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Background: Hyperglycemia and type 2 diabetes mellitus (T2DM) pose a significant risk for cardiovascular diseases and associated complications in individuals with hyperlipidemia. Statin therapy, effective in reducing cholesterol and cardiovascular risks, paradoxically increases incident T2DM risk due to its adverse impact on glucose homeostasis. Therefore, there is a pressing need for safe, and effective adjunctive or alternative therapies to manage hyperglycemia in hyperlipidemic individuals. There is growing body of pharmacological evidence suggesting that Amla and Olive extract supplementation can be beneficial in managing hyperglycemia in individuals with hyperlipidemia., Objective: The present study aimed to assess for the first time the potential synergistic antihyperglycemic effects of a daily co-supplementation of 1,000 mg Amla fruit and 50 mg Olive fruit standardized extracts (Cholesfytol NG ® ) over a 2-months period in hyperlipidemic adults with T2DM or prediabetes., Methods: This retrospective cross-sectional observational study analyzed treatment outcomes in 191 hyperlipidemic adults under the care of their physicians at 57 General Practitioner clinics in Belgium during real-life clinical practice between March 19, 2020, and January 31, 2022. These participants received Cholesfytol NG ® as supplementary therapy to improve their metabolic health. The supplement was prescribed in an open-label, non-randomized manner, tailored to each participant's need., Results: After 2-months of Cholesfytol NG ® supplementation, participants showed significant reductions in glycemia levels: in the T2DM group, levels decreased by 42.7 ± 17.9 mg/dL (27.9%, p  < 0.0001), and in the prediabetic group, by 2.26 ± 11.5 mg/dL (4.7%, p  = 0.0020). Conversely, no significant change was observed in participants with normal baseline glycemia (1.55 ± 10.3 mg/dL, p  = 0.088). Overall, glycemia levels decreased from 96.4 ± 18.2 mg/dL to 94.0 ± 13.5 mg/dL (mean decrease of 2.4 ± 14.5 mg/dL, p  < 0.0001). The supplement was well tolerated and no side-effects, serious adverse events, or treatment-emergent effects were reported., Conclusion: The findings of this real-life clinical study highlight the potential synergistic antihyperglycemic effects of co-supplementation with Amla and Olive fruit extracts in managing hyperglycemia, particularly in individuals with hyperlipidemia. These results suggest that this botanical combination may help mitigate risks associated with hyperglycemia and cardiovascular disease in hyperlipidemic population., Clinical Trial Registration: ClinicalTrials.gov, NCT06187298., Competing Interests: IJ and YD were employed by Laboratoire Tilman, Baillonville, Belgium. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hermans, Ahn, Rousseau, Seidel, Albert, Janssens, Dierckxsens and Khan.)

Background: Hyperlipidemia is associated with a higher rate of cardiovascular, cerebrovascular, and peripheral vascular disease. Conventional drugs such as statins are effective in controlling hyperlipidemia; however, they are associated with various side effects, especially myalgia. Nutraceutical lipid-lowering interventions are becoming increasingly popular, particularly among patients who are intolerant or refractory to statins. Substantial preclinical and clinical evidence suggests that extracts of amla, walnut, and olive, and red yeast rice (RYR) powder possess significant antihyperlipidemic effects. Aims: This study aimed to evaluate the efficacy, safety, and patient satisfaction of a combined supplementation of standardized dry extracts of amla fruit (500 mg), walnut leaves (50 mg), olive fruit (25 mg), and RYR powder (33.6 mg) (Cholesfytol NG®) in hypercholesterolemic patients. Methods: This was a real-life setting , retrospective, observational, single-arm, non-randomized study in hypercholesterolemic patients (total cholesterol (TC) ≥ 200 mg/dL or low-density lipoprotein-cholesterol (LDL-C) ≥ 130 mg/dL), enrolled at 57 general practitioner (GP) surgeries in Belgium from March 2020 to January 2022. These patients received a GP-prescribed daily single dosage of two oral tablets of Cholesfytol NG® supplementation for 2 months to overcome their hypercholesterolemia in the absence of a conventional lipid-lowering drug (n = 208) or with a lipid-lowering drug (n = 13). At 2-month follow-up, the lipid profile was re-evaluated, alongside a patient's questionnaire on treatment general satisfaction and willingness to pursue supplementation. Results: After supplementation, TC decreased by 15%, LDL-C by 19%, non-high-density lipoprotein-cholesterol (non-HDL-C) by 20% (all p < 0.0001), triglycerides (TG) by 9% ( p = 0.0028) (-18.4%, p = 0.0042, in patients with baseline TG > 180 mg/dL, n = 58), and remnant cholesterol (RC) by 12% ( p = 0.0001). These changes were unaffected by statin intolerance status in patients who received Cholesfytol NG® alongside statin. The supplement was well tolerated by all patients, and no serious adverse events or supplement-emergent effects were reported. Most patients were satisfied with the supplementation and wanted to pursue the nutraceutical. Conclusion: According to the results of this study, a combined supplementation of amla, walnut, and olive extracts, and RYR powder exerts a significant antihyperlipidemic effect, leading to a decrease in circulatory LDL-C and RC levels in patients with hypercholesterolemia. The supplementation bears excellent safety and tolerability, and is rated as satisfactory and pursuable, even among patients with statin intolerance. Clinical Trial Registration: clinicaltrials.gov; identifier number: NCT06002893., Competing Interests: Authors YD and IJ were employed by Laboratoire Tilman, Belgium. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hermans, Dierckxsens, Janssens, Seidel, Albert, Ahn, Rousseau and Khan.)

