Showing papers in "Current Atherosclerosis Reports in 2004"

Omega-3 fatty acids and inflammation

Abstract: Dietary omega-3 (n-3) fatty acids have a variety of anti-inflammatory and immune-modulating effects that may be of relevance to atherosclerosis and its clinical manifestations of myocardial infarction, sudden death, and stroke. The n-3 fatty acids that appear to be most potent in this respect are the long-chain polyunsaturates derived from marine oils, namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and this review is restricted to these substances. A variety of biologic effects of EPA and DHA have been demonstrated from feeding studies with fish or fish oil supplements in humans and animals. These include effects on triglycerides, high-density lipoprotein cholesterol, platelet function, endothelial and vascular function, blood pressure, cardiac excitability, measures of oxidative stress, pro- and anti-inflammatory cytokines, and immune function. Epidemiologic studies provide evidence for a beneficial effect of n-3 fatty acids on manifestations of coronary heart disease and ischemic stroke, whereas randomized, controlled, clinical feeding trials support this, particularly with respect to sudden cardiac death in patients with established disease. Clinically important anti-inflammatory effects in man are further suggested by trials demonstrating benefits of n-3 fatty acids in rheumatoid arthritis, psoriasis, asthma, and inflammatory bowel disorders. Given the evidence relating progression of atherosclerosis to chronic inflammation, the n-3 fatty acids may play an important role via modulation of the inflammatory processes.

Antidiabetic Actions of Estrogen: Insight from Human and Genetic Mouse Models

Abstract: There is increasing evidence both in humans and rodents linking the endogenous estrogen 17b-estradiol (E2) to the maintenance of glucose homeostasis. Postmenopausal women develop visceral obesity and insulin resistance and are at increased risk for type 2 diabetes mellitus, but hormone replacement therapy leads to a reduction in the incidence of diabetes. In various spontaneous rodent models of type 2 diabetes, female rodents are protected against hyperglycemia unless they are ovariectomized, and E2 perfusion reverses diabetes in male rodents. Finally, the study of transgenic mice and mice with genetic alteration of E2 secretion or E2 action has shed light on the antidiabetic properties of E2 at a tissue-specific level. Thus, E2 secretion and action in rodents seems to be implicated 1) in adipose tissue biology and the prevention of obesity, 2) in the stimulation of liver fatty acid metabolism and suppression of hepatic glucose production, and 3) in the protection of pancreatic b-cell function/survival and insulin secretion in conditions of oxidative stress.

Whole grain intake and cardiovascular disease: a review.

Abstract: Prospective epidemiologic and feeding studies find possible health benefits of whole cereal grain foods (which include the bran, germ, and endosperm in their naturally occurring proportions), especially for prevention of atherosclerotic cardiovascular diseases and type 2 diabetes. We review 17 articles that consistently found a 20% to 40% reduction in long-term risk of these diseases comparing habitual consumers of whole grains to those who rarely eat these foods. Another 12 studies found a similar risk reduction according to amount of cereal fiber consumed. Feeding studies show improvements in risk factors for these diseases when whole grain foods are consumed. Some authors have tried to explain the reduced risk by invoking cereal fiber, with no attention to nonfiber constituents. We interpret the data as supportive of a synergy of the whole grain constituents, including fiber as only one such constituent.

Cardiovascular risk factors and Alzheimer's disease.

Abstract: Alzheimer’s disease is a devastating condition that is increasing in prevalence. No known prevention or cure exists for Alzheimer’s disease. Cardiovascular risk factors are prevalent and increase in the elderly, and there have been conflicting reports of associations between modifiable cardiovascular risk factors and Alzheimer’s disease. The mechanisms for these associations are uncertain, but they are likely to be the result of a combination of direct and cerebrovascular disease-related mechanisms. From this standpoint, diabetes and hyperinsulinemia seem to have the strongest evidence from laboratory, clinical, and epidemiologic studies. Studies have also indicated that hypertension, hyperlipidemia, hyperhomocysteinemia, and smoking are potentially important risk factors for Alzheimer’s disease.

