Showing papers by "Scott M. Grundy published in 2005"

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

Abstract: 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 …

Intensive lipid lowering with atorvastatin in patients with stable coronary disease.

Abstract: background Previous trials have demonstrated that lowering low-density lipoprotein (LDL) cholesterol levels below currently recommended levels is beneficial in patients with acute coronary syndromes. We prospectively assessed the efficacy and safety of lowering LDL cholesterol levels below 100 mg per deciliter (2.6 mmol per liter) in patients with stable coronary heart disease (CHD). methods A total of 10,001 patients with clinically evident CHD and LDL cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) were randomly assigned to double-blind therapy and received either 10 mg or 80 mg of atorvastatin per day. Patients were followed for a median of 4.9 years. The primary end point was the occurrence of a first major cardiovascular event, defined as death from CHD, nonfatal non–procedure-related myocardial infarction, resuscitation after cardiac arrest, or fatal or nonfatal stroke. results The mean LDL cholesterol levels were 77 mg per deciliter (2.0 mmol per liter) during treatment with 80 mg of atorvastatin and 101 mg per deciliter (2.6 mmol per liter) during treatment with 10 mg of atorvastatin. The incidence of persistent elevations in liver aminotransferase levels was 0.2 percent in the group given 10 mg of atorvastatin and 1.2 percent in the group given 80 mg of atorvastatin (P<0.001). A primary event occurred in 434 patients (8.7 percent) receiving 80 mg of atorvastatin, as compared with 548 patients (10.9 percent) receiving 10 mg of atorvastatin, representing an absolute reduction in the rate of major cardiovascular events of 2.2 percent and a 22 percent relative reduction in risk (hazard ratio, 0.78; 95 percent confidence interval, 0.69 to 0.89; P<0.001). There was no difference between the two treatment groups in overall mortality. conclusions Intensive lipid-lowering therapy with 80 mg of atorvastatin per day in patients with stable CHD provides significant clinical benefit beyond that afforded by treatment with 10 mg of atorvastatin per day. This occurred with a greater incidence of elevated aminotransferase levels.

Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population

Abstract: Despite the increasing prevalence of nonalcoholic fatty liver disease (NAFLD), the criteria used to diagnose the disorder remain poorly defined. Localized proton magnetic resonance spectroscopy (MR...

Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement: Executive Summary.

Abstract: This Executive Summary is a synopsis of the full scientific statement from the American Heart Association (AHA) and the National Heart, Lung, and Blood Institute (NHLBI), which is intended to provide up to date guidance for professionals on the diagnosis and management of the metabolic syndrome in adults. The metabolic syndrome has received increased attention in the past few years. It consists of multiple, interrelated risk factors of metabolic origin that appear to directly promote the development of atherosclerotic cardiovascular disease (ASCVD). This constellation of metabolic risk factors is strongly associated with type 2 diabetes mellitus or the risk for this condition. The metabolic risk factors consist of atherogenic dyslipidemia (elevated triglycerides and apolipoprotein B, small LDL particles, and low HDL cholesterol [HDL-C] concentrations), elevated blood pressure, elevated plasma glucose, a prothrombotic state, and a proinflammatory state. At present, it is not clear whether the metabolic syndrome has a single cause, and it appears that it can be precipitated by multiple underlying risk factors. The most important of these underlying risk factors are abdominal obesity and insulin resistance. Other associated conditions include physical inactivity, aging, hormonal imbalance, and genetic or ethnic predisposition. Prospective population studies show that the metabolic syndrome confers an &2-fold increase in relative risk for ASCVD events, and in individuals without established type 2 diabetes mellitus, an &5-fold increase in risk for developing diabetes as compared with people without the syndrome. This finding implies that the metabolic syndrome imparts a relatively high long-term risk for both ASCVD and diabetes. In the absence of diabetes, the absolute short-term (10-year) risk for major coronary heart disease (CHD) events is not necessarily high. In the Framingham Heart Study data, the 10-year risk for CHD depends on other risk factors in addition to the metabolic syndrome components contained in Framingham scoring …

