Search

Since heterozygous familial hypercholesterolemia (HeFH) is a disease that exposes the individual from birth onwards to severe hypercholesterolemia with the development of early cardiovascular disease, a clear consensus on the management of this disease in young patients is necessary. In Belgium, a panel of paediatricians, specialists in (adult) lipid management, general practitioners and representatives of the FH patient organization agreed on the following common recommendations.1.Screening for HeFH should be performed only in children older than 2 years when HeFH has been identified or is suspected (based on a genetic test or clinical criteria) in one parent.2.The diagnostic procedure includes, as a first step, the establishment of a clear diagnosis of HeFH in one of the parents. If this precondition is satisfied, a low-density-lipoprotein cholesterol (LDL-C) level above 3.5mmol/L (135mg/dL) in the suspected child is predictive for differentiating affected from non-affected children.3.A low saturated fat and low cholesterol diet should be started after 2 years, under the supervision of a dietician or nutritionist.4.The pharmacological treatment, using statins as first line drugs, should usually be started after 10 years if LDL-C levels remain above 5mmol/L (190mg/dL), or above 4mmol/L (160mg/dL) in the presence of a causative mutation, a family history of early cardiovascular disease or severe risk factors. The objective is to reduce LDL-C by at least 30% between 10 and 14 years and, thereafter, to reach LDL-C levels of less than 3.4mmol/L (130mg/dL).Conclusion: The aim of this consensus statement is to achieve more consistent management in the identification and treatment of children with HeFH in Belgium. © 2011 Elsevier Ireland Ltd.

Statins are the cornerstone for lowering low-density lipoprotein cholesterol (LDL-C) for cardiovascular disease (CVD) prevention. Moreover, as reported recently, the benefits of statin therapy extend similarly to men and women [1]. While statins are safe and well tolerated, like all treatments, a proportion of patients report side effects. Muscle symptoms are the most prevalent side effects reported with statin therapy, and one of the main reasons for non-adherence or discontinuation of treatment. While it is recognised that statins do cause a rare side effect known as myositis, defined as muscle symptoms in association with a substantially elevated serum creatine kinase [CK] concentration, most statin-associated muscle symptoms (SAMS) are not accompanied by marked CK elevation.

While risk scores are invaluable tools for adapted preventive strategies, a significant gap exists between predicted and actual event rates. Additional tools to further stratify the risk of patients at an individual level are biomarkers. A surrogate endpoint is a biomarker that is intended as a substitute for a clinical endpoint. In order to be considered as a surrogate endpoint of cardiovascular events, a biomarker should satisfy several criteria, such as proof of concept, prospective validation, incremental value, clinical utility, clinical outcomes, cost-effectiveness, ease of use, methodological consensus, and reference values. We scrutinized the role of peripheral (i.e. not related to coronary circulation) noninvasive vascular biomarkers for primary and secondary cardiovascular disease prevention. Most of the biomarkers examined fit within the concept of early vascular aging. Biomarkers that fulfill most of the criteria and, therefore, are close to being considered a clinical surrogate endpoint are carotid ultrasonography, ankle-brachial index and carotid-femoral pulse wave velocity; biomarkers that fulfill some, but not all of the criteria are brachial ankle pulse wave velocity, central haemodynamics/wave reflections and C-reactive protein; biomarkers that do no not at present fulfill essential criteria are flow-mediated dilation, endothelial peripheral arterial tonometry, oxidized LDL and dysfunctional HDL. Nevertheless, it is still unclear whether a specific vascular biomarker is overly superior. A prospective study in which all vascular biomarkers are measured is still lacking. In selected cases, the combined assessment of more than one biomarker may be required.

Various local criteria of the abdominal aortic aneurysm (AAA) damage are used in the literature though their experimental validation is needed. The results of numerical flow simulation in AAAs show that the wall pressure, which is of vital importance for the risk of rupture, depends on several factors, one being the location of the intraluminal thrombus (ILT). The inclusion of ILT features in stress analysis of AAA is of importance and would likely increase the accuracy of predicting risk of AAA rupture. The ambiguous role of ILT needs to be clarified, since on one hand it contributes to the reduction of stress values forces, acting as mechanical buffer, but on the other hand it has been associated with higher AAA growth rates due to generation of elastolytic enzymes, leading to wall degradation and thus predisposing to weakening of the AAA wall. Folkesson et al., in their interesting paper, showed that thick ILTs with multiple layers contain substantial amounts of proteases, but their activity is limited to the luminal layer. Proteases in the abluminal layer are mostly inactive and are consequently unable to directly participate in the pathogenesis of AAA. These findings correspond to several laboratory studies on material from the wall of human aneurysms suggesting various associations with AAA diameter and rupture. One of the studies suggested that acid-base imbalance in aneurysmal tissue could be one of the possible mechanisms of local wall destruction and its rupture [1]. An early return of reflected waves and the backward propagation of the arterial pressure wave from the aortic bifurcation to

