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Altered metabolic function has many detrimental effects on the body that can manifest as cardiovascular and liver diseases. Traditional approaches to understanding and treating metabolic dysfunction-associated disorders have been organ-centered, leading to silo-type disease care. However, given the broad impact that systemic metabolic dysfunction has on the human body, approaches that simultaneously involve multiple medical specialists need to be developed and encouraged to optimize patient outcomes. In this review, we highlight how several of the treatments developed for cardiac care may have a beneficial effect on the liver and vice versa, suggesting that there is a need to target the disease process, rather than specifically target the cardiovascular or liver specific sequelae of metabolic dysfunction., Competing Interests: Declaration of competing interest GG received research grants from Gilead, ViiV, MERCK, Jansen and Pfizer; attended advisory boards and received speaker honoraria from Gilead, ViiV, MERCK and Pfizer. JM received speaker honoraria from Gilead and ViiV. MGS has served as an advisor for Gilead, Ipsen, Advanz, Pfizer, Roche, Abbott and Novo Nordisk; as speaker for Abbott; and has received clinical trial or research grant support from Gilead, BMS, CymaBay, Intercept, Genfit, Pfizer, Ipsen, Novartis, Astra Zeneca, GSK, Celgene, Novo Nordisk, Axcella Health Inc., Merck, Galectin Therapeutics, Calliditas Therapeutics, AbbVie, Kowa. Giada Sebastiani has acted as speaker for Merck, Gilead, AbbVie, Novo Nordisk, Pfizer, served as an advisory board member for Pfizer, Merck, Novo Nordisk, Gilead, and has received unrestricted research funding from Theratecnologies Inc. PR is a member of the advisory board of Amgen, Novo Nordisk, and Novartis., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Whether apoB adds significantly to the assessment of the risk and therapy of the atherogenic dyslipoproteinemias has been vigorously contested over many years. That trapping of apoB lipoprotein particles within the arterial wall is fundamental to the initiation and maturation of atherosclerotic lesions within the arterial wall is now widely accepted. At the same time, the concept that primary prevention should be based on the risk of a cardiovascular event, a measure that integrates the effects of age, sex, blood pressure, lipids and other factors, has also become widely accepted. Within the risk framework, the issue becomes whether apoB adds significantly to the assessment of risk. On the other hand, it can be argued that the risk model undervalues how important a role that LDL and blood pressure play as causes of atherosclerosis and that when considered as causes, the importance of apoB emerges. These are the two sides of the debate that will be presented in the article that follows: one will highlight the pros of measuring apoB, the second the cons. The reader can make up his or her mind which side of the issue they favour., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The increase in the cardiovascular disease (CVD)-associated mortality rate in the Middle East (ME) is among the highest in the world. The aim of this article is to review the current prevalence of dyslipidaemia and known gaps in its management in the ME region, and to propose initiatives to address the burden of dyslipidaemia. Published literature on the epidemiology of dyslipidaemia in the ME region was presented and discussed at an expert meeting that provided the basis of this review article. The high prevalence of metabolic syndrome, diabetes, familial hypercholesterolaemia (FH) and consanguineous marriages, in the ME region, results in a pattern of dyslipidaemia (low high-density lipoprotein cholesterol and high triglycerides) that is different from many other regions of the world. Early prevention and control of dyslipidaemia is of paramount importance to reduce the risk of developing CVD. Education of the public and healthcare professionals and developing preventive programs, FH registries and regional guidelines on dyslipidaemia are the keys to dyslipidaemia management in the ME region., (Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Background and Aims: Untreated individuals with familial hypercholesterolaemia (FH) are at increased risk of developing premature cardiovascular disease (CVD). Early diagnosis and treatment can result in a normal life expectancy. A recent survey commissioned by the European Atherosclerosis Society (EAS) reported a lack of awareness of FH in the general population. We conducted a survey to assess knowledge among healthcare professionals involved in the assessment and management of cardiovascular risk and disease in the United Kingdom., Methods: A survey designed to assess knowledge of diagnostic criteria, risk assessment, the role of cascade screening, and management options for patients with FH was distributed to 1000 healthcare professionals (response rate 44.3%). The same survey was redistributed following attendance at an educational session on FH., Results: 151 respondents (40.5%) reported having patients under their care who would meet the diagnostic criteria for FH, but just 61.4% recognized that cardiovascular risk estimation tools cannot be applied in FH, and only 22.3% understood the relative risk of premature CVD compared to the general population. Similarly, just 65.9% were aware of recommendations regarding cascade screening., Conclusions: The prevalence and associated risk of FH continue to be underestimated, and knowledge of diagnostic criteria and treatment options is suboptimal. These results support the recent Consensus Statement of the EAS and production of quality standards by the National Institute for Health and Care Excellence. Further work is required to formulate interventions to improve FH awareness and knowledge, and to determine the effect these interventions have on patient outcomes., (Crown Copyright © 2016. Published by Elsevier Ireland Ltd. All rights reserved.)

