Arrigo Cicero | AICCON - Associazione Italiana per la Promozione della Cultura della Cooperazione e del Non Profit (original) (raw)
Papers by Arrigo Cicero
Mediterranean Journal of Nutrition and Metabolism, 2009
The aim of our study was to directly compare the metabolic effect of monounsaturated fatty acid r... more The aim of our study was to directly compare the metabolic effect of monounsaturated fatty acid rich oils and polyunsaturated fatty acid rich oils on the plasma lipid pattern of moderately hypercholesterolaemic subjects under controlled isocaloric condition. After a 30-day run-in diet, 44 healthy Caucasian subjects with moderate hypercholesterolaemia were randomly assigned to one of four different isocaloric diets, differing only regarding the oil used (corn oil, corn oil supplemented with vitamin E, extra-virgin olive oil or different self-selected oils), for 45 days. At the end of the study, when compared to the baseline value, low-density lipoprotein (LDL)-cholesterolaemia was significantly lower only in patients taking corn oil (-13.9%; 95%CI -5.9 to -20.1; p = 0.02) or corn oil with added vitamin E (-19.1%; 95%CI -6.9 to -24.1; p = 0.03). Differences in plasma high-density lipoprotein (HDL)-cholesterol and triglyceride levels from baseline levels and between the four diets did not reach statistical significance.
Nutrition Journal, 2015
Overweight subjects easily develop alterations of the glucose and lipid metabolism and are expose... more Overweight subjects easily develop alterations of the glucose and lipid metabolism and are exposed to an increased cardiometabolic risk. This condition is potentially reversible through the improvement of dietary and behavioural habits. However, a well-assembled nutraceutical would be a useful tool to better improve the metabolic parameters associated to overweight and insulin resistance. To evaluate the effect of a combined nutraceutical containing berberine, chlorogenic acid and tocotrienols, we performed a double blind, cross-over designed trial versus placebo, in 40 overweight subjects with mixed hyperlipidaemia. After the first 8 weeks of treatment (or placebo), patients were asked to observe a 2-week washout period, and they were then assigned to the alternative treatment for a further period of 8 weeks. Clinical and laboratory data associated to hyperlipidaemia and insulin resistance have been obtained at the baseline, at the end of the first treatment period, after the washout, and again after the second treatment period. Both groups experienced a significant improvement of anthropometric and biochemical parameters versus baseline. However, total cholesterol, LDL cholesterol, triglycerides, non-HDL cholesterol, fasting insulin, HOMA-IR, GOT and Lipid Accumulation Product decreased more significantly in the nutraceutical group versus placebo. This combination seems to improve a large number of metabolic and liver parameters on the short-term in overweight subjects. Further studies are needed to confirm these observations on the middle- and long-term.
Mediterranean Journal of Nutrition and Metabolism, 2008
Numerous randomized clinical trials, systematic reviews and meta-analyses have confirmed the anti... more Numerous randomized clinical trials, systematic reviews and meta-analyses have confirmed the antidyslipidaemic activity of different dietary supplements, nutraceuticals and herbal remedies. International guidelines for cardiovascular disease prevention have begun to consider dietary supplements as an evidence-based approach to improve patients' plasma lipid levels. They already suggest to increasing or supplementing the dietary intake of soluble fibre (especially psyllium), soy proteins, plant sterols, niacin, and fish oil. Among the nutraceuticals, mevacoline and policosanol are both able to reduce plasma LDL-C by a mean of 20%. A preliminary clinical study of berberine has shown it to be the most powerful antihyperlipidaemic natural compound, reducing plasma LDL-C by 25% and triglycerides by 35%. Among the herbal remedies, several placebo-controlled randomized clinical trials have confirmed the anti-hypercholesterolaemic, and antihypertriglyceridaemic properties of aged garlic powder, artichoke leaf extracts, guggul, and fenugreek. Single small clinical trials have also suggested that Korean ginseng, green tea, onion, yarrow, holy basil and arjun have an antihypercholesterolaemic effect.
Expert opinion on drug safety, 2014
To answer the need of a better low-density lipoprotein (LDL) cholesterol control in statin-treate... more To answer the need of a better low-density lipoprotein (LDL) cholesterol control in statin-treated patients at high risk for cardiovascular disease, new injectable lipid-lowering drugs with innovative mechanisms of action are in advanced phase of development or have just been approved. Evolocumab and alirocumab are fully human monoclonal antibodies inhibiting the proprotein convertase subtilisin/kexin type 9 (PCSK9) that binds to hepatic LDL receptor and prevents it from normal recycling by targeting it for degradation. Mipomersen specifically binds to a segment of the human apolipoprotein B100 messenger RNA, blocking the translation of the gene product. Phase II (for evolocumab and alirocumab) and III (for evolocumab) trials show that PCSK9 inhibitors are equally well tolerated, with adverse events mainly limited to mild-to-moderate nasopharyngitis, injection-site pain, arthralgia and back pain. Mipomersen use is mainly associated to hepatosteatosis, increased transaminases (> 3...
Advances in clinical and experimental medicine : official organ Wroclaw Medical University
Oxidation makes LDL an immunogenic substrate, stimulating the production of specific autoantibodi... more Oxidation makes LDL an immunogenic substrate, stimulating the production of specific autoantibodies against oxidized LDL (ox-LDL Ab). The demonstration of ox-LDL Ab presence in serum indicates the existence of a long-term lipid peroxidation in vivo. The aim of the study is to evaluate the influence of a large number of dietary variables on the dosage of ox-LDL Ab in pharmacologically untreated healthy subjects. The Brisighella Heart Study (BHS) is a prospective, population-based longitudinal epidemiological investigation involving 2939 randomly selected adult subjects, resident in the northern Italian rural town of Brisighella. For this study, we analyzed the dietary, clinical and laboratory data of 265 (M: 101, W: 164) pharmacologically untreated non-smoker subjects, evaluating the factors potentially affecting their ox-LDL Ab dosage. In a multivariate analysis, including age, BMI, hemodynamic and laboratory parameters, the only significant predictor of log-ox-LDL Ab level was age ...
