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Reducing levels of low-density lipoprotein cholesterol (LDL-C) below recommended thresholds is a core component of cardiovascular prevention strategies. We hypothesized that the addition of bempedoic acid to patients already on statin-ezetimibe therapy was more effective than titrating the statin dose in reducing LDL-C. The study enrolled 120 patients at high cardiovascular risk and with LDL-C above 70 mg/dL. They were randomly divided into two groups: the bempedoic acid (BA) group, taking bempedoic acid in addition to statin plus ezitimibe, and the statin titration (ST) group, including patients who doubled the dose of statin. At 12 weeks, the BA group presented a more significant decrease in LDL-C compared to the ST group (-22.9% vs. 7.5% p 0.002). The total cholesterol decreased significantly in the BA group compared to ST (-14.8% vs.-4.7%; p 0.013) No significant between-group changes in HDL and triglycerides occurred. At 12 weeks, the number of patients who reached LDL-C lower than 70 mg/dL was 38 (63%) in the BA group versus 22 (37%) in the ST group (between groups, p 0.034). In the BA group, the LDL-lowering effect of bempedoic acid was similar between patients taking atorvastatin and rosuvastatin. No side effects occurred during the follow up period. In conclusion, the addition of bempedoic acid to statin-ezetimibe combined treatment was more effective than doubling the dose of statin in reducing LDL-C levels and increased the number of patients reaching the LDL-C goal.

Cardiac rehabilitation (CR) following acute myocardial infarction (AMI) improves physical capacities and decreases hospitalizations and cardiovascular mortality. L-arginine is the substrate used by nitric oxide (NO) synthase to generate NO and it has been shown to exert its beneficial effects on endothelium driving vasodilatation, reducing inflammation, and ameliorating physical function. We hypothesized that L-arginine could enhance physical capacities in patients who underwent CR after AMI. We designed a study aimed to assess the effects of L-arginine administration on the physical capacity of patients who underwent coronary revascularization after AMI. The trial was carried out amid the COVID-19 pandemic. Patients were assigned, with a 2:1 ratio, to add to their standard therapy one bottle containing 1.66 g of L-arginine or one bottle of identical aspect apart from not containing L-arginine, twice a day orally for 3 weeks. Patients performed a 6-minute walking test (6MWT), and their Borg modified 0-10 rating of perceived exertion (BRPE) was assessed before starting and at the end of the treatment. Seventy-five patients receiving L-arginine, and 35 receiving placebo successfully completed the study. The 6MWT distance increased significantly in the L-arginine group compared with both baseline and placebo ( P < 0.0001). Additionally, we observed a significant improvement in the BRPE in patients treated with L-arginine but not in the placebo group. Taken together, our data indicate that L-arginine potentiates the response to CR independently of age, sex, baseline functional capacity, and comorbid conditions. SIGNIFICANCE STATEMENT: This study shows for the first time that oral supplementation of L-arginine potentiates the response to cardiac rehabilitation after myocardial infarction and cardiac revascularization. Indeed, we observed a significant improvement in two fundamental parameters, namely, the 6-minute walking test and the Borg modified 0-10 rating of perceived exertion. Strikingly, the beneficial effects of L-arginine were independent of age, sex, comorbid conditions, and baseline functional capacity., (Copyright © 2022 by The American Society for Pharmacology and Experimental Therapeutics.)

High-dose statin (HDS) therapy is recommended to reduce low-density lipoprotein cholesterol (LDL-C); however, some patients are unable to tolerate the associated side effects. Nutraceuticals have shown efficacy in lowering LDL-C. The aim of this study was to evaluate whether the combination of low-dose statin (LDS) plus ezetimibe (EZE) or LDS plus nutraceutical (Armolipid Plus [ALP] containing red yeast rice, policosanol, and berberine) can lead to a higher proportion of high-risk patients achieving target LDL-C. A secondary objective was to assess the efficacy of triple combination LDS + EZE + ALP in resistant patients (LDL-C >70 mg/dl). A randomized, prospective, parallel-group, single-blind study was conducted in patients with coronary artery disease (n = 100) who had undergone percutaneous coronary intervention in the preceding 12 months, were HDS-intolerant, and were not at LDL-C target (<70 mg/dl) with LDS alone. Patients received either LDS + EZE or LDS + ALP. Of the 100 patients, 33 patients (66%) treated with LDS + EZE and 31 patients (62%) treated with LDS + ALP achieved target LDL-C after 3 months, which was maintained at 6 months. Patients who did not achieve the therapeutic goal received a triple combination of LDS + EZE + ALP for a further 3 months. At 6 months, 28 of 36 patients (78%) achieved LDL-C target. Overall, 92% of patients enrolled in this study were at target LDL-C at 6 months. No patients in any group experienced major side effects. In conclusion, in HDS-intolerant coronary artery disease patients, the combination of LDS plus EZE and/or ALP represents a valuable therapeutic option allowing most patients to reach target LDL-C within 3 to 6 months., (Copyright © 2018. Published by Elsevier Inc.)

