Effects of fenofibrate treatment on cardiovascular disease risk in 9,795 individuals with type 2 diabetes and various components of the metabolic syndrome: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study

OBJECTIVE—We explored whether cardiovascular disease (CVD) risk and the effects of fenofibrate differed in subjects with and without metabolic syndrome and according to various features of metabolic syndrome defined by the Adult Treatment Panel III (ATP III) in subjects with type 2 diabetes in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.RESEARCH DESIGN AND METHODS—The prevalence of metabolic syndrome and its features was calculated. Cox proportional models adjusted for age, sex, CVD status, and baseline A1C levels were used to determine the independent contributions of metabolic syndrome features to total CVD event rates and the effects of fenofibrate.RESULTS—More than 80% of FIELD participants met the ATP III criteria for metabolic syndrome. Each ATP III feature of metabolic syndrome, apart from increased waist circumference, increased the absolute risk of CVD events over 5 years by at least 3%. Those with marked dyslipidemia (elevated triglycerides ≥2.3 mmol/l and low HDL cholesterol) were at the highest risk of CVD (17.8% over 5 years). Fenofibrate significantly reduced CVD events in those with low HDL cholesterol or hypertension. The largest effect of fenofibrate to reduce CVD risk was observed in subjects with marked dyslipidemia in whom a 27% relative risk reduction (95% CI 9–42, P = 0.005; number needed to treat = 23) was observed. Subjects with no prior CVD had greater risk reductions than the entire group.CONCLUSIONS—Metabolic syndrome components identify higher CVD risk in individuals with type 2 diabetes, so the absolute benefits of fenofibrate are likely to be greater when metabolic syndrome features are present. The highest risk and greatest benefits of fenofibrate are seen among those with marked hypertriglyceridemia.Subjects with metabolic syndrome have a higher risk for future cardiovascular disease (CVD) events and are more likely to develop diabetes (1). The various components of metabolic syndrome (abdominal obesity, dyslipidemia, hypertension, and glucose deregulation) confer differential risk for CVD based on the extent to which they deviate from healthy normality. The guidelines most commonly used clinically to define metabolic syndrome are the National Cholesterol Education Program Adult Treatment Panel III (ATP III) guidelines (2). The exact role of each individual metabolic syndrome component in modifying risk once diabetes is present has varied in previous studies (3,4).The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study was designed to assess the long-term effect of fenofibrate on CVD events in subjects with type 2 diabetes (5–7). The cohort of 9,795 subjects followed for an average of 5 years was sufficient to explore whether CVD event rates were increased in subjects with or without various metabolic syndrome features. Because fenofibrate modifies lipid parameters by changing LDL particle morphology, increasing HDL cholesterol, and reducing triglycerides, CVD event rates may be reduced to a larger degree in those with metabolic syndrome features reflecting a more atherogenic lipid profile at baseline.In this article, we explored the clinical relevance of metabolic syndrome and its features when type 2 diabetes is established and whether reductions in CVD event rates with fenofibrate differ according to the presence of metabolic syndrome or its particular features. We also explored the value of a higher cut point for marked dyslipidemia, using an elevated triglyceride level (≥2.3 mmol/l) either alone or in combination with a low plasma HDL cholesterol level as defined in the Helsinki Heart Study (HHS) (8).     

