Obesity and metabolic syndrome as related to cardiovascular disease

The metabolic syndrome (MetS) constitutes a multifaceted disorder, including obesity, dyslipidemia, hyperglycemia and hypertension, associated with an increased propensity towards cardiovascular disease (CVD). Besides this, accumulating data suggest the involvement of nontraditional, novel, cardiovascular risk factors in MetS. Among them, insulin resistance seems to possess a predominant role in MetS-related CVD in obese patients. Furthermore, adipose tissue fatty acid metabolism, increased incidence of oxidative stress and endothelial dysfunction, and excessive production of adipocyte derivatives, known as adipokines, have all been proposed to contribute to the pathogenesis of CVD in obese patients with MetS. Lifestyle interventions, such as weight loss and increased physical activity, have long been the cornerstone for the treatment of obesity-related disorders. With the exception of obesity, pharmaceutical interventions targeting each disorder of MetS have yielded considerable improvement in cardiovascular morbidity and mortality. The long-term management of obesity and its complications seems promising but requires further investigation.     

Hepatic insulin resistance,metabolic syndrome and cardiovascular disease

BackgroundThe metabolic syndrome is a constellation of common metabolic disorders that is associated with cardiovascular disease. Insulin resistance has a central role in the pathophysiology of metabolic syndrome.Recent advancesIt is now commonly accepted that chronic inflammation associated with visceral obesity induces insulin resistance in the liver. Chronic inflammation is characterized by the production of abnormal adipokines and cytokines such as TNF-α, FFA, IL-1, IL-6, leptin and resistin. These factors inhibit insulin signalling in hepatocytes by activating SOCS proteins, several kinases such as JNK, IKK-β and PKC and protein tyrosine phosphatases such as PTP1B and PTEN, that in turn impair insulin signalling at insulin receptor and insulin receptor substrate (IRS) level. Hepatic insulin resistance in turn causes impaired suppression of glucose production by insulin in hepatocytes leading to hyperglycemia. An important and early complication of hepatic insulin resistance is the induction of hepatic VLDL production, via changes in the rate of apoB synthesis and degradation and de novo lipogenesis, or increased FFA flux from adipose tissue into the liver. Insulin resistance also stimulates the production of CRP and PAI-1, both markers of an inflammatory state. All metabolic abnormalities related to hepatic insulin resistance have been shown to directly or indirectly promote atherosclerosis. Hyperglycemia induces a series of alterations including endothelial dysfunction, cellular proliferation, changes in extracellular matrix conformation and impairment of LDL receptor-mediated uptake decreasing the in vivo clearance of LDL. Small dense LDLs associated with high circulating VLDL have higher affinity to the intimal proteoglycans leading to the penetration of more LDL particles into the arterial wall. CRP can also accelerate atherosclerosis by increasing the expression of PAI-1 and adhesion molecules in endothelial cells, inhibition of nitric oxide formation and increasing LDL uptake into macrophages.ConclusionsOverall, growing evidence suggests that hepatic insulin resistance is sufficient to induce several components of the metabolic syndrome and promote progression to cardiovascular disease. Many unresolved questions remain however on the molecular and cellular mechanisms that trigger hepatic insulin resistance and promote the development of clinical metabolic syndrome.     

代谢综合征与糖尿病和心血管疾病

1999年世界卫生组织(WHO)公布了代谢综合征(metabolic syndrome,MS)的工作定义(简称WHO定义)。此后6～7年间,世界各国及多个学术组织对其相继提出了不同定义。众多不同定义在一定程度上造成了对MS的认识及临床应用上的混乱;也造成了MS的国际间交流和比较上的     

Gender differences in the metabolic syndrome and their role for cardiovascular disease