International journal of nephrology and renovascular disease, 2010
A relatively large body of evidence supports the notion that glomerular capillary wall and mesang... more A relatively large body of evidence supports the notion that glomerular capillary wall and mesangial alterations in diabetic nephropathy involve biochemical alterations of glycoproteins in these structures. Evidence in experimental animals rendered diabetic reveals that the administration of heparin and other anionic glycoproteins can effectively prevent the biochemical alterations that promote albuminuria. Moreover, angiotensin II inhibits heparan sulfate synthesis, while heparins modulate angiotensin II signaling in glomerular cells, inhibiting aldosterone synthesis and lowering proteinuria in diabetes patients. Sulodexide, a mixture of heparin and dermatan sulfate, appears to be a promising treatment for diabetic proteinuria partially resistant to renin-angiotensin system blocking agents. Sulodexide prevents heparan sulfate degradation, thus allowing reconstruction of heparan sulfate content and restoration of glomerular basement membrane ionic permselectivity. The antiproteinuri...
Journal of endocrinological investigation
Sex hormones and adipokines seem to differently interact in both genders at different ages. To co... more Sex hormones and adipokines seem to differently interact in both genders at different ages. To comparatively evaluate the serum level of adipokines and sex hormones in healthy non-pharmacologically treated premenopausal women, post-menopausal women, and elderly women, and in age-matched men. From the historical cohort of the Brisighella Heart Study we selected 199 adult healthy subjects (males: 89; females: 110), aged 62.5±12.4 yr. Men and women included in the age-class subgroups were matched for body mass index (BMI), waist circumference, blood pressure, heart rate, fasting plasma glucose, plasma lipids. Leptin did not differ among various age classes in men, while pre-menopausal women displayed significantly lower serum leptin than post-menopausal women (-6.7 ± 2.2 pg/ml, p=0.036). Post-menopausal women had significantly greater serum leptin when compared with age-matched men (+13.1 ± 2.0 pg/ml, p<0.001); the same was observed for elderly women when compared with elderly men (...
Vascular health and risk management, 2007
Persistence on treatment affects the efficacy of antihypertensive treatment. We prospectively inv... more Persistence on treatment affects the efficacy of antihypertensive treatment. We prospectively investigated the persistence on therapy and the extent of blood pressure (BP) control in 347 hypertensive patients (age 59.4 +/- 6 years) randomly allocated to a first-line treatment with: angiotensin-converting enzyme (ACE) inhibitors, calcium-channel blockers (CCBs), beta-blockers, angiotensin-II receptor blockers (ARBs), or diuretics and followed-up for 24-months. Persistence on treatment was higher in patients treated with ARBs (68.5%) and ACE inhibitors (64.5%) vs CCBs (51.6%; p < 0.05), beta-blockers (44.8%, p < 0.05), and diuretics (34.4%, p < 0.01). No ARB, ACE inhibitor, beta-blocker, or diuretic was associated with a higher persistence in therapy compared with the other molecules used in each therapeutic class. The rate of persistence was significantly higher in patients treated with lercanidipine vs others CCBs (59.3% vs 46.6%, p < 0.05). Systolic and diastolic BP was...
Vascular health and risk management, 2007
Familial combined hyperlidemia (FCH) is a common metabolic disorder characterized by: (a) increas... more Familial combined hyperlidemia (FCH) is a common metabolic disorder characterized by: (a) increase in cholesterolemia and/or triglyceridemia in at least two members of the same family, (b) intra-individual and intrafamilial variability of the lipid phenotype, and (c) increased risk of premature coronary heart disease (CHD). FCH is very frequent and is one of the most common genetic hyperlipidemias in the general population (prevalence estimated: 0.5%-2.0%), being the most frequent in patients affected by CHD (10%) and among acute myocardial infarction survivors aged less than 60 (11.3%). This percentage increases to 40% when all the myocardial infarction survivors are considered without age limits. However, because of the peculiar variability of laboratory parameters, and because of the frequent overlapping with the features of metabolic syndrome, this serious disease is often not recognized and treated. The aim of this review is to define the main characteristics of the disease in ...
Current opinion in investigational drugs (London, England : 2000), 2006
Hyperlipidemia is a well-established risk factor for atherogenesis and cardiovascular disease. St... more Hyperlipidemia is a well-established risk factor for atherogenesis and cardiovascular disease. Statins have been the cornerstone of treatment for hyperlipidemia in recent years and have significantly contributed to the improvement of cardiovascular disease therapy. However, novel antihyperlipidemic agents that have been developed over the last decade possess the capacity to significantly reduce plasma lipoproteins. This review analyzes the pharmacological profile, effectiveness and safety of some promising drugs that are either already in clinical use (eg, ezetimibe and nicotinic acid) or under study (eg, acyl-CoA cholesterol acyltransferase inhibitors, cholesteryl ester transfer protein inhibitors and apolipoprotein A-IMilano).
