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Natriuretic peptides are widely used in clinical practice as cardiac markers for early diagnosis, prognosis and for the monitoring of treatment efficiency of heart Failure (HF). According to the clinical relevance of natriuretic peptides testing, it is important to assess the performances of novel platform for testing. Our study showed the overall good performances of a new NT-proBNP ABEI-based automated immunoassay.

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 [...]

Purpose: Non-alcoholic fatty liver (NAFL) is comorbid to obesity, metabolic syndrome and type 2 diabetes mellitus (T2DM). It is unclear whether NAFLD constitutes a direct risk factor for macrovascular disease in T2DM. This study aimed at revisiting the cardiometabolic traits linked to NADL and micro-/ macrovascular complications in a biethnic Caucasian and African cohort. Methods: Cross-sectional analysis of 568 of T2DM patients (515 Caucasians; 53 Africans) in whom the presence of NAFL was identified by ultrasonography and the cardiometabolic phenotype was exhaustively characterized, including carbohydrate homeostasis, comprehensive lipidogram including Lp(a), cumulative exposure to hyperglycemia, and prevalent micro/macrovascular complications. Results: FL was present in 73% of Caucasians and 36% of Africans (p − in both groups. A marked reduction in diabetic retinopathy (DR), ocular hypertonia and cataracts were found in FL+ of the two ethnicities. In FL+ Caucasians, relative risk of DR was −38%, cataracts −35%, and ocular hypertonia −42%. In FL+ Africans, risk of overall microangiopathy was −66% and that of DR −86%. Conclusions: An inverse association was observed between NAFL and the presence of diabetic retinopathy, cataract and ocular hypertonia. The ophthalmoprotection conferred by liver steatosis was found in Caucasians and Africans. Among the latter, hepatic steatosis was linked to lower lipoprotein(a) levels. There was no association between hepatic steatosis and prevalent macrovascular complications in neither of the two ethnic groups.

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.

Background: Pulmonary transit time (PTT) from first-pass perfusion imaging is a novel parameter to evaluate hemodynamic congestion by cardiac magnetic resonance (cMR). We sought to evaluate the additional prognostic value of PTT in heart failure with reduced ejection fraction over other well-validated predictors of risk including the Meta-Analysis Global Group in Chronic Heart Failure risk score and ischemic cause. Methods: We prospectively followed 410 patients with chronic heart failure with reduced ejection fraction (61±13 years, left ventricular (LV) ejection fraction 24±7%) who underwent a clinical cMR to assess the prognostic value of PTT for a primary endpoint of overall mortality and secondary composite endpoint of cardiovascular death and heart failure hospitalization. Normal reference values of PTT were evaluated in a population of 40 asymptomatic volunteers free of cardiovascular disease. Results PTT was significantly increased in patients with heart failure with reduced ejection fraction as compared to controls (9±6 beats and 7±2 beats, respectively, P 2 to improve, 12.3; hazard ratio, 1.35 [95% CI, 1.16–1.58]; P 2 to improve=20.1; hazard ratio, 1.23 [95% CI, 1.21–1.60]; P Conclusions: Despite limitations in temporal resolution, PTT derived from first-pass perfusion imaging provides higher and independent prognostic information in heart failure with reduced ejection fraction than clinical and other cMR parameters, including LV and RV ejection fraction or feature tracking global longitudinal strain. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03969394.

BACKGROUND: New recommendations call for lowering LDL-C < 55 mg/dL and non-HDL-C < 85 mg/dL in very-high cardiovascular risk (VH-CVR) patients with type 2 diabetes (T2DM). This study assessed the proportion of VH-CVR diabetics currently meeting these primary and secondary lipid targets, and which therapies/phenotypes predict combined goals achievement. METHODS: We analysed the cardiometabolic phenotype, use of lipid-modulatind drugs (LMD), pre- and post-LMD lipids levels, and CV complications among 1196 T2DM with high (n = 221; 18%) or VH-CVR (n = 975; 82%). Among the latter, the characteristics of combined lipid goal-achievers (n = 158) were compared to those of non-achievers (n = 817), with subgroup analyses of on-statin patients (n = 732) and those with established CVD taking statins (n = 362). Presence of statin-associated muscle symptoms (SAMS) was also recorded. RESULTS: 75% of VH-CVR patients were on statins. Both LDL-C and non-HDL-C goals were achieved by 16.2% of all VH-CVR, 19.3% of on-statin VH-CVR, and 24.3% of patients with established CVD taking statins. Achieving both targets was associated with high-intensity statins, specifically rosuvastatin, [statin + ezetimibe] combination, lower baseline LDL-C, smaller LDLs, lower TG and lipoprotein(a), and reduced metabolic syndrome frequency. SAMS reporting did not differ between achievers and non-achievers. CONCLUSIONS: More than 80% of patients are above targets. To bridge this gap, apart from treating more LMD-naive/refractory diabetics, one should consider for LDL-C to put most patients on high-intensity statins, more often with ezetimibe and, within statins, to switch preferably to rosuvastatin. As regards non-HDL-C, the off-target patients' phenotype suggests that intensifying lifestyle measures against metabolic syndrome should supplement current therapies.