The EAS has already highlighted the underdiagnosis and undertreatment of familial hypercholesterolaemia (FH) in the 2013 EAS Consensus Panel Position Paper [1]. This paper has driven numerous initiatives, including FH-Connect [2], under the umbrella of the International Atherosclerosis Society. However, to make policymakers aware of issues in FH care, as a precursor to initiating change, it is essential to obtain information on the contemporary burden of FH. In response, the EAS launched the FH Studies Collaboration (FHSC) [http://www.eas-society.org/fhsc.aspx], an international registry of observational studies on FH. According to EAS President Professor Alberico L. Catapano, University of Milan, Italy: ‘The FH Studies collaboration shows that the Society has the capability to rise to the challenge posed by the unmet clinical needs of this common genetic condition.’ The FHSC aims to provide information on how patients are currently screened and managed, what are the barriers to effective treatment, as well as the impact of patient-specific, genetic, and societal factors on treatment efficacy. The FHSC is led by Professor Kausik Ray, Imperial College, London UK; to date more than 30 countries have already agreed to take part. A substudy of the FHSC will focus on homozygous autosomal dominant hypercholesterolaemia (hoADH), to evaluate the true prevalence and phenotypic and genetic characterisation of this severe form of FH. This substudy (HoADH International Clinical Collaboration, HICC), is jointly led by Professor Derick Raal, University of the

15 p.-6 fig., Mitophagy is a critical cellular process that selectively targets damaged mitochondria for autophagosomal degradation both under baseline conditions and in response to stress preventing oxidative damage and cell death. Recent studies have linked alterations in mitochondria function and reduced autophagy with the development of age-related pathologies. However, the significance of mitochondrial autophagy in vessel wall in response to atherogenic lipid stressors is not known. In the present study, we investigated the role of mitophagy on human vascular smooth muscle cells (VSMC) apoptosis induced by oxidized low-density lipoproteins (LDL). We reported for the first time that the engulfment of defective mitochondria by autophagosomes occurred in human VSMC in response to oxidized LDL. The molecular mechanism mediating mitophagy in human VSMC involved dynamin-related protein 1 (Drp1)-mediated mitochondrial fission, accumulation of PTEN-induced putative kinase 1 (PINK1) and the recruitment of the E3 ubiquitin ligase Parkin to mitochondria. Likewise, we found increased voltage-dependent anion channel 1 (VDAC1) and mitofusin 2 (Mnf2) mitochondrial proteins ubiquitination and LC3 association to mitochondria. Using flow cytometry in the presence of lysosomal inhibitors, we showed that PINK1 and Parkin silencing impaired mitophagy flux and enhanced oxidized LDL-induced VSMC apoptosis. In addition, overexpression of PINK1 and Parkin were protective by limiting cell death. Moreover, reduced Bax levels found in VSMC-overexpressing Parkin indicated cross talk among mitophagy and mitochondrial apoptotic signalling pathways. Altogether these data demonstrate that mitophagy is a safeguard mechanism against human VSMC apoptosis induced by atherogenic stressors and highlight mitophagy as a potential target to stabilize atherosclerotic plaque., This work was supported by grants from l’Institut National de la Santé et de la Recherche Médicale (INSERM) and Fondation de France [2013-38581 to C.V] and FU2015-64623-R to PB.

The value of cellulose acetate electrophoresis for the determination of human lipoprotein patterns was studied over a 3 year period in 1,283 patients. Comparative studies were done using other electrophoretic media such as paper and polyacrylamide gel. Factors affecting chylomicron migration were also studied. Chylomicron migration from the origin to the pre-beta zone of the cellulose acetate strip is a major problem and can lead to errors in the diagnosis of hyperlipoproteinemia.