Background: chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) frequently coexist in older people, reducing patients' quality of life (QoL) and increasing morbidity and mortality., Objective: we studied the feasibility and efficacy of an integrated telerehabilitation home-based programme (Telereab-HBP), 4 months long, in patients with combined COPD and CHF. The primary outcome was exercise tolerance evaluated at the 6-min walk test (6MWT). Secondary outcomes were time-to-event (hospitalisation and death), dyspnoea (MRC), physical activity profile (PASE), disability (Barthel) and QoL (MLHFQ and CAT)., Study Design: randomised, open, controlled, multicenter trial., Methods: the Telereab-HBP included remote monitoring of cardiorespiratory parameters, weekly phone-calls by the nurse, and exercise programme, monitored weekly by the physiotherapist. All outcomes were studied again after 2 months of a no-intervention period., Results: in total, 112 patients were randomised, 56 per group. Their mean (SD) age was 70 (9) years, and 92 (82.1%) were male. After 4 months, the IG were able to walk further than at baseline: mean (95% CI) Δ6MWT was 60 (22.2,97.8) m; the CG showed no significant improvement: -15 (-40.3,9.8) m; P = 0.0040 between groups. In IG, the media time to hospitalisation/death was 113.4 days compared with 104.7 in the CG (P = 0.0484, log-rank test). Other secondary outcomes: MRC (P = 0.0500), PASE (P = 0.0015), Barthel (P = 0.0006), MLHFQ (P = 0.0007) and CAT (P = 0.0000) were significantly improved in the IG compared with the CG at 4 months. IG maintained the benefits acquired at 6 months for outcomes., Conclusions: this 4-month Telereab-HBP was feasible and effective in older patients with combined COPD and CHF., (© The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.All rights reserved. For permissions, please email: journals.permissions@oup.com)

