Showing papers by "Scott M. Grundy published in 2004"
TL;DR: The trials confirm the benefit of cholesterol-lowering therapy in high-risk patients and support the ATP III treatment goal of low-density lipoprotein cholesterol (LDL-C) <100 mg/dL, and confirm that older persons benefit from therapeutic lowering of LDL-C.
Abstract: The Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program issued an evidence-based set of guidelines on cholesterol management in 2001. Since the publication of ATP III, 5 major clinical trials of statin therapy with clinical end points have been published. These trials addressed issues that were not examined in previous clinical trials of cholesterol-lowering therapy. The present document reviews the results of these recent trials and assesses their implications for cholesterol management. Therapeutic lifestyle changes (TLC) remain an essential modality in clinical management. The trials confirm the benefit of cholesterol-lowering therapy in high-risk patients and support the ATP III treatment goal of low-density lipoprotein cholesterol (LDL-C) <100 mg/dL. They support the inclusion of patients with diabetes in the high-risk category and confirm the benefits of LDL-lowering therapy in these patients. They further confirm that older persons benefit from therapeutic lowering of LDL-C. The major recommendations for modifications to footnote the ATP III treatment algorithm are the following. In high-risk persons, the recommended LDL-C goal is <100 mg/dL, but when risk is very high, an LDL-C goal of <70 mg/dL is a therapeutic option, ie, a reasonable clinical strategy, on the basis of available clinical trial evidence. This therapeutic option extends also to patients at very high risk who have a baseline LDL-C <100 mg/dL. Moreover, when a high-risk patient has high triglycerides or low high-density lipoprotein cholesterol (HDL-C), consideration can be given to combining a fibrate or nicotinic acid with an LDL-lowering drug. For moderately high-risk persons (2+ risk factors and 10-year risk 10% to 20%), the recommended LDL-C goal is <130 mg/dL, but an LDL-C goal <100 mg/dL is a therapeutic option on the basis of recent trial evidence. The latter option extends also to moderately high-risk persons with a baseline LDL-C of 100 to 129 mg/dL. When LDL-lowering drug therapy is employed in high-risk or moderately high-risk persons, it is advised that intensity of therapy be sufficient to achieve at least a 30% to 40% reduction in LDL-C levels. Moreover, any person at high risk or moderately high risk who has lifestyle-related risk factors (eg, obesity, physical inactivity, elevated triglycerides, low HDL-C, or metabolic syndrome) is a candidate for TLC to modify these risk factors regardless of LDL-C level. Finally, for people in lower-risk categories, recent clinical trials do not modify the goals and cutpoints of therapy.
6,944 citations
TL;DR: Although ATP III identified CVD as the primary clinical outcome of the metabolic syndrome, most people with this syndrome have insulin resistance, which confers increased risk for type 2 diabetes, when diabetes becomes clinically apparent, CVD risk rises sharply.
Abstract: The National Cholesterol Education Program’s Adult Treatment Panel III report (ATP III)1 identified the metabolic syndrome as a multiplex risk factor for cardiovascular disease (CVD) that is deserving of more clinical attention. The cardiovascular community has responded with heightened awareness and interest. ATP III criteria for metabolic syndrome differ somewhat from those of other organizations. Consequently, the National Heart, Lung, and Blood Institute, in collaboration with the American Heart Association, convened a conference to examine scientific issues related to definition of the metabolic syndrome. The scientific evidence related to definition was reviewed and considered from several perspectives: (1) major clinical outcomes, (2) metabolic components, (3) pathogenesis, (4) clinical criteria for diagnosis, (5) risk for clinical outcomes, and (6) therapeutic interventions.
