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Les inhibiteurs du cotransporteur sodium-glucose de type 2 (iSGLT2) sont de plus en plus recommandes comme traitement de l’insuffisance cardiaque en raison d’un benefice cardio-renal et d’un effet favorable sur la mortabilite. L’utilisation de biomarqueurs pour suivre l’efficacite de ce traitement pourrait s’averer utile et notamment le Fibroblaste Growth Factor 23 (FGF-23) en raison de la relation entre ses taux circulants et le pronostic cardiovasculaire. D’autre part, la mesure de FGF-23 lors du traitement par un iSGLT2 pourrait permettre de suivre les repercussions sur le metabolisme phosphocalcique.

Handedness is a tangible manifestation of cerebral motor lateralization. It is partly hereditary, it arises early in foetal life, and is modulated by intrauterine, perinatal and epigenetic factors. While the molecular bases of handedness have yet to be formally established, genetic studies have hinted at a polygenic origin partly under the control of molecular mechanisms establishing left–right body asymmetry. A previous report had found that non-right-handed (non-RH) patients with type 2 diabetes mellitus (T2DM) had better insulin sensitivity (IS) than their right-handed (RH) counterparts, which was unrelated to differences in obesity, body composition and physical activity. It was also observed that gastrointestinal intolerance to metformin was associated with a lower prevalence of ischaemic heart disease and with being left-handed (LH), whereas being non-RH was over-represented among metabolically-healthy normal-weight T2DM patients without the metabolic syndrome (MetS). Yet, there are virtually no data on lipids, lipoproteins or apolipoprotein (apo) levels as a function of motor laterality. For this reason, our present analysis was performed to determine whether laterality could modulate lipids/lipoproteins, including lipoprotein(a) [Lp(a)], in DM patients [...]

Objectives This study sought to compare the prognostic value of 2-dimensional (2D) right ventricular (RV) speckle tracking (STE) against cardiac magnetic resonance (CMR) RV ejection fraction (EF) and feature tracking (FT) and conventional echocardiographic parameters on overall and cardiovascular (CV) survival in patients with heart failure with reduced EF (HFrEF). Background Prior works showed that RV systolic function predicts prognosis in HFrEF. 2D RVSTE had recently been proposed as new echocardiographic method to evaluate RV dysfunction. Methods A total of 266 patients with HFrEF (mean LVEF 23 ± 7%, 60 ± 14 years of age; 29% women) underwent RV function assessment using CMR and 2D echocardiography and were followed for a primary endpoint of overall death and secondary endpoint of CV death. Results Average CMR-RVEF was 42 ± 15%, average STE RV global longitudinal strain (STE-RVGLS) was −18.0 ± 4.9%, and average CMR-FT-RVGLS was −11.8 ± 4.3%. After a median follow-up of 4.7 years, 102 patients died, 84 of a CV cause. RVEF, FT-RVGLS, tricuspid annulus plane systolic excursion (TAPSE), fractional area change (FAC), and STE-RVGLS were significant univariate predictors of overall and cardiac death. In multivariate Cox regression, age, ischemic etiology, diabetes, New York Heart Association functional class III to IV, and beta-blocker treatment were independent clinical predictors of overall mortality. CMR-RVEF (chi-square to enter = 3.9; p 15 mm, 1.6 (95% CI: 1.02 to 2.49) for FAC >39%, 1.93 (95% CI: 1.25 to 2.99) for RVEF >41%, and 1.87 (95% CI: 1.10 to 3.19) for CMR-FT-RVGLS Conclusions 2D RVGLS provides strong additional prognostic value to predict overall and CV mortality in HFrEF, with higher predictive value than CMR-RVEF, CMR-FT-RVGLS, TAPSE, or FAC. This supports use of STE-RVGLS to identify higher-risk HFrEF patients.

The role of high-density lipoprotein cholesterol (HDL-C) as modifiable risk factor for cardiovascular (CV) disease is increasingly debated, notwithstanding the finding that small-dense and dysfunctional HDL are associated with the metabolic syndrome and T2DM. In order to better clarify the epidemiological risk related to HDL of different size/density, without resorting to direct measures, it would seem appropriate to adjust HDL-C to the level of its main apolipoprotein (apoA-I), thereby providing an [HDL-C/apoA-I] ratio. The latter allows not only to estimate an average size for HDLs, but also to derive indices on particle number, cholesterol load, and density. So far, the potential usefulness of this ratio in diabetes is barely addressed. To this end, we sorted 488 male patients with T2DM according to [HDL-C/apoA-I] quartiles (Q), to determine how the ratio relates to cardiometabolic risk, β-cell function, glycaemic control, and micro- and macrovascular complications. Five lipid parameters were derived from the combined determination of HDL-C and apoA-I, namely HDL size; particle number; cholesterol load/particle; apoA-I/particle; and particle density. An unfavorable cardiometabolic profile characterized patients from QI and QII, in which HDLs were pro-atherogenic, denser and apoA-I-depleted. By contrast, QIII patients had an [HDL-C/apoA-I] ratio close to that of non-diabetic controls. QIV patients had better than average HDL size and composition, and in those patients whose [HDL-C/apoA-I] ratio was above normal, a more favorable phenotype was observed regarding lifestyle, anthropometry, metabolic comorbidities, insulin sensitivity, MetS score/severity, glycaemic control, and target-organ damage pregalence in small or large vessels. In conclusion, [HDL-C/apoA-I] and the resulting indices of HDL composition and functionality predict macrovascular risk and β-cell function decline, as well as overall microangiopathic risk, suggesting that this ratio could serve both in cardiometabolic assessment and as biomarker of vascular complications.

Background Limited data are available regarding the prognostic value of right ventricular (RV) systolic dysfunction (RVSD) in patients with coronary artery disease. Our objective was to evaluate the effect of RVSD assessed by cardiac magnetic resonance on survival of patients with low left ventricular (LV) ejection fraction (EF) undergoing coronary bypass grafting (CABG). Methods We prospectively assessed overall and cardiovascular death of 107 consecutive patients (94 men; age, 66 ± 10 years) undergoing CABG who had a LVEF of 0.35 or less by cardiac magnetic resonance before CABG. Results Mean LVEF was 0.25 ± 0.07, and mean RVEF was 0.46 ± 0.16. RVSD, defined by RVEF of 0.35 or less, was present in 32 patients (30%). In-hospital mortality rate (n = 8) was significantly higher in patients with RVSD (18.7% vs 2.7%, p = 0.004). Over a median follow-up of 4.7 years, 44 patients died, 33 of a cardiovascular cause. The primary end point of cardiovascular death was reached by 15 of 32 patients with RVSD and 18 of 75 patients without RVSD (47% vs 24%, p = 0.019). Univariate survival analysis showed that age, New York Heart Association Functional Classification, diabetes, estimated glomerular filtration rate, LVEF, LV indexed end-diastolic volume, RVEF, RV indexed end-diastolic volume, RV systolic function, and The Society of Thoracic Surgeons risk score were independent predictors of the primary end point of cardiovascular death. By multivariable analysis, the Society of Thoracic Surgeons risk score (hazard ratio, 1.32; 95% confidence interval, 1.13 to 1.55; p = 0.001) and RVSD (hazard ratio, 2.14; 95% confidence interval, 1.06 to 4.31; p = 0.034) remained significant independent predictors of cardiovascular death. Conclusions RVSD strongly and independently predicts cardiovascular death in patients with coronary artery disease and low EF undergoing CABG. Evaluation of RV function should thus be part of preoperative evaluation of such patients.