Background Lipoprotein(a) (Lp(a)), a variant low-density lipoprotein (LDL), is a major genetic risk factor for cardiovascular disease. It is unknown whether an inverse relationship exists between Lp(a) and β-cell function (BCF), as for LDL-cholesterol (LDL-C) lowering by statins. We therefore assessedthe cardiometabolic phenotype of 340 men with type 2 diabetes mellitus (T2DM) in relation to Lp(a), focusing on BCF and hyperbolic product [BxS], which adjusts BCF to insulin sensitivity and secretion. Methods Two groups were analyzed according to Lp(a) quartiles (Q): a (very-)low Lp(a) (Q1;n = 85) vs a normal-to-high Lp(a) group (Q2-Q4;n = 255). Results In the overall cohort, mean Lp(a) was 52 nmol.L−1. Median Lp(a) was 6 nmol.L−1 (Q1) vs 38 nmol.L−1 (Q2-Q4). There were no differences between groups regarding age; education; diabetes duration; body mass index; body composition and smoking. Q1 had significantly worse glycemic control, higher systolic blood pressure, more severe metabolic syndrome, and more frequent hepatic steatosis. Insulin sensitivity was significantly lower (− 37%) in Q1, who also had lesser hyperbolic product (− 27%), and higher [BxS] loss rate (+ 15%). Q1 also had higher frequency (+31%) and severity (+20%) of atherogenic dyslipidemia. Microangiopathy and neuropathy were higher in Q1 (+ 34% and + 48%, respectively), whereas Q2-Q4 patients had increased macroangiopathy (+ 51%) and coronary artery disease (CAD; + 94%). Conclusions Low Lp(a) appears both beneficial and unhealthy in T2DM. It is associated with unfavourable cardiometabolic phenotype, lesser BCF, poorer glycemic control, and increased microvascular damage despite being linked to markedly reduced CAD, suggesting that Lp(a)-related vascular risk) follows a J-shaped curve.

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.

Aims Besides regulating calcium‐phosphate metabolism, fibroblast growth factor 23 (FGF‐23) has been associated with incident heart failure (HF) and left ventricular hypertrophy. However, data about FGF‐23 in HF and preserved ejection fraction (HFpEF) remain limited. The aim of this study was to assess the association between FGF‐23 levels, clinical and imaging characteristics, particularly diffuse myocardial fibrosis, and prognosis in HFpEF patients. Methods and results We prospectively included 143 consecutive HFpEF patients (78 ± 8 years, 61% female patients) and 31 controls of similar age and gender (75 ± 6 years, 61% female patients). All subjects underwent a complete two‐dimensional echocardiography and cardiac magnetic resonance with extracellular volume (ECV) assessment by T1 mapping. FGF‐23 was measured at baseline. Among the patients, differences in clinical and imaging characteristics across tertiles of FGF‐23 levels were analysed with a trend test across the ordered groups. Patients were followed over time for a primary endpoint of all‐cause mortality and first HF hospitalization and a secondary endpoint of all‐cause mortality. Median FGF‐23 was significantly higher in HFpEF patients compared with controls of similar age and gender (247 [115; 548] RU/mL vs. 61 [51; 68] RU/mL, P