Low-density lipoprotein particle number and risk for cardiovascular disease.

Abstract: The key role played by low-density lipoprotein (LDL) particles in the pathogenesis of coronary heart disease (CHD) is well accepted, as is the benefit of lowering LDL in high-risk patients. What remains controversial is whether we are using the best measure(s) of LDL to identify all individuals who would benefit from therapy. Many studies have shown that, at a given level of LDL cholesterol, individuals with predominantly small LDL particles (pattern B) experience greater CHD risk than those with larger-size LDL. However, it is not clear from this observation that small LDL particles are inherently more atherogenic than large ones because, at a given level of LDL cholesterol, individuals with small LDL have more LDL particles in total. The phenotype of small LDL particle size co-segregates with a cluster of metabolic factors, including elevated triglycerides and reduced HDL cholesterol, and in multivariate analyses has generally been found not to be independently associated with CHD risk. In contrast, LDL particle number measured by nuclear magnetic resonance has consistently been shown to be a strong, independent predictor of CHD.

Inflammation, insulin resistance, and obesity.

Abstract: Obesity, in particular visceral obesity, has strong associations with cardiovascular disease and is related to many factors that are constituents of the metabolic syndrome. Increasing evidence suggests that features of the metabolic syndrome, including visceral obesity, are associated with a low-grade inflammatory state. Indeed, visceral fat is a source of several molecules, such as leptin, adiponectin, tumor necrosis factor-alpha, and interleukin 6, that are collectively called adipokines. All of them may induce a proinflammatory state and oxidative damage, leading to initiation and progression of atherosclerosis. Reduced-energy diets might represent an effective and healthful approach for long-term weight loss in patients with metabolic syndrome by reducing the underlying inflammatory condition.

Matrix metalloproteinases and atherosclerosis.

Abstract: Atherosclerosis is a major cause of coronary heart disease, and matrix metalloproteinases (MMPs) play an important role in atherosclerosis by degrading the extracellular matrix, which results in cardiovascular remodeling. Recent studies have identified enhanced expression of MMPs in the atherosclerotic lesion and their contribution to weakening of the vascular wall by degrading the extracellular matrix. The transcription, enzyme processing, and specific inhibition of MMPs by tissue inhibitors of matrix metalloproteinase (TIMPs) regulate these effects. These processes are also modified by inflammatory cytokines and cell-cell contact signaling. Both animal experiments and clinical sample analysis have shown that balance in expression and activation of MMPs and inhibition by TIMPs is critical for the development of stenotic and aneurysmal change. Polymorphism in the MMP gene promoter contributes to inter-individual differences in susceptibility to coronary heart disease. The development of therapeutic drugs specifically targeting MMPs may thus be useful for the prevention of atherosclerotic lesion progression, plaque rupture, and restenosis.

The role of fibrates in managing hyperlipidemia: mechanisms of action and clinical efficacy.

Abstract: At a time when the lipid management guidelines give more and more emphasis to the identification and treatment of high-risk patients with the metabolic syndrome and diabetes, there is an obvious need to balance the known effects of low-density lipoprotein (LDL) lowering with the new evidence of clinical efficacy derived from the adjustment of high-density lipoprotein (HDL) and triglyceride levels. Whereas the statins remain the drug of choice for patients who need to reach the LDL goal, fibrate therapy may represent the best intervention for subjects with atherogenic dyslipidemia and an LDL already close to goal. In addition, the concomitant use of fibrates may significantly reduce cardiovascular risk in patients whose LDL is controlled by statin therapy. In this review, we evaluate the pharmacologic properties of the fibrate drugs, with particular attention to the effects of peroxisome proliferator activated receptor α activation in the control of dyslipidemia as well as in the attenuation of arterial inflammation. Clinical trials of fibrates, such as the Helsinki Heart Study, Veterans Affairs High-density lipoprotein Intervention Trial, Diabetes Atherosclerosis Intervention Study, and Bezafibrate Infarction Prevention trial, have conjured up a scenario for the clinical utility of fibrates and their possible superiority to statins in the management of obese, insulin-resistant, and diabetic patients presenting with near-goal LDL and inappropriate HDL and triglyceride levels.

