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

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

The metabolic syndrome: diagnosis and treatment

The metabolic syndrome is a clustering of risk factors that, in the aggregate, sharply increase the risk of cardiovascular disease (CVD). The syndrome is characterized by abdominal obesity, a characteristic atherogenic dyslipidemia, hypertension, insulin resistance with or without hyperglycemia, a prothrombotic state, and a proinflammatory state. CVD is the most important clinical sequela of the metabolic syndrome. The syndrome also carries a greatly increased risk for development of type 2 diabetes mellitus, which in turn increases cardiovascular risk even further. Conventional risk formulas may underestimate actual CVD risk in metabolic syndrome patients because of their concentration of nontraditional risk factors. Management of the metabolic syndrome should focus on weight loss, increased physical activity, and improvement of atherogenic diet. Pharmacologic therapy for lipids and blood pressure will be needed in most cases. The atherogenic dyslipidemia includes high triglyceride, low high-density lipoprotein cholesterol levels and small, dense low-density lipoprotein cholesterol particles. Management should allow for statin in virtually all cases, accompanied by a triglyceride-lowering agent in many cases. Hypertension should be managed aggressively, with a blood pressure target of 130/80 mm Hg. Multiple agents are usually required to treat hypertension. Simultaneous management of multiple risk factors has the potential to greatly reduce the incidence of CVD in individuals with the metabolic syndrome.     

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 metabolic syndrome: concepts and controversy

The metabolic syndrome is an insulin-resistant state characterized by a cluster of cardiovascular risk factors, including various combinations of abdominal obesity, glucose intolerance, hypertension, and atherogenic dyslipidemia (elevated triglyceride values, low high-density lipoprotein cholesterol levels, and small dense low-density lipoprotein cholesterol particles). The current epidemic of obesity and physical inactivity has led to an increased prevalence of this disorder. In this review, we discuss the history and pathogenesis of the metabolic syndrome, the controversy regarding the appropriateness of considering it a distinct diagnosis, and the importance of lifestyle modification in its prevention and treatment. The need for all cardiovascular risk factors to be treated, whether or not they are components of the metabolic syndrome, is emphasized. Recent discussions in the literature regarding the continued use of the term metabolic syndrome should be considered a healthy academic debate that hopefully will stimulate Ideas and innovative research to improve patient care.     

Diagnosing and treating metabolic syndrome

Recent studies have shown that approximately 22% of adults in the United States have metabolic syndrome, a loosely defined clustering of cardiovascular risk factors, including abdominal obesity, hypertriglyceridemia, low levels of high-density lipoprotein cholesterol (HDL-C), hypertension, and insulin resistance. With this syndrome looming as one of the most prevalent diseases of mankind (as well as one of the most preventable), it is imperative that practitioners have a thorough understanding of this condition so that they can effectively diagnose and appropriately manage it in their practices.     

Cardiovascular Risk Study: A Comparison Between Northeast Ohio Cardiovascular Nurses and the Nation

The purpose of this study was to determine if cardiovascular (CV) nurses exhibit lower coronary heart disease (CHD) risk factors than the nation. The CHD risk factors measured were: prehypertension, hypertension, elevated total cholesterol, low high-density lipoprotein (HDL) cholesterol, increased waist circumference (WC), cigarette smoking, and the presence of diabetes. When compared to US national averages, CV nurses in northeast Ohio demonstrated lower rates of smoking and abdominal obesity. No significant differences were found in cholesterol, HDL cholesterol, incidence of diabetes, or metabolic syndrome. These CV nurses did demonstrate higher blood pressures when compared to national averages for prehypertension. These findings illustrate a need to address CV nurses' specific CHD risk factors.     