Background and Aims: Non-alcoholic fatty liver (FL) is comorbid with obesity, metabolic syndrome and type 2 diabetes. Atherogenic dyslipidaemia (AD), frequent in FL, is associated with risk of micro- and macrovascular complications. Given the paradoxical ocular protection of FL in T2DM, we studied how FL modulates micro- and macrovascular complications as a function of AD., Methods: Cross-sectional factorial analysis of 744 diabetic patients in whom FL, identified by ultrasonography, was present in 68%. AD, defined by low HDL-C plus elevated TG, was present in 45%. Four groups were analysed as regards cardiometabolic features, micro-/macroangiopathies, cataract and ocular hypertonia: FL[-]AD[-] (n = 171); FL[-]AD[+] (n = 66); FL[+]AD[-] (n = 235); and FL[+]AD[+] (n = 272)., Results: Age, gender and glycemic control were similar across groups. Prevalence of overall macroangiopathy and coronary artery disease were higher in patients with AD, irrespective of FL. Overall macroangiopathy was higher, by 64% in FL[-]AD[+] and by 38% in FL[+]AD[+]. Coronary artery disease was higher, by 128%, in FL[-]AD[+], and by 67%, in FL[+]AD[+]. (Micro)albuminuria was more frequent (+55%) in FL[-] AD[+] compared to FL[-] AD[-]. Retinopathy prevalence was 35% in FL[-], unaffected by AD. Retinopathy frequency was much lower in FL[+], irrespective of AD, decreased by -47% in FL[+]AD[-] and -32% in FL[+]AD[+] (vs. FL[-]AD[-]). Ocular hypertonia was present in 13%, and its prevalence was also markedly lower (-31%) in FL[+]. Cataract frequency was 29%, also lesser in FL[+] (24% vs. 39%), irrespective of AD., Conclusions: Multi-level eye protection in diabetes is linked to non-alcoholic fatty liver independently of atherogenic dyslipidemia., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2022 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Objectives: To determine concentrations of heart-type fatty acid-binding protein (HFABP) in patients with heart failure with reduced ejection fraction (HFrEF) and its potential value for prognostic assessment., Methods: Circulating levels of HFABP were measured with an automated chemiluminescent immunoassay in 25 healthy volunteers and 60 HFrEF patients., Results: Concentrations of HFABP were significantly increased in heart failure patients in comparison to healthy volunteers. HFABP levels were significantly correlated to New York Heart Association classes and to established biomarkers of cardiac dysfunction and remodeling (amino-terminal pro-B-type natriuretic peptide [NT-proBNP], fibroblast growth factor 23, and galectin-3). HFABP concentrations were also predictive of cardiovascular (CV) death and combination with NT-proBNP might be synergistic for risk assessment., Conclusions: HFABP levels are increased in HFrEF patients, related to adverse CV outcomes, and might assist physicians for patient's management., Competing Interests: Competing interests: D. Gruson received research support from Snibe diagnostics. The other authors do not have any conflicts of interest and do not have to declare any funding to support this article., (© 2021 Damien Gruson et al., published by De Gruyter, Berlin/Boston.)

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: 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 <0.001), and correlated not only with New York Heart Association class, cMR-LV and cMR-right ventricular (RV) volumes, cMR-RV and cMR-LV ejection fraction, and feature tracking global longitudinal strain, but also with cardiac output. Over 6-year median follow-up, 182 patients died and 200 reached the secondary endpoint. By multivariate Cox analysis, PTT was an independent and significant predictor of both endpoints after adjustment for Meta-Analysis Global Group in Chronic Heart Failure risk score and ischemic cause. Importantly in multivariable analysis, PTT in beats had significantly higher additional prognostic value to predict not only overall mortality (χ 2 to improve, 12.3; hazard ratio, 1.35 [95% CI, 1.16-1.58]; P <0.001) but also the secondary composite endpoints (χ 2 to improve=20.1; hazard ratio, 1.23 [95% CI, 1.21-1.60]; P <0.001) than cMR-LV ejection fraction, cMR-RV ejection fraction, LV-feature tracking global longitudinal strain, or RV-feature tracking global longitudinal strain. Importantly, PTT was independent and complementary to both pulmonary artery pressure and reduced RV ejection fraction<42% to predict overall mortality and secondary combined endpoints., 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 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., Competing Interests: Disclosure of conflicts interest The authors declare that they have no conflict of interest., (Copyright © 2020 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

