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Cardiovascular (CV) diseases account for over 4 million deaths every year in Europe and over 220 000 deaths in Italy, representing the leading cause of morbidity and mortality worldwide. The European Society of Cardiology (ESC) guidelines have visionary included in the at very high CV risk group patients without previous acute ischemic events, such as those with subclinical atherosclerosis, chronic coronary syndrome or peripheral arterial disease, familial hypercholesterolemia, diabetes mellitus with target organ damage or multiple associated risk factors, and those with high calculated CV risk score, recommending to consider them and to achieve the same LDL-cholesterol targets as for secondary prevention patients. The aim of this position paper is to provide an updated overview of ESC guidelines that focuses on these patient categories to raise awareness within the clinical community regarding CV risk reduction in this specific epidemiological context.

Background: Elevated cholesterol levels and systemic inflammation are considered relevant risk factors for cardiovascular disease (CVD) development and progression. Increasing evidence suggests that cholesterol-lowering and inflammation-lowering nutraceuticals are useful in the management of moderate hypercholesterolemia. Here, we describe the study protocol of a clinical trial aimed to evaluate the cholesterol and inflammatory lowering effect of an innovative dietary supplement (BruMeChol™, Mivell S.r.l., Italy), composed of a mixture of extracts of bergamot and olive fruits in association with vitamin K2 in subjects with mild hypercholesterolemia., Methods: The study was planned as a randomized, double-blind, placebo-controlled, parallel group clinical trial for 12 weeks at the Cardiology Unit of the IRCCS INRCA of Ancona, Italy. A total of 125 subjects (age ≥ 40 years) with mild hypercholesterolemia (total serum cholesterol levels ≥ 200 and ≤ 250 mg/dl) will be recruited. Intervention arm participants will take one capsule of dietary supplement two times a day, 15 min before the main meal. Control arm participants will receive one capsule of placebo in the same way. The dietary supplement capsule contains the following ingredients: phytosterols, flavonoid-rich extract of bergamot fruit (Citrus bergamia), flavonoid-rich extract of olive fruit (Olea europaea), and vitamin K2. Participants will undergo a medical evaluation and chemical-clinical examinations, which include lipid profile, glycemia, biomarkers of renal, liver and cardiac/muscular functions, interleukins (IL 6, IL-32, IL-37, and IL-38), and innovative mediators of inflammation such as inflamma-miRs (miR-21 and miR-146a), at baseline, and after 6 and 12 weeks of treatment. The decrease in total cholesterol levels and inflammatory biomarkers will be the primary and secondary endpoints of the study., Discussion: This protocol study, planned to verify the effects of BruMeChol™ dietary supplementation in subjects with mild hypercholesterolemia, could also contribute to new study designs for next large-scale multicenter clinical trials., Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12619000170123 . Retrospectively registered on 5 February 2019.

High levels of LDL cholesterol (LDL-C) represent a causal factor for cardiovascular diseases on an atherosclerotic basis, with a direct correlation between these and mortality or cardiovascular events, such that the reduction of both is associated proportionally and linearly with the reduction of LDL-C.Statins and ezetimibe are used for LDL-C lowering but may not be sufficient to achieve the targets defined by the ESC/EAS guidelines, which recommend use of PCSK9 inhibitors for further LDL-C reduction in patients not at goal.This project submitted 86 clinical scenarios to a group of experts, cardiologists, internists and lipidologists, collecting their opinion on the appropriateness of different behaviors and decisions. We used the RAND/UCLA method of assessing the appropriateness of clinical interventions, validated to combine the best scientific evidence available with expert judgment. To this end, the benefit-risk ratio was evaluated in the proposed clinical scenarios. Each indication was classified as "appropriate", "uncertain" or "inappropriate" based on the average score given by the participants.This document presents the results of a consensus process that led to the development of recommendations for the management of clinical scenarios on the treatment of patients with dyslipidemia, which cannot always be solved with scientific evidence alone.