Racial and Ethnic Differences in the Presentation of Metabolic Syndrome

This paper explores the effectiveness of the Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III) recommendations for diagnosing metabolic syndrome in people from specific racial and ethnic groups. More than 50 million adult Americans have metabolic syndrome. Some racial and ethnic minority groups have much higher percentages of the metabolic syndrome than general population estimates suggest. However, some minority populations in the United States such as Hispanics appear to be underdiagnosed. A literature review was conducted to determine whether the general ATP III guidelines have sufficient screening criteria for detecting metabolic syndrome in various racial and ethnic minority groups. Research articles published in the United States from 2000 to 2005 were reviewed. Studies were included that presented data related to black, Hispanic, and Asian American male and female subjects older than age 18. Waist circumference appears to be the most predictive screening factor among the metabolic syndrome criteria. Patients with normal body mass indexes may still have elevated waist circumferences that meet the ATP III risk criteria for metabolic syndrome. Blacks have high rates of hypertension even without considering metabolic syndrome, and they may have more disease risk than other populations. Hispanics have an increased risk of diabetes associated with metabolic syndrome. Because the criteria may not be sufficient to diagnose metabolic syndrome in Asian Americans as a result of different body types, the diagnosis might be missed in this group. There is a need for more research on how the diagnosis of metabolic syndrome presents in different racial and ethnic minority groups in the United States. Practitioners need evidence-based screening tools that will provide the most accurate information for evaluating persons of racial and ethnic groups who are most at risk of diabetes, cardiovascular disease, and stroke. The determination of the applicability of screening criteria to diverse patient populations is vital to providers who are obligated to provide culturally competent care to their patients. This paper synthesizes selected literature and presents recommendations to assist nurse practitioners in the assessment of metabolic syndrome in specific racial and ethnic minority groups.     

The metabolic syndrome and 11-year risk of incident cardiovascular disease in the atherosclerosis risk in communities study

OBJECTIVE: To assess the magnitude of the association between the National Cholesterol Education Program's Third Adult Treatment Panel Report (ATP III) definition of the metabolic syndrome and cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS: Cox regression was used to estimate the relative risk of incident coronary heart disease (CHD) and stroke among 12,089 black and white middle-aged individuals in the Atherosclerosis Risk in Communities (ARIC) study. RESULTS: The metabolic syndrome was present in approximately 23% of individuals without diabetes or prevalent CVD at baseline. Over an average of 11 years of follow-up, 879 incident CHD and 216 ischemic stroke events occurred. Among the components of the metabolic syndrome, elevated blood pressure and low levels of HDL cholesterol exhibited the strongest associations with CHD. Men and women with the metabolic syndrome were approximately 1.5 and 2 times more likely to develop CHD than control subjects after adjustment for age, smoking, LDL cholesterol, and race/ARIC center (sex interaction P < 0.03). Similar associations were found between the metabolic syndrome and incident ischemic stroke. Comparison of receiver operating characteristic curves indicated that the metabolic syndrome did not materially improve CHD risk prediction beyond the level achieved by the Framingham Risk Score (FRS). CONCLUSIONS: Individuals without diabetes or CVD, but with the metabolic syndrome, were at increased risk for long-term cardiovascular outcomes, although statistical models suggested that most of that risk was accounted for by the FRS. Nevertheless, identification of individuals with the metabolic syndrome may provide opportunities to intervene earlier in the development of shared disease pathways that predispose individuals to both CVD and diabetes.     

Critical evaluation of adult treatment panel III criteria in identifying insulin resistance with dyslipidemia

OBJECTIVE: The goal of this study was to evaluate the efficacy of the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III) in identifying insulin resistance. RESEARCH DESIGN AND METHODS: This study included 74 nondiabetic Caucasians who were evaluated for insulin resistance and risk factors associated with the metabolic syndrome. Glucose disposal rate (GDR) was measured by hyperinsulinemic-euglycemic clamp and was used to quantify insulin resistance. Sensitivity and specificity of ATP III criteria in detecting insulin resistance were calculated for various cutoffs of GDR. RESULTS: Insulin resistance was associated with increased waist circumference, fasting glucose, blood pressure, triglycerides, and decreased levels of HDL cholesterol. Only 12.2% of study subjects met ATP III criteria for metabolic syndrome, and ATP III criteria exhibited low sensitivity for detecting insulin resistance. Although high in specificities (>90%), the sensitivities of ATP III criteria ranged only between 20 and 50% when insulin resistance was defined as various GDR cutoff values below 10 to 12 mg.kg(-1).min(-1). The larger number of subjects who were insulin resistant but did not meet ATP III criteria were found to have an adverse cardiovascular disease risk profile, including higher BMI, waist circumference, fasting glucose, triglycerides, and an unfavorable lipoprotein subclass profile determined by nuclear magnetic resonance compared with insulin-sensitive individuals (i.e., increased large VLDL, increased small LDL, and decreased large HDL particle concentrations). CONCLUSIONS: ATP III criteria have low sensitivity for identifying insulin resistance with dyslipidemia in nondiabetic individuals who are at increased risk for cardiovascular disease and diabetes. More sensitive criteria should be developed for clinical assessment of metabolic and cardiovascular disease risk relevant to the metabolic syndrome.     

