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Familial hypercholesterolemia (FH) is a common genetic disorder of lipid metabolism, still underdiagnosed and undertreated in the general population. Pathology registers could play a crucial role in the creation of a comprehensive and integrated global approach to cover all aspects of this disease. Systematic data collection of patients affected by FH has increased dramatically worldwide in the past few years. Moreover, results from registers already established for the longest time showed their potentialities in the implementation of the knowledge of FH, comparing country-specific approaches and providing real-world data about identification, management and treatment of FH individuals in the clinical practice. The potential fields of research through registers are related to the deepening of the genetic basis of disease, the study of genotype-phenotype correlation, the local adaption and implementation of diagnostic algorithms, the comparison of pharmacological approaches and treatment gaps in real-life clinical practice, the evaluation of specific subpopulations, and the identification of factors modifying cardiovascular disease risk. Registers could become also a valid resource for other rare dyslipidaemias, contributing towards the evidence-based enhancement in the worldwide care of uncommon diseases.

Post-acute coronary syndrome (ACS) patients are at very high cardiovascular risk. Despite current guidelines strongly recommend to reduce LDL-C levels and initiation of high-intensity statins as early as possible in patients admitted with an ACS, less than half of ACS patients receive a high intensity statin, and a high percentage of has LDL-C well above the goal despite therapy. There are multiple reasons for that, including physician lack of guideline adherence, patient lack of compliance with treatment, and lack of standardized procedures. Furthermore, although the prevalence of familial hypercholesterolemia is higher among patients with ACS, this condition remains poorly estimated. To fill these gaps, some European countries have launched local initiatives for the in-hospital and post-discharge ACS patient lipid management. It appears that ensuring optimal therapy during hospitalization and dedicated follow-up protocols results in a significant improvement of lipid levels in these very high risk patients, which may translate into a reduced risk of recurrent future events.

Objectives Familial hypercholesterolemia (FH) is the most common monogenic lipid disorder associated with premature coronary heart disease. Early cholesterol-lowering therapy could effectively reduce cardiovascular disease morbidity and mortality in these patients. However, the majority of people with FH are undiagnosed, also due to low awareness and knowledge of FH in general practice, despite the high number of contacts GPs have with most of their patients which allows a systematic and effective approach to the detection of this condition. Here, we present a simple method to improve detection and to enhance awareness of FH in primary care using GP electronic health records. Methods We used electronic data from the Co.S. Consortium, involving more than 600 Italian affiliated GPs. Electronic data include demographic information, laboratory test results, recorded history of vascular disease and prescription of an HMG-CoA reductase inhibitor class medication. We performed a partial assessment of the Dutch Lipid Clinic Network (DLCN) score using those data that were recorded or available. We also sought to determine the prevalence of possible FH based on age-specific LDL-cholesterol thresholds employed by the diagnostic criteria of MEDPED and the non-age adjusted cut-off point (LDL-C ≥190 mg/dL). Results Data on LDL-C were available for 162,864 subjects. Mean LDL-C levels (SD) were 124.3 (33.6) mg/dL for non-treated subjects and 106.4 (38.5) mg/dL for statin-treated subjects. The cut-off of LDL-C ≥190 mg/dL yielded a prevalence of 2.9% among non-treated subjects and of 3.5% among statin-treated patients. Using the cut-off of ≥250 mg/dL, the prevalence was 0.1% among non-treated subjects and 0.3% among statin-treated patients. Using the cut-off ≥330 mg/dL (suggesting a probable diagnosis of FH according to the DLCN score) the prevalence was 0.01% and 0.02%. According to the stratification proposed by MEDPED criteria for the general population, the age-specific LDL-cholesterol thresholds identified 0.7% among non-treated subjects and 18.5% among statin-treated patients. Conclusion The diagnosis of FH is possible in general medicine and should be an integral part of the GP's activity.

A key strategy in preventing cardiovascular (CV) disease is the reduction of low-density lipoprotein cholesterol (LDL-C). Statins are a crucial therapy for achieving LDL-C reductions, with the highest tolerated dose often prescribed, especially for patients who are at the greatest risk of CV disease. However, statin intolerance, heterogeneous responses to statins and non-adherence make alternative therapies necessary in some cases. Statins can be combined with a multitude of therapies with synergistic mechanisms of action to effectively manage lipid profiles, while improving safety and tolerability profiles. Addition of a cholesterol absorption inhibitor, bile acid sequestrant or fibrate to statin therapy leads to greater numbers of patients achieving and maintaining LDL-C goals. Furthermore, combination therapies can alter the plasma profiles of other molecules involved in hypercholesterolaemia, including triglycerides and high-density lipoprotein cholesterol. An additional strategy is proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition therapy, for use in patients who are statin intolerant, patients with heterozygous or homozygous familial hypercholesterolaemia, and patients at very high CV risk, as a potential means for achieving large LDL-C reductions and maintaining LDL-C goals. Clinical trials have demonstrated that PCSK9 inhibition therapy is not only effective but can also be combined with statin therapy to ensure greater reductions in LDL-C. Current, ongoing studies are investigating the efficacy of novel therapies, including selective peroxisome proliferator-activated receptor (PPAR) alpha modulators, PCSK9-specific ribonucleic acid (RNA) interference and anti-inflammatory therapies.

