible to measure blood flow by contrast echocardiography. In the coronary circulation, the transit time of contrast microbubbles varies according to their interaction with coronary microcirculation, and to the characteristics of contrast agents as flow tracers. Echo contrast agents with small microbubbles have been injected into the coronary branches of experimental animals, under both coronary autoregulation and maximal coronary dilation, providing good estimates of coronary blood flow. The accuracy of these measurements might improve when new contrast agents, with characteristics closer to those of a flow tracer, are available. If a tracer is injected before a bifurcation, and provided it mixes adequately, the amount of tracer distributed to each branch is proportional to the corresponding blood flow. A similar situation is encountered when an echo contrast agent is injected into the aortic root or into the left main coronary artery. Here, the ratio between myocardial signal intensity in the different perfusion territories reflects the corresponding ratio of blood flows. The validity of this approach has been previously demonstrated in experimental animals and validated in patients with coronary stenoses. The injection of contrast agents into the coronary circulation at baseline and under coronary hyperaemia has the potential for measuring coronary blood flow reserve. However, what is still unclear is whether contrast echo changes reflect changes in coronary blood flow (i.e. flow reserve), coronary blood volume (i.e. coronary recruitment) or both, and also whether they influence the different types of contrast agent. Finally, myocardial contrast echocardiography can provide information on the spatial distribution of myocardial perfusion, i.e. the presence, site and extent of perfused myocardium. Thus, in models where myocardial perfusion may be either present or absent, contrast echo can provide an accurate estimate of perfusion abnormalities.

Objectives. This study sought to assess the value of dipyridamole echocardiography in predicting reinfarction in patients evaluated early after uncomplicated acute myocardial infarction. Background. The identification of future nonfatal reinfarction seems an elusive target for physiologic testing. However, a large sample population is needed to detect minor differences in phenomena with a low event rate. Methods. We assessed the value of dipyridamole echocardiography in predicting reinfarction in 1,080 patients (mean [±SD] age 56 ± 9 years; 926 men, 154 women) evaluated early (10 ± 5 days) after uncomplicated acute myocardial infarction and followed up for 14 ± 10 months. Results. Submaximal studies due to limiting side effects occurred in 14 patients (1.3%); these test results were included in the analysis. Results of dipyridamole echocardiography were positive in 475 patients (44%). During follow-up, there were 50 reinfarctions: 45 nonfatal, 5 fatal (followed by cardiac death ≤4 days after reinfarction). Reinfarction (either nonfatal or fatal) occurred in 30 patients with positive and 20 with negative results (6.3% vs. 3.3%, p Conclusions. Dipyridamole echocardiographic positivity identifies patients evaluated early after uncomplicated acute myocardial infarction at higher risk of reinfarction, especially fatal reinfarction.

Vitamin D (25-OHD) physiological functions have been expanded beyond traditional bone health, increasing the importance of its estimation in Laboratory Medicine, which renders validation of available methods mandatory.We evaluated some preanalytical and analytical aspects of 25-OHD determination and the effects of potentially confounding clinical variables by using the DiaSorin "LIAISON 25-OH Vitamin D TOTAL".25-OHD samples were extremely stable, at least in the short term, without requiring special transport or storage. Precision intervals (CV%) were: within run (7-11%) and total precision (8-11.5%). Mean (SD) recovery was 96 (2)%. The assay was linear on dilution. Comparison with radioimmunoassay (RIA) yielded acceptable correlation (Inter-rater agreement/kappa coefficient=0.94) and clinical equivalence in the interval from 6 to 55 ng/mL. The assay was evaluated on a general population (N=476, age: 60±14 years, 65 males). The status of 25-OHD resulted inversely related to parathyroid hormone levels (r=-0.21, p0.001), and aging (r=-0.17, p0.001), but not to sex. Levels of 25-OHD were found to be sufficient (≥30 ng/mL) only in 54 samples (12%). Marked seasonal 25-OHD variations were observed in 13 subjects (p0.05). Moreover, a marked seasonal fluctuation was seen in samples collected during the period of February 2010-October 2011 (p≤0.01). Lower 25-OHD concentration was observed in subjects with diabetes (19±9 vs 14±7 ng/mL, p0.01) and hypertension (20±9 vs 17±9 ng/mL, p0.01). Moreover, 25-OHD inversely correlated with BMI (r=-0.25, p0.001). Conversely, no difference in 25-OHD levels was observed between subjects due to smoking habits and dyslipidemia. In multiple logistic regression models, aging is the only significant independent risk factor for low 25-OHD levels (Odds ratio, 95% confidence intervals: 3.1, 1.3-7.3; p≤0.01).Results confirm the LIAISON 25-OHD assay as a useful tool for 25-OHD estimation in the clinical practice. Lack of vitamin D is common among Italian adults, and appears associated with several cardiovascular risk factors.

AIMS To evaluate the prognostic significance of oxidative stress on the rate of major adverse cardiovascular events (MACEs: cardiac and all-cause death, nonfatal myocardial infarction, coronary revascularization-PTCA/CABG) in CAD. METHODS We studied 97 angiographically proven CAD patients (78 males, age: 67±11 years, mean± SD). Reactive oxygen metabolites and total antioxidant status, assessed by commercially assays (d-ROMs and OXY-Adsorbent Test; Diacron, Grosseto, GR, Italy), were used to calculate the oxidant/antioxidant balance. Patient data were collected from the Institute's electronic databank, which saves demographic, clinical, instrumental and follow-up data of all patients admitted to our department. RESULTS Kaplan-Meier survival estimates showed a significantly worst outcome in patients presenting with elevated oxidative stress levels (>75th percentile, p