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• W2047195246 abstract "Cardiovascular risk in chronic kidney disease. National Kidney Foundation guidelines define chronic kidney disease (CKD) as persistent kidney damage (confirmed by renal biopsy or markers of kidney damage) and/or glomerular filtration rate (GFR) <60 mL/min/1.73m2 for greater than three months.Patients with CKD experience higher mortality and adverse cardiovascular (CV) event rates, which remains significant after adjustment for conventional coronary risk factors. This progressive CV risk associated with worsening renal function may be explained by other factors that become increasingly important with renal decline. In this regard, more investigation of nonconventional factors that have received a lot of attention includes associations with inflammation, albuminuria, reduced vascular compliance, and homocysteine.In addition, individuals with CKD encounter the problem of “therapeutic nihilism,” in which there is a lack of appropriate risk factor modification and intervention, despite established awareness of their high cardiovascular risk. Several studies suggest that these individuals derive as much, if not more, benefit from evidence-based cardiovascular therapies and strategies. Greater educational efforts are needed to reduce this therapeutic gap. Cardiovascular risk in chronic kidney disease. National Kidney Foundation guidelines define chronic kidney disease (CKD) as persistent kidney damage (confirmed by renal biopsy or markers of kidney damage) and/or glomerular filtration rate (GFR) <60 mL/min/1.73m2 for greater than three months. Patients with CKD experience higher mortality and adverse cardiovascular (CV) event rates, which remains significant after adjustment for conventional coronary risk factors. This progressive CV risk associated with worsening renal function may be explained by other factors that become increasingly important with renal decline. In this regard, more investigation of nonconventional factors that have received a lot of attention includes associations with inflammation, albuminuria, reduced vascular compliance, and homocysteine. In addition, individuals with CKD encounter the problem of “therapeutic nihilism,” in which there is a lack of appropriate risk factor modification and intervention, despite established awareness of their high cardiovascular risk. Several studies suggest that these individuals derive as much, if not more, benefit from evidence-based cardiovascular therapies and strategies. Greater educational efforts are needed to reduce this therapeutic gap. A large population of individuals entering the transition phase toward end-stage renal disease (ESRD) is emerging. National Kidney Foundation guidelines define these individuals as having chronic kidney disease (CKD)1.Summaries for patients. Diagnosis and evaluation of patients with chronic kidney disease: Recommendations from the National Kidney Foundation.Ann Intern Med. 2003; 139: I36Google Scholar. CKD is defined as persistent kidney damage (confirmed by renal biopsy or markers of kidney damage) and/or glomerular filtration rate (GFR) <60 mL/min/1.73m2 for greater than three months1.Summaries for patients. Diagnosis and evaluation of patients with chronic kidney disease: Recommendations from the National Kidney Foundation.Ann Intern Med. 2003; 139: I36Google Scholar. Using these criteria, current estimates account for at least 11 million individuals and rising1.Summaries for patients. Diagnosis and evaluation of patients with chronic kidney disease: Recommendations from the National Kidney Foundation.Ann Intern Med. 2003; 139: I36Google Scholar. Many community-based studies have documented that individuals with CKD have a rising prevalence of cardiovascular (CV) disease associated with progressive renal decline2.McCullough P.A. Cardiorenal risk: An important clinical intersection.Rev Cardiovasc Med. 2002; 3: 71-76Abstract Full Text PDF PubMed Google Scholar, 3.Luft F.C. Renal disease as a risk factor for cardiovascular disease.Basic Res Cardiol. 