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

Abstract: This Executive Summary is a synopsis of the full scientific statement from the American Heart Association (AHA) and the National Heart, Lung, and Blood Institute (NHLBI), which is intended to provide up to date guidance for professionals on the diagnosis and management of the metabolic syndrome in adults. The metabolic syndrome has received increased attention in the past few years. It consists of multiple, interrelated risk factors of metabolic origin that appear to directly promote the development of atherosclerotic cardiovascular disease (ASCVD). This constellation of metabolic risk factors is strongly associated with type 2 diabetes mellitus or the risk for this condition. The metabolic risk factors consist of atherogenic dyslipidemia (elevated triglycerides and apolipoprotein B, small LDL particles, and low HDL cholesterol [HDL-C] concentrations), elevated blood pressure, elevated plasma glucose, a prothrombotic state, and a proinflammatory state. At present, it is not clear whether the metabolic syndrome has a single cause, and it appears that it can be precipitated by multiple underlying risk factors. The most important of these underlying risk factors are abdominal obesity and insulin resistance. Other associated conditions include physical inactivity, aging, hormonal imbalance, and genetic or ethnic predisposition. Prospective population studies show that the metabolic syndrome confers an &2-fold increase in relative risk for ASCVD events, and in individuals without established type 2 diabetes mellitus, an &5-fold increase in risk for developing diabetes as compared with people without the syndrome. This finding implies that the metabolic syndrome imparts a relatively high long-term risk for both ASCVD and diabetes. In the absence of diabetes, the absolute short-term (10-year) risk for major coronary heart disease (CHD) events is not necessarily high. In the Framingham Heart Study data, the 10-year risk for CHD depends on other risk factors in addition to the metabolic syndrome components contained in Framingham scoring …

Trends in serum lipids and lipoproteins of adults, 1960-2002.

Abstract: ContextSerum total and low-density lipoprotein (LDL) cholesterol contribute significantly to atherosclerosis and its clinical sequelae. Previous analyses of data from the National Health and Nutrition Examination Surveys (NHANES) showed that mean levels of total cholesterol of US adults had declined from 1960-1962 to 1988-1994, and mean levels of LDL cholesterol (available beginning in 1976) had declined between 1976-1980 and 1988-1994.ObjectiveTo examine trends in serum lipid levels among US adults between 1960 and 2002, with a particular focus on changes since the 1988-1994 NHANES survey.Design, Setting, and ParticipantsBlood lipid measurements taken from 6098 to 15 719 adults who were examined in 5 distinct cross-sectional surveys of the US population during 1960-1962, 1971-1974, 1976-1980, 1988-1994, and 1999-2002.Main Outcome MeasuresMean serum total cholesterol, LDL cholesterol, high-density lipoprotein (HDL) cholesterol, and geometric mean serum triglyceride levels, and the percentage of adults with a serum total cholesterol level of at least 240 mg/dL (≥6.22 mmol/L).ResultsBetween 1988-1994 and 1999-2002, total serum cholesterol level of adults aged 20 years or older decreased from 206 mg/dL (5.34 mmol/L) to 203 mg/dL (5.26 mmol/L) (P=.009) and LDL cholesterol levels decreased from 129 mg/dL (3.34 mmol/L) to 123 mg/dL (3.19 mmol/L) (P<.001). Greater and significant decreases were observed in men 60 years or older and in women 50 years or older. The percentage of adults with a total cholesterol level of at least 240 mg/dL (≥6.22 mmol/L) decreased from 20% during 1988-1994 to 17% during 1999-2002 (P<.001). There was no change in mean HDL cholesterol levels and a nonsignificant increase in geometric mean serum triglyceride levels (P = .06).ConclusionsThe decrease in total cholesterol level observed during 1960-1994 and LDL cholesterol level observed during 1976-1994 has continued during 1999-2002 in men 60 to 74 years and women 50 to 74 years. The target value of no more than 17% of US adults with a total cholesterol level of at least 240 mg/dL (≥6.22 mmol/L), an objective of Healthy People 2010, has been attained. The increase in the proportion of adults using lipid-lowering medication, particularly in older age groups, likely contributed to the decreases in total and LDL cholesterol levels observed. The increased prevalence of obesity in the US population may have contributed to the increase in mean serum triglyceride levels.

Diagnosis and management of the metabolic syndrome. An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Executive summary.