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 < 0.05), FT-RVGLS (chi-square to enter 3.7; p = 0.05), FAC (chi-square to enter 6.2; p = 0.02), and TAPSE (chi-square to enter = 4.1; p = 0.04) provided additional prognostic value over these baseline parameters, but the additional predictive value of STE-RVGLS (chi-square to enter = 10.8; p < 0.001) was significantly (p < 0.05) higher than the other tests. Additional hazard ratio to predict overall mortality was 2.5 (95% confidence interval [CI]: 1.6 to 3.9) for STE-RVGLS <-19%, 2.15 (95% CI: 1.34 to 3.43) for TAPSE >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 <-15%., 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., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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 B 100 , 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 < 0.0001)., 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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: 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., Methods: 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., Results: 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., Conclusions: 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., (© 2018 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Aims: Non-Caucasian migrants require dedicated approaches in diabetes management due to specific genetic; socio-cultural; demographic and anthropological determinants. Documenting such phenotypes allows for better understanding unmet needs and management priorities., Methods: This age- and sex-adjusted case-control (1:6 ratio) study compared 56 T2DM Turkish migrants (70% males) resident in Belgium [Tu] with 336 T2DM Caucasians [Ca], all benefiting from state-funded healthcare., Results: The 2 groups did not differ regarding BMI; waist circumference; fat mass; visceral fat; muscle mass; insulin sensitivity; insulinemia; metabolic syndrome; hypertension; lipid-modifying drugs; and macroangiopathy. They also had similar renal function and (micro)albuminuria. Education (low/high) and ethanol consumption were lower among [Tu]: 83/17% and 2.0 U/wk vs 43/57% and 13.6 U/wk in [Ca] (p < 0.0001). β-cell function loss (BCF) was higher in [Tu]: 1.58(0.45) vs 1.35(0.54)%/yr (p 0.0027), as was HbA1c: 8.39(1.91) vs 7.48(1.35)% in [Ca] (p < 0.0001). Diabetes duration and insulin use were increased in [Tu]: 19(9)yr and 70% vs 16(8)yr and 48% in [Ca] (p 0.0111 and 0.0024). Atherogenic dyslipidemia (AD) was more prevalent in [Tu]: 64% vs 49% (p 0.0309), who had higher non-HDL-C; apolipoprotein B 100 ; LDL-C; and triglycerides; and lower HDL-C and apolipoprotein A-I levels (all p < 0.05). Overall microangiopathy; retinopathy; and neuropathy were more prevalent in [Tu]: 55-35-37% vs 40-18-20% in [Ca] (all p < 0.05)., Conclusions: These results should raise concerns about poor glycaemic control; rapid BCF loss; severe AD; and microangiopathy among Turkish migrants with T2DM. Targeting AD could improve the cardiometabolic profile of this minority given the relationship between AD and residual vascular risk., (Copyright © 2018 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Aims: Although women have higher high-density lipoprotein cholesterol (HDL-C) than have men, their HDL particles are also prone to become small, dense, and dysfunctional in case of type 2 diabetes mellitus (T2DM). To assess the vascular risk related to HDLs of different sizes/densities without direct measurement, we adjusted HDL-C to its main apolipoprotein (apoA-I) as [HDL-C/apoA-I]. This ratio estimates HDL sizes and provides indices as to their number, cholesterol load, and density., Methods: We stratified 280 Caucasian T2DM women according to [HDL-C/apoA-I] quartiles (Q) to determine how they are segregated according to cardiometabolic risk, β-cell function, glycaemic control, and vascular complications. Five parameters were derived from combined determination of HDL-C and apoA-I: HDL size, HDL number, cholesterol load per particle (pP), apoA-I pP, and HDL density., Results: An adverse cardiometabolic profile characterized QI and QII patients whose HDLs were denser and depleted in apoA-I, whereas QIII patients had HDLs with characteristics closer to those of controls. QIV patients had HDLs of supernormal size/composition and a more favourable phenotype in terms of fat distribution; insulin sensitivity (64% vs 41%), metabolic syndrome, and β-cell function (32% vs 23%); exogenous insulin (44 vs 89 U·d -1 ); and glycaemic control (glycated haemoglobin, 56 vs 61 mmol·mol -1 ), associated with lower prevalence of microvascular/macrovascular complications: all-cause microangiopathy 47% vs 61%; retinopathy 22% vs 34%; all-cause macroangiopathy 19% vs 31%; and coronary artery disease 6% vs 24% (P < .05)., Conclusion: [HDL-C/apoA-I] can stratify T2DM women according to metabolic phenotype, macrovascular and coronary damage, β-cell function, microangiopathic risk, and retinopathy. This ratio is a versatile and readily available marker of cardiometabolic status and vascular complications in T2DM women., (Copyright © 2017 John Wiley & Sons, Ltd.)

Cholesfytol ® , a lipid-lowering dietary supplement with antioxidant and anti-atherosclerotic properties, combines red yeast rice (RYR) and olive extract (5mg hydroxytyrosol equivalent) and represents an alternative for patients who do not wish or are unable to use chemical statins, including individuals with previous statin-associated muscle symptoms (SAMS). A 2-months observational non-randomized study was performed to evaluate the efficacy, tolerance and safety of Cholesfytol ® (1 tablet/day) in 642 hypercholesterolemic patients (mean age: 59 yrs; total cholesterol (TC) ≥200; LDL-C ≥140mg/dl). Patients were followed by 126 GPs, and included irrespective of SAMS history and/or diabetes. None of the patients were taking statins or other lipid-modifying therapy at inclusion. At baseline, 26% had fasting glucose >100 ≤125mg/dL, and 5% >125mg/dL; 32% (n=194) had a SAMS history; and 21% had atherogenic dyslipidemia (AD). In the entire cohort, pre-treatment TC; non-HDL-C; LDL-C; and TG were 259; 200; 168; 158mg/dL, respectively, and decreased significantly on treatment (-17.5% (TC) and -23.3% (LDL-C)). Fasting glucose and HbA 1c decreased between visits. The reduction in lipids was greater in patients with higher values at baseline. For comparable pre-treatment values, patients with SAMS history had reductions in TC, LDL-C, non-HDL-C, and apoB 100 slightly less than patients without myalgia. AD patients had greater on-treatment decrease in TG. Overall, 13 patients reported minor side-effects, and 4 patients reporting myalgia had antecedent SAMS. In conclusion, a substantial decrease in LDL-C was obtained with a combination of RYR and olive extract in high-risk hypercholesterolemic patients, without inducing new-onset SAMS., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

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.

