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International Atherosclerosis |
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Featured IAS Commentaries These Commentaries, including all information, text, graphics, images, and other material are for general educational purposes only and are not intended to be used for the purposes of providing medical treatment or attention or making medical or health-related decisions. These Commentaries are not a substitute or replacement for medical advice. If you are seeking medical advice, we encourage you to consult a physician or other medical professional. The views expressed in these Commentaries are those of the authors and are not necessarily those of IAS. COMMENTARIES POSTED IN MARCH 2010 Our understanding of cardiovascular diseases – from genes to therapy – has increased significantly in the past decades, which is best reflected by our understanding of “the classical” risk factors of atherosclerosis, including the application of drugs that have been developed based on this knowledge, e.g. statins. However, currently known risk factors can only be made responsible for maximum of 75% of all CVDs, indicating the need to search for and define new risk factors for CVDs. Despite the fact that the cardiovascular system is highly exposed to environmental factors, the impact of the environment, particularly on CVD initiation, progression, or outcome has up to now hardly been investigated. Recent data on particulate matter, for example, which (below a particle size of 2.5 µm) can enter the circulation, have highlighted the relevance of this interaction, suggesting that particulate matter is a novel risk factor for CVDs [1]. Food or Poison: the Multiple Effects of Berberine on Glucose,
Lipids, and Cholesterol Metabolism Complicate Its Potential
as a Drug Candidate This commentary is to introduce our study on berberine which is published in Cell Research [1]. Specificity is always important for a potential drug compound. However, studies often raise more questions than solve problems. Our observations do not help us to understand berberine with regard to its insulin-sensitizing effect, but raise instead a question as to its safety for the potential treatment of atherosclerosis. Metabolic syndrome, which recognizes the importance of insulin resistance in increasing the risk of developing cardiovascular disease and diabetes, is a combination of physiological disorders. The physiological disorders related to metabolic syndrome include abdominal obesity, impaired fasting glucose, high triglyceride levels, low HDL-cholesterol concentrations, and increased blood pressure [2]. Anyone with some or all of these disorders is at increased risk of cardiovascular disease and diabetes. To alleviate the metabolic syndrome, researchers are constantly searching for insulin-sensitizing compounds for drug development. Tools for Interpretation of Coronary Artery Calcium Author: Robyn L. McClelland, Ph.D. Coronary artery calcium (CAC) has been demonstrated to be associated with the risk of coronary heart disease [1]. The most frequently used measure in the literature is the Agatston score, which measures the amount of calcium at each lesion scaled by an attenuation factor and summed over all lesions [2]. Often cut points are used to define a "high" CAC score which do not have a formal basis on the distributional nature of CAC, either as a predictor of events, or in a healthy population (e.g. CAC > 100). Interpretation of an observed CAC score is challenging, and we have used information on the distribution and predictive value of CAC to provide some tools that may be useful in this regard. There are two components to interpretation of an observed CAC score: the retrospective and the prospective, similar to diagnosis and prognosis. It is of interest to know if the CAC score for a patient is high, relative to others of the same age, gender, and race. This may indicate the presence of modifiable risk factors, and/or a need for further testing in order to understand what led to the unusually high CAC value. A related but clearly distinct question is what the associated risk of a coronary heart disease event is for that patient given their CAC level, and how to convey this risk in understandable terms. Scoring Diet and Prediction of Heart Disease Authors: Fumiaki Imamura, Ph.D. and Alice H Lichtenstein, D.Sc. In this commentary, we would like to introduce our study published in the American Journal of Clinical Nutrition [1] and its relevancy to non-dietary studies. The main point of this recent work is novel in the nutrition field, but not necessarily in other fields, such as biomarkers and genetics. Therefore, after a description of the background, findings, and significance of our work, we will discuss the applicability of our finding to non-dietary studies. In the past two decades, observational epidemiologic studies of single nutrients or foods and dietary patterns have provided evidence for an association between diet and chronic disease risk. Epidemiological evidence supports the hypothesis that dietary modification can reduce mortality and morbidity from cardiovascular diseases [2-7]. However, current data remain