ATP III viewed CVD as the primary clinical outcome of metabolic syndrome. Most individuals who develop CVD have multiple risk factors. In 1988, Reaven2 noted that several risk factors (eg, dyslipidemia, hypertension, hyperglycemia) commonly cluster together. This clustering he called Syndrome X , and he recognized it as a multiplex risk factor for CVD. Reaven and subsequently others postulated that insulin resistance underlies Syndrome X (hence the commonly used term insulin resistance syndrome ). Other researchers use the term metabolic syndrome for this clustering of metabolic risk factors. ATP III used this alternative term. It avoids the implication that insulin resistance is the primary or only cause of associated risk factors. Although ATP III identified CVD as the primary clinical outcome of the metabolic syndrome, most people with this syndrome have insulin resistance, which confers increased risk for type 2 diabetes. When diabetes becomes clinically apparent, CVD risk rises sharply. Beyond CVD and type 2 diabetes, individuals with metabolic syndrome seemingly are susceptible to other conditions, notably polycystic ovary syndrome, fatty liver, cholesterol gallstones, asthma, sleep disturbances, and some …
6,238 citations
TL;DR: The prevalence of hepatic steatosis was greater in men than women among whites, but not in blacks or Hispanics, and significant ethnic and sex differences in the prevalence may have a profound impact on susceptibility to Steatosis‐related liver disease.
3,429 citations
TL;DR: Although ATP III identified CVD as the primary clinical outcome of the metabolic syndrome, most people with this syndrome have insulin resistance, which confers increased risk for type 2 diabetes, when diabetes becomes clinically apparent, CVD risk rises sharply.
Abstract: The National Cholesterol Education Program’s Adult Treatment Panel III report (ATP III)1 identified the metabolic syndrome as a multiplex risk factor for cardiovascular disease (CVD) that is deserving of more clinical attention. The cardiovascular community has responded with heightened awareness and interest. ATP III criteria for metabolic syndrome differ somewhat from those of other organizations. Consequently, the National Heart, Lung, and Blood Institute, in collaboration with the American Heart Association, convened a conference to examine scientific issues related to definition of the metabolic syndrome. The scientific evidence related to definition was reviewed and considered from several perspectives: (1) major clinical outcomes, (2) metabolic components, (3) pathogenesis, (4) clinical criteria for diagnosis, (5) risk for clinical outcomes, and (6) therapeutic interventions.
ATP III viewed CVD as the primary clinical outcome of metabolic syndrome. Most individuals who develop CVD have multiple risk factors. In 1988, Reaven2 noted that several risk factors (eg, dyslipidemia, hypertension, hyperglycemia) commonly cluster together. This clustering he called Syndrome X , and he recognized it as a multiplex risk factor for CVD. Reaven and subsequently others postulated that insulin resistance underlies Syndrome X (hence the commonly used term insulin resistance syndrome ). Other researchers use the term metabolic syndrome for this clustering of metabolic risk factors. ATP III used this alternative term. It avoids the implication that insulin resistance is the primary or only cause of associated risk factors. Although ATP III identified CVD as the primary clinical outcome of the metabolic syndrome, most people with this syndrome have insulin resistance, which confers increased risk for type 2 diabetes. When diabetes becomes clinically apparent, CVD risk rises sharply. Beyond CVD and type 2 diabetes, individuals with metabolic syndrome seemingly are susceptible to other conditions, notably polycystic ovary syndrome, fatty liver, cholesterol gallstones, asthma, sleep disturbances, and some …
1,252 citations
TL;DR: The variable characteristics of obesity are examined; this will be followed by an examination of the relation of obesity to the metabolic syndrome; and the relationship of the metabolic Syndrome to ASCVD will be reviewed.
