ORal anticoaGulants in diAbetic and Nondiabetic patients with nOn-valvular atrial fibrillatioN (ORGANON).

BACKGROUND: Diabetes represents a pro-thrombotic condition. OBJECTIVES: The primary objective was to evaluate the effects of Vitamin K Antagonist (VKA) compared to direct oral anticoagulants (DOACs) in diabetic and nondiabetic patients with non-valvular atrial fibrillation, newly diagnosed. The secondary objective was to evaluate the effects on the risk of bleeding. METHODS: We enrolled 300 patients with newly diagnosed atrial fibrillation. One hundred and sixteen patients were taking warfarin, 31 acenocumarol, 22 dabigatran, 80 rivaroxaban, 34 apixaban, and 17 edoxaban. We evaluated: anthropometric parameters, glycated hemoglobin (HbA1c), fasting and post-prandial glucose (FPG, and PPG), lipid profile, Lp(a), small and dense low-density lipoprotein (SD-LDL), oxidized LDL (Ox-LDL), I-troponin (I-Tn), creatinine, transaminases, iron, red blood cells (RBC); hemoglobin (Hb), platelets (PLT), fibrinogen, D-dimer, anti-thrombin III, C-reactive protein (Hs-CRP), Metalloproteinases-2 (MMP-2), Metalloproteinases-9 (MMP-9), and incidence of bleeding. RESULTS: We did not record any differences among nondiabetic patients between VKA and DOACs. However, when we considered diabetic patients, we found a slight, but significant improvement of triglycerides and SD-LDL. As regards incidence of bleeding, minor bleeding was more frequent in VKA diabetic group compared to DOACs diabetic group; furthermore, the incidence of major bleeding was higher with VKA in nondiabetic and diabetic group, compared to patients with DOACs. Among DOACs, we recorded a higher incidence of bleeding (minor and major) with dabigatran compared to rivaroxaban, apixaban and edoxaban in nondiabetic and diabetic patients. CONCLUSION: DOACs seem to be metabolically favourable in diabetic patients. Regarding incidence of bleeding, DOACs with the exception of dabigatran, seem better than VKA in diabetic patients.

Lipid-lowering nutraceuticals update on scientific evidence.

: Cardiovascular diseases (CVDs) are the main cause of mortality worldwide. Risk factors of CVD can be classified into modifiable (smoking, hypertension, diabetes, hypercholesterolemia) through lifestyle changes or taking drug therapy and not modifiable (age, ethnicity, sex and family history). Elevated total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) levels have a lead role in the development of coronary heart disease (CHD), while high levels of high-density lipoprotein-cholesterol (HDL-C) seem to have a protective role.The current treatment for dyslipidemia consists of lifestyle modification or drug therapy even if not pharmacological treatment should be always considered in addition to lipid-lowering medications.The use of lipid-lowering nutraceuticals alone or in association with drug therapy may be considered when the atherogenic cholesterol goal was not achieved.These substances can be classified according to their mechanisms of action into natural inhibitors of intestinal cholesterol absorption, inhibitors of hepatic cholesterol synthesis and enhancers of the excretion of LDL-C. Nevertheless, many of them are characterized by mixed or unclear mechanisms of action.The use of these nutraceuticals is suggested in individuals with borderline lipid profile levels or with drug intolerance, but cannot replace standard lipid-lowering treatment in patients at high, or very high CVD risk.Nutraceuticals can also have vascular effects, including improvement in endothelial dysfunction and arterial stiffness, as well as antioxidative properties. Moreover, epidemiological and clinical studies reported that in patients intolerant of statins, many nutraceuticals with demonstrated hypolipidemic effect are well tolerated.

Effects on oral fat load of a nutraceutical combination of fermented red rice, sterol esters and stanols, curcumin, and olive polyphenols: A randomized, placebo controlled trial.