Objectives The purpose of this study was to evaluate the impact of hypertrabeculation and left ventricular (LV) myocardial noncompaction phenotype by cardiac magnetic resonance (CMR) on outcomes of patients with nonischemic dilated cardiomyopathy (DCM). Background Myocardial trabeculations and noncompaction are increasingly observed in patients with DCM, but their prognostic impact remains unknown. Methods We prospectively evaluated outcomes of 162 consecutive patients (102 men; age 55 ± 15 years; ejection fraction [EF] 25 ± 8%) with DCM undergoing CMR. The amount of noncompaction was quantified as noncompacted/compacted (NC/C) length in the long-axis view and as the ratio of NC/C mass in the short-axis view and compared against 48 healthy control subjects (age 60 ± 10 years). Results Fifty-eight DCM patients (36%) had NC/C length ≥2.3, and 71 (44%) had NC/C mass greater than the 95% confidence interval (CI) of control subjects. NC/C length and NC/C mass did not correlate with any clinical, echocardiographic, or CMR parameters. Over a 3.4-year median follow-up, 29 patients experienced major adverse cardiovascular events (MACE) (12 cardiovascular deaths, 8 heart transplantations, 4 LV assist device implantations, and 5 resuscitated cardiac arrests or appropriate device shocks). Cox univariate analysis identified smoking, New York Heart Association functional class, blood pressure, LV and right ventricular end-diastolic and end-systolic volumes, LV EF, right ventricular EF, and late gadolinium enhancement as predictors of MACE. In multivariate analysis, only LV EF and late gadolinium enhancement were independent predictors of MACE-free survival (hazard ratio: 0.922, 95% CI: 0.878 to 0.967, p = 0.001 and HR: 1.096, 95% CI: 1.004 to 1.197, p = 0.04, respectively). Neither NC/C length nor NC/C mass had significant predictive value for MACE-free survival, either unadjusted or after adjustment for baseline variables. Also, there was no difference in cardioembolic event rate between groups with high and low NC/C length or mass. Conclusions Cardiovascular outcomes of adult patients with nonischemic DCM do not appear to be influenced by the degree of trabeculation. This argues against a noncompaction phenotype designating a more severe form of DCM.

Biomarkers offer new perspectives for a more personalized management of patients with heart failure (HF). Hyperparathyroidism is common in HF patients and parathyroid hormone (PTH) testing might provide added value for the prognostication of HF patients. Our objectives were therefore to determine the efficiency of multiple biomarker strategy based on PTH and natriuretic peptides measurement for the risk stratification of patients with HF. Circulating concentrations of bioactive PTH 1-84 and natriuretic peptides, B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP), were measured with automated immunoassays in 45 healthy individuals and 137 HF patients with reduced left ventricular ejection fraction. Circulating levels of PTH 1-84 and natriuretic peptides were significantly increased in HF patients in comparison to HF patients. Over a long-term follow-up, baseline PTH 1-84 levels were related to the risk of cardiovascular death. Furthermore, in multiple biomarker approach, PTH measurement was additive to BNP and NT-proBNP testing for the cardiovascular risk assessment of HF patients. In conclusion, the combination of PTH 1-84 and natriuretic peptides testing improves the prognostication of HF patients and might allowed more personalized approach for risk stratification and treatment selection in HF patients.

Galectin-3 (Gal-3) testing is emerging as a valuable tool for the prognosis of heart failure (HF). Our objectives were to determine the clinical validity and cost-effectiveness of the recently developed ARCHITECT Gal-3 automated immunoassay.Gal-3 levels were measured in HF patients with reduced left ventricular ejection fraction with the ARCHITECT i2000SR Gal-3 assay as well as with the reference Gal-3 ELISA assay. The relationship between Gal-3 levels determined with the automated assay and HF severity as well as its predictive value for long-term cardiovascular death were evaluated. The impact of Gal-3 testing on the diagnostic related group (DRG) based reimbursement was also estimated.Gal-3 levels measured with the ARCHITECT assay were related to the severity of HF based on New York Heart Association functional classes (p0.001) and were also significantly and positively correlated to BNP concentrations (r=0.35, p0.001). Gal-3 values higher than 19.2 ng/mL were predictive of long-term cardiovascular death in patients with systolic HF and also provided incremental prognostic information to BNP testing. In addition, Gal-3 testing was estimated to save DRG in comparison to standard of care.Our results demonstrated the clinical validity of the ARCHITECT Gal-3 automated immunoassay for the risk stratification of HF patients. The automation of Gal-3 testing was also cost-effective and might help to preserve hospital budget.

BACKGROUND: T2DM management requires tight control of 3 critical quality indicators to prevent vascular complications: LDL-C, SBP, and HbA1c. This study evaluated the rate of T2DM patients attaining these critical quality indicators, and the pathophysiological or cardiometabolic traits predicting goal achievement. PATIENTS AND METHODS: Cross-sectional analysis evaluating combined goal achievement (LDL-C

Comparison of fibroblast growth factor 23, soluble ST2 and Galectin-3 for prognostication of cardiovascular death in heart failure patients

Circulating levels of galectin-3 (Gal-3), a marker of cardiac fibrosis and remodeling, contribute to the risk stratification of patients with heart failure (HF). The aim of our study was to determine the analytical validity and clinical validity of a novel automated Gal-3 assay in HF patients with reduced ejection fraction. We showed an excellent agreement between the VIDAS® Gal-3 automated assay and the ELISA reference method (r = 0.90, p.