Drugs & aging, 2005
One of the categories of drugs most frequently used by the elderly, and probably the most commonl... more One of the categories of drugs most frequently used by the elderly, and probably the most commonly self-prescribed class of drug in this age group, is NSAIDs. However, NSAIDs are one of the primary causes of adverse drug reactions and are notorious for their gastric toxicity. They also inhibit renal function and reduce the efficacy of diuretics and ACE inhibitors, drugs that are commonly used by elderly patients. Recent studies have shown that cyclo-oxygenase (COX)-2 is important in renal physiology. This means that selective COX-2 inhibitors, while undoubtedly safer than NSAIDs in terms of gastric toxicity, are not devoid of renal toxicity (in addition to their now clearly established adverse effects on coronary heart disease risk). Both the gastric and renal toxicities induced by traditional NSAIDs and selective COX-2 inhibitors seem to be related to inhibition of prostaglandin, but not leukotriene, synthesis. Maintaining the correct balance between prostaglandins and leukotrienes...
Advances in Clinical and Experimental Medicine, 2014
Recent preclinical evidence and data from adult subjects suggests that statins could improve the ... more Recent preclinical evidence and data from adult subjects suggests that statins could improve the proinflammatory profile of hypercholesterolemic subjects. We aim to compare the serum levels of a set of proinflammatory chemokines in elderly statistical twins taking or not taking statins. Among the historical cohort of the Brisighella Heart Study, we chose 40 healthy elderly subjects continuously treated with statins for at least 1 year and 40 cross-matched subjects not treated with statins (M : F = 1 : 1) characterized by similar age, body mass index (BMI), leisure-time and working activity, smoking habits, history of cardiovascular disease, systolic and diastolic blood pressure, fasting plasma glucose, plasma lipids, uric acid, and creatinine. The proinflammatory chemokine serum level is similar in statin untreated and treated statistical twins. The OR to have a serum level of monocyte chemoattractant protein (MCP-1) lower than the 50th percentile of the distribution in statin-treated subjects compared to the statin untreated subjects is 0.669 (95% CI 0.193; 2.327), the OR for interleukin-8 (IL-8) = 0.818 (95% CI 0.236; 2.835), the OR for γ-interferon inducible protein-10 (IP-10) = 1.361 (95% CI 0.358; 5.175), and for interleukin-18 (IL-18) = 0.545 (95% CI 0.155; 1.914). In relatively healthy, elderly subjects selected from a randomized general population sample, we did not observe differences in the serum levels of the selected set of proinflammatory chemokines in statin treated and untreated subjects with similar LDL-C level, suggesting that cholesterol reduction per se could be a main determinant of statin anti-inflammatory effects.
The authors hypothesized that matrix metalloproteinase (MMP)-2, -9, and tissue inhibitor metallop... more The authors hypothesized that matrix metalloproteinase (MMP)-2, -9, and tissue inhibitor metalloproteinase (TIMP)-1, -2 would be abnormal in acute coronary syndromes (ACSs). MMP-2, -9, and TIMP-1, -2 plasma levels were measured in diabetic patients with ACSs compared to nondiabetic patients with ACSs. A total of 46 diabetic and 78 nondiabetic patients with ACSs were enrolled. The following parameters were measured: body mass index (BMI), glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), fasting plasma insulin (FPI), homeostasis model assessment index (HOMA index), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (Tg), lipoprotein(a) [Lp(a)], plasminogen activator inhibitor-1 (PAI-1), homocysteine (Hct), fibrinogen (Fg), high-sensitivity C-reactive protein (hs-CRP), and plasma levels of MMP-2, MMP-9, TIMP-1, and TIMP-2. Significant HbA1c, FPG, FPI, HOMA index, DBP, Tg, Hct, and Fg increases were present in the diabetic group with ACSs, whereas hs-CRP was lower in these patients compared to nondiabetic patients with ACSs. MMP-9, TIMP-1, and TIMP-2 plasma levels were higher in diabetic patients with ACSs compared to nondiabetic patients with ACSs. MMP-9, TIMP-1, and TIMP-2 plasma levels were increased in diabetic patients with ACSs, which may reflect abnormal extracellular matrix metabolism in diabetes during acute event.
Current Vascular Pharmacology, 2014
ABSTRACT Metabolic syndrome (MetS) is a world-wide epidemic disease associated with increased mor... more ABSTRACT Metabolic syndrome (MetS) is a world-wide epidemic disease associated with increased morbidity and mortality. Treatment strategies include pharmacologic and non-pharmacologic methods, with varying degrees of success rate all over the world. Pharmaceutical interest in this field is growing, together with patients requests' for supplementary (or "alternative") treatments. The knowledge of nutraceuticals beneficial effects in subjects with the MetS could help us to better define the appropriate treatment for these subjects, in particular those with contraindications for commonly used drugs, or to achieve guidelines suggested targets. On the other side, it could be not convenient to use a nutraceutical to treat each metabolic syndrome component (i.e.: from 3 to 5) in each affected subjects. Thus, this review tries to focus on widely marketed nutraceuticals with clinically demonstrated effects on more than one component of the MetS, namely omega-3 fatty acids, berberine, psyllium and other soluble fibers, cinnamon, chromium picolinate, banaba, and bitter gourd.