The nature of lipoprotein and elastin associated with hyaluronate in human atherosclerotic plaque tissue was studied by digesting the tissues with elastase. The elastase-solubilized lipoprotein-hyaluronate complexes, isolated by Bio-Gel A-50m column chromatography, contained 7.8 mg calcium/100 mg protein. The Sephadex G-200 chromatography of delipidated complexes yielded high (fraction I) and low (fraction II) molecular weight protein fractions. Dialysis of the complexes against 0.01% EDTA resulted in removal of fraction II. Fraction I reacted immunologically against antihuman LDL, and its amino acid composition resembled that of human apoB. Fraction II contained 5 peptide fragment and had high levels of nonpolar amino acids that are characteristic of elastin. However, these peptides also contained high levels of polar amino acids, thus resembling the plaque elastin. These findings suggest that certain regions of plaque elastin may have affinity for apoB containing lipoproteins and calcium.

1. (1) Acidic glycosaminoglycans (AGAG) were prepared from the inner and outer layers of human aorta and fractionated by Dowex 1-X2 columns. The anticoagulant activity of the fractionated AGAG was measured by the partial thromboplastin time. 2. (2) Heparan sulfates were the main AGAG in the 1.25 M NaCl fraction and were more abundant in the outer layer than in the inner. Likewise, there was more dermatan sulfate in the outer layer. 3. (3) The AGAG in the outer layer showed much greater anticoagulant activity than those in the inner layer, both in the 1.25 M and 1.75 M NaCl fractions. 4. (4) Anticoagulant activity was attributed to the heparan sulfates in the 1.25 M fraction and to the dermatan sulfate in the 1.75 M fraction.

A steam-distilled and an ether extract of onion have both been found to enhance blood fibrinolysis without depressing fibrinogen content in groups of human volunteers. Chemical analysis has shown which sulphur-containing compounds were in highest concentration and common to both and thus likely to carry this property, but their very intense and prolonged flavour precludes their clinical use. One sulphur containing but nearly odourless compound has been identified as having indirect fibrinolytic potential. A species difference in respect of fibrinolysis has been found between English and Spanish onion but is of little importance.

From the 4th to the 7th decades of life, the period in which cerebral atherosclerosis increases in frequency and severity, the macromolecules and macromolecular complexes of the intimal connective tissue of the lesion-free specimens of cerebral arteries undergo spontaneous modifications, reflected by changes in: chemical components, reactive groups, electrical charge, susceptibility to enzymatic digestions and chemical extractions. These age-related changes determine: (i) the differentiation in the newly formed intimal connective tissue of two sublayers, displaying a distinct pattern of macromolecular composition, organization and aggregation; (ii) the increase, in the outer intimal sublayer, of various cross-links between carbohydrates, non-collagen proteins, elastin and collagen macromolecules, resulting in an abnormal state of aggregation which prevents enzyme-substrate interactions, in vitro , on tissue sections; (iii) the transformation of some limited areas of the inner intimal sublayer into a loose-mucoid and edematous tissue process which seems to be preceded by a spontaneous and progressive dissolution of some constituents of the ground substance, reticular, elastic and collagen fibers; (iv) the diminution of the histochemical reactivity of the sulfate groups, due to a progressive blockade of these radicals by basic proteins.

Rats were injected via cardiac puncture with an equivalent radiolabeled amount of 35 SO 4 =(Group I), l -ascorbic acid (20 mg) plus 35 SO 4 =(Group II), and 35 S- l -ascorbic acid 2-sulfate (20 mg) (Group III) in order to investigate the relationship between these compounds and 35 S-cholesterol sulfate excretion. Urine and feces were analyzed periodically. Blood and adrenal glands were analyzed at the termination of the experiment (45–48 h). Total 35 S-activity, 35 S-cholesterol sulfate, 35 S-inorganic sulfate and 35 S-organic sulfate were quantified. The 35 S-cholesterol sulfate was found primarily in the feces in the following yield based upon the injected 35 S-dose: I, 0.15 %; II, 0.3%; III, 7.1 %. Both l -ascorbic acid and l -ascorbic acid 2-sulfate elevated the radiochemically labeled cholesterol sulfate excreted (2 × and 50 ×, respectively). These data prove the existence of a 35 S-sulfate transfer from 35 S-ascorbic acid 2-sulfate to cholesterol resulting in the formation of 35 S-cholesterol sulfate, whether direct or indirect, and may in part explain the reported, but controversial, hypocholesterolemic effects of l -ascorbic acid.

