Obesity--the risk factor of cardiovascular disease in patients with chronic kidney disease?

In general population obesity is regarded as a predisposing factor for chronic disease such as type 2 diabetes and cardiovascular disease. Obesity increases the risk of kidney disease and adversely affects the progress of kidney disease among patients with diagnosed kidney disease. The main reason of mortality in chronic kidney disease patients is cardiovascular disease, however, the real meaning of obesity as a risk factor of cardiovascular diseases is still uncertain. While in a general population obesity causes higher cardiovascular mortality, many studies reflect inverse association in chronic kidney disease patients. Obesity is associated with better survival, contrary to general population obesity appears to be a protective factor of cardiovascular disease. The name of this phenomenon is "reverse epidemiology" or "obesity paradox", in dialysis patients known as a "risk-factor-paradox". Some studies do not confirm this paradox association in patients with chronic kidney disease.     

The paradox of obesity cardiomyopathy and the potential for weight loss as a therapy

Obesity is an independent risk factor for developing heart failure and the combination of the two disease states will prove to be a significant health burden over the coming years. Obesity is likely to contribute to the development of heart failure through a variety of mechanisms, including structural and functional changes, lipotoxicity and steatosis and altered substrate selection. However, once heart failure has developed, it seems that obesity confers a beneficial influence on prognosis in what has been termed the ‘obesity paradox’. This may be a statistical phenomenon, but it should be considered that there is truly a protective state in the physiology of obesity. There is little evidence regarding the impact of weight loss in obese heart failure and whether or not this is beneficial. There have been small studies regarding the cardiovascular effects of both dietary weight loss and bariatric surgery, but few in heart failure. This is an important and increasingly relevant clinical question which must be addressed.     

Adipokines: A link between obesity and cardiovascular disease

Obesity is a risk factor for various cardiovascular diseases including hypertension, atherosclerosis, and myocardial infarction. Recent studies aimed at understanding the microenvironment of adipose tissue and its impact on systemic metabolism have shed light on the pathogenesis of obesity-linked cardiovascular diseases. Adipose tissue functions as an endocrine organ by secreting multiple immune-modulatory proteins known as adipokines. Obesity leads to increased expression of pro-inflammatory adipokines and diminished expression of anti-inflammatory adipokines, resulting in the development of a chronic, low-grade inflammatory state. This adipokine imbalance is thought to be a key event in promoting both systemic metabolic dysfunction and cardiovascular disease. This review will focus on the adipose tissue microenvironment and the role of adipokines in modulating systemic inflammatory responses that contribute to cardiovascular disease.     

Obesity, Age, and Cardiac Risk

Obesity is a highly prevalent metabolic disorder affecting all sections of society from young children to adults and the elderly. Obesity is a well-established risk factor for several conventional cardiovascular (CV) risk factors such as hypertension (HTN), type 2 diabetes mellitus, and dyslipidemia. Obesity is also a very potent independent risk factor for CV diseases (CVD), including coronary heart disease (CHD), heart failure (HF), peripheral arterial disease (PAD), atrial fibrillation (AF), and sudden cardiac death (SCD), and is also associated with increased CV and all-cause morbidity. Despite this adverse association between obesity and CV risk factors and several CVDs, numerous studies have identified the phenomenon called the “obesity paradox” or “reverse epidemiology”, meaning better short- and long-term survival in overweight and obese subjects with HTN, HF, CHD, PAD, and AF. This review summarizes the adverse impact of obesity on CV risk factors and CVDs, effects of obesity and aging in the elderly, and the puzzling phenomenon of the “obesity paradox” in the above-mentioned special populations and the elderly.     

Reverse epidemiology of conventional cardiovascular risk factors in patients with chronic heart failure

Traditional risk factors of a poor clinical outcome and mortality in the general population, including body mass index (BMI), serum cholesterol, and blood pressure (BP), are also found to relate to outcome in patients with chronic heart failure (CHF), but in an opposite direction. Obesity, hypercholesterolemia, and high values of BP have been demonstrated to be associated with greater survival among CHF patients. These findings are in contrast to the well-known associations of over-nutrition, hypercholesterolemia, and hypertension with a poor outcome in the general population. The association between traditional cardiovascular risk factors and an adverse clinical outcome in CHF patients is referred to as "reverse epidemiology." The mechanisms for this inverse association in CHF is not clear. There are other populations with a similar risk factor reversal phenomenon, including patients with end-stage renal disease receiving dialysis, those with advanced malignancies, and individuals with advanced age. Several possible causes are hypothesized: the time discrepancy of the competing risk factors may play a role; the presence of the "malnutrition-inflammation complex syndrome" in CHF patients may explain the existence of reverse epidemiology; and a decreased level of lipoprotein molecules may distort their endotoxin-scavenging role, predisposing CHF patients with a low serum cholesterol level to inflammatory consequences of endotoxemia. It is possible that new goals for such traditional risk factors as BMI, serum cholesterol, and BP should be developed for CHF. Reverse epidemiology of conventional cardiovascular risk factors is observed in CHF and may have a bearing on the management of these patients; thus, it deserves further investigation.     