Background: OSAS, a frequently neglected, yet frequent comorbidity in T2DM, is associated with obesity, metabolic syndrome and central fat. OSAS is better documented in males, and this study explored novel gender dimorphisms in T2DM. Methods: Cross-sectional study: 815 T2DM (541 males; 274 females) classified into OSAS[-] and OSAS[+] were assessed for cardiometabolic risk factors, glucose homeostasis, micro/macroangiopathies, CV risk, autoimmune thyroid disease (AITD); and GAD65 antibodies. Results: There was a gender dimorphism in glucose control (worse in females), apolipoprotein B100 (higher in females), with apoB100/apoA1 and log(TG)/HDL-C sexually dimorphic. There was also a marked gender dimorphism in GAD65 positivity, higher (+793%) in OSAS[+] females vs. males. There were clear sexual dimorphisms in macro-/microangioathies, regarding stroke, retinopathy and polyneuropathy. OSAS was not sexually dimorphic regarding age; education; and diabetes duration. There was a significant dimorphism in ethnicity. There were no gender-specific dimorphisms related to OSAS in anthropometrics, nor in hypertension, insulin sensitivity, or hyperbolic product loss rate. Conclusion: We report a series of novel OSAS-related sexual dimorphisms, concerning GAD65 auto-antibodies; polyneuropathy; atherogenic dyslipidemia [all increased in females]; diabetic retinopathy; North-Caucasian ethnicity; metabolic control; and TIA/stroke prevalence [all lower in females]. These findings raise challenging questions regarding the reciprocal pathophysiology between obstructive sleep disorders and cardiometabolic risk in T2DM. © 2013 Diabetes. Published by Elsevier Ltd. All rights reserved.

Objectives: Parathyroid hormone (PTH) is a major systemic calcium-regulating hormone. Recent evidence has suggested that measurement of PTH might provide complementary information for the diagnosis and risk stratification of patients with heart failure (HF). The aim of our study was to compare intact and bioactive PTH assays in patients with severe heart failure. Design and methods: The following measurements were carried out in blood samples from 73 patients with severe heart failure: bioactive PTH (1-84) assay, intact PTH assay, non-PTH (1-84), 25-hydroxyvitamin D, B-type natriuretic peptide (BNP), N-terminal proBNP (Nt-proBNP), Galectin-3 and high sensitive troponin T (hsTnT). Results: The correlation between intact and bioactive PTH assays was very high in HF patients. However, the bioactive PTH concentrations were lower than those measured with the intact assay. Intact and bioactive PTH as well as non-PTH (1-84) was significantly and positively correlated to BNP, Nt-proBNP, and galectin-3 but not to hsTnT. The strongest relationships with these cardiac biomarkers and with cardiovascular death were observed with the bioactive PTH assay. Conclusions: The PTH concentrations obtained with intact and bioactive assays are not comparable in patients with severe HF. The specificity of PTH assays might therefore impact on the potential diagnosis and prognosis values of PTH testing in patients with heart failur

BACKGROUND: Familial history of early-onset CHD (EOCHD) is a major risk factor for CHD. Familial diabetes history (FDH) impacts β-cell function. Some transmissible, accretional gradient of CHD risk may exist when diabetes and EOCHD familial histories combine. We investigated whether the impact of such combination is neutral, additive, or potentiating in T2DM descendants, as regards cardiometabolic phenotype, glucose homeostasis and micro-/macroangiopathies. METHODS: Cross-sectional retrospective cohort study of 796 T2DM divided according to presence (Diab[+]) or absence (Diab[-]) of 1st-degree diabetes familial history and/or EOCHD (CVD(+) and (-)). Four subgroups: (i) [Diab(-)CVD(-)] (n=355); (ii) [Diab(+)CVD(-)] (n=338); (iii) [Diab(-)CVD(+)] (n=47); and (iv) [Diab(+)CVD(+)] (n=56). RESULTS: No interaction on subgroup distribution between presence of both familial histories, the combination of which translated into additive detrimental outcomes and higher rates of fat mass, sarcopenia, (hs)CRP and retinopathy. FDH(+) had lower insulinemia, insulin secretion, hyperbolic product, and accelerated hyperbolic product loss. An EOCHD family history affected neither insulin secretion nor sensitivity. There were significant differences regarding macroangiopathy/CAD, more prevalent in [Diab(-)CVD(+)] and [Diab(+)CVD(+)]. Among CVD(+), the highest macroangiopathy prevalence was observed in [Diab(-)CVD(+)], who had 66% macroangiopathy, and 57% CAD, rates higher (absolute-relative) by 23%-53% (overall) and 21%-58% (CAD) than [Diab(+)CVD(+)], who inherited the direst cardiometabolic familial history (p 0.0288 and 0.0310). CONCLUSIONS: A parental history for diabetes markedly affects residual insulin secretion and secretory loss rate in T2DM offspring without worsening insulin resistance. It paradoxically translated into lower macroangiopathy with concurrent familial EOCHD. Conjunct diabetes and CV familial histories generate multi-faceted vascular outcomes in offspring, including lesser macroangiopathy/CAD.

Background : It was recently reported that the prolonged use of statins may predispose to incident cataract in the general population. Cataract is a frequent comorbidity of diabetes, and statins are widely prescribed in patients with type 2 diabetes (T2D) both for primary and secondary cardiovascular prevention. For this reason, this study aimed to assess whether or not the use of statins was associated with an increased prevalence of cataract in such a high-risk population and, conversely, whether or not there was greater usage of statins, or any other lipid-lowering drugs, in T2D patients with cataract. Patients and methods : This was a cross-sectional analysis of 780 T2D outpatients, with a mean age (±1 SD) of 64±12 years and diabetes duration of 13±9 years. Diabetic retinopathy (DR) was found in 23%, and cataract was diagnosed in 16.8% (n=131). Age and diabetes duration of the patients with cataract were significantly higher than those of patients without cataract (n=649): 75±9 vs 62±11 years, and 20±11 vs 12±8 years, respectively (both P