Background and aims In type 2 diabetes mellitus (T2DM), sexual dimorphisms modulate the natural histories of hyperglycemia, anthropophysical/cardiometabolic phenotype, and susceptibility to chronic micro and macrovascular complications. The purpose of this work was to revisit known or new dimorphisms within a multiethnic cohort. Methods Among 1238 T2DM patients, men (63%) were compared to women (37%), including leading ethnicities: Whites (67.4%; 542 men; 293 women); Maghrebians (9.4%; 62 men; 54 women); and Blacks (12.5%; 92 men; 63 women). Results Age, BMI, diabetes duration, insulin sensitivity, B-cell function loss, HbA1c, and hyperglycemia index were similar in both genders. All-cause microangiopathy and cerebrovascular disease did not differ between sexes. Women had significantly more retinopathy (27% vs. 21%) and men more microalbuminuria (25% vs. 19%), all-cause macroangiopathy (40% vs. 26%), CAD (29% vs. 17%) and PAD (11% vs. 6%). Among Blacks, sexual dimorphism in terms of retinopathy was more pronounced (24% in women vs. 11%), while there was no sexual dimorphism in all-cause macroangiopathy, CAD or PAD. B-cell function loss was faster among North African men (+15%), who also had more hepatic steatosis (+27%) than women. Conclusions T2DM abolishes the CV protection provided by the female gender in Blacks. In White women, the loss of CV protection in diabetes is limited to cerebrovascular disease. In Black women, a markedly increased risk of retinopathy is present, despite glycemic exposure similat to men. Sexual dimorphisms do not affect glucose homeostasis and metabolic control in all ethnicities, except for lesser B-cell function loss in Maghrebian women.

Background Assessment of congestion and cardiac function has been shown to have both therapeutic and prognostic implication for the management of patient with CHF. Pulmonary transit time (PTT) assessed by cMR is a novel parameter, which reflects not only hemodynamic congestion but also LV and RV function. Purpose We sought to explore the prognostic value of the pulmonary transit time assessed in seconds (PTT) and in beats (PTB) and the pulmonary blood volume indexed (PBVi) above conventional well-known risk factors including cMR-RVEF and estimated pulmonary artery pressure (eSPAP) in predicting outcomes. PBVi is defined by the product of PTB and the stroke volume indexed to body surface area. Methods 401 patients in sinus rhythm with a LVEF Results Average cMR-LVEF was 23±7%, cMR-RVEF was 43±15%, average estimated systolic pulmonary pressure (eSPAP) was 33±12mmH, average PTT was 11±6s, PTB 8.9±5.6 bpm and average PBVi 305.5±254.9ml/m2. After a median follow-up of 6 years, 182 reached the primary endpoint. In univariate cox regression, age, ischemic cardiomyopathy, hypertension, diabetes, NYHA class III-IV, eSPAP >40mmHg, E/A ratio, e/e'ratio, cMR-RVEF, LV scar, PTT, PTB, PBVi, GFR, beta blockers and diuretics were associated with overall mortality. For the multivariate analysis, a baseline model was created where age, ischemic etiology, NYHA functional class III-IV, eSPAP >40 mmHg, beta-blockers and cMR-RVEF were found to be significantly and independently associated with the primary endpoint. PTT (X2 to improve = 5.3, HR: 1.03; 95% CI: [1.01; 1.06]; P=0.015), PTB (X2 to improve = 11.8, HR: 1.06; 95% CI: [1.03; 1.09]; P Conclusion Pulmonary transit time and pulmonary blood volume provide higher prognostic information over well-known risk factors including cMR-RVEF and eSPAP with high power to stratify prognosis in HF-rEF and might be promising tools to identify patients at higher risk among HF patients. Acknowledgement/Funding Fond National de recherche scientifique (FNRS)

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.

Background The usefulness of C-reactive protein (CRP) to predict cardiovascular disease (CVD) in type 2 diabetes (T2DM) remains controversial. As many factors linked to obesity can modulate CRP in T2DM, we comprehensively revisited the cardiometabolic phenotype of patients with normal or raised CRP, taking into account the sexual dimorphism of its serum value. Methods 1005 T2DM patients (651 males, 354 females; macroangiopathy 38%; coronary artery disease 26%; microangiopathy 47%) were divided depending on whether CRP level was ≤ or >3 mg/L. Thirty percent of men (n = 195) and 39% of women (n = 137) had raised CRP. Their cardiometabolic phenotype and presence of micro- and macrovascular complications were compared to those with normal CRP. Results In both gender, patients with elevated CRP had higher body mass index, waist circumference, fat mass, visceral fat, insulinemia, HbA1c, and lower muscle mass and insulin sensitivity. They had more atherogenic dyslipidemia, higher non-HDL-C and apolipoprotein B100, and more lipoprotein(a) (+59% in men and +38% in women). In both sexes, there was no difference between patients with normal or high CRP regarding overall macroangiopathy (42% vs. 45% [men]; 27% vs. 28% [women]), coronary and peripheral artery disease, or stroke. Only in men, microangiopathy was more prevalent when CRP was raised (61% vs 44%; p Conclusions This study shows major sex-related differences in microangiopathies in T2DM patients with high CRP levels. The latter are unrelated to prevalent CVD despite an unfavorable metabolic phenotype. By contrast, increased CRP may represent an extended biomarker of microvascular risk in men with T2DM.