Global coronary heart disease risk assessment of individuals with the metabolic syndrome in the U.S

OBJECTIVE—Although metabolic syndrome is related to an increased risk of coronary heart disease (CHD) events, individuals with metabolic syndrome encompass a wide range of CHD risk levels. This study describes the distribution of 10-year CHD risk among U.S. adults with metabolic syndrome.RESEARCH DESIGN AND METHODS—Metabolic syndrome was defined by the modified National Cholesterol Education Program (NCEP)/Third Adult Treatment Panel (ATP III) definition among 4,293 U.S. adults aged 20–79 years in the National Health and Nutrition Examination Survey 2003–2004. Low-, moderate-, moderately high–, and high-risk statuses were defined as <6, 6 to <10, 10–20, and >20% probability of CHD in 10 years (based on NCEP/ATP III Framingham risk score algorithms), respectively; those with diabetes or preexisting cardiovascular disease were assigned to high-risk status.RESULTS—The weighted prevalence of metabolic syndrome by NCEP criteria in our study was 29.0% overall (30.0% in men and 27.9% in women, P = 0.28): 38.5% (30.7% men and 46.9% women) were classified as low risk, 8.5% (7.9% men and 9.1% women) were classified as moderate risk, 15.8% (23.4% men and 7.6% women) were classified as moderately high risk, and 37.3% (38.0% men and 36.5% women) were classified as high risk. The proportion at high risk increased with age but was similar among Hispanics, non-Hispanic whites, and non-Hispanic blacks.CONCLUSIONS—Although many subjects with metabolic syndrome have a low calculated risk for CHD, about half have a moderately high or high risk, reinforcing the need for global risk assessment in individuals with metabolic syndrome to appropriately target intensity of treatment for underlying CHD risk factors.The metabolic syndrome is a cluster of risk factors often linked to insulin resistance that has been shown to increase the risk for development of cardiovascular disease (CVD). Individuals with metabolic syndrome have an increased risk of coronary heart disease (CHD) and CVD mortality (1,2). Global risk assessment using Framingham risk prediction algorithms is often the initial evaluation of CHD risk in subjects with multiple risk factors, including those with metabolic syndrome (3). Although it is often assumed that individuals with metabolic syndrome have a high risk of CVD, many have only borderline elevations in risk factors and thus may actually have either a low or intermediate risk of CVD (4). Therefore, assessment of global risk of CHD in individuals with metabolic syndrome may be helpful to most appropriately target the intensity of cardiometabolic risk factor interventions for prevention of diabetes or cardiovascular disease.The aim of this article was to calculate the global risk of CHD in adults with metabolic syndrome in the U.S. to better characterize the diversity in their risk of CHD using the data from the National Health and Nutrition Examination Survey (NHANES) 2003–2004. In addition, we will examine the global risk of CHD in individuals with metabolic syndrome across sex, ethnicity, and age-groups and examine goal attainment and distance to recommended levels for key CHD risk factors.     

A guideline-driven assessment of need for cardiovascular disease risk intervention in persons with chronic paraplegia

OBJECTIVE: To examine percentages of persons with chronic paraplegia who qualify for lipid-lowering therapeutic lifestyle intervention (TLI) as assessed by authoritative guidelines. DESIGN: Cross-sectional. SETTING: Academic medical center. PARTICIPANTS: Forty-one subjects (mean age +/- standard deviation, 34+/-11 y) with motor-complete paraplegia (American Spinal Injury Association grade A or B) at T6-L1 levels for greater than 2 years. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Percentages of subjects qualifying for TLI were independently assessed and then compared using National Cholesterol Education Project Adult Treatment Panel (ATP) II (1994) and ATP III (2002) Guidelines. RESULTS: A total of 34.1% of subjects qualified for intervention based on the ATP II Guidelines and 63.4% based on ATP III (chi1(2) test=4.53; 2-tailed, P=.003). Seventy-six percent (31/41) of study participants had high-density lipoprotein cholesterol levels below the high-risk criterion of 40 mg/dL established by ATP III. Almost one third of subjects had hypertension, and 34.1% satisfied criteria for diagnosis of the metabolic syndrome. CONCLUSIONS: A high percentage of young, apparently healthy people with chronic paraplegia are at risk for cardiovascular disease and qualify for lipid-lowering TLI. Updated guidelines of the ATP III have increased the urgency for early risk assessment and intervention.     

