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This executive document reflects and updates the key points of a Consensus document on Cardiovascular (CV) Prevention realized through the contribution of a number of Italian Scientific Societies and coordinated by the Italian Society of Cardiovascular Prevention (SIPREC). The aim of this executive document is to analyze and discuss the new recommendations introduced by international guidelines for the management of major CV risk factors, such as hypertension, dyslipidemias and type 2 diabetes, consisting in the identification of lower therapeutic targets, in the promotion of combination fixed drug therapies and in the introduction in routine clinical practice of new effective pharmacological classes. Moreover, the document highlights the importance of effective CV prevention strategies during the the coronavirus disease 2019 (COVID-19) outbreak which has dramatically changed the priorities and the use of available resources by the national healthcare systems and have caused a reduction of programmed follow-up visits and procedures and even of hospital admissions for severe acute pathologies. In addition, the pandemic and the consequent lockdown measures imposed have caused a widespread diffusion of unhealthy behaviors with detrimental effects on the CV system. In such a context, reinforcement of CV prevention activities may play a key role in reducing the future impact of these deleterious conditions. [ABSTRACT FROM AUTHOR]

Background: Microparticles (MPs) are vesicular structures shed from endothelial or circulating blood cells, after activation or apoptosis, and can be considered markers of vascular damage. We aimed to determine the levels of circulating MPs, their content of miRNA-126-3p and 5p, and their relationship with early endothelial activation/damage, in patients with different degree of glucose tolerance. Methods: CD62E+, CD62P+, CD142+, CD45+ circulating MPs, their apoptotic (AnnexinV+) fractions, and miRNA-126 expression were determined in 39 prediabetic (PreDM), 68 type 2 diabetic (T2DM), and 53 control (NGT) subjects, along with main anthropometric and biochemical measurements. MPs were analysed by flow cytometry. miRNA-126 was measured by quantitative real-time PCR. Plasma antioxidant capacity was determined by electronic spin resonance; ICAM-1, and VCAM-1 by ELISA. Results: Activated endothelial cell-derived MPs (CD62E+) were significantly increased in PreDM and T2DM in comparison to NGT (p < 0.0001). AnnexinV+/CD62E+ MPs and Annexin V+ MPs were significantly increased in T2DM compared to PreDM and NGT (p < 0.001); other MPs were not significantly different among groups. Plasma antioxidant capacity was significantly decreased in PreDM and T2DM compared to NGT (p = 0.001); VCAM-1 significantly increased in PreDM and T2DM in comparison to NGT (p = 0.001). miR-126-3p expression, but not miR-126-5p, in MPs, decreased significantly and progressively from NGT, to PreDM, and T2DM (p < 0.001). In PreDM and T2DM, CD62E+ MPs level was significantly and negatively associated with plasma glucose (p = 0.004). Conclusion: We show for the first time that circulating CD62E+ MPs level and miR-126-3p content in MPs are abnormal in subjects with pre-diabetes; the content of miR-126-3p correlates with markers of endothelial inflammation, such as VCAM-1, plasma antioxidant capacity, and microparticles, well-accepted markers of endothelial dysfunction. [ABSTRACT FROM AUTHOR]