Elevated levels of plasma lipoprotein (a) [Lp(a)] have been considered as a strong risk factor for premature cardiovascular diseases. Plasminogen activator inhibitor-1 (PAI-1) is the major physiological inhibitor of plasminogen activators (PA). Increases in PAI-1 levels with or without a reduction in PA levels have been frequently found in coronary artery disease patients. The present paper examined the effects of oxidized Lp(a) on the production of PAI-1 in cultured human umbilical vein endothelial cells (HUVEC). Lp(a) and Lp(a)-free, low density lipoprotein (LDL) were prepared using lysine-Sepharose 4B affinity chromatography. Incubations with 10 −8 M levels of native Lp(a) moderately increased the levels of biologically active PAI-1 in post-culture medium of HUVEC compared to that with equimolar concentrations of native Lp(a)-free LDL. The release of PAI-1 induced by Lp(a) was enhanced by oxidative modification with copper ion. The stimulation of oxidized Lp(a) on PAI-1 production reached plateau in EC treated with 10–20 nM oxidized Lp(a) modified by 5 μ M CuSO 4 . Treatment with 0.2 μ g/ml of actinomycin D significantly reduced native and oxidized Lp(a)-induced PAI-1 overproduction in EC. Increases in the steady state levels of PAI-1 mRNA were detected in native or oxidized Lp(a)-treated EC. The effect of Lp(a)-free oxidized LDL on PAI-1 production was significantly weaker than the equimolar amount of oxidized Lp(a) but stronger than that of native LDL. Treatments with oxidized Lp(a) increased cell-associated PAI-1 to a similar extent as that in native Lp(a)-treated EC. The results of the present paper demonstrate that oxidative modification enhances Lp(a)-induced PAI-1 production in vascular endothelial cells at RNA transcription level, which suggests that oxidization potentially amplifies the anti-fibrinolytic and thrombotic effect of Lp(a).

Atherosclerosis is an inflammatory disease that can lead to several complications such as ischemic heart disease, stroke, and peripheral vascular disease. Therefore, researchers and clinicians rely heavily on the use of imaging modalities to identify, and more recently, quantify the burden of atherosclerosis in the aorta, carotid arteries, coronary arteries, and peripheral vasculature. These imaging techniques vary in invasiveness, cost, resolution, radiation exposure, and presence of artifacts. Consequently, a detailed understanding of the risks and benefits of each technique is crucial prior to their introduction into routine cardiovascular screening. Additionally, recent research in the field of microvascular imaging has proven to be important in the field of atherosclerosis. Using techniques such as contrast-enhanced ultrasound and superb microvascular imaging, researchers have been able to detect blood vessels within a plaque lesion that may contribute to vulnerability and rupture. This paper will review the strengths and weaknesses of the various imaging techniques used to measure atherosclerotic burden. Furthermore, it will discuss the future of advanced imaging modalities as potential biomarkers for atherosclerosis.

Background and aims Genetic identification is a public health care concern for management of familial hypercholesterolemia (FH) associated cardiovascular morbidity and mortality. This study presents the spectrum and distribution of LDLR, APOB, PCSK9 gene mutations in Asia. Methods Databases were searched for English papers from 1950 to 2019. The spectrum of the variants was investigated in 8994 FH families in 48 Asian countries. We determined the frequency of variants, zygosity, and clinical features. Results Twenty countries have studied LDLR variants. A total of 629 mutations were reported and twenty variants were accounted as common variants in different populations. China, Japan, India and Taiwan constituted 68% of published articles. The most frequent mutation was reported in Japan but was not common in other countries. Other missense variants accounted for 50% of the mutations, frameshifts 19%, and nonsense 11%. The pooled frequency of variation was estimated in 1867 individuals. Approximately 67% of Iranian families were homozygous.,The common variant was p.Ser130Ter. p.Arg3527Trp in APOB was common among 184 heterozygous patients; the common variant of PCSK9 was p.Glu32Lys. Conclusions This is the first systematic review of LDLR, APOB, PCSK9 mutations in FH patients in Asia. These findings underscore the need to fill in the gap of studies on different populations in Asia. It also underlies the importance of early detection and management to decrease atherosclerosis and cardiovascular risk in different ethnicities.