Prevalence and factor analysis of metabolic syndrome in an urban Korean population

OBJECTIVE: The aim of this study was to explore the prevalence and pattern of the metabolic syndrome and its association with hyperinsulinemia in an urban Korean population of 269 men and 505 women. RESEARCH DESIGN AND METHODS: The National Cholesterol Education Program Adult Treatment Panel (ATP) III guidelines were used to calculate the sex-specific prevalence of the metabolic syndrome. After excluding individuals taking medication for hypertension, diabetes, or dyslipidemia, we used factor analysis to examine the pattern of the metabolic syndrome in 206 men and 449 women. RESULTS: The prevalence of metabolic syndrome was 16.0% in men and 10.7% in women aged 30-80 years. However, ATP III criteria for central obesity are not optimal for an Asian-Pacific population; when waist circumference is reduced from 102 to 90 cm in men and 88 to 80 cm in women, the prevalence of the metabolic syndrome increased to 29.0 and 16.8%, respectively. Sex-specific factor analysis showed four factors in men (obesity, glucose intolerance, hypertension, and dyslipidemia) and three in women (obesity-hypertension, glucose intolerance, and obesity-dyslipidemia). Insulin resistance estimated from fasting insulin levels clustered with three of the four factors in men and two of the three factors in women. By ATP III or Asian-Pacific waist circumference criteria, the prevalence of the metabolic syndrome increased with increasing tertiles of insulin resistance, which was estimated by a homeostasis model assessment. CONCLUSIONS: The metabolic syndrome is common in an urban Korean population when using Asian-Pacific waist criteria. The prevalence of the metabolic syndrome increased with increasing tertiles of insulin resistance.     

Successful control of dyslipidemia in patients with metabolic syndrome: focus on lifestyle changes

Approaches to controlling dyslipidemia in patients with metabolic syndrome must take into consideration a patient's individual characteristics and underlying lipid disorder. Some patients will require pharmacologic therapy, whereas others can be controlled with lifestyle changes alone. The National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) guidelines recommend that patients with at least 3 of the following clinical variables be designated as having metabolic syndrome: abdominal obesity as reflected in increased waist circumference; a low high-density lipoprotein cholesterol (HDL-C) level; an elevated triglyceride level; elevated blood pressure or treatment with antihypertensive medications; and/or elevated fasting plasma glucose or treatment with antidiabetic medications. Unless patients with metabolic syndrome change their lifestyle, existing cardiovascular and metabolic risk factors will worsen or new risk factors will develop. This helps explain why these patients are at increased risk for developing type 2 diabetes mellitus (DM) and coronary heart disease (CHD). The lifestyle changes recommended by NCEP ATP III for controlling dyslipidemia (i.e., elevated levels of triglycerides and decreased levels of HDL-C) in patients with metabolic syndrome or type 2 DM include (1) reduced intake of saturated fats and dietary cholesterol, (2) intake of dietary options to enhance lowering of low-density lipoprotein cholesterol, (3) weight control, and (4) increased physical activity. If lifestyle changes are not successful for individuals at high risk of developing CHD, or for those who currently have CHD, a CHD risk equivalent, or persistent atherogenic dyslipidemia, then pharmacotherapy may be necessary as defined by NCEP ATP III guidelines.     