Abstract: This Executive Summary is a synopsis of the full scientific statement from the American Heart Association (AHA) and the National Heart, Lung, and Blood Institute (NHLBI), which is intended to provide up to date guidance for professionals on the diagnosis and management of the metabolic syndrome in adults. The metabolic syndrome has received increased attention in the past few years. It consists of multiple, interrelated risk factors of metabolic origin that appear to directly promote the development of atherosclerotic cardiovascular disease (ASCVD). This constellation of metabolic risk factors is strongly associated with type 2 diabetes mellitus or the risk for this condition. The metabolic risk factors consist of atherogenic dyslipidemia (elevated triglycerides and apolipoprotein B, small LDL particles, and low HDL cholesterol [HDL-C] concentrations), elevated blood pressure, elevated plasma glucose, a prothrombotic state, and a proinflammatory state. At present, it is not clear whether the metabolic syndrome has a single cause, and it appears that it can be precipitated by multiple underlying risk factors. The most important of these underlying risk factors are abdominal obesity and insulin resistance. Other associated conditions include physical inactivity, aging, hormonal imbalance, and genetic or ethnic predisposition. Prospective population studies show that the metabolic syndrome confers an &2-fold increase in relative risk for ASCVD events, and in individuals without established type 2 diabetes mellitus, an &5-fold increase in risk for developing diabetes as compared with people without the syndrome. This finding implies that the metabolic syndrome imparts a relatively high long-term risk for both ASCVD and diabetes. In the absence of diabetes, the absolute short-term (10-year) risk for major coronary heart disease (CHD) events is not necessarily high. In the Framingham Heart Study data, the 10-year risk for CHD depends on other risk factors in addition to the metabolic syndrome components contained in Framingham scoring …

Effectiveness and tolerability of simvastatin plus fenofibrate for combined hyperlipidemia (the SAFARI trial)

Abstract: Patients with combined hyperlipidemia (elevated triglyceride [TG] levels, elevated low-density lipoprotein [LDL] cholesterol, and multiple lipoprotein abnormalities) are at increased risk for coronary heart disease. We conducted a multicenter (in the United States), randomized, double-blind, active-controlled, 18-week study to determine if combination therapy with simvastatin plus fenofibrate is more effective in reducing elevated TG levels, thus improving the lipoprotein pattern in patients with combined hyperlipidemia compared with simvastatin monotherapy, and to evaluate safety and tolerability. Patients (aged 21 to 68 years) with a diagnosis of combined hyperlipidemia (fasting TG levels >/=150 and 130 mg/dl) received simvastatin monotherapy (20 mg/day, n = 207) or simvastatin 20 mg plus fenofibrate (160 mg/day) combination therapy (n = 411) for 12 weeks following a 6-week diet and placebo run-in period. From baseline to week 12, median TG levels decreased 43.0% (combination therapy) and 20.1% (simvastatin monotherapy [treatment difference -23.6%, p <0.001]). Mean LDL cholesterol levels decreased 31.2% and 25.8% (treatment difference -5.4%, p <0.001), and high-density lipoprotein cholesterol levels increased 18.6% and 9.7% (treatment difference 8.8%, p <0.001) in the combination therapy versus monotherapy groups, respectively. No drug-related serious adverse experiences were observed. No patient experienced clinical myopathy or severe abnormalities in liver function. Combination therapy with simvastatin 20 mg and fenofibrate 160 mg in patients with combined hyperlipidemia resulted in additional improvement in all lipoprotein parameters measured compared with simvastatin 20 mg monotherapy and was well tolerated. Thus, this combination therapy is a beneficial therapeutic option for managing combined hyperlipidemia.

Joint distribution of non-HDL and LDL cholesterol and coronary heart disease risk prediction among individuals with and without diabetes.

