Showing papers in "Current Atherosclerosis Reports in 2000"

Diabetes and cardiovascular disease.

Abstract: Cardiovascular disease (CVD) is the most frequent and costly complication of type 2 diabetes. In this review, we examine the impact of diabetes on CVD. Shedding some light on the diabetes/CVD relationship are epidemiologic studies, which focused on Native Americans, who collectively experienced little or no diabetes or CVD in the past, but experience both conditions in epidemic proportions today. Almost half of the Native Americans studied had diabetes at baseline. When CVD events were stratified by diabetic status, the relative CVD risk among diabetic men was twice that of nondiabetic men, and the risk among diabetic women was threefold that of nondiabetic women. Among all CVD events, diabetes accounted for 56% in men and 78% in women; most CVD deaths occurred in those with diabetes. Recent attention has focused on defining the relative strength of CVD risk factors in diabetic populations. In many populations, low-density lipoprotein (LDL) cholesterol is lower in diabetic individuals. However, in American Indians, every 10-mg/dL increase in LDL cholesterol has been associated with a 12% increase in CVD risk and every 10-mg/dL decrease in high-density lipoprotein (HDL) cholesterol was associated with an 8% increase in CVD risk. Albuminuria is an important predictor of CVD in diabetic populations. Those with macroalbuminuria had a CVD risk that was four to five times that of diabetic individuals without albuminuria. Other CVD risk factors in diabetes that have come under recent scrutiny in other populations are increased levels of fibrinogin, and C-reactive protein, and leukocytosis. Angiogenic response may be lower in diabetic individuals, and the possible role of infection is being examined in diabetic patients. LDL cholesterol and albuminuria should be the targets of preventive strategies, and promising new areas such as cytokines, growth factor, and the role of infection should be further explored.

Pleiotropic effects of statins.

Abstract: The advent of statin therapy has revolutionized the ability of the clinician to manage patients at risk for the development of an ischemic event due to dyslipidemia. Large-scale clinical trials involving thousands of patients in both primary and secondary prevention have clearly demonstrated that statin therapy will reduce cardiovascular mortality across a broad spectrum of patient subgroups. Additionally, in adequately powered trials, total mortality has been successfully decreased by the use of statin therapy. However, the precise mechanism underlying the benefit of statin therapy has been controversial due to the multiplicity of potential benefits that statins have demonstrated in addition to pure lipid lowering. The causal theory of pharmacologic benefit reiterates the lipid hypothesis, which states that dyslipidemia is central to the process of atherosclerosis and the clinical benefit which accrues from statin therapy is a function of the degree of lipid lowering. The noncausal theory supports the premise that clinical benefits are related primarily to pleiotropic effects of statins (endothelial function, inflammation, coagulation and plaque vulnerability) as being the major modulators of clinical benefit. This review will focus on the potential beneficial effects of statin therapy on a number of the pleiotropic effects of statins and the potential role that these activities play in the reduction of risk for ischemic events.

Atherosclerosis and diabetes: the RAGE connection.

Abstract: Diabetes mellitus begins as a disorder of glucose metabolism that progressively compromises the function of virtually every organ system as the secondary complications inexorably develop. The quality of life for patients with diabetes is diminished by the consequences of these complications. Accelerated and aggressive atherosclerosis is the greatest cause of morbidity and mortality with diabetes, emphasizing the importance of determining underlying mechanisms. This review highlights the role of the multiligand receptor for advanced glycation endproducts (RAGE) and two of its ligands, advanced glycation endproducts (AGEs) and S100/calgranulins, in the pathogenesis of atherosclerosis associated with diabetes. The results of the studies reviewed herein suggest that RAGE is a potential therapeutic target for macrovascular disease in diabetes.

Mechanism of action of niacin on lipoprotein metabolism.