BACKGROUND: In literature, there are several studies about the effects of nutraceutical combinations at fasting, but data in post-prandial phase are lacking. PURPOSE: We planned a study to evaluate the efficacy and safety of a nutraceutical agent containing fermented red rice, phytosterols and olive polyphenols compared to placebo in a sample of Caucasian patients with low cardiovascular risk, both at fasting and after an oral fat load. STUDY DESIGN: Eighty patients were randomized to receive, as addition to diet and physical activity, a nutraceutical combination containing fermented red rice, sterol esters and stanols, curcumin, and olive polyphenols or placebo (control group), once a day. METHODS: We evaluated at baseline, and after 3 months: body mass index, fasting plasma glucose, lipid profile, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and soluble endothelial-leukocyte adhesion molecule-1. We evaluated these parameters both at fasting, and after an oral fat load. RESULTS: Nutraceutical combination gave a reduction of total cholesterol, triglycerides, and low-density lipoprotein cholesterol, both compared to baseline (p < 0.05 for all), and to placebo (p < 0.05 for all). We recorded a reduction of soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and sE-selectin in the group treated with nutraceutical combination, both compared to baseline (p < 0.05 for all), and to placebo (p < 0.05 for all). Parameters recorded during oral fat load improved compared to the oral fat load performed at baseline with the nutraceutical combination. CONCLUSIONS: The nutraceutical combination of fermented red rice, sterol esters and stanols, curcumin, and olive polyphenols seems to be effective in improving lipid profile and markers of endothelial damage in dyslipidemic patients in primary prevention at low risk for developing cardiovascular disease. The true novelty of this study, however, is the improvement of endothelial damage after an oral fat load compared to placebo.

High-dose atorvastatin versus moderate dose on early vascular protection after ST-elevation myocardial infarction.

BACKGROUND AND AIM: Clinical benefits of early high-dose statin therapy after acute coronary syndromes are widely known; however, there is poor evidence on the specific setting of ST-elevation myocardial infarction (STEMI) and dose-dependent effects of this therapy on endothelial function and inflammatory biomarkers in the most vulnerable phase after acute coronary syndromes: the postdischarge period. In our study, we compared the short-term effects of high (80 mg) vs moderate doses of atorvastatin (20 mg) in patients with STEMI undergoing primary percutaneous coronary intervention on endothelial function and vascular inflammation. The aim of our study was the evaluation of dose-dependent short-term effects. SUBJECTS AND METHODS: We enrolled 52 patients within 48 hours of a STEMI to atorvastatin 80 mg (n=26) or 20 mg (n=26). Every patient underwent endothelial function evaluation by the reactive hyperemia-peripheral arterial tonometry (RH-PAT) index on the first day and 1 month after the STEMI. At the same time, we measured lipid profile and serum levels of high-sensitivity CRP, IL6, TNFα, and oxidized LDL. RESULTS: After 1 month of therapy, we observed differences in high-sensitivity CRP levels (0.04±0.02 mg/dL vs 0.36±0.3 mg/dL, P=0.001), IL6 (1.12±0.93 pg/mL vs 3.13±2.84 pg/mL, P=0.03), and improvement in RH-PAT index (1.96±0.16 vs 1.72±0.19, P=0.002) in the group treated with high-dose vs moderate-dose atorvastatin. There was no significant difference in levels of TNFα or oxidized LDL with atorvastatin 20 mg, while there was a reduction in these variables in the group treated with atorvastatin 80 mg. We observed a correlation between high-sensitivity polymerase chain reaction and RH-PAT index on the 30th day after STEMI (r=0.5, P=0.001). CONCLUSION: Higher dose statin therapy in patients with STEMI undergoing primary percutaneous coronary intervention showed early greater vascular protective effects that moderate dose.

Homocysteine and heart failure: an overview.

An elevated plasma level of homocysteine (HCY) is associated with increased risk of thrombotic and atherosclerotic vascular disease. Several studies and recent patents have demonstrated that hyper-homocysteinemia (HHCY) is an independent risk factor for vascular disease. An elevated homocysteine level has been also reported to be a risk factor for the development of congestive heart failure (CHF) in individuals free of myocardial infarction. Animal studies showed that experimental HHCY induces systolic and diastolic dysfunction, as well as an increased BNP expression. Moreover, hyperhomocysteinemic animals exhibit an adverse cardiac remodeling characterized by accumulation of interstitial and perivascular collagen. The mechanisms leading from an elevated HCY level to reduced pump function and adverse cardiac remodeling are a matter of speculation. Existing data indicate that direct effects of HCY on the myocardium, as well as nitric oxide independent vascular effects, are involved. Preliminary data from small intervention trials have initiated the speculation that HCY lowering therapy by micronutrients may improve clinical as well as laboratory markers of CHF. In conclusion, HHCY might be a potential etiological factor in CHF. Future studies need to explore the exact pathomechanisms of HHCY in CHF. Moreover, larger intervention trials are needed to clarify whether modification of plasma HCY by B-vitamin supplementation improves the clinical outcome in CHF patients.