Summary Women live longer than men and develop cardiovascular disease (CVD) at an older age. The metabolic syndrome represents a major risk factor for the development of CVD, and gender¹ differences in this syndrome may contribute to gender differences in CVD. In recent years, the metabolic syndrome has been more prevalent in men than in women. Prevalence is increasing and this increase has been steeper in women, particularly in young women, during the last decade. The contributions of the different components of the metabolic syndrome differ between genders and in different countries. In a recent survey in Germany, 40% of the adult population had been diagnosed with disturbed glucose tolerance or type 2 diabetes. Undiagnosed diabetes was more frequent in men than in women, and risk factors for undiagnosed diabetes differed between the sexes. Worldwide, in individuals with impaired glucose tolerance, impaired fasting glucose was observed more frequently in men, whereas impaired glucose tolerance occurred relatively more often in women. Lipid accumulation patterns differ between women and men. Premenopausal women more frequently develop peripheral obesity with subcutaneous fat accumulation, whereas men and postmenopausal women are more prone to central or android obesity. In particular, android obesity is associated with increased cardiovascular mortality and the development of type 2 diabetes. Visceral adipocytes differ from peripheral adipocytes in their lipolytic activity and their response to insulin, adrenergic and angiotensin stimulation and sex hormones. Visceral fat is a major source of circulating free fatty acids and cytokines, which are directly delivered via the portal vein to the liver inducing insulin resistance and an atherogenic lipid profile. Inflammation increases cardiovascular risk particularly in women. A relatively greater increase in cardiovascular risk by the appearance of diabetes in women has been reported in many studies. Thus, the presently available data suggest that the pathophysiology of the metabolic syndrome and its contribution to the relative risk of cardiovascular events and heart failure show gender differences, which might be of potential relevance for prevention, diagnostics, and therapy of the syndrome. ¹ "Gender" is used to include biological sex as well as gender in its strict sense Supported by the DFG (grants to V. Regitz–Zagrosek) and the BMBF (Competence Network Heart Failure) An erratum to this article can be found at     

The metabolic syndrome, depression, and cardiovascular disease: interrelated conditions that share pathophysiologic mechanisms

This article introduces the metabolic syndrome as a clinical phenotype with consequences for diagnosis and treatment that go beyond the different clinical specialties involved. A life-course approach is suggested as a means of understanding the complex interrelations between the metabolic syndrome, depression, and cardiovascular disease. Pathophysiologic mechanisms that these conditions share are discussed in detail. These considerations provide arguments for a more integrative approach to patients in general that surpass the current disease-centered services such as endocrinology, psychiatry, and cardiology.     

The metabolic syndrome increases cardiovascular mortality in Taiwanese elderly

Background   The prevalence of the metabolic syndrome (MetS) is high among the elderly. However, evidence that mortality increases with MetS is rare. In this study, we investigated the relationship between MetS, cardiovascular disease (CVD) and all cause mortality in the elderly.
Materials and methods   A total 10 547 participants, aged 65 years and older, of baseline cohort were recruited from four nationwide Health Screening Centres in Taiwan from 1998 to 1999. The metabolic syndrome was defined according to the America Heart Association/National Heart Lung Blood Institute definition. Cox proportional hazards regression analyses were used to estimate the relative risks (RRs) of CVD and all cause mortality for those with MetS for up to 8 years of follow-up.
Results   The baseline prevalence of MetS was 50·1% (45·6% in men and 54·4% in women, respectively). A total of 1312 participants died; of these, 300 participants died from CVD. Adjusted for age, gender, smoking, total cholesterol and estimated glomerular filtration rate, the RRs for CVD and all cause mortality among participants with MetS were 1·48 (95% confidence interval = 1·16–1·90) and 1·16 (1.03–1.30), respectively, for participants compared to those without MetS. The mean RRs for CVD, however, ranged from 1·21 to 5·31 among different combinations of MetS components.
Conclusion   The elderly with MetS, compared to those without MetS, had a higher CVD and all cause mortality in Taiwan. Furthermore, different combinations of MetS components posed different risks to the mortality, which deserves further research in the future.     

