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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. 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). 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. 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. • Sexual dimorphisms and ethnicity modulate cardiometabolic phenotype and susceptibility to vascular complications. • This study revisited gender dimorphisms in a multi-ethnic cohort with T2DM. • In Black women, retinopathy risk was higher and gender did not confer macrovascular protection. • In White women, loss of gender-related protection was about cerebrovascular risk. [ABSTRACT FROM AUTHOR]

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). 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. 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. 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%. 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. [ABSTRACT FROM AUTHOR]

Abstract 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. [ABSTRACT FROM AUTHOR]

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 HbA1c 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 apoB100 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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). 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. Multi-level eye protection in diabetes is linked to non-alcoholic fatty liver independently of atherogenic dyslipidemia. • Fatty liver is comorbid with atherogenic dyslipidaemia and type 2 diabetes mellitus. • Atherogenic dyslipidaemia predicts risk of microvascular complications. • This study investigated the cross-effect of fatty liver and atherogenic dyslipidaemia on microangiopathies. • Fatty liver is linked to multi-level eye protection independent of atherogenic dyslipidaemia. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The therapeutic management of heart failure has evolved over the past 20 years. Indeed, before 1997, patients with heart failure with reduced ejection fraction (HFrEF) were mainly treated with angiotensin-converting enzyme inhibitors (ACEi). After 1997, several clinical trials demonstrated the benefit of beta-blockers and from 2012, the use of mineralocorticoid receptor antagonists (MRAs) were recommended by AHA guidelines. We prupose to evaluate and analyze clinical characteristics, treatment evolution and long-term outcomes in a large cohort of HFrEF ≤ 35%. Three time periods based on changes in clinical practice according to HF guidelines were defined. Between 1994 and 2020, 2512 patients were included at St-Luc University Hospital at the time of diagnosis of HFrEF and prospectively followed for a primary endpoint of all-cause mortality at 5 years. Patients were classified and compared according to the time of enrolment (group 1: before 1997, group 2: 1997–2012, group 3: 2013–2020). All-cause mortality was analysed using univariate Cox regression analysis. Of the 2512 patients, 67 patients were included in group 1, 1805 in group 2 and 640 in group 3. Patients in groups 2 and 3 were significantly older, had more comorbidities such as hypertension and chronic obstructive pulmonary disease than patients in group 1 (Table 1). Over time, the prevalence of ischemic heart disease decreased and the use of beta-blockers and MRAs increased. A total of 925 (37%) patients died after five years. After adjustment for age and ischaemic etiology, 5-year all-cause mortality was lower in group 2 (HR: 0.41, 95% CI: 0.29 to 0.58, P ≤ 0.001) and group 3 (HR: 0.43, 95% CI: 0.30 to 0.61, P ≤ 0.001) compared to group 1 (Fig. 1). In heart failure with reduced ejection fraction, a significant improvement in survival was observed over the last 20 years, clearly related to better therapeutic management. [ABSTRACT FROM AUTHOR]

Background T2DM management requires tight control of 3 critical quality indicators to prevent vascular complications: LDL-C, SBP, and HbA 1c . 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 HbA 1c < 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. [ABSTRACT FROM AUTHOR]

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 T2DMdescendants,with worsened insulin resistance and atherogenic dyslipidemia among 1st-degree offspring. [ABSTRACT FROM AUTHOR]

Abstract: 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 &y& Elsevier]

Abstract: 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, hsCRP 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 &y& Elsevier]

Abstract: 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 &y& Elsevier]

Abstract: 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. [ABSTRACT FROM AUTHOR]

Abstract: 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 HbA1c was higher by 0.54% in MetS (+). Hypertension prevalence was twice higher in MetS (+) patients, who had increased systolic blood pressure by +7mmHg. 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. [Copyright &y& Elsevier]

Abstract: 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%, HbA1c 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 <0.003). MACE and coronary artery disease (CAD) prevalence were 61 and 63% higher in OSAS (+) (61% vs. 38%; p <0.01 and 44% vs. 27%; p <0.03), who showed a higher stroke prevalence (15% vs. 8%; NS). 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. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

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]pgml−1 in MetS (−) (n =75) versus 6.7 [5.2–9.1]pgml−1 in MetS (+) (n =380; P <0.0001). There was a progression in Big ET-1 across MetS scores: 6.3 [5.2–8.5]pgml−1 in MetS (+) 3/5; 6.9 [5.1–9.4]pgml−1 in MetS (+) 4/5 and 7.3 [5.6–9.5]pgml−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]pgml−1 in MetS (−) Macro (−) versus 5.70 [4.60–7.50]pgml−1 in MetS (+) Macro (−) (P <0.0001), and 5.70 [5.20–7.60]pgml−1 in MetS (−) Macro (+) versus 7.60 [5.80–10.13]pgml−1 in MetS (+) Macro (+) (P <0.0001), respectively. Such patterns were not observed with natriuretic peptides. Comparison between MetS (+) Macro (−) versus MetS (−) Macro (+) confirms that such incremental differences should not be solely ascribed to parallel shifts in IR and/or compensatory hyperinsulinaemia. 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. [Copyright &y& Elsevier]

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)/ApoA1 ratios to rank diabetics according to dyslipidemia severity. Background: ApoB/ApoA1 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 ApoA1 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/ApoA1, respectively. The highest DRs were those of total C/HDL-C and non-HDL-C/HDL-C (2.33 and 2.38; p <0.05 and <0.02 versus the DR of LDL-C/HDL-C). The DR of ApoB/ApoA1 (2.12) was non-significantly higher than that of LDL-C/HDL-C (1.45). Conclusions: ApoB/ApoA1 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. [Copyright &y& Elsevier]

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 < 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. [ABSTRACT FROM AUTHOR]

An abstract of the paper "Can Viability Assessment by DE-MRI Predict Survival in Patients With Multivessel Disease and Low Ejection Fraction? Influence of Treatment Strategies," by Bernhard L. Gerber and colleagues is presented.

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 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. [ABSTRACT FROM AUTHOR]

Highlights: [•] ProBNP1–108, BNP and Nt-proBNP levels were measured in patients with systolic heart failure (HF). [•] 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. [•] The highest proBNP levels were related to patients with the highest risk of CV death. [ABSTRACT FROM AUTHOR]

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 &y& Elsevier]