Fibroblast growth factor 23 (FGF-23), a key hormone for the regulation of the phosphorus homeostasis, has also several direct effects on cardiac function. In heart failure (HF), the increase of FGF-23 participates to cardiac hypertrophy and remodeling. Measurement of the intact, biologically active hormone is now available. We determined intact FGF-23 in HF patients with reduced ejection fraction and assess its prognosis value for cardiovascular death over a long-term follow-up. We observed that intact FGF-23 is an independent predictor of cardiovascular death in HF patients and provides added value to the standard of care, natriuretic peptide, for risk estimation.

Background: We previously reported that T2DM patients with elevated lipoprotein(a) [Lp(a)] were characterized by lesser insulin resistance and high frequency of left-handedness. Objective: The aim of this work was therefore to characterize the lipids and lipoproteins in T2DM, to see if there were quantitative or qualitative differences depending on motor laterality. Methods: The cardiometabolic phenotype of 517 Caucasian patients with type 2 diabetes (T2DM) was determined according to laterality, 444 patients being right-handed (RHs; 86%) and 73 left-handed or ambidextrous (non-RHs; 14%). Besides routine lipids, Lp(a), non-Lp(a)-LDL-C, apoB100, apoA-I, and atherogenic dyslipidemia were also measured, including pre-/post-statin levels in treated paitients. Results: Non-RHs had a stronger family history of early-onset CVD, were more insulin- sensitive, and were less often treated with insulin. RHs and non-RHs did not differ as regards use and intensity of statins, routine lipids, apoB100, apoA-I, prevalence/severity of atherogenic dyslipidemia, and LDL size. In contrast, Lp(a) levels were significantly higher in non-RHs (median 37.0 vs. 18.7 nmol/L in RHs; p 0.0018), resulting in 32% of non-RHs having pathological Lp(a) vs. 20% in non-HRs (p 0.0467). Although pre-statin LDL-C was 15% higher in non-RHs, partly related to higher Lp(a), on-statin LDL-C did not differ between groups, suggesting better response/compliance to statins. Conclusion: Lp(a) levels are twice as high in left-handed diabetic patients, while routine lipids and lipoproteins are unaffected by motor laterality. Elevated Lp(a) in left-handers also underlies higher LDL-C before statins, yet on-treatment LDL-C in left-handers decreased more after statins than that of right-handers, hinting to better compliance and/or greater response to statins. Disclosure M.P. Hermans: Speaker's Bureau; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim GmbH, Mylan. Advisory Panel; Self; Novo Nordisk A/S, OmniPod. Speaker's Bureau; Self; Servier. Advisory Panel; Self; Sanofi-Aventis, Merck Sharp & Dohme Corp.. S.A. Ahn: None. M.F. Rousseau: None.