High Blood Pressure & Cardiovascular Prevention, 2014
One of the most frequent side effect of oral contraceptives use is a stable alteration of the lip... more One of the most frequent side effect of oral contraceptives use is a stable alteration of the lipid profile. This could be even more relevant in women affected by polycystic ovary syndrome (PCOS). Considering the importance of a balanced lipid profile in cardiovascular prevention and that the exposure to the drugs could be many years long, our aim was to investigate the possible beneficial effect of a largely tested low-dosed combined lipid-lowering nutraceutical on dyslipidemias induced by oestroprogestins prescribed to young women for different indications. We prospectively enrolled 84 patients in primary cardiovascular disease prevention, with low estimated cardiovascular disease risk (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;5 % according to the ESC/EAS guidelines), and LDL-C increased above normal value (LDL-C &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;130 mg/dL) after the use of at least two different oral oestroprogestins treatments. Forty-four women were prescribed oral oestroprogestins for PCOS, while 40 for pure contraception. The tested nutraceutical contained berberine 500 mg/tab and monacolins 3 mg/tab was prescribed to all enrolled patients, associated the previously prescribed standard lipid-lowering diet. After 3 months of nutraceutical treatment, we observed a significant improvement in BMI (-1.5 ± 0.8 %, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), FPG (-6.9 ± 5.8 %, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), HOMA index (-3.5 ± 5.6 %, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), TC (-20.1 ± 6.6 %, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), LDL-C (-25.3 ± 8.9 %, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), HDL-C (+14.1 ± 2.2 %, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), TG (-29.9 ± 25.2 %, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and hsCRP (-2.5 ± 2.4 %, p = 0.019). Similar results have been obtained even repeating the analysis by subgroups, beyond hsCRP that significantly improved in PCOS patients compared to both the baseline and the non-PCOS group. It appears that the tested combined lipid-lowering nutraceutical is able to equally improve lipid metabolism in oral contraceptive induced hypercholesterolemia in women affected or not by PCOS.
High Blood Pressure & Cardiovascular Prevention, 2014
Serum uric acid (SUA) may contribute to the increased cardiovascular damage through direct injury... more Serum uric acid (SUA) may contribute to the increased cardiovascular damage through direct injury to the endothelium and alteration of cardiovascular function. To evaluate the association of SUA with the presence of the most recurrent electrographic alterations and with the length of the main ECG intervals in a large sample of general population. For this study, on the database of the Brisighella Heart Study, we evaluated the available data of 790 men and 849 women, excluding subjects affected by gout or taking antihyperuricemic agents, those taking drug increasing the QT interval and those using beta-blockers or non-dihydropyridine calcium channel blockers at the moment of the ECG registration. Multiple ascending stepwise regression analyses were carried out to determine the independent predictors of the predefined ECG alterations. The prevalence of predefined ECG alterations was comparable between genders, with the exception of sinus bradicardia, left-anterior fascicular block, atrio-ventricular blocks and left ventricular hypertrophy (LVH), which appeared to be more frequent in men. The multivariate analysis revealed that SUA was associated to ischaemic alterations, LVH, sinus tachycardia and tachyarrhytmias. Age was associated to all evaluated ECG alterations beyond sinus tachycardia and LVH. Male sex was associated to sinus bradicardia, atrio-ventricular blocks, anterior-left fascicular block and LVH. Blood pressure was associated to different ECG alterations, but with clinically relevant OR with ischaemic alterations and LVH. SUA level is related the prevalence of both organic and rhythm ECG alterations in a wide sample of general population.
Internal and Emergency Medicine, 2012
Metabolic Syndrome and Related Disorders, 2013
Abstract Background: Nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome are strongly... more Abstract Background: Nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome are strongly related from both an epidemiological and a pathological point of view. The main aim of our study was to evaluate if two validated indexes of NAFLD are able to predict the 4-year metabolic syndrome incidence in a large population sample of pharmacologically untreated subjects without metabolic syndrome, type 2 diabetes, history of alcohol abuse, or known liver diseases at the baseline. From the database of the Brisighella Heart Study, we selected a subsample of 824 pharmacologically untreated subjects (male, 401; female, 423) without metabolic syndrome, type 2 diabetes, alcohol abuse, or known liver diseases at the 2004 survey and revisited in 2008. The Hepatic Steatosis Index (HSI) and Lipid Accumulation Product (LAP) values were calculated for everyone to evaluate their predictive role for metabolic syndrome through a Cox-regression analysis adjusted by metabolic syndrome components. We observed 46 new cases of metabolic syndrome (male, 25; female, 21) with a cumulative incidence of 5.6% (1.4% per year): 6.2% in men (1.5% per year), 4.9% in women (1.2% per year). In women, the 4-year metabolic syndrome predictors (R(2)=0.680) were age [odds ratio (OR) 1.13, 95% confidence interval (CI) 1.12-1.15], HSI (OR 1.20, 95% CI 1.15-1.26), and lnLAP (OR 1.16, 95% CI 1.14-1.17), whereas in men they were (R(2)=0.554) age (OR 1.13, 95% CI 1.11-1.14) and lnLAP (OR 1.17, 95% CI 1.15-1.18). HSI and LAP differently predict the 4-year incidence of metabolic syndrome. In women, both indexes can be considered significant predictors, whereas in men only LAP can be considered predictive.