Abstract: OBJECTIVE —To assess coronary heart disease (CHD) risk within levels of the joint distribution of non-HDL and LDL cholesterol among individuals with and without diabetes. RESEARCH DESIGN AND METHODS —We used four publicly available data sets for this pooled post hoc analysis and confined the eligible subjects to white individuals aged ≥30 years and free of CHD at baseline (12,660 men and 6,721 women). Diabetes status was defined as either “reported by physician-diagnosed and on medication” or having a fasting glucose level ≥126 mg/dl at the baseline examination. The primary end point was CHD death. Within diabetes categories, risk was assessed based on lipid levels (in mg/dl): non-HDL RESULTS —Of the subjects studied, ∼6% of men and 4% of women were defined as having diabetes. A total of 773 CHD deaths occurred during the average 13 years of follow-up time. A Cox proportional hazard model was used to estimate the relative risk (RR) of CHD death. Those with diabetes had a 200% higher RR than those without diabetes. In a multivariate model, CHD risk in those with diabetes did not increase with increasing LDL, whereas it did increase with increasing non-HDL: RR (95% confidence interval) for group 1: 5.7 (2.0–16.8); group 2: 5.7 (1.6–20.7); group 3: 7.2 (2.6–19.8); and group 4: 7.1 (3.7–13.6). CONCLUSIONS —Non-HDL is a stronger predictor of CHD death among those with diabetes than LDL and should be given more consideration in the clinical approach to risk reduction among diabetic patients.

Metabolic Syndrome Scientific Statement by the American Heart Association and the National Heart, Lung, and Blood Institute

Abstract: The metabolic syndrome is a constellation of risk factors that are associated with increased risk for atherosclerotic cardiovascular disease (ASCVD), type 2 diabetes, and their complications. This constellation consists of 5 metabolic risk factors that together increase the risk for ASCVD. These include atherogenic dyslipidemia, elevated blood pressure, elevated glucose, a prothrombotic state, and a proinflammatory state. Atherogenic dyslipidemia consists of elevations of serum total apolipoprotein B (apoB), triglycerides, small particles in low density lipoprotein (LDL), and low levels of high density lipoproteins (HDL). An elevated glucose can be in the range of impaired fasting glucose (IFG), which is called prediabetes, or at the level of diabetes. Available evidence suggests that all of the metabolic risk factors are independently atherogenic. Moreover, individuals with metabolic syndrome, particularly when IFG is present, have a high likelihood of progression to type 2 diabetes. See Circulation . 2005;112:e285 The metabolic syndrome has a multifactorial causation. The predominant underlying risk factors are obesity (especially abdominal obesity) and insulin resistance. These often occur together, and their relative contributions to the syndrome have not been fully defined. Nonetheless, there is a general agreement that the increasing prevalence of obesity in the United States and worldwide is mainly responsible for the increasing occurrence of the syndrome. …

Relationship Between C-Reactive Protein and Subclinical Atherosclerosis The Dallas Heart Study

Abstract: Background— Elevated levels of C-reactive protein (CRP) are associated with increased risk for incident cardiovascular events on the basis of observations from several prospective epidemiological studies. However, less is known regarding the relationship between CRP levels and atherosclerotic burden. Methods and Results— We measured CRP in 3373 subjects 30 to 65 years of age who were participating in the Dallas Heart Study, a multiethnic, population-based, probability sample. Electron-beam CT scans were used to measure coronary artery calcification (CAC) in 2726 of these subjects, and MRI was used to measure aortic plaque in 2393. CRP levels were associated with most traditional cardiovascular risk factors. Subjects with CAC had higher median CRP levels than those without CAC (men: median, 2.4 versus 1.8 mg/L, P<0.001; women: median, 5.2 versus 3.6 mg/L, P<0.001), and there was a modest trend toward increasing CRP levels with increased CAC levels in men (P for trend=0.003) but not in women (P for trend=0....

ENPP1/PC-1 K121Q Polymorphism and Genetic Susceptibility to Type 2 Diabetes

Abstract: Genetic susceptibility modulates the impact of obesity on risk for type 2 diabetes. The present study evaluates the role of ENPP1 K121Q polymorphism in prediction of type 2 diabetes in three populations that differ in susceptibility to diabetes and environmental exposure. The three cohorts included 679 nonmigrant South Asians living in Chennai, India (223 with type 2 diabetes); 1,083 migrant South Asians living in Dallas, Texas (121 with type 2 diabetes); and 858 nonmigrant Caucasians living in Dallas, Texas (141 with type 2 diabetes). Patients with type 2 diabetes were included in these cohorts if they had diabetes onset before the age of 60 years. The prevalence of subjects carrying the polymorphic ENPP1 121Q allele was 25% in the nondiabetic group and 34% in the diabetic group of South Asians living in Chennai (P = 0.01). The prevalence in the nondiabetic and diabetic groups were 33 and 45% (P = 0.01) for the South Asians living in Dallas and 26 and 39% (P = 0.003) for the Caucasians. Although further replication studies are necessary to test the validity of the described genotype-phenotype relationship, our study supports the hypothesis that ENPP1 121Q predicts genetic susceptibility to type 2 diabetes in both South Asians and Caucasians.

