Centro Dislipidemie

Milano, Italy

Centro Dislipidemie

Milano, Italy
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Ferri N.,University of Padua | Corsini A.,University of Milan | Sirtori C.,Centro Dislipidemie | Ruscica M.,University of Milan
Expert Opinion on Investigational Drugs | Year: 2017

Introduction: Non-fasting plasma triglyceride (TG) and remnant cholesterol levels, cholesterol content of triglyceride-rich lipoproteins, have been suggested to be an additional cause of cardiovascular diseases; thus, pharmacological TG-lowering with fibrates, activators of PPAR-alpha system, has been linked to risk reduction. Areas covered: This manuscript reviews available evidence on clinical trials involving highly selective PPAR-α agonists (i.e., pemafibrate) and drugs used in the pre-clinical and experimental setting (e.g., WY14,643). Original publications in English were selected, as well as Abstracts of international meetings’ presentations. Clinical trials were identified using the clinicaltrial.gov database and the EU Clinical Trials Register (clinicaltrialsregister.eu). Expert opinion: In addition to the aim of improving lipid profile with fibrates, the interest in new PPAR-α activators stems from the need to overcome some of the clinical problems encountered with dose-dependent adverse events; a rise of plasma creatinine, gallstone formation, drug-drug interactions (i.e. gemfibrozil), and myopathy. New PPAR-α agonists improved TG and HDL-C levels as well as other parameters related to TG metabolism (remnant cholesterol and apoB), without raising liver enzymes. Although the use of fibrates is rated ‘second choice’ by many clinicians, new PPAR-α agonists may offer a more accessible route to the management of hypertriglyceridemia, a frequent clinical condition. © 2017 Informa UK Limited, trading as Taylor & Francis Group.


Gomaraschi M.,University of Milan | Ossoli A.,University of Milan | Castelnuovo S.,Centro Dislipidemie | Simonelli S.,University of Milan | And 10 more authors.
Journal of Lipid Research | Year: 2017

The aim of this study was to evaluate the vasoprotective effects of HDL isolated from carriers of LCAT deficiency, which are characterized by a selective depletion of LpA-I:A-II particles and predominance of preβ migrating HDL. HDLs were isolated from LCAT-deficient carriers and tested in vitro for their capacity to promote NO production and to inhibit vascular cell adhesion molecule-1 (VCAM-1) expression in cultured endothelial cells. HDLs from carriers were more effective than control HDLs in promoting eNOS activation with a gene-dose-dependent effect (PTrend = 0.048). As a consequence, NO production induced by HDL from carriers was significantly higher than that promoted by control HDL (1.63 ± 0.24-fold vs. 1.34 ± 0.07-fold, P = 0.031). HDLs from carriers were also more effective than control HDLs in inhibiting the expression of VCAM-1 (homozygotes, 65.0 ± 8.6%; heterozygotes, 53.1 ± 7.2%; controls, 44.4 ± 4.1%; PTrend = 0.0003). The increased efficiency of carrier HDL was likely due to the depletion in LpA-I:A-II particles. The in vitro findings might explain why carriers of LCAT deficiency showed flow-mediated vasodilation and plasma-soluble cell adhesion molecule concentrations comparable to controls, despite low HDL-cholesterol levels. These results indicate that selective depletion of apoA-II-containing HDL, as observed in carriers of LCAT deficiency, leads to an increased capacity of HDL to stimulate endothelial NO production, suggesting that changes in HDL apolipoprotein composition may be the target of therapeutic interventions designed to improve HDL functionality. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.


Mombelli G.,Centro Dislipidemie | Pavanello C.,University of Milan | Castelnuovo S.,Centro Dislipidemie | Bosisio R.,Centro Dislipidemie | And 3 more authors.
Current Vascular Pharmacology | Year: 2017

Background: Cardiovascular risk (CV) factors associated with the metabolic syndrome (MetS) may vary in different populations. In some, hypertension may be the major determinant, in others are low high-density lipoprotein cholesterol (HDL-C), high triglycerides, or another component. Subjects and Methods: Subjects included in this analysis were identified in 2006, among those attending the Lipid Clinic of the Niguarda Hospital, and followed up through to 2013. Patient characteristics (including the occurrence of CV events) were obtained from electronic medical records. MetS was diagnosed according to the American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLBI) guidelines. The carotid intima media thickness (cIMT) was also followed in these patients over the years. Results: After 7 years a total of 858 subjects had a complete follow-up; 271 of those had MetS. Patients developing a CV event showed elevated baseline cIMT (e.g. cIMTmax ≥ 2.4 mm in males and ≥ 2.2 mm in females); moreover the cIMT in MetS patients was higher at baseline and the rise over 7 years was larger compared with patients without MetS. By examining each body variable for MetS we found that a waist to height ratio (WHtR) ≥ 0.5 was present in nearly all subjects with a CV event. Conclusion: The follow-up data of a series of Italian patients with and without MetS, clearly indicates that the former have a raised cIMT and their arterial IMT progression is greater and the presence of a larger WHtR is apparently linked to a higher incidence of CV events. © 2017 Bentham Science Publishers.