Two papers in this issue of Atherosclerosis explore different aspects of the role of leptin in cardiovascular disease, and here we review each paper in turn. Leptin plays a key role in the regulation of body weight and inflammatory responses, and its role in atherosclerosis has been described in several studies [1,2]. Elevated plasma concentrations of leptin are independently associated with the intima-media thickness of the common carotid artery, and with the degree of coronary artery calcification in patients with type 2 diabetes mellitus, after controlling for adiposity and CRP. Hyperleptinemia is also involved in the increased risk of post-angioplasty restenosis. Obesity and the co-existing metabolic syndrome eventually lead to leptin resistance with attenuation of leptin signalling at a cellular level. The development and mechanism of leptin resistance however is still poorly understood, and it is likely that it encompasses different events that are distinct in underlying mechanisms and pathophysiological implications. As to how leptin resistance develops in the vascular system and whether it is a cause or an effect of atheroma formation is still unclear. A key early event in atherosclerosis is endothelial dysfunction. Caveolin-1 is a structural protein of caveolae, which plays an important regulatory role in cell signalling, development of atherosclerosis and obesity. Caveolin levels are increased with obesity and caveolin deficiency results in a lean phenotype [3,4]. However, the interaction between leptin and caveolin has not been studied so far. In the current issue of Atherosclerosis Singh et al. [5] describe a novel feed-back loop of caveolin-1-mediated down regulation of leptin signalling. The important and novel findings reported are that leptin induces caveolin-1 protein expression, and in addition, increased caveolin-1 expression impairs leptin signalling. As caveolin-1 is pro-atherogenic, leptin may cause a direct atherogenic effect, while increased caveolin-1 expression may contribute to the development of endothelial leptin resistance and eventually, atherosclerosis. In vivo studies are necessary to confirm the relevance of these findings and also to elucidate the time course of the events establishing the cause and effect relationship between leptin, caveolin-1 upregulation and leptin resistance. Also, the mechanisms leading to these effects need to be delineated. Leptin levels increase with obesity. Despite being discovered more than a decade ago, human studies investigating the relationship of leptin to coronary artery disease are still conflicting. Thus, this relationship needs to be investigated in large prospective studies. In this issue of Atherosclerosis Ku et al. [6] report the results of such an analysis, in The Heart and Soul Study, a prospective cohort study investigating the effect of psychosocial factors on prognosis in 981 patients with chronic stable CAD. The authors report that low baseline leptin levels predicted subsequent CV events and death. Although subjects with low leptin had fewer co-morbidities and more favorable metabolic and inflammatory profiles, they had a worse prognosis than subjects with high leptin. Furthermore, BMI modified the effect of leptin on mortality, and lower leptin predicted mortality in patients with normal BMI but not in patients with high BMI. Again, these effects may be explained by increased leptin resistance in obesity. Leptin has been shown to have both protective as well as atherogenic effects, depending on the dose of leptin used in the different studies. Unfortunately, in this paper, no functional effects of leptin were studied, thus understanding the mechanistic effects of leptin in the cardiovascular system may provide insights into the relationship between obesity and heart disease. Also, most patients in this study were men and had coronary artery disease, so whether these effects apply to the general population, who do not have heart disease, is unclear and this still needs to be delineated. Overall these studies give interesting insights into the multiple roles this novel hormone is having in influencing human health and disease, but many areas remain to be explored to elucidate in detail the mechanisms involved.

The authors regret that an error occurred in this paper, by publishing a figure which compromises patient anonimity by showing name, ender, and date of birth. Even though they had permission from the patient to do so, this information was not a necessary addition to he paper, and contravenes the Journals Guidelines to Authors. The authors would like to apologize for any inconvenience this may have aused to the patient, authors of this article and readers of the journal.

