Nuove linee guida americane 2013 ACC/AHA sul trattamento del colesterolo plasmatico per ridurre il rischio cardiovascolare aterosclerotico: confronto con le raccomandazioni ESC/EAS per la gestione delle dislipidemie

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Class II Phosphoinositide 3-Kinases Contribute to Endothelial Cells Morphogenesis

PMCID: PMC3539993This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Transatlantic lipid guideline divergence: same data but different interpretations

Despite consensus that excessive circulating concentrations of apoB-lipoproteins is a key driver for the atherosclerotic process and that treatments that low-density lipoprotein cholesterol lowering by up-regulation of low-density lipoprotein cholesterol receptor expression reduces that risk, divergent viewpoints on interpretation of study data have resulted in substantial differences in European and American lipid guideline recommendations. This article explores those differences and highlights the importance of understanding guideline-based lipid management to improve patient care and reduce the risk of clinical atherosclerotic cardiovascular disease

Familial hypercholesterolemia: The Italian Atherosclerosis Society Network (LIPIGEN)

Primary dyslipidemias are a heterogeneous group of disorders characterized by abnormal levels of circulating lipoproteins. Among them, familial hypercholesterolemia is the most common lipid disorder that predisposes for premature cardiovascular disease. We set up an Italian nationwide network aimed at facilitating the clinical and genetic diagnosis of genetic dyslipidemias named LIPIGEN (LIpid TransPort Disorders Italian GEnetic Network)

Real-World Identification Of European Patients With Statin-Associated Symptoms: Clinical Practice Compared With Clinical Guidelines

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Lipid-lowering treatment and LDL-C goal attainment in high and very high cardiovascular risk patients: Evidence from the SANTORINI study-The Italian experience

The SANTORINI study is an observational study that enrolled 9602 adult individuals at high or very high cardiovascular (CV) risk across Europe, aimed at providing information on the current status of the management of dyslipidaemias, in light of the most recent 2019 EAS/ESC guidelines. Italy participated in the study with 1977 patients, 1531 (77.4%) of whom were classified at very high CV risk and 446 (22.6%) at high CV risk. Overall, in the Italian population, 79.31% of the patients had a history of atherosclerotic cardiovascular disease (ASCVD). At enrolment, the mean level of LDL-C in the total population was 98.4 mg/dL. LDL-C levels were lower in the very high-risk group (94.6 mg/dL) than in the high-risk group (111.4 mg/dL). Considering the therapeutic goals recommended by the most recent 2019 ESC/EAS guidelines (LDL-C <55 mg/dL or <70 mg/dL respectively in very high or high-risk patients, respectively), only 20.3% of the overall study population achieved such goals (19.9% of very high-risk patients and 21.8% of high-risk patients). About one-third of the patients included in the study (32.6%) were not prescribed any therapy, one-third received statin monotherapy (34.4%), and only one-third (33%) were taking combination therapy; these percentages were comparable in the two risk subgroups. Based on the most recent 2019 ESC/EAS guidelines, the use of cholesterol-lowering therapies is not always optimal to achieve the therapeutic goals even in patients with very high CV risk. This means that about 80% of patients are far from the recommended therapeutic goals for their risk category

Lipoprotein(a) Genotype Influences the Clinical Diagnosis of Familial Hypercholesterolemia

Background Evidence suggests that LPA risk genotypes are a possible contributor to the clinical diagnosis of familial hypercholesterolemia (FH). This study aimed at determining the prevalence of LPA risk variants in adult individuals with FH enrolled in the Italian LIPIGEN (Lipid Transport Disorders Italian Genetic Network) study, with (FH/M+) or without (FH/M-) a causative genetic variant. Methods and Results An lp(a) [lipoprotein(a)] genetic score was calculated by summing the number risk-increasing alleles inherited at rs3798220 and rs10455872 variants. Overall, in the 4.6% of 1695 patients with clinically diagnosed FH, the phenotype was not explained by a monogenic or polygenic cause but by genotype associated with high lp(a) levels. Among 765 subjects with FH/M- and 930 subjects with FH/M+, 133 (17.4%) and 95 (10.2%) were characterized by 1 copy of either rs10455872 or rs3798220 or 2 copies of either rs10455872 or rs3798220 (lp(a) score ≥1). Subjects with FH/M- also had lower mean levels of pretreatment low-density lipoprotein cholesterol than individuals with FH/M+ (t test for difference in means between FH/M- and FH/M+ groups &lt;0.0001); however, subjects with FH/M- and lp(a) score ≥1 had higher mean (SD) pretreatment low-density lipoprotein cholesterol levels (223.47 [50.40] mg/dL) compared with subjects with FH/M- and lp(a) score=0 (219.38 [54.54] mg/dL for), although not statistically significant. The adjustment of low-density lipoprotein cholesterol levels based on lp(a) concentration reduced from 68% to 42% the proportion of subjects with low-density lipoprotein cholesterol level ≥190 mg/dL (or from 68% to 50%, considering a more conservative formula). Conclusions Our study supports the importance of measuring lp(a) to perform the diagnosis of FH appropriately and to exclude that the observed phenotype is driven by elevated levels of lp(a) before performing the genetic test for FH

Red yeast rice for dyslipidaemias and cardiovascular risk reduction: A position paper of the International Lipid Expert Panel.