Aim: Oncostatin M (OSM) is an inflammatory cytokine of the gp130 family. OSM could participate in adverse cardiovascular remodeling through regulation of FGF23., Materials & Methods: OSM levels were determined in 80 heart failure patients with reduced left ventricular ejection fraction (HFrEF)., Results: OSM levels are significantly increased in HFrEF patients compared with healthy subjects. We have also demonstrated that, in HFrEF patients, plasma OSM levels are correlated to parathyroid hormone PTH(1-84) and 1,25(OH) 2 D, two other biomarkers related to bone and mineral metabolism and associated to adverse cardiovascular outcomes., Conclusion: OSM concentrations are elevated in HFrEF patients and could interplay with parathyroid hormone and vitamin D impacting cardiovascular function. Nevertheless, the prognostic value of OSM testing appears limited.

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., (Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

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 < 0.01). Concentration of sFlt-1 was related to HF severity (p < 0.001) and was correlated to NT-proBNP (ρ = 0.37, p < 0.01), soluble ST2 (ρ = 0.52, p < 0.01), Galectin-3 (ρ = 0.38, p < 0.01), aldosterone (ρ = 0.25, p = 0.01) and PTH(1-84) (ρ = 0.38, p < 0.01). Furthermore, sFlt-1 levels were associated to long-term CV risk. These results suggest a potential role of sFlt-1 in HF and its potential role as biomarker of CV risk.

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., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

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 <25.0 and a MetS score ≥3/5. Among NW (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 HbA1c, and lower insulin sensitivity. Non-right-handedness was twice-higher (18%) in NW-MetS[-]. NW-MetS[+] had higher apoB100 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., (Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

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 (R(2)  = 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., (Copyright © 2015 John Wiley & Sons, Ltd.)

Objectives: Vitamin D deficiency and hyperparathyroidism are common in patients with heart failure (HF). There is a growing body of evidence supporting the role of vitamin D and parathyroid hormone (PTH) in cardiac remodeling and worsening of HF. Lack of reliable automated testing of 1,25-dihydroxyvitamin D (1,25(OH)2D), the biologically active metabolite of vitamin D, has limited its contribution to the prognostic assessment of HF. Here, the association of 1,25(OH)2D and PTH(1-84) levels was evaluated for prediction of cardiovascular death in chronic HF patients., Methods: We conducted a single center prospective cohort including 170 chronic HF patients (females n = 36; males n = 134; NYHA II-IV; mean age: 67 years; etiology: ischemic n = 119, dilated cardiomyopathy n = 51; mean LVEF: 23%). The primary outcome was cardiovascular death., Results: Serum levels of 1,25(OH)2D decreased markedly with increased HF severity. Medians were 33.3 pg/mL for NYHA-II patients, 23.4 pg/mL for NYHA-III, and 14.0 pg/mL for NYHA-IV patients (p<0.001). Most patients had levels of 25(OH)D below 30ng/mL, and stratification by NYHA functional class did not show significant differences (p = 0.249). The 1,25(OH)2D to PTH(1-84) ratio and the (1,25(OH)2D)2 to PTH(1-84) ratio were found to be the most significantly related to HF severity. After a median follow-up of 4.1 years, 106 out of 170 patients reached the primary endpoint. Cox proportional hazard modeling revealed 1,25(OH)2D and the 1,25(OH)2D to PTH(1-84) ratios to be strongly predictive of outcomes., Conclusions: 1,25(OH)2D and its ratios to PTH(1-84) strongly and independently predict cardiovascular mortality in chronic HF.

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., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Diabetes is a major cardiovascular risk factor. However, its influence on the rate of occurrence of cardiovascular (CV) events during a clinical trial that included a diabetes subgroup has not yet been quantified., Aims: To establish equations relating baseline diabetes prevalence and incident CV events, based on comparator arms data of major lipid-modifying trials., Methods: Meta-analysis of primary outcomes (PO) rates of key prospective trials, for which the baseline proportion of diabetics was reported, including studies having specifically reported CV outcomes within their diabetic subgroups., Results: 47 studies, representing 330,376 patients (among whom 124,115 diabetics), were analyzed as regards the relationship between CV outcomes rates (including CHD) and the number of diabetics enrolled. Altogether, a total of 18,445 and 16,156 events occurred in the comparator and treatment arms, respectively. There were significant linear relationships between diabetes prevalence and both PO and CHD rates (%/year): y = 0.0299*x + 3.12 [PO] (p = 0.0128); and y = 0.0531*x + 1.54 [CHD] (p = 0.0094), baseline diabetes predicting PO rates between 3.12 %/year (no diabetic included) and 6.11 %/year (all patients diabetic); and CHD rates between 1.54 %/year (no diabetic) and 6.85 %/year (all patients diabetic). The slopes of the equations did not differ according to whether they were derived from primary or secondary prevention trials., Conclusions: Absolute and relative CV risk associated with diabetes at inclusion can be readily predicted using linear equations relating diabetes prevalence to primary outcomes or CHD rates.

