Chronic Kidney Disease as a Coronary Artery Disease Risk Equivalent

Chronic kidney disease (CKD) is associated with accelerated cardiovascular disease (CVD) risk and a higher CVD event rate. Substantial data from prospective cohort studies support the concept that dialysis patients as well as those with advanced stage (stages 3–5) CKD are associated with an increased risk for all-cause and cardiovascular mortality. The risk for coronary artery disease (CAD) increases exponentially with declining kidney function, i.e., stage 3 or higher CKD. Indeed, CVD accounts for more than 50 % of deaths in patients with CKD. CKD patients are more likely to die of CVD than to progress to end stage kidney disease. This increase in CV risk is commonly attributed to co-existence of numerous traditional and nontraditional risk factors for the development of CVD that frequently accompany reduced kidney function. Therefore, CKD itself is now considered an independent CVD risk factor and a coronary artery disease (CAD) equivalent for all-cause mortality. All patients at risk for CAD should be evaluated for kidney disease. Treatments used for management of established CAD might have similar benefits for patients with concomitant CKD.     

Cardiovascular Disease in Chronic Kidney Disease: Data from the Kidney Early Evaluation Program (KEEP)

Diabetes mellitus (DM) and hypertension (HTN) are leading joint risk factors for both cardiovascular disease (CVD) and chronic kidney disease (CKD). In the nationwide KEEP (Kidney Early Evaluation Program) an estimated glomerular filtration rate less than 60 mL/min/1.73 m² or a urine albumin:creatinine ratio ≥30 mg/g (3.4 mg/mmol) defines CKD. Overall in KEEP, the rates of identified CKD and self-reported CVD are 25.7% and 22.1%, respectively. The presence of CKD has been associated with younger ages of self-reported myocardial infarction and stroke. The combination of CVD and CKD in KEEP has been associated with shorter survival time. Finally, the presence of CVD or a prior history of coronary revascularization has been associated with modestly better rates of CVD risk factor control; however, the majority of patients with CKD have suboptimally controlled blood pressure, glucose, or lipids. These data suggest that patients with CKD are not only at higher risk for CVD and subsequent mortality, but are also ideal for targeted community—and practice-based interventions to improve risk factor control and, hopefully, reduce rates of subsequent cardiovacular events.     

Chronic kidney disease: a public health priority and harbinger of premature cardiovascular disease

Abstract. Stenvinkel P (Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden). Chronic kidney disease: a public health priority and harbinger of premature cardiovascular disease (Review). J Intern Med 2010; 268 : 456–467. The epidemics of cardiovascular disease, obesity, diabetes, HIV and cancer have all received much attention from the public, media and policymakers. By contrast, chronic kidney disease (CKD) has remained largely a ‘silent’ epidemic. This is unfortunate because early diagnosis of renal disease based on proteinuria and/or reduced estimated glomerular filtration rate could enable early intervention to reduce the high risks of cardiovascular events, end‐stage renal disease (ESRD) and death that are associated with CKD. Given the global increase in the incidence of the leading causes of CKD – hypertension, obesity and diabetes mellitus – better disease management and prevention planning are needed, as effective strategies are available to slow the progression of CKD and reduce cardiovascular risk. CKD may be regarded as a clinical model of accelerated vascular disease and premature ageing, and the risk‐factor profile changes during the progression from mild/moderate CKD to ESRD. Although many randomized controlled trials in patients with mild to moderate CKD have shown beneficial effects of interventions aimed at preventing the progression of CKD, most trials have been unable to demonstrate a beneficial effect of interventions aimed at improving outcome in ESRD. Thus, novel treatment strategies are needed in this high‐risk patient group.     

Breaking Barriers: Mobile Health Interventions for Cardiovascular Disease

Cardiovascular disease (CVD) is a leading global cause of death and morbidity and prevention needs to be strengthened to tackle this. Mobile health (mHealth) might present a novel and effective solution in CVD prevention, and interest in mHealth has grown dramatically since the advent of the smartphone. In this review, we discuss mHealth interventions that target multiple cardiovascular risk factors simultaneously in the context of primary as well as secondary prevention. There is some evidence that mHealth interventions improve a range of individual CVD risk factors, but a relative paucity of evidence on mHealth interventions improving multiple CVD risk factors simultaneously. The existing data suggest mHealth programs improve overall CVD risk, at least in the short term. Interpretation of the evidence is difficult in the context of poor methodology and mHealth modalities often being a part of large complex interventions. In this review we identify a number of unanswered questions including: which mode of mHealth (or combination of interventions) would be most effective, what is the durability of intervention effects, and what degree of personalization and interactivity is required.     

