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.     

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.     

Insulin resistance,the metabolic syndrome,and risk of incident cardiovascular disease in nondiabetic american indians: the Strong Heart Study

OBJECTIVE: Insulin resistance (IR) and the metabolic syndrome (MS) are associated with type 2 diabetes and adverse cardiovascular disease (CVD) risk factor profiles. Whether IR and MS predict CVD independently of diabetes and other CVD risk factors is not known. This study examines whether IR and/or presence of MS are independently associated with CVD in nondiabetic American Indians (AI). RESEARCH DESIGN AND METHODS: We examined 2283 nondiabetic AI who were free of CVD at the baseline examination of the Strong Heart Study (SHS). CVD risk factors were measured, IR was quantified using the homeostasis model assessment (HOMA), and MS as defined by the National Cholesterol Education Program Adult Treatment Panel (ATP III) was assessed for each participant. Incident CVD and diabetes were ascertained during follow-up. RESULTS: MS was present in 798 individuals (35%), and 181 participants (7.9%) developed CVD over 7.6 +/- 1.8 years of follow-up. Age, BMI, waist circumference, and triglyceride levels increased and HDL cholesterol decreased across tertiles of HOMA-IR. Risk of diabetes increased as a function of baseline HOMA-IR (6.3, 14.6, and 30.1%; P < 0.001) and MS (12.8 vs. 24.5%). In Cox models adjusted for CVD risk factors, risk of CVD did not increase either as a function of baseline HOMA-IR or MS, but individual CVD risk factors predicted subsequent CVD. CONCLUSIONS: Among nondiabetic AI in the SHS, HOMA-IR and MS both predict diabetes, but neither predicts CVD independently of other established CVD risk factors.     

Managing cardiovascular risk inpatients with metabolic syndrome

The metabolic syndrome is a constellation of risk factors that contribute to the onset of type 2 diabetes mellitus and cardiovascular disease (CVD). CVD has been identified by the National Cholesterol Education Program (NCEP) as the primary clinical outcome of the metabolic syndrome. Although no algorithm is currently available for estimating the absolute risk of CVD for patients with the metabolic syndrome, screening for cardiovascular (CV) risk in these patients involves testing for lipoprotein abnormalities (namely, an analysis of specific low-density lipoprotein particle numbers) and an assessment of various surrogate markers for subclinical coronary artery disease. Such screening can be used to help predict the development of CVD and thereby allow for effective interventions to help prevent coronary events. Strategies for reducing CV risk in patients with the metabolic syndrome are multifactorial. In addition to placing an emphasis on therapeutic lifestyle changes that increase levels of physical activity, dietary modification, and weight reduction, several pharmacologic therapies are available. One novel approach for managing CV risk in patients with the metabolic syndrome involves the inhibition of the endocannabinoid system, including the use of rimonabant. A review of CV risk factors in patients with the metabolic syndrome is beneficial for clinicians to apply in the care of their patients, along with a discussion about strategies for identifying at-risk patients and managing CVD risk for these patients.     

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.     

Managing cardiovascular risk in patients with metabolic syndrome

Metabolic syndrome consists of a cluster of cardiovascular (CV) and metabolic risk factors (e.g., abdominal obesity, hypertension, elevated levels of fasting plasma glucose and triglycerides, and low levels of high-density lipoprotein cholesterol [HDL-C]) and is associated with an increased risk for type 2 diabetes mellitus (DM) and cardiovascular disease (CVD). Because the risks for CVD and type 2 DM are highly variable among patients with metabolic syndrome, it is essential to assess a patient's risks before identifying specific treatment or lifestyle interventions. The major risk factors for CVD are smoking, hypertension, elevated levels of total and low-density lipoprotein cholesterol, low levels of HDL-C, and older age. In patients at low risk for CV events, lifestyle interventions (i.e., weight loss and increased physical activity) may be sufficient to control the components of metabolic syndrome and to reduce the risk for type 2 DM and CVD. Patients who are at high risk, however, must receive aggressive drug therapy in addition to lifestyle interventions. The following factors need to be targeted: obesity (particularly abdominal obesity), dyslipidemia, hypertension, and prothrombotic/proinflammatory states. Drugs with various and complementary mechanisms of action, including drugs targeting lipid metabolism, may be effective in controlling these factors and thereby delaying or preventing CV events and type 2 DM.     

