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Atherosclerosis has a long preclinical phase, and the risk of cardiovascular (CV) events may be high in asymptomatic subjects. Conventional risk factors provide information for the statistical probability of developing CV events, but they lack precision in asymptomatic subjects. This review aims to summarize the role of some widely publicized indicators of early atherosclerosis in predicting CV events. The earliest measurable indicator of the atherosclerotic process is endothelial dysfunction, measured by flow-mediated dilation (FMD) of the brachial artery. However, reduced FMD is a stronger predictor of future CV events in patients with existing CV disease than in apparently healthy persons. Alternatively, measurement of carotid artery intima-media thickness does not improve the predictive value of risk factor scores, while detection of asymptomatic atherosclerotic plaques in carotid or common femoral arteries by ultrasound indicates high CV risk. Coronary calcium is a robust and validated help in the estimation of vascular changes and risk, which may improve risk stratification beyond traditional risk factors with relatively low radiation exposure. Arterial stiffness of the aorta, measured as the carotid-femoral pulse wave velocity is an independent marker of CV risk at the population level, but it is not recommended as a routine procedure because of measurement difficulties. Low ankle-brachial index (ABI) indicates flow-limiting atherosclerosis in the lower limbs and indicates high CV risk, while normal ABI does not rule out advanced asymptomatic atherosclerosis. Novel circulating biomarkers are associated with the atherosclerotic process. However, because of limited specificity, their ability to improve risk classification at present remains low., (Copyright © 2022. Published by Elsevier B.V.)

Background and Aims: Statins are the drugs of choice for decreasing elevated low-density lipoprotein cholesterol. Based mostly on animal studies and case reports, they are forbidden to pregnant women and in the preconception period because of their possible teratogenic effects, for which causality has never been proven. The aim of this study was to systematically review the existing studies and to perform a meta-analysis on this topic., Methods: The databases PubMed/MEDLINE, Scopus, and Web of Science were searched since the inception until May 16, 2020. The risk of bias for each clinical trial was evaluated using the Cochrane handbook criteria for systematic reviews. The National Institutes of Health (NIH) quality assessment tool was used for the evaluation of cohort and cross-sectional studies. Meta-analysis was performed on the extracted data. Heterogeneity was assessed using I 2 measure and Cochrane's Q statistic. We calculated a pooled estimate of odds ratio (OR) and 95% confidence intervals (CI) using a random-effects model., Results: 23 studies (nine cohort studies, six case reports, six case series, one population-based case-referent study and one clinical trial) with 1,276,973 participants were included in the systematic review and 6 of them (n = 1,267,240 participants) were included in meta-analysis. The results of the critical review did not suggest a clear-cut answer to the question whether statin treatment during pregnancy is associated with an increased rate of birth defects or not, while the results of the meta-analysis indicated that statin use does not increase birth defects [OR (95%CI): 1.48 (0.90, 2.42), p = 0.509], including cardiac anomalies [2.53 (0.81, 7.93), p = 0.112] and other congenital anomalies [1.19 (0.70, 2.03), p = 0.509)]., Conclusions: We observed no significant increase of birth defects after statin therapy. Thus, there is still no undoubtful evidence that statin treatment during pregnancy is teratogenic, and this issue still needs to be investigated, especially there are more and more pregnant women at high CVD risk that could have benefited from the statin therapy., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Aims: Management of familial hypercholesterolaemia (FH) may vary across different settings due to factors related to population characteristics, practice, resources and/or policies. We conducted a survey among the worldwide network of EAS FHSC Lead Investigators to provide an overview of FH status in different countries., Methods: Lead Investigators from countries formally involved in the EAS FHSC by mid-May 2018 were invited to provide a brief report on FH status in their countries, including available information, programmes, initiatives, and management., Results: 63 countries provided reports. Data on FH prevalence are lacking in most countries. Where available, data tend to align with recent estimates, suggesting a higher frequency than that traditionally considered. Low rates of FH detection are reported across all regions. National registries and education programmes to improve FH awareness/knowledge are a recognised priority, but funding is often lacking. In most countries, diagnosis primarily relies on the Dutch Lipid Clinics Network criteria. Although available in many countries, genetic testing is not widely implemented (frequent cost issues). There are only a few national official government programmes for FH. Under-treatment is an issue. FH therapy is not universally reimbursed. PCSK9-inhibitors are available in ∼2/3 countries. Lipoprotein-apheresis is offered in ∼60% countries, although access is limited., Conclusions: FH is a recognised public health concern. Management varies widely across countries, with overall suboptimal identification and under-treatment. Efforts and initiatives to improve FH knowledge and management are underway, including development of national registries, but support, particularly from health authorities, and better funding are greatly needed., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Familial chylomicronaemia syndrome (FCS) is a rare, inherited disorder characterised by impaired clearance of triglyceride (TG)-rich lipoproteins from plasma, leading to severe hypertriglyceridaemia (HTG) and a markedly increased risk of acute pancreatitis. It is due to the lack of lipoprotein lipase (LPL) function, resulting from recessive loss of function mutations in the genes coding LPL or its modulators. A large overlap in the phenotype between FCS and multifactorial