This study investigated the isolated and crossed effects of familial histories (FH) of early onset coronary heart disease (EOCHD) and type 2 diabetes mellitus (T2DM) on diabetic offspring.The cardiometabolic phenotype of 1098 T2DM patients was analyzed according to an FH of T2DM and/or EOCHD, including body composition, fasting insulinemia, insulin sensitivity, β-cell function (BCF), lipids, lipoprotein(a), high-density lipoprotein (HDL) number and functionality, and micro- and macrovascular complications.Mean age and T2DM duration were 69 and 18 years, respectively; 64% of patients were male, 50% (n = 550) had an FH of T2DM (DM[+]), and 13% (n = 145) had an FH of EOCHD (EOCHD[+]). Four subgroups were generated by crossing FHs: DM[-]EOCHD[-] (44%; n = 487); DM[+]EOCHD[-] (42%; n = 466); DM[-]EOCHD[+] (6%; n = 61); and DM[+]EOCHD[+] (8%; n = 84). Microangiopathies were highest among DM[+] patients, whose BCF was deteriorating the fastest. More numerous/dysfunctional HDLs characterized EOCHD[+] patients. The greatest frequency of cardiovascular disease (CVD; 69%) was observed in DM[-]EOCHD[+] patients, whose lipoprotein(a) and insulinemia were also highest (81 nmol/L and 140 pmol/L, respectively). The lowest frequency of CVD (30%) was observed in DM[+]EOCHD[-] patients.Familial histories of DM and EOCHD predispose to increased microvascular and macrovascular risk, respectively, with hyperinsulinemia, lipoprotein(a), and dysfunctional HDLs standing out as mediators of the inherited macrovascular risk. Yet, crossing these FHs did not randomly redistribute vascular risk, because patients with parental T2DM had fewer macrovascular diseases regardless of familial EOCHD. The odds of being left-handed were unexpectedly greater in patients with crossed parental histories.摘要: 背景 这项研究调查了早发冠心病(early onset coronary heart disease,EOCHD)与2型糖尿病家族史对糖尿病后代有何独立影响以及交叉影响。 方法 按照2型糖尿病和/或EOCHD家族史进行分层, 分析了1098名2型糖尿病患者的心脏代谢表型, 包括身体成分、空腹血胰岛素、胰岛素敏感性、β细胞功能、脂质、脂蛋白(a)、高密度脂蛋白(HDL)数量与功能以及微血管与大血管并发症。 结果 2型糖尿病患者的平均年龄与病程分别为69岁与18年;64%的患者为男性,50%的患者(n = 550)有2型糖尿病家族史(DM[+]),13%的患者(n = 145)有EOCHD家族史(EOCHD[+])。根据交叉的家族史产生了4个亚组:DM[−]EOCHD[−](44%;n = 487);DM[+]EOCHD[−](42%;n=466);DM[−]EOCHD[+](6%;n = 61);以及DM[+]EOCHD[+](8%;n = 84)。在DM[+]患者组中微血管病变最高, 他们的β细胞功能恶化最快。EOCHD[+]组患者的特征为HDLs数量更多/功能失调更明显。观察到的心血管疾病(CVD;69%)发生率最高的是DM[−]EOCHD[+]组患者, 他们的脂蛋白(a)与血胰岛素水平也是最高的(分别为81 nmol/L与140 pmol/L)。观察到CVD发生率最低(30%)的是DM[+]EOCHD[−]组患者。 结论 DM与EOCHD家族史分别容易导致微血管与大血管风险增加, 并且遗传性大血管风险的介质是高胰岛素血症、脂蛋白(a)与功能失调的HDLs。然而, 这些家族史交叉并不会导致血管风险随机重新分布, 因为父母患有2型糖尿病的患者无论是否有家族性EOCHD他们的大血管疾病都较少。出乎意料的是在父母有交叉病史的患者中出现左撇子的几率更大。.

Background The metabolic syndrome (MetS) predicts cardiovascular risk and incident type 2 diabetes mellitus. The presence of a MetS is defined by the clustering of ≥3 out of 5 cardiometabolic criteria (hyperglycemia; hypertension; enlarged waist; low high-density lipoprotein-cholesterol; and hypertriglyceridemia), each of which is connected with insulin resistance. It is not known whether the severity of MetS, ranked from the sextet of scores range [0/5 to 5/5], is linearly related to reduced insulin sensitivity (IS) and/or lesser hyperbolic product across the glycemic spectrum. Patients and methods A total of 839 adults (54 normoglycemic; 785 with abnormal glucose homeostasis, among whom 711 type 2 diabetes mellitus) had insulin sensitivity assessed together with their cardiometabolic phenotype. Results There was a significant gradient according to interval-scale MetS score in insulinemia; body mass index; (visceral) fat; hepatic steatosis; and macroangiopathy. There was an inverse linear relationship between increasing MetS scores and decreased insulin sensitivity, allowing to define an insulin resistance-predicting linear equation: IS (%) = [−15.1 × MetS score] + 109.4 (R2 = 0.221). For each MetS category, mean IS values did not significantly differ between groups of patients across the glycemic spectrum. The hyperbolic product (β-cell function × IS) and/or its loss rate were inversely related to MetS severity. Conclusion Insulin sensitivity is linearly and inversely related to MetS severity across the 6 scores. This novel way to exploit information intrinsic to the MetS criteria provides an easy and low cost means to quantify insulin sensitivity across the glycemic spectrum. Moreover, a higher MetS score is associated with lesser residual insulin secretion, and faster B-cell function loss. Copyright © 2015 John Wiley & Sons, Ltd.