Flavonoids for reduction of atherosclerotic risk.

Abstract: Flavonoids are polyphenolic compounds found in fruits, vegetables, and beverages derived from plants. Foods thought historically by many societies to have healing properties--cocoa, red wine, and tea--are particularly rich in flavonoids. A majority of prospective cohort studies demonstrate a significant inverse association between flavonoid consumption and cardiovascular risk. Short-term studies demonstrate numerous plausible mechanisms by which flavonoids may confer cardiovascular protection: they inhibit low-density lipoprotein oxidation, reduce thrombosis, improve endothelial function, and reduce inflammation. No long-term, randomized, controlled trials of flavonoids with hard clinical endpoints have been conducted. Although there are no recommended daily intake goals for flavonoids, the data presented provide additional rationale to eat a diet containing a variety of flavonoid-rich foods and beverages.

Robotics and other devices in the treatment of patients recovering from stroke.

Abstract: Stroke is the leading cause of permanent disability in the United States despite advances in prevention and novel interventional treatments. Randomized controlled studies have demonstrated the effectiveness of specialized post-stroke rehabilitation units, but administrative orders have severely limited the length of stay, so novel approaches to the treatment of recovery need to be tested in outpatients. Although the mechanisms of stroke recovery depend on multiple factors, a number of techniques that concentrate on enhanced exercise of the paralyzed limb have demonstrated effectiveness in reducing the motor impairment. For example, interactive robotic devices are new tools for therapists to deliver enhanced sensorimotor training for the paralyzed upper limb, which can potentially improve patient outcome and increase their productivity. New data support the idea that for some post-stroke patients and for some aspects of training-induced recovery, timing of the training may be less important than the quality and intensity of the training. The positive outcome that resulted in the interactive robotic trials contrasts with the failure to find a beneficial result in trials that used a noninteractive device that delivered continuous passive motion only. New pilot data from novel devices to move the wrist demonstrate benefit and suggest that successive improvement of the function of the arm progressing to the distal muscles may eventually lead to significant disability reduction. These data from robotic trials continue to contribute to the emerging scientific basis of neuro-rehabilitation.

Novel features of nitric oxide, endothelial nitric oxide synthase, and atherosclerosis.

Abstract: There is a complex pathophysiologic scenario involving nitric oxide (NO), endothelial nitric oxide synthase (eNOS), and the development of atherosclerosis and unstable atheroma. Endothelial damage induced by atherosclerosis leads to the reduction in bioactivity of ENOS with subsequent impaired release of NO. An important mechanism is local enhanced degradation of NO by increased generation of reactive oxygen species and other free radicals, with subsequent cascade of oxidation-sensitive mechanisms in the arterial wall. Novel molecular approaches have resulted in the development of new strains of mice lacking eNOS. These experimental models will help to understand how to implement NO-based therapies against atherosclerosis. L-arginine, the precursor of NO, has demonstrated beneficial effects in atherosclerosis and disturbed shear stress. The target or goal for new drugs should be the complete restoration of NO-mediated signaling pathways in atherosclerotic arteries.

Lipoprotein lipase and its role in regulation of plasma lipoproteins and cardiac risk.

Abstract: For over 50 years, biologists and clinicians have studied lipoprotein lipase (LPL) and learned about its structure, function, cellular production, physiology, and human genetics. LPL is the principal enzyme that removes triglyceride from the bloodstream. It also determines plasma levels of high-density lipoprotein. Surprisingly, within the past several years, a number of new and unexpected proteins have been discovered that regulate the actions of LPL. These include the very low-density lipoprotein receptor, angiopoetin-like protein 3, and apolipoprotein A-V. In addition, mouse genetic studies have confirmed tissue culture findings of nonenzymatic roles of LPL both in lipid metabolism and atherogenesis. These basic observations are now being related to new information on human genetic polymorphism in this gene that is likely to affect clinical evaluation of lipoprotein disorders and cardiac risk.