Pavanello C.,University of Milan | Lammi C.,University of Milan | Ruscica M.,University of Milan | Bosisio R.,University of Milan | And 6 more authors.
Journal of Functional Foods | Year: 2017

The study had the objective of evaluating the effects of a lupin protein concentrate on plasma lipids and other cardiovascular risk factors, e.g. blood pressure and insulin resistance, compared to a skimmed milk powder. Fifty subjects followed a randomised, parallel, double-blind, single-centre study, consisting in a 12-week intervention: half of the participants consumed a lupin protein concentrate (30 g/day of protein), the other half a lactose-free skimmed milk powder (30 g/day of protein), both integrated into a mixed low-lipid diet. At the end of intervention, both groups showed similar reductions of total cholesterol concentrations versus baseline (−6.7%, and −7.2%, respectively), but the reductions of LDL-cholesterol (−8.0%), non-HDL-cholesterol (−7.5%), and proprotein convertase subtilisin/kexin type 9 (PCSK9) (−12.7%) levels were statistically significant only after the lupin diet. A significant reduction of HDL-cholesterol concentration was observed only after the milk diet. The differences between the two groups, however, were not statistically significant. © 2017 Elsevier Ltd


Ruscica M.,Centro Dislipidemie | Ruscica M.,University of Milan | Gomaraschi M.,Centro Dislipidemie | Gomaraschi M.,University of Milan | And 14 more authors.
Journal of Clinical Lipidology | Year: 2014

Background Primary cardiovascular prevention may be achieved by lifestyle/nutrition improvements and specific drugs, although a relevant role is now emerging for specific functional foods and nutraceuticals. Objectives The aim of this study was to evaluate the usefulness of a nutraceutical multitarget approach in subjects with moderate cardiovascular risk and to compare it with pravastatin treatment. Subjects Thirty patients with moderate dyslipidemia and metabolic syndrome (according to the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults) were included in an 8-week randomized, double-blind crossover study and took either placebo or a nutraceutical combination that contained red yeast rice extract, berberine, policosanol, astaxanthin, coenzyme Q10, and folic acid (Armolipid Plus). Subsequently, they were subjected to another 8-week treatment with pravastatin 10 mg/d. This dosage was selected on the basis of its expected -20% efficacy in reducing low-density lipoprotein-cholesterol. Results Treatment with Armolipid Plus led to a significant reduction of total cholesterol (-12.8%) and low-density lipoprotein-cholesterol (-21.1%), similar to pravastatin (-16% and -22.6%, respectively), and an increase of high-density lipoprotein-cholesterol (4.8%). Armolipid Plus improved the leptin-to-adiponectin ratio, whereas adiponectin levels were unchanged. Conclusions These results indicate that this nutraceutical approach shows a lipid-lowering activity comparable to pravastatin treatment. Hence, it may be a safe and useful option, especially in conditions of moderate cardiovascular risk, in which a pharmacologic intervention may not be appropriate. © 2014 National Lipid Association. All rights reserved.


Pavanello C.,Centro Dislipidemie | Mombelli G.,Centro Dislipidemie
Clinical Lipidology | Year: 2015

Numerous clinical studies with objectives such as mortality and morbidity of cardiovascular (CV) have reported the benefit of treatment for dyslipidemia with lipid-lowering therapy, in particular using the statins. But the trials conducted in past years did not consider the gender differences of statin effect, because women were poorly represented. All the results in terms of response, efficacy, reduction of LDL cholesterol and CV risk in primary and secondary prevention refer to men. In these recent years, it emerges the need to consider the different lipoprotein profile during lifetime and CV risk between men and women. Furthermore it is necessary to consider that, in patients with coronary artery disease, the lipid goal achieved is different between the two genders. Finally, we have to evaluate the side effects mostly present in women. In conclusion, there is a different prescription of these treatments in particular in the dosage used, that it is insufficient in women with cardiovascular disease. More recently it has emerged the exigency to use new guidelines that clearly indicate how should be the medical care, therefore, the specific way to treat men and women. © 2015 Future Medicine Ltd.