Low-density lipoprotein cholesterol (LDL-C) reduction is associated with a significant decrease in mortality, and statins represent the most effective drugs to achieve this. However, side effects of statins are very common and may lead to treatment discontinuation. Nutraceuticals are a combination of natural components that have shown efficacy in lowering LDL-C concentration when used alone or in association with other agents in patients who are intolerant to high-dose statins. Our aim was to compare the efficacy and tolerability of low-dose statin (LDS) therapy versus combined therapy of LDS plus a nutraceutical combination containing red yeast rice, policosanol, berberine, folic acid, coenzyme Q10 and astaxanthin (Armolipid Plus) in high-risk patients. We performed a randomized (1:1), prospective, parallel group, single-blind trial in which participants had coronary artery disease (n = 100), had undergone percutaneous coronary intervention in the preceding 12 months, were high-dose statin intolerant, and did not achieve ≥50% reduction in LDL-C with LDS treatment alone. After 3 months, patients in the LDS + Armolipid Plus (n = 50) group presented with a significantly greater reduction of LDL-C and total cholesterol (p <0.0001), and 70% of patients in this group achieved the therapeutic target (LDL-C <70 mg/dl), whereas patients in the LDS group did not. Six patients (3 from each group) dropped out due to myalgia. In conclusion, in patients with coronary artery disease and high-dose statin intolerance, the combination of LDS and nutraceuticals represents a valuable therapeutic option., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Statins are a main curbstone in the prevention of cardiovascular disease (CVD), pandemic in 21st century. CVD displays evident sex and gender differences, not only in clinical manifestation and outcomes but also in pharmacological treatment. Whether statin therapy should be differentially prescribed according to sex is a matter of debate. Aside a different pharmacological action, statins are not proven to be less effective in one gender comparing to the other, nor to be less safe. Nevertheless, up to date evidence shows that statins have not been adequately tested in women, especially in primary prevention trials. Since data-lacking, making a treatment decision on women is potentially harmful, although female individuals represent the majority of the population and they have a greater lifetime CVD risk. Therefore, adequately powered randomized control trials with longer follow-up are warranted to establish if a benefit on CV events and mortality prevention exists in both sexes. The aim of the present review is to summarize the sex and gender differences in statin use: it raises concerns and updates perspectives towards an evidence-based and sex-tailored prevention of CVD management., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: The ultimate goal of antihypertensive therapy is cardiovascular risk (CVR) reduction. The aim of this study was to compare the efficacy and safety of once-daily fixed combination (ODFC) versus free-drug combination (FDC) of 3antihypertensive agents and statin., Methods: The ALL-IN-ONE trial was a 12-week randomized, prospective, multicenter trial. A total of 305 hypertensive patients were randomized 1:1. The "fixed group" was given an ODFC of perindropil 10mg plus indapamide 2.5mg plus amlodipine 5 or 10mg plus atorvastatin 20mg. The "free group" was given a FDC of the 3antihypertensive agents plus atorvastatin 20mg. Primary end-points were the differences in clinic BP, cholesterol levels and CVR risk between the 2 groups after treatments. Secondary end-points included intragroup differences in clinic BP. Safety and compliance were also assessed., Results: At 12-weeks, the fixed group had lower systolic BP and similar diastolic BP compared to the free group. BP targets at week 12 were more commonly reached with fixed than free combination (89% and 80% respectively, p=0.048). For cholesterol serum in both groups there was a significant reduction of values. Also CVR reduction was greater in those taking ODF. Safety was not significantly different between the 2 groups. Conversely, compliance was significantly greater in the fixed-group vs. the free-group., Conclusion: This randomized trial shows that ODF combination of perindropil, indapamide and amlodipine is as safe as free combination of the 3 drugs, but is associated with a greater efficacy in BP control, compliance and, associated with statin, in cholesterol reduction. A better cardiovascular risk control is achieved with ODF combination than with a free administration. ClinicalTrials.gov ID: NCT02710539., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Statins are extensively used to treat dyslipidemia, but, because of their low tolerability profile, they are discontinued in a significant proportion of patients. Ezetimibe and nutraceuticals have been introduced as alternative therapies and have proved to be effective and well tolerated. A single-blind, single-center, randomized, prospective, and parallel group trial comparing a combination of nutraceuticals (red yeast rice, policosanol, berberine, folic acid, coenzyme Q10 and astaxanthin), called Armolipid Plus, and ezetimibe for 3 months in terms of efficacy and tolerability. Patients who did not achieve their therapeutic target (low-density lipoprotein cholesterol <100 mg/dl) could add the alternative treatment on top of randomized treatment for another 12 months: 100 patients who are dyslipidemic with ischemic heart disease treated with percutaneous coronary intervention were enrolled (ezetimibe n = 50, nutraceutical n = 50). Efficacy (lipid profile) and tolerability (adverse events, transaminases, and creatine kinase) were assessed after 3 and 12 months. After 3 months, 14 patients in the nutraceutical group achieved their therapeutic target, whereas none of the patients in the ezetimibe group did. At 1-year follow-up, 58 patients (72.5%) of the combined therapy group (n = 86) and 14 (100%) of the nutraceutical group reached the therapeutic goal. No patients experienced important undesirable effects. In conclusion, nutraceuticals alone or in combination with ezetimibe are well tolerated and improve the lipid profile in statin-intolerant patients with coronary heart disease. Further studies are needed to assess long-term effects of nutraceuticals on mortality., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: The present study attempts to identify appropriate elements that may contribute to clarify the broad clinical features (diagnosis, care, complication and prognosis) of Takotsubo-like cardiomyopathy for improving its management., Design Study: Observational study., Setting: Primary level of care referred to the emergency department of Vannini Hospital, Rome, Italy., Participants: The study population consisted of 75 patients, 72 of the them were women and 3 were men with a mean age of 71.9±9.6 years., Methods: From February 2004 to November 2010, prospectively included 84 consecutive patients diagnosed for suspected Takotsubo-like cardiomyopathy. To be eligible, patients had to meet all the Mayo clinic criteria in the absence of neurological trauma or intracranial haemorrhage. Moreover, those patients that at follow-up still presented alteration of acute phase at ECG and echocardiogram were excluded. Thus, 75 patients comprised the study population. To follow-up 19 patients were lost., Results: None of 75 patients died in acute phase. All patients were promptly discharged (8.4±4.4 days), since they recovered their normal functional status without symptoms. Follow-up information was available for 56 patients. At a mean follow-up time of 2.2±2 years (range, 0.1-6.8 years) two octogenarian patients (2.6%) died because of sudden cardiac death and pulmonary embolism, respectively. The Takotsubo-like cardiomyopathy recurred in one patient., Conclusions: The results of this study support the previous reports about the good prognosis, also in critically ill patients, of Takotsubo-like cardiomyopathy. Further assessment will be needed to determine a careful and sustained follow-up for choosing the best care and foreseeing the recurrences of this emerging condition.