Background and aims The new coronavirus disease (Covid-19) is a systemic disease. Mounting evidence depict signs and symptoms involving multiple organs, most of which supported by pathological data. A plausible link to these manifestations is vascular and endothelial dysfunction/damage. However, much of the current knowledge relies on opinion and incipient evidence. We aim to objectively appraise current evidence on the association between Covid-19 and vascular disease, specifically endotheliitis and vasculitis. Methods Two researchers independently entered the search terms Covid-19 OR SARS-CoV-2 AND vasculitis, endotheliitis OR endothelium in the following online platforms: MedRxiv and LitCovid (PubMed). The search period was set from November 1, 2019 to August 28, 2020. Manuscripts with unavailable full texts, not in English, mainly on pre-clinical data, presenting only study designs or not directly related to the topics of this review were excluded. Retrospective and prospective studies, especially longitudinal ones, were given priority to the purpose of this review. Since there was paucity of prospective controlled evidence, case reports/series were also considered. Results A total of 318 manuscripts were initially found. Sixty-seven (21%) were excluded: 59 (18.5%) met exclusion criteria and 8 (2.5%) were duplicates. One hundred and forty-two manuscripts (44,6%) did not provide original data and were also excluded: 35 (11%) were comments, 108 (33.9%) reviews; 1 (0.3%) position paper. One hundred and seven (33.6%) studies were considered for the present scoping review: 81 (25,5%) case reports/series; 18 (5.7%) prospective; 8 (2.5%) retrospective. Viral inclusions in endothelial cells, mononuclear cell infiltrates in the intima of small vessels and markers of endothelial cell apoptosis were demonstrated. Specificities of Covid-19 may lead to diverse vascular manifestations in different levels of the vascular bed. Conclusions Evidence indicates that Covid-19 targets vasculature and endothelium. However, high quality data is still lacking and studies with prospective designs and appropriately matched controls are needed., Graphical abstract Mechanisms of SARS-CoV-2-related vasculitis/endotheliitis. Covid-19 may affect the endothelium and smooth muscle cells of the arterial and venous wall at different levels and through multiple ways, namely: inflammation/immune response, hypercoagulability and increased vascular reactivity. ACE-2: angiotensin-converting enzyme 2; Angpt: angiopoietin; CEC: circulating endothelial cells; CRP: C-reactive protein; DIC: disseminated intravascular coagulopathy; IFN-1: interferon type 1; IL: interleukin; MCP-1: monocyte chemotactic protein-1; NETs: neutrophil extracellular traps; NO: nitric oxide; sVCAM-1: soluble vascular cell adhesion molecule-1; sVCAM-1: soluble vascular cell adhesion molecule-1; TMA: thrombotic microangiopathy; TNF- α: tumor necrosis factor – α; VAP-1: vascular adhesion protein-1.Image 1

Background and aims: The lysosomal cysteine proteases cathepsin B and S have been implicated in the atherosclerotic process. The present paper investigates the association between serum levels of cathepsin B and S and cardiovascular events and mortality in patients with stable coronary heart disease. Methods: The CLARICOR trial is a randomised, placebo-controlled trial investigating the effect of clarithromycin versus placebo in patients with stable coronary heart disease. The outcome was time to either a cardiovascular event or all-cause mortality. The placebo group was used as discovery sample and the clarithromycin group as replication sample: n = 1998, n = 1979; mean age (years) 65, 65; 31%, 30% women; follow-up for 10 years; number of composite outcomes n = 1204, n = 1220; respectively. We used a pre-defined multivariable Cox regression model adjusting for inflammation, established cardiovascular risk factors, kidney function, and use of cardiovascular drugs. Results: Cathepsin B was associated with an increased risk of the composite outcome in both samples after multivariable adjustment (discovery: multivariable ratio (HR) per standard deviation increase 1.12, 95% confidence interval (CI) 1.05–1.19, p < 0.001, replication; HR 1.14, 95% CI 1.07–1.21, p < 0.001). There was no significant association between cathepsin S and the composite outcome in either the discovery or replication sample after multivariable adjustment (p>0.45). Secondary analyses suggest that cathepsin B was predominantly associated with mortality rather than specific cardiovascular events. Conclusions: Cathepsin B, but not serum cathepsin S, was associated with an increased risk of cardiovascular events in patients with stable coronary heart disease. The clinical implications of our findings remain to be established.

Background and aims The relationship between serum uric acid (UA) and the risk of intracerebral hemorrhage (ICH) remains controversial. The aim of our systematic review and meta-analysis was to ascertain the association between serum UA concentrations and the risk of ICH. Methods We systematically searched databases of Embase, Pubmed, Web of Science and Cochrane Library up to December 30, 2017, and additional papers were identified through a manual search. Mean difference (MD) for serum UA levels with 95% confidence intervals (CI) was calculated. Six studies, including 345 ICH patients, 574 ischemic stroke patients and 535 healthy controls, were identified for meta-analysis. Results Our results revealed no statistically significant differences in the comparison of UA between ICH and healthy controls (95% CI = −9.04-15.61); UA levels in patients with ischemic stroke were significantly higher than those in healthy controls (95% CI = 3.91–56.32); further subgroup analysis of age showed higher UA levels in ICH patients over 65 years than healthy controls (age≥65: 95% CI = 1.44–35.96). Subgroup of ethnicity (Asians: CI = −9.06-21.00; Caucasians: 95% CI = −68.43-8.43), gender (Men: 95% CI = −56.08-4.73; Women: 95% CI = −27.19-35.91) and sample size (large samples: 95% CI = −20.54-41.05; small samples: 95% CI = −25.41-13.78) with respect to UA levels between ICH and healthy controls did not change these results. Conclusions This meta-analysis showed that serum UA levels did not increase the risk of ICH probably because of the dual roles of UA, i.e. pro-oxidant and antioxidant, in the progression of atherosclerosis. However, serum UA may be a potential risk factor for ICH in the elderly. There were no race-specific differences in UA levels between Asians and Caucasians as well as gender-related differences between men and women in the risk of ICH.