Abstract: Obesity is rampant in the United States and is becoming increasing common worldwide. The increase in obesity prevalence is due to two major factors, plentiful supplies of inexpensive foods and sedentary jobs. Both are driven in no small part by technology. Thanks to technology, production of large quantities of cheap food is possible, and manual work is rapidly disappearing. In areas of the world in which these advances have not penetrated, obesity is not a significant public health problem. Thus, obesity is a direct result of technological advance and represents a major challenge for technological society. Obesity must also be recognized as a product of free society in which a multitude of food choices and job opportunities are available. A public health approach to the problem of obesity that restricts choice will not be acceptable to a free society. This fact puts increased responsibility on the individual to recognize the underlying causes of obesity and modify behavior to reduce the personal burden of obesity. That obesity extracts a social cost is well recognized. The costs in physical health are less well recognized by the general public. The foremost physical consequence of obesity is atherosclerotic cardiovascular disease (ASCVD) (1). A substantial portion of the ASCVD resulting from obesity is mediated by type 2 diabetes. But obesity is accompanied by several other risk factors for ASCVD. The sum of the risk factors that predisposes to ASCVD goes by the name of metabolic syndrome. In addition, obesity is accompanied by other medical complications other than ASCVD and diabetes; these include fatty liver, cholesterol gallstones, sleep apnea, osteoarthritis, and polycystic ovary disease. These disorders are commonly found in individuals who carry the metabolic syndrome. Obesity can be called an underlying risk factor for cardiovascular disease (ASCVD) (2). It is called this because it raises the risk for ASCVD through other risk factors. The latter include the major risk factors (hypercholesterolemia, hypertension, hyperglycemia) and emerging risk factors (atherogenic dyslipidemia, insulin resistance, proinflammatory state, prothrombotic state). The relationship of obesity to major and emerging risk factors varies, depending on the genetic and acquired characteristics of individuals. The majority of obese persons who develop ASCVD typically have a clustering of major and emerging risk factors (metabolic syndrome). The constellation of major and emerging risk factors that make up the metabolic syndrome can be called metabolic risk factors (3). This article will first examine the variable characteristics of obesity; this will be followed by an examination of the relation of obesity to the metabolic syndrome; and finally, the relation of the metabolic syndrome to ASCVD will be reviewed. Categories of obesity Obesity can be defined as an excess of body fat. A surrogate marker for body fat content is the body mass index (BMI), which is determined by weight (kilograms) divided by height squared (square meters). In clinical terms, a BMI of 25–29 kg/m 2 is called overweight; higher BMIs (30 kg/m 2 ) are called obesity (4). A better way to define obesity would be in terms of percent total body fat (4). This can be measured by several methods (skin-fold thickness, bioelectrical impedance, underwater weighing). In terms of percent body fat, obesity can be defined as 25% or greater in men and 35% or greater in women. The measurement of percent body fat is rarely used in clinical practice, however, because of inconvenience and cost.
1,186 citations
TL;DR: The present report summarizes a second conference devoted to clinical management of the metabolic syndrome, which was sponsored by the AHA in partnership with the NHLBI and cosponsored by the American Diabetes Association (ADA).
Abstract: The National Cholesterol Education Program’s Adult Treatment Panel III report (ATP III)1 identified the metabolic syndrome as a multiplex risk factor for cardiovascular disease (CVD) that is deserving of more clinical attention. Subsequently, the National Heart, Lung, and Blood Institute (NHLBI), in collaboration with the American Heart Association (AHA), convened a conference to examine scientific issues related to definition of the metabolic syndrome.2 The present report summarizes a second conference devoted to clinical management of the metabolic syndrome, which was sponsored by the AHA in partnership with the NHLBI and cosponsored by the American Diabetes Association (ADA). This latter conference considered the following issues: (1) pathogenesis and presentation of the metabolic syndrome, (2) management of underlying risk factors, (3) management of metabolic risk factors, and (4) unresolved issues and research challenges.
The conference on definition2 confirmed CVD as a major clinical outcome of metabolic syndrome and identified 6 major components of the syndrome: abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, insulin resistance ± glucose intolerance, a proinflammatory state, and a prothrombotic state. The follow-up conference on management was structured around therapies for these components. Clinical recognition of the metabolic syndrome is generally based on finding several well-recognized signs in clinical practice: abdominal obesity, elevated triglycerides, reduced HDL cholesterol, raised blood pressure, and elevated plasma glucose. In addition, research shows that other components not routinely measured commonly aggregate with the major components: elevated apolipoprotein B, small LDL particles, insulin resistance and hyperinsulinemia, impaired glucose tolerance (IGT), elevated C-reactive protein (CRP), and variation in coagulation factors (eg, plasminogen activator inhibitor [PAI]-1 and fibrinogen). The conference on definition2 also emphasized that risk for type 2 diabetes is higher in persons with metabolic syndrome and that diabetes is a major risk factor for CVD. It also examined various criteria for …
965 citations
TL;DR: Beneficial effects of TZDs on glycemia and cardiovascular risk factors have made them attractive agents in patients with type 2 diabetes who are at high risk for CVD, there is a growing recognition, however, that edema can occur in patients treated with either drug.