chylomicronaemia syndrome (MCS) contributes to the inconsistency in how patients are diagnosed and managed worldwide, whereas the incidence of acute hypertriglyceridaemic pancreatitis is more frequent in FCS. A panel of European experts provided guidance on the diagnostic strategy surrounding FCS and proposed an algorithm-based diagnosis tool for identification of these patients, which can be readily translated into practice. Features included in this FCS score comprise: severe elevation of plasma TGs (fasting TG levels >10 mmol/L [885 mg/dL] on multiple occasions), refractory to standard TG-lowering therapies, a young age at onset, the lack of secondary factors (except for pregnancy and oral oestrogens) and a history of episodes of acute pancreatitis. Considering 53 FCS patients from three cohorts and 52 MCS patients from three cohorts, the overall sensitivity of the FCS score (≥10) was 88% (95% confidence interval [CI]: 0.76, 0.97) with an overall specificity of 85% (95% CI: 0.75, 0.94). Receiver operating characteristic curve area was 0.91. Pragmatic clinical scoring, by standardising diagnosis, may help differentiate FCS from MCS, may alleviate the need for systematic genotyping in patients with severe HTG and may help identify high-priority candidates for genotyping., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Familial hypercholesterolaemia (FH) is a hereditary disorder predisposing to premature coronary heart disease (CHD) and is until now mainly diagnosed clinically on the basis of a classical phenotype. Its prevalence varies and is estimated around 1 in 200-500; in patients with established CHD the prevalence is less well documented., Methods and Results: In EUROASPIRE IV data were collected in coronary patients from 24 European countries by means of a standardized interview, bioclinical examination and venous blood sampling. Potential FH was estimated using an adapted version of the Dutch Lipid Clinic Network Criteria. Among the 7044 patients eligible for analysis, the prevalence of potential FH was 8.3%; 7.5% in men and 11.1% in women. The prevalence was inversely related to age with a putative prevalence of 1:5 in those with CHD <50 yrs of age in both sexes. Even among women aged 70 the prevalence was 1:10. Irrespective of age and gender, prevalence differed substantially between European regions; potential FH patients were more likely to smoke, had higher triglycerides levels and their blood pressure was less well controlled. The use of cardioprotective drugs and the prevalences of diabetes, obesity and central obesity were similar., Conclusions: The prevalence of potential FH in coronary patients is high; the results underscore the need to promote identification of FH in CHD patients and to improve their risk factor profile., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Lysosomal acid lipase deficiency (LAL-D) is a rare autosomal recessive lysosomal storage disease caused by deleterious mutations in the LIPA gene. The age at onset and rate of progression vary greatly and this may relate to the nature of the underlying mutations. Patients presenting in infancy have the most rapidly progressive disease, developing signs and symptoms in the first weeks of life and rarely surviving beyond 6 months of age. Children and adults typically present with some combination of dyslipidaemia, hepatomegaly, elevated transaminases, and microvesicular hepatosteatosis on biopsy. Liver damage with progression to fibrosis, cirrhosis and liver failure occurs in a large proportion of patients. Elevated low-density lipoprotein cholesterol levels and decreased high-density lipoprotein cholesterol levels are common features, and cardiovascular disease may manifest as early as childhood. Given that these clinical manifestations are shared with other cardiovascular, liver and metabolic diseases, it is not surprising that LAL-D is under-recognized in clinical practice. This article provides practical guidance to lipidologists, endocrinologists, cardiologists and hepatologists on how to recognize individuals with this life-limiting disease. A diagnostic algorithm is proposed with a view to achieving definitive diagnosis using a recently developed blood test for lysosomal acid lipase. Finally, current management options are reviewed in light of the ongoing development of enzyme replacement therapy with sebelipase alfa (Synageva BioPharma Corp., Lexington, MA, USA), a recombinant human lysosomal acid lipase enzyme., (Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Objective: Dyslipidaemia is among the most important risk factors for coronary heart disease (CHD). The lowering of LDL-cholesterol (LDL-C) yields significant reduction in both morbidity and mortality rates, particularly in patients with established CHD. The aim of this survey was to assess how dyslipidaemia is managed following a coronary event in different places in Europe., Methods: CHD patients' data from centres in 22 European countries were gathered using standardised methods. In total, 8467 CHD patients with lipid measurements in one central laboratory were included. Trends from 8 countries participating in all three EUROASPIRE surveys (1994-1995, 1999-2000, 2006-2007) were also investigated., Results: 51.1% of CHD patients had elevated total cholesterol (≥4.5 mmol/L), 54.5% had raised LDL-C (≥2.5 mmol/L), 36.7% had low HDL-C (<1.0 mmol/L for men and <1.2 mmol/L for women), and 34.7% had increased triglycerides (≥1.7 mmol/L). The use of lipid lowering drugs was 79.8% but it varied considerably, ranging from only 41.6% (Lithuania) to 95.4% (Finland). Over the past decade, in 8 countries the prevalence of hypercholesterolaemia (≥4.5 mmol/L) in CHD patients has decreased from 94.5% in the first to 76.7% in the second and 46.2% in the third survey (p < 0.0001). The use of lipid-lowering drugs increased from 32.3% in the first, to 62.7% in the second and 88.8% in the third survey (p < 0.0001)., Conclusions: Although management of dyslipidaemia in CHD patients is improving, a large majority of CHD patients with dyslipidaemia is still inadequately treated and many patients on lipid-lowering therapy are not reaching the treatment goals. Therefore, a considerable potential still exists throughout Europe to reduce CHD mortality and morbidity rates through better treatment of dyslipidaemia., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)