2000; 95: I72-I76Crossref PubMed Google Scholar, 4.Foley R.N. Parfrey P.S. Sarnak M.J. Epidemiology of cardiovascular disease in chronic renal disease.J Am Soc Nephrol. 1998; 9: S16-S23Crossref PubMed Scopus (30) Google Scholar, 5.Sarnak M.J. Levey A.S. Schoolwerth A.C. et al.Kidney disease as a risk factor for development of cardiovascular disease: A statement from the American Heart Association Councils on kidney in cardiovascular disease, high blood pressure research, clinical cardiology, and epidemiology and prevention.Hypertension. 2003; 42: 1050-1065Crossref PubMed Scopus (864) Google Scholar. A higher rate of adverse CV events is noted among this cohort when compared with those with normal renal function5.Sarnak M.J. Levey A.S. Schoolwerth A.C. et al.Kidney disease as a risk factor for development of cardiovascular disease: A statement from the American Heart Association Councils on kidney in cardiovascular disease, high blood pressure research, clinical cardiology, and epidemiology and prevention.Hypertension. 2003; 42: 1050-1065Crossref PubMed Scopus (864) Google Scholar, 6.McCullough P.A. Why is chronic kidney disease the “spoiler” for cardiovascular outcomes?.J Am Coll Cardiol. 2003; 41: 725-728Abstract Full Text Full Text PDF PubMed Scopus (172) Google Scholar, 7.Wright R.S. Reeder G.S. Herzog C.A. et al.Acute myocardial infarction and renal dysfunction: A high-risk combination.Ann Intern Med. 2002; 137: 563-570Crossref PubMed Scopus (504) Google Scholar. Indeed, although there has been an appropriate emphasis on reducing the risk of progression to dialysis of patients with CKD, these individuals are much more likely to die from cardiovascular causes8.Sarnak M.J. Coronado B.E. Greene T. et al.Cardiovascular disease risk factors in chronic renal insufficiency.Clin Nephrol. 2002; 57: 327-335Crossref PubMed Scopus (177) Google Scholar. Evidence for increasing CVD morbidity and mortality tracking with mild to moderate renal dysfunction has mainly stemmed from community-based studies. These have included the Framingham Heart study, NHANES I, ARIC, and the Hoorn studies8.Sarnak M.J. Coronado B.E. Greene T. et al.Cardiovascular disease risk factors in chronic renal insufficiency.Clin Nephrol. 2002; 57: 327-335Crossref PubMed Scopus (177) Google Scholar, 9.Coresh J. Astor B.C. Greene T. et al.Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey.Am J Kidney Dis. 2003; 41: 1-12Abstract Full Text Full Text PDF PubMed Scopus (2211) Google Scholar, 10.Garg A.X. Clark W.F. Haynes R.B. House A.A. Moderate renal insufficiency and the risk of cardiovascular mortality: Results from the NHANES I.Kidney Int. 2002; 61: 1486-1494Abstract Full Text Full Text PDF PubMed Scopus (254) Google Scholar, 11.Culleton B.F. Hemmelgarn B.R. Is chronic kidney disease a cardiovascular disease risk factor?.Semin Dial. 2003; 16: 95-100Crossref PubMed Scopus (37) Google Scholar. All of these studies documented an inverse relationship between renal function and risk of an adverse cardiovascular outcome8.Sarnak M.J. Coronado B.E. Greene T. et al.Cardiovascular disease risk factors in chronic renal insufficiency.Clin Nephrol. 2002; 57: 327-335Crossref PubMed Scopus (177) Google Scholar, 9.Coresh J. Astor B.C. Greene T. et al.Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey.Am J Kidney Dis. 2003; 41: 1-12Abstract Full Text Full Text PDF PubMed Scopus (2211) Google Scholar, 10.Garg A.X. Clark W.F. Haynes R.B. House A.A. Moderate renal insufficiency and the risk of cardiovascular mortality: Results from the NHANES I.Kidney Int. 2002; 61: 1486-1494Abstract Full Text Full Text PDF PubMed Scopus (254) Google Scholar, 11.Culleton B.F. Hemmelgarn B.R. Is chronic kidney disease a cardiovascular disease risk factor?.Semin Dial. 2003; 16: 95-100Crossref PubMed Scopus (37) Google Scholar. The influence of mild to moderate renal impairment post acute coronary syndrome has been shown to increase cardiovascular mortality and morbidity at 30 and 180 days12.Gibson C.M. Pinto D.S. Murphy S.A. et al.Association of creatinine and creatinine clearance on presentation in acute myocardial infarction with subsequent mortality.J Am Coll Cardiol. 