Background: To describe the characteristics (therapeutic, physical and behavioural) associated with achievement of tight blood pressure (BP) control and its prevalence in type 2 diabetes (T2DM) patients. Methods: Cross-sectional observational cohort study. 673 hypertensive patients with T2DM, treated with one or more antihypertensive drugs. Sociodemographic, clinical and laboratory variables compared between patients achieving BP targets (goal-achievers [GAs]) and non-goal-achievers (non-GAs). Results: Only 111 patients (16%) achieved BP goals. Markers-factors connected with failure of BP control in non-GAs were: sub-Saharan African ethno-geographical origin, high alcohol consumption and low educational level. Total cholesterol was significantly lower and glycaemic control significantly better in GAs. In addition, prevalence of micro- or macro-albuminuria was clearly lower in GAs. As regards cardiovascular drugs, statins were used to a greater extent by the GAs. Finally, GAs and non-GAs had the same pattern of micro- and macro-vascular diabetic diseases, as well as similar estimated 10-year absolute cardiovascular risk scores. Conclusions: This cross-sectional study characterized variables associated with an unmet need in drug-treatment of hypertension in T2DM. One might surmise that using higher dosage and/or number of antihypertensive agents will be required in most T2DM patients in order to reach targets, including new antihypertensive agents. © 2010 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Aims: It is much debated whether metabolic syndrome (MetS) is a predictor for microvascular disease in hyperglycemic states. Whether present scoring systems for MetS provide additional risk assessment knowledge related to the severity of the score (from 1/5 to 5/5) remains to be determined for macro- and microangiopathy. Moreover, atherogenic dyslipidemia (low HDL-C and high triglycerides), which provides 2 out of 5 identifying MetS components, is increasingly considered as an emerging risk factor for residual vascular risk. Material and Methods: We therefore analyzed a T2DM cohort (M:F ratio 63:37) with comparable age and diabetes duration with (MetS (+); n = 593) or without MetS (MetS (-); n = 145) regarding both macro- and microangiopathy prevalence and risk factors of both types of complications. MetS was defined according to AHA/NHLBI criteria. Blood pressure, glycemic control, insulin resistance (IR), hyperbolic product (B × S) and B × S loss rate, atherogenic dyslipidemia and low-grade systemic inflammatory markers were compared. We also determined whether there was a gradient for microangiopathy alongside MetS scores. Results: Mean MetS score was 1.8 in MetS (-) vs. 4.0 in MetS (+), with hypertension as paramount non-glycemic contributor in MetS (-). BMI, waist, relative/absolute fat mass, visceral fat, conicity and IR were all significantly increased in MetS (+). Current triglycerides levels were almost twice as high in MetS (+) than in MetS (-), while HDL-C was lower by 20%. Mean HbA 1c was higher by 0.54% in MetS (+). Hypertension prevalence was twice higher in MetS (+) patients, who had increased systolic blood pressure by +7 mm Hg. Albuminuria was markedly elevated in MetS (+). Inflammatory markers ( hsCRP, leucocytes and urate) were significantly higher in MetS (+). Retinopathy was diagnosed in 14% of MetS (-) vs. 27% of MetS (+), polyneuropathy in 21% of MetS (-) vs. 31% of MetS (+) and macroangiopathy in 17% of MetS (-) vs. 36% of MetS (+), either as peripheral artery disease (PAD), coronary artery disease (CAD) and/or TIA (transient ischaemic attack)/stroke: 7, 10, and 5% (PAD, CAD, TIA/stroke) in MetS (-) vs. 11, 26, and 8% in MetS (+) (NS, p < 0.0001, and NS, respectively). Significant trends for increasing prevalence of all three types of microvascular complications were observed according to MetS scores severity from 1/5 to 5/5. Conclusion: Further to macroangiopathy, there was a marked association between MetS and the presence of all types of microvascular complications in T2DM patients. Microangiopathy prevalence was also associated with MetS score severity in a gradient-type relationship. © 2010 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Recent studies showed that right ventricular systolic dysfunction (RVSD) predicts worse prognosis in patients with heart failure (HF). We thus sought to evaluate the prognostic value of RVSD assessed by cardiac magnetic resonance (CMR) in HF patients with low ejection fraction due to idiopathic (DCM

Background Obstructive sleep apnoea syndrome (OSAS), an obesity comorbidity, is an independent risk factor for diabetes (T2DM) and major adverse cardiovascular events (MACE). While OSAS prevalence and association with MACE are well documented in the general population, such information is not available in T2DM. Methods We analyzed 467 consecutive male T2DM outpatients in whom OSAS was diagnosed through Epworth's Sleepiness Scale (ESS), overnight oximetry and polysomnography. OSAS (+) ( n = 43) were compared to OSAS (−) ( n = 424) regarding cardiovascular (CV) risk factors and/or MACE. Results Mean (1 SD) age was 64 (12) years, diabetes duration 13 (9) years. Metabolic syndrome prevalence was 77%, HbA 1c 7.6 (1.6) %. OSAS prevalence was 9%. There were no differences in age, diabetes duration, smoking, blood pressure and lipids between OSAS (+) and (−). There were significant differences in ESS score, ethanol intake, hypertension, BMI, waist, relative/absolute fat, conicity index, and visceral fat, all significantly higher in OSAS (+). Nasal continuous positive airway pressure was used by 37% of OSAS (+). HOMA hyperbolic product was significantly lower in OSAS (+), as a result of more severe insulin resistance. OSAS (+) were less often in primary prevention (PP) for CV disease than OSAS (−) (43% vs. 66%; p p p Conclusions OSAS is frequent in male T2DM patients. With gender and diabetes ruled out as confounders, our results indicate a strong association between OSAS and CV risk factors, such as hypertension, BMI, waist, relative/absolute/visceral fat, conicity, liver steatosis and hypoandrogenicity. Using the T2DM-specific UKPDS calculator, CVD risk estimates were high though not different between OSAS subgroups in primary CV prevention. OSAS patients with T2DM showed a marked increase in MACE/CAD, making a case for aggressive tertiary prevention.

Summary Aims An unfavourable upregulation of neurohormonal profile is present in type 2 diabetes (T2DM). Little is known regarding neurohormonal profile and cardiovascular (CV) risk in diabetic women in primary prevention. Methods We therefore explored gender-associated disparities in neurohormonal profile and modeled cardiovascular risk in this population ( n = 231) and modeled its 10-year risk of lethal and non-lethal coronary heart disease (CHD) and stroke using the UKPDS Risk Engine, a diabetes-specific risk calculator. Results There were significant differences between female and male patients ( n = 311) with respect to all measured neurohormones, which were higher in women by a mean 27% for N-terminal pro-atrial natriuretic peptide, 8% for Big endothelin-1 (Big ET-1), 25% for brain natriuretic peptide and 24% for urotensin II. While risk estimates for women were significantly lower than those in males with respect to non-fatal and fatal CHD, fatal CHD, non-fatal and fatal stroke, they were nevertheless worryingly high for females, reaching 68%, 72%, and 76% of the corresponding risks in males. Female patients with T2DM in primary prevention with a high prevalence of hypertension and metabolic syndrome (MetS) exhibit a significant sexual dimorphism in circulating neurohormones. Conclusions We conclude that these incremental differences may intervene in raising the true CV risk observed in female subjects with diabetes or insulin resistance, or in accruing the predicted risk computed by models such as the UKPDS Risk Engine.