Background and Aims: HCV is associated with an increased risk of cardiovascular events (CV). Whether HCV clearance by direct-acting antivirals (DAA) reduces incident CV disease is poorly understood. We investigate whether HCV eradication reduces CV events., Methods: In a prospective multicentre study, 2204 HCV patients (F0-F2:29.5%, F3-F4: 70.5%) were enrolled. Males were 48%, median age was 68 (59-74) years and BMI 25.9 (23.1-28); 24.7% were smokers, 18% had diabetes, 13.2% had cholesterol levels >200 mg/dl and 9.1% took statins, 44% had hypertension. During an overall median follow-up of 28 (24-39) months, incident CV events, such as ischemic heart disease (IHD) and ischemic cerebral stroke (ICS), were recorded. An overall of 2204 patients were evaluated as control group and 1668 patients after HCV elimination were followed as a case group. Factors associated with CV events were evaluated by uni- and multi-variate analyses., Results: Incident CV rates per 100 patient years in pre-treatment and untreated controls and treated cases were 1.12, 1.14 and 0.44 (p = 0.0001 vs. controls), respectively, and a decreased of relative risk (RR = 0.379; p = 0.0002) was observed. CV risk was 2.0-3.5 times lower then in controls (HR 3.671; 95%C.I.:1.871-7.201; p < 0.001). The calculated number of patients to be treated to get a benefit in a patient was 55.26. The annual incidence reduction of CV events was 0.68%. HCV clearance was independently associated with CV events reduction (OR, 4.716; 95% C.I.:1.832-12.138; p = 0.001)., Conclusions: HCV clearance by DAA reduces CV events (IHD and ICS) with both clinical and socio-economic benefits., Competing Interests: Declaration of competing interest The authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Aims: In the association between hypercholesterolemia (HC) and thrombotic risk platelet hyper-reactivity plays an important role. The inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) to reduce plasma LDL-cholesterol merges as effective therapeutic strategy to prevent cardiovascular (CV) events. Aim of this study was to verify whether a treatment up to 12 months with the monoclonal antibodies (mAbs) anti-PCSK9 influences platelet function in primary HC., Methods and Results: In patients affected by primary HC (n = 24), all on background of statin and 17 on acetyl salicylic acid (ASA), platelet function parameters were evaluated at baseline up to 12 months of treatment with the mAb anti-PCSK9 alirocumab or evolocumab. From baseline, the treatment with anti-PCSK9 mAbs: i) in ASA HC patients, significantly decreased platelet aggregation detected in platelet-rich plasma by light transmission aggregometry and in whole blood Platelet Function Analyzer-100 assay; ii) in all HC patients, significantly decreased platelet membrane expression of CD62P and plasma levels of the in vivo platelet activation markers soluble CD40 Ligand, Platelet Factor-4, and soluble P-Selectin. Furthermore, CD62P expression, and sP-Selectin, PF-4, sCD40L levels significantly correlated with serum PCSK9., Conclusion: Besides markedly lowering LDL-c levels, our results suggest that HC patients benefit from anti-PCSK9 mAb treatment also for reducing platelet reactivity and increasing platelet sensitivity to the inhibitory effects of aspirin. These effects on platelets could play a role in the reduction of CV event incidence in patients treated with PCSK9 inhibitors., (Copyright © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Elevated levels of LDL-C represent a major risk factor for cardiovascular (CV) disease and recent guidelines recommended early and appropriate interventions in hypercholesterolemic patients in order to reduce the risk of CV events. The current lipid lowering therapies (mainly statins and ezetimibe) not always allow patients to reach their appropriate LDL-C goals. This is particularly true in patients affected by genetic forms of hypercholesterolemia as well as in those who need to attain low LDL-C due to their high cardiovascular risk. In this context, the recent availability of monoclonal antibodies directed against the PCSK9 protein (PCSK9i) represent a novel therapeutic strategy to control resistant forms of hypercholesterolemia. In this review, we will examine the clinical pharmacology of PCSK9i and we will dedicated particular attention to review the results of the two pivotal cardiovascular prevention trials, FOURIER and ODISSEY OUTCOMES that demonstrated the benefit of PCSK9i in prevention of cardiovascular events in patients at very high risk not at LDL-C goal with conventional LDL-lowering therapies. The PCSK9i has been approved for use in Italy under specific criteria and following a strict prescription procedures. We will examine the epidemiology of use of PCSK9i in Italy and will underlying the potential factors influencing the access and availability to this therapy.