Gestational diabetes mellitus increases the risk of cardiovascular disease in women with a family history of type 2 diabetes

OBJECTIVE: We sought to determine whether a history of gestational diabetes mellitus (GDM) further increases the risk of cardiovascular disease (CVD) in parous women with first-degree relatives with type 2 diabetes. RESEARCH DESIGN AND METHODS: Women with (n = 332) and without (n = 663) a history of GDM were compared regarding 1) the revised National Cholesterol Education Program Adult Treatment Panel III metabolic syndrome criteria, 2) the prevalence of type 2 diabetes, and 3) self-reported CVD. RESULTS: Women with prior GDM were younger (48.6 +/- 0.7 vs. 52.4 +/- 0.6 years [means +/- SE];P < 0.001) and less likely to be postmenopausal (48.3 vs. 57.9%; P < 0.005). Although both groups were obese (BMI 34.4 +/- 1.2 vs. 33.7 +/- 0.6 kg/m(2)), women with prior GDM were more likely to have metabolic syndrome (86.6 vs. 73.5%; P < 0.001) and type 2 diabetes (93.4 vs. 63.3%; P < 0.001). Moreover, they had a higher prevalence of CVD (15.5 vs. 12.4%; adjusted odds ratio 1.85 [95% CI 1.21-2.82];P = 0.005) that occurred at a younger age (45.5 +/- 2.2 vs. 52.5 +/- 1.9 years;P = 0.02) and was independent of metabolic syndrome (1.74 [1.10-2.76]; P = 0.02) and type 2 diabetes (1.56 [1.002-2.43];P < 0.05). CONCLUSIONS: Among women with a family history of type 2 diabetes, those with prior GDM were even more likely to not only have CVD risk factors, including metabolic syndrome and type 2 diabetes, but also to have experienced CVD events, which occurred at a younger age. Thus, women with both a family history of type 2 diabetes and personal history of GDM may be especially suitable for early interventions aimed at preventing or reducing their risk of CVD and diabetes.     

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).     

Predictive power of cardiovascular risk factors for detecting peripheral vascular disease

OBJECTIVES: Peripheral vascular disease (PVD) is underdiagnosed in primary care due to the absence of established criteria to warrant diagnostic testing. Our goal was to establish a risk factor hierarchy to enable earlier diagnosis of PVD. METHODS: Data sets of 142 patients with abnormal ankle brachial indices (ABI) were randomly selected from our patient database to determine the prevalence of specific cardiovascular risk factors and demographic data. An ABI score < 0.90 is diagnostic of PVD. Patients were stratified into mild (0.75-0.89), moderate (0.50-0.74), and severe disease (< 0.50). RESULTS: Mean age was 69 +/- 9.9, ABI 0.65 +/- 0.16. Risk factor prevalence: diabetes, 42%; hypertension, 87%; tobacco use, 34%; hyperlipidemia, 53%; obesity, 24%; cardiovascular disease (CVD), 69%; stroke, 15%. Total risk factors per patient v = 3.2 +/- 1.3. Disease severity stratifications: mild, n = 46 (age v = 68.6 +/- 10.4, ABI v = 0.82 +/- 0.05); moderate, n = 72 (age v = 69.9 +/- 9.4, ABI v = 0.62 +/- 0.07); severe, n = 24 (age v = 67.5 +/- 10.9, ABI v = 0.40 +/- 0.06). Independent variable mean differences: hypertension-CVD (P = 0.0002); CVD-hyperlipidemia (P = 0.002); hyperlipidemia-diabetes (P = 0.0008); diabetes-tobacco use (P = 0.001); tobacco use-obesity (P = 0.0003); obesity-stroke (P = 0.05). Independent variable mean differences were significant across disease severity (P < 0.00001). CONCLUSIONS: Our study establishes the following hierarchy of cardiovascular risk factors as predictors of PVD: hypertension, cardiovascular disease, hyperlipidemia, diabetes, tobacco use, obesity, stroke.     