Summary Background and objectives Insulin modulates key regulators of vascular tone, including endothelin-1 (ET-1), hence insulin resistance (IR) and/or hyperinsulinemia may contribute to the pathogenesis of hypertension and cardiovascular disease (CVD). Imbalance in ET-1/nitric oxide may link IR to CVD. Little is known on the relation between neurohormones, metabolic syndrome (MetS) categories (1–5/5) in type 2 diabetes (T2DM). We therefore sought to assess the relationship between neurohormonal profile, CVD and MetS in a large T2DM cohort, as well as the associations between neurohormones, insulinaemia, insulin sensitivity, CVD markers and events within MetS categories. Methods In 455 consecutive T2DM patients with or without MetS [MetS (+)/(−)] defined according to AHA/NHLBI , we assessed the following: MetS categories, HOMA-S, circulating Big-endothelin-1 (Big ET-1), natriuretic peptides and macroangiopathy [Macro (+)/(−)]. Results Big ET-1 was higher by 30%, in MetS (+) (median [IQ range]): 5.2 [4.3–6.0] pg ml −1 in MetS (−) ( n = 75) versus 6.7 [5.2–9.1] pg ml −1 in MetS (+) ( n = 380; P −1 in MetS (+) 3/5; 6.9 [5.1–9.4] pg ml −1 in MetS (+) 4/5 and 7.3 [5.6–9.5] pg ml −1 in MetS (+) 5/5 (NS). The incremental difference in Big ET-1 between MetS (+) and MetS (−) was found out both in the absence or presence of macroangiopathy: 4.55 [4.03–5.25] pg ml −1 in MetS (−) Macro (−) versus 5.70 [4.60–7.50] pg ml −1 in MetS (+) Macro (−) ( P −1 in MetS (−) Macro (+) versus 7.60 [5.80–10.13] pg ml −1 in MetS (+) Macro (+) ( P Conclusions Big ET-1 is raised in T2DM patients with MetS, and its level proceeds stepwise to MetS categories. Elevated Big ET-1 is present in all categories of MetS patients, with or without macroangiopathy. The ascent in Big ET-1 found in MetS (+) without macrovascular disease is of the same magnitude as that conferred by the presence of macroangiopathy.

Summary Objectives We sought to use the Discriminant Ratio (DR) method to compare the respective performance of low-density lipoprotein-cholesterol (LDL-C)/high-density lipoprotein (HDL)-C and apolipoprotein B (ApoB)/ApoA 1 ratios to rank diabetics according to dyslipidemia severity. Background ApoB/ApoA 1 was proposed as robust alternative to well-established LDL-C/HDL-C in ranking subjects according to their cardiovascular risk, while non-HDL-C was advocated as secondary target in metabolic syndrome. Nevertheless, the discriminatory superiority of these new markers remains unknown in diabetes. Methods Forty-five subjects with types 1 ( n = 23) and 2 diabetes ( n = 22) were studied. Total-, HDL-C and triglycerides were measured by enzymatic assays and ApoB and ApoA 1 by immunonephelometry. DR is the ratio of the underlying between-subject standard deviation (S.D.) to the within-subject S.D., calculated from log duplicates sampled on different days. Correlation coefficients between pairs of measurements were adjusted to include an estimate of the underlying correlation, since standard coefficients tend to underestimate the true correlation between tests due to the presence of within-subject variation. Results Mean values (day 1 (±1S.D.)) were 2.25 (0.87) for LDL-C/HDL-C, and 0.63 (0.20) for ApoB/ApoA 1 , respectively. The highest DRs were those of total C/HDL-C and non-HDL-C/HDL-C (2.33 and 2.38; p 1 (2.12) was non-significantly higher than that of LDL-C/HDL-C (1.45). Conclusions ApoB/ApoA 1 does not provide greater discrimination than LDL-C/HDL-C to rank a diabetic population. The best approach is obtained with total C/HDL-C and new candidate marker non-HDL-C/HDL-C, both easy and cost-effective means to stratify diabetics according to their lipid profile.

We investigated whether ranolazine therapy improves exercise-induced angina pectoris and myocardial ischemia compared with placebo or with standard doses of atenolol in patients who had chronic angina and evaluated the effects on hemodynamics at rest and during exercise. In this trial, 158 patients who had symptom-limited exercise discontinued beta-blocker therapy and were randomized into a double-blind, 3-period, crossover study of 400 mg of immediate-release ranolazine 3 times daily, 100 mg/day of atenolol, or placebo, each administered for 1 week. Exercise tests were administered at the end of each treatment period. Therapy with ranolazine or atenolol produced statistically significant improvement in all 3 exercise end points compared with placebo. Compared with atenolol therapy, ranolazine therapy resulted in significantly longer total exercise duration and was statistically indistinguishable from atenolol for time to onset of angina and ST-segment depression. Except for a modest increase in systolic blood pressure at peak exercise during ranolazine therapy, hemodynamic measurements did not differ significantly during ranolazine and placebo therapies. In contrast, atenolol significantly decreased blood pressure, heart rate, and rate-pressure product at rest and during exercise compared with placebo or ranolazine. In conclusion, ranolazine therapy prolonged exercise duration and decreased exercise-induced ischemia and angina with quantitative effects equal to or greater than those with atenolol. Unlike atenolol, the anti-ischemic and antianginal effects of ranolazine occurred without decreases in blood pressure, heart rate, or rate-pressure product.

BACKGROUND: Plasma concentrations of atrial and brain natriuretic peptides (ANP, BNP), of their N-terminal pro-peptides, of endothelin-1 (ET-1), and big endothelin-1 (big ET-1) have diagnostic and prognostic significance in congestive heart failure (CHF). However, their respective values as a predictor of survival remain controversial and have never been directly compared in severe CHF. METHODS AND RESULTS: We analyzed, in 47 patients with severe CHF (New York Heart Association [NYHA] class III to IV; age 66 +/- 8 years, ejection fraction 20 +/- 6%), the prognostic performance of a panel of neurohormones and assays (N-terminal pro-ANP 1-25, 68-98 by radioimmunoassay [RIA], and 1-98 by enzyme-linked immunosorbent assay [ELISA], BNP by RIA and immunoradiometric assay [IRMA], N-terminal pro-BNP by Elisa, ET-1 by RIA, and big ET-1 by RIA and Elisa. Data were compared with 40 patients with mild to moderate CHF [NYHA I-II] and 30 healthy subjects. After a follow-up of 81 +/- 15 months, there were 34 deaths and 1 heart transplant. All neurohormones were significantly higher at baseline in patients with severe than in mild to moderate CHF or healthy subjects (all P < .001). Although all neurohormones but BNP IRMA were significant predictors of survival in univariate analysis, only big ET-1 RIA and ET-1 were independent predictors of survival (improvement chi(2): 7.5 and 4.6, P < .01 and P < .05). Using medians as cutpoints of big ET-1 RIA and ET-1, 2 severe CHF populations were defined with a different outcome (5-year survival: 55 versus 18%, P < .01). CONCLUSIONS: Big ET-1 and ET-1 are strong independent predictors of survival in patients with severe CHF and better for this purpose than natriuretic peptides or their pro-peptides. These markers allow easily to identify a population with a very high risk mortality eligible for more aggressive therapies.