Introducion: Treatment strategies for patients with pre-hypertension and low-moderate cardiovascular (CV) risk may include nutraceutical compounds (NCs)., Aim: To investigate the efficacy and safety of a new-generation of NC in lowering BP values and improving metabolic profile, in a group of hyper-cholesterolemic subjects with pre-hypertension., Methods: 131 subjects with pre-hypertension (systolic BP 130-139 mmHg and/or diastolic BP 85-89 mmHg) without organ damage and history of CV diseases were enrolled. 66 subjects were treated with a once-daily oral formulation of a NC (red yeast rice, Berberine, Coenzyme Q10, folic acid and chrome) added to diet for 3 months, while 65 patients followed a diet only. Differences in serum total cholesterol (TC), low- and high-density lipoprotein cholesterol (LDLC and HDLC), triglycerides (TG), glycemia, creatine phosphokinase (CPK), aspartate aminotransferase (AST) alanine aminotransferase (ALT) and body mass index (BMI) were evaluated., Results: At the end of treatment, significant reductions of TC, LDLC, TG glucose levels were observed in both treatment groups, while HDLC values increased in the active treatment group only. A greater reduction of TC, LDLC and glycemia was observed in the treatment group. TG levels were not different within the two groups. BP and BMI levels remained unchanged, as well AST, ALT; CPK slightly increased in both groups, but it remained in the normal range., Conclusions: In patients with pre-hypertension, NC supplementation was safe, well tolerated and effective in improving lipid pattern and glucose levels and in preventing the progression to overt hypertension.

Statins are a class of drugs registered and prescribed to lower total and LDL-cholesterol. Clinical trials performed in the last 25 years have shown that these agents are effective in improving cardiovascular outcomes in several different clinical settings. However, in some cases statin treatment may be associated with significant side effects and adverse reactions. The occurrence of such adverse events during statin therapy may cause discontinuation of treatment together with the impossibility of achieving recommended lipid goals. The clinical condition in which patients experience major unacceptable symptoms and/or develop laboratory abnormalities during statin therapy is defined as statin intolerance. This document outlines the diagnostic and therapeutic pathways for the clinical management of patients with hypercholesterolemia and statin intolerance.

LDL-cholesterol (LDL-C) reduction after acute coronary syndromes (ACS) is associated with a significant reduction in ischemic recurrences. Accordingly, international guidelines recommend a reduction of LDL-C below 70 mg/dl in ACS patients. Such a result can be accomplished by using high intensity statins, possibly associated with ezetimibe in selected cases. This document outlines the management strategies that can be consistently implemented in clinical practice in order to achieve and maintain guideline-recommended therapeutic goals.

The aim of the paper is to disentangle the roles that patients, physicians and technology can have on patient health outcomes. The analysis focuses on patients suffering from hypercholesterolemia. Using a large and detailed dataset of patients collected by the Italian College of General Practitioners (SIMG) over the period 2001-2006, we observe the existence of heterogeneity in the time needed to reach an optimal level of health stock. We firstly explore whether patients recovering faster exhibit lower hospitalization rates. Secondly, we study the determinants of the speed of recovery to a good health status. Results suggest that a 10% increase in the speed of recovery reduces hospitalization rates by 1% in the general sample and by 1.25% in patients in primary prevention. Furthermore, we show that recovering to a good health status is a multifaceted phenomenon, with technology explaining from 54 to 68% of the total effect.