Cardiovascular disease in U.S. patients with metabolic syndrome, diabetes, and elevated C-reactive protein

OBJECTIVE: C-reactive protein (CRP) independently predicts cardiovascular disease (CVD); whether it can stratify risk in those with metabolic syndrome and diabetes is not well documented. We evaluated whether elevated CRP levels modify the relationship of metabolic syndrome and diabetes with CVD in U.S. adults. RESEARCH DESIGN AND METHODS: In a cross-sectional study of 3,873 subjects (weighted to 156 million) aged >/=18 years participating in the National Health and Nutrition Examination Survey 1999-2000, subjects were classified as having diabetes, metabolic syndrome according to modified National Cholesterol Education Program criteria, or neither condition by low (<1 mg/l), intermediate (1-3 mg/l), or high (>3 mg/l) CRP levels. Logistic regression examined the odds of CVD by disease condition and CRP group. RESULTS: After adjusting for age, sex, smoking, and total cholesterol, compared with those with neither metabolic syndrome nor diabetes and low CRP levels, the odds of CVD were 1.99 (95% CI 1.10-3.59) for those with no disease and high CRP levels and 2.67 (1.30-5.48) for those with metabolic syndrome and intermediate CRP. Persons with metabolic syndrome but high CRP had an odds ratio (OR) of 3.33 (1.80-6.16), similar to those with diabetes and low CRP (3.21 [1.27-8.09]). The likelihood of CVD was highest in those with diabetes who had intermediate CRP levels (6.01 [2.54-14.20]) and in those with diabetes and high CRP (7.73 [3.99-14.95]). CONCLUSIONS: In this cross-sectional analysis, CVD is more common in those with metabolic syndrome or diabetes who have elevated CRP. Stratification by CRP may add prognostic information in patients with metabolic syndrome or diabetes.     

Management of cardiovascular disease in African-American women: utility of the metabolic syndrome guidelines

Cardiovascular disease (CVD) is the leading cause of death in the Unites States and is disproportionately more prevalent among African-American women than members of other ethnic groups. The National Cholesterol Education Adult Treatment Panel III (ATP III) metabolic syndrome guidelines are useful in clinical practice to identify individuals who are at risk for developing CVD. Amendments to the ATP III criteria might be indicated to enhance early identification of CVD risk factors among African-American women, even when only one or two of the criteria are met. The addition of body mass index (BMI) and the identification of acanthosis nigricans as a marker of insulin resistance to the ATP III metabolic syndrome guidelines might facilitate early CVD risk identification, strategy implementation, and reduction of premature morbidity and mortality within this population.     

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.     

The National Cholesterol Education Program - Adult Treatment Panel III, International Diabetes Federation, and World Health Organization definitions of the metabolic syndrome as predictors of incident cardiovascular disease and diabetes

OBJECTIVE: The clinical value of metabolic syndrome is uncertain. Thus, we examined cardiovascular disease (CVD) and diabetes risk prediction by the National Cholesterol Education Program (NCEP)-Adult Treatment Panel III (ATPIII), International Diabetes Federation, and World Health Organization definitions of the metabolic syndrome. RESEARCH DESIGN AND METHODS: We analyzed the risks associated with metabolic syndrome, the NCEP multiple risk factor categories, and 2-h glucose values in the San Antonio Heart Study (n = 2,559; age range 25-64 years; 7.4 years of follow-up). RESULTS: Both ATPIII metabolic syndrome plus age > or = 45 years (odds ratio 9.25 [95% CI 4.85-17.7]) and multiple (two or more) risk factors plus a 10-year coronary heart disease (CHD) risk of 10-20% (11.9 [6.00-23.6]) had similar CVD risk in men without CHD, as well as CHD risk equivalents. In women counterparts, multiple (two or more) risk factors plus a 10-year CHD risk of 10-20% was infrequent (10 of 1,254). However, either a 10-year CHD risk of 5-20% (7.72 [3.42-17.4]) or ATPIII metabolic syndrome plus age > or = 55 years (4.98 [2.08-12.0]) predicted CVD. ATPIII metabolic syndrome increased the area under the receiver operating characteristic curve of a model containing age, sex, ethnic origin, family history of diabetes, and 2-h and fasting glucose values (0.857 vs. 0.842, P = 0.013). All three metabolic syndrome definitions imparted similar CVD and diabetes risks. CONCLUSIONS: Metabolic syndrome is associated with a significant CVD risk, particularly in men aged > or = 45 years and women aged > or = 55 years. The metabolic syndrome predicts diabetes beyond glucose intolerance alone.     

Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men

OBJECTIVE: In men, hypoandrogenism is associated with features of the metabolic syndrome, but the role of sex hormones in the pathogenesis of the metabolic syndrome and diabetes is not well understood. We assessed the association of low levels of testosterone and sex hormone-binding globulin (SHBG) with the development of the metabolic syndrome and diabetes in men. RESEARCH DESIGN AND METHODS: Concentrations of SHBG and total and calculated free testosterone and factors related to insulin resistance were determined at baseline in 702 middle-aged Finnish men participating in a population-based cohort study. These men had neither diabetes nor the metabolic syndrome. RESULTS: After 11 years of follow-up, 147 men had developed the metabolic syndrome (National Cholesterol Education Program criteria) and 57 men diabetes. Men with total testosterone, calculated free testosterone, and SHBG levels in the lower fourth had a severalfold increased risk of developing the metabolic syndrome (odds ratio [OR] 2.3, 95% CI 1.5-3.4; 1.7, 1.2-2.5; and 2.8, 1.9-4.1, respectively) and diabetes (2.3, 1.3-4.1; 1.7, 0.9-3.0; and 4.3, 2.4-7.7, respectively) after adjustment for age. Adjustment for potential confounders such as cardiovascular disease, smoking, alcohol intake, and socioeconomic status did not alter the associations. Factors related to insulin resistance attenuated the associations, but they remained significant, except for free testosterone. CONCLUSIONS: Low total testosterone and SHBG levels independently predict development of the metabolic syndrome and diabetes in middle-aged men. Thus, hypoandrogenism is an early marker for disturbances in insulin and glucose metabolism that may progress to the metabolic syndrome or frank diabetes and may contribute to their pathogenesis.     

Pulse wave velocity study in middle-aged migraineurs at low cardiovascular disease risk

(Headache 2011;51:1239‐1244) Background.— Migraine is associated with an increased risk for ischemic stroke and cardiovascular disease (CVD). Recent studies have suggested vascular dysfunction in the aorta, the brachial and femoral artery. Little is known about such arterial changes in Japanese midlife migraineurs. We aimed to evaluate arterial pulse wave velocity (PWV) and ankle–brachial index (ABI) in middle‐aged migraineurs at low CVD risk. Methods.— Brachial–ankle PWV (baPWV) and ABI, using an oscillometric technique, were measured in 111 migraineurs (81 women and 30 men) and 110 controls. All participants had no CVD risk factors. Statistical comparison of baPWV and ABI between both groups and the relationship to clinical variables of migraineurs were analyzed. Results.— Twenty‐two subjects had migraine with aura and 89 had migraine without aura. Mean age (SD) of migraineurs was 44.4 (8.4) years. Mean duration (SD) was 18.0 (10.8) years. Attack frequency was 60 subjects in ≥1 time/month and 51 subjects in <1 time/month. Mean score (SD) of Headache Impact Test‐6 (HIT‐6) was 61.4 (8.7). CVD risk profile did not differ statistically between migraineurs and controls. Mean baPWV (SD) of migraineurs was 1247 (189) cm/second in women and 1356 (126) in men. That of controls was 1138 (136) in women and 1250 (121) in men. baPWV was increased significantly in female and male migraineurs. Mean ABI (SD) was 1.05 (0.06; 1.04 [0.07] in men and 1.05 [0.06] in women) in migraineurs and 1.06 (0.07) in controls (1.05 [0.08] in men and 1.06 [0.08] in women). ABI did not differ statistically between migraineurs and controls. Migraine subtypes, duration, attack frequency, and HIT‐6 score were not associated with baPWV and ABI. Conclusion.— The present study indicated higher baPWV in midlife migraineurs without CVD risk factors. This pathogenesis could reflect distinct vascular reactivity rather than arterial stiffness due to atherosclerosis.     

Trend in the prevalence of the metabolic syndrome and its impact on cardiovascular disease incidence: the San Antonio Heart Study