Abstract: It is generally accepted that the increased concentrations of apolipoprotein (apo) B containing very low-density lipoproteins (VLDL) and low-density lipoproteins (LDL), and decreased levels of apo AI containing high-density lipoproteins (HDL) are correlated to atherosclerotic cardiovascular disease. Current evidence indicates that the post-translational apo-B degradative processes regulate the hepatic assembly and secretion of VLDL and the subsequent generation of LDL particles. The availability of triglycerides (TG) for the addition to apo B during intracellular processing appears to play a central role in targeting apo B for either intracellular degradation or assembly and secretion as VLDL particles. Based on the availability of TG, the liver secretes either dense TG-poor VLDL2 or large TG-rich VLDL1 particles, and these particles serve as precursors for the formation of more buoyant or small, dense LDL particles by lipid transfer protein- and hepatic lipase-mediated processes. HDLs are a heterogenous class of lipoproteins, and apo AI (the major protein of HDL) participates in reverse cholesterol transport, a process by which excess cholesterol is eliminated. Recent studies indicate that HDL particles containing only apo A-I (LPA-I) are more effective in reverse cholesterol transport and more anti-atherogenic than HDL particles containing both apo A-I and apo A-II (LPA-I+A-II).

The good smooth muscle cells in atherosclerosis.

Abstract: The formation of a fibrous cap made up of intimal smooth muscle cells and connective tissue is part of an attempt by the vessel wall to encapsulate the toxic products accumulating in the necrotic core of atherosclerotic lesions, and should be viewed as a beneficial healing response. In this review, we discuss the development of the intima and the potential origins of the intimal smooth muscle cell with a focus on the unique properties of these cells. We further discuss the role of intimal smooth muscle cells in plaque rupture and in wound healing, and the relationship of wound healing to the loss of lumen that occurs with development of advanced atherosclerotic lesions.

Lifestyle factors and stroke risk: exercise, alcohol, diet, obesity, smoking, drug use, and stress.

Abstract: Various lifestyle factors have been associated with increasing the risk of stroke. These include lack of exercise, alcohol, diet, obesity, smoking, drug use, and stress. Guidelines endorsed by the Centers for Disease Control and Prevention and the National Institutes of Health recommend that Americans should exercise for at least 30 minutes of moderately intense physical activity on most, and preferably all, days of the week. Recent epidemiologic studies have shown a U-shaped curve for alcohol consumption and coronary heart disease mortality, with low-to-moderate alcohol consumption associated with lower overall mortality. High daily dietary intake of fat is associated with obesity and may act as an independent risk factor or may affect other stroke risk factors such as hypertension, diabetes, hyperlipidemia, and cardiac disease. Homocysteine is another important dietary component associated with stroke risk, while other dietary stroke risk factors are thought to be mediated through the daily intake of several vitamins and antioxidants. Smoking, especially current smoking, is a crucial and extremely modifiable independent determinant of stroke. Despite the obstacles to the modification of lifestyle factors, health professionals should be encouraged to continue to identify such factors and help improve our ability to prevent stroke.

Triglyceride, Small, Dense Low-density Lipoprotein, and the Atherogenic Lipoprotein Phenotype

Abstract: This review provides an overview of the recent data evaluating triglyceride and low-density lipoprotein (LDL) size, two highly interrelated, genetically influenced, risk factors for cardiovascular disease (CVD). An examination of new epidemiologic studies continues to demonstrate that plasma triglyceride levels predict CVD. The first prospective study of the familial forms of hypertriglyceridemia has shown that relatives in familial-combined hyperlipidemia families are at increased risk for CVD mortality and that triglyceride levels predicted 20-year, CVD mortality among relatives in familial hypertriglyceridemia families. A meta-analysis of three, large-scale, prospective studies in men, and the first study to examine the correlation of LDL particle size distribution and vascular changes measured by B-mode ultrasound, add to growing evidence that small, dense LDL is atherogenic. Quantitative genetic analysis has recently shown substantial pleiotropic (common) genetic effects on triglyceride and LDL size. At least part of this may be explained by variation at the cholesterol ester transfer protein locus on chromosome 16, possibly through its role in reverse cholesterol transport. Taken together, these data provide new insights into the importance of triglyceride and LDL particle size for understanding genetic susceptibility to cardiovascular disease and its prevention.