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.

BACKGROUND: Obstructive sleep apnoea syndrome (OSAS) is a risk factor for type 2 diabetes mellitus (T2DM) and promotes cardiovascular events, especially in men. The prevalence of sleep apnoea and its association with microvascular and macrovascular diseases and glycaemic control are poorly documented in T2DM women. METHODS: A total of 305 T2DM women were sleep apnoea diagnosed through (hetero)anamnesis, Epworth's score, oximetry and polysomnography. Sleep apnoea[+] (n = 25) were compared with sleep apnoea[-] (n = 280) regarding cardiovascular risk factors, glucose homeostasis, micro/macrovascular complications and the United Kingdom Prospective Diabetes Study (UKPDS) 10-year risk. RESULTS: Mean (1 SD) age was 66 (12) years, diabetes duration 15 (9) years, sleep apnoea prevalence 8.2% and metabolic syndrome 86%. There were no differences in age, diabetes duration, education, smoking and blood pressure between groups. Sleep apnoea[+] had significantly higher values of body mass index, waist, relative/absolute fat, conicity, visceral fat (all p < 0.0001) and lower skeletal muscle (p = 0.0008). The sleep apnoea[+] group was more insulin resistant [homeostasis model assessment (HOMA S): 37 (20)% versus 59 (44)%; p < 0.0001] and had lesser residual insulin secretion (HOMA B × S: 20 (12)% versus 30 (19)%; p = 0.0006), increased hyperbolic product loss (p = 0.0442) and poorer glycaemic control (HbA1c 69 (12) versus 62 (13) mmol mol(-1) ; p = 0.0099). All atherogenic dyslipidaemia components and inflammatory markers were worsened in sleep apnoea[+]. Women with sleep apnoea had higher UKPDS risk of CAD: 18 (11)% versus 12 (10)% (p = 0.0136). Prevalent micro/macrovascular complications were not different between groups. CONCLUSIONS: Sleep apnoea, a frequent comorbidity of T2DM women, is associated with central fat, atherogenic dyslipidaemia, inflammation, worsening β-cell function, poorer glycaemic control and coronary artery disease risk. Sleep apnoea may increase residual vascular risk for microvascular and macrovascular events in T2DM women.

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: Our objective was to determine soluble ST2 (sST2) concentrations in heart failure (HF) patients with a point-of-care (POCT) assay. METHODS: sST2 levels were measured in 71 HF patients with both POCT and ELISA methods. The concentrations of sST2 were correlated to HF severity and to some established biomarkers of cardiovascular risk. RESULTS: sST2 levels measured with the ASPECT-PLUS POCT method were significantly correlated with the comparison ELISA assay (r = 0.94, p < 0.01) and were related to HF severity. Levels of sST2 measured with the POCT assay were significantly correlated to NT-proBNP (r = 0.57, p < 0.001), BNP (r = 0.75, p < 0.001), Galectin-3 (r = 0.40, p < 0.01) and PTH (1-84) (r = 0.39, p < 0.01). CONCLUSIONS: POCT and ELISA methods for sST2 testing were significantly correlated, and our results confirmed also the clinical reliability of the sST2 POCT assay. Furthermore, the POCT method allows a faster delivery of results to physicians.

Soluble fms-like tyrosine kinase-1 (sFlt-1) is an endogenous inhibitor of endothelial growth factors, such as placental growth factor (PlGF), which modulates cardiovascular (CV) remodeling. We determine sFlt-1 levels in patients with heart failure (HF) and its relationship to adverse cardiovascular (CV) events and biomarkers of cardiovascular risk. Levels of sFlt-1 and PlGF levels were also determined in healthy volunteers and patients with type 2 diabetes mellitus (T2DM). SFlt-1 and PlGF were clearly increased in HF patients in comparison to T2DM patients or healthy subjects (p