OBJECTIVE: With the current obesity epidemic, one would expect a prevalence increase in the metabolic syndrome. Therefore, in the San Antonio Heart Study, a population-based study with worsening obesity, we examined the metabolic syndrome and its effect on incident cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS: We enrolled 5,158 subjects in two cohorts: 1979-1982 and 1984-1988. We reexamined 3,682 (71.4%) subjects in 1987-1990 (cohort 1) and 1991-1996 (cohort 2) and assessed a 7.5-year incidence of CVD in 4,635 (90.0%) participants. We used the metabolic syndrome definition of the National Cholesterol Education Program-Adult Treatment Panel III. RESULTS: At baseline, the metabolic syndrome was less prevalent in cohort 1 than in cohort 2: in men, 20.4 vs. 29.3% (P < 0.001); in women, 16.3 vs. 26.3% (P < 0.001). The prevalence increased in men and women of both Mexican-American and non-Hispanic white ethnic groups between 1979-1982 and 1991-1996 (P for trend <0.001 for each of the groups). There was an excess of incident CVD in cohort 2 relative to cohort 1 (odds ratio 1.37 [95% CI 1.02-1.84]) after adjustment for age, sex, ethnic origin, socioeconomic status, history of CVD, diabetes, total cholesterol, smoking, and family history of heart attack. Further adjustment for the metabolic syndrome reduced this difference (1.26 [0.93-1.71]) because the metabolic syndrome predicted incident CVD (1.58 [1.14-2.18]). CONCLUSIONS: In San Antonio, Texas, an increase in the prevalence of the metabolic syndrome between 1979-1982 and 1984-1988 contributes to explain a higher CVD incidence.     

The metabolic syndrome and cardiovascular disease

The metabolic syndrome, which is very common in the general population, is defined by the clustering of several classic cardiovascular risk factors, such as type 2 diabetes, hypertension, high triglycerides and low high-density lipoprotein cholesterol (HDL). Central obesity and insulin resistance, which are the two underlying disorders of the syndrome, are further risk factors for cardiovascular disease. Moreover, a panel of novel (non-traditional) risk factors are ancillary features of the metabolic syndrome. They include biomarkers of chronic mild inflammation (e.g. C-reactive protein, CRP), increased oxidant stress (e.g. oxidized low density lipoprotein, LDL), thrombophilia (e.g. plasminogen activator inhibitor-1, PAI-1) and endothelial dysfunction (e.g. E-selectin). Therefore, subjects with the metabolic syndrome are potentially at high risk of developing atherosclerosis and clinical cardiovascular events.In recent years several longitudinal studies have confirmed that subjects with the metabolic syndrome present with atherosclerosis and suffer from myocardial infarction and stroke at rates higher than subjects without the syndrome. The risk of cardiovascular disease (CVD) is particularly high in women with the syndrome and in subjects with pre-existing diabetes, CVD and/or high CRP. However, an increased risk is already present in subjects with a cluster of multiple mild abnormalities. The risk related to the metabolic syndrome is definitely higher when subjects affected are compared to subjects free of any metabolic abnormality.     

Serum 25-hydroxyvitamin D,cardiovascular risk markers,and incident cardiovascular disease in a high risk community population

BackgroundIt is unclear whether vitamin D status is related to cardiovascular risk beyond that explained by conventional risk markers. We examined the relationship between serum 25-hydroxy (OH) vitamin D and incident cardiovascular disease (CVD; heart attack/stroke) after adjusting for individual- and community-level covariates from laboratory, administrative and survey data.MethodsPatients receiving their first 25-OH vitamin D test in Calgary, Alberta from 2009 to 2013 without a past CVD diagnosis but an electrocardiogram and body mass index (BMI) +/− 3 months from testing were included. The following was merged to this data: first results for laboratory-measured CVD risk markers (lipid profile, fasting plasma glucose, and HbA1c) measured +/− 3 months from testing; Census Dissemination Area (CDA)-level indicators of socioeconomic status (SES) in 2011; and CVD diagnoses > 3 months from testing between 2009 and 2016. Linear and Poisson regression were used to examine associations between 25-OH vitamin D quartile and covariates, and Cox proportional hazard models were used to examine associations with incident CVD before and after adjusting for covariates.ResultsAmong 72 348 patients, there were 1898 CVD events over a median of 6.0 years. Increasing quartile of 25-OH vitamin D was associated with improved lipid and glycemic profiles (p < 0.01), higher proportion of CDA-level indicators of high SES (p < 0.01), and a lower risk of CVD (Q4 vs Q1: HR: 0.72, 95% CI: 0.63–0.81, p for trend < 0.01) after adjusting for age, sex and average daily hours of sunlight during month of testing. The association with CVD was unchanged after adjusting for BMI, slightly attenuated after adjusting for SES but completely abolished after adjusting for laboratory-measured cardiovascular risk markers.ConclusionsVitamin D status likely offers no additional information on CVD risk over conventional laboratory-measured risk markers.