Despite a recent health claim by the European Agency on Food Safety, the effect of high doses of dietary monacolin supplements from red yeast rice on cholesterolemia has not been tested in Italian subjects. Our aim via a crossover, double-blind, placebo-controlled randomized clinical trial was to test if a short-term treatment with 10 mg monacolins could improve lipid pattern, high-sensitivity C-reactive protein (hs-CRP), and vascular remodeling biomarkers in a small cohort of Mediterranean subjects. Thus, 25 healthy, mildly hypercholesterolemic subjects were enrolled, and after 4 weeks of a stabilization diet, subjects were randomized to the sequence placebo-washout-monacolins or monacolins-washout-placebo, with each period being 4 weeks long. At each study step, a complete lipid pattern, safety parameters, hs-CRP, and matrix metalloproteinases 2 and 9 levels were measured. When compared to the placebo group, monacolins-treated patients experienced a more favorable percent change in total cholesterol (-12.45%, 95% CI -16.19 to -8.71), low-density lipoprotein cholesterol (-21.99%, 95% CI -26.63 to -17.36), non-high-density lipoprotein cholesterol (-14.67%, 95% CI -19.22 to -10.11), matrix metalloproteinase 2 (-28.05%, 95% CI -35.18 to -20.93), matrix metalloproteinase 9 (-27.19%, 95% CI -36.21 to -18.15), and hs-CRP (-23.77%, 95% CI -30.54 to -17.01). No significant differences were observed in regards to triglycerides, high-density lipoprotein cholesterol, and safety parameters. On the basis of our data, we demonstrate that a 10-mg monacolin nutraceutical appears to safely reduce cholesterolemia, hs-CRP, and markers of vascular remodeling in Italian subjects. These results have to be confirmed in larger patient samples and longer studies., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The primary aim of the STAR Study (Statins Target Assessment in Real practice) was to determine the LDL-cholesterol reduction and to analyse patient's and therapeutic factors associated to LDL-cholesterol target attainment in newly treated subjects with statins in an unselected population in clinical practice setting. Administrative databases (including pharmaceutical prescriptions and hospital admissions) and laboratory test databases (including LDL-cholesterol values) of five local health units, distributed in Emilia Romagna, Toscana and Umbria, were linked. A retrospective cohort study was conducted and all subjects aged > or =18 years with a first prescription for statins (newly treated subjects) between January 1st, 2007 and June 30th, 2008 were included. All statin prescriptions over a 12 months follow-up period were considered and used to calculate adherence to treatment. Baseline and follow-up LDL-cholesterol, respectively, were defined according to the nearest determination to the first prescription for statins and to the end of the follow-up period. A total of 3.232 subjects was included, 1.516 males (47%) and 1.716 females (53%), with an average age equal to 65.9 +/- 11.3 years. Among included subjects, 22.,6% had a gap to LDL-cholesterol target <10%, 30.0% between 10 and 29%, 20.7% between 30 and 49%, and 26.7% . or =50%. Among those with a gap to target > or =50%, 30-49%, and 10-29%, respectively, LDL-cholesterol target was attained by 7.1%, 41.8%, and 62.% of subjects. LDL-cholesterol target attainment was associated to gap to target, adherence with treatment, and type of statin.

Background and Aim: Some clinical evidence supports a statin antihypertensive effect. Our aim is to evaluate the statin effect on blood pressure control in hypertensive patients in the setting of clinical practice, and the role of some predetermined individual patient characteristics (age, gender, baseline BP levels, pre-treatment LDL-C levels) on the supposed statin BP lowering effect., Methods and Results: Two hundred and fifty-four hypertensive patients with hypercholesterolemia were enrolled in the Ambulatory service of the Hypertension Research Unit of Bologna University Hospital. After 2-4 weeks of a run-in period patients were allocated to statin treatment and followed-up for 24 weeks. The blood pressure response to statins was compared in several subgroups of patients according to age, gender, baseline BP and pre-treatment cholesterolemia. In the overall study population, the use of statins was associated with a significant reduction in systolic (-7.6+/-4 mmHg, p<0.05) and diastolic blood pressures (-5.2+/-3 mmHg, p<0.05) in comparison to baseline. The blood pressure decrease was more pronounced in patients younger than 65 years (p<0.05), with higher baseline systolic blood pressure (p<0.005), and in those with higher cholesterolemia before statins (p<0.05)., Conclusions: Our study suggests a BP-lowering effect of statins, consistent with some other literature. Some parameters like age, baseline systolic blood pressure and cholesterolemia influence the antihypertensive effect of statins. The lack of consideration for these confounding factors may be one of the reasons for the conflicting results about the BP lowering effects of statins., (Copyright 2009 Elsevier B.V. All rights reserved.)