High-density lipoprotein subfractions and risk of coronary artery disease.

Abstract: Numerous studies have shown that levels of high-density lipoprotein (HDL) cholesterol are inversely related to coronary artery disease risk. The HDL subfractions, however, seem to differ in their capacity to confer protection, with the large HDL2 subfraction appearing to be more important than the small HDL3 subfraction. Lipid-modifying drugs differ in their HDL-raising efficacy, and they also differ in how they affect HDL subfractions. Clinical trials show that raising total HDL cholesterol improves clinical and angiographic outcomes. It remains to be determined, however, whether a shift in distribution of HDL particles provides greater benefit than just an increase in total HDL.

A Dietary portfolio: Maximal reduction of low-density lipoprotein cholesterol with diet

Abstract: Over the past two decades, cholesterol-lowering drugs have proven to be effective and have been found to significantly reduce the risk of coronary heart disease (CHD). However, diet and lifestyle factors are still recognized as the first line of intervention for CHD risk reduction by the National Cholesterol Education Program and the American Heart Association, which now advocate use of viscous fibers and plant sterols, and soy protein and nuts, respectively. In a series of metabolically controlled studies, we have combined these four cholesterol-lowering dietary components in the same diet (ie, a dietary portfolio of cholesterol-lowering foods) in an attempt to maximize low-density lipoprotein cholesterol reduction. We have found that the portfolio diet reduced low-density lipoprotein cholesterol by approximately 30% and produced clinically significant reductions in CHD risk. These reductions were the same as found with a starting dose of a first-generation statin drug.

Inflammatory and oxidative markers in atherosclerosis: relationship to outcome.

Abstract: Inflammation and oxidative processes are key components of atherosclerosis, from fatty streak formation to plaque rupture and thrombosis. Recent basic and clinical studies have identified a number of inflammatory and oxidative processes that appear to play a direct role in atherothrombosis and identify potentially clinically useful markers of inflammation and oxidative stress. In this review, we highlight recent results on several of the more promising markers of inflammation for cardiovascular disease risk assessments, such as C-reactive protein, myeloperoxidase, and soluble CD40 ligand and nitrotyrosine, as well as other potential markers.

Postprandial lipid oxidation and cardiovascular disease risk.

Abstract: A mild pro-oxidative state accompanies meal ingestion, which results in an increase in biomarkers of inflammation, adhesion, and endothelial dysfunction, all of which are factors in the development of cardiovascular disease. Both fat and carbohydrate can cause the effect, which is additive and exacerbated by diabetes. The presence of lipid, glucose, and cholesterol oxidation products of dietary or endogenous origin may contribute to postprandial oxidative stress. However, the generation of excess superoxide due to abundant energy substrate after the meal may be a predominate factor resulting in oxidative stress and a decrease in nitric oxide, which is important to endothelial function. Remediation of postprandial oxidative stress through direct reduction of superoxide generation and simultaneous consumption of antioxidants with each meal should be a focus of future research.

Inflammation and atherosclerosis

Abstract: Inflammation plays a pivotal role in all stages of atherogenesis, from foam cell to plaque formation to rupture and ultimately to thrombosis. Insight gained from recent basic and clinical data linking inflammation to atherosclerosis has yielded important diagnostic and prognostic information. Low-grade chronic inflammation as measured by high sensitivity C-reactive protein predicts future risk of acute coronary syndrome independent of traditional cardiovascular risk factors. In addition, individuals with higher "inflammatory burden" gain the largest absolute risk reduction with aggressive risk-lowering therapy. The link between inflammation and atherosclerosis provides a new venue for future pharmacologic agents that may slow the progression of atherosclerosis by inhibiting inflammation.

Diet, fatty acids, and regulation of genes important for heart disease.