Cardiovascular complications are important in hyperthyroidism because of their high frequency in ... more Cardiovascular complications are important in hyperthyroidism because of their high frequency in clinical presentation and increased mortality and morbidity risk. The cause of hyperthyroidism, factors related to the patient, and the genetic basis for complications are associated with risk and the basic underlying mechanisms are important for treatment and management of the disease. Besides cellular effects, hyperthyroidism also causes hemodynamic changes, such as increased preload and contractility and decreased systemic vascular resistance causes increased cardiac output. Besides tachyarrythmias, impaired systolic ventricular dysfunction and diastolic dysfunction may cause thyrotoxic cardiomyopathy in a small percentage of the patients, as another high mortality complication. Although the medical literature has some conflicting data about benefits of treatment of subclinical hyperthyroidism, even high-normal thyroid function may cause cardiovascular problems and it should be treated. This review summarizes the cardiovascular consequences of hyperthyroidism with underlying mechanisms. K Ke ey y w wo or rd ds s: : hyperthyroidism, subclinical hyperthyroidism, overt hyperthyroidism, atrial fibrillation, Graves' disease, toxic nodular goitre. C Co or rr re es sp po on nd di in ng g a au ut th ho or r: :
Mediterranean Journal of Nutrition and Metabolism, 2009
The aim of our study was to directly compare the metabolic effect of monounsaturated fatty acid r... more The aim of our study was to directly compare the metabolic effect of monounsaturated fatty acid rich oils and polyunsaturated fatty acid rich oils on the plasma lipid pattern of moderately hypercholesterolaemic subjects under controlled isocaloric condition. After a 30-day run-in diet, 44 healthy Caucasian subjects with moderate hypercholesterolaemia were randomly assigned to one of four different isocaloric diets, differing only regarding the oil used (corn oil, corn oil supplemented with vitamin E, extra-virgin olive oil or different self-selected oils), for 45 days. At the end of the study, when compared to the baseline value, low-density lipoprotein (LDL)-cholesterolaemia was significantly lower only in patients taking corn oil (-13.9%; 95%CI -5.9 to -20.1; p = 0.02) or corn oil with added vitamin E (-19.1%; 95%CI -6.9 to -24.1; p = 0.03). Differences in plasma high-density lipoprotein (HDL)-cholesterol and triglyceride levels from baseline levels and between the four diets did not reach statistical significance.
Nutrition Journal, 2015
Overweight subjects easily develop alterations of the glucose and lipid metabolism and are expose... more Overweight subjects easily develop alterations of the glucose and lipid metabolism and are exposed to an increased cardiometabolic risk. This condition is potentially reversible through the improvement of dietary and behavioural habits. However, a well-assembled nutraceutical would be a useful tool to better improve the metabolic parameters associated to overweight and insulin resistance. To evaluate the effect of a combined nutraceutical containing berberine, chlorogenic acid and tocotrienols, we performed a double blind, cross-over designed trial versus placebo, in 40 overweight subjects with mixed hyperlipidaemia. After the first 8 weeks of treatment (or placebo), patients were asked to observe a 2-week washout period, and they were then assigned to the alternative treatment for a further period of 8 weeks. Clinical and laboratory data associated to hyperlipidaemia and insulin resistance have been obtained at the baseline, at the end of the first treatment period, after the washout, and again after the second treatment period. Both groups experienced a significant improvement of anthropometric and biochemical parameters versus baseline. However, total cholesterol, LDL cholesterol, triglycerides, non-HDL cholesterol, fasting insulin, HOMA-IR, GOT and Lipid Accumulation Product decreased more significantly in the nutraceutical group versus placebo. This combination seems to improve a large number of metabolic and liver parameters on the short-term in overweight subjects. Further studies are needed to confirm these observations on the middle- and long-term.
Mediterranean Journal of Nutrition and Metabolism, 2008
Numerous randomized clinical trials, systematic reviews and meta-analyses have confirmed the anti... more Numerous randomized clinical trials, systematic reviews and meta-analyses have confirmed the antidyslipidaemic activity of different dietary supplements, nutraceuticals and herbal remedies. International guidelines for cardiovascular disease prevention have begun to consider dietary supplements as an evidence-based approach to improve patients' plasma lipid levels. They already suggest to increasing or supplementing the dietary intake of soluble fibre (especially psyllium), soy proteins, plant sterols, niacin, and fish oil. Among the nutraceuticals, mevacoline and policosanol are both able to reduce plasma LDL-C by a mean of 20%. A preliminary clinical study of berberine has shown it to be the most powerful antihyperlipidaemic natural compound, reducing plasma LDL-C by 25% and triglycerides by 35%. Among the herbal remedies, several placebo-controlled randomized clinical trials have confirmed the anti-hypercholesterolaemic, and antihypertriglyceridaemic properties of aged garlic powder, artichoke leaf extracts, guggul, and fenugreek. Single small clinical trials have also suggested that Korean ginseng, green tea, onion, yarrow, holy basil and arjun have an antihypercholesterolaemic effect.
Expert opinion on drug safety, 2014
To answer the need of a better low-density lipoprotein (LDL) cholesterol control in statin-treate... more To answer the need of a better low-density lipoprotein (LDL) cholesterol control in statin-treated patients at high risk for cardiovascular disease, new injectable lipid-lowering drugs with innovative mechanisms of action are in advanced phase of development or have just been approved. Evolocumab and alirocumab are fully human monoclonal antibodies inhibiting the proprotein convertase subtilisin/kexin type 9 (PCSK9) that binds to hepatic LDL receptor and prevents it from normal recycling by targeting it for degradation. Mipomersen specifically binds to a segment of the human apolipoprotein B100 messenger RNA, blocking the translation of the gene product. Phase II (for evolocumab and alirocumab) and III (for evolocumab) trials show that PCSK9 inhibitors are equally well tolerated, with adverse events mainly limited to mild-to-moderate nasopharyngitis, injection-site pain, arthralgia and back pain. Mipomersen use is mainly associated to hepatosteatosis, increased transaminases (> 3...
Advances in clinical and experimental medicine : official organ Wroclaw Medical University
Oxidation makes LDL an immunogenic substrate, stimulating the production of specific autoantibodi... more Oxidation makes LDL an immunogenic substrate, stimulating the production of specific autoantibodies against oxidized LDL (ox-LDL Ab). The demonstration of ox-LDL Ab presence in serum indicates the existence of a long-term lipid peroxidation in vivo. The aim of the study is to evaluate the influence of a large number of dietary variables on the dosage of ox-LDL Ab in pharmacologically untreated healthy subjects. The Brisighella Heart Study (BHS) is a prospective, population-based longitudinal epidemiological investigation involving 2939 randomly selected adult subjects, resident in the northern Italian rural town of Brisighella. For this study, we analyzed the dietary, clinical and laboratory data of 265 (M: 101, W: 164) pharmacologically untreated non-smoker subjects, evaluating the factors potentially affecting their ox-LDL Ab dosage. In a multivariate analysis, including age, BMI, hemodynamic and laboratory parameters, the only significant predictor of log-ox-LDL Ab level was age ...