Background In the studies of left ventricular dysfunction (SOLVD), enalapril reduced mortality in patients with symptomatic but not asymptomatic left ventricular systolic dysfunction during the trial. We did a 12-year follow-up of SOLVD to establish if the mortality reduction with enalapril among patients with heart failure was sustained, and whether a subsequent reduction in mortality would emerge among those with asymptomatic ventricular dysfunction. Methods Of the 6797 patients previously enrolled in the SOLVD prevention and treatment trials, we ascertained the subsequent vital status of 5165 individuals who were alive when the trials had been completed. Follow-up was done through direct contacts in Belgium and linkages with national death registries and federal beneficiary or historic tax summary files in the USA and Canada. Findings Follow-up was 99.8% (6784/6797) complete. In the prevention trial, 50.9% (1074/2111) of the enalapril group had died compared with 56.4% (1195/2117) of the placebo group (generalised Wilcoxon p=0.001). In the treatment trial, 79.8% (1025/1285) of the enalapril group had died compared with 80.8% (1038/1284) of the placebo group (generalised Wilcoxon p=0.01). The reductions in cardiac deaths were significant and similar in both trials. When data for the prevention and treatment trials were combined, the hazard ratio for death was 0.90 for the enalapril group compared with the placebo group (95% Cl 0.84-0.95, generalised Wilcoxon p=0.0003). Enalapril extended median survival by 9.4 months in the combined trials (95% CI 2.8-16.5, p=0.004). Interpretation Treatment with enalapril for 3-4 years led to a sustained improvement in survival beyond the original trial period in patients with left ventricular systolic dysfunction, with an important increase in life expectancy.

OBJECTIVES: We sought to evaluate the effects of spironolactone on neurohormonal factors in patients with severe congestive heart failure (CHF). BACKGROUND: In the Randomized ALdactone Evaluation Study (RALES), spironolactone, an aldosterone receptor antagonist, significantly reduced mortality in patients with severe CHF. However, the mechanism of action and neurohormonal impact of this therapy remain to be clarified. METHODS: The effects of spironolactone (25 mg/day; n = 54) or placebo (n = 53) on plasma concentrations of the N-terminal portion of atrial natriuretic factor (N-proANF), brain natriuretic peptide (BNP), endothelin-1 (ET-1), norepinephrine (NE), angiotensin II (AII), and aldosterone were assessed in a subgroup of 107 patients (New York Heart Association functional class III to IV; mean ejection fraction 25%) at study entry and at three and six months. RESULTS: Compared with the placebo group, plasma levels of BNP (-23% at 3 and 6 months; p = 0.004 and p = 0.05, respectively) and N-proANF (-19% at 3 months, p = 0.03; -16% at 6 months, p = 0.11) were decreased after spironolactone treatment. Over time, spironolactone did not modify the plasma levels of NE and ET-1. Angiotensin II increased significantly in the spironolactone group at three and six months (p = 0.003 and p = 0.001, respectively). As expected, a significant increase in aldosterone levels was observed over time in the spironolactone group (p = 0.001). CONCLUSIONS: Spironolactone administration in patients with CHF has opposite effects on circulating levels of natriuretic peptides (which decrease) and aldosterone and AII (which increase). The reduction in natriuretic peptides might be related to changes in left ventricular diastolic filling pressure and/or compliance, whereas the increase in AII and aldosterone probably reflects activated feedback mechanisms. Further studies are needed to link these changes to the beneficial effects on survival and to determine whether the addition of an AII antagonist could be useful in this setting.

OBJECTIVES We investigated the acute and long-term hemodynamic and neurohumoral effects of the vasopeptidase inhibitor omapatrilat in human heart failure. BACKGROUND Angiotensin-converting enzyme (ACE) inhibition constitutes a major advance in the treatment of chronic heart failure (CHF). Simultaneous inhibition of both neutral endopeptidase and ACE with omapatrilat may represent a new treatment strategy in CHF. METHODS Three hundred and sixty-nine patients with symptomatic heart failure were randomized to double-blind treatment with omapatrilat (first 190 patients: 2.5 mg, 5 mg or 10 mg; last 179 patients: 2.5 mg, 20 mg or 40 mg once daily) for 12 weeks. RESULTS Acutely, the 10 mg, 20 mg and 40 rug doses of omapatrilat produced greater reductions in pulmonary capillary, wedge pressure (PCWP), systolic blood pressure (SBP) and systemic vascular resistance compared with 2.5 mg. Higher doses were associated with greater increases in vasodilator and natriuretic peptides, in addition to ACE inhibition. After 12 weeks, omapatrilat 20 mg and 40 mg showed greater fills from baseline in PCWP (40 mg: 0 h to 12 h average change -7.3 +/- 0.8 mm Hg) and SBP (40 mg: -11.7 +/- 1.7 min Hg) than 2.5 mg (both p < 0.01 vs. 2.5 mg). The incidence of adverse experiences and patient withdrawal were similar in all groups. CONCLUSIONS In CHF, the acute hemodynamic benefit seen with higher doses of omapatrilat was associated with increases in plasma vasodilator and natriuretic peptide levels in addition to ACE inhibition. After 12 weeks, the hemodynamic benefit was maintained. Omapatrilat may be a promising new agent in CHF.