代谢综合征与心血管疾病的关系及其组分间的交互作用

目的探讨代谢综合征(MS)及其组分与心血管病(CVD)的关系,以及MS组分间对CVD的影响是否存在交互作用。方法对舟山群岛新区8685名研究对象,按照多代谢异常和代谢综合征防治研究统一设计调查表。完成基线和随访调查包括病史问卷调查,人体指标测量及相关实验室检查,观察其组分交互作用的变化情况。结果按研究对象基线是否诊断为MS或是否具体有某项MS组分为协变量入COX比例风险模型,单因素分析显示MS与其组分中除腰围和低高密度脂蛋白外均与CVD有联系(模型1),其中血压升高的相对危险度(RR)最高3.96。模型2中调整了年龄、性别、吸烟、饮酒、高血压家属史、糖尿病家族史、高脂血症家病史、CVD家族史后,MS及其组分与CVD关系的aRR值有所下降,但MS、血压升高和高TG血症仍差异有统计学意义。模型3在模型2的基础上再对MS组间分进一步做了相互调查,发现除血压外,其他四项MS组分与CVD的关系均不显著。结论在MS组分中,血压是CVD的独立危险因素。血压与其他MS组分对于CVD的发生仅为各自的独立作用,当这些危险因素同时存在时并没有产生明显的交互作用。     

Inflammation,the metabolic syndrome and cardiovascular risk

Over the past ten years it has become clear that cardiovascular disease (CVD) and atherosclerosis have a 'microinflammatory' component and are often associated with low levels of inflammatory markers that are in the upper part of the 'normal' range. In particular, diseases that predispose to CVD, such as the metabolic syndrome and type 2 diabetes, appear to have a very strong inflammatory component. While the inflammatory process is very complicated, single measures, such as C-reactive protein (CRP) or fibrinogen, have clear benefits as they summarise many different parts of the inflammatory process and are easy to apply. However, it is important to remember that the process of inflammation includes coagulation, fibrinolysis, complement activation, antioxidation, immune response and hormonal regulation through the hypothalamic-pituitary-adrenal axis. Furthermore, genetic variation, differences in exposure to environmental influences and the mass of inflammation-producing tissue (e.g. adipose tissue) can all influence responses. Thus, the relationship between atherosclerosis, the metabolic syndrome and inflammation is extraordinarily complex. Inflammatory markers such as CRP exhibit strong CVD-risk prediction that is consistent across sexes and a number of different populations. They reflect risk not only for 'vulnerable plaque' and myocardial infarction (MI) but also for other cardiovascular diseases. In fact, inflammation is associated with several, if not all, of the chronic diseases of old age, and it is now clear that there are important links between inflammation and general metabolism. For instance, visceral adiposity exerts a major influence on inflammation status. Medications that affect atherosclerosis appear to do so at least in part by influencing inflammation (for instance, the emerging pleiotropic effects of statins), and this has far-reaching ramifications for chronic diseases of old age and their treatment.     

Risk of metabolic syndrome, cardiovascular disease, and diabetes in androgen deprivation therapy

Men with prostate cancer may be at increased risk for metabolic syndrome, cardiovascular disease, and diabetes from androgen deprivation therapy (ADT). This article reviews current literature related to potential adverse effects of using ADT for localized prostate cancer. The use of gonadotropin-releasing hormone agonist therapy for prostate cancer in the early 1990s compared to the late 1990s is addressed. Oncology nurses play an important role in educating men about strategies for preventing and reducing side effects of cancer treatment. Therefore, having knowledge regarding the impact of hormone therapy on men's health will be important to prostate cancer survivors.     

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.     