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., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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<100 mg/dL; SBP<130 mmHg and HbA1c<7.0%) in 1005 T2DM outpatients (654 men) followed in a university hospital multidisciplinary department. Triple-goal achievers were compared to non-achievers regarding sociodemographics; anthropometrics; homeostatic model assessment (HOMA; β-cell function (B); insulin sensitivity (S); hyperbolic product (B×S)); CV and glucose-lowering drugs; micro-/macro-vascular outcomes; and 10-year UKPDS risk., Results: Eighty-eight patients (9%; ((3 targets) group) reached all goals, whereas 917 patients (91%; ((0-2 target(s)) group) missed 1, 2 or all 3 goals. Compared to (0-2 target(s)), (3 targets) had shorter diabetes duration; less familial diabetes history; lower waist/visceral fat; higher β-cell function and hyperbolic product (B×S); lower (B×S) loss rate and less metabolic syndrome (all p<0.05). They had lower apoB and triglycerides; and a 28% prevalence of atherogenic dyslipidemia (vs. 40% in (0-2 target(s)); p 0.0398). Microangiopathy (36% vs. 53%) and 10-year CAD risk (13% vs. 18%) were also significantly lower in (3 targets)., Conclusions: The subset of T2DM patients achieving all critical quality indicators are characterized by a less severe cardiometabolic phenotype, while exhibiting a less pronounced alteration of their residual β-cell function. These differences are related to fewer microvascular outcomes and lower 10-year CV risk., (Copyright © 2014 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Background: Non-fasting triglyceride-rich lipoproteins cholesterol (TRL-C) contributes to cardiovascular risk, in that it includes remnant cholesterol (RC). TRL-C is computed as total C - [LDL-C + HDL-C]. Such calculation applies only if LDL-C is directly measured, or obtained from a non-Friedewald's formula, a method as yet never benchmarked against independent markers of TRL burden., Methods: The Discriminant Ratio (DR) methodology was used in 120 type 2 diabetic patients in order: (i) to compute TRL-C from non-fasting lipids; (ii) to establish the performance of TRL-C and TRL-C/apoA-I (vs. TG-based markers) to grade TRLs and atherogenic dyslipidemia (AD); and (iii) to relate TRL-C with non-fasting TG., Results: Depending on apoB100 availability, TRL-C (mg/dL) can be derived from non-fasting lipids in two ways: (a) total cholesterol (TC) - [(0.0106 * TC - 0.0036 * TG + 0.017 * apoB100 - 0.27) * 38.6] - HDL-C; and (b) TC - [(0.0106 * TC - 0.0036 * TG + 0.017 * [0.65 * (TC - HDL-C) + 6.3] - 0.27) * 38.6] - HDL-C. Discrimination between log[TG] and TRL-C was similar (DR 0.94 and 0.84, respectively), whereas that of log[TG]/HDL-C was better than TRL-C/apoA-I (DR 1.01 vs. 0.65; p 0.0482). All Pearson's correlations between pairs reached unity, allowing formulation of two unbiased equivalence equations: (a) TRL-C = 97.8 * log[TG] - 181.9; and (b) TRL-C/apoA-I = 8.15 * (log[TG]/HDL-C) - 0.18., Conclusions: TRL-C and log[TG] are as effective and interchangeable for assessing remnant atherogenic particles. For grading TRL-AD, it is best to use log[TG]/HDL-C, inherently superior to TRL-C/apoA-I, while measuring the same underlying variable.

Background: Non-diabetic offspring from long-lived parents benefit from lowered CV risk. No study investigated the effects of parental lifespan on their progeny when offspring have T2DM. This study assessed CV and metabolic features of T2DM offspring according to parental lifespan., Patients & Methods: 558 T2DM patients were questioned on parental longevity (paternal and/or maternal lifespan ≥ 80 years); mean age 66 (11) years; male:female 66:34; divided into 6 groups: long-lived father [LLF] (n = 143); short-lived father [SLF] (n = 262); long-lived mother [LLM] (n = 229); short-lived mother [SLM] (n = 176); long-lived father and long-lived mother [LLF & LLM] (n = 82); and short-lived father and/or short-lived mother [SLF &/or SLM] (n = 323)., Results: Age was similar in [LLF & LLM] and [SLF &/or SLM]. Diabetes duration was longer in [SLF &/or SLM] (p 0.0073). Body composition, hypertension, hepatic steatosis and metabolic syndrome (MetS) were similar in both groups, [SLF &/or SLM] having a higher MetS score: 3.79 (1.12) vs. 3.48 (1.12) (p 0.0257). Fasting insulinemia was higher in [SLF &/or SLM] (p 0.0001), who were more insulin resistant (+10%: p 0.0440). HbA1c was higher (+0.36%) in [SLF &/or SLM] (p 0.0138). LDL-C; non-HDL-C; and apoB100 were similar in both groups, whereas HDL-C and apoA-I were higher in [LLF & LLM] (p 0.0233 and p 0.0179). Prevalence and severity of atherogenic dyslipidemia were raised in [SLF &/or SLM], by 53% (prevalence) and 13% (log[TG]/HDL-C) (p 0.0172 and p 0.0067)., Conclusion: Bilateral reductions in parental longevity are linked to unfavorable cardiometabolic phenotype in T2DM descendants, with worsened insulin resistance and atherogenic dyslipidemia among 1st-degree offspring., (Copyright © 2014 Elsevier Inc. All rights reserved.)