Upon activation, neutrophils undergo histone citrullination by protein arginine deiminase (PAD)4, exocytosis of chromatin and enzymes as neutrophil extracellular traps (NETs), and death. In diabetes, neutrophils are primed to release NETs and die by NETosis. Although this process is a defense against infection, NETosis can damage tissue. Therefore, we examined the effect of NETosis on the healing of diabetic foot ulcers (DFUs). Using proteomics, we found that NET components were enriched in nonhealing human DFUs. In an independent validation cohort, a high concentration of neutrophil elastase in the wound was associated with infection and a subsequent worsening of the ulcer. NET components (elastase, histones, neutrophil gelatinase-associated lipocalin, and proteinase-3) were elevated in the blood of patients with DFUs. Circulating elastase and proteinase-3 were associated with infection, and serum elastase predicted delayed healing. Neutrophils isolated from the blood of DFU patients showed an increased spontaneous NETosis but an impaired inducible NETosis. In mice, skin PAD4 activity was increased by diabetes, and FACS detection of histone citrullination, together with intravital microscopy, showed that NETosis occurred in the bed of excisional wounds. PAD4 inhibition by Cl-amidine reduced NETting neutrophils and rescued wound healing in diabetic mice. Cumulatively, these data suggest that NETosis delays DFU healing. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- Postprandial glycemia is an independent risk factor for cardiovascular disease that is more powerful than fasting glycemia and determines myocardial perfusion defects in type 2 diabetes. We examined the efficacy of two different insulin regimes (regular insulin and insulin analog) in controlling postprandial hyperglycemia and in preventing myocardial perfusion abnormalities. RESEARCH DESIGN AND METHODS -- A total of 20 consecutive type 2 diabetic patients and 20 control subjects were enrolled in this randomized, three-way, cross-over, placebo-controlled study. Myocardial perfusion was assessed by myocardial contrast echocardiography (MCE) in fasting and postprandial (120 min) state. RESULTS -- Insulin analog was associated with lower, but not statistically significant, postprandial glycemia than regular insulin (glucose increase: 116 ± 8 vs. 136 ± 5%, P = NS). However, the area under the curve following insulin analog was significantly lower than regular insulin (18,354 ± 702 vs. 20,757 ± 738 mg per 120 min, P = 0.032). Fasting myocardial flow velocity (β), myocardial blood volume (MBV), and myocardial blood flow (MBF) did not differ between control and type 2 diabetic subjects. Postprandial β (0.67 ± 0.24 vs. 0.92 ± 0.25, P < 0.01), MBV (8.4 ± 2 vs. 10.9 ± 1.2, P < 0.01), and MBF (5.6 ± 2 vs. 9.9 ± 2.8, P < 0.01) increased significantly in control subjects. In type 2 diabetes, during placebo in the postprandial state, β increased (0.65 ± 0.27 vs. 0.89 ± 0.24, P < 0.01), while MBV (8.34 ± 1.2 vs. 4.3 ± 1.3, P < 0.01) and MBF (5.4 ± 1.5 vs. 3.4 ± 0.9, P < 0.01) decreased. Similar changes in MCE variables were observed after regular insulin: β increased (0.65 ± 0.22 vs. 0.92 ± 0.12, P < 0.01) and MBV (8.2 ± 2 vs. 5.2 ± 1.16, P < 0.01) and MBF (5.4 ± 1.9 vs. 4.2 ± 0.86, P < 0.01) were reduced. After insulin analog, postprandial β (0.66 β 0.18 vs. 0.9 β 0.18, P < 0.01), MBV (8.2 ± 1.6 vs. 9.6 ± 1.2, P < 0.01), and MBF (5.4 ± 2 vs. 7.2 ± 1.9, P < 0.01.) increased. Values of postprandial MBV and MBF were higher after insulin analog than regular insulin treatment. CONCLUSIONS -- insulin analog partially reversed myocardial perfusion abnormalities observed in postprandial state by improving glucose control. [ABSTRACT FROM AUTHOR]

Defective endothelium is a key event in the development of atherosclerosis in diabetes: alteration of the L-arginine-nitric oxide (NO) pathway has been suggested. We propose a modeling approach of the L-arginine-NO pathway in vivo in both control and type 2 diabetic subjects based on the intravenous bolus injection of L-[(15)N]arginine and subsequent noncompartmental and compartmental model analysis of L-[(15)N] arginine in plasma and [(15)N]nitrate in the urine. No differences in arginine kinetics were observed between normal subjects and diabetic patients. [(15)N]nitrates were detectable up to 48 h from the L-(15)[N]arginine administration; no differences were found in the tracer-to-tracee ratio in each urine collection. However, the NO synthesis in plasma from arginine was lower (P = 0.05 for the noncompartmental and 0.1208 for the compartmental analysis, by Mann-Whitney test) in diabetic patients than in control subjects when expressed both in absolute terms (50% decrease) and as percentage of NO turnover (30% decrease). This new modeling approach of L-arginine-NO pathway provides a detailed picture of arginine kinetics and nitrate metabolism. From our data, it appears that noncomplicated type 2 diabetic patients have a decreased conversion of arginine to NO. [ABSTRACT FROM AUTHOR]