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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.)

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.)

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: 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.

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.

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]

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]

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]

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. [ABSTRACT FROM AUTHOR]

Abstract 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. Highlights • FGF-23 is a key regulator of the phosphorus homeostasis. • FGF-23 has several direct effects on cardiac function. • We showed that intact FGF-23 is an independent predictor of cardiovascular death in HF. • Intact FGF-23 provides added value to NT-proBNP for prognostication of HF patients. [ABSTRACT FROM AUTHOR]