Functional foods and cardiovascular disease.

Abstract: Functional foods are foods that, by virtue of physiologically active food components, provide health benefits beyond basic nutrition. Many functional foods have been found to be potentially beneficial in the prevention and treatment of cardiovascular disease, the leading cause of mortality in the United States. These foods include soybeans, oats, psyllium, flaxseed, garlic, tea, fish, grapes, nuts, and stanol- and sterol ester enhanced margarine. When eaten in adequate amounts on a consistent basis, these foods may aid in decreasing the risk of cardiovascular disease by several potential mechanisms: lowering blood lipid levels, improving arterial compliance, reducing low-density lipoprotein oxidation, decreasing plaque formation, scavenging free radicals, and inhibiting platelet aggregation.

Alcohol and cardiovascular disease.

Abstract: Alcohol in moderation is associated with lower risk of coronary heart disease in healthy men and women. New evidence suggests that this association, described in over 70 epidemiologic studies, is causal and can be explained, in part, by alcohol's beneficial effects on serum lipids and clotting factors. Recently, the inverse association between alcohol and cardiovascular disease also has been reported in populations with adult-onset diabetes and among individuals with previous cardiovascular disease. Although mounting evidence strongly supports the cardiovascular benefits of moderate alcohol consumption in most populations, clinical advice to abstainers to initiate daily alcohol consumption has not yet been substantiated in the literature and must be taken with caution and given on an individual basis.

Niacin dosing: Relationship to benefits and adverse effects

Abstract: Because of the original observation by Altschul et al., that nicotinic acid (niacin), not nicotinamide, in pharmacologic doses lowered human serum cholesterol levels, an avalanche of reports have been published over the past 45 years on the plasma lipid-regulating properties of this drug and its beneficial cardiovascular effects. A myriad of studies that have examined efficacy, safety, adverse effects, and pharmacologic properties of niacin rendered convincing evidence that niacin, used alone or combined with other agents, has favorable effects on serum lipoprotein regulation and on containment of atherothrombotic cardiovascular diseases. However, because of the unusual side effect profile of niacin and the availability of various formulations of this drug, niacin must be used prudently and with careful instruction and monitoring of patients. This review summarizes the pertinent and recent literature on niacin that impacts its therapeutic use. We also discuss some controversial issues and personal clinical experience and opinions on this topic.

Diet and Syndrome X.

Abstract: Syndrome X is a cluster of abnormalities, associated with resistance to insulin-mediated glucose uptake, that increases risk of coronary heart disease. Increased carbohydrate intake (with reciprocal decreased fat intake) within the boundaries of menus that can be followed in the free-living state have not been shown to decrease insulin resistance directly, by enhancing insulin sensitivity, or indirectly, by producing and maintaining weight loss. Moreover, such diets accentuate the metabolic abnormalities that constitute Syndrome X. Substitution of monounsaturated fat, polyunsaturated fat, or both for saturated fat results in the same reduction in low-density lipoprotein-cholesterol concentration as seen in diets low in fat and high in carbohydrates but without any untoward effects on the various manifestations of Syndrome X. Consequently, substituting unsaturated fat for saturated fat, without increasing intake of dietary protein or carbohydrate, may be useful for patients with hypercholesterolemia, Syndrome X, or both.