The available data suggest that Urocortin (UCN), a cardioprotective and vasoactive peptide known from fish neuroendocrinology, is involved in cardiac regulation. The aim of this study was to determine UCN plasma concentrations in patients with heart failure (HF). Plasma concentrations of UCN were measured in 42 fully treated HF patients. UCN was determined using a specific ELISA assay after acidic extraction using Sep-Pak C18 columns. Circulating levels of other neurohormones Nt-proBNP, Nt-proANP and Big ET-1 were also determined. Reference values for these were obtained from 20 healthy age- and sex-matched subjects. In comparison with controls, UCN plasma concentrations (geometric mean [95% CI]) were significantly increased in HF patients (88 pmol/L [75-105] vs 46 [39-54], p

Introduction L'analyse d'essais cliniques historiques indique une augmentation du risque de coronaropathie liee au LDL-C a l'inclusion, en particulier en cas de diabete de type 2, tant en prevention primaire (PP) que secondaire (PS). Nous avons examine dans quelle mesure la prevalence de diabete au debut d'une etude predit l'incidence de cardiopathie ischemique, de maniere a etablir une equation associant la survenue d'evenements cardiovasculaires (CV) au pourcentage de patients diabetiques enroles. Patients et methodes Meta-analyse des groupes controles [ n =107 144] de 29 grands essais cliniques de PP et/ou de PS. Ces etudes ont inclus 212 850 patients [âge moyen (1ET) 62 6 ans ; 81 % d'hommes ; 85 % Caucasiens]: 4S ; AFCAPS/Tex-CAPS ; AIM-HIGH ; ALERT ; ALLHAT-LLT ; Alpha-Omega ; ASCOT-LLA ; AURORA ; BIP ; CARE ; CDP ; dal-OUTCOMES ; GISSI-Preven-zione ; GREACE ; HHS ; HPS-MRC/BHF ; HPS2-THRIVE ; IDEAL ; ILLUMINATE ; LEADER ; LIPID ; LIPS ; PERFORM ; Post-CABG ; PROSPER ; SHARP ; TNT ; VA Cooperative Study ; VA-HIT ; and their DM substudies: 4S ; ASCOT-LLA ; AURORA ; CARE ; GREACE ; HHS ; HPS-MRC/BHF ; TNT ; & VA-HIT. Resultats La prevalence moyenne du diabete etait de 21 11 % ( n =51 632). Sur un suivi moyen de 4,2 (1,5) ans, 12 767 evenements CV majeurs ont ete enregistres dans les bras comparateur/placebo, correspondant a un taux moyen de 3,7 (2,0) %/an. Il y avait une relation lineaire significative ( p =0,0041) entre la survenue d'evenements CV majeurs (y ; %/an) et la prevalence du diabete (x ; %) selon l'equation (y=0.031.x + 3,06). Celle-ci permet de determiner le pourcentage annuel de survenue d'evenements CV attribuable a la frequence de diabete au debut d'un essai clinique. Ce pourcentage varie de 3,1 %/an (aucun diabetique inclus) a 6,2 %/an (100 % de diabetiques). Conclusion Cette meta-analyse montre que la relation entre la prevalence de diabete a la randomisation et l'incidence d'evenements CV est substantielle et lineaire. Une composante significative de survenue de cardiopathie ischemique peut ainsi etre deduite du pourcentage de diabetiques presents a l'inclusion. Declaration d’interet Les auteurs declarent ne pas avoir d'interet direct ou indirect (financier ou en nature) avec un organisme prive, industriel ou commercial en relation avec le sujet presente.

OBJECTIVES: The aim of this study was to assess the cardiovascular effects of BAY y 5959, a calcium promoter modulating myocardial calcium channels, in the presence or absence of congestive heart failure. BACKGROUND: There is still a clinical need for short-term administration of intravenous positive inotropes. BAY y 5959 was developed as a new approach to increase myocardial performance by selectively enhancing calcium influx in the myocytes. METHODS: Forty-one patients (21 without and 20 with congestive heart failure) were studied in an open label, dose-ranging study. Hemodynamic variables (including left ventricular [LV] angiography) and plasma samples were obtained at baseline and after 20 min of intravenous infusion of BAY y 5959 at doses ranging from 0.25 to 4.5 microg/kg body weight per min. RESULTS: In both study groups, BAY y 5959 produced dose-dependent increases in the indexes of inotropic state, without affecting isovolumetric relaxation rate. The magnitude of the response was comparable in patients with or without heart failure (average 38% increase in maximal first derivative of LV pressure [dP/dt max] at plasma levels of 100 microg/liter). BAY y 5959 also induced mild but statistically significant bradycardia and significantly decreased end-systolic volume while producing a leftward shift of the pressure-volume loop. Mean aortic pressure was unaffected at doses up to 3.0 microg/kg per min, and cardiac index improved in patients with heart failure at doses of 2.0 microg/kg per min (+23%, p < 0.05). However, at a dose of 4.5 microg/kg per min, mean aortic pressure and LV systolic wall stress increased, suggesting systemic vasoconstriction. The QT interval was also prolonged significantly at most doses. CONCLUSIONS: BAY y 5959 exhibits positive inotropic effects in patients with and without heart failure. The optimal response--combining bradycardia, reduced preload and improved cardiac output--appeared to be achieved at a dose of approximately 2.0 microg/kg per min. The impact of QT prolongation with regard to potential antiarrhythmic or proarrhythmic effects is unclear at this time.

OBJECTIVES: This study sought to assess the hemodynamic and cardiac effects of two dose levels of mibefradil in patients with varying degrees of ischemic left ventricular dysfunction. BACKGROUND: Mibefradil is a new, selective T-type and L-type calcium channel blocking agent. Because L-type channel blockade may depress myocardial performance, an invasive hemodynamic study was performed to assess the safety of this agent. METHODS: We performed an open label study, examining the effects of two intravenous doses of mibefradil, selected to produce plasma levels comparable to those measured after oral administration of 50 mg (dose 1: 400 ng/ml) or 100 mg (dose 2: 800 ng/ml) of the drug. Variables studied included the indexes of left ventricular function and neurohormone levels. Patients were stratified according to ejection fraction (EF) (> or = 40%, n = 26; < 40%, n = 24) and the presence (n = 15) or absence (n = 35) of heart failure. RESULTS: In patients with preserved systolic function, dose 1 had no clinically significant hemodynamic effects, but dose 2 decreased mean aortic pressure and systemic vascular resistance (-8.5 mm Hg, -12%, both p < 0.01) and also reduced end-systolic stress and volume, thus improving EF (52% to 58%, p < 0.01). Heart rate tended to decrease. In patients with depressed EF, heart rate decreased significantly with both doses. The effects of dose 1 mimicked those observed after dose 2 in patients with preserved EF. Dose 2 (plasma levels 1,052 +/- 284 ng/ml) still decreased left ventricular systolic wall stress and improved EF (24.0% to 28.5%, p < 0.05) but also significantly depressed the maximal first derivative of left ventricular pressure. Examination of individual pressure-volume loops in two patients with heart failure showed a clear rightward shift of the loop despite a decrease in systolic pressure, suggesting negative inotropy. Neurohormone levels were unchanged at both dose levels and in all subgroups. CONCLUSIONS: Intravenous mibefradil was well tolerated and produced an overall favorable cardiovascular response. However, high plasma concentrations might produce myocardial depression in patients with heart failure, and caution should be exerted in this setting.

