Scott M. Grundy

Diagnosis and Management of the Metabolic Syndrome: An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement

The metabolic syndrome has received increased attention in the past few years. This statement from the American Heart Association (AHA) and the National Heart, Lung, and Blood Institute (NHLBI) is intended to provide up-to-date guidance for professionals on the diagnosis and management of the metabolic syndrome in adults. The metabolic syndrome is a constellation of interrelated risk factors of metabolic origin— metabolic risk factors —that appear to directly promote the development of atherosclerotic cardiovascular disease (ASCVD).1 Patients with the metabolic syndrome also are at increased risk for developing type 2 diabetes mellitus. Another set of conditions, the underlying risk factors , give rise to the metabolic risk factors. In the past few years, several expert groups have attempted to set forth simple diagnostic criteria to be used in clinical practice to identify patients who manifest the multiple components of the metabolic syndrome. These criteria have varied somewhat in specific elements, but in general they include a combination of both underlying and metabolic risk factors. The most widely recognized of the metabolic risk factors are atherogenic dyslipidemia, elevated blood pressure, and elevated plasma glucose. Individuals with these characteristics commonly manifest a prothrombotic state and a pro-inflammatory state as well. Atherogenic dyslipidemia consists of an aggregation of lipoprotein abnormalities including elevated serum triglyceride and apolipoprotein B (apoB), increased small LDL particles, and a reduced level of HDL cholesterol (HDL-C). The metabolic syndrome is often referred to as if it were a discrete entity with a single cause. Available data suggest that it truly is a syndrome, ie, a grouping of ASCVD risk factors, but one that probably has more than one cause. Regardless of cause, the syndrome identifies individuals at an elevated risk for ASCVD. The magnitude of the increased risk can vary according to which components of the syndrome are …

Implications of Recent Clinical Trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines

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.

Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity.

A cluster of risk factors for cardiovascular disease and type 2 diabetes mellitus, which occur together more often than by chance alone, have become known as the metabolic syndrome. The risk factors include raised blood pressure, dyslipidemia (raised triglycerides and lowered high-density lipoprotein cholesterol), raised fasting glucose, and central obesity. Various diagnostic criteria have been proposed by different organizations over the past decade. Most recently, these have come from the International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute. The main difference concerns the measure for central obesity, with this being an obligatory component in the International Diabetes Federation definition, lower than in the American Heart Association/National Heart, Lung, and Blood Institute criteria, and ethnic specific. The present article represents the outcome of a meeting between several major organizations in an attempt to unify criteria. It was agreed that there should not be an obligatory component, but that waist measurement would continue to be a useful preliminary screening tool. Three abnormal findings out of 5 would qualify a person for the metabolic syndrome. A single set of cut points would be used for all components except waist circumference, for which further work is required. In the interim, national or regional cut points for waist circumference can be used.

The metabolic syndrome

The metabolic syndrome is a common metabolic disorder that results from the increasing prevalence of obesity. The disorder is defined in various ways, but in the near future a new definition(s) will be applicable worldwide. The pathophysiology seems to be largely attributable to insulin resistance with excessive flux of fatty acids implicated. A proinflammatory state probably contributes to the syndrome. The increased risk for type 2 diabetes and cardiovascular disease demands therapeutic attention for those at high risk. The fundamental approach is weight reduction and increased physical activity; however, drug treatment could be appropriate for diabetes and cardiovascular disease risk reduction.

Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity.

