Showing papers in "Current Atherosclerosis Reports in 2009"
Journal Article•
436 citations
TL;DR: Individuals with elevated levels of hs-CRP of greater than 3 mg/L had a 1.6 and 1.3-fold increased risk for ischemic heart disease andIschemic cerebrovascular disease, respectively, compared with individuals with less than 1mg/L, but this was not associated with increased cardiovascular events.
Abstract: Results: Individuals with elevated levels of hs-CRP of greater than 3 mg/L had a 1.6and 1.3-fold increased risk for ischemic heart disease and ischemic cerebrovascular disease, respectively, compared with individuals with hs-CRP of less than 1 mg/L. Individuals with hs-CRP polymorphism had a 64% increase in hs-CRP, but this was not associated with increased cardiovascular events. In contrast, individuals with apolipoprotein E polymorphism had elevated cholesterol levels and increased risk for ischemic heart disease.
266 citations
TL;DR: The apoA-I mimetic peptide 4F increased the formation of pre-β high-density lipoprotein, increased cholesterol efflux, and reduced lipop protein oxidation in vitro; it increased antioxidants and vascular repair in type 1 diabetic rats; it improved high- density lipop Protein inflammatory properties in humans with coronary heart disease.
Abstract: Recent publications reveal the mechanism of action of apolipoprotein A-I (apoA-I) mimetic peptides to be the remarkable binding affinity that oxidized lipids have for these peptides compared with apoA-I. There was no difference in the binding affinity of oxidized lipids or in peptide efficacy in reducing inflammation and atherosclerosis in rabbits injected with peptides synthesized from all D- or all L-amino acids. The apoA-I mimetic peptide 4F increased the formation of pre-β high-density lipoprotein, increased cholesterol efflux, and reduced lipoprotein oxidation in vitro; it increased antioxidants and vascular repair in type 1 diabetic rats; it improved vasodilation, oxidative stress, myocardial inflammation, and angiogenic potential in a mouse model of scleroderma; it reduced renal inflammation in low-density lipoprotein receptor-null mice fed a Western diet; it reduced arthritis in a rat model; it reduced adiposity, increased adiponectin levels, and improved insulin sensitivity in obese mice; and it improved high-density lipoprotein inflammatory properties in humans with coronary heart disease.
183 citations
TL;DR: The role of OPN in vascular calcification (VC), which is closely related to chronic and active inflammation, is that of a negative regulator because it is an inhibitor of calcification and an active inducer of decalcification.
Abstract: Osteopontin (OPN) was initially identified in osteoblasts as a mineralization-modulatory matrix protein. Recently, OPN has been studied as a multifunctional protein that is upregulated in a variety of acute and chronic inflammatory conditions, such as wound healing, fibrosis, autoimmune disease, and atherosclerosis. OPN is highly expressed at sites with atherosclerotic plaques, especially those associated with macrophages and foam cells. In the context of atherosclerosis, OPN is generally regarded as a proinflammatory and proatherogenic molecule. However, the role of OPN in vascular calcification (VC), which is closely related to chronic and active inflammation, is that of a negative regulator because it is an inhibitor of calcification and an active inducer of decalcification. OPN expression and its regulatory molecular mechanisms remain elusive during the process of VC. Therefore, further research with regard to the role of OPN in diseases associated with VC is needed to identify potential OPN-related therapeutic targets.
168 citations
TL;DR: This article reviews the three known members of the paraoxonase family and the evidence that supports their likely role in the development and progression of atherosclerosis.
Abstract: Management of serum low-density lipoprotein has been a cornerstone of cardiovascular medicine for the past two decades. More recently, the attention paid to the protective role of high-density lipoprotein (HDL) in atherosclerosis has increased substantially, particularly with respect to the antioxidant properties of HDL. Considerable evidence supports the notion that the paraoxonase gene family is largely responsible for the antioxidant properties of HDL. This article reviews the three known members of the paraoxonase family and the evidence that supports their likely role in the development and progression of atherosclerosis.
117 citations
TL;DR: The purpose of this review is to examine the extent to which biomarkers like the omega-3 index qualify as coronary heart disease risk markers and/or risk factors based on new criteria from the American Heart Association and older guidelines proposed in 1965 by Sir Austin Bradford Hill.
