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Introduction: Inclisiran is a novel posttranscriptional gene silencing therapy that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9) synthesis by RNA interference and has a potent, dose-dependent, durable effect in lowering LDL-C, and therefore is an effective drug to treat dyslipidemia, reducing the risk for acute cardiovascular (CV) events. It is safe and well-tolerated. Areas covered: This paper aims to review the mechanism of action of inclisiran while evaluating its efficacy and safety in the treatment of dyslipidemia from data of the clinical trials in the ORION program. Expert opinion: Data from the clinical trials in the ORION program demonstrated efficacy and safety of inclisiran in patients with dyslipidemia. Adverse events were similar in the inclisiran and placebo groups in the clinical trials, although injection-site reactions were more frequent with inclisiran than with placebo. Although the combination of efficacy and safety makes inclisiran a good option for the treatment of dyslipidemia compared to other PCSK9 targeting therapeutic strategies, however, further studies should exclude the possibility that inclisiran, through lower-affinity interactions, may influence other mRNAs in the physiological milieu.

Inflammation is a marker of arterial disease stemming from cholesterol-dependent to -independent molecular mechanisms. In recent years, the role of inflammation in atherogenesis has been underpinned by pharmacological approaches targeting systemic inflammation that have led to a significant reduction in cardiovascular disease (CVD) risk. Although the use of nutraceuticals to prevent CVD has largely focused on lipid-lowering (e.g, red-yeast rice and omega-3 fatty acids), there is growing interest and need, especially now in the time of coronavirus pandemic, in the use of nutraceuticals to reduce inflammatory markers, and potentially the inflammatory CVD burden, however, there is still not enough evidence to confirm this. Indeed, diet is an important lifestyle determinant of health and can influence both systemic and vascular inflammation, to varying extents, according to the individual nutraceutical constituents. Thus, the aim of this Position Paper is to provide the first attempt at recommendations on the use of nutraceuticals with effective anti-inflammatory properties.

Introduction Red yeast rice (RYR) is an effective cholesterol-lowering nutraceutical reversibly inhibiting 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase. As liver damage is a possible (albeit rare) side effect of HMG-CoA inhibitors, it make sense to focus on the tolerability of the liver to RYR extracts. The aim of this paper is to offer an expert opinion on the risk of liver damage by the use of RYR extract. Methods A review of the available literature has been carried out and critically reviewed by the authors. Results According to a large meta-analysis of 53 randomized clinical trials comprising 112 treatment arms, which included 8535 subjects with 4437 in the RYR arm and 4303 in the control arm of the study, RYR administration was not associated with increased risk of Drug Induced Liver Injury (DILI) during RYR treatment. Single cases of DILI have been associated with the use of RYR supplements. Even if the causal relationship is hardly demonstrable, it is possible that products containing impurities or toxic elements such as citrinin or unstandardized dosages of bioactive compounds like monacolins, could be implicated in liver toxicity. Conclusion DILI associated with RYR intake are exceptional and hardly associated to RYR per se rather than to low-quality products. Nutrivigilance and stricter manufacturing regulations should be implemented and are recommended in order to protect consumers from low quality and potentially dangerous dietary supplements.

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Effect of a nutraceutical containing Ortosiphon stamineus leaf extract on blood pressure and metabolic syndrome components in hypertensive dyslipidaemic patients treated with calcium-channel blockers, or angiotensin converting enzyme inhibitors: a randomized clinical trial.

Despite advances in pharmacological treatment, diabetic nephropathy is still the leading cause of end-stage renal disease and an important cause of morbidity and mortality in diabetics. Glycosaminoglycans are long, unbranched mucopolysaccharides that play an important role in establishing a charge-selective barrier that restricts the passage of negatively charged molecules, such as albumin and other proteins, at the level of the glomerular basal membrane. Their loss is associated with loss of selectivity and proteinuria. Extensive preclinical evidence and some clinical trials suggest that glycosaminoglycans replacement is associated with improvement of glomerular selectivity and of proteinuria. Sulodexide could also have some other effects, potentially useful to reduce the renal damage and the cardiovascular disease associated with proteinuria, such as improvement of haemorheological and blood lipid parameters, an endothelium protective effect and anti-inflammatory action. This review will discuss the evidence supporting the potential nephroprotective effects of sulodexide and other glycosaminoglycans.

The aim of this study was to evaluate the effect of an oral glucose tolerance test (OGTT) on the level of endothelial dysfunction and vascular inflammation markers in healthy subjects (H) and diabetic overweight patients (D). We enrolled 256 healthy subjects and 274 type 2 diabetic patients. We evaluated blood glucose (BG), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), high-sensitivity C reactive protein (hsCRP), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), and tumor necrosis factor-alpha (TNF-alpha) at baseline and after OGTT. We observed that BG, sICAM-1, IL-6, hs-CRP, sVCAM-1, sE-selectin, and TNF-alpha values were higher in D group than in H group. In a large sample of adult healthy subjects and type 2 diabetics we observed that both answer to an OGTT with a significant increase in biomarkers of systemic low-grade inflammation and endothelial dysfunction such as hsCRP, IL-6, TNF-alpha, sICAM-1, sVCAM-1, and sE-selectin. Type 2 diabetics experienced, however, a more significant increase in TNF-alpha, and sE-selectin.