Objective: To investigate the possibility that statins reduce blood pressure as well as cholesterol concentrations through clinic and 24 hour ambulatory blood pressure monitoring., Design: Randomised placebo controlled double blind trial., Setting: 13 hospitals in Italy, Participants: 508 patients with mild hypertension and hypercholesterolaemia, aged 45 to 70 years., Intervention: Participants were randomised to antihypertensive treatment (hydrochlorothiazide 25 mg once daily or fosinopril 20 mg once daily) with or without the addition of a statin (pravastatin 40 mg once daily). Main outcome measures Clinic and ambulatory blood pressure measured every year throughout an average 2.6 year treatment period., Results: Both the group receiving antihypertensive treatment without pravastatin (n=254) (with little change in total cholesterol) and the group receiving antihypertensive treatment with pravastatin (n=253) (with marked and sustained reduction in total cholesterol and low density lipoprotein cholesterol) had a clear cut sustained reduction in clinic measured systolic and diastolic blood pressure as well as in 24 hour, and day and night, systolic and diastolic blood pressure. Pravastatin performed slightly worse than placebo, and between group differences did not exceed 1.9 (95% confidence interval -0.6 to 4.3, P=0.13) mm Hg throughout the treatment period. This was also the case when participants who remained on monotherapy with hydrochlorothiazide or fosinopril throughout the study were considered separately., Conclusions: Administration of a statin in hypertensive patients in whom blood pressure is effectively reduced by concomitant antihypertensive treatment does not have an additional blood pressure lowering effect. Trial registration BRISQUI&#95;*IV&#95;2004&#95;001 (registered at Osservatorio Nazionale sulla Sperimentazione Clinica dei Medicinali-National Monitoring Centre on Clinical Research with Medicines).

Background and Aims: Plant sterols, added to several food sources, lower serum cholesterol concentrations. Plant sterol-induced cholesterol lowering is paralleled by a mild decrease in plasma levels of the antioxidant beta-carotene, the amount of this decrease being considered clinically non-significant. Whether the effect on lipid profile of daily consumption of plant sterol-enriched low-fat fermented milk (FM) is paralleled by a concomitant variation in a reliable marker of the oxidative burden like plasma isoprostane levels is unresolved., Methods and Results: The effect of plant sterol consumption on plasma lipid and isoprostane levels of hypercholesterolemic patients was evaluated in a multicenter, randomized double blind study. Hypercholesterolemic patients consumed a FM daily for 6 weeks. Subjects were randomized to receive either 1.6g of plant sterol-enriched FM (n=60) or control FM product (n=56). After 6 weeks of plant sterol-enriched FM consumption, LDL cholesterol was reduced from 166.2+/-2.0 to 147.4+/-2.8 mg/dL (p=0.01). A significant reduction was observed for total cholesterol (from 263.5+/-2.6 to 231.0+/-3.2mg/dL, p=0.01). There was greater LDL cholesterol lowering among hypercholesterolemic patients with higher LDL cholesterol at baseline. We found a reduction of plasma 8-isoprostane in patients taking plant sterol-enriched FM (from 43.07+/-1.78 to 38.04+/-1.14 pg/ml, p=0.018) but not in patients taking the control product (from 42.56+/-2.12 to 43.19+/-2.0 pg/ml, p=NS). Campesterol and beta-sitosterol levels were not influenced by phytosterol consumption., Conclusions: Daily consumption of low-fat plant sterol dairy product favourably changes lipid profile by reducing LDL-cholesterol, and may also have an anti-oxidative effect through a reduction of plasma isoprostanes.

Background: An increase in carotid intima-media thickness (CIMT) represents an early phase of the atherosclerotic process. The aim of this study was to evaluate whether a reduction in CIMT could be seen with only 16 weeks of treatment with rosuvastatin (10 mg/day)., Methods/results: Sixty-six participants of the ACADIM Study with hypercholesterolemia and carotid atherosclerosis at baseline carotid ultrasound investigation (CUI) were examined, with repeat CUI after 16 weeks of treatment. Demographic and lifestyle data were collected, as well as physical examination and fasting venous blood samples. Total cholesterol, low density lipoprotein cholesterol (LDL-C) and triglycerides decreased significantly (p < 0.0001), while high density lipoprotein cholesterol (HDL-C) increased significantly (p < 0.0001) during the intervention. The mean decrease in IMT of the right and left common carotid arteries (CCAs) was 0.35 and 0.38 mm, respectively (p < 0.05 for each). Age and lipid profile parameters were significant predictors of change in CIMT in linear regression analyses after adjustment for established atherosclerosis risk factors., Conclusions: Treatment with rosuvastatin in adults with evidence of subclinical atherosclerosis significantly reduced the CIMT of both CCAs, as well as improving lipid and lipoprotein levels.