History and development of plant sterol and stanol esters for cholesterol-lowering purposes.

Abstract: Plant stanol esters provide a novel approach to lowering plasma low-density lipoprotein (LDL) cholesterol by dietary means. Their development was preceded by a long period of research into the cholesterol-lowering properties of plant sterols and, recently, plant stanols. Both classes of compound competitively inhibit the absorption of cholesterol and thus lower its level in plasma. Initial impressions were that stanols were more effective and safer than sterols, but the negative outcome of a study led to the recognition that the lipid solubility of free stanols was very limited. This was overcome by esterifying them with fatty acids, with the resultant stanol esters being freely soluble in fat spreads. This led to the launch of Benecol (margarine; Raisio Group, Raisio, Finland) in 1995. The coincident publication of the year-long North Karelia study conclusively demonstrated the long-term LDL-lowering efficacy of plant stanol esters. Variables that might influence the efficacy of stanol esters include dose, frequency of administration, food vehicle in which the stanol ester is incorporated, and background diet. The effective dose is 1 to 3 g/day, expressed as free stanol, which, in placebo-controlled studies, decreased LDL cholesterol by 6% to 15%. This effect is maintained, appears to be similar with once-daily or divided dosage, and is independent of the fat content of the food vehicle. Short-term studies suggest that equivalent amounts of plant sterol and stanol esters are similarly effective in lowering LDL, the main difference being that plasma plant sterol levels increase on plant sterols and decrease on plant stanols. The clinical significance of these changes remains to be determined.

The issue of statin safety: where do we stand?

Abstract: Statins are first-line therapy for reducing low-density lipoprotein (LDL) levels in patients at high risk for atherosclerotic cardiovascular disease (ASCVD).1,2 These agents are being used in millions of high-risk people worldwide. Many others receive statins for primary prevention. The total number can only be expected to rise with time. Although favorable results from a large number of controlled clinical trials underpin the benefits of statin therapy,2 it is not surprising that the safety of statins has received much attention. Controlled trials and clinical practice have demonstrated that they generally are safe; in fact, the frequency of clinically significant side effects is quite low. In rare patients, nonetheless, side effects can occur and occasionally are serious. Most serious among these is severe myopathy (rhabdomyolysis), which can cause acute renal failure. In a small percentage of patients, statins elevate serum transaminases. There is little or no evidence that statins cause progressive liver disease3; nevertheless, persistent elevations in transaminases can be perplexing. Other less serious side effects may occur. One of these that was demonstrated recently is low-grade proteinuria, likely due to a statin-induced inhibition of proximal tubular reabsorption of protein.4 To date, no evidence exists that this is accompanied by pathological tubular injury or progression to chronic renal failure. See p 3051 Side effects of statins tend to be dose related. Most side effects, including myopathy, disappear on withdrawal of the medication. Even with severe myopathy, most patients survive with supportive measures, although fatalities occasionally occur. For example, Omar and Wilson5 reported that between November 1997 and March 2000, 871 cases of statin-associated severe myopathy were reported to the US Food and Drug Administration (FDA); among these reports, however, only 38 cases were listed as fatal. Six statins currently are available by prescription in the United …

Influence of extended-release nicotinic acid on nonesterified fatty acid flux in the metabolic syndrome with atherogenic dyslipidemia.