We evaluated the effect of an oral glucose tolerance test (OGTT) on the level of biomarkers of vascular remodelling. We enrolled 256 Caucasian overweight healthy subjects (H) and 274 overweight type 2 diabetic patients (D). All patients underwent basal measurements of blood glucose (BG), nitrites/nitrates, adiponectin (ADP), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9) before and after OGTT. Nitrites/nitrates decrease was present after 60, 90, 120, and 180 min in both groups. Nitrite/nitrate levels were decreased at baseline, after 30 and 60 min in D group compared to H group. ADP decrease was present after 90, 120, and 180 min, in both groups. ADP levels were lower in D group than in H group during OGTT. MMP-2 increase was present after 60, 90, and 120 min in H group, while MMP-2 increase was observed after 90, 120, and 180 min in D group. MMP-2 levels were higher in D group than in H group during OGTT. MMP-9 increase was present in H group after 60, 90, 120, and 180 min, while MMP-9 increase was observed after 90, 120, and 180 min in D group. MMP-9 levels were higher in D group than in H group during OGTT. Postprandial glycemia induces an acute increase in biomarkers of vascular remodelling.

OBJECTIVE: To evaluate the effect on coagulation and fibrinolysis parameters and on non-conventional cardiovascular risk factors of metformin plus nateglinide or glibenclamide in naïve type 2 diabetes patients. PATIENTS AND METHODS: A total of 248 type 2 diabetic patients were enrolled and randomly assigned to receive nateglinide or glibenclamide, and metformin for 12 months. We assessed body mass index (BMI), glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), postprandial plasma insulin (PPI), homeostasis model assessment index (HOMA index), lipid profile with lipoprotein (a) [Lp(a)], fibrinogen (Fg), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (t-PA), homocysteine (Hcy), systolic blood pressure (SBP), diastolic blood pressure (DBP). RESULTS: After 9 months of treatment, both tested drug combinations were similarly associated with a significant reduction in FPG (nateglinide, -17.2%; glibenclamide, -16.9%, both p

Background: Albuminuria is the best and most readily available marker for glomerular damage and progressive renal function loss in patients with diabetic nephropathy. Recently, administration of the oral glycosaminoglycan sulodexide (a mixture of 80% fast-moving heparin and 20% dermatan sulphate) was shown to effectively decrease albumin excretion rate in diabetics with nephropathy. Aims: To evaluate whether the hypoalbuminuric effect of sulodexide is associated with improvement of the renal vascular or tubule function. Methods: Forty-five type 1 diabetic patients, affected by diabetic nephropathy with albuminuria for at least 5 years, were randomly allocated to sulodexide or untreated. Those allocated to sulodexide were given 100 mg of sulodexide daily for 120 days. Renal vascular function (DIR) and N-acetyl-β-D-glucosaminidase (NAG) excretion were estimated before and at the end of the study, the former in thesulodexide group only. DIR was measured as two Crcl lasting 120 min (before and during 2 µg/kg b.w. i.v. dopamine). Results: The analysis of trends during the study demonstrated a marked reduction of albuminuria in the sulodexide group (from 126.1 ± 15.41 to 93.6 ± 13.7 mg/day). DIR rose from 13.2 ± 2.1% to 15.44 ± 1.9% (relative increase: +16.9%), and NAG excretion showed a decreasing trend decreased in the sulodexide group only (from 5.1 ± 0.62 to 4.7 ± 0.40 U/gcreat). Conclusion: The findings presented in this study indicate for the first time that orally available sulodexide may favorably affect the renal vascular function in type 1 diabetic patients with nephropathy and microalbuminuria. The effect of sulodexide on NAG is strongly influenced by the baseline NAG values, with a significant NAG reduction in the patients with the highest baseline NAG values.

Liver steatosis is a common feature of overweight dyslipidaemic patients, suggested by some recent literature to increase the risk cardiovascular disease. Preliminary data suggest that berberine can improve liver steatosis. The aim of our study was to evaluate the effect of berberine in dyslipidaemic patients treated with a standardized lipid-lowering nutraceutical with or without berberine. 39 subjects (19 M, 20 W) affected by mixed dyslipidemia (LDL-C>130 mg/dL and TG>200 mg/dL) and liver steatosis were randomized to be treated with a Monascus puipureus (3 mg monakoline) lipid-lowering nutraceutical or with Monascus pmpureus plus berberine (Armolipid Plus (R)) for 8 weeks. The effect on liver was evaluated monitoring Hepatic Steatosis Index [8 x (GPT/GOT ratio) + BMI (+2 if women; +2 if DM). All patients tolerated the treatment. No increase in transaminases was observed. Both treatments experienced a significant improvement of LDL-C cholesterolemia (-22%), whereas only berberine-monascus lowered significantly TG (-25%). Considering HSI, it did not change in monascus treated patients (T0=362 +/- 2.0 vs T8= 35.5 +/- 1.4 p>0.05), while it significantly improved in the berberine-monascus treated ones (T0=365 +/- 1.8 vs T8= 35.3 +/- 1.3, t= 4.750, p