In the Studies of Left Ventricular Dysfunction (SOLVD), treatment with enalapril reduced short-term mortality for patients with symptomatic but not asymptomatic left ventricular systolic dysfunction. We reported here data from a 27-year follow-up of SOLVD to determine the long-term effect of early

To assess the long-term changes in cardiac function in asymptomatic patients with severe left ventricular dysfunction, left ventricular (cineangiography) and right ventricular (radionuclide angiography) function were assessed at baseline in 49 patients enrolled in the prevention arm of the Studies of Left Ventricular Dysfunction. After an average follow-up period of 12.4 months, 30 patients (11 randomized to the placebo group and 19 to the enalapril group) could be restudied to assess the progression of ventricular dysfunction. After 1 year of follow-up, the changes in heart rate, left ventricular end-diastolic and systolic pressure and right ventricular volumes were comparable in both groups. However, there were modest but opposite changes in left ventricular end-diastolic volume (+ 9 ml/m2with placebo vs. −10 ml/m2with enalapril, p < 0.05) and end-systolic volume (+ 5 ml/m2with placebo vs. −13 ml/m2with enalapril, p < 0.05). Mean systolic wall stress increased insignificantly in both groups, whereas ejection fraction increased from 29% to 31% in the placebo group and from 28% to 32% with enalapril (p = NS, placebo vs. enalapril).Even in asymptomatic patients with severe left ventricular dysfunction, there was a slow progression of left ventricular dilation. Enalapril administration appeared to slow this progression, but wall stress was not normalized by the treatment at the doses used in the study, indicating that at least one of the stimuli for further remodeling remained present.

Left ventricular (LV) diastolic filling is impaired in hearts with healed myocardial infarction. Possible hemodynamic parameters related to impaired LV filling include left atrial pressure, time constant of isovolumic relaxation, chamber stiffness and wall motion asynchrony. Previous studies demonstrated univariate correlations between each of these parameters and LV filling. The current study was designed to compare relative importance of these parameters in patients with a myocardial infarction. Left ventriculograms with simultaneous LV pressure measurement were analyzed in 15 patients with a myocardial infarction and in 10 control subjects. Every frame of the left ventriculogram was divided into 8 segments and the volume of each segment was obtained frame-by-frame by planimetry and area-length method. Asynchrony was quantitated as the sum of areas of discrepancy between each segmental and global volume-time curve. Patients with myocardial infarction had greater asynchrony (20 +/- 2 vs 10 +/- 1%, p < 0.01), greater atrial filling fraction (46 +/- 4 vs 35 +/- 5%, p < 0.05) and slower peak early filling rate (2.5 +/- 0.1 vs 4.1 +/- 0.4 end-diastolic volume/s, p < 0.01) than the control subjects. Multiple regression analyses with hemodynamic variables (asynchrony, LV pressure at mitral valve opening, time constant of LV isovolumic pressure decrease and LV chamber stiffness constant) showed that asynchrony and LV pressure at mitral valve opening were significant determinants of LV filling in patients with myocardial infarction, whereas LV pressure at mitral valve opening was the only significant determinant in control subjects.

T he internal mammary artery is considered the best available conduit for coronary artery bypass grafting.1-4 The high long-term patency rate of mammary artery grafts as opposed to saphenous vein grafts seems to result from favorable biologic properties that could protect this vessel against the atherosclerotic process. Recent studies have emphasized the role of endothelium in triggering or modulating mechanisms controlling the growth, metabolism and contractile status of smooth muscle cell~.~-r~ Endothelial cells produce 2 agents, prostacyclin and endothelium-derived relaxing factor (EDRF). Both are able to modulate the vasomotor tone and to prevent platelet adhesion and aggregation, which may be implicated in atherogenesis. Major differences, however, exist among different vessels in the amount of EDRF released in basal conditions, in the agents stimulating its production and in the sensitivity of vascular smooth muscle to that factor.9J0 Similarly, various areas of the vascular system are different in their ability to produce prostacyclin. l 1,12 Although laboratory experiments have demonstrated the potent role of endothelium in modulating the effects of vasoconstrictor agents in segments of internal mammary arteries, obtained intraoperatively from patients, 9~13 the vasomotor response of human mammary arteries to pharmacologic constrictor agonists has not been studied in vivo. We evaluated the effect on internal mammary artery diameter of an intravenous infusion of methylergometrine maleate, a powerful constrictor agent, before and after grafting on the coronary vessels. Additionally, we tried to evaluate the vasodilator reserve of ungrafted and grafted mammary arteries by intraarterial infusion of isosorbide dinitrate. Nineteen men (mean age 58 years; range 41 to 69) were studied during diagnostic cardiac catheterization.

Soluble fms-like tyrosine kinase-1 (sFlt-1) is an endogenous inhibitor of endothelial growth factors involved in cardiovascular (CV) remodeling. Our objectives were to determine sFlt-1 levels in heart failure (HF) patients with reduced ejection fraction (EF) as well as its relationship with

Introduction Un taux abaisse en 25 (OH) vitamine D (vitD) est frequent, chez les diabetiques de type 2 (DT2). Chez des sujets non-diabetiques, une association inverse a ete rapportee entre vitD et triglycerides (TG). La dyslipidemie atherogene (DA) est frequente dans le DT2, et est caracterisee par la presence conjointe d’un abaissement du HDL-C et d’une elevation des TG a jeun. Le but du travail etait de documenter l’association entre la vitD et le phenotype cardiometabolique de patients DT2, notamment la presence et/ou la severite de la DA. Patients et methodes 208 patients DT2 (âge moyen (1 ET) 67 (11) ans ; duree du diabete 16 (10) ans) ont ete divises en 2 groupes, selon la vitD : un groupe quartile inferieur [QI] (n = 52) de vitD (taux moyen 7,6 (2,1) sng/mL), et un groupe combinant les quartiles II a IV [QII-IV] (n = 156), chez lesquels le taux moyen de vitD etait 21,5 (8,2) ng/mL. Resultats L’utilisation d’hypolipemiants (statines-fenofibrate-ezetimibe) etait semblable dans les 2 groupes (%): 77–31–4 [QI] vs. 79–23–8 [QII-IV]. Il existait des differences significatives entre les 2 groupes concernant : les TG a jeun : 213 (119) [QI] vs. 182 (124) mg/dL [QII-IV] (p 0,0277) ; la proportion de patients avec TG a jeun Conclusion Les patients DT2 avec un taux abaisse de vitD sont caracterises par une hypertriglyceridemie nette et une dyslipidemie atherogene plus prononcee que les DT2 avec des taux plus eleves en vitD. L’hypovitaminose D dans le DT2 est par consequent associee a un risque residuel cardiovasculaire plus eleve du fait d’une dyslipidemie atherogene non associee aux LDL.