Background: Many studies have indicated the adequate use of lipid-lowering drugs (LLDs) as a factor in reducing the risk of cardiovascular disease. However, in clinical practice, a very high percentage of patients are not adequately treated., Objective: To analyze the management of hypercholesterolemia in a non-experimental setting and to estimate the factors associated with poor adherence to treatment., Methods: A longitudinal study was performed using clinical and demographic data recorded in the General Practitioners' database. The sample included all patients, aged 30 years or over, with total blood cholesterol measured between 1 January and 31 December 2000. Utilization of LLDs was defined as the standardized daily dose of the drugs purchased during the 12 months preceding the cholesterol measurement., Results: The study included 4764 patients (mean age 59.4+/-14.1 years, 40.7% males). Of the subjects with a total cholesterol higher than a 6.5 mmol/l, approximately 17% were treated with LLDs. About 39% of the patients with previous atherosclerotic diseases were taking statins. Analysis of patients taking LLDs showed that 40.6% of subjects took less than half of the defined daily dose. Factors associated with poor adherence to treatment were: absence of previous atherosclerotic diseases, absence of concomitant diseases, and smoking. A total cholesterol of less than 5 mmol/l was achieved in 19.9% of patients., Conclusions: Analyzing the data contained in the general medicine database made it possible to evaluate the use of LLDs in clinical practice and to establish the need to pay greater attention to achieving the objective set by the treatment.

Background: Stroke represents worldwide the second and seventh cause of death and invalidity, respectively. Patients with ischaemic stroke or transitory ischaemic attack (TIA) are at high risk of recurrence, therefore requiring intensive treatment. Hypercholesterolaemia is a modifiable risk factor for stroke. The general practitioners attitude towards detection and treatment of dyslipidaemia among patients with stroke or TIA in Italy is unknown; we therefore aimed to address this issue taking advantage of the database of The Italian College of General Practitioners., Methods: Prevalence of the monitored factors (lipid levels, statin prescription, and lipid level control with hypolipidaemic agents prescription) were analysed on a patient population of 465 061., Results: A total of 2555 (49% women and 51% men) patients with a diagnosis of stroke and 2755 patients (52% women and 48% men) with a diagnosis of TIA were included in the study. Total plasma cholesterol (TC) was reported in more than 60% of the patients and low-density lipoprotein cholesterol (LDLc) and high-density lipoprotein cholesterol (HDLc) in less than half. Total plasma cholesterol and LDLc were controlled in 70.3 and 72.8% of the patients, respectively. The percentage of controlled patients decreased to 64% when both LDLc and TC were considered. Statins and fibrates were prescribed in a small proportion of patients (16.9 and 3.5%, respectively). An acceptable control of blood lipids was achieved in a majority of those patients (60.2%). However a relatively large number of patients (646) with high plasma lipids remained untreated., Conclusions: Monitoring and intervention strategies on plasma lipid levels in patients with a diagnosis of stroke or TIA need to be improved.

In recent years, the concept of "global cardiovascular risk assessment" has grown in interest for its role in primary prevention of cardiovascular diseases. Interventions for reducing the risk of relapse for persons with cardiovascular past history are well agreed-on. But for persons without such a history, the risk of a first attack varies greatly and this variability implies a range in the intensity of interventions. In several countries, guidelines for general practitioners have been diffused about pharmaceutical prescriptions in the different risk classes. In particular, in Italy, a governmental drug management commission has established that Statins, the most used cholesterol lowering medicines, can be refunded by the National Healthcare System only if they are prescribed to hyper-cholesterol patients with a global risk greater than 20%. The question is: how to calculate the risk? We performed a review of both the web and the literature and we found a lot of different "risk calculators". By means of a simulation study, we showed that these tools, when used for the same person, may lead to very different results. We estimated the economic impact of using one or another calculator.

In August 2001, cerivastatin was removed from European and USA markets because of a higher risk of rhabdomyolysis associated with its use in comparison with other statins. The objective of this study was to compare cholesterol-lowering drug use in Italy before and after the withdrawal of cerivastatin from the market, and to evaluate if the withdrawal influenced patients compliance and physicians prescribing habits. After August 2001, 48% of cerivastatin users discontinued any statin treatment. The major risk factor for discontinuation was a concomitant use of fibrate during the first 7 months of 2001 (OR = 2.3; 95% CI = -2.9). Comparing the discontinuation of statin therapy between 2001 and 2000 we can estimate that there was a 5% increase, corresponding to about 200,000 patients, who discontinued statin therapy during autumn 2001 because of cerivastatin emergency.