Components of the metabolic syndrome and risk of cardiovascular disease and diabetes in Beaver Dam

OBJECTIVE: To determine whether components of the metabolic syndrome precede the 5-year incidence of cardiovascular disease and diabetes. RESEARCH DESIGN AND METHODS: A population of individuals aged 43-84 years was evaluated from 1988 to 1990 and again 5 years later. Medical history, blood pressure, and laboratory measures were obtained at both examinations following the same protocols. Subjects without diabetes were classified according to level of glycemia, high blood pressure, high-risk lipid levels, high uric acid levels, and proteinuria at baseline. History of incident myocardial infarction, angina, stroke, and diabetes was obtained at follow-up. RESULTS: Of the 4,423 subjects without diabetes, 6.9% had elevated levels of glycemia, 18.4% had high blood pressure, 82.7% had high-risk lipid levels (either high serum total cholesterol or low HDL cholesterol or high ratio of these two levels), 27% had elevated uric acid levels, 33.2% had high BMI, and 3.3% had proteinuria (> or =30 mg/dl). The risk of incident cardiovascular disease 5 years later increased with the number of the components present; 2.5% of those with one component developed cardiovascular disease, whereas 14.9% of those with four or more components developed cardiovascular disease. Of those with one component, diabetes developed in 1.1% 5 years later, whereas diabetes developed in 17.9% of those with four or more components. CONCLUSIONS: Components of the metabolic syndrome are common and are associated with incident cardiovascular disease and diabetes after 5 years. Interventions to alter BMI, lipid levels, and blood pressure may decrease incident diabetes and cardiovascular disease.     

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.     

Highly active antiretroviral therapy-associated metabolic syndrome and cardiovascular risk

The introduction of highly active antiretroviral therapy (HAART) has significantly modified the course of human immunodeficiency virus (HIV) disease, with longer survival and improved quality of life of HIV-infected subjects. However, HAART regimens, especially those including protease inhibitors, have been shown to cause in a high proportion of HIV-infected patients a metabolic syndrome (lipodystrophy/lipoatrophy, dyslipidemia, type 2 diabetes mellitus, insulin resistance) that may be associated with an increased risk of cardiovascular disease (coronary artery disease and stroke). A careful stratification of the cardiovascular risk and cardiovascular monitoring of patients under HAART is needed according to the most recent clinical guidelines.     

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.     

高尿酸血症对代谢综合征和心血管病的影响与防治

尿酸是嘌呤代谢的终末产物,血尿酸(SUA)增高影响动脉粥样斑块的稳定性,增加冠心病患者心肌梗 死、心力衰竭的发生率和全因死亡率,尤其是女性患者冠心病的发病率显著增加。与正常血压青少年相比,SUA 每增 加1mg/L,青少年高血压前期或高血压的患病风险增加50%,男性高于女性。高尿酸血症(HUA)增加糖耐量异常、 糖尿病以及糖尿病肾病的患病风险。一定程度上加重胰岛素抵抗、肥胖、脂质代谢紊乱等代谢综合征表现。尽管 HUA增加心血管疾病的患病率风险。但对于无症状HUA 的治疗国内外专家尚有不同推荐建议。     

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.     

Gap analysis of pediatric reference intervals for risk biomarkers of cardiovascular disease and the metabolic syndrome

The childhood obesity epidemic has begun to compromise the health of the pediatric population by promoting premature development of atherosclerosis and the metabolic syndrome (MS), both of which significantly increase the risk of cardiovascular disease (CVD) early in life. As a result, recently, there has been increased recognition of the need to assess and closely monitor children and adolescents for risk factors of CVD and components of the MS. Serum/Plasma biomarkers including total cholesterol, triglycerides, HDL-C, LDL-C, insulin and C-peptide have been used for this purpose for many years. Recently, emerging biomarkers such as apolipoprotein AI, apolipoprotein B, leptin, adiponectin, free fatty acids, and ghrelin have been proposed as tools that provide valuable complementary information to that obtained from traditional biomarkers, if not more powerful predictions of risk. In order for biomarkers to be clinically useful in accurately diagnosing and treating disorders, age-specific reference intervals that account for differences in gender, pubertal stage, and ethnic origin are a necessity. Unfortunately, to date, many critical gaps exist in the reference interval database of most of the biomarkers that have been identified. This review contains a comprehensive gap analysis of the reference intervals for emerging and traditional risk biomarkers of CVD and the MS and discusses the clinical significance and analytical considerations of each biomarker.