Despite the increasing prevalence of nonalcoholic fatty liver disease (NAFLD), its pathogenesis and clinical significance remain poorly defined. In this study, we examined and compared the distribution of hepatic triglyceride content (HTGC) in 2,287 subjects from a multiethnic, population‐based sample (32.1% white, 48.3% black, and 17.5% Hispanic) using proton magnetic resonance spectroscopy. HTGC varied over a wide range (0.0%‐41.7%; median, 3.6%) in the population. Almost one third of the population had hepatic steatosis, and most subjects with hepatic steatosis had normal levels of serum alanine aminotransferase (79%). The frequency of hepatic steatosis varied significantly with ethnicity (45% in Hispanics; 33% in whites; 24% in blacks) and sex (42% in white men; 24% in white women). The higher prevalence of hepatic steatosis in Hispanics was due to the higher prevalence of obesity and insulin resistance in this ethnic group. However, the lower frequency of hepatic steatosis in blacks was not explained by ethnic differences in body mass index, insulin resistance, ethanol ingestion, or medication use. The prevalence of hepatic steatosis was greater in men than women among whites, but not in blacks or Hispanics. The ethnic differences in the frequency of hepatic steatosis in this study mirror those observed previously for NAFLD‐related cirrhosis (Hispanics > whites > blacks). In conclusion, the significant ethnic and sex differences in the prevalence of hepatic steatosis documented in this study may have a profound impact on susceptibility to steatosis‐related liver disease. (HEPATOLOGY 2004;40:1387–1395.)

Diabetes and cardiovascular disease: A statement for healthcare professionals from the american heart association

This statement examines the cardiovascular complications of diabetes mellitus and considers opportunities for their prevention. These complications include coronary heart disease (CHD), stroke, peripheral arterial disease, nephropathy, retinopathy, and possibly neuropathy and cardiomyopathy. Because of the aging of the population and an increasing prevalence of obesity and sedentary life habits in the United States, the prevalence of diabetes is increasing. Thus, diabetes must take its place alongside the other major risk factors as important causes of cardiovascular disease (CVD). In fact, from the point of view of cardiovascular medicine, it may be appropriate to say, “diabetes is a cardiovascular disease.” The most prevalent form of diabetes mellitus is type 2 diabetes. This disorder typically makes its appearance later in life. The underlying metabolic causes of type 2 diabetes are the combination of impairment in insulin-mediated glucose disposal (insulin resistance) and defective secretion of insulin by pancreatic β-cells. Insulin resistance develops from obesity and physical inactivity, acting on a substrate of genetic susceptibility.1 2 Insulin secretion declines with advancing age,3 4 and this decline may be accelerated by genetic factors.5 6 Insulin resistance typically precedes the onset of type 2 diabetes and is commonly accompanied by other cardiovascular risk factors: dyslipidemia, hypertension, and prothrombotic factors.7 8 The common clustering of these risk factors in a single individual has been called the metabolic syndrome. Many patients with the metabolic syndrome manifest impaired fasting glucose (IFG)9 even when they do not have overt diabetes mellitus.10 The metabolic syndrome commonly precedes the development of type 2 diabetes by many years11 ; of great importance, the risk factors that constitute this syndrome contribute independently to CVD risk. Recently, new criteria have been accepted for the diagnosis of diabetes.9 The upper threshold of fasting plasma glucose for the …

AHA Guidelines for Primary Prevention of Cardiovascular Disease and Stroke: 2002 Update Consensus Panel Guide to Comprehensive Risk Reduction for Adult Patients Without Coronary or Other Atherosclerotic Vascular Diseases

The initial Guide to the Primary Prevention of Cardiovascular Diseases was published in 1997 as an aid to healthcare professionals and their patients without established coronary artery disease or other atherosclerotic diseases.1 It was intended to complement the American Heart Association (AHA)/American College of Cardiology (ACC) Guidelines for Preventing Heart Attack and Death in Patients with Atherosclerotic Cardiovascular Disease (updated2) and to provide the healthcare professional with a comprehensive approach to patients across a wide spectrum of risk. The imperative to prevent the first episode of coronary disease or stroke or the development of aortic aneurysm and peripheral arterial disease remains as strong as ever because of the still-high rate of first events that are fatal or disabling or require expensive intensive medical care. The evidence that most cardiovascular disease is preventable continues to grow. Results of long-term prospective studies consistently identify persons with low levels of risk factors as having lifelong low levels of heart disease and stroke.3,4⇓ Moreover, these low levels of risk factors are related to healthy lifestyles. Data from the Nurses Health Study,5 for example, suggest that in women, maintaining a desirable body weight, eating a healthy diet, exercising regularly, not smoking, and consuming a moderate amount of alcohol could account for an 84% reduction in risk, yet only 3% of the women studied were in that category. Clearly, the majority of the causes of cardiovascular disease are known and modifiable. This 2002 update of the Guide acknowledges a number of advances in the field of primary prevention since 1997. Research continues to refine the recommendations on detection and management of established risk factors, including evidence against the safety and efficacy of interventions once thought promising (eg, antioxidant vitamins).6 This, in turn, has …