Atherosclerosis is the leading cause of death worldwide. Research on the pathophysiological mechanisms of atherogenesis has made tremendous progress over the past two decades. However, despite great advances there is still a lack of therapies that reduce adverse cardiovascular events to an acceptable degree. This review addresses successes, but also questions, challenges, and chances regarding the translation of basic science results into clinical practice, i.e. the capability to apply the results of basic and/or clinical research in order to design therapies suitable to improve patient outcome. Specifically, it discusses problems in translating findings from the most broadly used murine models of atherosclerosis into clinically feasible therapies and strategies potentially improving the results of clinical trials. Most likely, the key to success will be a multimodal approach employing novel imaging methods as well as large scale screening tools-summarized as "omics" approach. Using individually tailored therapies, plaque stabilization and regression could prevent adverse cardiovascular events thereby improving outcome of a large number of patients., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Coronary artery calcium (CAC) scanning is a reliable, noninvasive technique for estimating overall coronary plaque burden and for identifying risk for future cardiac events. Arthur Agatston and Warren Janowitz published the first technique for scoring CAC scans in 1990. Given the lack of available data correlating CAC with burden of coronary atherosclerosis at that time, their scoring algorithm was remarkable, but somewhat arbitrary. Since then, a few other scoring techniques have been proposed for the measurement of CAC including the Volume score and Mass score. Yet despite new data, little in this field has changed in the last 15 years. The main focus of our paper is to review the implications of the current approach to scoring CAC scans in terms of correlation with the central disease - coronary atherosclerosis. We first discuss the methodology of each available scoring system, describing how each of these scores make important indirect assumptions in the way they account (or do not account) for calcium density, location of calcium, spatial distribution of calcium, and microcalcification/emerging calcium that might limit their predictive power. These assumptions require further study in well-designed, large event-driven studies. In general, all of these scores are adequate and are highly correlated with each other. Despite its age, the Agatston score remains the most extensively studied and widely accepted technique in both the clinical and research settings. After discussing CAC scoring in the era of contrast enhanced coronary CT angiography, we discuss suggested potential modifications to current CAC scanning protocols with respect to tube voltage, tube current, and slice thickness which may further improve the value of CAC scoring. We close with a focused discussion of the most important future directions in the field of CAC scoring., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Unlabelled: Pilot study to validate a Computerized Decision Support Systems (CDS) (HTE-DLP) for improving treatment of hyperlipidemia., Methods: HTE-DLP was programmed to offer automatic specific reminders for lipid treatment. Seventy-seven patients with high cardiovascular risk were randomized. 10 expert physicians in cardiovascular-risk management were recruited. We assessed number of patients at LDL <70 mg/dl after 12 weeks of treatment., Results: A greater proportion of intervention group reached the LDL-C <70 mg/ml [55.0% vs 12.5%, p = 0.003; OR: 3.26 IC (1.16-9.15)]. "High potency statins" and combined therapy were used more frequently in the intervention group than the control group (p = 0.001). Seven adverse effects were documented in the intervention group and two in the control group. An acceptable relationship was observed with regard to costeffectiveness in the intervention group. Physicians expressed good agreement with HTE-DLP (86.1%) and comfortable ease-of-use (85%)., Conclusions: Use of a CDSS in high-risk cardiovascular patients resulted in a significant reduction in LDL-C levels., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Unlabelled: 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) levelabove 3.5 mmol/L (135 mg/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 5 mmol/L (190 mg/dL), or above 4 mmol/L (160 mg/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 3.4 mmol/L (130 mg/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., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Triglycerides-rich lipoproteins are related to residual cardiovascular risk in patients on lipid-lowering treatment who achieve low-density