Abstract: Blood levels of omega-3 fatty acids reflect the interplay of metabolism and the intake of omega-3-rich foods (eg, oily fish). Multiple lines of evidence link reduced tissue and/or blood levels of omega-3 fatty acids, as reflected in the erythrocyte eicosapentaenoic acid plus docosahexaenoic acid level (ie, the omega-3 index), with increased risk for coronary heart disease, especially sudden cardiac death. The purpose of this review is to examine the extent to which biomarkers like the omega-3 index qualify as coronary heart disease risk markers and/or risk factors based on new criteria from the American Heart Association and older guidelines proposed in 1965 by Sir Austin Bradford Hill. These standards include consistency, strength of association, biological plausibility, coherence, dose-response relationship, clinical utility, cost effectiveness, and prospective validation. The omega-3 index appears to fulfill many of the requirements for a risk marker and, more importantly, for a risk factor.
114 citations
TL;DR: This review examines the published studies about the use of carotenoids, especially lycopene and astaxanthin, in the treatment of cardiovascular diseases to suggest that more hypothesisdriven and rigorous clinical trial designs are needed.
Abstract: Carotenoids are a class of natural fat-soluble pigments found principally in plants. They have potential antioxidant biological properties due to their chemical structure and interaction with biological membranes. The most abundant carotenoids in the diet are β-carotene, lycopene, lutein, β-cryptoxanthin, zeaxanthin, and astaxanthin. Numerous epidemiologic studies have supported the hypothesis that antioxidants could be used as an inexpensive means of prevention, and possibly treatment, of cardiovascular diseases, even though findings from interventional trials have been mixed, with some positive findings, many null findings, and some suggestion of harm in certain high-risk populations. Recent smaller interventional studies with carefully chosen populations, such as those under high levels of oxidative stress, have yielded largely positive results. This suggests that we need more hypothesisdriven and rigorous clinical trial designs. The aim of this review is to examine the published studies about the use of carotenoids, especially lycopene and astaxanthin, in the treatment of cardiovascular diseases.
107 citations
TL;DR: The fact that Wnt5A signaling can be modulated by anti-inflammatory mediators makes this effector molecule an attractive target for therapeutic intervention in inflammatory diseases.
Abstract: Wnt proteins are members of the highly conserved wingless family of proteins responsible for cell differentiation and development and for neoplastic and degenerative processes. Recently, Toll-like receptor-mediated Wnt signaling was found to be associated with innate immunity in Drosophila. Upregulation of Wnt5A in human macrophages upon microbial challenge indicated a similar mechanism. Toll-like receptor-mediated Wnt5A expression is a key process for sustained inflammatory macrophage activation through autocrine and paracrine signaling. Downregulation of Wnt5A expression and subsequent attenuation of inflammatory macrophage responses by activated protein C supports the link between inflammation and coagulation, another highly conserved biologic system. Direct evidence for the relevance of Wnt5A in severe systemic inflammation is provided by the finding of higher Wnt5A levels in patients with sepsis than in healthy individuals. The fact that Wnt5A signaling can be modulated by anti-inflammatory mediators makes this effector molecule an attractive target for therapeutic intervention in inflammatory diseases.
85 citations
TL;DR: This review focuses on recent work identifying circulating oxylipins, primarily esterified with lipoprotein lipids, and their effects on markers of endothelial dysfunction.
Abstract: Eicosanoids, including epoxyeicosatrienoic acids, hydroxyeicosatetraenoic acids, and other oxylipins derived from polyunsaturated fatty acids, have emerging roles in endothelial inflammation and subsequent atherosclerosis. Unlike eicosanoids in the prostanoid series, they are known to be esterified in cell lipids such as phospholipids and triglycerides; however, our understanding of these reservoirs is in its infancy. This review focuses on recent work identifying circulating oxylipins, primarily esterified with lipoprotein lipids, and their effects on markers of endothelial dysfunction. These oxylipins are known to be released by at least one lipase (lipoprotein lipase) and to mediate increased expression of inflammatory markers in endothelial cells, which coincides with the known roles of lipoproteins in endothelial dysfunction. The implications of the lipolytic release of lipoproteinbound oxylipins for the inflammatory response, challenges to analysis of this oxylipin compartment, and the potential importance of non-arachidonatederived oxylipins are discussed.