2003; 42: 1535-1543Abstract Full Text Full Text PDF PubMed Scopus (222) Google Scholar, 13.Januzzi Jr, J.L. Snapinn S.M. Dibattiste P.M. et al.Benefits and safety of tirofiban among acute coronary syndrome patients with mild to moderate renal insufficiency: Results from the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) trial.Circulation. 2002; 105: 2361-2366Crossref PubMed Scopus (85) Google Scholar, 14.Newby L.K. Bhapkar M.V. White H.D. et al.Predictors of 90-day outcome in patients stabilized after acute coronary syndromes.Eur Heart J. 2003; 24: 172-181Crossref PubMed Scopus (39) Google Scholar, 15.Freeman R.V. Mehta R.H. Al Badr W. et al.Influence of concurrent renal dysfunction on outcomes of patients with acute coronary syndromes and implications of the use of glycoprotein IIb/IIIa inhibitors.J Am Coll Cardiol. 2003; 41: 718-724Abstract Full Text Full Text PDF PubMed Scopus (149) Google Scholar. Longer-term outcome data related to a broader spectrum of renal dysfunction have been limited, partly related to smaller cohorts and exclusion of individuals with renal dysfunction. Studies that have examined the relationship between renal function and cardiovascular outcomes among high CV risk cohorts with left ventricular dysfunction with longer follow-up have included the Studies of Left Ventricular Dysfunction (SOLVD), Trandolapril Cardiac Evaluation (TRACE), Survival and Ventricular Enlargement (SAVE), and Valsartan in Acute Myocardial Infarction (VALIANT) trials16.Al Ahmad A. Rand W.M. Manjunath G. et al.Reduced kidney function and anemia as risk factors for mortality in patients with left ventricular dysfunction.J Am Coll Cardiol. 2001; 38: 955-962Abstract Full Text Full Text PDF PubMed Scopus (604) Google Scholar, 17.Sorensen C.R. Brendorp B. Rask-Madsen C. et al.The prognostic importance of creatinine clearance after acute myocardial infarction.Eur Heart J. 2002; 23: 948-952Crossref PubMed Scopus (64) Google Scholar, 18.Anavekar N.S. Mcmurray J.V. Velazquez E.J. et al.Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction.N Engl J Med. 2004; 351: 13Crossref PubMed Scopus (1581) Google Scholar (Table 1). Although these studies excluded individuals with baseline serum creatinine of ≥2.5 mg/dL, approximately a third of patients had CKD based upon National Kidney Foundation estimated glomerular filtration rate (eGFR) criteria1.Summaries for patients. Diagnosis and evaluation of patients with chronic kidney disease: Recommendations from the National Kidney Foundation.Ann Intern Med. 2003; 139: I36Google Scholar. In all of these studies, reduced renal function was associated with significantly higher mortality and adverse CV event rates independent of other comorbidities, with an especially marked rise in event rates below an eGFR of 60 mL/min/1.73m2Figure 1; any short-term risk conferred at baseline also persisted in the longer term following acute myocardial infarction (AMI).Table 1Influence of baseline renal function on cardiovascular outcomes in cohorts with left ventricular dysfunctionTrialYearNumber of patientsHazard ratio for CV events for every 10 mL/min/1.73m2 decrease in baseline eGFRStudies of Left Ventricular Dysfunction (SOLVD)200166351.1Trandolapril Cardiac Evaluation (TRACE)200262521.2Survival And Ventricular Enlargement (SAVE)200321841.5Valsartan in Acute Myocardial Infarction Trial (VALIANT)2003145271.1 Open table in a new tab Mechanisms as to why renal dysfunction portends increased CV risk are still being elucidated. Several explanations have been provided, inclusive of high proportions of coronary risk factors and comorbidities2.McCullough P.A. Cardiorenal risk: An important clinical intersection.Rev Cardiovasc Med. 2002; 3: 71-76Abstract Full Text PDF PubMed Google Scholar,19.McCullough P.A. Scope of cardiovascular complications in patients with kidney disease.Ethn Dis. 2002; 12: S3-S8PubMed Google Scholar. Increasing expression of nonconventional risk factors that may be acting alone or synergistically with existing coronary risks, and lack of appropriate risk factor modification and intervention are all considered to be contributing factors. Individuals with renal impairment usually have complex medical histories consisting of multiple comorbidities, and several studies have documented an increasing prevalence of traditional coronary risk factors with reduced renal function4.Foley R.N. Parfrey P.S. Sarnak M.J. Epidemiology of cardiovascular disease in chronic renal disease.J Am Soc Nephrol. 