The obesity epidemic and its cardiovascular consequences

PURPOSE OF REVIEW: Obesity has reached global epidemic proportions because of an increasingly obesogenic environment. This review examines the association between obesity, and in particular visceral fat, as a risk factor for cardiovascular disease and mortality. RECENT FINDINGS: The World Health Organization defines obesity based on the body mass index. Recently the waist-to-hip ratio has been shown to be a significantly stronger predictor of cardiovascular events than body mass index. The metabolic syndrome and its evolving definition represent a cluster of metabolic risk factors which help predict cardiovascular disease and mortality. Although insulin resistance plays a central role in the pathophysiology of the metabolic syndrome, there is limited support for therapy with insulin sensitizers, thiazolidinediones, in patients with coronary artery disease. The current anti-obesity drugs, orlistat and sibutramine, have only a modest effect on weight loss. The blockade of the endocannabinoid system with rimonabant, however, may be a promising new strategy. SUMMARY: Obesity is associated with significant increase in cardiovascular risk. Lifestyle modification remains the cornerstone of management although anti-obesity medications may be indicated in high risk individuals with comorbid disease.     

Adipositas und kardiale Kachexie bei chronischer Herzinsuffizienz

Obesity as well as cardiac cachexia in heart failure patients are not fully understood and therefore of high scientific interest. Obesity as a common risk factor for cardiovascular disease is associated with a high mortality. In contrast obesity in patients suffering from chronic heart failure seems to be accompanied with a favorable outcome in contrast to people with normal weight, known as the obesity paradox. In the last decade there has been growing interest in cachexia, which is common in advanced stages of chronic diseases, such as heart failure, chronic obstructive pulmonary disease (COPD), cancer and renal failure and is associated with a poor prognosis. Until now cachexia has been underdiagnosed and undertreated. This review discusses the complex underlying pathomechanisms as well as potential therapeutic approaches.     

Obesity and cardiovascular disease. Pathogenetic role of the metabolic syndrome and therapeutic implications

Since obesity is a major risk factor for cardiovascular disease (CVD), the increasing prevalence and degree of obesity in all developed countries has the potential to significantly offset the current efforts to decrease CVD burden in our population. Obesity is pathogenetically related to several clinical and sub-clinical abnormalities that contribute to the development of atherosclerotic placks and their complication, leading to the onset of cardiovascular events. Obesity seems to interact with inheritable factors in determining the onset of insulin resistance, a metabolic abnormality that is responsible for altered glucose metabolism and predisposition to type 2 diabetes, but that also has a major role in the development of dyslipidemia, hypertension and many other sub-clinical abnormalities that contribute to the atherosclerotic process and onset of cardiovascular events. Inheritable factors seem to modulate the onset of type 2 diabetes, dyslipidemia, hypertension and various insulin resistance-related sub-clinical abnormalities, often in a clustering pattern that is commonly referred to as the "metabolic syndrome." Inheritable factors also are involved in the onset of CVD in a given population or individuals with various components of the metabolic syndrome. Intense research is currently undergoing to better understand the molecular mechanisms that could explain the relationship between environmental and inheritable factors that lead from obesity to atherosclerosis and cardiovascular event. The elucidation of these mechanisms will provide improved therapeutic strategies to reduce cardiovascular risk in the obese patients. However, effective therapeutic tools that control each of the known pathophysiological steps mediating CVD in obese patients are already available and should be used more aggressively. Patient education and coordinated approach of physicians, nurses and other health care providers in a multidisciplinary treatment of the obese patient is of fundamental importance to reduce CVD burden in our population.     

Sleep disordered breathing and risk factors for cardiovascular disease

Patients with sleep disordered breathing (SDB) are at increased risk for cardiovascular disease including hypertension, angina, myocardial infarction, and stroke. Neurohumoral and hemodynamic responses to untreated sleep apnea are likely mechanisms that produce functional and structural changes within the cardiovascular system. Obesity, higher blood pressure, and advancing age, which are common characteristics of patients with SDB, contribute to the overall risk for cardiovascular disease. Recent studies indicate that OSA is associated with or aggravates other risk markers for cardiovascular disease. These factors include leptin, C-reactive protein, homocysteine, and insulin resistance syndrome. Elevations in C-reactive protein and glucose intolerance may be correlated with the severity of SDB. The impact of alleviating SDB on these cardiovascular risk factors has not been fully elucidated. Regardless, assessment of overall cardiovascular risk in patients with sleep apnea is warranted to identify those individuals that are high-risk who require immediate attention and intervention or in those that should be treated more aggressively.     