Background Type 2 diabetes (T2DM) is associated with obesity, insulin resistance and the metabolic syndrome (MetS). In non-diabetic populations, features of metabolic obesity (MO) are observed in a minority of normal-weight (NW) subjects. The cardiometabolic status of metabolically obese but normal-weight (MONW) individuals has not yet been phenotyped in T2DM. Patients and methods Prevalence and features of MONW were analyzed in 1244 T2DM patients, in whom MONW was identified as a BMI n = 262; 21%), those without MetS ( n = 152; NW-MetS[−]) were compared to NW-MetS[+] ( n = 110; i.e. 42% of NW and 9% of all T2DM). Results There were no differences between groups in age; gender; diabetes duration; smoking; BP; and LDL-C. NW-MetS[+] had higher BMI; waist; fat mass; visceral fat; liver steatosis and HbA 1c , and lower insulin sensitivity. Non-right-handedness was twice-higher (18%) in NW-MetS[−]. NW-MetS[+] had higher apoB 100 and triglycerides, and lower HDL-C and LDL size. Macroangiopathy was present in 39% of NW-MetS[+] vs. 22% of NW-MetS[−], as coronary (23% vs. 14%) or peripheral artery disease (14% vs. 5%) and TIA/stroke (15% vs. 7%). Microangiopathy was present in 54% of NW-MetS[+] vs. 32% of NW-MetS[−], as retinopathy (25% vs. 13%); neuropathy (29% vs. 18%); and albuminuria (39% vs. 20%). Conclusions MONW among T2DM represents a significant minority (about 1 in 10). Their cardiometabolic phenotype deserves attention due to multiple comorbidities, including a twice-higher prevalence of micro-/macrovascular damage in patients wrongly perceived at lower risk due to normal BMI. Unexpectedly, non-right-handedness was over-represented among metabolically healthy patients.

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: Imbalance in nitric oxide (NO), an atheroprotective vasodilator, is associated with endothelial dysfunction, cardiovascular diseases (CVD) and diabetic complications. Various endothelial NO synthase (eNOS) polymorphisms may affect NO bioavailability, thereby promoting adverse cardiovascular milieu. MATERIALS AND METHODS: To analyze glucose homeostasis, cardiometabolic phenotype, and micro- and macroangiopathies associated with eNOS G894T gene polymorphism in type 2 diabetes (T2DM). 210 T2DM outpatients (mean age (1SD) 70 (12); diabetes duration 19 (9) years; males:females 64:36%; metabolic syndrome 87%) had insulin sensitivity and b-cell function modelled with HOMA, alongside routine laboratory and endothelin measurements. RESULTS: GG, GT and TT genotypes represented 48% (n = 100), 39% (n = 83) and 13% (n = 27). Overall microangiopathy (retinopathy, neuropathy and/or nephropathy) was present in 74%, and overall macroangiopathy (CAD, PAD and/or TIA/stroke) in 45%. The TT genotype did not translate into a more severe vascular phenotype, as TT patients carrying the proposed risk genotype did not suffer a higher rate of micro- and macrovascular complications. On the other hand, erectile dysfunction, present in 60% of males (n = 135), was much more prevalent in TT males: 57% [GG & GT] vs. 93% in TT (p 0.0088). Ocular hypertension/glaucoma frequency (18% of the whole group) was also markedly different, albeit in opposing directions, between eNOS G894T gene polymorphism subgroups: 21% [GG & GT] vs. 0% prevalence (TT; p 0.0057). CONCLUSIONS: eNOS G894T gene polymorphism in homozygous TT carriers translates into opposing effects on erectile function (detrimental) and ocular hypertension/glaucoma (protective) in T2DM, without affecting glucose homeostasis determinants or the presence of micro- and macrovascular complications.

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

Heart failure (HF) is a frequent chronic disease in elderly people and represents a major health and economic burden. The accurate diagnosis of HF and the identification of high risk patients is manda-tory to select the appropriate therapy and care. HF is associated to cardiac remodeling and inflamma-tion and to the release of neurohormones. If natriuretic peptides remain the biomarkers of choice for the diagnosis and the prognosis of HF, several biomarkers related to cardiac remodeling and inflammation are available for testing and may add valuable information for the risk estimation of HF pa-tients and for the selection of the most appropriated therapy. Furthermore, the quest for new efficient biomarkers of cardiac remodeling and inflammation is still ongoing and new candidates have been identified for a potential use in daily clinical practices. However, before their potential translation to routine parameters several challenges ranging form the analytical validation to the cost-effectiveness estimation should be considered.

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.