The prevalence of the metabolic syndrome among arab americans

OBJECTIVE: To estimate the prevalence of the metabolic syndrome in Arab Americans by age, sex, and BMI and to examine the association between insulin resistance and each of the components of the metabolic syndrome. RESEARCH DESIGN AND METHODS: We studied a representative, cross-sectional, population-based sample of 542 Arab Americans aged 20-75 years. The metabolic syndrome was defined by Adult Treatment Panel III (ATP III) and World Health Organization (WHO) diagnostic criteria. Insulin resistance was estimated by homeostasis model assessment (HOMA-IR). RESULTS: The age-adjusted prevalence of the metabolic syndrome was 23% (95% CI 19-26%) by the ATP III definition and 28% (24-32%) by the WHO definition. Although the prevalence increased significantly with age and BMI in both sexes by both definitions, differences in estimates were noted. With ATP III, the age-specific rates were similar for men and women aged 20-49 years but were significantly higher for women aged >/=50 years. With WHO, rates were higher for men than women aged 20-49 years and similar for those aged >/=50 years. The most common component of the metabolic syndrome in men and women was low HDL cholesterol with the ATP III and the presence of glucose intolerance and HOMA-IR with the WHO. Strong associations between HOMA-IR and individual components of the metabolic syndrome were observed. After fitting a model with HOMA-IR as the outcome, waist circumference, triglyceride level, and fasting plasma glucose level were significantly associated with HOMA-IR. CONCLUSIONS: The metabolic syndrome is common among Arab Americans and is related to modifiable risk factors.     

Metabolic Syndrome: Comparison of Occurrence Using Three Definitions in Hypertensive Patients

Objective: To compare the frequency of occurrence of metabolic syndrome using three international definitions and to study the distribution of cardiovascular risk factors among newly diagnosed hypertensive Nigerian subjects.Design: Cross sectional study.Settings: Cardiology unit of LAUTECH Teaching Hospital, Osogbo, Nigeria.Participants: One hundred forty newly diagnosed hypertensive Nigerian subjects, and 70 normotensive controls (age- and sex-matched) were included in this study.Methods: Clinical history and relevant laboratory investigations were performed on all study participants. The definition of metabolic syndrome was based on three international definitions: World Health Organization (WHO), International Diabetes Federation (IDF), and National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III). Ethical approval was obtained for the study. Statistical analyses were performed using SPSS 16.0.Results: There was no difference in age and gender distribution between the hypertensive subjects and controls. (55.14 ± 10.83 years, females 53.6% vs. 54.67 ± 10.89 years, females 52.9% respectively, P>0.05). The frequency of occurrence of metabolic syndrome among hypertensives was 34.5% according to WHO, 35.0% according to NCEP ATP III, and 42.5% according to IDF criteria. Visceral obesity and reduced high-density lipoprotein (HDL) were the other common cardiovascular risk factors among newly diagnosed hypertensive subjects. Female hypertensives had a higher prevalence of visceral obesity and low HDL.Conclusion: Frequency of occurrence of metabolic syndrome was similar using the NCEP ATP III and WHO definitions. However, the IDF definition resulted in a higher frequency because of the lower cut-off for waist circumference used for identification of visceral obesity. Metabolic syndrome is present in a significant proportion of newly diagnosed hypertensive subjects. Therefore, appropriate screening and treatment are required.     

The metabolic syndrome in older individuals: prevalence and prediction of cardiovascular events: the Cardiovascular Health Study

OBJECTIVE: The prevalence of the metabolic syndrome, a potent risk factor for cardiovascular diseases (CVDs), has not been adequately explored in older individuals. Moreover, two sets of criteria have been proposed for the definition of metabolic syndrome, one by the World Health Organization (WHO) and one by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII). We therefore investigated the prevalence of this syndrome in a subgroup of older participants from the Cardiovascular Health Study (CHS) who were free of CVD at baseline. We also compared the prognostic significance of the two definitions of the metabolic syndrome. RESEARCH DESIGN AND METHODS: A total of 2,175 subjects from the CHS who were free of CVD at baseline and not taking antihypertensive or lipid-lowering medications were studied. Prevalence of the metabolic syndrome was assessed with both the WHO and ATPIII criteria. The incidence of coronary or cerebrovascular disease was ascertained during a median follow-up time of 4.1 years. RESULTS: Prevalence of the metabolic syndrome was 28.1% by ATPIII criteria and 21.0% by WHO criteria. The two sets of criteria provided concordant classification for 80.6% of participants. Multivariate Cox propotional hazard models showed that the metabolic syndrome defined with the ATPIII criteria, but not with the WHO criteria, was an independent predictor of coronary or cerebrovascular events and was associated with a 38% increased risk (hazard ratio 1.38 [95% CI 1.06-1.79], P < 0.01). CONCLUSIONS: Prevalence of the metabolic syndrome in older individuals is approximately 21-28% (depending on the definition used). The two sets of criteria have 80% concordance in classifying subjects. As defined by the ATPIII criteria, the metabolic syndrome yields independent prognostic information, even after adjusting for traditional cardiovascular risk factors and the individual domains of the metabolic syndrome.     