insufficient to establish strong evidence in support of precise dietary recommendations. We attribute this limitation, in part, to the lack of an adequate tool with which to evaluate the effectiveness and efficacy of dietary practices. The Evolution of ApoA-I Mimetic Peptide Investigation: Past Work, Present Controversies, and Future Directions Authors:Geoffrey D. Wool, Catherine A. Reardon, and Godfrey S. Getz Pharmacologically enhancing HDL has been called the next frontier in the prevention of coronary artery disease (CAD) [1]. Several studies have demonstrated the continued risk of CAD in patients with adequately lowered LDL; their risk is inversely correlated with HDL-C level [2,3]. This commentary focuses on the apolipoprotein A-I (apoA-I) mimetic peptides that boost various anti-inflammatory properties of HDL without consistently raising the lipoprotein concentration. These peptides may have beneficial effects independent of HDL. Apolipoprotein B Versus LDL Cholesterol Authors: Helena Vaverkova, Prof., M.D Cardiovascular diseases are the major cause of mortality and morbidity in all developed and many developing countries. Lipids play a key role in the development of atherosclerosis and its clinical manifestations. In most countries LDL cholesterol (LDL-C) is considered to be the major lipid risk factor and the main target of lipid-altering therapy [1,2]. However, many prospective studies proved that apolipoprotein (Apo) B is a better marker of coronary heart disease (CHD) risk than LDL-C [recently reviewed in 3-5]. Large randomized trials (especially statin ones) proved that lowering of LDL-C leads to a reduced occurrence of coronary and cardiovascular endpoints. But even persons subjected to an active therapy in these trials display a high residual risk. One of reasons of such high residual risk may be the fact that LDL-C need not be the best risk marker in all individuals. Moreover, several studies revealed that during statin therapy the predictive power of LDL-C disappeared while ApoB, and particularly ApoB/ApoA-1 ratio, remained good risk markers of cardiovascular diseases. The Value of Ultrasonographic Parameters of Carotid Atherosclerosis as Marker of Subclinical Coronary Disease Authors: Nicola Cicorella, Francesca Fozzato, and Luisa Zanolla There is interest in identifying subjects who will develop cardiovascular disease, but the conventional risk factor assessment may not be sufficient to assess total risk. Atherosclerosis is a systemic process and its detection in one vascular bed implies a high likelihood of atherosclerosis presence in a different anatomical area [1]. Recently, we have looked for a technique to detect preclinical (asymptomatic) atherosclerosis, in order to allow early and intensive therapy. Carotid atherosclerosis is an independent predictor of the presence of coronary artery disease (CAD), and, moreover, it represents a risk factor for cardiovascular death and nonfatal myocardial infarction (MI) [2]. Decades of silent arterial wall abnormalities and gradual thickening of the intima-media precede vascular clinical events, which then reflect advanced atherosclerotic disease. A Promising Computational Model for Improving the Diagnostic Power of Lipoprotein Profiles Authors: Daniël B. van Schalkwijk, M.Sc, Ben van Ommen, Ph.D., and Albert A. de Graaf, Ph.D. Lipoprotein profiles have been around for quite a while. They are the most recent in a series of improvements in cholesterol-related diagnostics. The first widely-used diagnostic was total cholesterol. Later, density gradient separation made the distinction between LDL and HDL cholesterol possible, which proved to be a large improvement for risk prediction and therapy response monitoring. Measuring apolipoprotein levels (apoB, apoA) was a next step forward. Finally, lipoprotein profiles contain even more detailed information due to the separation of lipoprotein particles, either by density [1] or by size [2-4]. So, lipoprotein profiles contain potentially useful information, but the question is how to best extract this information for practical use in the clinic. Apolipoprotein E: From Atherosclerosis to Alzheimer's Disease to AIDS Authors: Robert W. Mahley, M.D., Ph.D. For more than 40 years I have had the pleasure of studying this amazing protein. I believe that in the near future we will be able to take advantage of our knowledge of apolipoprotein (apo) E to develop therapies to cure or prevent its detrimental effects and to enhance its protective lipid transport functions. I have been asked to give a historical overview of the life and times of apoE from my perspective. In the late 1960s, Robert L. Hamilton, Ph.D., Professor Emeritus, University of California, San Francisco, and one of my Ph.D. mentors at Vanderbilt University, saw spherical particles in the hepatic Golgi apparatus by electron microscopy and hypothesized that they were nascent plasma very low density lipoproteins (VLDL). Along with Thomas Bersot (an M.D./Ph.D. student at Vanderbilt and now a Gladstone investigator), we isolated the rat liver Golgi apparatus and established that these spherical particles were in fact the precursors of VLDL [1].
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