Abstract: Diets rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs), such as alpha-linoleic acid, eicosapentaenoic acid, and docosahexaenoic acid, are associated with decreased incidence and severity of coronary heart disease. Similarly, conjugated linoleic acids (CLAs), which are found in meat and dairy products, have beneficial effects against atherosclerosis, diabetes, and obesity. The effects of n3-PUFAs and CLAs are in contrast to fatty acids with virtually identical structures, such as linoleic acid and arachidonic acid (ie, n-6 PUFAs). This article discusses the possibility that cognate receptors exist for fatty acids or their metabolites that are able to regulate gene expression and coordinately affect metabolic or signaling pathways associated with coronary heart disease. Three nuclear receptors are emphasized as fatty acid receptors that respond to dietary and endogenous ligands: peroxisome proliferator activated receptors, retinoid X receptors, and liver X receptors.

Homocysteine and cardiovascular disease.

Abstract: Research over the past decade has shown that elevated levels of homocysteine have a strong association with all forms of atherothrombotic disease and venous thromboembolism. This association is particularly strong for coronary disease and newer data indicate that screening for homocysteine levels may be warranted in those with unexplained thrombotic tendencies and in young patients who develop coronary events or disease without the usual predisposing factors such as hypertension, smoking, hypercholesterolemia, or diabetes. Although the link between hyperhomocysteinemia and cardiac disease has not been conclusively shown to be causal as yet, data are emerging that lowering homocysteine levels may be beneficial in patients at high risk. Such lowering can be done safely and inexpensively with increased intake of fruits and vegetables and in those patients who are particularly at high risk using supplementation with folic acid and the B vitamins. Preliminary studies have shown that lowering homocysteine levels in this manner may slow the progression of atherosclerosis in coronary and carotid vessels. No mortality data exist yet showing that reducing homocysteine reduces cardiac or total mortality, although it is likely that ongoing and planned trials that are underway will shed light on these important questions soon.

Effects of omega-3 fatty acids on cytokines and adhesion molecules.

Abstract: The dietary intake of omega-3 (n-3) polyunsaturated fatty acids has emerged, over the past 20 years, as an important way to modify cardiovascular risk. This likely occurs through beneficial effects at all stages in the natural history of vascular disease, from the inception of atherosclerotic lesions, to their growth and acute complications (plaque rupture in most instances), up to protection of myocardium from the consequences of ensuing acute myocardial ischemia. This review specifically focuses on the modulating effects of n-3 fatty acids on biologic events involved in early atherogenesis, including important properties of these natural substances on endothelial expression of adhesion molecules and cytokines, processes collectively denoted as “endothelial activation.” By decreasing the endothelial responsiveness to proinflammatory and proatherogenic stimuli, n-3 fatty acids act on molecular events not targeted by any other drugs or interventions, and thereby complementary to those of already implemented pharmacologic treatments.

Use of genetic mouse models in the study of diabetic nephropathy.

Abstract: The study of experimental diabetic nephropathy in rodent models has led to many changes in the clinical management of human diabetic nephropathy. With the development of technology to generate knockout and transgenic animals, the mouse has become a favored species in medical research. There are several genetic mouse models of diabetes, with the majority being models of type 2 diabetes mellitus. These include the hypoinsulinemic non-obese diabetic mouse, the Kkay mouse, the New Zealand obese mouse, the hyperinsulinemic ob/ob mouse, and the different strains of obese hyperinsulinemic db/db mouse. Each of these models displays some renal changes, but by far the best model of renal disease and the one that is the most studied is the db/db mouse. The db/db mouse displays substantial glomerular pathology, including mesangial matrix expansion and modest albuminuria. It has been reported that the db/db mouse has a decline in creatinine clearance after 5 months of age, but more specific approaches are warranted to confirm these findings. A number of intervention studies show renoprotection in this model. Although mice have many advantages, such as being able to be cross-bred with genetically manipulated animals, in many ways they are not very similar to humans, and in some respects the rat may be a better choice, particularly in relation to some features of end-organ injury.