77 citations
TL;DR: Diet and lifestyle modification, combined with pharmacologic treatment of hypertension and high lipid levels (if necessary), could prevent the vast majority of CHD events.
Abstract: Coronary heart disease (CHD) stems from the interplay between genetic and environmental factors. However, modifiable environmental factors, especially diet and lifestyle, are largely responsible for increased risk of CHD at population levels. Although cigarette smoking, obesity, and physical inactivity are well-established causes of CHD, the role of specific dietary factors has not been clearly defined until more recently. Cumulative evidence indicates that types of fats and carbohydrates are more important than total amounts in determining risk of CHD. Epidemiologic and clinical trial data strongly support that dietary patterns rich in fruits, vegetables, whole grains, and nuts can reduce risk of CHD. Diet and lifestyle modification, combined with pharmacologic treatment of hypertension and high lipid levels (if necessary), could prevent the vast majority of CHD events.
69 citations
TL;DR: Emerging evidence suggests that MCP-1 plasma levels have prognostic value in the acute and chronic phase following ACS, providing information independent of standard clinical variables.
Abstract: The CC chemokine monocyte chemoattractant protein (MCP)-1/CCL2 is involved in the formation, progression, and destabilization of atheromatous plaques and plays an essential role in postinfarction remodeling. These properties generated significant interest in the potential significance of MCP-1 as a biomarker in acute coronary syndromes (ACS). Emerging evidence suggests that MCP-1 plasma levels have prognostic value in the acute and chronic phase following ACS, providing information independent of standard clinical variables. The mechanisms responsible for adverse prognosis in patients with elevated plasma MCP-1 following ACS remain unknown. High plasma MCP-1 levels may reflect a higher burden of atherosclerotic disease, may exert prothrombotic effects resulting in recurrent coronary events, or may identify patients who mount a more intense cardiac inflammatory reaction following a coronary event, resulting in enhanced adverse remodeling. Beyond its prognostic significance, the MCP-1 axis may be an attractive target for therapy in patients with ACS.
TL;DR: The demonstration of a circadian variation in frequency of onset of myocardial infarction, sudden cardiac death, and stroke provides an opportunity to gain insight into the mechanism of transformation from chronic stable to acute unstable manifestation of cardiovascular disease.
Abstract: The demonstration of a circadian variation in frequency of onset of myocardial infarction, sudden cardiac death, and stroke provides an opportunity to gain insight into the mechanism of transformation from chronic stable to acute unstable manifestation of cardiovascular disease. Contributing physiologic changes that exhibit a morning peak include arterial pressure, heart rate, and vascular tone, which promote plaque rupture, together with increased platelet reactivity and reduced fibrinolytic activity. The study of circadian rhythm also has implications for triggering of disease onset by external stressors. Further study of this area will provide insight into new approaches to prevent disease onset.
TL;DR: The multiple adverse effects and implicated pathways are consistent with the observed strong associations of TFA consumption with CHD risk, and explain why T FA consumption may adversely impact other non-CHD diseases and end points.
Abstract: Consumption of industrially produced trans-fatty acids (TFA) is associated with substantial risk of coronary heart disease (CHD). The magnitude of this relationship, as well as emerging associations with end points such as diabetes and sudden cardiac death, cannot be fully explained by the well-established adverse effects of TFA on serum lipids. We review the evidence for effects of TFA intake on nonlipid risk factors. Based on evidence from randomized controlled trials, observational studies, animal experiments, and in vitro studies, these include effects on systemic inflammation, endothelial dysfunction, visceral adiposity, insulin resistance, and arrhythmic risk. The types and strength of evidence for each of these nonlipid effects varies, but the overall constellation of findings is qualitatively and quantitatively unique among dietary fats. The multiple adverse effects and implicated pathways are consistent with the observed strong associations of TFA consumption with CHD risk. These nonlipid effects also explain why TFA consumption may adversely impact other non-CHD diseases and end points.
TL;DR: The analytical power of modern proteomic technologies could facilitate the understanding of vulnerable plaques and lead to the discovery of novel therapeutic targets and diagnostic biomarkers.