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., (Copyright © 2013 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

The study objectives were to determine the circulating levels of proBNP1-108, the precursor of B-type natriuretic peptide (BNP) and amino-terminal pro-BNP (NT-proBNP), in patients with systolic heart failure (HF) and to assess their prognosis value for cardiovascular (CV) death over a long-term follow-up. Seventy-three patients with systolic HF and 68 healthy volunteers were included. ProBNP1-108, BNP and NT-proBNP levels were measured with automated immunoassays and their predictive value for long-term survival was assessed through an 8 years follow-up. ProBNP1-108 levels were markedly increased in patients with systolic HF in comparison to healthy volunteers. In univariate proportional hazard model, survival was related to proBNP1-108, BNP, NT-proBNP, age, EF and glomerular filtration rate (eGFR). Kaplan-Meier survival curves according to proBNP tertiles diverged significantly, and the highest proBNP levels were related to patients with the highest risk of CV death. In a multivariate analysis including age, EF, proBNP1-108, BNP, NT-proBNP, and eGFR levels, NT-proBNP was the strongest predictor of long term CV death. Our study therefore demonstrated that high levels of proBNP1-108, measured with an assay with enhanced analytical specificity, are related to the long-term risk of cardiovascular death in systolic heart failure., (Copyright © 2013 Elsevier Inc. 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., (Copyright © 2013 John Wiley & Sons, Ltd.)

Background: Apolipoprotein B100 (ApoB100) determination is superior to low-density lipoprotein cholesterol (LDL-C) to establish cardiovascular (CV) risk, and does not require prior fasting. ApoB100 is rarely measured alongside standard lipids, which precludes comprehensive assessment of dyslipidemia., Objectives: To evaluate two simple algorithms for apoB100 as regards their performance, equivalence and discrimination with reference apoB100 laboratory measurement., Methods: Two apoB100-predicting equations were compared in 87 type 2 diabetes mellitus (T2DM) patients using the Discriminant ratio (DR). Equation 1: apoB100 = 0.65*non-high-density lipoprotein cholesterol + 6.3; and Equation 2: apoB100 = -33.12 + 0.675*LDL-C + 11.95*ln[triglycerides]. The underlying between-subject standard deviation (SDU) was defined as SDU = √ (SD2B - SD2W/2); the within-subject variance (Vw) was calculated for m (2) repeat tests as (Vw) = Σ(xj -xi)2/(m-1)), the within-subject SD (SDw) being its square root; the DR being the ratio SDU/SDW., Results: All SDu, SDw and DR's values were nearly similar, and the observed differences in discriminatory power between all three determinations, i.e. measured and calculated apoB100 levels, did not reach statistical significance. Measured Pearson's product-moment correlation coefficients between all apoB100 determinations were very high, respectively at 0.94 (measured vs. equation 1); 0.92 (measured vs. equation 2); and 0.97 (equation 1 vs. equation 2), each measurement reaching unity after adjustment for attenuation., Conclusion: Both apoB100 algorithms showed biometrical equivalence, and were as effective in estimating apoB100 from routine lipids. Their use should contribute to better characterize residual cardiometabolic risk linked to the number of atherogenic particles, when direct apoB100 determination is not available.

Background: BNP (Brain Natriuretic Peptide) and Nt-proBNP (N-terminal-pro-Brain Natriuretic Peptide) are valuable markers for the diagnosis and prognosis of heart failure (HF). The AQT90 FLEX is a newly released random access analyzer for point-of-care (POCT) measurement. The aim of our study was to determine Nt-pro-BNP concentrations in HF patients with the POCT assay., Methods: Nt-proBNP levels were measured in seventy seven HF patients and in thirty seven healthy volunteers. The results were compared with a central laboratory assay., Results: Nt-proBNP levels measured with the AQT90 FLEX were significantly correlated with the comparison Nt-proBNP assay and were related to HF severity., Conclusions: Nt-proBNP testing with the AQT 90 FLEX analyzer is comparable to the central lab assay and may offer the advantages of POCT testing for the diagnosis and prognosis of heart failure.