lipoprotein cholesterol (LDL-C) goals. This study examined the predictive value of remnant lipoprotein levels for cardiovascular events in patients with coronary artery disease (CAD) with LDL-C levels <100mg/dL on lipid-lowering therapy., Methods: Serum levels of remnant lipoproteins (remnant-like lipoprotein particles cholesterol; RLP-C) were measured by an immunoseparation method in 560 patients with CAD who had LDL-C levels <100mg/dL on lipid-lowering therapy, including statin (58%), fibrate (13%) or diet only (29%). All the patients were followed prospectively for a period of ≤ 36 months or until occurrence of one of the following events: cardiac death, non fatal myocardial infarction, unstable angina requiring coronary revascularization, or ischemic stroke., Results: During a mean follow-up period of 33 months, 40 events occurred. Stepwise multivariate Cox proportional hazard analysis showed that RLP-C was a significant predictor of cardiovascular events after adjustment for known risk factors and lipid variables including triglycerides, non-high-density lipoprotein (HDL)-C, and total apolipoprotein B (HR 1.53, 95% CI 1.35-1.97, p<0.01). The c-statistics showed that addition of RLP-C had a greater incremental effect on the predictive value of conventional risk factors than addition of non-HDL-C or total apolipoprotein B., Conclusions: RLP-C was superior to non-HDL-C for predicting cardiovascular events in CAD patients with LDL-C levels <100mg/dL on lipid-lowering treatment. Remnant lipoprotein may therefore be an important target for residual risk reduction after LDL-C goals on lipid lowering therapy., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Previous trials indicate that surgical management of small abdominal aortic aneurysms (AAA) does not reduce mortality. The medical management of AAA, however, has to a large degree been ignored until recently. Medical management is not only needed to limit the expansion of small AAAs but also to reduce the high incidence of other cardiovascular events in these patients. In this review current evidence regarding medical therapy for patients with small AAAs is discussed. Four current randomised controlled trials are examining the efficacy of exercise, doxycycline and angiotensin converting enzyme inhibition in limiting AAA progression. A further trial using a mast cell stabilisation agent is expected to start soon. It is anticipated that a range of novel therapies for small AAAs will be identified within the next decade., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: Recently, several major organizations have proposed a unified definition for the metabolic syndrome (MetS), which should be evaluated in multiethnic groups. The effect of Mets on the incidence of cardiovascular disease needs to be assessed after adjusting for serum low density lipoprotein cholesterol (LDLC), a major risk factor for atherosclerotic diseases. This is especially needed to be evaluated in Asian populations with low incidence of coronary artery disease (CAD)., Methods: We conducted a 13-year prospective study of 4939 Japanese living in an urban area. The MetS was defined using a unified classification that included cut-off points for waist circumference in Asians. The multivariable adjusted hazard ratios (HRs) of MetS for CAD and stroke were calculated using a Cox proportional model adjusted for other potential confounding factors with LDLC., Results and Conclusion: During the follow-up period, there were 155 cases of CAD and 204 of stroke including 118 cerebral infarctions. In participants under 65 years old, the multivariable HRs of MetS for CAD were 1.21 (95% C.I., 0.64-2.28) in men and 4.44 (95% C.I., 1.73-11.4) in women; the HRs for ischemic stroke were 3.24 (95% C.I., 1.55-6.77) in men and 3.99 (95% C.I., 1.34-11.8) in women. In participants aged 65 years old and over, MetS only showed a significant association with CAD in men (HR 1.89, 95% C.I., 1.11-3.21). Serum LDLC was associated with increased risk of CAD in men irrespective of age group; however, it was not associated with CAD in women. There was no association between serum LDLC and ischemic stroke in any group stratified by sex and the age of 65. These results indicate that the new uniform MetS definition is useful for detecting high risk individuals, especially for middle-aged population. However, continuous screening for hypercholesterolemia is necessary to prevent CAD, especially in men, even in Asian countries such as Japan., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: The clinical value of exercise ankle brachial index (ABI) is still unclear, especially in patients with normal resting ABI., Method: 2164 patients performed a single-stage treadmill exercise test to diagnose or evaluate PAD. The population was divided into two groups: a