Peroxisome proliferator-activated receptors in vascular biology and atherosclerosis: Emerging insights for evolving paradigms

Abstract: Peroxisome Proliferator-Activated Receptors (PPARs), members of the steroid hormone nuclear receptor superfamily, act as ligand-activated transcription factors controlling the expression of specific target genes. Known PPAR isoforms include PPAR gamma, important in adipogenesis and lipid metabolism, PPAR alpha, implicated in fatty acid metabolism, and PPAR delta, about which the least is known. Recent work implicates PPAR alpha and gamma in vascular biology and atherosclerosis, and will be reviewed here. Such effects may have clinical implications given PPAR agonists in use as pharmacologic agents (eg, thiazolidinediones as insulin sensitizers [gamma] and fibric acids as lipid lowering agents [alpha]).

The role of proteinases in angiogenesis, heart development, restenosis, atherosclerosis, myocardial ischemia, and stroke: insights from genetic studies.

Abstract: The development of novel gene technologies in mice has provided an elegant tool to identify gene products that are causally linked to certain physiologic processes as well as the pathogenesis of numerous disorders. Using these techniques, three major proteolytic systems -- the plasminogen, the matrix metalloproteinase (MMP) and the coagulation systems -- have been shown to be involved in cardiovascular diseases, which still constitute the leading cause of death in Western societies. This overview summarizes the role of these proteolytic systems in angiogenesis, arterial stenosis, allograft transplant stenosis, vein graft stenosis, atherosclerosis, myocardial infarction, cardiac development and ischemic stroke and discusses possible therapeutic implications.

Dietary fiber prevents carbohydrate-induced hypertriglyceridemia.

Abstract: Plant foods rich in carbohydrate and dietary fiber have many health benefits. One concern often expressed about higher carbohydrate, lower fat diets is that they may increase fasting serum triglycerides. Recently the importance of hypertriglyceridemia as an independent risk factor for coronary heart disease has been reaffirmed. For 40 years, clinicians have noted “carbohydrate-induced hypertriglyceridemia” when persons were fed high-carbohydrate, low-fiber diets. The role of fiber in protecting from carbohydrate-induced hypertriglyceridemia has not been discussed by many reviewers. Systematic review of the literature documents that high fiber intakes clearly protect from carbohydrate-induced hypertriglyceridemia. These are reviewed. Thus, recent and earlier research indicates that use of a higher carbohydrate, higher fiber diet compared with a lower carbohydrate, higher fat diet is associated with a small reduction in fasting serum triglyceride values.

Dietary fiber and cardiovascular disease: experimental and epidemiologic advances.

Abstract: Recently reported experimental studies offer insight into the various mechanisms through which dietary fiber may reduce the risk of cardiovascular disease (CVD) in humans. Although most work has focused on traditional risk factors, studies have begun to explore less studied areas of risk such as fibrinolysis. Epidemiologic results have consistently demonstrated inverse associations between dietary fiber, particularly cereal fiber and whole grain foods, and the development of CVD morbidity and mortality. These associations have been observed in both men and women and are not accounted for by potential confounders such as other dietary and lifestyle factors; nor can they be fully explained by body habitus, antioxidants, and other nutrients found in fiber-rich foods. The evidence to date supports clear recommendations for a diet based on fiber-rich foods.

Does differing metabolism by cytochrome p450 have clinical importance

Abstract: The cytochrome P450 (CYP) is a group of enzymes that oxidatively modify drugs to a more water-soluble form for renal excretion. Nearly 50% of all clinically used medications and endogenous steroids are metabolized by the CYP enzyme 3A4, which explains why many of the important potential drug interactions involved this enzyme. Despite an excellent safety record, CYP 3A4 statins (lovastatin, simvastatin, atorvastatin) taken concomitantly with a potent CYP 3A4 inhibitor may increase the risk for adverse events (myopathy, rhabdomyolysis). This article describes the clinical significance of CYP metabolism as the pathways relate to the use of statins, including brief discussions on statins, fibrates, cyclosporine, and calcium channel blockers. In light of these potential interactions, continued vigilance by physicians is necessary to ensure the safe use of statins.

Postprandial lipemia and coronary risk.