Low ankle-brachial pressure index predicts increased risk of cardiovascular disease independent of the metabolic syndrome and conventional cardiovascular risk factors in the Edinburgh Artery Study

OBJECTIVE: To investigate whether a low ankle-brachial pressure index (ABI) predicts increased risk of cardiovascular disease (CVD) independent of the metabolic syndrome and conventional cardiovascular risk factors. RESEARCH DESIGN AND METHODS: The Edinburgh Artery Study is a population-based cohort study in which subjects were followed up until their death or for approximately 15 years. Low ABI at baseline was defined as <0.9; subjects with ABI >1.4 (n = 13) were excluded from the analyses. We used a modified version of the definition of the metabolic syndrome published in the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, replacing waist circumference criteria with BMI criteria. Data on relevant parameters were available for 1,467 men and women ages 55-74 years at baseline. Cox proportional hazards models were used to study cardiovascular morbidity and mortality before and after adjusting for potential confounding factors. RESULTS: We determined that 25% of the study population had the metabolic syndrome and that a low ABI was more prevalent among people with than without the metabolic syndrome (24 vs. 15%; P < 0.001). During the follow-up period, there were 226 deaths from CVD and 462 nonfatal cardiovascular events. The hazard ratio (95% CI) for low ABI after adjusting for age, sex, baseline CVD, diabetes, smoking status, LDL cholesterol, and metabolic syndrome was 1.5 (1.1-2.1) for CVD mortality and 1.5 (1.2-1.8) for all CVD outcomes. CONCLUSIONS: Low ABI is associated with increased risk of CVD independent of the metabolic syndrome and other major CVD risk factors.     

The importance of waist circumference in the definition of metabolic syndrome: prospective analyses of mortality in men

OBJECTIVE: The purpose of this study was to compare the predictive ability of the National Cholesterol Education Panel (NCEP), revised NCEP (NCEP-R), and International Diabetes Federation (IDF) metabolic syndrome criteria for mortality risk, and to examine the effects of waist circumference on mortality within the context of these criteria. RESEARCH DESIGN AND METHODS: The sample included 20,789 white, non-Hispanic men 20-83 years of age from the Aerobics Center Longitudinal Study. The main outcome measures were all-cause and cardiovascular disease (CVD) mortality over 11.4 years of follow-up. RESULTS: The proportions of men with the metabolic syndrome were 19.7, 27, and 30% at baseline, respectively, according to NCEP, NCEP-R, and IDF criteria. A total of 632 deaths (213 CVD) occurred. The relative risks (RRs) and 95% CIs of all-cause mortality were 1.36 (1.14-1.62), 1.31 (1.11-1.54), and 1.26 (1.07-1.49) for the NCEP, NCEP-R, and IDF definitions, respectively. The corresponding RRs for CVD mortality were 1.79 (1.35-2.37), 1.67 (1.27-2.19), and 1.67 (1.27-2.20). Additionally, there was a significant trend for a higher risk of CVD mortality across waist circumference categories (<94, 94-102, and >102 cm) among men with at least two additional metabolic syndrome risk factors (P = 0.01). CONCLUSIONS: The prediction of mortality with IDF and NCEP metabolic syndrome criteria was comparable in men. Waist circumference is a valuable component of metabolic syndrome; however, the IDF requirement of an elevated waist circumference warrants caution given that a large proportion of men with normal waist circumference have multiple risk factors and an increased risk of mortality.     