normal resting ABI (resting ABI≥0.90) and PAD (resting ABI<0.90). Patients with a normal resting ABI were divided into 4 exercise ABI groups: exercise ABI<0.90, 0.90-0.99, 1.00-1.09 and 1.10-1.29 (reference)., Results: Mean follow-up was 5 years. Exercise ABI added significant prognostic information on all cause long-term mortality only in patients with normal resting ABI (p-value 0.014, HR 0.99 95% CI (0.98-0.99)), not in patients with PAD. Fifty years or older (OR 2.93 95% CI (1.65-5.20)) and resting systolic blood pressure>140 mmHg (OR 2.18 95% CI (1.35-3.55)) were associated with an abnormal exercise ABI in patients with a normal resting ABI. Mortality rate increased when the exercise ABI became worse (p trend 0.0001) with a 2.5-fold increase mortality risk in patients with a normal resting ABI but exercise ABI <0.90 (HR 2.56, 95% CI (1.11-5.91))., Conclusion: In patients with a normal resting ABI, treadmill exercise ABI added important prognostic information on long-term mortality. Based on our results we recommend that at least all patients suspected for PAD, with a resting ABI≥0.90, who are 50 years or older and having hypertension should undergo treadmill exercise testing., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: ABI is a good predictor of morbidity and mortality in diabetic subjects with no known cardiovascular disease. However, its prognostic value in diabetic patients with prior coronary or cerebrovascular disease has not previously been evaluated., Methods: Multicenter, prospective study of 1 year of follow-up, in 1096 patients (73.6 years, 65% males, 45.4% with diabetes) with cardiovascular disease and without known peripheral arterial disease. The main outcome measure was the first occurrence of a major cardiovascular event (non-fatal acute coronary syndrome, non-fatal stroke, revascularization procedure, or cardiovascular death). Secondary endpoints included major cardiovascular events, cardiovascular death and death from any cause., Results: Prevalence of an abnormal ABI (<0.9 or >1.4) was 38.2% in diabetic and 26.8% in non-diabetic subjects. There were 150 major cardiovascular events (38.3/1000 person-years in diabetics vs. 30.6/1000 person-years in non-diabetics subjects, p=0.012) and 60 cardiovascular deaths (11.8/1000 person-years in diabetics vs. 10.7/1000 person-years in non-diabetics subjects, p=0.156). Patients with abnormal ABI had a higher rate of vascular complications. There was a significant interaction between ABI and diabetes. In non-diabetic patients, an abnormal ABI was associated with an increase risk of the primary endpoint (HR 2.71; 95% CI 1.54-4.76), cardiovascular mortality (HR 4.62; 95% CI 1.47-14.52) and total mortality (HR 2.80; 95% CI 1.08-7.27). These associations were not observed in patients with diabetes., Conclusion: In patients with cardiovascular disease, ABI is a good predictor of risk of recurrent cardiovascular events and death, only in non-diabetic subjects., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

The Society of Atherosclerosis Imaging and Prevention, in collaboration with the International Atherosclerosis Society, conducted an appropriate use review of common clinical scenarios where carotid intima media thickness testing may be considered. The indications for this review were drawn from common applications or anticipated uses, as well as from current clinical practice guidelines. Thirty-three clinical scenarios were developed by a writing committee and scored by a separate technical panel on a scale of 1-9 to designate appropriate use, inappropriate use, or uncertain use. Clinical scenarios included the clinical application of CIMT for risk assessment in the absence of known coronary heart disease, risk assessment in patients with known CHD, and serial CIMT imaging for monitoring of CHD risk status. Appropriate indications were largely clustered within the detection of CHD risk among intermediate risk patients, metabolic syndrome, and older patients. There were no appropriate indications for serial testing. Inappropriate indications generally were seen among use of CIMT in low risk patients, and high risk patients. This document is intended to provide a practical guide to clinicians and promote optimal use of testing which includes both the avoidance of under and over testing. It is intended that these criteria will be updated as the evidence on CIMT imaging continues to evolve., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