Abstract: Acute coronary syndromes (ACS), such as unstable angina, acute myocardial infarction, and sudden cardiac death, are commonly associated with the presence of vulnerable plaques in coronary arteries. Rupture or erosion of vulnerable plaques results in the formation of luminal thrombi due to the physical contact between platelets and thrombogenic elements within the atherosclerotic lesions. Considering the socioeconomic burden of ACS, it is imperative that the scientific community achieves a clear understanding of the multifaceted pathophysiology of vulnerable atheroma to identify accurate prognostic biomarkers and therapeutic targets. The analytical power of modern proteomic technologies could facilitate our understanding of vulnerable plaques and lead to the discovery of novel therapeutic targets and diagnostic biomarkers.
TL;DR: Current evidence on the association between dietary cholesterol and the risk of CHD is reviewed and higher plasma levels of low-density cholesterol are associated with an increased risk of coronary disease.
Abstract: Coronary heart disease (CHD) remains one of the leading causes of death in the United States and other industrialized nations. A better understanding of modifiable risk factors for CHD is critical in order to effectively prevent this disease. Dietary factors known to influence the risk of CHD include saturated fats, trans-fats, and polyunsaturated fatty acids. Although higher plasma levels of low-density lipoprotein cholesterol are associated with an increased risk of coronary disease and lipid-lowering therapy has been shown to reduce the risk of cardiovascular disease, the relation between dietary cholesterol and the risk of CHD is not clearly understood. This article reviews the current evidence on the association between dietary cholesterol and the risk of CHD.
TL;DR: Sustained selective release of proinflammatory mediators without degranulation may also occur at sites of chronic inflammation, suggesting a novel link between inflammation and atherogenesis.
Abstract: Mast cells (better known as allergy cells) are proinflammatory effector cells present in the human arterial intima and in evolving atherosclerotic lesions. Experiments in vitro, in vivo experiments in animals, and immunohistologic studies of human coronary samples have uncovered mechanisms by which activated mast cells could participate in the development of the lesions. When activated, mast cells acutely expel a fraction of their cytoplasmic granules, which are filled with a wide selection of heparin-bound preformed mediators. These include histamine, neutral proteases, growth factors, and proinflammatory cytokines. The microenvironmental targets of these effector molecules are various lipoprotein particles in the intimal fluid, components of the extracellular matrix, and intimal cells neighboring the activated mast cells. Importantly, sustained selective release of proinflammatory mediators without degranulation may also occur at sites of chronic inflammation. The activities of the various mediators are suggested to contribute to fatty streak formation and to the generation of unstable plaques susceptible to rupture. Thus, mast cells appear to provide a novel link between inflammation and atherogenesis.
TL;DR: There remains an unmet need to reduce elevated low-density lipoprotein cholesterol (LDL-C) in patients who are maximized on current therapy or intolerant to statins.
Abstract: There remains an unmet need to reduce elevated low-density lipoprotein cholesterol (LDL-C) in patients who are maximized on current therapy or intolerant to statins. Several novel agents have been developed to lower LDL-C, either as monotherapy or in combination with statins. These novel therapies include squalene synthase inhibitors, microsomal triglyceride transfer protein inhibitors, and antisense apolipoprotein B. Although each of these novel therapies effectively lowers LDL-C, challenges remain in the clinical development to assess long-term safety.
TL;DR: This article presents a series of examples from prominent published studies in which apoB and non-HDL-C differ so dramatically that diagnosis and therapy would truly differ depending on which index was used by the physician.
Abstract: The high correlation between apolipoprotein B (apoB) and non-high-density lipoprotein cholesterol (non-HDL-C) is the chief argument employed against introducing apoB into clinical practice. However, high correlation does mean that non-HDL-C and apoB will often yield similar clinical information. Nevertheless, the critical issue is not how often the two tests agree, but how often, and how substantially, they differ. In other words, how often would an apoB result change a clinical decision based on a value for non-HDL-C? This article presents a series of examples from prominent published studies in which apoB and non-HDL-C differ so dramatically that diagnosis and therapy would truly differ depending on which index was used by the physician. These examples establish that apoB and non-HDL-C are not clinical equivalents.