International journal of nephrology and renovascular disease, 2010
A relatively large body of evidence supports the notion that glomerular capillary wall and mesang... more A relatively large body of evidence supports the notion that glomerular capillary wall and mesangial alterations in diabetic nephropathy involve biochemical alterations of glycoproteins in these structures. Evidence in experimental animals rendered diabetic reveals that the administration of heparin and other anionic glycoproteins can effectively prevent the biochemical alterations that promote albuminuria. Moreover, angiotensin II inhibits heparan sulfate synthesis, while heparins modulate angiotensin II signaling in glomerular cells, inhibiting aldosterone synthesis and lowering proteinuria in diabetes patients. Sulodexide, a mixture of heparin and dermatan sulfate, appears to be a promising treatment for diabetic proteinuria partially resistant to renin-angiotensin system blocking agents. Sulodexide prevents heparan sulfate degradation, thus allowing reconstruction of heparan sulfate content and restoration of glomerular basement membrane ionic permselectivity. The antiproteinuri...
Journal of endocrinological investigation
Sex hormones and adipokines seem to differently interact in both genders at different ages. To co... more Sex hormones and adipokines seem to differently interact in both genders at different ages. To comparatively evaluate the serum level of adipokines and sex hormones in healthy non-pharmacologically treated premenopausal women, post-menopausal women, and elderly women, and in age-matched men. From the historical cohort of the Brisighella Heart Study we selected 199 adult healthy subjects (males: 89; females: 110), aged 62.5±12.4 yr. Men and women included in the age-class subgroups were matched for body mass index (BMI), waist circumference, blood pressure, heart rate, fasting plasma glucose, plasma lipids. Leptin did not differ among various age classes in men, while pre-menopausal women displayed significantly lower serum leptin than post-menopausal women (-6.7 ± 2.2 pg/ml, p=0.036). Post-menopausal women had significantly greater serum leptin when compared with age-matched men (+13.1 ± 2.0 pg/ml, p<0.001); the same was observed for elderly women when compared with elderly men (...
Vascular health and risk management, 2007
Persistence on treatment affects the efficacy of antihypertensive treatment. We prospectively inv... more Persistence on treatment affects the efficacy of antihypertensive treatment. We prospectively investigated the persistence on therapy and the extent of blood pressure (BP) control in 347 hypertensive patients (age 59.4 +/- 6 years) randomly allocated to a first-line treatment with: angiotensin-converting enzyme (ACE) inhibitors, calcium-channel blockers (CCBs), beta-blockers, angiotensin-II receptor blockers (ARBs), or diuretics and followed-up for 24-months. Persistence on treatment was higher in patients treated with ARBs (68.5%) and ACE inhibitors (64.5%) vs CCBs (51.6%; p < 0.05), beta-blockers (44.8%, p < 0.05), and diuretics (34.4%, p < 0.01). No ARB, ACE inhibitor, beta-blocker, or diuretic was associated with a higher persistence in therapy compared with the other molecules used in each therapeutic class. The rate of persistence was significantly higher in patients treated with lercanidipine vs others CCBs (59.3% vs 46.6%, p < 0.05). Systolic and diastolic BP was...
Vascular health and risk management, 2007
Familial combined hyperlidemia (FCH) is a common metabolic disorder characterized by: (a) increas... more Familial combined hyperlidemia (FCH) is a common metabolic disorder characterized by: (a) increase in cholesterolemia and/or triglyceridemia in at least two members of the same family, (b) intra-individual and intrafamilial variability of the lipid phenotype, and (c) increased risk of premature coronary heart disease (CHD). FCH is very frequent and is one of the most common genetic hyperlipidemias in the general population (prevalence estimated: 0.5%-2.0%), being the most frequent in patients affected by CHD (10%) and among acute myocardial infarction survivors aged less than 60 (11.3%). This percentage increases to 40% when all the myocardial infarction survivors are considered without age limits. However, because of the peculiar variability of laboratory parameters, and because of the frequent overlapping with the features of metabolic syndrome, this serious disease is often not recognized and treated. The aim of this review is to define the main characteristics of the disease in ...
Current opinion in investigational drugs (London, England : 2000), 2006
Hyperlipidemia is a well-established risk factor for atherogenesis and cardiovascular disease. St... more Hyperlipidemia is a well-established risk factor for atherogenesis and cardiovascular disease. Statins have been the cornerstone of treatment for hyperlipidemia in recent years and have significantly contributed to the improvement of cardiovascular disease therapy. However, novel antihyperlipidemic agents that have been developed over the last decade possess the capacity to significantly reduce plasma lipoproteins. This review analyzes the pharmacological profile, effectiveness and safety of some promising drugs that are either already in clinical use (eg, ezetimibe and nicotinic acid) or under study (eg, acyl-CoA cholesterol acyltransferase inhibitors, cholesteryl ester transfer protein inhibitors and apolipoprotein A-IMilano).