Background and aims Despite worldwide reductions in active smoking, non-smokers continue to be exposed to environmental tobacco smoke, especially at home or workplace. There is a well-recognised association between active smoking and peripheral arterial disease, however, a relationship to environmental tobacco smoke exposure is less substantiated. The aims of this paper are to review the literature regarding the association between environmental tobacco smoke and peripheral arterial disease and identify the public health implications of the findings. Methods Selected electronic databases (Medline, EMBASE, CINAHL, PsychINFO and Scopus) were searched for studies published up to August 2017. Key words and inclusion/exclusion criteria applied. A manual search of reference lists of studies selected for review was also performed. Results Of the initial 150 studies identified, 12 met inclusion criteria for review. Three studies showed a positive association between environmental tobacco smoke exposure and definitive diagnosis of peripheral arterial disease, 6 studies demonstrated a positive association with features of vascular injury, and 3 studies found no significant positive or negative association. Conclusions An association between exposure to environmental tobacco smoke and development of peripheral arterial disease or clinically significant arterial injury in non-smokers is supported by moderate quality evidence in the literature. Larger, longitudinal observational studies addressing current limitations, including sources of bias, inconsistency and imprecision, are needed to provide more robust and consistent evidence. Regardless, evidence of potential detrimental impacts supports ongoing restrictions on freedom to smoke in public areas, including the workplace, and has implications for those exposed in the home environment.

Background Despite the greater prevalence of familial hypercholesterolemia (FH) in subjects with ischemic heart disease (IHD), premature IHD, and severe hypercholesterolemia (low-density lipoprotein ≥190 mg/dl), overall prevalence estimates are not available. Objectives The aim of this study was to provide worldwide estimates of FH prevalence in subjects with IHD, premature IHD, and severe hypercholesterolemia compared with those in the general population. Methods In this systematic review and meta-analyses, Embase, PubMed, and the Web of Science were searched until June 3, 2019, for peer-reviewed papers and conference abstracts reporting heterozygous FH prevalence in nonfounder populations, revealing 104 studies eligible for inclusion. Results Estimates of FH prevalence were pooled using random-effects meta-analyses and were 0.32% (95% confidence interval [CI]: 0.26% to 0.39% [corresponding to 1:313]) among 10,921,310 unique subjects in the general population (33,036 patients with FH) on the basis of 44 studies, 3.2% (95% CI: 2.2% to 4.3% [1:31]) among 84,479 unique subjects with IHD (2,103 patients with FH) on the basis of 28 studies, 6.7% (95% CI: 4.9% to 8.7% [1:15]) among 31,316 unique subjects with premature IHD (1,471 patients with FH) on the basis of 32 studies, and 7.2% (95% CI: 4.6% to 10.8% [1:14]) among 17,728 unique subjects with severe hypercholesterolemia (920 patients with FH) on the basis of 7 studies. FH prevalence in the general population was similar using genetic versus clinical diagnoses. Seventeen of 195 countries (9%) in the world have reported FH prevalence for the general population, leaving 178 (91%) countries in the world with unknown prevalence. Conclusions Compared with 1:313 among subjects in the general population, FH prevalence is 10-fold higher among those with IHD, 20-fold higher among those with premature IHD, and 23-fold higher among those with severe hypercholesterolemia. The prevalence of FH is unknown in 90% of countries in the world.

Background and aims Chinese dragon's blood has been used to treat blood stasis for thousands of years. Its total phenolic extract (Longxuetongluo capsule, LTC) is used for the treatment of ischemic stroke; however, its protective effect against atherosclerosis remains poorly understood. This paper aims to investigate the antiatherosclerotic effect of LTC and the underlying mechanisms in high-fat diet (HFD)-induced ApoE −/− mice. Methods The levels of plasma lipid and areas of atherosclerotic lesions in the aortic sinus in ApoE −/− mice were evaluated. The effect of LTC on the nitric oxide (NO) production in oxidized low-density lipoprotein (ox-LDL)-stimulated human umbilical vein endothelial cells ( HUVECs ) was determined. The adhesion of monocytes to ox-LDL-stimulated HUVECs was further studied. Results LTC at low, medium, and high doses markedly decreased the atherosclerotic lesion areas of the aortic sinus in HFD-induced ApoE −/− mice by 26.4% ( p p p HUVECs ( p p HUVECs , and inhibit the adhesion of monocytes to HUVECs via the MAPK/IKK/I κ B/NF- κ B signaling pathway, thus decrease atherosclerotic lesions in the aortic sinus in HFD-induced ApoE −/− mice. Conclusions These findings suggest the potential of LTC for use as an effective agent against atherosclerosis.