Abstract: Nicotinic acid has favorable effects on atherogenic dyslipidemia. However, in some patients who have diabetes, crystalline nicotinic acid decreases glycemic control; this effect could be due to a marked rebound of nonesterified fatty acids (NEFAs) observed after nicotinic acid suppression of lipolysis in adipose tissue. Recent reports have indicated that small doses of extended-release nicotinic acid do not cause a substantial decrease in glucose levels. Therefore, in this study, we examined whether 2 g/day of extended-release nicotinic acid abolishes the NEFA rebound that is reported with crystalline nicotinic acid. Seventeen men who had the metabolic syndrome (8 did not have type 2 diabetes and 9 did) were treated for 4 months. At baseline and at 4 months, measurements were made of plasma glucose, insulin, and NEFA during an oral glucose tolerance test. At 3 months, effects of extended-release nicotinic acid on NEFA levels and flux rates were determined on 3 separate days at 3 separate intervals after the final dose of nicotinic acid (4, 9, and 28 hours). Values obtained at 28 hours were taken as baseline (i.e., no nicotinic acid remaining in the circulation). After 4 hours (percent baseline), NEFA levels were -30% without diabetes and -37% with diabetes, and flux rates were -21% without diabetes and -25% with diabetes; after 9 hours, NEFA levels were 43% without diabetes and 50% with diabetes, and flux rates were 38% without diabetes and 70% with diabetes. Extended-release nicotinic acid did not abolish NEFA rebound. Nonetheless, the rebound was much less than previously reported for crystalline nicotinic acid. Moreover, after 4 months of nicotinic acid therapy, levels of NEFA, glucose, and insulin during the oral glucose tolerance test were not significantly different from those before institution of nicotinic acid therapy, suggesting minimal changes in insulin sensitivity.

Relation between atherogenic dyslipidemia and the Adult Treatment Program-III definition of metabolic syndrome (Genetic Epidemiology of Metabolic Syndrome Project)

Abstract: Genetic Epidemiology of Metabolic Syndrome is a multinational, family-based study to explore the genetic basis of the metabolic syndrome. Atherogenic dyslipidemia (defined as low plasma high-density lipoprotein cholesterol with elevated triglycerides ( 75th percentile for age, gender, and country, respectively) identified affected subjects for the metabolic syndrome. This report examines the frequency at which atherogenic dyslipidemia predicts the metabolic syndrome of the National Cholesterol Education Program Adult Treatment Panel III (ATP-III). One thousand four hundred thirty-six (854 men/582 women) affected patients by our criteria were compared with 1,672 (737 men/935 women) unaffected persons. Affected patients had more hypertension, obesity, and hyperglycemia, and they met a higher number of ATP-III criteria (3.2 ± 1.1 SD vs 1.3 ± 1.1 SD, p 35 years. In subjects aged

Point: The Metabolic Syndrome Still Lives

Abstract: Dr. Gerald Reaven’s report (1) of the death of the metabolic syndrome may be exaggerated. Whether his obituary relates specifically to the National Cholesterol Education Program’s Adult Treatment Panel III (ATP III) (2) definition of metabolic syndrome or to all attempts at making a clinical definition of the metabolic syndrome is unclear. Regardless, he does a thorough autopsy on the ATP III report and appears to find widespread systemic disease. After reading his postmortem examination, however, one wonders whether he is reporting on the death of the syndrome or rather is dissecting it while it is still alive. The editors of Clinical Chemistry have given me a last chance to resuscitate what appears to be a badly mangled body. In my examination of the corpus, however, I see signs of life. Thanks to advances of modern medicine, it may be possible achieve survival. This is my assigned task. Of interest is the fact that Dr. Reaven’s sharp blade cuts only into the ATP III definition of the metabolic syndrome. Other definitions escape his knife, specifically those of the WHO (3), the European Group on Insulin Resistance (EGIR) (4), and the American Association of Clinical Endocrinologists (AACE) (5). The definitions put forward by these organizations are similar to those of ATP III, but apparently Dr. Reaven believes that the ATP III is the most flawed of the group. Because I was a member of the team that issued the ATP III criteria, perhaps I can offer a rationale for having done so. Several points can be made in their defense. In 1993, the ATP II report (6) placed increased emphasis on management of obesity to reduce risk for atherosclerotic cardiovascular disease (ASCVD). This emphasis was not widely adopted by practicing physicians, and by all accounts, the problem of obesity in the …

Stanol Esters as a Component of Maximal Dietary Therapy in the National Cholesterol Education Program Adult Treatment Panel III Report

Abstract: Use of plant stanols/sterols in forms that are sufficiently bioavailable for therapeutic effect should be a key element of maximal dietary therapy. This principle was recognized by National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) and has been amply confirmed by experimental studies in humans. Since the introduction of statins, dietary therapy for control of elevated low-density lipoprotein (LDL) cholesterol levels has received less attention. The time has come, however, to reassert the importance of maximal dietary therapy as a cost-effective means for treatment of elevated LDL concentrations and for lifetime prevention of coronary heart disease.