Drugs & aging, 2005
One of the categories of drugs most frequently used by the elderly, and probably the most commonl... more One of the categories of drugs most frequently used by the elderly, and probably the most commonly self-prescribed class of drug in this age group, is NSAIDs. However, NSAIDs are one of the primary causes of adverse drug reactions and are notorious for their gastric toxicity. They also inhibit renal function and reduce the efficacy of diuretics and ACE inhibitors, drugs that are commonly used by elderly patients. Recent studies have shown that cyclo-oxygenase (COX)-2 is important in renal physiology. This means that selective COX-2 inhibitors, while undoubtedly safer than NSAIDs in terms of gastric toxicity, are not devoid of renal toxicity (in addition to their now clearly established adverse effects on coronary heart disease risk). Both the gastric and renal toxicities induced by traditional NSAIDs and selective COX-2 inhibitors seem to be related to inhibition of prostaglandin, but not leukotriene, synthesis. Maintaining the correct balance between prostaglandins and leukotrienes...
Advances in Clinical and Experimental Medicine, 2014
Recent preclinical evidence and data from adult subjects suggests that statins could improve the ... more Recent preclinical evidence and data from adult subjects suggests that statins could improve the proinflammatory profile of hypercholesterolemic subjects. We aim to compare the serum levels of a set of proinflammatory chemokines in elderly statistical twins taking or not taking statins. Among the historical cohort of the Brisighella Heart Study, we chose 40 healthy elderly subjects continuously treated with statins for at least 1 year and 40 cross-matched subjects not treated with statins (M : F = 1 : 1) characterized by similar age, body mass index (BMI), leisure-time and working activity, smoking habits, history of cardiovascular disease, systolic and diastolic blood pressure, fasting plasma glucose, plasma lipids, uric acid, and creatinine. The proinflammatory chemokine serum level is similar in statin untreated and treated statistical twins. The OR to have a serum level of monocyte chemoattractant protein (MCP-1) lower than the 50th percentile of the distribution in statin-treated subjects compared to the statin untreated subjects is 0.669 (95% CI 0.193; 2.327), the OR for interleukin-8 (IL-8) = 0.818 (95% CI 0.236; 2.835), the OR for γ-interferon inducible protein-10 (IP-10) = 1.361 (95% CI 0.358; 5.175), and for interleukin-18 (IL-18) = 0.545 (95% CI 0.155; 1.914). In relatively healthy, elderly subjects selected from a randomized general population sample, we did not observe differences in the serum levels of the selected set of proinflammatory chemokines in statin treated and untreated subjects with similar LDL-C level, suggesting that cholesterol reduction per se could be a main determinant of statin anti-inflammatory effects.
The authors hypothesized that matrix metalloproteinase (MMP)-2, -9, and tissue inhibitor metallop... more The authors hypothesized that matrix metalloproteinase (MMP)-2, -9, and tissue inhibitor metalloproteinase (TIMP)-1, -2 would be abnormal in acute coronary syndromes (ACSs). MMP-2, -9, and TIMP-1, -2 plasma levels were measured in diabetic patients with ACSs compared to nondiabetic patients with ACSs. A total of 46 diabetic and 78 nondiabetic patients with ACSs were enrolled. The following parameters were measured: body mass index (BMI), glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), fasting plasma insulin (FPI), homeostasis model assessment index (HOMA index), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (Tg), lipoprotein(a) [Lp(a)], plasminogen activator inhibitor-1 (PAI-1), homocysteine (Hct), fibrinogen (Fg), high-sensitivity C-reactive protein (hs-CRP), and plasma levels of MMP-2, MMP-9, TIMP-1, and TIMP-2. Significant HbA1c, FPG, FPI, HOMA index, DBP, Tg, Hct, and Fg increases were present in the diabetic group with ACSs, whereas hs-CRP was lower in these patients compared to nondiabetic patients with ACSs. MMP-9, TIMP-1, and TIMP-2 plasma levels were higher in diabetic patients with ACSs compared to nondiabetic patients with ACSs. MMP-9, TIMP-1, and TIMP-2 plasma levels were increased in diabetic patients with ACSs, which may reflect abnormal extracellular matrix metabolism in diabetes during acute event.
Current Vascular Pharmacology, 2014
ABSTRACT Metabolic syndrome (MetS) is a world-wide epidemic disease associated with increased mor... more ABSTRACT Metabolic syndrome (MetS) is a world-wide epidemic disease associated with increased morbidity and mortality. Treatment strategies include pharmacologic and non-pharmacologic methods, with varying degrees of success rate all over the world. Pharmaceutical interest in this field is growing, together with patients requests' for supplementary (or "alternative") treatments. The knowledge of nutraceuticals beneficial effects in subjects with the MetS could help us to better define the appropriate treatment for these subjects, in particular those with contraindications for commonly used drugs, or to achieve guidelines suggested targets. On the other side, it could be not convenient to use a nutraceutical to treat each metabolic syndrome component (i.e.: from 3 to 5) in each affected subjects. Thus, this review tries to focus on widely marketed nutraceuticals with clinically demonstrated effects on more than one component of the MetS, namely omega-3 fatty acids, berberine, psyllium and other soluble fibers, cinnamon, chromium picolinate, banaba, and bitter gourd.