In this study, we aimed to evaluate whether serum uric acid (UA) was associated with the severity and morphology of coronary atherosclerotic plaques (CAP) shown by multidetector computed tomography (MDCT). The study population consisted of 982 patients (58% men) who underwent dual-source 64 slice MDCT for the assessment of coronary artery disease (CAD). Coronary arteries were evaluated on 16 segment basis and critical coronary plaque was described as luminal narrowing >50%, whereas plaque morphology was assessed on per segment basis. Serum UA levels were determined using commercially available assay kits. The critical atherosclerotic lesions were detected in 454/982 (46.2%) subjects by MDCT. Serum UA levels were found to be higher in patients with any coronary plaque (6.9 ± 1.5mg/dL vs. 5.1 ± 1.3mg/dL, p<0.01). Also UA level was higher in patients with critical stenosis compared to non-critical stenosis (6.1 ± 1.5mg/dL vs. 5.4 ± 1.3mg/dL, p<0.001). Subjects having primarily calcified plaques have higher UA levels compared to other plaque subtypes (5.5 ± 1.3 for non-calcified plaques, and 5.6 ± 1.2 for mixed plaques, 6.6 ± 1.6 for calcified plaques, p<0.001). This independent association was remained after multinominal regression analysis (OR: 1,987; 95% CI; 1.69-2.32; p<0.01). Our study demonstrated that serum UA level was significantly associated with the severity and the calcified morphology of CAP detected by MDCT. Further prospective clinical studies are needed to clarify the exact physiopathologic role of UA in CAD., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Introduction: The early identification of the unstable carotid plaque together with the best medical treatment, are two missing parts of the stroke-prevention puzzle. This review summarizes the available evidence on the effects of statins on carotid plaque morphology., Methods: A systematic review of the PubMed, Scopus and Cochrane Library databases was performed. Studies evaluating the effect of statins on plaque imaging features other than intima media thickness as well as on the serum inflammatory profile were eligible for inclusion., Results: Seventeen studies were eligible for inclusion. The majority of the studies used MRI and ultrasound imaging. Plaque composition (fibrous cap and lipid core size), and size (plaque area and volume) were mainly used to evaluate the changes in plaque morphology. All studies showed slower progression, remodelling or even regression of the plaque even after only 1 month of statin administration, although the type, dosage and duration of treatment varied significantly between them. Intensive statin treatment was suggested to have a more pronounced effect on plaque morphology, however, that was mainly associated with maintaining LDL-levels <100 mg/mL and not with the intensity of the dosage. Seven studies measured CRP, four of which found significantly decreased levels with statin use., Conclusion: This review suggests that statins may have a beneficial effect on plaque morphology and the inflammatory response. Further validation of whether this is an LDL-associated effect or a separate pleiotropic phenomenon of statins is needed. There are significant inherent limitations to the safe extraction of solid conclusions from the studies due to data heterogeneity and publication bias., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Objective: Although contour analysis of pulse waves has been proposed as a non-invasive means in assessing arterial stiffness in atherosclerosis, accurate determination of the conventional parameters is usually precluded by distorted waveforms in the aged and atherosclerotic objects. We aimed at testing reliable indices in these patient populations., Methods: Digital volume pulse (DVP) curve was obtained from 428 subjects recruited from a health screening program at a single medical center from January 2007 to July 2008. Demographic data, blood pressure, and conventional parameters for contour analysis including pulse wave velocity (PWV), crest time (CT), stiffness index (SI), and reflection index (RI) were recorded. Two indices including normalized crest time (NCT) and crest time ratio (CTR) were also analysed and compared with the known parameters., Results: Though ambiguity of dicrotic notch precluded an accurate determination of the two key conventional parameters for assessing arterial stiffness (i.e. SI and RI), NCT and CTR were unaffected because the sum of CT and T(DVP) (i.e. the duration between the systolic and diastolic peak) tended to remain constant. NCT and CTR also correlated significantly with age, systolic and diastolic blood pressure, PWV, SI and RI (all P<0.01)., Conclusion: NCT and CTR not only showed significant positive correlations with the conventional parameters for assessment of atherosclerosis (i.e. SI, RI, and PWV), but they also are of particular value in assessing degree of arterial stiffness in subjects with indiscernible peak of diastolic wave that precludes the use of conventional parameters in waveform contour analysis., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Prospective studies of coronary heart disease