Metabolic syndrome: a multiplex cardiovascular risk factor

CONTEXT: The metabolic syndrome (MetS) is a multiplex risk factor for cardiovascular disease. The syndrome develops through interplay of obesity and metabolic susceptibility. OBJECTIVE: This article addresses whether the MetS construct has clinical utility. POSITION: The National Cholesterol Education Program and other organizations have proposed that the MetS can be recognized clinically by a clustering of simple clinical measures including waist circumferences, blood pressure, triglycerides, high-density lipoproteins, and glucose. People with this clustering have most or all of the components of the MetS. Identifying the MetS has several advantages. It discovers persons who are at increased risk for cardiovascular disease. A diagnosis focuses more clinical attention on the underlying causes, notably obesity and other lifestyle factors; it thereby reinforces the utility of lifestyle changes in clinical practice. A diagnosis further informs physicians on choice and intensity of drug therapy for elevated cholesterol, aspirin prophylaxis, and blood pressure and glucose control. The introduction of the MetS has led to a large number of epidemiological, metabolic, and genetic studies that have heightened our understanding of the condition's prevalence and pathogenesis. It has been a stimulus to the development of new drugs or drug combinations that will modify multiple risk factors simultaneously. CONCLUSIONS: This author holds that the MetS counts as a multiplex cardiovascular risk factor that is clinically useful and will lead to advances in diagnosis and treatment of an important cause of cardiovascular disease.     

Metabolic syndrome and risk of cardiovascular events after myocardial infarction

OBJECTIVES: We aimed to assess the prevalence and prognostic role of metabolic syndrome (METS) and diabetes in post-myocardial infarction (MI) patients. BACKGROUND: Diabetes is a well known risk factor for patients with previous MI, but glycemic dysmetabolism develops over a protracted period of time. Scanty data are available on the role of METS in patients with previous MI. METHODS: Adjusted Cox's regression models, having diabetes, death, major cardiovascular events (CVE), and hospitalization for congestive heart failure (CHF) during follow-up as outcome events, were fitted on 11,323 patients with prior MI enrolled in the GISSI-Prevenzione Trial. RESULTS: At baseline, 21% and 29% of patients had diabetes mellitus and METS, respectively. The METS patients had a significant (93%) increased risk of diabetes during follow-up. As compared with control subjects, the probability of death and CVE were higher in both METS (+29%, p = 0.002; +23%, p = 0.005) and diabetic patients (+68%, p <0.0001; +47%, p <0.0001), although diabetic but not METS patients were more likely to be hospitalized for CHF (+89%, p <0.0003 and +24%, p = 0.241). Moderate (-6% to -10%) and substantial (>-10%) weight reduction were associated with a significant (18% and 41%, respectively) decreased risk of diabetes. Weight gain was significantly associated with increased risk of diabetes. The risk conferred by METS and diabetes tended to be higher among women. CONCLUSIONS: In patients with MI, METS and diabetes were highly prevalent and are associated with increased risk of death and CVE. Diabetes is also associated with increased risk of hospitalization for CHF. Weight reduction significantly decreased the risk of becoming diabetic in patients with METS.     

Metabolic syndrome and risk of cardiovascular disease: a meta-analysis

Purpose

The use of different definitions of the metabolic syndrome has led to inconsistent results on the association between the metabolic syndrome and risk of cardiovascular disease. We examined the association between the metabolic syndrome and risk of cardiovascular disease.

Methods

A MEDLINE search (1966-April 2005) was conducted to identify prospective studies that examined the association between the metabolic syndrome and risk of cardiovascular disease. Information on sample size, participant characteristics, metabolic syndrome definition, follow-up duration, and endpoint assessment was abstracted.

Results

Data from 21 studies met the inclusion criteria and were included. Individuals with the metabolic syndrome, compared to those without, had an increased mortality from all causes (relative risk [RR] 1.35; 95% confidence interval [CI], 1.17-1.56) and cardiovascular disease (RR 1.74; 95% CI, 1.29-2.35); as well as an increased incidence of cardiovascular disease (RR 1.53; 95% CI, 1.26-1.87), coronary heart disease (RR 1.52; 95% CI, 1.37-1.69) and stroke (RR 1.76; 95% CI, 1.37-2.25). The relative risk of cardiovascular disease associated with the metabolic syndrome was higher in women compared with men and higher in studies that used the World Health Organization definition compared with studies that used the Adult Treatment Panel III definition.