Background: Atherogenic dyslipidemia (AD), defined as low HDL-C plus elevated triglycerides (TG), comorbid to T2DM, increases cardiometabolic risk for CAD even when LDL-C is at target. In T2DM males, AD was shown to correlate with β-cell function loss, yet it is not established whether this applies across gender., Aim: To establish the prevalence and severity of AD in T2DM females, and to determine how it relates to cardiometabolic phenotype, glucose homeostasis, micro- and macrovascular complications, and 10-year absolute CV risk (UKPDS Risk Engine)., Methods: 340 T2DM females were ranked according to quintiles (Q) of the continuous variable log(TG)/HDL-C, with AD prevalence defined as HDL-C <50 mg.dL(-1) plus TG ≥150 mg.dL(-1), and β-cell function assessed with HOMA., Results: AD prevalence was 35%; mean HDL-C and TG were 52 (15) and 160 (105) mg.dL(-1). AD was significantly related to central fat, metabolic syndrome, sedentarity and skeletal sarcopenia, as well as to (hs)CRP, fibrinogen, uric acid, cystatin-C, Big ET-1, and 10-year UKPDS CV risk. AD correlated stepwise with lower β-cell function and hyperbolic product, and with accelerated loss of residual insulin secretion, higher HbA(1c) and prevalent microangiopathy., Conclusions: log(TG)/HDL-C is a simple means to grade AD and residual macrovascular risk in T2DM females. This ratio associates with major non-LDL cardiometabolic variables and ranks predicted CAD risk. In addition, log(TG)/HDL-C identifies worsening glucose homeostasis, poorer glycemic control, and prevalent microangiopathy.

Fibroblast growth factor 23 (FGF23) is a bone-derived hormone involved in the regulation of phosphate and calcium metabolism. We have evaluated the levels of C-terminal FGF23 (Ct-FGF23) in 73 patients presenting heart failure with reduced ejection fraction (HF-REF) and assess their potential predictive value for long-term survival through a 6 years follow-up. Ct-FGF23 levels were markedly increased in HF-REF. In univariate proportional hazard model, survival was related to glomerular filtration rate (eGFR), intact parathyroid hormone (PTH), B-type natriuretic peptides (BNP) and Ct-FGF23. In a multivariate analysis including age, EF, PTH, BNP, Ct-FGF23, calcium, phosphorus and eGFR levels, Ct-FGF23 is the strongest predictor of long term CV death., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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., (© 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation.)

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., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to evaluate the impact of myocardial viability assessment by delayed-enhanced cardiac magnetic resonance (DE-CMR) and of revascularization therapy on survival in patients with coronary artery disease (CAD) and low ejection fraction (EF)., Background: Prior studies have shown that DE-CMR predicts recovery of left ventricular (LV) dysfunction after revascularization., Methods: The authors prospectively evaluated survival of 144 consecutive patients (130 males, age 65 ± 11 years) with CAD and LV dysfunction (EF: 24 ± 7%) undergoing DE-CMR. Eighty-six patients underwent complete revascularization of dysfunctional myocardium (79 coronary artery bypass grafting, 7 percutaneous coronary intervention), whereas 58 patients remained under medical treatment., Results: Over the 3-year median follow-up, 49 patients died. Three-year survival was significantly worse in medically treated patients with dysfunctional viable than with nonviable myocardium (48% vs. 77% survival, p = 0.02). By contrast, in revascularized patients, survival was similar whether myocardium was viable or not (88% and 71% survival, respectively, p = NS). Hazard of death of viable myocardium remaining under medical treatment versus complete revascularization was 4.56 (95% confidence interval [CI]: 1.93 to 10.8). Cox multivariate analysis indicated that interaction of revascularization and viability provided significant additional value (chi-square test = 13.1, p = 0.004) to baseline predictors of survival (New York Heart Association functional class, wall motion score, and peripheral artery disease). More importantly, in 43 pairs of propensity score-matched patients, hazard of death (hazard ratio: 2.5 [95% CI: 1.1 to 6.1], p = 0.02) remained significantly higher for medically treated patients rather than for those with fully revascularized viable myocardium., Conclusions: Without revascularization, presence of dysfunctional viable myocardium by DE-CMR is an independent predictor of mortality in patients with ischemic LV dysfunction. This observation may be useful for pre-operative selection of patients for revascularization., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of our study was to determine NT-proBNP concentrations in heart failure (HF) patients with a luminescent oxygen channeling immunoassay (LOCI)., Design and Methods: Seventy HF patients were enrolled. NT-proBNP levels were measured with LOCI method and compared to a reference NT-proBNP assay., Results: LOCI NT-proBNP levels were significantly correlated with the reference NT-proBNP assay and were related to HF severity., Conclusions: LOCI assay demonstrates performances close to the comparative assay for NT-proBNP testing and allows a significant reduction of the time of analysis., (Copyright © 2011. Published by Elsevier Inc.)

Aims: Myostatin (Mstn), a member of the transforming growth factors (TGF)-β family that regulate skeletal muscle growth, has been identified as a regulator of cardiomyocyte growth. The aim of our study was to measure Mstn plasma concentrations in patients with congestive heart failure (CHF) and to evaluate their relationship with other neurohormones released in CHF., Methods and Results: concentrations of Mstn were measured using a competitive immunoassay, in 76 CHF patients who were receiving optimal treatment and 60 healthy controls. Circulating levels of other neurohormones N-terminal pro-atrial natriuretic peptide (NT-proANP), B-type natriuretic peptide (BNP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and Big ET-1 were also measured. Plasma Mstn was higher in CHF patients than in controls (63.0 vs. 43.0 ng/mL; P < 0.001). In CHF, Mstn levels correlated positively with NT-proANP (r=0.25; P=0.03), BNP (r=0.33; P<0.01), NT-proBNP (r=0.32; P<0.01), and Big ET-1 (r=0.26; P=0.02). No significant correlations were observed with age and creatinine., Conclusion: Our results demonstrate that plasma concentrations of Mstn are significantly increased in CHF patients and that Mstn correlates with biomarkers related to HF severity. Our study confirms the activation of Mstn in patients with heart failure.