patients with disorders of insulin resistance, metabolic syndrome (MetSyn) and type 2 diabetes (T2DM), have shown that these patients usually display high levels of low-density lipoprotein particles (LDL-P) and low levels of high-density lipoprotein particles (HDL-P). In multiple prospective studies, high levels of LDL-P are more predictive of CHD risk than low-density lipoprotein cholesterol (LDL-C). The conventional goal of lipid lowering treatment is to lower LDL-C levels; however LDL-C is unrelated to the severity of insulin resistance. Among high cardiometabolic risk patients with LDL-C <100 mg/dL, about two-thirds of patients have a high LDL-P (>1000 nmol/L) despite this "optimal" level of LDL-C. For high cardiometabolic risk patients, LDL-P should be considered a primary goal of therapy due to its stronger association with cardiovascular risk. Further, we propose that certain lipid-altering therapies may be particularly useful in reducing cardiovascular events in statin-treated patients, not simply due to their improvement in LDL-C goal attainment, but due to their effects on lowering the number of low-density lipoprotein particles (LDL-P)., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Treatment of carotid artery stenosis by endarterectomy or stenting can significantly reduce stroke risk, but is also associated with surgery related mortality and morbidity. At present it is neither possible to assess whether a carotid plaque will become symptomatic or not, nor to define the time when symptoms will occur. Identification of carotid plaques which confer excess risk of neurologic events is fundamental in the selection of patients for vascular intervention. Molecular processes such as inflammation, lipid accumulation, apoptosis, proteolysis, thrombosis and angiogenesis have shown to be highly related with plaque vulnerability. Serum biomarkers reflecting these processes may distinguish unstable from stable carotid artery stenosis and thus be a powerful tool in the selection of patients for carotid surgery. Until now, no serum biomarker has qualified for regular clinical use in carotid artery disease. However, several biomarkers, especially markers of inflammatory or proteolytic activity seem to be promising in the identification of vulnerable carotid plaques. Therefore, it is anticipated that non-invasive risk assessment in carotid artery disease by determination of serum biomarker levels may play an important future role in clinical practice improving better selection criteria for vascular intervention., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Imaging atherosclerosis may help to identify subjects harboring rupture-prone atherosclerotic plaques who may benefit from preventive interventions. Potential of plaques to rupture depends on their structural changes and metabolic activation, which are difficult to assess using anatomic imaging modalities. Recent studies suggested that functional imaging with positron emission tomography (PET) utilizing fluorine-18-labeled 2-deoxy-d-glucose (FDG) has the potential to assess plaque metabolism and add to prediction of vascular risk. Aortic, iliac, and carotid plaques can be detected with FDG-PET, even though not all plaques exhibit high FDG uptake. Detection of coronary artery plaques is more cumbersome due to technical limitations of PET and fast movement of these vessels during cardiac and respiratory cycles. Studies on substrate accumulating FDG in plaques are contradictory and mostly do not extend beyond correlation analyses. Vascular FDG uptake has an excellent short-term stability, but larger fluctuations of uptake long-term, which may complicate interpretation of such changes in therapeutic trials. FDG uptake in major arteries correlates with some cardiovascular risk factors and atherosclerosis markers, but clinical utility of such correlations is unclear. What is more important is that recently reported studies in cancer patients showed correlation between higher baseline FDG uptake and subsequent cardiovascular mortality. Anti-atherogenic therapy and therapeutic lifestyle changes seem to decrease vascular FDG uptake but it is not clear whether the latter predicts subsequent lower morbidity and mortality. These initial findings suggest that vascular FDG-PET may in the future find some utility in management of patients with atherosclerosis, but a number of important issues need to be addressed first. We need to: (1) determine optimal standard ways of performing imaging and quantifying vascular FDG uptake; (2) understand molecular mechanisms governing FDG accumulation in plaques; (3) perform studies prospectively linking vascular FDG uptake to cardiovascular events in non-cancer patients. As of today, vascular FDG-PET is not ready for its prime time in clinical