Conclusion

This analysis strongly suggests that the metabolic syndrome is an important risk factor for cardiovascular disease incidence and mortality, as well as all-cause mortality. The detection, prevention, and treatment of the underlying risk factors of the metabolic syndrome should become an important approach for the reduction of the cardiovascular disease burden in the general population.     

Metabolic syndrome and cardiovascular risk prediction in peripheral arterial disease

Background and aimsMetabolic syndrome (MetS) was reported to be associated with increased cardiovascular risk in various settings, however its prognostic impact in peripheral arterial disease (PAD) is scanty.Methods and resultsWe prospectively studied 173 patients with intermittent claudication and ankle/brachial index (ABI) <0.90, in whom MetS was defined using the criteria of both the revised version of the Adults Treatment Panel III (rATP III) and the International Diabetes Federation (IDF). Of these patients, 52.6% met the rATP III and 54.9% the IDF criteria for MetS. During a median follow-up of 31 months, 54 cardiovascular events occurred. Kaplan–Meier curves showed a greater incidence of ischemic events in patients with MetS than in those without. However, adjusted Cox analyses revealed that only IDF-MetS was independently associated with increased cardiovascular risk (HR = 1.91, 95% CI 1.03–3.51, p = 0.038). Kaplan–Meier curves for the four groups of patients delineated according to the bootstrapped ABI cut-off value (0.73) and the presence or absence of IDF-MetS revealed that the syndrome improved the predictive power of ABI alone. Actually, among patients with an ABI ≤ 0.73, those with IDF-MetS had a higher cardiovascular risk than those without the syndrome (HR = 2.55, 95% CI 1.22–5.12, p = 0.012). This was confirmed by c-statistic, which was 0.56 for ABI alone and increased to 0.65 (p = 0.046) when IDF-Mets was added to the pressure index.ConclusionIn PAD, IDF-MetS, but not rATP III-MetS, is associated with an increased risk of cardiovascular events. Furthermore, IDF-MetS adds to the prognostic value of ABI, currently the most powerful prognostic indicator in PAD.     

Metabolic syndrome, subclinical coronary atherosclerosis, and cardiovascular risk

The metabolic syndrome is a constellation of cardiovascular disease risk factors, and it is associated with the presence of advanced subclinical coronary atherosclerosis. The presence of the metabolic syndrome appears to provide incremental predictive value on top of the Framingham risk score in predicting future cardiovascular events. Traditional risk-prediction formulas fail to account for a significant portion of coronary heart disease morbidity and mortality. The metabolic syndrome may be particularly useful in predicting risk among individuals classified as low or intermediate risk by Framingham risk score.     

Metabolic syndrome and cardiovascular risk in survivors after hematopoietic cell transplantation

Increasing numbers of hematopoietic cell transplantations (HCTs) are being performed annually with a greater number of long-term survivors. There is increasing concern regarding the late complications and long-term effects that are secondary to treatment exposures before HCT as well as during the HCT conditioning therapy. In both the autologous as well as allogeneic transplant setting, transplant survivors experience mortality rates higher than the general population and the risk of premature cardiovascular (CV)-related death is increased 2.3-fold compared with the general population. The etiology of CV-related deaths in HCT survivors is multifactorial; however, increasing evidence suggests that HCT survivors are at higher risk of developing adverse CV risk factors leading to the development of the metabolic syndrome (a constellation high triglyceride levels, low high-density lipoprotein-cholesterol, hypertension, high fasting blood sugars and increased waist circumference), which then predisposes individuals to risk for early CV-related death. Resistance to insulin is the primary underlying pathophysiologic mechanism that contributes to the development of metabolic syndrome and HCT survivors have been shown to be more likely to develop hypertension, hyperlipidemia and to be insulin resistant. However, the relationship between HCT-related treatment exposures (total body irradiation, high dose chemotherapy, calcineurin inhibitors, steroids, etc) and transplant-related complications (such as GVHD) with the development of CV risk factors and insulin resistance is still in the early stages of investigation. Greater knowledge of the concern regarding CV risk in HCT survivors among both patients and care providers will provide the opportunity for appropriate screening as well as interventions for modifiable risk factors.     