Primary and secondary prevention strategy for cardiovascular disease in diabetes mellitus

The majority of individuals with diabetes die from cardiovascular disease (CVD) and related complications. The risk of CVD is 2 to 4 fold greater in diabetes and largely magnified by co-morbidities that aggregate along with it. Sufficient evidence-based data now exist to support multifactorial risk intervention with specific targets for goal-directed therapy for both primary and secondary prevention. These interventions have shown survival benefit in addition to prevention of vascular complications. Prevention of diabetes and delaying its onset should also be an important aspect in future health care strategy and research to confront the oncoming tsunami of CVD related to diabetes.     

慢性肾脏疾病的最新调脂进展

血脂异常是慢性肾脏疾病的常见并发症,也是导致动脉粥样硬化性心血管疾病的独立危险因素.慢性肾脏病患者心血管疾病的发病率及病死率明显增加.尽管许多研究证实他汀降脂药物可以明显降低心血管疾病的发病率及死亡率,但是对于慢性肾脏疾病患者的调脂治疗能否降低心血管疾病的发病率及死亡率仍存在争议.现主要针对慢性肾脏疾病患者采取药物调脂治疗,降低心血管事件及保护肾脏的有效性及药物的安全性等问题的最新临床研究现状进行综述.     

Pharmacological and Non Pharmacological Strategies in the Management of Coronary Artery Disease and Chronic Kidney Disease

Patients with advanced chronic kidney disease (CKD), including those treated with dialysis, are at high risk for the development of cardiovascular disease (CVD). CVD accounts for 45-50% of deaths among dialysis patients. Therapy of acute and chronic coronary heart disease (CHD) that is effective in the general population is frequently less effective in patients with advanced CKD. Drug therapy in such patients may require dose modification in some cases. Oral anti-platelet drugs are less effective in those with advanced CKD than in persons with normal or near normal renal function. The intravenous antiplatelet drugs eptifibatide and tirofiban both require dose reductions in patients with advanced CKD. Enoxaparin requires dose reduction in early stage CKD and is contraindicated in hemodialysis patients. Unfractionated heparin and warfarin maybe used without dose adjustment in CKD patients. Atenolol, acetbutolol and nadolol may require dose adjustments in CKD. Metoprolol and carvedilol do not. Calcium channel blockers and nitrates do not require dose adjustment, whereas ranolazine does. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers may safely be used in CKD patients with close observation for hyperkalemia. The safety of spironolactone in such patients is questionable. Statins are less effective in reducing cardiovascular complication in CKD patients and their initiation is not recommended in dialysis patients. Coronary artery bypass grafting is associated with higher short-term mortality, but better long-term morbidity and mortality than percutaneous coronary interventions in patients with advanced CKD with non-ST segment ACS and chronic CHD.     

Micronutrients and cardiorenal disease: insights into novel assessments and treatment

Chronic kidney disease (CKD) is a recognized risk multiplier for development of cardiovascular disease (CVD), with CVD events representing the leading cause of morbidity and mortality in patients with CKD. The nature of CKD as a risk state relates both to the nature of CKD and the antecedent development of CVD. In addition, patients with CKD have increased rates of multiple conventional cardiac risk factors. The essence of the relationship appears to be bidirectional, and therapy directed at improving natural history of chronic disease on one system generally improves prognosis in the other. Hence the term 'cardiorenal syndrome' (CRS) is used to describe the complex interrelationships between the two organ systems. While focus on therapeutic targets has been dominated by interest in neurohormonal mechanisms, little attention has been given to micronutrients and their potential effects in CRS. As renal function declines, cellular metabolism changes profoundly, and when artificial means of solute removal are initiated by peritoneal dialysis or hemodialysis, there are considerable shifts of many micronutrients that may affect cardiovascular health predominantly through the mechanism of increasing labile iron-dependent oxidative stress. Release of labile iron at the tissue level appears to be most important in acute CRS, whereas phosphate and sodium retention play more of a role in chronic CRS. Attention will be given to selected micronutrients which may call for novel assessments and intervention for optimal cardiorenal outcomes.     