practice., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Objective: We analyzed typical morphological features of coronary atherosclerotic plaques in acute coronary syndromes (ACS) using contrast-enhanced coronary Dual-Source CT angiography (CTA) in comparison to stable coronary lesions., Patients and Methods: Fifty-five patients with ACS and 55 controls with stable angina pectoris (SAP) with similar atherosclerotic risk profile were studied. CT angiography was performed using a Dual-Source CT scanner (330 ms rotation, 2 x 64 x 0.6mm collimation, 60-80 mL contrast agent i.v. at 6 mL/s) before invasive catheterization. We analyzed plaque volume (mm(3)), mean and minimal CT density (HU), remodeling index, plaque type (calcified/non-calcified/mixed) and presence of "spotty" calcifications as well as presence of contrast rims., Results: In patients with ACS and SAP, 28 and 10 lesions showed both calcified and non-calcified components, but in a greater proportion of non-calcified material, 6 and 23 lesions showed a greater proportion of calcified material and 21 and 8 lesions were completely non-calcified, respectively. None of the culprit plaques in ACS and 14 of the lesions in SAP were completely calcified. A "spotty" pattern of calcification within the plaque and a central filling defect surrounded by a rim of contrast were present in 11 and 14 of 55 ACS cases, but never in SAP lesions. For culprit lesions in ACS and for lesions in patients with SAP, mean plaque volumes were 192.8 + or - 114.9 mm(3) and 103.8+/-51.8 mm(3) (p=0.001), mean and minimal CT densities were 85.6 + or - 45.1HU and 47.2 + or - 33.7 HU versus 143.8 + or - 104.1 HU and 95.9 + or - 84.0 HU (p<0.01) and mean remodeling indices were 1.6 + or - 0.4 and 0.97 + or - 0.17 (p<0.001), respectively., Conclusion: Plaques of culprit lesions in ACS show specific morphologic characteristics in non-invasive coronary CT angiography. As compared to stable lesions, culprit lesions in ACS display greater proportion of non-calcified material and presence of "spotty" calcifications/contrast rims as well as larger plaque volumes, lower CT attenuation and higher remodeling indices., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

While there is an appreciable understanding of the importance of collagen breakdown in contributing to atherosclerotic plaque vulnerability and rupture, little is known about changes in collagen maturation in the atherosclerotic plaque. This is achieved through the formation of the covalent intermolecular cross-links pyridinoline (Pyd) and deoxypyridinoline (Dpd). In this study we collected carotid endarterectomy specimens from patients and undertook (i) histological assessment of collagen and inflammatory cell distribution and (ii) biochemical analysis of total collagen and cross-link content. Greater collagen deposition, increased presence of CD68 positive cells and an increased Pyd:Dpd ratio (an indicator of lysyl hydroxylase (LH-1) activity) were found in plaque versus normal vascular tissue. These findings are the first measurements of Pyd and Dpd cross-links in normal and atherosclerotic vascular tissue. The observed differences in cross-links in the plaque may adversely affect tensile strength and may have relevance to the mechanisms underlying rupture of vulnerable plaques., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: Average wall shear-stress (AWSS), average wall shear-stress gradient (AWSSG), oscillatory shear index (OSI) and relative residence time (RRT) are believed to predict areas vulnerable to plaque formation in the coronary arteries. Our aim was to analyze the correlation of these parameters in patients' vessels before the onset of atherosclerosis to the specific plaque sites thereafter, and to compare the parameters' sensitivity and positive predictive value., Methods: We obtained 30 patient-specific geometries (mean age 67.1 (+ or - 9.2) years, all with stable angina) of the right coronary artery (RCA) using dual-source computed tomography (CT) and virtually removed any plaque present. We then performed computational fluid dynamics (CFD) simulations to calculate the wall shear parameters., Results: For the 120 total plaques, AWSS had on average a higher sensitivity for the prediction of plaque locations (72 + or - 25%) than AWSSG (68 + or - 36%), OSI (60 + or - 30%, p<0.05), and RRT (69 + or - 59%); while OSI had a higher positive predict value (PPV) (68 + or - 34%) than AWSS (47 + or - 27%, p<0.001), AWSSG (37 + or - 23, p<0.001) and RRT (59 + or - 34%). A significant difference was also found between AWSSG and RRT (p<0.01) concerning PPV., Conclusions: OSI and RRT are the optimal parameters when the number of false positives is to be minimized. AWSS accurately identifies the largest number of plaques, but produces more false positives than OSI and RRT., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