Population data of 15 short tandem repeat loci of the AmpFlSTR® next generation multiplex (NGM)™ were obtained from a sample of 835 individuals. The loci are the ten short tandem repeats (STRs) in the SGM Plus® Kit plus the EDNAP- and ENSFI-recommended STRs D10S1248, D22S1045, D2S441, D1S1656, and D12S391. Allele frequency and other forensically relevant statistics data were generated for the NGM loci into five current country macroregions of Brazil (North, Northeast, Central West, Southeast, and South). All the analyzed loci meet Hardy-Weinberg equilibrium expectations and no linkage disequilibrium in all pairs of loci. The observed and expected heterozygosity, power of discrimination, polymorphic information content, and the other population-genetic indices were calculated. The overall power of discrimination was greater than 0.99999999999999999996 and the combined power of exclusion was greater than 0.9999998 in all Brazilian populations. Comparative analysis between populations from different Brazilian macroregions as well as between Brazil and Caucasian, African Americans, and Hispanic US populations are presented.

Objectives: To reduce risks, discomfort, cost, and operative time for percutaneous patent foramen ovale (PFO) closure, we propose to perform this procedure under transesophageal echo-guidance using a 10 Fr. catheter introduced through nasal way (TEENW)., Background: Transesophageal or intracardiac echocardiography is commonly used to guide percutaneous PFO closure. Sedation needed quite frequently during transesophageal echocardiography, increased patients' discomfort, procedure prolongation, costs, use of both femoral veins, and additional intracardiac manipulations are the main limitations of standard techniques., Methods: We enrolled 20 consecutive patients with a history of cerebral ischemia and PFO with right-to-left shunt. In 15 patients Amplatzer PFO occluder was used, whereas in five patients with longer PFO tunnel (>10 mm) Cardia Intrasept was selected. Without sedation, a multifrequency monoplane probe, developed for intracardiac echocardiography, was introduced into the nostril and advanced forward the esophagus. Then under echo guidance, the closing device was presented, opened and released., Results: Procedure lasted for an average of 33.3 min, and no complications were seen. At procedure's completion, six patients showed persistence of reduced shunt during Valsalva manoeuvre. At six-month follow-up, shunts disappeared in all patients., Conclusion: TEENW is safe and well tolerated, and images' quality is high enough to deserve widespread adoption of this technique for PFO closure., (2008 Wiley-Liss, Inc.)

Percutaneous device closure of patent foramen ovale (PFO) has become an effective and safe alternative to medical or surgery treatment. Transesophageal echocardiography (TEE), as commonly used to guide this procedure, has the limitation to require general anesthesia. Recently, intracardiac echocardiography (ICE) with AcuNav probe was used to guide percutaneous PFO closure. We report a 42 year-old man with two previous cryptogenetic strokes in whom both diagnosis and guidance of PFO closure were performed by means of TEE using the AcuNav catheter introduced through nasal way (TEENW). This technique, that does not require general anesthesia, provided adequate and complete view of the Amplatzer procedure. TEENW might offer a feasible and equivalent echocardiographic alternative either to standard TEE or ICE as a guide to percutaneous PFO closure.