Responsiveness of plasma lipids and lipoproteins to plant stanol esters.

Abstract: Plant stanols have been shown to reduce serum levels of low-density lipoprotein (LDL) cholesterol, and they are an attractive adjunct in dietary therapy for elevated LDL cholesterol. This investigation addressed 3 questions through metabolic studies in human subjects: (1) whether plant stanol esters given at higher doses than the 2-g/day dose recommended by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) will provide additional LDL-lowering efficacy (study 1); (2) whether substantial reduction in LDL cholesterol can be obtained in postmenopausal women with hypercholesterolemia by addition of plant stanol esters to the diet (study 2); and (3) whether ATP III goals can be obtained by adding plant stanol esters to an LDL-lowering regimen in high-risk patients who retain LDL cholesterol levels in the above-optimal range (ie, 2.6 to 3.3 mmol/L [100 to 129 mg/dL]), despite ongoing statin therapy (study 3). Study 1 showed that maximal LDL lowering with plant stanols in the form of esters can be achieved at a dose of 2 g/day. Higher doses do not provide additional efficacy. Study 2 demonstrated that stanol esters can reduce LDL cholesterol levels in postmenopausal women by about 13%, which makes use of stanol esters attractive as a component of nondrug therapy in these women who generally are at relatively low risk for coronary heart disease. Finally, study 3 found that plant stanols provide additional lowering of LDL cholesterol when added to ongoing statin therapy. This makes plant stanols an attractive dietary component to help to achieve the goals of LDL-lowering therapy in patients requiring an LDL-lowering drug.

Metabolic syndrome: therapeutic considerations.

Abstract: The metabolic syndrome is a constellation of metabolic risk factors for atherosclerotic cardiovascular disease (ASCVD) occurring in one individual. There are five cardiovascular risk factors that accompany the metabolic syndrome: atherogenic dyslipidemia [elevated apolipoprotein B (apo B), elevated triglyceride, small low-density lipoprotein (LDL) particles, and low high-density lipoprotein (HDL)cholesterol], elevated blood pressure, elevated glucose, a prothrombotic state, and a proinflammatory state. The likelihood of an individual developing metabolic syndrome is enhance by underlying risk factors, notably, obesity, insulin resistance, lack of physical activity, advancing age, and hormonal factors (e.g., androgens and corticosteroids). Besides being at higher risk for ASCVD, persons with the metabolic syndrome are at increased risk for type 2 diabetes. Persons with the metabolic syndrome deserve management in the clinical setting to reduce the risk for both ASCVD and type 2 diabetes. The two major therapeutic strategies for treatment of affected persons are modification of the underlying risk factors and separate drug treatment of the particular metabolic risk factors when appropriate. First-line therapy for underlying risk factors is therapeutic lifestyle changes, i.e., weight loss in obese persons, increased physical activity, and anti-atherogenic diet. These changes will improve all of the metabolic risk factors. Whether use of drugs to reduce insulin resistance is effective, safe, and cost-effective before the onset of diabetes awaits the results of more clinical research. Turning to individual risk components, for atherogenic dyslipidemia, drug therapies that promote lowering of apo B and raise HDL cholesterol will be needed for higher risk patients. Treatment of categorical hypertension with drugs has become standard practice. When hyperglycemia reaches the diabetic level, glucose-lowering agents will become necessary when dietary control is no longer effective, and reduction of a prothrombotic state with low-dose aspirin may be indicated in higher-risk patients.

Intensive Lipid Lowering With Atorvastatin in Patients With Stable Coronary Disease

Abstract: s since January 1975, a full-text search capacity, and a personal archive for saving articles and search results of interest. All articles can be printed in a format that is virtually identical to that of the typeset pages. Beginning six months after publication, the full text of all Original Articles and Special Articles is available free to nonsubscribers who have completed a brief registration. The New England Journal of Medicine Downloaded from nejm.org at COLUMBIA UNIV HEALTH SCIENCES LIB on April 18, 2012. For personal use only. No other uses without permission. Copyright © 2005 Massachusetts Medical Society. All rights reserved.