Cardiovascular risk study: a comparison between northeast Ohio cardiovascular nurses and the nation

The purpose of this study was to determine if cardiovascular (CV) nurses exhibit lower coronary heart disease (CHD) risk factors than the nation. The CHD risk factors measured were: prehypertension, hypertension, elevated total cholesterol, low high-density lipoprotein (HDL) cholesterol, increased waist circumference (WC), cigarette smoking, and the presence of diabetes. When compared to US national averages, CV nurses in northeast Ohio demonstrated lower rates of smoking and abdominal obesity. No significant differences were found in cholesterol, HDL cholesterol, incidence of diabetes, or metabolic syndrome. These CV nurses did demonstrate higher blood pressures when compared to national averages for prehypertension. These findings illustrate a need to address CV nurses' specific CHD risk factors.     

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.     

Type 2 diabetes mellitus is associated with multiple cardiometabolic risk factors

The risk for cardiovascular disease (CVD) is multifactorial and includes such risk factors as diabetes, hypertension, smoking, and dyslipidemia. Thus, targeting the hyperglycemia in type 2 diabetes mellitus (DM) alone will not eliminate all of the excess cardiovascular risk; rather aggressive treatment is needed for all of the modifiable cardiometabolic risk factors. Therapeutic lifestyle change is considered primary therapy for hyperglycemia in type 2 DM. Currently, however, the focus in treatment is on preventing CVD rather than controlling glucose, lipid, or blood pressure (BP) levels. The American Diabetes Association guidelines identify low-density lipoprotein cholesterol as the first priority of lipid lowering, with optimal level set at <100 mg/dL (2.6 mmol/L). To reach the target BP level of <130/85 mm Hg, >65% of patients with DM and hypertension will require 2 or more different antihypertensive drugs. Strategies that combine thiazolidinediones and statins may have complementary effects on cardiovascular risk-factor profiles in type 2 DM, in addition to controlling glycemia. Despite the range of treatment options available, therapeutic agents that target new steps in the progression of CVD are needed, as patients with type 2 DM remain at increased risk and many do not achieve therapeutic targets with the drugs available.     

Are nutrition-induced epigenetic changes the link between socioeconomic pathology and cardiovascular diseases?

The prevalence of cardiovascular diseases (CVD) and diabetes mellitus type 2 (DM 2) is decreasing in developed countries despite the increase in the percentage of subjects with obesity and other well-recognized cardiovascular risk factors. In contrast, the recent transition of the economic model experienced by developing countries, characterized by the adoption of a Western lifestyle, that we have named "socioeconomic pathology," has led to an increase in the burden of CVD. It has been demonstrated that conventional cardiovascular risk factors in developed and developing countries are the same. Why then does the population of developing countries currently have a higher incidence of CVD than that of developed countries if they share the same risk factors? We have proposed the existence of a higher susceptibility to the development of systemic inflammation at low levels of abdominal obesity in the population of developing countries and the consequent endothelial dysfunction, insulin resistance, DM 2, and CVD. In contrast, an important percentage of obese people living in developed countries have a healthy phenotype and low risk of developing CVD and DM 2. Human epidemiologic studies and experimental dietary interventions in animal models have provided considerable evidence to suggest that nutritional imbalance and metabolic disturbances early in life may later have a persistent effect on an adult's health that may even be transmitted to the next generations. Epigenetic changes dependent on nutrition could be key in this evolutionary health behavior, acting as a buffering system, permitting the adaptation to environmental conditions by silencing or increasing the expression of certain genes.     

Epidemiology and treatment of the metabolic syndrome

Recent definitions of the metabolic syndrome from the World Health Organization (WHO) and National Cholesterol Education Program (NCEP) have given us a clearer picture of the prevalence of the metabolic syndrome and the risks it poses for cardiovascular disease and type 2 diabetes. Solid epidemiological and trial evidence support lifestyle changes as the main modifiable risk factors, including abdominal obesity, sedentary lifestyle and a diet rich in saturated fat and low in fiber content, in the treatment of individual components of the metabolic syndrome. Physical activity may prevent the metabolic syndrome as defined by the WHO and NCEP, but the evidence for lifestyle changes using these definitions is still sparse. No trials on the treatment of the metabolic syndrome to prevent diabetes have been published. However, both the Finnish Diabetes Prevention Study and the Diabetes Prevention Program found that moderate lifestyle interventions in persons with impaired glucose tolerance, a condition related to the metabolic syndrome. decreased the incidence of type 2 diabetes by 58%. Some drugs may also prevent diabetes. Further research on lifestyle modifications in the prevention and treatment of the metabolic syndrome, and on how best to promote lifestyle changes, is needed. In the meantime, efforts to curb obesity and overweight, increase physical activity and improve compliance with current dietary recommendations should continue.     