Lowering low-density lipoprotein cholesterol (LDL-C) levels is associated with a well-documented reduction in cardiovascular (CV) disease (CVD) risk. Current guidelines and literature support lifestyle interventions as the primary strategy for reducing CV risk. Association of dietary modifications (such as the Mediterranean diet), physical activity and the cessation of smoking with reduced CV morbidity and mortality has been evidenced. Where lifestyle interventions are not adequate for lowering LDL-C levels and CV risk, pharmacological therapies, most commonly statins, may also be considered. The benefits of lifestyle and pharmacological interventions in the prevention of CVD are widely known, but poor adherence and persistence to these necessitate an approach that aims to improve LDL-C lowering for CVD prevention. Nutraceuticals (targeted functional foods or dietary supplements of plant or microbial origin) are included in EU guidelines as lifestyle interventions and may provide an additional approach to controlling LDL-C levels when a pharmaceutical intervention is not (yet) indicated. However, among different nutraceuticals, the level of clinical evidence supportive of efficacy for lipid lowering needs to be considered. Meta-analyses of randomised clinical trials have demonstrated that some nutraceuticals (e.g. red yeast rice and berberine) and some nutraceutical combinations improve lipid profiles, including lowering of LDL-C, total cholesterol and triglyceride levels. Therefore, nutraceuticals may be considered in specific patient groups where there is appropriate evidence to support the efficacy and safety.

Low-density lipoprotein (LDL) cholesterol (LDL-C) is the primary target in cardiovascular (CV) disease prevention and is commonly used in estimating CV risk; however, alternative markers may be needed when LDL-C is not an appropriate marker (e.g. in the presence of low LDL-C levels or elevated triglyceride [TG] levels). Non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B (apoB) are markers of atherogenic lipoproteins with evidenced associations with CV risk and are, therefore, recommended as secondary targets, appropriate for use in the presence of elevated TG levels. The reported strength of the associations of non-HDL-C and apoB in comparison to LDL-C is conflicting between studies, potentially due to discordance of the markers which can alter their predictive pattern. Although LDL-C levels are commonly managed with statin treatment, a residual risk of CV events still remains, and an abnormal lipid profile can persist. Combination therapy to further reduce LDL-C levels can be beneficial; a statin therapy combined with other LDL-C-lowering therapy further reduced the number of CV events. In addition, targeting other markers, including non-HDL-C, apoB, total cholesterol and TGs may also be beneficial, specifically in patients with low HDL-C and elevated TG levels. More clinical evidence is required before definitive recommendations can be made; however, a statin–fenofibrate combination demonstrated favourable reductions in major CV events in these specific patients.

Background: Although omega-3 fatty acids have well documented properties which would reduce the cardiovascular (CV) disease risk, the evidence from randomized controlled trials (RCTs) remains inconclusive. We performed a meta-analysis of the available RCTs for investigating the CV preventive effect of administrating at least 1 gram/day, and for at least 1 year, omega-3 fatty acid supplements to patients with existing CV disease. Methods: RCTs published up to March 2013 were searched from PubMed, EMBASE, and the Cochrane Library. Two of us independently reviewed and selected eligible trials. Results: Of 360 articles retrieved, 11 randomized, double-blind, placebo controlled trials fulfilling inclusion criteria, overall involving 15,348 patients with a history of CV disease, were considered in the final analyses. No statistically significant association was observed for all-cause mortality (RR, 0.89; 95% CI, 0.78 to 1.02) and stroke (RR, 1.31; 95% CI, 0.90 to 1.90). Conversely, statistically significant protective effects were observed for cardiac death (RR, 0.68; 95% CI, 0.56 to 0.83), sudden death (RR, 0.67; 95% CI, 0.52 to 0.87), and myocardial infarction (RR, 0.75; 95% CI, 0.63 to 0.88). Conclusion: Overall, our results supply evidence that long-term effect of high dose omega-3 fatty acid supplementation may be beneficial for the onset of cardiac death, sudden death and myocardial infarction among patients with a history of cardiovascular disease. © 2013 Elsevier Ireland Ltd.

In Europe, cardiovascular disease (CVD) represents the main cause of morbidity and mortality, costing countries euro 190 billion yearly (2006). CVD prevention remains unsatisfactory across Europe largely due to poor control of CVD risk factors (RFs), growing incidence of obesity and diabetes, and sedentary lifestyle/poor dietary habits. Hypercholesterolaemia is a proven CVD RF, and LDL-C lowering slows atherosclerotic progression and reduces major coronary events. Lipid-lowering therapy is cost-effective, and intensive treatment of high-risk patients further improves cost effectiveness. In Italy, models indicate that improved cholesterol management translates into potential yearly savings of euro 2.9-4 billion. Identifying and eliminating legislative and administrative barriers is essential to providing optimal lipid care to high-risk patients. Public health and government policy can influence clinical practice rapidly, and guideline endorsement via national health policy may reduce the CVD burden and change physician and patient behaviour. Action to reduce CVD burden should ideally include the integration of strategies to lower the incidence of major CV events, improvement in total CV risk estimation, database monitoring of CVD trends, and development of population educational initiatives on CVD prevention. Failure to bridge the gap between science and health policy, particularly in relation to lipid management, could result in missed opportunities to reverse the burgeoning epidemic of CVD in Europe.