The risk of atherosclerotic cardiovascular disease (ASCVD) is strongly related to lifetime exposure to low-density lipoprotein (LDL)-cholesterol in longitudinal studies. Lipid-lowering therapy (using statins, ezetimibe and PCSK9 inhibitors) substantially ameliorates the risk and is associated with long-term reduction in cardiovascular (CV) events. The robust evidence supporting these therapies supports their continued (and expanding) role in risk reduction. In addition to these 'conventional' therapeutics, while waiting for other innovative therapies, growing evidence supports the use of a range of 'nutraceuticals' (constituents of food prepared as pharmaceutical formulations) including preparations of red yeast rice (RYR), the product of yeast (Monascus purpureus) grown on rice, which is a constituent of food and is used in traditional Chinese medicine. The major active ingredient, monacolin K, is chemically identical to lovastatin. RYR preparations have been demonstrated to be safe and effective in reducing LDL-C, and CV events. However, surprisingly, RYR has received relatively little attention in international guidelines - and conventional drugs with the strongest evidence for event reduction should always be preferred in clinical practice. Nevertheless, the absence of recommendations relating to RYR may preclude the use of a product which may have clinical utility in particular groups of patients (who may anyway self-prescribe this product), what in the consequence might help to reduce population CV risk. This Position Paper of the International Lipid Expert Panel (ILEP) will use the best available evidence to give advice on the use of red-yeast rice in clinical practice

Treatment gaps in the implementation of LDL cholesterol control among high- and very high-risk patients in Europe between 2020–2021: the multinational observational SANTORINI study

Background European data pre-2019 suggest statin monotherapy is the most common approach to lipid management for preventing cardiovascular (CV) events, resulting in only one-fifth of high- and very high-risk patients achieving the 2019 ESC/EAS recommended low-density lipoprotein cholesterol (LDL-C) goals. Whether the treatment landscape has evolved, or gaps persist remains of interest. Methods Baseline data are presented from SANTORINI, an observational, prospective study that documents the use of lipid-lowering therapies (LLTs) in patients ≥18 years at high or very high CV risk between 2020 and 2021 across primary and secondary care settings in 14 European countries. Findings Of 9602 enrolled patients, 9044 with complete data were included (mean age: 65.3 ± 10.9 years; 72.6% male). Physicians reported using 2019 ESC/EAS guidelines as a basis for CV risk classification in 52.0% (4706/9044) of patients (overall: high risk 29.2%; very high risk 70.8%). However, centrally re-assessed CV risk based on 2019 ESC/EAS guidelines suggested 6.5% (308/4706) and 91.0% (4284/4706) were high- and very high-risk patients, respectively. Overall, 21.8% of patients had no documented LLTs, 54.2% were receiving monotherapy and 24.0% combination LLT. Median (interquartile range [IQR]) LDL-C was 2.1 (1.6, 3.0) mmol/L (82 [60, 117] mg/dL), with 20.1% of patients achieving risk-based LDL-C goals as per the 2019 ESC/EAS guidelines. Interpretation At the time of study enrolment, 80% of high- and very high-risk patients failed to achieve 2019 ESC/EAS guidelines LDL-C goals. Contributory factors may include CV risk underestimation and underutilization of combination therapies. Further efforts are needed to achieve current guideline-recommended LDL-C goals. Trial registration ClinicalTrials.gov Identifier: NCT04271280. Funding This study is funded by Daiichi Sankyo Europe GmbH, Munich, Germany

Associations Between Very Low Concentrations of LDL-Cholesterol, hs-CRP and Health Outcomes in the Reasons for Geographical and Racial Differences in Stroke (REGARDS) Study

Introduction: Recent findings have demonstrated the important contribution of inflammation to the risk of cardiovascular disease (CVD) in individuals with optimally managed low density lipoprotein cholesterol (LDL-C). We explored relationships between LDL-C, high sensitivity C-reactive protein (hsCRP) and clinical outcomes in a free-living US population. Methods: We used data from the REasons for Geographical And Racial Differences in Stroke (REGARDS), and selected individuals at “high risk” for coronary events with a Framingham Coronary Risk Score of >10% or atherosclerotic cardiovascular disease (ASCVD) risk >7.5% in order to explore relationships between low LDL-C (70 mg/dl [1.8 mmol/L]); hs-CRP <2 compared to ≥2 mg/L and clinical outcomes (all-cause mortality, incident coronary heart disease [CHD] and incident stroke). To assess the association between the LDL-C and hs-CRP categories and each outcome, a series of incremental Cox proportional hazards models were employed on complete cases. To account for missing observations, the most adjusted model was used to interrogate the data using multiple imputation with chained equations (MICE). Results: In this analysis, 6136 REGARDS high risk participants were included. In the MICE analysis, participants with high LDL-C (>70 mg/dl) and low hs-CRP (<2 mg/L) had a lower risk of incident stroke (hazard ratio [HR] 0.69, 0.47-0.997) incident CHD (HR 0.71, 0.53- 0.95) and CHD death (HR 0.70, 0.50-0.99) than those in the same LDL-C category high hs- CRP (≥2 mg/L). In participants with high hsCRP (≥2 mg/dL), low LDL-C (<70 mg/dL [1.8 mmol/L]) was not associated with additional risk reduction of any investigated outcome, but with the significant increase of all-cause mortality (HR 1.37, 1.07-1.74). Conclusions: In this high-risk population, we found that low hsCRP (<2mg/L) appeared to be associated with reduced risk of incident stroke, incident CHD and CHD death, whereas low LDL-C (<70 mg/dL) was not associated with protective effects. Thus, our results support other data with respect to the importance of inflammatory processes in the pathogenesis of CVD