Chronic kidney disease and cardiovascular risk

Chronic kidney disease (CKD) is a global public health concern, and there is emerging a strong relationship between CKD and increased cardiovascular disease (CVD) risk. CKD in the presence of other co-morbidities such as type 2 diabetes mellitus (T2DM) and hypertension (HTN) can lead to early progression to end-stage renal disease (ESRD/stage V CKD) and confer a greater risk for CVD morbidity and mortality. CVD events are the leading cause of premature death in patients with CKD, even before their progression to ESRD, with the rate of CVD progression being twice as common compared with the general population. The higher mortality from CVD persists even after adjusting for most of the traditional risk factors, suggesting the possible contributions of uremia-related, nontraditional risk factors. This has led to the current understanding that the pathophysiology of CVD in CKD involves a complex interplay of both the traditional as well as nontraditional, uremia-related risk factors. This review will elaborate on the pathophysiology of CVD in CKD and will discuss the role of microalbuminuria (MAU)-proteinuria as a potential diagnostic and prognostic tool for CVD in CKD risk assessment.     

Cardiovascular Risk Stratification and Management in Pre-Diabetes

Prediabetes, covering individuals with impaired fasting glycemia, impaired glucose tolerance, or high-risk HbA_1c levels, is associated with a ～20 % increased risk of developing cardiovascular disease (CVD) compared with normoglycemic individuals. It is well-known that lifestyle or pharmacologic interventions can prevent diabetes in prediabetic people; however, the evidence is less clear regarding prevention of CVD. Most diabetes prevention trials have failed to show beneficial effects on CVD morbidity and mortality despite significant improvements of CVD risk factors in individuals with prediabetes. Another challenge is how to estimate CVD risk in prediabetic people. In general, prediction models for CVD do not take glucose levels or prediabetes status into account, thereby underestimating CVD risk in these high-risk individuals. More evidence within risk stratification and management of CVD risk in prediabetes is needed in order to recommend useful and effective strategies for early prevention of CVD.     

Progression of Renal Dysfunction in Patients with Cardiovascular Disease

It has been established that patients with chronic kidney disease (CKD) suffer from frequent cardiovascular events. On the other hand, recent studies suggest that renal damage tends to worsen in patients with cardiovascular diseases (CVD). Although the mechanisms for the cardiorenal association are unclear, the presence of arteriosclerotic risk factors common to both CVD and CKD is important. In arteriosclerosis, vascular derangement progresses not only in the heart but also in the kidney. In addition, heart failure, cardiac catheterization and hesitation of medical treatments due to renal dysfunction may explain the progression of renal damage. Therefore, the goal of treatments is a total control of arteriosclerotic risk factors. Medication should be selected among agents with protective effects on both heart and kidney. It is important to always consider the presence of CKD for the treatment of the cardiovascular disease and strictly control the risk factors.Key Words: CKD, angiotensin II, aldosterone, ARB, hypertension.     

Cardiovascular Disease Risk in Young People with Type 1 Diabetes

Cardiovascular disease (CVD) is the most frequent cause of death in people with type 1 diabetes (T1D), despite modern advances in glycemic control and CVD risk factor modification. CVD risk identification is essential in this high-risk population, yet remains poorly understood. This review discusses the risk factors for CVD in young people with T1D, including hyperglycemia, traditional CVD risk factors (dyslipidemia, smoking, physical activity, hypertension), as well as novel risk factors such as insulin resistance, inflammation, and hypoglycemia. We present evidence that adverse changes in cardiovascular function, arterial compliance, and atherosclerosis are present even during adolescence in people with T1D, highlighting the need for earlier intervention. The methods for investigating cardiovascular risk are discussed and reviewed. Finally, we discuss the observational studies and clinical trials which have thus far attempted to elucidate the best targets for early intervention in order to reduce the burden of CVD in people with T1D.     