TL;DR: The results of these trials have supported the viability of the potential of HDL and/or apoA-I infusions as a possible therapeutic strategy for the treatment of coronary artery disease.
Abstract: Strategies to decrease the progression and burden of atherosclerosis by capitalizing on the protective effect of high-density lipoprotein (HDL) and/or apolipoprotein A1 (apoA-I) levels remain active. Although efforts to raise HDL through the administration of oral agents are still being pursued, the disappointing results demonstrated with torcetrapib, an agent that elevated serum HDL and apoA-I levels through the inhibition of cholesterol ester transfer protein, have raised questions regarding this approach. An alternate strategy that consists of short-term infusions of reconstituted HDL or apoA-I is currently under evaluation. Several infusion compounds have been evaluated in clinical trials that utilize cardiovascular imaging technologies and biomarkers to assess potential clinical efficacy. Although these compounds are still in early-stage development, the results of these trials have supported the viability of this line of investigation. This review addresses the potential of HDL and/or apoA-I infusions as a possible therapeutic strategy for the treatment of coronary artery disease.
TL;DR: New findings indicate that niacin does the following: 1) it inhibits hepatic diacylglycerol acyltransferase 2, resulting in inhibition of triglyceride synthesis and decreased apolipoprotein B-containing lipoproteins; 2) it decreases the surface expression of hepatic adenosine triphosphate synthase β-chain, leading to decreased holoparticle high- density lipoprotein catabolism and increased high-density lipop Protein levels.
Abstract: Niacin has long been used in the treatment of dyslipidemia and cardiovascular disease. Recent research on niacin has been focused on understanding the mechanism of action of niacin and preparation of safer niacin formulations. New findings indicate that niacin does the following: 1) it inhibits hepatic diacylglycerol acyltransferase 2, resulting in inhibition of triglyceride synthesis and decreased apolipoprotein B-containing lipoproteins; 2) it decreases the surface expression of hepatic adenosine triphosphate synthase β-chain, leading to decreased holoparticle high-density lipoprotein catabolism and increased high-density lipoprotein levels; and 3) it increases redox potential in arterial endothelial cells, resulting in inhibition of redox-sensitive genes. Flushing, an adverse effect of niacin, results from niacin receptor GPR109A-mediated production of prostaglandin D2 and E2 via DP1 and EP2/4 receptors. DP1 receptor antagonist (laropiprant) attenuates the niacin flush. A reformulated preparation of extended-release niacin (Niaspan; Abbott, Abbott Park, IL) lowers flushing compared with an older Niaspan formulation. These advancements in niacin research have rejuvenated its use for the treatment of dyslipidemia and cardiovascular disease.
TL;DR: Cardiovascular risk appears especially elevated at 25-hydroxy-vitamin D levels below 10 or 15 ng/mL, and optimal levels may be at least 30 ng/L, among individuals who are not receiving substantial exposure to sun, intakes of 1000 to 2000 IU may be needed to achieve levels of at least30 ng/ mL.
Abstract: Recent studies indicate that deficient vitamin D status may increase risk of both ischemic and nonischemic cardiovascular diseases independently of established cardiovascular risk factors. The role of vitamin D in potentially regulating many functions in the cardiovascular system is just beginning to be understood. Among the potentially relevant mechanisms for cardiovascular diseases, vitamin D may influence blood pressure through the renin-angiotensin system, parathyroid hormone levels, myocardial function, inflammation, and vascular calcification. Cardiovascular risk appears especially elevated at 25-hydroxy-vitamin D levels below 10 or 15 ng/mL, and optimal levels may be at least 30 ng/mL. Among individuals who are not receiving substantial exposure to sun, intakes of 1000 to 2000 IU may be needed to achieve levels of at least 30 ng/mL. Further study, including properly designed randomized control trials, is required to further establish the role of vitamin D on cardiovascular diseases.
TL;DR: Routine serum creatinine monitoring is advisable in fibrate-treated patients, particularly in those with preexisting renal disease, and a 30% increase in serum Creatinine values in the absence of other causes of serumCreatinine change warrants discontinuation of fibrates.