Are omega-3 fatty acids the most important nutritional modulators of coronary heart disease risk?

Abstract: With each passing year, the evidence linking an increased risk for coronary heart disease (CHD) death with a chronic dietary deficiency in long-chain omega-3 (n-3) fatty acids (FAs) grows stronger. Recently, a federally mandated evidence-based review in the United States concluded that n-3 FAs, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have clear cardioprotective effects, and national and international expert panels and health organizations have begun to call for increased EPA and DHA intakes. Consumption of between 450 and 1000 mg/d is recommended for those without and with known CHD, respectively. Based on animal and isolated cell studies, these FAs were presumed to have antiarrhythmic effects. The first direct evidence for this in humans was recently published, as were new data linking low n-3 FA intakes with risk for developing atrial fibrillation. The strength of the n-3 story has now led to a proposal that blood levels of EPA plus DHA be considered a new, modifiable, and clinically relevant risk factor for death from CHD.

Noninvasive atherosclerosis imaging for predicting cardiovascular events and assessing therapeutic interventions.

Abstract: Noninvasive assessment of atherosclerosis offers an opportunity to provide individual cardiovascular risk management and an opportunity to monitor the efficacy of therapy targeted toward atherosclerosis. The three imaging modalities that currently hold the most promise at the clinical and research levels are ultrasound for carotid intima-media thickness, computed tomography for coronary artery calcification, and magnetic resonance imaging for carotid and aortic plaque imaging. The following review describes the evidence that validates each technique as a surrogate marker of atherosclerosis, with an emphasis on cardiovascular events and the progression of disease. Both the particular strengths and limitations of each imaging modality are discussed.

The metabolic syndrome: A crossroad for genotype-phenotype associations in atherosclerosis

Abstract: The metabolic syndrome comprises a set of metabolic and physiologic risk factors associated with elevated cardiovascular disease risk. The expression of each one of its major factors (hypertriglyceridemia, low high-density lipoprotein cholesterol levels, hypertension, abdominal obesity, and insulin resistance) has been found to be the result of complex interactions between genetic and environmental factors. Moreover, obesity may play a major role in triggering the metabolic syndrome by interacting with genetic variants at candidate genes for dyslipidemia, hypertension, and insulin resistance. In support of this hypothesis, several studies at multiple candidate genes have already demonstrated the significance of these interactions; however, the data and their reliability are still very limited, and in many cases replication studies are still lacking in the literature. Therefore, more studies with better epidemiologic design and standardized adiposity measures are needed to estimate the contribution of body weight and fat distribution to the genetic predisposition to the metabolic syndrome, which is the most common cardiovascular disease risk factor in industrialized societies.

Intravascular ultrasound assessment of atherosclerosis.

Abstract: Atherosclerosis imaging has taken on increasing importance in the understanding of the natural history of coronary artery disease and the processes leading to luminal narrowing, as well as the assessment of disease burden and therapy efficacy. Intravascular ultrasound (IVUS) has emerged as the new gold standard for atherosclerosis imaging because it provides cross-sectional images of both the arterial wall and lumen with excellent resolution, reveals the diffuse nature of atherosclerosis and the involvement of reference segments, and takes into account vessel wall remodeling. In addition to its clinical indications, IVUS is now widely used as the primary efficacy assessment measure of several antiatherosclerotic approaches in randomized clinical trials. Advantages of IVUS include its ability to reveal antiatherosclerotic effects within a relatively short period of time and with a reasonable sample size, which is in contrast to trials assessing angiographic changes or clinical events. IVUS can also help to determine dose-response relationships in the development of novel pharmacologic agents. IVUS is currently the ideal imaging modality for clinical trials of atherosclerosis progression/regression.

The cardioprotective effects of statins.