The art of cardiovascular risk assessment

Cardiovascular disease (CVD) remains the leading cause of death in the United States. Healthcare expenditures have been principally allocated toward treatment of CVD at the end of the health/disease continuum, rather than toward health promotion and disease prevention. A focused effort on both primordial and primary prevention can promote cardiovascular health and reduce the burden of CVD. Risk‐factor assessment for predicting atherosclerotic CVD events serves as the foundation of preventive cardiology and has been driven by population‐based scoring algorithms based on traditional risk factors. Incorporating individual nontraditional risk factors, biomarkers, and selective use of noninvasive measures may help identify more at‐risk patients as well as truly low‐risk individuals, allowing for better targeting of treatment intensity. Using a combination of validated population‐based atherosclerotic CVD risk‐assessment tools, nontraditional risk factors, social health determinants, and novel markers of atherosclerotic disease, we should be able to improve our ability to assess CVD risk. Through scientific evidence, clinical judgment, and discussion between the patient and clinician, we can implement an effective evidence‐based strategy to assess and reduce CVD risk.     

Determinants and Prevention of Coronary Disease in Patients With Chronic Kidney Disease

Chronic kidney disease (CKD) is associated with premature cardiovascular morbidity and mortality. Traditional Framingham risk factors contribute partially to the malignant form of cardiovascular disease in CKD. Uremic-specific risk factors including chronic inflammation, retention of uremic toxins, and abnormal bone mineral metabolism have independently been linked to the pathogenesis of premature vascular aging, atherosclerosis, and cardiovascular disease. In this review we explore the mechanisms by which premature aging occurs in CKD through its pathologic effects on cardiovascular health, and the determinants of cardiac disease in patients with CKD. We outline strategies for prevention and therapeutic interventions in this vulnerable population.     

Childhood Obesity and Cardiovascular Disease Risk: Working Toward Solutions

The prevalence of obesity in childhood is high and continues to increase globally. It is currently estimated that 381 million children worldwide have overweight or obesity. This disease stems from multiple complex pathways that can present early in life. This is particularly concerning because childhood obesity is associated with cardiovascular risk factors that can lead to early atherosclerosis and premature cardiovascular disease (CVD). Hypertension, dysglycemia, dyslipidemia, and systemic inflammation are associated with vascular changes in childhood, and these contribute to increased risk of cardiovascular events in adulthood if not adequately treated. Interventions to treat childhood obesity include multicomponent family-based behaviour modification programs, which have been demonstrated to have moderate short-term effects on weight-related outcomes; their effects on cardiovascular risk factors, however, are less well understood. Although supervised, structured exercise interventions result in improvements in blood pressure, inflammation, carotid artery intima media thickness, dysglycemia, dyslipidemia, and endothelial dysfunction in children with obesity in the short term, our understanding of how to translate these interventions into long-term sustainable exercise or physical activity recommendations remains uncertain. Research focus in these areas will help in treating childhood obesity and associated CVD risk factors to prevent CVD development in adulthood.     

Dyslipidaemia and cardiorenal disease: mechanisms, therapeutic opportunities and clinical trials

Dyslipidaemia is an important risk factor for the development of chronic kidney disease (CKD) and cardiovascular disease (CVD). CKD generates an atherogenic lipid profile, characterised by high triglycerides, low high-density lipoprotein (HDL) cholesterol and accumulation of small dense low-density lipoprotein (LDL) particles, comparable to that in the metabolic syndrome. These changes are due specifically to the effects of CKD on key enzymes, transfer proteins and receptors involved in lipid metabolism. Dyslipidaemia is further compounded by dialysis, immunosuppressive drugs, and concomitant diseases such as diabetes mellitus. Post hoc analyses from large intervention trials suggest the benefit of statins in patients with early CKD, but prospective clinical trials in haemodialysis (HD) and renal transplant recipients have not conclusively shown improvements in hard cardiovascular end-points. The lack of efficacy of statins in late-stage CKD could be a consequence of other disease processes, such as calcific arteriopathy and insulin resistance, which are not modified by lipid-lowering agents. Despite uncertainty and pending the results of ongoing statin trials such as Study of Heart and Renal Protection (SHARP) and AURORA (A study to evaluate the Use of Rosuvastatin in subjects On Regular haemodialysis: an Assessment of survival and cardiovascular events), major international guidelines continue to support statin therapy in CKD and renal transplant patients to reduce cardiovascular risk burden. Because of increased risk of toxicity, particularly myopathy, statins and other lipid-regulating agents should be used cautiously in CKD and renal transplant recipients.     