1998; 9: S16-S23Crossref PubMed Scopus (30) Google Scholar, 12.Gibson C.M. Pinto D.S. Murphy S.A. et al.Association of creatinine and creatinine clearance on presentation in acute myocardial infarction with subsequent mortality.J Am Coll Cardiol. 2003; 42: 1535-1543Abstract Full Text Full Text PDF PubMed Scopus (222) Google Scholar, 13.Januzzi Jr, J.L. Snapinn S.M. Dibattiste P.M. et al.Benefits and safety of tirofiban among acute coronary syndrome patients with mild to moderate renal insufficiency: Results from the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) trial.Circulation. 2002; 105: 2361-2366Crossref PubMed Scopus (85) Google Scholar. Atherosclerotic disease in those with CKD appears to be markedly accelerated, with more extensive anatomic disease present at younger ages consistent with a cardiovascular risk similar to older aged non-CKD counterparts. Many coronary risk factors, particularly diabetes mellitus and hypertension, are well-established predictors for renal disease progression20.Eknoyan G. Hostetter T. Bakris G.L. et al.Proteinuria and other markers of chronic kidney disease: A position statement of the national kidney foundation (NKF) and the national institute of diabetes and digestive and kidney diseases (NIDDK).Am J Kidney Dis. 2003; 42: 617-622Abstract Full Text Full Text PDF PubMed Scopus (297) Google Scholar; a bilateral relationship exists in which conventional coronary risk factors contribute to renal disease, and this decline in renal function appears to close the loop on a vicious cycle whereby progressive renal decline heightens the potency of traditional and novel risk factors promoting accelerated atherosclerosis Figure 2. Although CV risk attributed to CKD has been found to be independent of various comorbidities, the significant CV risks associated with diabetes and hypertension still persist among those with CKD4.Foley R.N. Parfrey P.S. Sarnak M.J. Epidemiology of cardiovascular disease in chronic renal disease.J Am Soc Nephrol. 1998; 9: S16-S23Crossref PubMed Scopus (30) Google Scholar. Dyslipidemia is a common finding among CKD cohorts21.Culleton B.F. Wilson P.W. Cardiovascular disease: Risk factors, secular trends, and therapeutic guidelines.J Am Soc Nephrol. 1998; 9: S5-15PubMed Google Scholar. Worsening CKD is associated with changes in lipid profiles. In mild to moderate stages of CKD, low high-density lipoprotein (HDL) levels, increased triglycerides, and increased levels of intermediate density lipoproteins are often noted8.Sarnak M.J. Coronado B.E. Greene T. et al.Cardiovascular disease risk factors in chronic renal insufficiency.Clin Nephrol. 2002; 57: 327-335Crossref PubMed Scopus (177) Google Scholar,22.Chertow G.M. Normand S.L. Silva L.R. Mcneil B.J. Survival after acute myocardial infarction in patients with end-stage renal disease: Results from the cooperative cardiovascular project.Am J Kidney Dis. 2000; 35: 1044-1051Abstract Full Text Full Text PDF PubMed Scopus (150) Google Scholar. As CKD approaches ESRD, there appears to be increased oxidation of low-density lipoprotein (LDL), with progressive lowering of total cholesterol levels. The influence of dyslipidemia upon CV outcomes appears to demonstrate a “U”-shaped relationship, with increased CV event rates seen among those with severe CKD (i.e., ESRD) having low cholesterol levels8.Sarnak M.J. Coronado B.E. Greene T. et al.Cardiovascular disease risk factors in chronic renal insufficiency.Clin Nephrol. 2002; 57: 327-335Crossref PubMed Scopus (177) Google Scholar. Explanations for this “low cholesterol paradox” have been attributed to the effects of chronic malnutrition and inflammation, which become increasingly important with severe CKD4.Foley R.N. Parfrey P.S. Sarnak M.J. Epidemiology of cardiovascular disease in chronic renal disease.J Am Soc Nephrol. 