Microvesicles are formed under many circumstances, especially in atheromatous plaques. Erythrocyte-derived microvesicles (ErMVs) have been proved to promote atherosclerosis by promoting hypercoagulation, mediating inflammation and inducing cell adhesion. Several clinical studies have reported potential roles of ErMVs in cardiovascular disease diagnosis, but the current understanding of ErMVs remains insufficient. In this paper, we will review current research on the formation and degradation of ErMVs and the possible effects of ErMVs in atherosclerosis, discuss potential clinical applications in cardiovascular disease, and hope to raise awareness of the relation with atherosclerosis.

Background and aims The presence of atrial fibrillation (AF) markedly increases the risk of stroke and mortality in patients. Whether AF is a risk factor for myocardial infarction (MI) is discrepant from current studies. The aim of this meta-analysis was to ascertain the association of AF with incident MI. Methods Studies were identified through PubMed, CENTRAL, EMBASE, reviews and reference lists of relevant papers. Results of the MI outcome were presented as hazard ratio (HR) and 95% confidence interval (CI). Statistical analyses were performed with Stata 12.0 (Stata Corp LP, College Station, Texas, USA). Results Twelve studies, with a total of 169,306 patients, were included in the analysis. AF was associated with a 47% increased risk of MI (HR:1.47; 95% CI: 1.21–1.80; p = 0.000; I 2 = 84.1%), while in patients free of coronary heart disease at baseline the risk could be increased by 71% (HR:1.71; 95% CI: 1.36–2.14; p = 0.000; I 2 = 83.1%). Moreover, patients with AF had higher MI risk in the studies with lower mean age ( p = 0.000; I 2 = 82.9%) than in the studies with higher mean age (≥60 years) (HR:1.35; 95% CI: 1.00–1.82; p = 0.000; I 2 = 84.9%). Sex difference also existed, and the association between AF and MI was stronger in women (HR:2.02; 95% CI: 1.60–2.56; p = 0.017; I 2 = 61.0%) than in men (HR:1.44; 95% CI: 1.13–1.84; p = 0.000; I 2 = 76.1%). Conclusions AF is associated with an increased risk of incident MI, especially in patients free of coronary heart disease at baseline, young patients and women. The findings need confirmation in well-designed observational trials.

Objective Lipoprotein (a) [Lp(a)] harbors atherogenic potential but its role as a risk factor for ischemic stroke remains controversial. We conducted a meta-analysis to determine the relative strength of the association between Lp(a) and ischemic stroke and identify potential subgroup-specific risk differences. Methods A systematic search using the MeSH terms "lipoproteins" OR "lipoprotein a" AND "stroke" was performed in PubMed and ScienceDirect for case–control studies from June 2006 and prospective cohort studies from April 2009 until December 20th 2014. Data from eligible papers published before these dates were reviewed and extracted from previous meta-analyses. Studies that assessed the relationship between Lp(a) levels and ischemic stroke and reported generic data—i.e. odds ratio [OR], hazard ratio, or risk ratio [RR]—were eligible for inclusion. Studies that not distinguish between ischemic and hemorrhagic stroke and transient ischemic attack were excluded. Random effects meta-analyses with mixed-effects meta-regression were performed by pooling adjusted OR or RR. Results A total of 20 articles comprising 90,904 subjects and 5029 stroke events were eligible for the meta-analysis. Comparing high with low Lp(a) levels, the pooled estimated OR was 1.41 (95% CI, 1.26–1.57) for case–control studies (n = 11) and the pooled estimated RR was 1.29 (95% CI, 1.06–1.58) for prospective studies (n = 9). Sex-specific differences in RR were inconsistent between case–control and prospective studies. Study populations with a mean age of ≤55 years had an increased RR compared to older study populations. Reported Lp(a) contrast levels and ischemic stroke subtype significantly contributed to the heterogeneity observed in the analyses. Conclusion Elevated Lp(a) is an independent risk factor for ischemic stroke and may be especially relevant for young stroke patients. Sex-specific risk differences remain conflicting. Further studies in these subgroups may be warranted.