Metabolic syndrome, abdominal obesity, and cardiovascular risk in elderly women

BackgroundMetabolic syndrome and abdominal obesity are risk factors for cardiovascular diseases in middle age women but, not completely understood in older people. In this study we analyzed the association between metabolic syndrome and abdominal obesity and the occurrence of cardiovascular events in these elderly women.MethodsA prospective follow-up study included 516 consecutive women aged 60–84 years who sought medical care at a geriatric outpatient facility. The presence of metabolic syndrome and higher quartiles of waist circumference and waist-to-hip ratio were analyzed as predictive variables, and were adjusted for age, smoking, and previous cardiovascular diseases. The outcomes were the occurrence of stroke, myocardial infarction, evidence of coronary artery disease, or cardiovascular death.ResultsDuring a mean follow-up of 6.6 years, 94 (18.2%) cardiovascular events were observed (48 fatal and 46 non-fatal). Metabolic syndrome was diagnosed in 206 women (39.9%). After adjustments for confounding variables, metabolic syndrome and waist-to-hip ratio above the 75th percentile (> 0.98) were predictors of the outcomes, but greater waist circumference (> 96 cm) was not. Adjusted hazard ratios for these variables were: metabolic syndrome, 1.66, 95% CI − 1.11 to 2.47, p = 0.01; waist-to-hip ratio, 1.72, 95% CI − 1.05 to 2.82; p = 0.03 and waist circumference, 1.37, 95% CI − 0.91 to 2.07, p = 0.12.ConclusionMetabolic syndrome and high waist-to-hip ratio were associated with increased risk of cardiovascular events in the studied sample.     

Metabolic syndrome and the risk of cardiovascular disease in older adults.

OBJECTIVES: The purpose of this study was to assess whether metabolic syndrome (MetSyn) predicts a higher risk for cardiovascular events in older adults. BACKGROUND: The importance of MetSyn as a risk factor has not previously focused on older adults and deserves further study. METHODS: We studied the impact of MetSyn (38% prevalence) on outcomes in 3,035 participants in the Health, Aging, and Body Composition (Health ABC) study (51% women, 42% black, ages 70 to 79 years). RESULTS: During a 6-year follow-up, there were 434 deaths overall, 472 coronary events (CE), 213 myocardial infarctions (MI), and 231 heart failure (HF) hospital stays; 59% of the subjects had at least one hospital stay. Coronary events, MI, HF, and overall hospital stays occurred significantly more in subjects with MetSyn (19.9% vs. 12.9% for CE, 9.1% vs. 5.7% for MI, 10.0% vs. 6.1% for HF, and 63.1% vs. 56.1% for overall hospital stay; all p < 0.001). No significant differences in overall mortality was seen; however, there was a trend toward higher cardiovascular mortality (5.1% vs. 3.8%, p = 0.067) and coronary mortality (4.5% vs. 3.2%, p = 0.051) in patients with MetSyn. After adjusting for baseline characteristics, patients with MetSyn were at a significantly higher risk for CE (hazard ratio [HR] 1.56, 95% confidence interval [CI] 1.28 to 1.91), MI (HR 1.51, 95% CI 1.12 to 2.05), and HF hospital stay (HR 1.49, 95% CI 1.10 to 2.00). Women and whites with MetSyn had a higher coronary mortality rate. The CE rate was higher among subjects with diabetes and with MetSyn; those with both had the highest risk. CONCLUSIONS: Overall, subjects over 70 years are at high risk for cardiovascular events; MetSyn in this group is associated with a significantly greater risk.     

Metabolic syndrome and risk factors for cardiovascular disease: are nonagenarians protected?

This study assessed cardiovascular disease risk factors in three groups of human subjects aged 20–34 [young, 20 male (M)/33 female (F)], 60–74 (aged, 29M/29F), and > 90 years (nonagenarian, 47M/50F). Components of the metabolic syndrome, cardiovascular disease, and markers of inflammation and oxidative stress were assessed. Nonagenarians weighed less than the two other groups (P < 0.001); however, there was no difference in percent fat among the three groups. Aged individuals had the highest prevalence of the metabolic syndrome (P < 0.001) according to the Adult Treatment Panel III classification. Both fibrinogen and homocysteine concentrations were significantly higher in the nonagenarians compared to younger groups. However, there were no significant differences between groups in fasting insulin, high sensitive C-reactive protein, and plasminogen activator inhibitor 1 concentrations. There were also no relationships between inflammation/ oxidative stress and the metabolic syndrome or cardiovascular disease although nonagenarians appear to be protected from oxidative damage to DNA. Louisiana Healthy Aging Study  Meghan Allen, Arturo M. Arce, Mark A. Batzer, Lauri O. Byerley, Pauline Callinan, Cathy M. Champagne, Katie E. Cherry, Yu-wen Chiu, James P. DeLany, Melissa J. deVeer, Devon A. Dobrosielski, Andrea Ermolao, Elizabeth T. Fontham, Paula J. Geiselman, Valentina Greco, Sibte Hadi, Tiffany Hall, Karri Hawley, Scott W. Herke, Hui-Chen Hsu, Sangkyu Kim, Beth Kimball, Christina King-Rowley, Kim Landry, Li Li, Hui-Yi Lin, Kay Lopez, John D. Mountz, Emily Olinde, Kim Pedersen, Henry Rothschild, Ryan A. Russell, Donald Scott, Jennie Silva, Nicole Standberry, Jessica Thomson, Crystal Traylor, Cruz Velasco-Gonzalez, Jerilyn A. Walker, Xui Yun Wang, Michael A. Welsch, Robert H. Wood, Pili Zhang. Support  This research was supported by the Louisiana Board of Regents through the Millennium Trust Health Excellence Fund [HEF(2001–06)-02], by the National Institute on Aging (P01AG022064), and by the National Institute of General Medical Sciences (GM42056 and GM15431).     