Abstract: A number of cross-sectional studies have demonstrated that the magnitude of postprandial lipemia or single postprandial triglyceride values predict asymptomatic and symptomatic atherosclerosis, independent of risk factors measured in the fasting state. Postprandial lipemia reflects an integrated measure of an individual's triglyceride metabolic capacity. Numerous genetic and environmental factors that are known or suspected to affect triglyceride transport contribute to the magnitude of postprandial lipemia. In this article, mechanisms linking postprandial lipemia with the development and progression of atherosclerosis are described, and determinants of the extent and duration of postprandial lipemia are discussed.

Re-emergence of fibrates in the management of dyslipidemia and cardiovascular risk.

Abstract: It is now widely accepted that low-density lipoprotein (LDL) is not the only atherogenic component of the lipid profile and that abnormalities in the metabolism and plasma levels of triglycerides and high-density lipoprotein (HDL) may lead to accelerated growth of atherosclerotic lesions. Fibrates are the drugs of first choice in the management of hypertriglyceridemia, and are also able to substantially raise HDL. The recently published Veterans Administration-High-density Lipoprotein Intervention Trial (VA-HIT) trial showed that fibrate treatment in patients with coronary heart disease (CHD), low HDL, modestly elevated triglycerides, and normal LDL reduces the risk of a recurrent coronary event by 25%. A reasonable approach to the dyslipidemic patient with high CHD risk is to tailor the intervention to the specific lipoprotein abnormality. Under these assumptions fibrate therapy should become widespread, considering that the most common lipid alteration in CHD and patients with diabetes is low HDL and high triglycerides.

Diet and coronary heart disease: clinical trials.

Abstract: Dietary intervention trials using coronary heart disease (CHD) mortality and morbidity as endpoints have demonstrated that restriction of dietary total and saturated fat or replacement of the latter with polyunsaturated fatty acids (PUFAs), in particular n-3 PUFAs, is of great benefit with respect to CHD risk. This is likewise the case for intervention trials using angiographic endpoints, with many studies showing that such diets not only retard progression of coronary atherosclerosis but can cause regression as well. The role that antioxidants, such as vitamin E, may play in the development and progression of CHD is less clear. The results of large-scale clinical trials evaluating the effect of vitamin E supplementation on CHD risk do not support the concept that this agent is cardioprotective. The purpose of this report is to review dietary intervention trials that support a direct relationship between diet, lipoproteins, and CHD risk.

The role of lipoprotein[a] in atherosclerosis.

Abstract: Recent studies confirm and extend previous evidence that lipoprotein[a] (Lp[a]) plays a significant role in atherosclerosis and is one of the top five or six risk factors for cardiovascular disease. In Japanese patients, Lp[a] levels and apo[a] phenotypes are significant predictors for myocardial infarction. Lp[a] levels are significantly higher in ischemic stroke patients than in controls. However, plasma concentrations of Lp[a] are not predictive of ischemic cerebral infarction in either men or women. Serum Lp[a] levels are significantly higher in patients with carotid plaques or measurable intima-media thickness than in controls without. Despite these associations, there is no significant relationship between Lp[a] level and arterial endothelial function, smooth muscle response, or carotid wall thickness, even though other lipid risk factors like low-density lipoprotein cholesterol (LDL-C) and LDL-C/high-density lipoprotein cholesterol (HDL-C) ratio are correlated with abnormal arterial function and structure. There is new evidence that the association of Lp[a] with extracellular matrix (ECM) secreted by arterial smooth muscle cells increases two- to threefold the subsequent specific binding of LDL. Alpha-defensins released from activated or senescent neutrophils stimulate the binding of Lp[a] to ECM of endothelial cells. Several factors that affect the accumulation of Lp[a] and oxidized LDL in the arterial intima have been identified. Several recent studies have provided new insights into the physiologic role that Lp[a] might play in compromising fibrinolysis. The interaction of Lp[a] with cells is clearly distinct from that with ECM and with fibrinogen; the regulation sites within Lp[a] and plasminogen for these regulatory molecules are not identical. These recent advances bring us significantly closer to understanding how Lp[a] exerts its atherogenic and thrombogenic properties.