Cardiovascular disease and modifiable cardiometabolic risk factors

Cardiovascular disease (CVD) is the leading cause of death in the United States and many parts of the world. Potentially modifiable risk factors for CVD include tobacco use, physical inactivity, hypertension, elevated low-density lipoprotein cholesterol, and a cluster of interrelated metabolic risk factors. Over the last several decades, efforts to prevent or treat CVD risk factors have resulted in significantly lower rates of CVD-related mortality. However, many patients never achieve adequate control of CVD risk factors even when these factors have been identified. In addition, the growing prevalence of obesity and type 2 diabetes mellitus (DM) threatens to undermine the improvements in CVD that have been achieved. In the United States, approximately two thirds of adults are overweight or obese, and even modest excess body weight is associated with a significantly increased risk of CVD-related mortality. Lifestyle interventions to promote weight loss reduce the risk of CVD-related illness but are difficult for patients to sustain over long periods of time. The increased incidence of obesity has also contributed to significant increases in the prevalence of other important CVD risk factors, including hypertension, dyslipidemia, insulin resistance, and type 2 DM. Pharmacologic therapies are currently available to address individual CVD risk factors, and others are being evaluated, including endocannabinoid receptor antagonists, inhibitors of peroxisome proliferator-activated receptor subtypes alpha and gamma, and several agents that modulate the activity of glucagon-like peptide-1. The new agents have the potential to significantly improve several CVD risk factors with a single medication and may provide clinicians with several new strategies to reduce the long-term risk of CVD.     

Dyslipidemia therapy update: the importance of full lipid profile assessment

Lipid guidelines typically focus on total cholesterol ± low-density lipoprotein cholesterol levels with less emphasis on high-density lipoprotein cholesterol (HDL-C) or triglyceride assessment, thus potentially underestimating cardiovascular (CV) risk and the need for lifestyle or treatment optimization. In this article, we highlight how reliance on isolated total cholesterol assessment may miss prognostically relevant lipid abnormalities; we describe from the European Systematic COronary Risk Evaluation (SCORE) data set how incorporation of HDL-C may improve estimation of CV risk; and, finally, we critically evaluate the evidence base surrounding triglycerides and CV risk.     

Metabolic syndrome and risk of stroke

Stroke is one of the leading causes of death in the United States and worldwide. Metabolic syndrome, comprising abdominal obesity, elevated triglyceride levels, low levels of high-density lipoprotein cholesterol, elevated blood pressure, and impaired glucose metabolism, greatly increases the risk of cardiovascular disease, including stroke. The high prevalence of metabolic syndrome among individuals who experience stroke makes the metabolic syndrome a target for aggressive intervention and therapy. In addition to lifestyle changes, therapy with statins, angiotensin-converting enzyme inhibitors, insulin sensitizers, and antithrombotic agents to aggressively treat elements of metabolic syndrome is warranted. Statins favorably affect both lipid and nonlipid risk factors for stroke, making them a useful tool for stroke prevention.     