Statins and Renal Disease: Friend or Foe?

The role of statins in the treatment and prevention of cardiovascular diseases, such as coronary artery disease, acute coronary syndromes, diabetes, or stroke, is well established. However, there are still some questions regarding the role of statins in patients with chronic kidney disease (CKD). Dyslipidemia is a known cardiovascular risk factor in individuals without CKD. In these patients, however, the relation of dyslipidemia to cardiovascular risk is complex, and the underlying pathobiological mechanisms are complex. Statins have proven to be highly effective in patients with initial stages of CKD; however, their effects in patients with advanced-stage CKD have been neutral despite a low-density lipoprotein cholesterol–lowering effect. In this review, we summarize the findings of the recent clinical trials of statins in renal disease and make recommendations for our patients.     

Natriuretic Peptides and Assessment of Cardiovascular Disease Risk in Asymptomatic Persons

Current tools for cardiovascular disease (CVD) risk assessment in asymptomatic individuals are imperfect. Preventive measures aimed only at individuals deemed high risk by current algorithms neglect large numbers of low-risk and intermediate-risk individuals who are destined to develop CVD and who would benefit from early and aggressive treatment. Natriuretic peptides have the potential both to identify individuals at risk for future cardiovascular events and to help detect subclinical CVD. Choosing the appropriate subpopulation to target for natriuretic peptide testing will help maximize the performance and the cost effectiveness. The combined use of multiple risk markers, including biomarkers, genetic testing, and imaging or other noninvasive measures of risk, offers promise for further refining risk assessment algorithms. Recent studies have highlighted the utility of natriuretic peptides for preoperative risk stratification; however, cost effectiveness and outcomes studies are needed to affirm this and other uses of natriuretic peptides for cardiovascular risk assessment in asymptomatic individuals.     

The Role of Novel Biomarkers of Cardiovascular Disease in Chronic Kidney Disease: Focus on Adiponectin and Leptin

Cardiovascular disease (CVD) remains a major cause of premature death in patients with chronic kidney disease (CKD), including renal transplant recipients. Both interplay of traditional cardiovascular and renal specific risk factors have been shown to be associated with an increased risk of cardiovascular death in patients with CKD. Recently, there has been great interest in the role of novel biomarkers, in particular adiponectin and leptin, and its association with CVD in the CKD population. Adiponectin is a multifunctional adipocyte-derived protein with anti-inflammatory, antiatherogenic and insulin sensitizing activity. Recent observational studies have shown adiponectin to be a novel risk marker of CVD in patients with stages 1 to 5 CKD. Leptin is an adipocyte-derived hormone that promotes weight loss by decreasing food intake. Similarly, there are observational studies to support an association between leptin and CVD, including patients with CKD. In the CKD population, leptin may be associated with uremic cachexia and subsequent increased mortality. This review aims to summarize the pathophysiological and potential clinical roles of these cardiovascular biomarkers in patients with CKD.Key Words: Biomarker, cardiovascular disease, adiponectin, leptin, kidney disease.     

Efficacy of Angiotensin Receptor Blockers in Cardiovascular Disease

The cardiovascular continuum describes the progression of pathophysiologic events from cardiovascular risk factors to symptomatic cardiovascular disease (CVD) and life-threatening events. Pharmacologic intervention early in the continuum may prevent or slow CVD development and improve quality of life. The renin–angiotensin–aldosterone system (RAAS) is central to the pathophysiology of CVD at many stages of the continuum. Numerous clinical trials of angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have shown that RAAS blockade provides benefits to patients across the continuum. ARBs are as effective as ACE inhibitors in the treatment of hypertension; however tolerability and adherence to therapy appear to be improved with ARBs. Large clinical trials have shown that ARBs may provide therapeutic benefits beyond blood pressure control in patients with diabetes, heart failure or at risk of heart failure following a myocardial infarction. In addition, ARBs have been shown to provide protective effects in patients with impaired renal function or left ventricular hypertrophy. Additional clinical trials are ongoing to further characterize the role of ARBs in CVD management.