In symptom-free subjects, exercise tolerance testing (ETT) has a doubtful utility for detecting latent coronary heart disease (CHD) because of frequent false positives, but it may be valuable for predicting future CHD. To clarify the latter question, we calculated CHD incidence associated with presence or absence of ETT-induced abnormalities of ST-segment depression, exercise capacity, and heart rate using published prospective ETT studies in primary prevention populations. Based on 5-23 years of follow-up, yearly incidence of fatal and non-fatal CHD ranged from 0.9 to 5.8% in the presence of ST-segment depression and from 1.2 to 1.7% in the presence of impaired maximal heart rate, and pooling of all data provided a linear positive relationship between pre- and post-test CHD incidence. Yearly incidence of CHD death was 0.8% in the presence of ST-segment depression, 0.2-0.3% in the presence of impaired heart rate recovery, and 0.5% in the presence of low exercise capacity. Absence of ST-segment depression was associated with <1.5% yearly incidence of fatal and non-fatal CHD events, except for one study and <0.2% yearly incidence of CHD or CVD death in all populations analyzed. Lastly ETT-induced ST-segment depression conveys a CHD risk superior to that associated with ETT-induced heart rate and exercise capacity abnormalities. This may be due to difference in pretest CHD incidences in ETT studies.

Smoking and other forms of tobacco use are major risk factors for cardiovascular disease. The effect of cigarette smoking on cardiovascular health is evident even at the lowest levels of exposure. Yet, the adverse effects of smoking are reversible, with cardiovascular risk decreasing substantially within the first 2 years of smoking cessation. Significantly, the mortality from coronary heart disease is reduced more through smoking cessation than by other secondary preventive therapies such as cholesterol lowering. Smoking cessation is a highly effective way to improve cardiovascular health in smokers and extremely cost-effective. However, smoking cessation therapies are not implemented maximally if they are implemented at all, perhaps because smoking is seen as a lifestyle choice or because smokers frequently relapse, as indicated by very low long-term quit rates. Too often, healthcare professionals, including lipidologists and cardiologists, do little to address their patients' smoking status, in spite of its impact on cardiovascular health. With the advent of new therapies to treat the nicotine addiction that results from smoking and other tobacco use, it is hoped that physicians will be more proactive in encouraging and implementing smoking cessation programs for their patients, with the goal of increasing long-term quit rates, and reducing the morbidity and mortality associated with cardiovascular disease.

Progress is slow in the integration of coronary heart disease prevention into daily clinical practice by cardiologists and other physicians working in cardiology, internal medicine and primary healthcare. This is not due to a lack of professional recommendations on coronary prevention. As new knowledge has become available, new generations of recommendations have been published. In surveys of secondary prevention practice, risk factor recording and management falls short of these recommendations and there is considerable potential to further reduce the risk of another major ischemic event in patients with established coronary disease. The most recent recommendations from the Joint Task Force of the European Society of Cardiology, European Atherosclerosis Society and European Society of Hypertension reinforce the importance of secondary prevention and how they can be extended to primary prevention by targeting high-risk individuals in the general population. It is hoped that development of guidelines at a national level will ensure a common approach to coronary heart disease prevention throughout Europe.

There is unequivocal evidence that reduction of modifiable risk factors for coronary heart disease (CHD), such as elevated serum cholesterol, high blood pressure and smoking, decreases cardiovascular mortality. However, levels of intervention appear to be poor and there is often little evidence of a combined multiple risk factor approach to intervention, which is likely to be the optimal way to lower a patients overall risk of developing CHD. Attention has recently focused on bridging the gap between knowledge in the field of preventive cardiology and its application in everyday clinical practice. This can only be accomplished by the development of uncomplicated, practical guidelines that are evidenced-based and that provide specific targets for risk factors and indications for drug therapy.