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.     

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.     

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.     

Managing metabolic syndrome in women

Cardiovascular disease (CVD) death rates in women in the United States are rising. This is attributed to the obesity epidemic and its contribution to cardiometabolic risk. Various gender-related factors and strategies must be considered to effectively manage metabolic syndrome in women and improve outcomes.     

Treatment of hypertension and other cardiovascular risk factors in patients with metabolic syndrome

Metabolic syndrome (MetS), a concurrence of hypertension, abdominal obesity, impaired fasting glucose, and dyslipidemia, has been shown to be a risk factor for cardiovascular disease. Insulin resistance has been thought to be one of the pathophysiologies of the syndrome. Reduction of the underlying causes of MetS, such as obesity, physical inactivity, and atherogenic diet, is first-line therapy. Treatment of hypertension and other cardiometabolic risk factors of MetS is also required. This article reviews the treatment of the metabolic syndrome with a focus on the importance of lifestyle changes and treatment of hypertension.     

Glycemic status, metabolic syndrome, and cardiovascular risk in children

The metabolic syndrome and adult manifestation of prediabetes and diabetes are major public health problems that begin in childhood. Prevention must be considered as a serious public health issue. Health education and health promotion of school children needs incorporation as a community effort.     

Highly active antiretroviral therapy-associated metabolic syndrome: pathogenesis and cardiovascular risk

The introduction of highly active antiretroviral therapy (HAART) has significantly modified the course of HIV disease, with longer survival and improved quality of life of HIV-infected subjects. However, HAART regimens, especially those including protease inhibitors (PIs) have been shown to cause in a high proportion of HIV-infected patients a metabolic syndrome that may be associated with an increased risk of cardiovascular disease (about 1.4 cardiac events per 1,000 years of therapy according to the Framingham score). Metabolic features associated with somatic changes (lipodystrophy/lipoatrophy) include dyslipidemia (about 70% of patients), insulin resistance (elevated C-peptide and insulin), type 2 diabetes mellitus (8%-10% of the patients), hypertension (up to 75% of patients), coagulation abnormalities (25% of patients), lactic acidemia, and elevated hepatic transaminases (nonalcoholic steatohepatitis). HAART-associated metabolic syndrome is an increasingly recognized clinical entity. A better understanding of the molecular mechanisms responsible for this syndrome will lead to the discovery of new drugs that will reduce the cardiovascular risk in patients under HAART. A careful stratification of the cardiovascular risk and cardiovascular monitoring of patients under HAART is needed according to the most recent clinical guidelines.     

Managing suicidal inpatients

Suicidality is the most common and vexing challenge presented by psychiatric inpatients. Although clinicians' ability to predict suicide is limited and suicide may inevitably occur, conscientious assessment of risk, effective distinction among various characteristics of the suicidal crisis, and thoughtful policies and procedures will help keep many patients from fatal outcomes.     

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.     

Ethnic differences in cardiovascular risk factors in healthy Caucasian and South Asian individuals with the metabolic syndrome

BACKGROUND: The metabolic syndrome is a cluster of atherothrombotic risk factors that are commonly associated with insulin resistance. OBJECTIVES: The aim of this study was to investigate ethnic differences in insulin resistance and non-traditional cardiovascular risk factors in relation to the International Diabetes Federation (IDF) definition of the metabolic syndrome. PATIENTS AND METHODS: A total of 245 healthy South Asians and 245 age- and sex-matched Caucasians were studied. C-reactive protein (CRP), complement C3, plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (t-PA) were measured and homeostasis model assessment-insulin resistance (HOMA-IR) was calculated from fasting plasma glucose and insulin levels. RESULTS: Fifty Caucasian (20%) and 95 (39%) South Asian subjects had the metabolic syndrome as defined by the IDF. In South Asian subjects, HOMA-IR, CRP, C3, PAI-1 and t-PA were significantly higher in subjects with the metabolic syndrome. In contrast, in Caucasian individuals there was no difference in HOMA-IR or C3 levels and only CRP, PAI-1 and t-PA were higher in subjects with the metabolic syndrome. In a logistic regression model, plasma levels of CRP and PAI-1 were independent predictors of the metabolic syndrome in Caucasians, whereas plasma levels of C3 and t-PA as well as HOMA-IR were independent predictors of the metabolic syndrome in South Asian subjects. CONCLUSIONS: In the cohort of individuals studied, the IDF definition of the metabolic syndrome was associated with insulin resistance in the South Asian but not the Caucasian population. This work also showed ethnic differences in non-traditional cardiovascular risk factors in the presence of the 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     

Managing atherosclerosis in patients with type 2 diabetes mellitus and metabolic syndrome

Diabetes mellitus with its increasing prevalence is a major global health problem in United States. Macrovascular complications, especially atherosclerosis, are the major cause of morbidity and mortality in patients with type 2 diabetes mellitus. Metabolic syndrome is considered to be a metabolic precursor of type 2 diabetes mellitus and is an independent risk factor in the pathogenesis of atherosclerosis. It is a constellation of proatherogenic metabolic abnormalities, which include obesity, hypertension, characteristic dyslipidemia, hyperglycemia, insulin resistance, and compensatory hyperinsulinemia. Recent epidemiological data have demonstrated a strong causal association between insulin resistance and coronary vascular disease independent of hyperglycemia associated with type 2 diabetes mellitus. Given the high prevalence of metabolic syndrome in the general population and its role in the pathogenesis of atherosclerosis, every attempt should be made to recognize early the metabolic syndrome and to modify the associated proatherogenic metabolic abnormalities. Management of atherosclerosis in insulin-resistant states like metabolic syndrome and type 2 diabetes is a multifactorial process involving nonpharmacological interventions like exercise, diet control, and pharmacological therapy directed at hypertension, hyperglycemia, and dyslipidemia. Further research is warranted to demonstrate the effects of these interventions unequivocally in preventing the progression of metabolic syndrome to overt type 2 diabetes mellitus with its associated macrovascular complications.     

慢性精神分裂症患者伴发代谢综合症临床研究

目的探讨长期服用氯氮平治疗的慢性精神分裂症患者伴发代谢综合症的发生率及其相关因素。方法对124例长期服用氯氮平治疗的慢性精神分裂症患者的一般资料进行统计整理，并测量身高、体重、腰围和血压，测定空腹血糖、血总胆固醇、甘油三脂、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇及氯氮平血药浓度，对检测结果进行相关分析。结果长期服用氯氮平的慢性精神分裂症患者中糖尿病发生率19．4％、高血压发生率12．1％、肥胖发生率54．0％、血脂紊乱发生率55．600，代谢综合症发生率14．5％，其中女性患者肥胖发生率显著高于男性（P〈0．05）。相关因素分析显示，血压、血脂与性别有关，血压、BMI、血脂及腰围与氯氮平最高剂量有关。结论长期服用氯氮平治疗的慢性住院精神分裂症患者伴发代谢综合症的发生率较高，其与性别及服用氯氮平的最大剂量有关。     

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.