Background: Currently available guidelines suggest that hypolipidemic drugs should be used in subjects at high risk for coronary heart disease (CHD). Very often, however, physicians fail to comply with the targets (total or LDL cholesterol) that are proposed by the Consensus Panels. The aim of this survey was to evaluate the efficacy of a hypocholesterolemic treatment in achieving the therapeutic target according to Adult Treatment Panel II guidelines in a sample of general practitioners from Lombardy, a region of northern Italy., Methods: Eighty-five general practitioners reported in a standardized manner data on the presence of major and minor coronary risk factors from at least 15 patients from their database for a total of 1275 patients. Treatment targets for LDL cholesterol were 100 mg/dl in patients with existing cardiovascular disease (class I), 130 mg/dl for patients with > or = 2 CHD risk factors (class II), and 160 mg/dl for the others (class III). Results on the efficacy of the therapy were divided into the following categories: 1) to target, 2) failure to reach the target by < or = 30 mg/dl, 3) failure to reach the target by > 30 mg/dl. Data were analyzed by means of the CSS statistical software., Results: Overall 58.2% of the patients were males and the average age of the population was 59.2 +/- 10.1 years; 20.4% were diabetics, 34.5% smokers, 48.8% hypertensives, 16.9% had a previous myocardial infarction, 14.9% were suffering of stable angina, and 8.1% had undergone coronary artery bypass grafting and/or coronary angioplasty. Moreover 33.9% had a positive family history for CHD. Class I patients were 31.7% of the population, class II 52.9%, and class III 15.4%. Plasma lipid levels before treatment were on average 294 +/- 37 mg/dl for total cholesterol, 211 +/- 37 mg/dl for LDL cholesterol, 45 +/- 16 mg/dl for HDL cholesterol, and 195 +/- 104 mg/dl for plasma triglycerides. Of the patients 78.8% received dietary counseling, while 94.7% received hypolipidemic treatment (89.9% were only on statins). The average post-treatment value for total cholesterol was 225 +/- 33 mg/dl (-23%), LDL cholesterol 145 +/- 34 mg/dl (-31%), HDL cholesterol 50 +/- 15 (+15%), and plasma triglycerides 151 +/- 55 (-17%). When patients were stratified according to their LDL cholesterol target, 29.9% were on target, 34.0% missed it by < or = 30 mg/dl, and 36.1% by > 30 mg/dl. In class I only 14.9% achieved the target, in class II 31.2%, in class III 61.8%., Conclusions: These data show that general practitioners do not aim at an aggressive lipid lowering in patients at high risk, perhaps because of the limited knowledge of the need for modulating treatment according to the global CHD risk.

In Italy and Europe, strokes are the third most common cause of death and resulting invalidity. In the ever-increasing 80-years-old-and-over people, strokes become more serious due to the clinical presentation during the acute phase and the ten-times higher mortality, but also in relation to the twice as high resulting disability as for younger subjects. However, stroke prevention is possible both through correct behavioural habits and pharmacological means. Besides the well-known preventive effects of an adequate anti-hypertensive, anti-diabetic and/or anti-aggregant/anti-coagulant therapy, there are increasing evidences of the effectiveness of the anti-hypercholesterolemic therapy in stroke prevention. Moreover, a great part of the risk factors for the cerebrovascular disease coincides with those for cardiovascular disease, for which the correction of the former automatically involves a reduction in incidence of both pathologies. In this context, a statin's rational use can therefore represent an important tool for the combined prevention of the two pathologies. Finally, different hypotheses link the origin of Alzheimer's disease to that of progressive cerebrovascular dementia caused by cerebral microcirculation damage. It is plausible that the application of a suitable early prevention of the cerebrovascular pathology could bring to a more late slatentisation and less serious demonstrations of Alzheimer's disease, when this is destined to develop.