Background: Apolipoprotein B100 (apoB) is a superior indicator of CV risk than total or LDL-C. Non-HDL-C represents a simple surrogate for apoB in hypertriglyceridemic and/or T2DM patients. ApoB and non-HDL-C show high correlation, although the degree of mutual concordance remains debated in CV risk evaluation., Objectives: We used the Discriminant Ratio (DR) methodology to compare the performance of non-HDL-C with that of apoB to rank diabetic patients according to dyslipidemia and to establish the underlying relationship between these variables taking measurement noise and intra-/intersubject variation into account, and to derive an unbiased equivalence equation., Methods: Fasting total C, HDL-C, apoB and triglycerides were measured in 45 diabetic patients. The DR of the underlying between-subject standard deviation (SD) to the within-subject SD was calculated from duplicates. Correlation coefficients between pairs were adjusted to include an estimate of the underlying correlation., Results: Mean values [day 1 (1SD)] were 143 (36) mg/dl (non-HDL-C) and 98 (24) mg/dl (apoB). The DR's of both parameters were similar (1.76 and 1.83) (p = 0.83). Pearson's product-moment correlation coefficient between tests was very high (0.94), reaching unity (1.00) after attenuation adjustment. The unbiased equation of equivalence relating apoB to non-HDL-C had a slope of 0.65 and an intercept of 6.3 mg/dl., Conclusions: The discrimination power of non-HDL-C is similar to that of apoB to rank diabetic patients according to atherogenic cholesterol and lipoprotein burden. Since true correlation between variables reached unity, non-HDL-C may provide not only a metabolic surrogate but also a candidate biometrical equivalent to apoB, as non-HDL-C calculation is readily available.

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 mandatory to select the appropriate therapy and care. HF is associated to cardiac remodeling and inflammation 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 patients 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: T2DM is associated with atherogenic dyslipidemia (AD), defined as decreased HDL-C plus raised triglycerides (TG). AD confers increased risk for CAD, even when LDL-C is at target. AD is rarely assessed due to lack of screening methods consensus., Aim: To establish the prevalence and severity of AD from log(TG)/HDL-C in T2DM males, and to determine how it relates to cardiometabolic phenotype, glucose homeostasis, micro- and macrovascular complications, and 10-year UKPDS CV risk., Methods: 585 T2DM males divided according to quintiles (Q) of log(TG)/HDL-C. AD prevalence defined as HDL-C <40 mg x dL(-1) plus TG ≥150 mg x dL(-1). β-cell function assessed with HOMA., Results: Mean HDL-C and TG were 44 (13) and 204 (155) mg x dL(-1). AD prevalence was 35%. AD correlated with lower β-cell function, with accelerated loss of insulin secretion, and with poorer HbA1c levels. AD was related to a high prevalence of CAD, and also to 10-year absolute CAD risk., Conclusions: log(TG)/HDL-C is a simple means to estimate AD and the residual CV risk it confers in T2DM. AD closely associates with major cardiometabolic and glucose homeostasis determinants and poorer metabolic control. The ratio also relates to macroangiopathy prevalence and ranks future CAD risk, and is well-suited to capture non-LDL-related macrovascular residual risk and major glycemic determinants.

Background: Erectile dysfunction (ED) is a frequent comorbidity in patients with type 2 diabetes mellitus (T2DM), and is now increasingly considered a surrogate marker of endothelial dysfunction as well as a sentinel predictor of new-onset macroangiopathic events. Less attention, however, has been directed at the potential association of ED and microangiopathy in hyperglycaemic states., Methods: We analyzed 221 consecutive male T2DM outpatients in whom ED was assessed by the International Index of Erectile Function (IIEF-5) questionnaire. ED(+) patients (IIEF-5 1-20; n=83) were compared with an age-matched ED(-) cohort (IIEF-5 21-25; n=51), with similar diabetes duration, in terms of cardiovascular (CV) risk factors, micro-/macroangiopathy and the United Kingdom Prospective Diabetes Study (UKPDS) risk score., Results: Mean age and diabetes duration were 58 and 10 years, respectively. IIEF-5 score (1 S.D) was 23 (1) in ED(-) vs 11 (6) in ED(+). Anamnestic impotence and erectogenic drug use were reported by 52% and 36%, respectively, of ED(+) vs 12% and 8%, respectively, of ED(-) (P<0.0002 and P<0.0001, respectively). The metabolic syndrome prevalence (88% vs 64%; P=0.002) and central adiposity markers (waist, waist/height and visceral fat) were all significantly higher in ED(+). HbA(1c) was similar in both groups: 7.5% (1.3%), and there were also no significant differences in smoking, blood pressure, HOMA insulin sensitivity, cholesterol and glomerular filtration rate. However, prevalences of retinopathy, polyneuropathy and elevated albuminuria, and the composite endpoint of peripheral artery disease, transient ischaemic attacks and/or stroke, were markedly increased in ED(+) (all P<0.05). No differences were observed in coronary artery disease prevalence or in the UKPDS 10-year CV risk between the two ED groups., Conclusion: IIEF-5-defined ED in men with T2DM is associated with a marked increase in the metabolic syndrome, central adiposity and microangiopathy. These data suggest that diagnosing ED in T2DM warrants detailed screening and monitoring for microangiopathy in target organs.