Epidemiology and treatment of the metabolic syndrome

Recent definitions of the metabolic syndrome from the World Health Organization (WHO) and National Cholesterol Education Program (NCEP) have given us a clearer picture of the prevalence of the metabolic syndrome and the risks it poses for cardiovascular disease and type 2 diabetes. Solid epidemiological and trial evidence support lifestyle changes as the main modifiable risk factors, including abdominal obesity, sedentary lifestyle and a diet rich in saturated fat and low in fiber content, in the treatment of individual components of the metabolic syndrome. Physical activity may prevent the metabolic syndrome as defined by the WHO and NCEP, but the evidence for lifestyle changes using these definitions is still sparse. No trials on the treatment of the metabolic syndrome to prevent diabetes have been published. However, both the Finnish Diabetes Prevention Study and the Diabetes Prevention Program found that moderate lifestyle interventions in persons with impaired glucose tolerance, a condition related to the metabolic syndrome, decreased the incidence of type 2 diabetes by 58%. Some drugs may also prevent diabetes. Further research on lifestyle modifications in the prevention and treatment of the metabolic syndrome, and on how best to promote lifestyle changes, is needed. In the meantime, efforts to curb obesity and overweight, increase physical activity and improve compliance with current dietary recommendations should continue.     

Fitness, inflammation, and the metabolic syndrome in men with paraplegia

OBJECTIVE: To determine the relations among peak aerobic capacity, physical activity, functional ability, components of the metabolic syndrome (high-density lipoprotein cholesterol [HDL-C], triglycerides [TG], glucose, insulin, abdominal obesity, high blood pressure), and inflammatory factors (interleukin-6 [IL-6], C-reactive protein [CRP]) in men with paraplegia. DESIGN: Cross-sectional exploratory design. SETTING: University research laboratory. PARTICIPANTS: Twenty-two men (age, 39+/-9y; duration of injury, 17+/-9y; level of injury, T2-L2) with functionally complete paraplegia volunteered to participate. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Peak aerobic capacity was measured using a graded peak exercise test with an arm ergometer, and physical activity was assessed by the Physical Activity and Disability Scale. Functional ability was assessed by the Self-Report Functional Measure. Circulating glucose, insulin, HDL-C, TG, total cholesterol, IL-6, and CRP levels were determined by specific enzyme or immunologic assays. Body fat was determined by dual-energy x-ray absorptiometry, and central obesity was estimated from abdominal sagittal diameters. RESULTS: Lower peak aerobic capacities were associated with lower HDL-C and lower physical activity levels ( P <.014). Lower physical activity levels were associated with higher fasting glucose, lower HDL-C level, and larger abdominal sagittal diameters ( P <.036). Larger abdominal sagittal diameters were associated with higher fasting glucose, higher fasting and postload insulin, lower HDL-C, higher TG, and higher CRP levels ( P <.05). CONCLUSIONS: Diet and exercise trials are needed to determine the efficacy and effectiveness of lifestyle interventions aimed at slowing the progression of the metabolic syndrome in people with spinal cord injury.     

Treatment options for patients with the metabolic syndrome

PURPOSE: To review clinical and laboratory findings that will enhance nurse practitioner (NP) recognition of the metabolic syndrome and to increase awareness of recent treatment guidelines and treatment options. DATA SOURCES: Professional association practice guidelines, government documents, original research articles, and journal articles. CONCLUSIONS: The metabolic syndrome is a prevalent condition characterized by a cluster of lipid and nonlipid abnormalities, including atherogenic dyslipidemia, elevated fasting blood glucose, hypertension, and abdominal obesity. Many persons with this syndrome are also insulin resistant. Prompt recognition and treatment of the metabolic syndrome can prevent or delay the development of type 2 diabetes and coronary heart disease. Clinical guidelines recommend treating the metabolic syndrome as a secondary target of lipid-lowering therapy after addressing the primary target, low-density lipoprotein cholesterol. IMPLICATIONS FOR PRACTICE: NPs are in an instrumental position to manage treatment for patients with the metabolic syndrome by (a) evaluating risk factors, including abdominal obesity, physical inactivity, atherogenic dyslipidemia, hypertension, and elevated fasting blood glucose; (b) assisting in the modification of lifestyle factors such as diet and exercise; (c) implementing pharmacological therapy when needed; and (d) providing psychosocial support to encourage therapeutic adherence.     