1998; 9: S16-S23Crossref PubMed Scopus (30) Google Scholar, 23.Menon V. Wang X. Greene T. et al.Relationship between C-reactive protein, albumin, and cardiovascular disease in patients with chronic kidney disease.Am J Kidney Dis. 2003; 42: 44-52Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar, 24.Cheung A.K. Sarnak M.J. Yan G. et al.Atherosclerotic cardiovascular disease risks in chronic hemodialysis patients.Kidney Int. 2000; 58: 353-362Abstract Full Text Full Text PDF PubMed Scopus (630) Google Scholar. In this context, the “U”-shaped relationship of cholesterol level for CV outcomes probably reflects the interplay of two mechanisms: at mild to moderate stages of CKD, high cholesterol levels are a contributing factor toward atherosclerosis4.Foley R.N. Parfrey P.S. Sarnak M.J. Epidemiology of cardiovascular disease in chronic renal disease.J Am Soc Nephrol. 1998; 9: S16-S23Crossref PubMed Scopus (30) Google Scholar, while in severe CKD, low cholesterol levels are probably identifying malnourished individuals with a high burden of chronic inflammatory activity23.Menon V. Wang X. Greene T. et al.Relationship between C-reactive protein, albumin, and cardiovascular disease in patients with chronic kidney disease.Am J Kidney Dis. 2003; 42: 44-52Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar and already established atherosclerosis. This paradox in ESRD has raised the question of utility of lipid-lowering therapy. However, recent data confirms higher risk of moderate CKD in statin trials and similar CV risk reduction25.Tonelli M. Moye L. Sacks F.M. et al.Pravastatin for secondary prevention of cardiovascular events in persons with mild chronic renal insufficiency.Ann Intern Med. 2003; 138: 98-104Crossref PubMed Scopus (255) Google Scholar,26.Tonelli M. Moye L. Sacks F.M. et al.Effect of pravastatin on loss of renal function in people with moderate chronic renal insufficiency and cardiovascular disease.J Am Soc Nephrol. 2003; 14: 1605-1613Crossref PubMed Scopus (285) Google Scholar. Conventional coronary risk factors alone cannot explain the significantly elevated CV risk and predisposition for adverse CV outcomes. Evidence for this stems from documented discrepancies between calculated Framingham coronary point scores, which seem to underestimate CV risk, compared with actual CV event rates11.Culleton B.F. Hemmelgarn B.R. Is chronic kidney disease a cardiovascular disease risk factor?.Semin Dial. 2003; 16: 95-100Crossref PubMed Scopus (37) Google Scholar,27.Albert M.A. Glynn R.J. Ridker P.M. Plasma concentration of C-reactive protein and the calculated Framingham Coronary Heart Disease Risk Score.Circulation. 2003; 108: 161-165Crossref PubMed Scopus (222) Google Scholar. Following adjustment for conventional coronary risk factors, reduced renal function has consistently been associated independently with significantly higher mortality and adverse CV event rates28.Al Suwaidi J. Reddan D.N. Williams K. et al.Prognostic implications of abnormalities in renal function in patients with acute coronary syndromes.Circulation. 2002; 106: 974-980Crossref PubMed Scopus (396) Google Scholar,29.Keeley E.C. Kadakia R. Soman S. et al.Analysis of long-term survival after revascularization in patients with chronic kidney disease presenting with acute coronary syndromes.Am J Cardiol. 2003; 92: 509-514Abstract Full Text Full Text PDF PubMed Scopus (138) Google Scholar. Progressive cardiovascular risk associated with worsening renal function unexplained by known risk factors requires a broader understanding of other factors that become increasingly important with renal decline (Table 2). Nonconventional factors that have received a lot of attention include associations with inflammation, albuminuria, anemia, reduced vascular compliance, and homocysteine.Figure 3Table 2Proposed factors associated with increased CV risk with worsening CKDConventionalAge Male gender Hypertension Diabetes Dyslipidemia SmokerUremic Lower creatinine clearance or eGFR Albuminuria Lower serum albumin AnemiaVascular Reduced vascular complianceOther Homocysteine, inflammation, oxidative stress Ca2+ PO43- procoagulation Open table in a new tab Atherosclerosis is an inflammatory disorder30.Libby P. Ridker P.M. Maseri A. Inflammation and atherosclerosis.Circulation. 