Relative risks of the metabolic syndrome according to the degree of insulin resistance in apparently healthy Korean adults

A new simple criterion for diagnosing metabolic syndrome was proposed in the third report of the NCEP (National Cholesterol Education Program). In the present study, we analysed the association between metabolic syndrome and insulin resistance to investigate the effects of the latter on the prevalence of metabolic syndrome based on the new criteria recommended in the ATP (Adult Treatment Panel) III report. A total of 7057 participants (4472 men and 2585 women), who underwent medical screening at the Sungkyunkwan University Kangbuk Samsung Hospital, were investigated. Fasting insulin levels were measured and components of the metabolic syndrome as defined by the ATP III report were determined. We also applied the criteria for abdominal obesity as defined by APC-WC (Asia-Pacific criteria for waist circumference). The prevalence of metabolic syndrome as defined by ATP III was 5.3% (5.0% in men and 5.8% in women) and 8.9% (8.1% in men and 10.3% in women) by APC-WC. The odds ratio for the metabolic syndrome was significantly higher in subjects with higher insulin resistance than in those with lower insulin resistance. The mean levels of HOMA (homoeostatic model assessment) and fasting insulin were significantly higher in those with more of the components of the metabolic syndrome. A high HOMA (> or =2.56) and fasting insulin concentration (> or =9.98 microIU/ml; where IU is international unit) were found to be independent risk factors of the metabolic syndrome by multiple regression analysis after adjusting for age, sex and body mass index (P<0.001). These results show that the metabolic syndrome is significantly correlated with the insulin resistance index, and that appropriate values of HOMA and fasting insulin concentration may serve as a helpful guide for the management of metabolic syndrome.     

Calculating insulin resistance in the primary care setting: why should we worry about insulin levels in euglycemic patients?

PURPOSE: To describe measures that would determine which patients are insulin resistant and at risk for the metabolic syndrome and its sequelae cardiovascular diseases (CVD) and to analyze methods to determine the presence of insulin resistance and the advantages or disadvantages of each. DATA SOURCES: Review of the multidisciplinary clinical and research literature. CONCLUSIONS: Insulin resistance occurs early in the trajectory of the metabolic syndrome, making it a prime candidate for timely interventions to reduce risk for both type 2 diabetes and CVD. Therefore, prompt recognition of insulin resistance prior to the development of the full metabolic syndrome, type 2 diabetes, and/or CVD may assist in the prevention of morbidity and premature mortality. Likewise, because many insulin-resistant patients belong to minority racial groups (i.e., African American, Hispanic, Native American, or Pacific Islanders), early identification may have a positive impact on the reduction of cardiovascular health disparities. IMPLICATIONS FOR PRACTICE: Documenting the presence of insulin resistance will assist the practitioner to determine if a low-risk patient is in jeopardy for development of type 2 diabetes and/or CVD. Early cardiovascular risk identification is important to clinical practice as it allows more time for the practitioner to counsel patients for the essential planning needed to make lifestyle changes.     

Metabolic syndrome: risk factor distribution and 18-year mortality in the multiple risk factor intervention trial

OBJECTIVE: To examine the long-term association of metabolic syndrome with mortality among those at high risk for cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS: A total of 10,950 Multiple Risk Factor Intervention Trial (MRFIT) survivors were followed for mortality an additional median 18.4 years (1980-1999). Proportional hazards models examined multivariate-adjusted risks associated with Adult Treatment Panel III-defined metabolic syndrome conditions, with BMI substituted for waist circumference. RESULTS: At MRFIT annual visit 6, 4,588 (41.9%) men, mean age (+/-SD) 53.0 +/- 5.9 years, had metabolic syndrome and 6,362 did not. Comparing men with metabolic syndrome to men without, adjusted hazard ratios (HRs) were 1.21 (95% CI 1.13-1.29), 1.49 (1.35-1.64), and 1.51 (1.34-1.70) for 18-year total, CVD, and coronary heart disease mortality, respectively. Among men with metabolic syndrome, elevated glucose (1.54 [1.34-1.78]) and low HDL cholesterol (1.45 [1.17-1.54]) were most predictive of CVD mortality, followed by elevated BMI (1.34 [1.17-1.54]), elevated blood pressure (1.25 [0.98-1.58]), and elevated triglycerides (1.06 [0.86-1.30]). In contrast, for men without metabolic syndrome, the HR for low HDL cholesterol was 1.02 (0.86-1.22). Among metabolic syndrome men with no nonfatal CVD event, smokers with elevated LDL cholesterol showed higher CVD mortality (1.79 [1.22-2.63]) compared with nonsmokers without elevated LDL cholesterol; this additional risk was even greater for metabolic syndrome men with a nonfatal CVD event (2.11 [1.32-3.38]). CONCLUSIONS: Metabolic syndrome is associated with an increased risk of mortality. Among those with metabolic syndrome, risk is further increased by having more metabolic syndrome conditions, by cigarette smoking, and by elevated LDL cholesterol. Primary prevention of each metabolic syndrome condition should be emphasized, and presence of each condition should be treated in accordance with current guidelines.     