Abstract: In addition to their lipid-modulating properties, statins have a large number of beneficial cardiovascular effects that have emerged over time and that were not anticipated during drug development. The lipid and nonlipid effects act in a concerted way to reduce the ischemic burden of the myocardium and to protect it against injury. By acting on the vessel wall, statins may prevent lesion initiation and repair injuries, enhance myocardial perfusion, slow lesion progression, and prevent coronary occlusion. They may also directly reduce myocardial damage, favor myocardial repair, and protect against immune injury. This review focuses on properties of statins that contribute to their cardioprotective effect. The first section includes information on modulation of vascular tone, endothelial permeability and function, inhibition of complement injury, curbing of foam cell formation, antioxidant and anti-inflammatory properties, and profibrinolytic and anticoagulant activities. The second section relates to reduction of myocardial necrosis, myocardial hypertrophy, blood pressure, and heart failure, as well as mobilization of endothelial progenitor cells for repair, angiogenic effects, and immunomodulation. In many instances, results of in vitro and animal studies have raised expectations and prompted studies in humans. Several clinical trials have confirmed these expectations and have strengthened the value of statins as valuable antiatherosclerotic and cardioprotective agents.

Therapeutic time window of thrombolytic therapy following stroke.

Abstract: Stroke is the third leading cause of death after myocardial infarction and cancer and the leading cause of permanent disability and of disability-adjusted loss of independent life-years in Western countries. Thrombolysis is the treatment of choice for acute stroke within 3 hours after symptom onset. Treatment beyond the 3-hour time window has not been shown to be effective in any single trial; however, meta-analyses suggest a somewhat less but still significant effect within 3 to 6 hours after stroke. It seems reasonable to apply improved selection criteria that would allow one to differentiate patients with a relevant indication for thrombolytic therapy from those who do not have one. We present an overview of a diagnostic approach to acute stroke management that allows the clinician to individualize patient management based on pathophysiologic reasoning and not rigid time windows established by randomized controlled trials. Therefore, this review concentrates on giving the reader an integrated knowledge of the current status of thrombolytic therapy in stroke and then develops a treatment algorithm based on pathophysiologic information rendered by a multiparametric stroke magnetic resonance imaging protocol.

Premature coronary artery disease: clinical risk factors and prognosis.

Abstract: Coronary artery disease (CAD) that becomes manifest in young adults can have devastating consequences. Additionally, the study of young patients with CAD may provide insight into the genetic basis of coronary disease. Over the past few years, our understanding of risk factors in this population has been expanded to include social, environmental, and emotional factors. The identification of genetic markers for disease is just beginning. Also, it has recently been shown that CAD in young adults has a poor long-term prognosis, meaning that clinicians caring for these patients must be aggressive in risk factor control.

Dietary fats and oils: Technologies for improving cardiovascular health

Abstract: The role of dietary lipids in the etiology of coronary heart disease (CHD) continues to evolve as we gain a better understanding of the metabolic effects of individual fatty acids and their impact on surrogate markers of risk. A recent meta-analysis of 60 human studies suggests that for each 1% energy replacement of carbohydrates in the diet with saturated fat or trans fat, serum low-density lipoprotein cholesterol concentrations increase by 0.032 (1.23 mg/dL) and 0.04 mmol/L (1.54 mg/dL), respectively. Current dietary recommendations to keep saturated fat and trans fat intake as low as possible, and to increase the intake of cis mono-unsaturated and polyunsaturated fatty acids, as well as growing recognition of these recommendations by consumers and food regulatory agencies in the United States, have been major driving forces for the edible oil industry and food manufacturers to develop alternative fats and oils with nutritionally improved fatty acid compositions. As solutions for use of trans fatty acids are being sought, oilseeds with modified fatty acid compositions are being viewed as a means to provide such solutions. Additionally, oilseeds with modified fatty acid composition, such as enhanced content of long-chain omega-3 fatty acids or conjugated linoleic acid, have been developed as a way to increase delivery of these fatty acids directly into the food supply or indirectly as use for feed ingredients for livestock. New processing technologies are being utilized around the world to create dietary fats and oils with specific physiologic functions relevant to risk factors for cardiovascular disease.