Abstract: Diabetes is a chronic, progressively worsening disease associated with a variety of microvascular and macrovascular complications. Cardiovascular disease (CVD) is the main cause of death in these patients (1,2). During the past decade, numerous drugs have been introduced for the treatment of type 2 diabetes that, used in monotherapy or in combination therapy, are effective in lowering blood glucose to achieve glycemic goals and in reducing diabetes-related end-organ disease.
Two such drugs, rosiglitazone and pioglitazone, belong to the class called thiazolidinediones (TZDs) (3). Troglitazone, the first agent of this class to be approved, was effective in controlling glycemia but was removed from the market because of serious liver toxicity. Both rosiglitazone and pioglitazone are indicated either as monotherapy or in combination with a sulfonylurea, metformin, or insulin when diet, exercise, and a single agent do not result in adequate glycemic control (4) (package insert Avandia [rosiglitazone maleate; GlaxoSmithKline] and Actos (5) [pioglitazone hydrochloride; Takeda Pharmaceuticals]). In addition to lowering blood glucose, both drugs may benefit cardiovascular parameters, such as lipids, blood pressure, inflammatory biomarkers, endothelial function, and fibrinolytic status (6,7).
These beneficial effects of TZDs on glycemia and cardiovascular risk factors have made them attractive agents in patients with type 2 diabetes who are at high risk for CVD. There is a growing recognition, however, that edema can occur in patients treated with either drug. Because people with diabetes are at increased risk for CVD and many have preexisting heart disease, the edema that sometimes accompanies the use of a TZD can be cause for concern, as it may be a harbinger or sign of congestive heart failure (CHF). An analysis of Medicare beneficiaries hospitalized with the diagnosis of diabetes and CHF indicated that the number of these patients discharged on TZDs had increased from …
662 citations
TL;DR: Experts in the fields of epidemiology, prevention, vascular biology, and clinical cardiology should be convened to begin discussing the merits of this proposal, which proposes the creation of an hsCRP-modified coronary risk score useful for global risk prediction in both men and women.
Abstract: Of novel risk factors for cardiovascular disease currently under investigation, high-sensitivity C-reactive protein (hsCRP) is the most promising. To date, more than 20 prospective epidemiologic studies have demonstrated that hsCRP independently predicts vascular risk, 6 cohort studies have confirmed that hsCRP evaluation adds prognostic information beyond that available from the Framingham Risk Score, and 8 cohort studies have demonstrated additive prognostic value at all levels of metabolic syndrome or in the prediction of type 2 diabetes. In contrast to several other biomarkers that also reflect biological aspects of inflammation, hypofibrinolysis, and insulin resistance, hsCRP measurement is inexpensive, standardized, widely available, and has a decade-to-decade variation similar to that of cholesterol. Given the consistency of prognostic data for hsCRP and the practicality of its use in outpatient clinical settings, we believe the time has come for a careful consideration of adding hsCRP as a clinical criterion for metabolic syndrome and for the creation of an hsCRP-modified coronary risk score useful for global risk prediction in both men and women. Toward this end, we believe experts in the fields of epidemiology, prevention, vascular biology, and clinical cardiology should be convened to begin discussing the merits of this proposal.
659 citations
TL;DR: The recommendations in this report focus on clinical management of patients with established CVD and those at high risk; however, it is essential that each country include a societal approach to CVD prevention.