Advances in neuroimaging of acute stroke.

Abstract: As therapeutic options for treating acute stroke evolve, neuroimaging strategies are assuming an increasingly important role in the initial evaluation and management of patients. There is a recognized need for objective neuroimaging methods to identify the best candidates for early intervention. Both acute and long-term treatment decisions for stroke patients should optimally incorporate information provided by neuroimaging studies regarding tissue viability (eg, size, location, vascular distribution, degree of reversibility of ischemic injury, presence of hemorrhage), vessel status (site and severity of stenoses and occlusions), and cerebral perfusion (size, location, and severity of hypoperfusion). The ability to acutely identify the ischemic penumbra and to use this information to make treatment decisions may be within reach, particularly with the multimodal data provided by magnetic resonance techniques. This article will review recent developments in the field of neuroimaging of acute stroke and discuss the clinical applications of specific techniques of magnetic resonance imaging, computed tomography, positron emission tomography, single photon emission tomography, catheter angiography, and ultrasound imaging.

Mouse Models of Lipodystrophy

Abstract: Lipodystrophies are a group of heterogeneous diseases characterized by the loss of adipose tissue and by abnormalities of carbohydrate and lipid metabolism, including insulin resistance, diabetes, and hyperlipidemia. In this review, we describe several mouse models that recapitulate various aspects of the lipodystrophy syndrome, offering insights into the etiology of this condition and potential therapeutic approaches. Studies on these mice suggest that adipose is the primary tissue affected in lipodystrophy, and that secondary leptin deficiency may be responsible for the associated insulin resistance.

High-density lipoprotein metabolism: molecular targets for new therapies for atherosclerosis.

Abstract: New therapeutic approaches to the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD) are needed. Plasma levels of high-density lipoprotein (HDL) cholesterol are inversely associated with risk of ASCVD. Genes involved in the metabolism of HDL represent potential targets for the development of such therapies. Because HDL metabolism is a dynamic process, the effect of a specific HDL-oriented intervention on atherosclerosis cannot necessarily be predicted by its effect on the plasma HDL cholesterol level. Based on available data in animal models, some gene products are candidates for pharmacologic upregulation, infusion, or overexpression, including apolipoprotein (apo)A-I, apoE, apoA-IV, lipoprotein lipase (LPL), ATP-binding cassette protein 1 (ABC1), lecithin cholesterol acyltransferase (LCAT), and scavenger receptor B-I (SR-BI). In contrast, some gene products are potential candidates for inhibition, including apoA-II, cholesteryl ester transfer protein (CETP), and hepatic lipase. The next decade will witness the transition from preclinical studies to clinical trials of a variety of new therapies targeted toward HDL metabolism and atherosclerosis.

Cholesterol, stroke risk, and stroke prevention.

Abstract: Serum cholesterol traditionally has been considered a poor predictor of total stroke risk; however, it is associated positively with ischemic stroke risk and associated negatively with hemorrhagic stroke risk. Although studies failed to demonstrate stroke reduction using older cholesterol-lowering medications, recent study of the statin class of medications shows both consistent stroke and other cardiovascular benefits. Ischemic stroke and coronary heart disease share similar underlying mechanisms, likely explaining much of the therapeutic benefit from statins. Current research is directed at further determining groups of patients most likely to benefit from lipid reduction in stroke prevention. In the interim, patients with established atherosclerosis should be treated with a statin to achieve a low-density lipoprotein cholesterol level less than 100 mg/dL.