脂肪因子与肥胖相关心血管疾病关系的研究进展

肥胖是各种心血管疾病（包括高血压、动脉粥样硬化和心肌梗死）的危险因素。通过对脂肪组织微环境以及对全身代谢影响的研究,可揭示肥胖相关心血管疾病的发病机制。脂肪组织具有分泌多种免疫调节蛋白的功能,这些免疫调节蛋白称为脂肪因子。肥胖可导致促炎性脂肪因子的表达增加和抗炎性脂肪因子的表达减少,从而产生一种慢性轻度的炎症状态。这种脂肪因子的失衡被认为是促进全身代谢功能障碍和心血管疾病的关键原因。     

Obesity and endothelial dysfunction

Obesity is becoming more prevalent in the developed world because of the abundance of food and the decrease of physical activity. Obesity is a risk factor for a host of diseases from arthritis to cardiovascular disease. The precise mechanisms by which obesity promotes cardiovascular disease are not well understood but are likely to include metabolic and inflammatory responses to the increased amount of stored fat. The endothelium plays a pivotal role in maintaining vascular health. Impaired endothelial function is an independent predictor of cardiovascular disease. Most studies of vascular function in obese subjects have demonstrated impaired endothelial function. This impairment of endothelial function becomes obvious early on, long before any vascular abnormalities become clinically relevant and detectable. Better understanding of the mediators of obesity-induced endothelial dysfunction may lead to the identification of new targets for interventions that may prevent or postpone the development of obesity-related cardiovascular disease.     

Links between adipose tissue and thrombosis in the mouse

Obesity has become a global epidemic and carries a considerable negative impact in regard to quality of life and life expectancy. A primary problem is that obese individuals are at increased risk of suffering from cardiovascular disease complications such as myocardial infarction and stroke. Because fat accumulation is a consistent aspect of obesity, mechanisms that may link adipose tissue to cardiovascular disease complications should be considered. Proteins expressed from adipose tissue, known as adipokines, are hypothesized to have important effects on the progression and incidence of cardiovascular disease complications. This review examines the evidence that adipokines play a direct role in vascular thrombosis, an important event in cardiovascular disease complications.     

Association of body mass index with mortality in cardiovascular disease: New insights into the obesity paradox from multiple perspectives

Over the past 4 decades, prevalence of obesity has increased rapidly at both the national and global level and presents a major public health challenge. Obesity is associated with increased risk of morbidity from cardiovascular diseases. Data suggesting that the presence of obesity may be protective in individuals with clinically manifest cardiovascular disease have led to discussion of an “obesity paradox”, stirring controversy and leading to unclear messaging regarding the true health risks of excess weight. This review explores the relationship between obesity and fatal and non-fatal outcomes in patients with prevalent cardiovascular disease and offers novel insights into the obesity paradox.     

Fifty years of Framingham Study contributions to understanding hypertension

The Framingham Study established hypertension as a major cardiovascular risk factor and quantified its atherogenic cardiovascular disease potential. An historical perspective is presented on the epidemiological insights about hypertension derived from 50 years of Framingham Study research into the prevalence, incidence, determinants and hazards of hypertension. Existing misconceptions about the presence of critical levels of blood pressure, the impact of the systolic and diastolic components of blood pressure, the hazard 'mild' hypertension, the impact in advanced age and the hazard of left ventricular hypertrophy. The importance of isolated systolic hypertension and the pulse pressure were demonstrated. It has been demonstrated that hypertension seldom occurs in isolation of other atherogenic risk factors, with which it tends to cluster. This clustering with other metabolically linked risk factors has been shown to reflect insulin resistance promoted by weight gain and abdominal obesity. Obesity was shown to be one of the major determinants of hypertension in the general population. Left ventricular hypertrophy was shown to be an ominous harbinger of cardiovascular disease rather than an incidental compensatory phenomenon. Multivariate risk profiles for coronary disease, stroke, peripheral artery disease and heart failure have been devised to facilitate incorporation of elevated blood pressure in a global, multivariate cardiovascular risk assessment.     

Impact of obesity on cardiovascular disease

The epidemiology of cardiovacular disease risk factors is changing rapidly with the obesity pandemic. Obesity is independently associated with the risks for coronary heart disease, atrial fibrillation, and heart failure. Intra-abdominal obesity is also unique as a cardiovascular risk state in that it contributes to or directly causes most other modifiable risk factors, namely, hypertension, dysmetabolic syndrome, and type 2 diabetes mellitus. Obesity can also exacerbate cardiovascular disease through a variety of mechanisms including systemic inflammation, hypercoagulability, and activation of the sympathetic and renin-angiotensin systems. Thus, weight reduction is a key strategy for simultaneous improvement in global cardiovascular risk, with anticipated improvements in survival and quality of life.     