Abstract: In the global effort to reduce suffering and death from CVD, the World Heart and Stroke Forum (WHSF) Guidelines Task Force of the World Heart Federation (WHF) recommends that every country develop a policy on CVD prevention. National policy should grow out of systematic and ongoing dialogue among governmental, public health, and professional clinical groups. National policy should set priorities for public health and clinical interventions appropriate to the country. It should also be the foundation for the development of national guidelines on CVD prevention, which are the focus of the present document. Cardiovascular disease (CVD) is a leading cause of global mortality, accounting for almost 17 million deaths annually. Nearly 80% of this global mortality and disease burden occurs in developing countries. In 2001, CVD was the leading cause of mortality in 5 of the 6 World Health Organization (WHO) worldwide regions. Of concern in developing countries is the projected increase in both proportional and absolute CVD mortality. This can be related to an increase in life expectancy due to public health advances, which reduce perinatal infections and nutritional deficiencies in infancy, childhood, and adolescence, and in some countries to improved economic conditions. This increasing longevity provides longer periods of exposure to CVD risk factors and thus a greater probability of clinically manifest CVD. The concomitant decline of infections and nutritional disorders (competing causes of death) also increases the proportional burden due to CVD. Adverse lifestyle changes accompanying industrialization, urbanization, and increased discretionary income increase the degree of exposure to CVD risk factors. Altered diet with increased fat and total caloric consumption and increased tobacco use are prevalent lifestyle trends. Demographic changes coupled with adverse lifestyle changes will accelerate the number of deaths due to CVD worldwide, many of which will be premature in the developing countries. Although continuation of this adverse trend is not inevitable, the CVD disease patterns now present in the economically developed countries are, in fact, becoming established in developing countries, as noted in the World Health Report 2002 1 (Data Supplement Figure I). Whereas the causes of CVD are common to all parts of the world, the approaches to its prevention at a societal or individual level will differ between countries for cultural, social, medical, and economic reasons. Although national guidelines will embrace the principles of CVD prevention recommended in this report, they may differ in terms of the organization of preventive cardiology, risk factor treatment thresholds and goals, and the use of medical therapies. The recommendations in this report focus on clinical management of patients with established CVD and those at high risk; however, it is essential that each country include a societal approach to CVD prevention. As stated in the WHO publication Integrated Management of Cardiovascular Risk, 2 “Epidemiological theory indicates that, compared with intensive individual treatment of high-risk patients, small improvements in the overall distribution of risk in a population will yield larger gains in disease reduction, when the underlying conditions that confer risk are widespread in the population.” Each country should seek to implement national clinical guidelines directed toward high-risk individuals and give equal importance to developing low-risk population strategies.
384 citations
TL;DR: A second conference devoted to clinical management of the metabolic syndrome was sponsored by the AHA in partnership with the NHLBI and cosponsored by the American Diabetes Association, which considered the following issues: pathogenesis and presentation, management of underlying risk factors, and management of metabolic risk factors.
Abstract: The National Cholesterol Education Program’s Adult Treatment Panel III report (ATP III)1 identified the metabolic syndrome as a multiplex risk factor for cardiovascular disease (CVD) that is deserving of more clinical attention. Subsequently, the National Heart, Lung, and Blood Institute (NHLBI), in collaboration with the American Heart Association (AHA), convened a conference to examine scientific issues related to definition of the metabolic syndrome.2 The present report summarizes a second conference devoted to clinical management of the metabolic syndrome, which was sponsored by the AHA in partnership with the NHLBI and cosponsored by the American Diabetes Association (ADA). This latter conference considered the following issues: (1) pathogenesis and presentation of the metabolic syndrome, (2) management of underlying risk factors, (3) management of metabolic risk factors, and (4) unresolved issues and research challenges.
The conference on definition2 confirmed CVD as a major clinical outcome of metabolic syndrome and identified 6 major components of the syndrome: abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, insulin resistance ± glucose intolerance, a proinflammatory state, and a prothrombotic state. The follow-up conference on management was structured around therapies for these components. Clinical recognition of the metabolic syndrome is generally based on finding several well-recognized signs in clinical practice: abdominal obesity, elevated triglycerides, reduced HDL cholesterol, raised blood pressure, and elevated plasma glucose. In addition, research shows that other components not routinely measured commonly aggregate with the major components: elevated apolipoprotein B, small LDL particles, insulin resistance and hyperinsulinemia, impaired glucose tolerance (IGT), elevated C-reactive protein (CRP), and variation in coagulation factors (eg, plasminogen activator inhibitor [PAI]-1 and fibrinogen). The conference on definition2 also emphasized that risk for type 2 diabetes is higher in persons with metabolic syndrome and that diabetes is a major risk factor for CVD. It also examined various criteria for …
249 citations
TL;DR: Plasma concentrations of the adipose tissue metabolites leptin and NEFAs are higher and that of adiponectin is lower in insulin-resistant Asian Indians compared with more insulin-sensitive Caucasians, which may contribute to the excessive prevalence of type 2 diabetes and cardiovascular disease in nonobese Asian Indians.