Assessment of cardiovascular risk by use of multiple-risk-factor assessment equations: A statement for healthcare professionals from the American Heart Association and the American College of Cardiology

The past decade has witnessed major strides in the prevention of coronary heart disease (CHD) through modification of its causes. The most dramatic advance has been the demonstration that aggressive medical therapy will substantially reduce the likelihood of recurrent major coronary syndromes in patients with established CHD (secondary prevention). The American Heart Association (AHA) and the American College of Cardiology (ACC) have published joint recommendations for medical intervention in patients with CHD and other forms of atherosclerotic disease.1 A similar potential exists for risk reduction in patients without established CHD (primary prevention). However, the risk status of persons without CHD varies greatly, and this variability mandates a range in the intensity of interventions. Effective primary prevention thus requires an assessment of risk to categorize patients for selection of appropriate interventions. The present statement is being published jointly by the AHA and ACC to outline current issues and approaches to global risk assessment for primary prevention. The approaches described in this statement can be used for guidance at several levels of primary prevention; however, the statement does not attempt to specifically link risk assessment to treatment guidelines for particular risk factors. Nonetheless, it provides critical background information that can be used in the development of new treatment guidelines. The major and independent risk factors for CHD are cigarette smoking of any amount, elevated blood pressure, elevated serum total cholesterol and low-density lipoprotein cholesterol (LDL-C), low serum high-density lipoprotein cholesterol (HDL-C), diabetes mellitus, and advancing age (Table 1⇓). The quantitative relationship between these risk factors and CHD risk has been elucidated by the Framingham Heart Study2 and other studies. These studies2 show that the major risk factors are additive in predictive power. Accordingly, the total risk of a person can be estimated by a summing of the risk …

Thiazolidinedione Use, Fluid Retention, and Congestive Heart Failure A Consensus Statement From the American Heart Association and American Diabetes Association

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 control4 (package insert Avandia [rosiglitazone maleate; GlaxoSmithKline] and Actos5 [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 7.2% to 16.2% over a …

AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients With Coronary and Other Atherosclerotic Vascular Disease: 2011 Update A Guideline From the American Heart Association and American College of Cardiology Foundation

Since the 2006 update of the American Heart Association (AHA)/American College of Cardiology Foundation (ACCF) guidelines on secondary prevention,1 important evidence from clinical trials has emerged that further supports and broadens the merits of intensive risk-reduction therapies for patients with established coronary and other atherosclerotic vascular disease, including peripheral artery disease, atherosclerotic aortic disease, and carotid artery disease. In reviewing this evidence and its clinical impact, the writing group believed it would be more appropriate to expand the title of this guideline to “Secondary Prevention and Risk Reduction Therapy for Patients With Coronary and Other Atherosclerotic Vascular Disease.” Indeed, the growing body of evidence confirms that in patients with atherosclerotic vascular disease, comprehensive risk factor management reduces risk as assessed by a variety of outcomes, including improved survival, reduced recurrent events, the need for revascularization procedures, and improved quality of life. It is important not only that the healthcare provider implement these recommendations in appropriate patients but also that healthcare systems support this implementation to maximize the benefit to the patient. Compelling evidence-based results from recent clinical trials and revised practice guidelines provide the impetus for this update of the 2006 recommendations with evidence-based results2–165 (Table 1). Classification of recommendations and level of evidence are expressed in ACCF/AHA format, as detailed in Table 2. Recommendations made herein are largely based on major practice guidelines from the National Institutes of Health and updated ACCF/AHA practice guidelines, as well as on results from recent clinical trials. Thus, the development of the present guideline involved a process of partial adaptation of other guideline statements and reports and supplemental literature searches. The recommendations listed in this document are, whenever possible, evidence based. Writing group members performed these relevant supplemental literature searches with key search phrases including but not limited …