Update on selected markers used in risk assessment for vascular disease.

CVD remains the greatest health risk in the U.S.. Assessment of laboratory data in establishing risk and treatment modalities has come to the forefront in patient primary care. Guidelines published in the ATP III document by the NCEP have incorporated lower limits of lipids and included a number of risk factors and conditions, such as the metabolic syndrome associated with insulin-resistance, as a means for earlier detection and intervention in CVD. Endothelial dysfunction and the associated inflammatory process, including soluble plasma markers, have lead to the addition of hs-CRP as an adjunct to other laboratory indicators of CVD. The precise mechanisms and interrelationships between these factors and atherosclerosis have yielded some confusing data, along with investigations of a number of associated substances and conditions. An emerging theme is the body's response to injury and stress; a lack of metabolic balance. While currently outside the domain of routine laboratory testing, future CVD risk assessment may include the metabolic by-products generated by chronic external pressures, including genetic predisposition or alterations associated with socioeconomic factors. Further studies are needed to better understand the significance each plays in assessing the individual's development and CVD risk.     

The metabolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association and the European Association for the Study of Diabetes

The term "metabolic syndrome" refers to a clustering of specific cardiovascular disease (CVD) risk factors whose underlying pathophysiology is thought to be related to insulin resistance. Since the term is widely used in research and clinical practice, we undertook an extensive review of the literature in relation to the syndrome's definition, underlying pathogenesis, and association with CVD and to the goals and impact of treatment. While there is no question that certain CVD risk factors are prone to cluster, we found that the metabolic syndrome has been imprecisely defined, there is a lack of certainty regarding its pathogenesis, and there is considerable doubt regarding its value as a CVD risk marker. Our analysis indicates that too much critically important information is missing to warrant its designation as a "syndrome." Until much needed research is completed, clinicians should evaluate and treat all CVD risk factors without regard to whether a patient meets the criteria for diagnosis of the "metabolic syndrome."     

Can we apply the National Cholesterol Education Program Adult Treatment Panel definition of the metabolic syndrome to Asians?

OBJECTIVE: Limited information is available about the metabolic syndrome in Asians. Furthermore, the definition of central obesity using waist circumference may not be appropriate for Asians. The objectives of this study were to determine the optimal waist circumference for diagnosing central obesity in Asians and to estimate the prevalence of the metabolic syndrome in an Asian population. RESEARCH DESIGN AND METHODS: We used data from the 1998 Singapore National Health Survey, a cross-sectional survey involving 4,723 men and women of Chinese, Malay, and Asian-Indian ethnicity aged 18-69 years. Receiver operating characteristic analysis suggested that waist circumference >80 cm in women and >90 cm in men was a more appropriate definition of central obesity in this population. The prevalence of the metabolic syndrome was then determined using the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria with and without the modified waist circumference criteria. RESULTS: In Asians, decreasing waist circumference increased the crude prevalence of the metabolic syndrome from 12.2 to 17.9%. Using the modified Asian criteria, the prevalence of the metabolic syndrome increased from 2.9% in those aged 18-30 years to 31.0% in those aged 60-69 years. It was more common in men (prevalence 20.9% in men versus 15.5% in women; P < 0.001) and Asian Indians (prevalence 28.8% in Asian-Indians, 24.2% in Malays, and 14.8% in Chinese; P < 0.001). CONCLUSIONS: NCEP ATP III criteria, applied to an Asian population, will underestimate the population at risk. With a lower waist circumference cutoff, the prevalence of the metabolic syndrome is comparable to that in Western populations. Ethnic differences are likely to exist between populations across Asia.