High Blood Pressure & Cardiovascular Prevention, 2014
One of the most frequent side effect of oral contraceptives use is a stable alteration of the lip... more One of the most frequent side effect of oral contraceptives use is a stable alteration of the lipid profile. This could be even more relevant in women affected by polycystic ovary syndrome (PCOS). Considering the importance of a balanced lipid profile in cardiovascular prevention and that the exposure to the drugs could be many years long, our aim was to investigate the possible beneficial effect of a largely tested low-dosed combined lipid-lowering nutraceutical on dyslipidemias induced by oestroprogestins prescribed to young women for different indications. We prospectively enrolled 84 patients in primary cardiovascular disease prevention, with low estimated cardiovascular disease risk (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;5 % according to the ESC/EAS guidelines), and LDL-C increased above normal value (LDL-C &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;130 mg/dL) after the use of at least two different oral oestroprogestins treatments. Forty-four women were prescribed oral oestroprogestins for PCOS, while 40 for pure contraception. The tested nutraceutical contained berberine 500 mg/tab and monacolins 3 mg/tab was prescribed to all enrolled patients, associated the previously prescribed standard lipid-lowering diet. After 3 months of nutraceutical treatment, we observed a significant improvement in BMI (-1.5 ± 0.8 %, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), FPG (-6.9 ± 5.8 %, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), HOMA index (-3.5 ± 5.6 %, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), TC (-20.1 ± 6.6 %, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), LDL-C (-25.3 ± 8.9 %, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), HDL-C (+14.1 ± 2.2 %, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), TG (-29.9 ± 25.2 %, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and hsCRP (-2.5 ± 2.4 %, p = 0.019). Similar results have been obtained even repeating the analysis by subgroups, beyond hsCRP that significantly improved in PCOS patients compared to both the baseline and the non-PCOS group. It appears that the tested combined lipid-lowering nutraceutical is able to equally improve lipid metabolism in oral contraceptive induced hypercholesterolemia in women affected or not by PCOS.
High Blood Pressure & Cardiovascular Prevention, 2014
Serum uric acid (SUA) may contribute to the increased cardiovascular damage through direct injury... more Serum uric acid (SUA) may contribute to the increased cardiovascular damage through direct injury to the endothelium and alteration of cardiovascular function. To evaluate the association of SUA with the presence of the most recurrent electrographic alterations and with the length of the main ECG intervals in a large sample of general population. For this study, on the database of the Brisighella Heart Study, we evaluated the available data of 790 men and 849 women, excluding subjects affected by gout or taking antihyperuricemic agents, those taking drug increasing the QT interval and those using beta-blockers or non-dihydropyridine calcium channel blockers at the moment of the ECG registration. Multiple ascending stepwise regression analyses were carried out to determine the independent predictors of the predefined ECG alterations. The prevalence of predefined ECG alterations was comparable between genders, with the exception of sinus bradicardia, left-anterior fascicular block, atrio-ventricular blocks and left ventricular hypertrophy (LVH), which appeared to be more frequent in men. The multivariate analysis revealed that SUA was associated to ischaemic alterations, LVH, sinus tachycardia and tachyarrhytmias. Age was associated to all evaluated ECG alterations beyond sinus tachycardia and LVH. Male sex was associated to sinus bradicardia, atrio-ventricular blocks, anterior-left fascicular block and LVH. Blood pressure was associated to different ECG alterations, but with clinically relevant OR with ischaemic alterations and LVH. SUA level is related the prevalence of both organic and rhythm ECG alterations in a wide sample of general population.
Internal and Emergency Medicine, 2012
Metabolic Syndrome and Related Disorders, 2013
Abstract Background: Nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome are strongly... more Abstract Background: Nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome are strongly related from both an epidemiological and a pathological point of view. The main aim of our study was to evaluate if two validated indexes of NAFLD are able to predict the 4-year metabolic syndrome incidence in a large population sample of pharmacologically untreated subjects without metabolic syndrome, type 2 diabetes, history of alcohol abuse, or known liver diseases at the baseline. From the database of the Brisighella Heart Study, we selected a subsample of 824 pharmacologically untreated subjects (male, 401; female, 423) without metabolic syndrome, type 2 diabetes, alcohol abuse, or known liver diseases at the 2004 survey and revisited in 2008. The Hepatic Steatosis Index (HSI) and Lipid Accumulation Product (LAP) values were calculated for everyone to evaluate their predictive role for metabolic syndrome through a Cox-regression analysis adjusted by metabolic syndrome components. We observed 46 new cases of metabolic syndrome (male, 25; female, 21) with a cumulative incidence of 5.6% (1.4% per year): 6.2% in men (1.5% per year), 4.9% in women (1.2% per year). In women, the 4-year metabolic syndrome predictors (R(2)=0.680) were age [odds ratio (OR) 1.13, 95% confidence interval (CI) 1.12-1.15], HSI (OR 1.20, 95% CI 1.15-1.26), and lnLAP (OR 1.16, 95% CI 1.14-1.17), whereas in men they were (R(2)=0.554) age (OR 1.13, 95% CI 1.11-1.14) and lnLAP (OR 1.17, 95% CI 1.15-1.18). HSI and LAP differently predict the 4-year incidence of metabolic syndrome. In women, both indexes can be considered significant predictors, whereas in men only LAP can be considered predictive.
Cardiovascular complications are important in hyperthyroidism because of their high frequency in ... more Cardiovascular complications are important in hyperthyroidism because of their high frequency in clinical presentation and increased mortality and morbidity risk. The cause of hyperthyroidism, factors related to the patient, and the genetic basis for complications are associated with risk and the basic underlying mechanisms are important for treatment and management of the disease. Besides cellular effects, hyperthyroidism also causes hemodynamic changes, such as increased preload and contractility and decreased systemic vascular resistance causes increased cardiac output. Besides tachyarrythmias, impaired systolic ventricular dysfunction and diastolic dysfunction may cause thyrotoxic cardiomyopathy in a small percentage of the patients, as another high mortality complication. Although the medical literature has some conflicting data about benefits of treatment of subclinical hyperthyroidism, even high-normal thyroid function may cause cardiovascular problems and it should be treated. This review summarizes the cardiovascular consequences of hyperthyroidism with underlying mechanisms. K Ke ey y w wo or rd ds s: : hyperthyroidism, subclinical hyperthyroidism, overt hyperthyroidism, atrial fibrillation, Graves' disease, toxic nodular goitre. C Co or rr re es sp po on nd di in ng g a au ut th ho or r: :