Oral administration of amino acidic supplements improves protein and energy profiles in skeletal muscle of aged rats: elongation of functional performance and acceleration of mitochondrial recovery in adenosine triphosphate after exhaustive exertion.

Sarcopenia is an inevitable age-related degenerative process chiefly characterized by decreased synthesis of muscle proteins and impaired mitochondrial function, leading to progressive loss of muscle mass. Here, we sought to probe whether long-term administration of oral amino acids (AAs) can increase protein and adenosine triphosphate (ATP) content in the gastrocnemius muscle of aged rats, enhancing functional performance. To this end, 6- and 24-month-old male Fisher 344 rats were divided into 3 groups: group A (6-month-old rats) and group B (24-month-old rats) were used as adult and senescent control group, respectively, while group C (24-month-old rats) was used as senescent treated group and underwent 1-month oral treatment with a mixture of mainly essential AAs. Untreated senescent animals exhibited a 30% reduction in total and fractional protein content, as well as a 50% reduction in ATP content and production, compared with adult control rats (p <0.001). Long-term supplementation with mixed AAs significantly improved protein and high-energy phosphate content, as well as the rate of mitochondrial ATP production, conforming their values to those of adult control animals (p <0.001). The improved availability of protein and high-energy substrates in the gastrocnemius muscle of treated aged rats paralleled a significant enhancement in functional performance assessed by swim test, with dramatic elongation of maximal exertion times compared with untreated senescent rats (p <0.001). In line with these findings, we observed that, after 6 hours of rest following exhaustive swimming, the recovery in mitochondrial ATP content was approximately 70% in adult control rats, approximately 60% in senescent control rats, and normalized in treated rats as compared with animals of the same age unexposed to maximal exertion (p <0.001). In conclusion, nutritional supplementation with oral AAs improved protein and energy profiles in the gastrocnemius of treated rats, enhancing functional performance and accelerating high-energy phosphate recovery after exhaustive exertion.

Urocortin promotes hemodynamic and bioenergetic recovery and improves cell survival in the isolated rat heart exposed to ischemia/reperfusion.

OBJECTIVES: This study evaluates the hemodynamic, bioenergetic and cytoprotective effects of urocortin (Ucn) in the isolated rat heart exposed to ischemia (I)/reperfusion (R). BACKGROUND: We have previously demonstrated that administration of exogenous Ucn reduces infarct size in ischemic-reperfused rat hearts. METHODS: Urocortin 10(-8)M was added to the perfusate before I, before I and during R, and during R alone in the isolated pulsed rat heart exposed to 35 min I followed by 60 min R. RESULTS: Partial to complete recovery of diastolic pressure and developed pressure was seen irrespective of when Ucn was perfused. In particular, beneficial effects are observed when Ucn is only given during R. Urocortin given only before I, and before I and over R, although not during R alone, also produces significant recovery of high-energy phosphate pools. In each group, improvement in ventricular function is associated with reduction both in myocardial damage, assessed by creatine phosphokinase release, and in endothelial cell and cardiomyocyte apoptosis, assessed by caspase 3 activity and fluorescent-based terminal deoxynucleotidyl transferase mediated nick end labelling enhanced with counterstains. These improvements in ventricular performance, bioenergetics and cell survival are not secondary to any inotropic effects of Ucn. CONCLUSIONS: This is the first report to show enhanced cardiac function induced by Ucn during I/R. Because the cytoprotective and functional benefits are still produced when Ucn is given only at R, these data suggest that Ucn may be useful clinically in the management of myocardial infarction.