Metabolic syndrome: time for action

The constellation of dyslipidemia (hypertriglyceridemia and low levels of high-density lipoprotein cholesterol), elevated blood pressure, impaired glucose tolerance, and central obesity is identified now as metabolic syndrome, also called syndrome X. Soon, metabolic syndrome will overtake cigarette smoking as the number one risk factor for heart disease among the U.S. population. The National Cholesterol Education Program-Adult Treatment Panel III has identified metabolic syndrome as an indication for vigorous lifestyle intervention. Effective interventions include diet, exercise, and judicious use of pharmacologic agents to address specific risk factors. Weight loss significantly improves all aspects of metabolic syndrome. Increasing physical activity and decreasing caloric intake by reducing portion sizes will improve metabolic syndrome abnormalities, even in the absence of weight loss. Specific dietary changes that are appropriate for addressing different aspects of the syndrome include reducing saturated fat intake to lower insulin resistance, reducing sodium intake to lower blood pressure, and reducing high-glycemic-index carbohydrate intake to lower triglyceride levels. A diet that includes more fruits, vegetables, whole grains, monounsaturated fats, and low-fat dairy products will benefit most patients with metabolic syndrome. Family physicians can be more effective in helping patients to change their lifestyle behaviors by assessing each patient for the presence of specific risk factors, clearly communicating these risk factors to patients, identifying appropriate interventions to address specific risks, and assisting patients in identifying barriers to behavior change.     

The association between fibrate use, change in high-density lipoprotein cholesterol, and the risk of cardiovascular disease: a retrospective chart review involving up to 8 years of follow-up

BACKGROUND: Clinical trials have indicated that the use of fibric acid derivatives confers a benefit against cardiovascular disease (CVD) in selected populations. However, whether fibrates provide a CVD risk reduction independent of changes in the traditional lipoprotein fractions and other known CVD risk factors is not clear. OBJECTIVE: This study examined whether the use of fibrate therapy in a general clinical setting provided cardiovascular benefits independent of changes in the traditional lipoprotein fractions. METHODS: This was a matched, retrospective cohort study. From the electronic records of a large health maintenance organization in the northwestern United States, we identified a population that had newly initiated fibrate pharmacotherapy between January 1, 1996, and December 31, 2000. We then identified a comparator group of patients not using fibrates, matching them to fibrate users based on high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) levels, age, sex, and year of HDL-C and TG measurement. Subjects were followed until a CVD hospitalization, termination from the health plan, or December 31, 2003, whichever came first. We then used multivariate analysis accounting for differences in followup to identify predictors of CVD incidence. RESULTS: The study population included 1722 matched pairs (56.6% male; mean [SD] age, 57.3 [11.1] years). The patients who had newly initiated fibrate pharmacotherapy had low baseline HDL-C levels (mean, 37.4 mg/dL) and very high TG levels (617 mg/dL). The 2 groups were similar overall, with the only significant differences between fibrate users and nonfibrate controls being a greater prevalence of diabetes (37.7% vs 34.3%, respectively; P=0.040) and greater use of angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (56.6% vs 51.6%, respectively; P=0.003), beta-blockers (53.7% vs 49.0%; P=0.006), calcium channel blockers (25.1% vs 20.9%; P=0.004), and niacin (11.7% vs 7.4%; P<0.001). Overall, CVD risk was 26% lower for every 5-mg/dL increment in HDL-C. After adjustment for age, sex, smoking history, diabetes, existing diagnosis of CVD, weight, systolic blood pressure, baseline HDL-C, change in HDL-C, total cholesterol, TG, and use of statins, niacin, and other CVD drugs, fibrate use did not confer an additional CVD risk reduction. CONCLUSIONS: In this cohort with low baseline HDL-C levels and very high TG levels, fibrate use did not confer an independent CVD risk reduction after adjustment for CVD risk factors. Given the current obesity epidemic in the United States and the corresponding rise in the number of patients with the metabolic syndrome, the apparent risk reduction observed in association with higher HDL-C levels should not be ignored.