Obesity paradox in joint replacement for osteoarthritis — truth or paradox?

GeroScience - Obesity is associated with an increased risk of cardiovascular disease (CVD) and other adverse health outcomes. In patients with pre-existing heart failure or coronary heart disease,...     

Obesity-associated hypertension: new insights into mechanisms

Obesity is strongly associated with hypertension and cardiovascular disease. Several central and peripheral abnormalities that can explain the development or maintenance of high arterial pressure in obesity have been identified. These include activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system. Obesity is also associated with endothelial dysfunction and renal functional abnormalities that may play a role in the development of hypertension. The continuing discovery of mechanisms regulating appetite and metabolism is likely to lead to new therapies for obesity-induced hypertension. Better understanding of leptin signaling in the hypothalamus and the mechanisms of leptin resistance should facilitate therapeutic approaches to reverse the phenomenon of selective leptin resistance. Other hunger and satiety signals such as ghrelin and peptide YY are potentially attractive therapeutic strategies for treatment of obesity and its complications. These recent discoveries should lead to novel strategies for treatment of obesity and hypertension.     

Obesity—A Critical Issue in Preventive Cardiology: The Bogalusa Heart Study

Obesity has become a major public health problem in the United States, with a marked upward trend occurring over the past three decades. It plays a critical role in the development of cardiovascular risk factors that mediate the evolution of asymptomatic cardiovascular disease. Longitudinal observations of children, adolescents, and young adults enrolled in the Bogalusa Heart Study show that obesity persists over time and is linked to the clustering of components of metabolic syndrome including hyperinsulinemia/ insulin resistance, dyslipidemia, and hypertension, thereby creating a long-term burden of cardiovascular risk beginning in childhood. This burden is associated with subclinical and adverse structural and functional changes of the cardiovascular system in youth. Ultimately, these changes can result in morbidity from disease, as exemplified in the Framingham Heart Study. Obesity is governed by the interplay of both genetic and environmental factors. Unlike genetic factors, lifestyle behaviors are amenable to modification. Since obesity is so widespread and underlying cardiovascular disease is so prevalent, health education beginning in childhood is suggested as an approach to prevention.     

Obesity--a critical issue in preventive cardiology: the Bogalusa Heart Study

Obesity has become a major public health problem in the United States, with a marked upward trend occurring over the past three decades. It plays a critical role in the development of cardiovascular risk factors that mediate the evolution of asymptomatic cardiovascular disease. Longitudinal observations of children, adolescents, and young adults enrolled in the Bogalusa Heart Study show that obesity persists over time and is linked to the clustering of components of metabolic syndrome including hyperinsulinemia/insulin resistance, dyslipidemia, and hypertension, thereby creating a long-term burden of cardiovascular risk beginning in childhood. This burden is associated with subclinical and adverse structural and functional changes of the cardiovascular system in youth. Ultimately, these changes can result in morbidity from disease, as exemplified in the Framingham Heart Study. Obesity is governed by the interplay of both genetic and environmental factors. Unlike genetic factors, lifestyle behaviors are amenable to modification. Since obesity is so widespread and underlying cardiovascular disease is so prevalent, health education beginning in childhood is suggested as an approach to prevention.     

Mechanisms of obesity-associated cardiovascular and renal disease

Obesity is the most common nutritional disorder in the United States. Growing evidence suggests that obesity initiates a cascade of disorders including hypertension, diabetes, atherosclerosis, and chronic renal disease, many of which are interdependent. Abnormal kidney function, caused by increased renal tubular reabsorption, initiates volume expansion and increased blood pressure during excess weight gain, and the hypertension and metabolic abnormalities associated with obesity, in turn, contribute to chronic renal disease. Obesity causes cardiac and vascular disease through well-known mediators such as hypertension, type II diabetes, and dyslipidemia, but there is evidence for less well-characterized mediators such as chronic inflammation and hypercoagulation. Although obesity is increasingly recognized as a serious health problem, there are still many unanswered questions about how the multiple disorders associated with excess weight gain interact to cause cardiovascular and renal disease. Also, there are few studies that have examined whether sustained weight loss in obese subjects can reverse these changes. In view of the "epidemic" of obesity in our country and the excess burden of cardiovascular and renal disease in minority populations, addressing these issues is of paramount importance for the Jackson Heart Study, as well as for other national health initiatives.