J Clin Hypertens(Greenwich). 2010;12:653-660. (c) 2010 Wiley Periodicals, Inc. Urotensin II (UII) exerts multiple effects on the cardiovascular system, acts as a diabetogenic agent, and may also contribute to the development of the metabolic syndrome (MetS). The aim of this study was to determine circulating UII in patients with type 2 diabetes mellitus (T2DM) and its relationship with MetS. A total of 360 consecutive patients with T2DM were included. MetS presence/absence (MetS [+]/[-]) was defined according to American Heart Association/National Heart, Lung and Blood Institute criteria. Plasma concentrations of UII were determined by radioimmunoassay. UII levels were significantly higher in MetS (+) than in MetS (-) T2DM patients (0.97 pg/mL [0.93-1.01], n=294 vs 0.82 pg/mL [0.75-0.88] pg/mL, n=66, respectively; P

Aims High ferritin levels are associated with insulin resistance and liver steatosis, both thought of as emerging cardiovascular risk factors. The association between ferritin and cardiovascular disease is poorly documented in cardiometabolic states with higher cardiovascular risk, such as diabetes and metabolic syndrome. We therefore characterized a cohort of males with Type 2 diabetes mellitus (T2DM) according to ferritin levels and prevalent macroangiopathy. Methods The presence of overall macroangiopathy, peripheral and/or coronary artery disease was documented in 424 consecutive T2DM males, who were divided according to ferritin quartiles (Q) as follows: QI-III, normal ferritin (NF; n = 318), mean +/- 1 sd ferritin 133 +/- 72 ng/ml; and QIV patients, high ferritin (HF; n = 106), ferritin 480 +/- 228 ng/ml. Results Age, age at diabetes diagnosis, smoking, ethanol intake, body mass index, waist circumference, blood pressure and presence of metabolic syndrome did not differ between groups. However, the prevalence of macroangiopathy was unexpectedly much lower in patients with high ferritin, as follows: 25% vs. 43% for overall macroangiopathy; 7% vs. 16% for peripheral artery disease; and 16% vs. 31% for coronary artery disease (P = 0.0009, P = 0.0140 and P = 0.0035, respectively, vs. NF patients). Insulin resistance index and prevalence of liver steatosis were higher in HF compared with NF patients as follows: 2.17% vs. 1.89% and 78% vs. 64% (P = 0.0345 and P = 0.0059, respectively). Liver enzymes (aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transferase) were significantly higher in HF, by 33%, 42% and 72%, respectively (all P < 0.0002), suggesting a higher prevalence of steatohepatitis. Glycated haemoglobin, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, triglycerides, urate, high-sensitivity C-reactive protein and albuminuria were not different between groups. Conclusions Our results demonstrate that T2DM males with high ferritin levels exhibit a markedly decreased prevalence of macroangiopathy, despite more severe insulin resistance and higher markers of steatohepatitis. High ferritin levels and/or steatosis may thus paradoxically confer a lowered cardiovascular risk in diabetic males.

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 Laterality is associated with various health conditions. No study has addressed the influence of handedness on Type 2 diabetes mellitus (T2DM) phenotype, including glucose homeostasis, glucose-lowering therapies and metabolic control. Methods Five hundred and seventy-six consecutive adult T2DM outpatients underwent homeostasis model assessment (HOMA) of pancreatic B-cell function (B), insulin sensitivity (S), hyperbolic product (B x S) and age-standardized B x S deficit. Right-handed patients (87.5%; RH; n = 504) had similar age, gender, diabetes duration and education than non-right-handed patients (12.5%; non-RH; n = 72). Results Non-RH were more insulin-sensitive: 66% (39%) vs. 52% (36%) [mean (1 sd); P = 0.0024] and had significantly higher B x S and lower age-adjusted B x S deficit: 35% (20%) vs. 26% (17%) and 1.08% (0.40%) vs. 1.32% (0.55%)/year (non-RH; P = 0.0005 and P < 0.0001, respectively). Conclusions Non-right-handed T2DM patients are more insulin-sensitive, have higher hyperbolic product and less age-standardized B x S deficit. These may modulate glucose-lowering therapy requirements and glycaemic control.

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.

OBJECTIVE: B-type natriuretic peptide (BNP) and N-terminal-pro-BNP (Nt-proBNP) are commonly used for the triage of patients in the emergency department (ED) with dyspnoea and/or chest pain. The aim of our study was to determine the accuracy of N-terminal-pro-ANP (Nt-proANP) in such patients. MATERIAL AND METHODS: Nt-proANP was measured by home-made radioimmunoassay in 137 ED patients admitted with cardiovascular and/or pulmonary disorders. BNP and Nt-pro-BNP were determined with automated assays. Final diagnosis was confirmed at discharge or after follow-up. RESULTS: Nt-proANP levels were significantly influenced by the diagnostic subgroups (ANOVA: p

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.