Abstract: Fibrates are a class of lipid-lowering medications primarily used as second-line agents behind statins. The adverse-effect profile of fibrates has been marked by a puzzling yet reversible rise in serum creatinine values with their use. It is not known whether this finding represents a true change in renal function. One proposed explanation for this phenomenon is that fibrates increase the production of creatinine, in which case a rise in serum creatinine values would not represent a true deterioration in renal function. An alternative theory is that fibrates reduce the production of vasodilatory prostaglandins, which would lead to a true change in renal function in patients who experience a rise in serum creatinine values. Routine serum creatinine monitoring is advisable in fibrate-treated patients, particularly in those with preexisting renal disease. A 30% increase in serum creatinine values in the absence of other causes of serum creatinine change warrants discontinuation of fibrate therapy. Serum creatinine values can take several weeks to return to their baseline values following discontinuation of a fibrate.
TL;DR: This article reviews recent studies that address the relationship of CRP gene polymorphisms to inflammation and cardiovascular risk and sets out the priorities for further research into this area.
Abstract: Interest in C-reactive protein (CRP) and the association of its serum level in apparently healthy individuals to their cardiovascular disease risk has soared over the past decade. Recent studies have shown that the interindividual variations in CRP levels not only reflect environmental cues but are also a consequence of the genetic variation in the CRP gene itself. The importance of the relationship of CRP gene variants to CRP serum level and cardiovascular disease risk is important to establish CRP gene profiling as a clinical risk prediction tool and also to help test the cause-effect relationship between CRP and vascular disease. This article reviews recent studies that address the relationship of CRP gene polymorphisms to inflammation and cardiovascular risk.
TL;DR: The results and implications of recent studies on the effects of lipoprotein lipase on vascular inflammation are summarized, expanding upon existing controversy among human postprandial studies, animal models, and in vitro experimental models.
Abstract: Although hypertriglyceridemia has repeatedly been implicated as an atherogenic condition, there are conflicting reports concerning the atherogenicity of products released from triglyceride-rich lipoproteins by lipoprotein lipase. The hydrolysis of triglyceride is a normal process by which chylomicrons and very low-density lipoproteins are metabolized and cleared from the circulation, which would suggest a beneficial role for lipoprotein lipase in reducing circulating levels of triglyceride and, therefore, reducing atherosclerotic burden. However, many in vitro studies have shown that lipolysis products such as fatty acids induce vascular cell inflammation, which can initiate or exacerbate atherosclerosis. This review summarizes the results and implications of recent studies on the effects of lipoprotein lipase on vascular inflammation, expanding upon existing controversy among human postprandial studies, animal models, and in vitro experimental models.
TL;DR: Therapeutic intervention with fibric acid derivatives and omega-3 fish oils is associated with significant reductions in both fasting and postprandial serum triglyceride concentrations, and a variety of prospective, placebo-controlled clinical trials have shown that these agents significantly impact risk for multiple cardiovascular end points.
Abstract: The reduction of low-density lipoprotein cholesterol in patients at risk for acute cardiovascular events is the cornerstone of lipid management in both the primary and secondary prevention settings. Serum triglyceride levels exceeding 150 mg/dL are abnormal and confer increased risk for developing coronary artery disease in both men and women. Serum triglycerides are derived from both dietary and endogenous biosynthetic pathways. Triglyceride metabolism has a complex regulatory circuitry and intimately impacts the production and disposal of multiple lipoprotein species. Hypertriglyceridemia is highly prevalent and is associated with multiple forms of dyslipidemia but tends to be undertreated. Therapeutic intervention with fibric acid derivatives and omega-3 fish oils is associated with significant reductions in both fasting and postprandial serum triglyceride concentrations. A variety of prospective, placebo-controlled clinical trials have also shown that these agents significantly impact risk for multiple cardiovascular end points.
TL;DR: This review summarizes current concepts of statin myopathy and presents strategies to minimize statinassociated myopathic complaints.
Abstract: 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are safe and effective in lowering low-density lipoprotein cholesterol As a result, they confer an all-cause mortality benefit across a wide range of patient groups The utility of statins is limited by their adverse effects, including myalgias and rhabdomyolysis These clinical events, plus other symptoms, constitute what is termed statin myopathy This review summarizes current concepts of statin myopathy and presents strategies to minimize statinassociated myopathic complaints
TL;DR: The favorable effects of n-3 PUFA in GISSI-HF suggest that marine fish oils could confer protection in HF mainly through their antiarrhythmic action and in part by influencing the mechanisms related to HF progression.