Background: Autosomal recessive hypercholesterolaemia (ARH) is caused by mutations in a putative adaptor protein called ARH. This recessive disorder, characterised by severe hypercholesterolaemia, xanthomatosis, and premature coronary artery disease, is rare except on the island of Sardinia, Italy. Our aim was to ascertain why ARH is more common on Sardinia than elsewhere., Methods: We obtained detailed medical histories, did physical examinations, measured concentrations of lipoproteins, and harvested genomic DNA from 28 Sardinians with ARH from 17 unrelated families. We sequenced the coding regions and consensus splice sites of ARH in probands from these families, and from 40 individuals of non-Sardinian origin who had an autosomal recessive form of hypercholesterolaemia of unknown cause., Findings: Two ARH mutations, a frameshift mutation (c432insA) in exon 4 (ARH1) and a nonsense mutation (c65G-->A) in exon 1 (ARH2), were present in all of the 17 unrelated families with ARH. Three of the ARH alleles contained both mutations, as a result of an ancient recombination between ARH1 and ARH2. No regional clustering of the three mutant alleles within Sardinia was apparent. Furthermore, four Italians from the mainland with autosomal recessive hypercholesterolaemia were homozygous for ARH1., Interpretation: The small number, high frequency, and dispersed distribution of ARH mutations on Sardinia are consistent with these mutations being ancient and maintained in the Sardinian population because of geographic isolation.

The authors confirm--by increasing the ambulatory randomized series in the territories which depend on Monfalcone and Grado (USL 2 Goriziana)--the results of previous studies of lipid improvement owing to the use of pravastatine. The average cholesterolemic rate has decreased of 26.50% in comparison with the initial value, that is from 310.44 +/- 52.587 mg% to 228.16 +/- 28.354 mg%; the addition of each individual rate from 19868 mg% to 14602 mg% (p < 0.001). Within the sample, the elder's undergroup reduced blood cholesterol by 25.76%, that is from 307.69 +/- 42.057 mg% to 228.44 +/- 28.126 mg%, with an addition from 13846 mg% to 10280 mg% (p < 0.001); the adults' undergroup of 28.26%, that is from 316.95 +/- 72.744 mg% to 227.47 +/- 29.654 mg%, with an addition from 6022 mg% to 4322 mg% (p < 0.001). The LDL-lipoprotein value showed a decrease from 30.66% in the average value, which lowered from 206.87 +/- 51.485 to 143.43 +/- 32.940 mg% (relative addition from 13239 mg% to 9179 mg%); in the old patients from 211.45 +/- 52.758 mg% to 143.66 +/- 35.654 mg% (relative addition from 9515 mg% to 6465 mg%), in the adults from 196.01 +/- 47.923 mg% to 142.86 +/- 26.264 mg% (relative addition from 3724 mg% to 2714 mg%. Triglyceridemia fell from 38.37%; the average circulating value fell from 245.13 +/- 348.415 mg% to 151.08 +/- 130.347 mg%; the complete series showed the same average decrease ie from 15688 mg% to 9669 mg%. In the elderly we showed a reduction from 207.87 +/- 250.784 mg% to 149.91 +/- 144.606 mg% (relative addition from 9354 mg% to 6746 mg%), in adults from 333.37 +/- 509.360 mg% to 153.846 +/- 91.321 mg% (relative addition from 6334 mg% to 2923 mg%).

This study compared the efficacy and safety of pravastatin and gemfibrozil in the treatment of primary hypercholesterolemia. Three hundred eighty-five outpatients from 13 lipid clinics in Italy participated in this randomized double-blind study. Patients were assigned to receive either 40 mg once daily of pravastatin or 600 mg of gemfibrozil twice daily after an initial diet lead-in period. After 24 weeks, mean reductions from baseline values of plasma total and low-density lipoprotein cholesterol were, respectively, 23% and 30% with pravastatin and 14% and 17% with gemfibrozil. Significant lipid-lowering effects were noted within 4 weeks. Apolipoprotein B decrease was 21% with pravastatin and 13% with gemfibrozil. A statistically significant increase of high-density lipoprotein cholesterol of 5% was achieved with pravastatin compared with a 13% increase for gemfibrozil. Serum triglyceride values decreased 5% with pravastatin and 37% with gemfibrozil. Familial and polygenic hypercholesterolemic patients were also examined separately. Pravastatin effectiveness in reducing low-density lipoprotein cholesterol was greater by 6% in polygenic than in familial hypercholesterolemic patients. Treatment for 25 patients (eight treated with pravastatin and 17 treated with gemfibrozil) was discontinued during the study. The incidence of clinical symptoms and laboratory alterations was low for both treatment groups. Pravastatin and gemfibrozil were well tolerated, but pravastatin was significantly more effective in reducing total and low-density lipoprotein cholesterol levels in primary (either familial or polygenic) hypercholesterolemias than gemfibrozil.