Metabolic acidosis-induced insulin resistance and cardiovascular risk

Microalbuminuria has been conclusively established as an independent cardiovascular risk factor, and there is evidence of an association between insulin resistance and microalbuminuria, the former preceding the latter in prospective studies. It has been demonstrated that even the slightest degree of metabolic acidosis produces insulin resistance in healthy humans. Many recent epidemiological studies link metabolic acidosis indicators with insulin resistance and systemic hypertension. The strongly acidogenic diet consumed in developed countries produces a lifetime acidotic state, exacerbated by excess body weight and aging, which may result in insulin resistance, metabolic syndrome, and type 2 diabetes, contributing to cardiovascular risk, along with genetic causes, lack of physical exercise, and other factors. Elevated fruits and vegetables consumption has been associated with lower diabetes incidence. Diseases featuring severe atheromatosis and elevated cardiovascular risk, such as diabetes mellitus and chronic kidney failure, are typically characterized by a chronic state of metabolic acidosis. Diabetic patients consume particularly acidogenic diets, and deficiency of insulin action generates ketone bodies, creating a baseline state of metabolic acidosis worsened by inadequate metabolic control, which creates a vicious circle by inducing insulin resistance. Even very slight levels of chronic kidney insufficiency are associated with increased cardiovascular risk, which may be explained at least in part by deficient acid excretory capacity of the kidney and consequent metabolic acidosis-induced insulin resistance.     

Metabolic syndrome: diabetes and cardiovascular disease

Metabolic syndrome is a complex constellation of risk factors which predispose to diabetes and coronary heart disease. Various components of the metabolic syndrome are: abdominal obesity, impaired glucose regulation, dyslipidemias and hypertension. Insulin resistance and obesity are characteristics of metabolic syndrome. The risk factors predispose to the development of type 2 diabetes and atherosclerosis. Changes in the life style, reduction of obesity and food habits are fundamental in reducing the risk factors. Some patients may, however, require pharmacological intervention for the control of hyperglycemia, obesity, hypertension and dyslipidemias.     

Metabolic syndrome and vascular risk estimation in a Mediterranean non-diabetic population without cardiovascular disease

AimsVascular risk equations are tools used to help prevent cardiovascular events. Our aim was to compare the REGICOR and SCORE equations in a general population and in persons with the metabolic syndrome (MS) according to the criteria of the International Diabetes Federation.Methods and resultsWe calculated the cardiovascular risk with both equations in a random sample of 838 non-diabetic persons aged 40–65 years without a history of cardiovascular disease, of whom 251 had the MS. Of the 838 persons, 3.6% had a high risk according to SCORE and 1.5% according to REGICOR, and of these, 53.3% and 61.5%, respectively, had the MS. The mean risk was greater in the persons with the MS than those without (REGICOR 4.6% vs. 2.6% and SCORE 1.7% vs. 1%; p < 0.01 for each). In comparison with the group without the MS, the percentage of persons with the MS who had a high risk was greater with both scales: REGICOR (3.2% vs. 0.8%, p = 0.027) and SCORE (6.4% vs. 2.4%, p = 0.004). The agreement (kappa index) classifying the subjects with a high risk, was 0.453 in the overall sample and 0.391 in the subgroup with the MS.ConclusionsThe percentage of persons classified as having a high cardiovascular risk differed between REGICOR and SCORE. Using these scales only a small percentage of non-diabetic persons with the MS have a high risk. The presence of the MS multiplies the percentage of non-diabetic persons with a high vascular risk two-fold with SCORE and four-fold with REGICOR.