Regulation of cell migration in atherosclerosis

Abstract: In response to vascular injury, monocytes and smooth muscle cells migrate to the intimal space, resulting in the formation of atherosclerotic and restenotic lesions. Several different growth factors and cytokines have been identified as mediators of cellular migration in the development of neointimal lesions. The principle mediator of monocyte adhesion and recruitment to the injured vascular wall is monocyte chemotactic protein-1. Moreover, recent studies have demonstrated that the atherogenic properties of angiotensin II are due to its ability to induce monocyte chemotactic protein-1 and promote monocyte migration to the vascular wall. Ligand-induced activation of receptor tyrosine kinases are the principle mechanism for smooth muscle cell migration following vascular injury. The signaling pathways mediating receptor-tyrosine kinase-induced migration of smooth muscle cells are also discussed.

The role of diet in the prevention and treatment of hypertension.

Abstract: An impressive body of evidence strongly supports the concept that multiple dietary factors influence blood pressure and that modification of diet can have powerful, beneficial effects on this highly prevalent, yet modifiable, cardiovascular risk factor. Dietary therapies with a proven ability to lower blood pressure include reduced sodium intake, weight loss, moderation of alcohol intake, increased potassium intake, and a diet that emphasizes fruits, vegetables, and low-fat dairy products that is low in fat and cholesterol. Several other dietary factors, such as an increased intake of protein or monounsaturated fatty acids, may also reduce blood pressure, but evidence to date is insufficient for policy recommendations. Still, widespread implementation of those therapies with a proven ability to lower blood pressure should have an enormous impact on the adverse patterns of blood pressure that remain highly prevalent in the United States and most other countries.

Antioxidants and vitamins to reduce cardiovascular disease.

Abstract: Cardiovascular disease is the leading cause of morbidity and mortality in Western populations. Several lines of evidence support the role of oxidative stress in atherogenesis. Dietary micronutrients with antioxidant properties and vitamins have also been shown to have a benefit with regards to cardiovascular disease. The most persuasive evidence relates to alpha tocopherol and folate and vitamin B(12). Although the evidence is mounting for supplementation with alpha tocopherol and folate and B(12) for secondary prevention of cardiovascular disease, no clear consensus can be reached for primary prevention of cardiovascular disease. This will have to await results of ongoing clinical trials.

Do pleiotropic effects of statins beyond lipid alterations exist in vivo? What are they and how do they differ between statins?

Abstract: The inhibition of cellular proliferation, the restoration of endothelial activity, the inhibition of platelet reactivity, and an antioxidant potential are only a few examples of pleiotropic effects of statins. This review analyzes the current knowledge on the pleiotropic properties of this class of drugs and examines the relevant data that support the presence of these effects in vivo. The favorable outcome of major trials of statins has indicated that pleiotropic factors indeed play a role in cardiovascular protection. In addition, recent data indicate that many pleiotropic effects influence mechanisms that belong to the extravascular compartment, as well. Perhaps, some of these properties may eventually justify additional indications for statins and improve the treatment of other diseases, including inflammation and cancer.

Perspectives on Cardiac Allograft Vasculopathy

Abstract: Allograft arteriopathy, the slowly progressive, diffuse, atherosclerosis noted often after heart transplant, and also called chronic rejection, is the most common cause of late cardiac graft failure and patient death. The process is multifactorial, rooted in both immune and nonimmune factors that can be coupled to passenger atherosclerosis moved with the donor heart, as well as initially nondiseased endothelium. Great insight has emerged from experimental models and intravascular ultrasound study of patients, but treatments are still crude and produce less than optimal results. Nonetheless, it has been demonstrated that diltiazem, pravastatin, ganciclovir, newer immunosuppressive agents, and photophoresis may be helpful. In the future, better control of the allograft immunologic response will likely be the key to attenuating development of this form of atherosclerosis.

Poor compliance: The hidden risk factor

Abstract: Poor compliance with prescribed regimens remains a potent barrier to good outcomes in coronary heart disease and other chronic diseases. Such poor compliance is related to disease, patient, provider, and treatment factors and has yet to be fully understood. In general, the less complex the regimen, the better informed the patient and the physician, and the more serious the disease, the better the compliance.