Abstract: Obesity-related insulin resistance is associated with changes in adipose tissue release of leptin, adiponectin, and nonesterified fatty acids (NEFAs). We have previously described that persons originating from the Indian subcontinent (Asian Indians) manifest excessive insulin resistance even in the absence of obesity. Therefore, in this study, we tested the hypothesis that nondiabetic, insulin-resistant Asian Indians differ from less insulin-resistant Caucasians of similar age and body composition in adipose tissue production of leptin and adiponectin, and in suppression of plasma NEFA concentrations during hyperinsulinemia. Seventy-nine Asian Indian men were compared with 61 Caucasian men. Higher plasma NEFAs and leptin in Asian Indians (P < 0.0001 and P = 0.003 for NEFAs and leptin, respectively) and lower plasma concentrations of adiponectin (P = 0.009) were not explained by body fat content and distribution. Oral glucose tolerance test studies revealed that Caucasian men had greater suppression of plasma NEFAs than Asian Indian men. We conclude that plasma concentrations of the adipose tissue metabolites leptin and NEFAs are higher and that of adiponectin is lower in insulin-resistant Asian Indians compared with more insulin-sensitive Caucasians. These differences may contribute to the excessive prevalence of type 2 diabetes and cardiovascular disease in nonobese Asian Indians.
TL;DR: The results of this study do not support an association between elevated plasma levels of plant sterols and atherosclerosis, despite the fact that cholesterol levels were significantly higher in subjects with coronary calcium.
Abstract: Objective— Sitosterolemia is characterized by elevated plasma levels of plant sterols, hypercholesterolemia and premature coronary heart disease (CHD). CHD develops in some subjects with sitosterolemia, despite having normal plasma cholesterol levels, suggesting that high circulating levels of plant sterols may be atherogenic. We tested whether elevated plasma levels of plant sterols (sitosterol and campesterol) were associated with atherosclerosis in genetically modified mice and in middle-aged men and women.
Methods and Results— Wild-type and hypercholesterolemic female mice with >20-fold higher plasma levels of plant sterols because of inactivation of the ATP-binding cassette (ABC) half transporters G5 and G8 ( G5G8 −/−mice) were fed chow or Western diets for 7 months. No significant differences in aortic lesion area were found when the sitosterolemic mice were compared with littermate controls. To determine whether plasma levels of plant sterols were associated with coronary atherosclerosis in humans, the relationship between plasma plant sterols and coronary calcium (detected by electron beam computer tomography) was examined in 2542 subjects aged 30 to 67 years. Plasma levels of cholesterol, but not sitosterol or campesterol, were significantly higher in subjects with coronary calcium.
Conclusions— The results of this study do not support an association between elevated plasma levels of plant sterols and atherosclerosis.
TL;DR: Blacks in the general population have a prevalence of coronary atherosclerosis similar to whites, and factors other than coronary Atherosclerotic burden contribute significantly to the higher CHD mortality rate in blacks.
TL;DR: The current data suggest that mevinolin alone ormevinolin plus bile acid depletion (i.e., ileal bypass or colestipol therapy) decreases plasma LDL levels primarily by raising the number of LDL receptors and, thus, enhancing the removal of LDL from plasma.
TL;DR: It is worthwhile to investigate individually the components of the obesity-induced metabolic syndrome for their atherogenic potential, because out of that investigation likely will come new targets for clinical or public health intervention to reduce the risk for cardiovascular disease.
TL;DR: For many patients with ASCVD, enhanced LDL lowering beyond that obtained with standard doses of statins may further reduce CVD events.
Abstract: Lowering low-density lipoproteins (LDL) by statin therapy to reduce the risk for major clinical events in patients with established atherosclerotic cardiovascular disease (ASCVD) represents a therapeutic triumph of modern medicine. With standard doses of statins, the risk for CVD events falls by approximately one third.1 Additional risk reduction occurs by adding other therapeutic modalities to statin therapy—antiplatelet drugs, antihypertensive agents, smoking cessation, and healthy lifestyle changes.2 Most of the benefit from these combined treatments appears to result from the stabilization of vulnerable plaques in patients who have advanced atherosclerotic disease; in other words, they reduce the likelihood of plaque ruptures that cause acute cardiovascular syndromes.