Magni P.,University of Milan | Magni P.,Centro Dislipidemie | Macchi C.,University of Milan | Morlotti B.,Centro Dislipidemie | And 4 more authors.
European Journal of Internal Medicine | Year: 2015

The use of statins for cardiovascular disease prevention is clearly supported by clinical evidence. However, in January 2014 the U.S. Food and Drug Administration released an advice on statin risk reporting that "statin benefit is indisputable, but they need to be taken with care and knowledge of their side effects". Among them the by far most common complication is myopathy, ranging from common but clinically benign myalgia to rare but life-threatening rhabdomyolysis. This class side effect appears to be dose dependent, with more lipophilic statin (i.e., simvastatin) carrying a higher overall risk. Hence, to minimize statin-associated myopathy, clinicians should take into consideration a series of factors that potentially increase this risk (i.e., drug-drug interactions, female gender, advanced age, diabetes mellitus, hypothyroidism and vitamin D deficiency). Whenever it is appropriate to stop statin treatment, the recommendations are to stay off statin until resolution of symptoms or normalization of creatine kinase values. Afterwards, clinicians have several options to treat dyslipidemia, including the use of a lower dose of the same statin, intermittent non-daily dosing of statin, initiation of a different statin, alone or in combination with nonstatin lipid-lowering agents, and substitution with red yeast rice. © 2015 European Federation of Internal Medicine. All rights reserved.


Magni P.,University of Milan | Magni P.,Centro Dislipidemie | MacChi C.,University of Milan | Sirtori C.R.,Centro Dislipidemie | And 2 more authors.
Clinical Chemistry and Laboratory Medicine | Year: 2016

Clear evidence supports a role for circulating and locally-produced osteocalcin (OC) in the pathophysiology of cardiovascular (CV) lesions and CV risk, also in combination with metabolic changes, including type 2 diabetes mellitus (T2DM). Reduced plasma OC levels are associated with greater incidence of pathological CV changes, like arterial and valvular calcification, coronary and carotid atherosclerosis and increased carotid intima-media thickness. The actual relationship between OC levels and incidence of major CV events is, however, still unclear. Moreover, reduced circulating OC levels have been mostly associated with insulin resistance, metabolic syndrome or T2DM, indicating relevant OC actions on pancreatic β-cells and insulin secretion and activity. Based on these observations, this review article will attempt to summarize the current evidence on the potential usefulness of circulating OC as a biomarker for CV and metabolic risk, also evaluating the currently open issues in this area of research. © 2016 Walter de Gruyter GmbH, Berlin/Boston 2016.


Ruscica M.,University of Milan | Ruscica M.,Centro Dislipidemie | MacChi C.,University of Milan | MacChi C.,Centro Dislipidemie | And 5 more authors.
European Journal of Internal Medicine | Year: 2014

The use of statins for cardiovascular disease (CVD) prevention is clearly supported by clinical evidence. Although statin therapy is rather well tolerated, recent data from prospective and retrospective clinical trials and related meta-analyses suggest an increased incidence of new-onset type 2 diabetes mellitus (T2DM) in association with such treatment. The incidence of this adverse effect is not negligible, especially for specific subsets of patients, such as women, elderly, presence of familial history of T2DM and Asian ethnicity. Statin-driven T2DM appears to be a medication class-effect, mostly not related to potency nor to individual statin, as well as to be independent of previous history of CVD. Therefore, implementation of strategies for identification of patients using statins and at specific risk of incident T2DM, as well as of different therapeutic options is important and is discussed in this article. As most authors emphasized that benefits of CVD reduction by statin therapy seem to far exceed the risk of T2DM development itself, these medications remain the cornerstone for primary and secondary CVD prevention, although a specific attention to glucose metabolism and metabolic syndrome features should be payed before and during statin treatment, especially in cohorts at greater risk. © 2014 European Federation of Internal Medicine.


PubMed | Centro Dislipidemie and University of Milan
Type: Journal Article | Journal: Journal of clinical lipidology | Year: 2014

Primary cardiovascular prevention may be achieved by lifestyle/nutrition improvements and specific drugs, although a relevant role is now emerging for specific functional foods and nutraceuticals.The aim of this study was to evaluate the usefulness of a nutraceutical multitarget approach in subjects with moderate cardiovascular risk and to compare it with pravastatin treatment.Thirty patients with moderate dyslipidemia and metabolic syndrome (according to the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults) were included in an 8-week randomized, double-blind crossover study and took either placebo or a nutraceutical combination that contained red yeast rice extract, berberine, policosanol, astaxanthin, coenzyme Q10, and folic acid (Armolipid Plus). Subsequently, they were subjected to another 8-week treatment with pravastatin 10 mg/d. This dosage was selected on the basis of its expected -20% efficacy in reducing low-density lipoprotein-cholesterol.Treatment with Armolipid Plus led to a significant reduction of total cholesterol (-12.8%) and low-density lipoprotein-cholesterol (-21.1%), similar to pravastatin (-16% and -22.6%, respectively), and an increase of high-density lipoprotein-cholesterol (4.8%). Armolipid Plus improved the leptin-to-adiponectin ratio, whereas adiponectin levels were unchanged.These results indicate that this nutraceutical approach shows a lipid-lowering activity comparable to pravastatin treatment. Hence, it may be a safe and useful option, especially in conditions of moderate cardiovascular risk, in which a pharmacologic intervention may not be appropriate.

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