Abstract: During the past three decades, the protective role of omega (n)-3 polyunsaturated fatty acids (PUFA), mainly eicosapentaenoic acid and docosahexaenoic acid, in patients with coronary heart disease has been widely reported. The Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico-Heart Failure (GISSI-HF) study, a large-scale clinical trial, recently showed that n-3 PUFA (850–882 mg/d) reduced mortality and admission to the hospital for cardiovascular reasons in patients with chronic heart failure (HF) who were already receiving recommended therapies. The favorable effects of n-3 PUFA in GISSI-HF suggest that marine fish oils could confer protection in HF mainly through their antiarrhythmic action and in part by influencing the mechanisms related to HF progression. This article reviews recent clinical and experimental evidence on the effect of n-3 PUFA in coronary heart disease, with particular attention on HF and its pathophysiologic mechanisms.
TL;DR: Clinical trial evidence strongly supports the notion that both red yeast rice and plant stanols and sterols effectively lower low-density lipoprotein (LDL) cholesterol and preliminary evidence supports the possibility that green tea catechins and black tea theaflavins may lower LDL.
Abstract: Hyperlipidemia is a risk factor for the development of coronary heart disease. Many patients decline prescription lipid-lowering agents and opt instead for supplements. Before any supplement can be routinely recommended it is crucial to examine the types of clinical trials that have been performed, the mechanism by which a supplement is felt to alter lipids, the population studied, potential adverse effects, and the possibility that investigators might be biased. Clinical trial evidence strongly supports the notion that both red yeast rice and plant stanols and sterols effectively lower low-density lipoprotein (LDL) cholesterol. Preliminary evidence supports the possibility that green tea catechins and black tea theaflavins may lower LDL. Data do not support an LDL-lowering claim for guggulipid, policosanol, or cinnamon. Finally, there is strong clinical trial evidence suggesting that marine omega-3 fatty acids lower triglycerides.
TL;DR: This review discusses the biology of GLP-1 and its effects on cardiovascular risk factors, and it also elaborates on the positive direct cardiovascular outcomes of GLp-1 in animal studies.
Abstract: Cardiovascular disease is a leading cause of death in the United States and across the world, and better therapies are constantly being sought to improve patient outcomes. Recent studies have brought our attention to the mechanisms of glucagon-like peptide 1 (GLP-1). Not only does it demonstrate beneficial effects in regard to cardiovascular risk factors (ie, diabetes, lipid management, and weight control), but it also has been shown in animal studies to have positive cardiac effects irrespective of its effects on glucose control and weight loss. This review discusses the biology of GLP-1 and its effects on cardiovascular risk factors, and it also elaborates on the positive direct cardiovascular outcomes of GLP-1 in animal studies.
TL;DR: It is unlikely that a prospective, randomized trial assessing the effect of pre- or poststroke statin treatment on initial stroke severity would be the most appropriate study design, given the benefits of these drugs in reducing the risk of cardiovascular events and stroke in high-risk populations.
Abstract: Cytoprotective or neuroprotective interventions would be of value if they could block the processes leading to delayed neuronal death or if they could delay the period between the onset of ischemia and irreversible necrotic injury, thereby lengthening the period for effective reperfusion therapy. Experimental studies in cell culture systems and laboratory animals show that statins have several potential cytoprotective actions, including promotion of angiogenesis, reduction of clot formation and facilitation of clot lysis, upregulation of endothelial nitric oxide synthase, downregulation of inducible nitric oxide synthase, reduction of excitotoxicity, and modulation of the inflammatory response. Clinically, statins appear to protect against vasospasm-related ischemic injury after subarachnoid hemorrhage. There have been no prospective randomized trials aimed at determining whether statins reduce acute stroke severity, and observational studies have had inconsistent results. Although a prospective, randomized trial assessing the effect of pre-or poststroke statin treatment on initial stroke severity would be the most appropriate study design to test for this type of effect, it is unlikely that such a trial will be conducted given the benefits of these drugs in reducing the risk of cardiovascular events and stroke in high-risk populations.