See p 3512
Although novel nonlipid therapies may well be developed in the future, persistent aberrations in lipid metabolism in the face of standard doses of statins remain attractive targets of therapy. Two of these potential lipid targets are residually elevated low-density lipoprotein cholesterol (LDL-C) and atherogenic dyslipidemia. Additional LDL lowering can be achieved either by yet higher doses of statins or by combining standard doses of statins with other LDL-lowering drugs (eg, bile acid sequestrants or ezetimibe). Atherogenic dyslipidemia consists of elevations of serum triglycerides, apolipoprotein B, and small LDL particles plus low levels of high-density lipoprotein cholesterol (HDL-C).1 Alternative therapies for atherogenic dyslipidemia available for combination with statins include fibrates and nicotinic acid.1
For many patients with ASCVD, enhanced LDL lowering beyond that obtained with standard doses of statins may further reduce CVD events. Current guidelines for cholesterol management in these patients set an LDL-C goal of <100 mg/dL.1 The recent Heart Protection Study (HPS) findings3 strongly suggest that high-risk patients with a baseline LDL-C <100 mg/dL will still benefit when LDL-C levels are reduced to well below 100 mg/dL by drug therapy. The Pravastatin or Atorvastatin …
TL;DR: This paper has been much cited (7081 times as of this writing) in part because it represents a solid method that, with various modifications, has been applicable for the study of lipoproteins for almost half a century.
Abstract: In 1956, the JCI published a paper by Richard Havel, Howard Eder, and Joseph Bragdon on a method using an ultracentrifuge to physically separate plasma lipoproteins and chemical methods to analyze their lipid constituents This paper has been much cited (7081 times as of this writing) in part because it represents a solid method that, with various modifications, has been applicable for the study of lipoproteins for almost half a century
01 May 2004
TL;DR: In this article, the authors address the question of the interaction between obesity and genetic susceptibility in the etiology of the metabolic syndrome, and find that genetic susceptibility appears at three levels: within adipose tissue itself, in insulin signaling pathways, and in regulation of individual risk factors.
Abstract: The metabolic syndrome consists of a clustering of metabolic risk factors in one individual. These risk factors consist of atherogenic dyslipidemia (high triglycerides, high apolipoprotein B [apo B], small LDL particles, and low HDL), elevated blood pressure, insulin resistance±elevated plasma glucose, a prothrombotic state, and a proinflammatory state. Although the metabolic syndrome is increasingly common around the world and represents an important cause of cardiovascular disease (CVD), its pathogenesis is not well understood. The two major underlying causes appear to be obesity or other disorders of adipose tissue and insulin resistance. There is little doubt that genetic susceptibility plays an important role in the development of the metabolic syndrome. This paper addresses the question of the interaction between obesity and genetic susceptibility in the etiology of the metabolic syndrome. Genetic susceptibility appears to exist at three levels: within adipose tissue itself, in insulin signaling pathways, and in regulation of individual risk factors. A major research challenge for the future is to unravel the complex genetic architecture that gives rise to the metabolic syndrome once a person becomes obese.
TL;DR: The lipid and lipoprotein responses to these diets were compared in nondiabetic and T2DM subjects by repeated measures analysis of variance model.
01 Jan 2004
TL;DR: In this article, Molina et al. present a Declaración Cientifica del Foro Mundial del Corazon y el Ictus (HTA) for Castellano.
Abstract: Declaracion Cientifica del Foro Mundial del Corazon y el Ictus* Sidney C. Smith, Jr, MD; Rod Jackson, MBChB, PhD; Thomas A. Pearson, MD, MPH, PhD; Valentin Fuster, MD, PhD; Salim Yusuf, MBBS, DPhil; Ole Faergeman, MD, DMSc; David A. Wood, MSc; Michael Alderman, MD; John Horgan, MD; Philip Home, MA, DPhil, DM; Marilyn Hunn, BS; Scott M. Grundy, MD, PhD Traduccion al Castellano: Dr. Rafael Molina. Grupo HTA. SAMFyC.