2002; 105: 1135-1143Crossref PubMed Scopus (5560) Google Scholar. Several large cross-sectional studies have identified C-reactive protein (CRP) as an independent risk factor for cardiac disease31.Blake G.J. Ridker P.M. C-reactive protein, subclinical atherosclerosis, and risk of cardiovascular events.Arterioscler Thromb Vasc Biol. 2002; 22: 1512-1513Crossref PubMed Scopus (49) Google Scholar. CRP levels provide an overall measure of systemic inflammatory activity; they increase dramatically in response to cytokine-mediated stimuli and appear to have fairly constant fractional clearance rates among normal subjects32.Ridker P.M. Clinical application of C-reactive protein for cardiovascular disease detection and prevention.Circulation. 2003; 107: 363-369Crossref PubMed Scopus (1892) Google Scholar. Several studies have documented increases in proinflammatory cytokines, elevated CRP levels, increased oxidative stress, reduced clearance of proinflammatory substances such as advanced glycosylation end products and products of carbonyl stress32.Ridker P.M. Clinical application of C-reactive protein for cardiovascular disease detection and prevention.Circulation. 2003; 107: 363-369Crossref PubMed Scopus (1892) Google Scholar, 33.Oberg B.P. Mcmenamin E. Lucas F.L. et al.Increased prevalence of oxidant stress and inflammation in patients with moderate to severe chronic kidney disease.Kidney Int. 2004; 65: 1009-1016Abstract Full Text Full Text PDF PubMed Scopus (555) Google Scholar, 34.Miyata T. Sugiyama S. Saito A. Kurokawa K. Reactive carbonyl compounds related uremic toxicity (“carbonyl stress”).Kidney Int. 2001; Suppl 78: S25-S31Crossref Google Scholar among both predialysis and dialysis patients23.Menon V. Wang X. Greene T. et al.Relationship between C-reactive protein, albumin, and cardiovascular disease in patients with chronic kidney disease.Am J Kidney Dis. 2003; 42: 44-52Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar,35.Iseki K. Tozawa M. Yoshi S. Fukiyama K. Serum C-reactive protein (CRP) and risk of death in chronic dialysis patients.Nephrol Dial Transplant. 1999; 14: 1956-1960Crossref PubMed Scopus (261) Google Scholar. These have all been strongly and independently linked with increasing rates of cardiovascular morbidity and mortality35.Iseki K. Tozawa M. Yoshi S. Fukiyama K. Serum C-reactive protein (CRP) and risk of death in chronic dialysis patients.Nephrol Dial Transplant. 1999; 14: 1956-1960Crossref PubMed Scopus (261) Google Scholar. CRP is a particularly attractive candidate of augmenting CV risk in CKD because it has been implicated as not just a marker, but as an actual promoter of atherosclerotic disease progression36.Ridker P.M. Stampfer M.J. Rifai N. Novel risk factors for systemic atherosclerosis: A comparison of C-reactive protein, fibrinogen, homocysteine, lipoprotein(a), and standard cholesterol screening as predictors of peripheral arterial disease.JAMA. 2001; 285: 2481-2485Crossref PubMed Scopus (1029) Google Scholar. In addition, inflammation has also been linked to alterations in protein metabolism. Many individuals with severe CKD suffer from malnutrition, which is partly explained by excessive protein losses coupled to an elevated catabolic state37.Kalantar-Zadeh K. Stenvinkel P. Pillon L. Kopple J.D. Inflammation and nutrition in renal insufficiency.Adv Ren Replace Ther. 2003; 10: 155-169Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar. Malnutrition as reflected by low serum albumin levels have been shown to strongly predict adverse outcomes among individuals with CKD, particularly those receiving renal replacement therapies38.Lindholm B. Heimburger O. Stenvinkel P. What are the causes of protein-energy malnutrition in chronic renal insufficiency?.Am J Kidney Dis. 2002; 39: 422-425Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar. Additionally, independent of nutritional status, albumin is also a negative acute phase protein whose synthesis decreases during inflammation39.Pecoits-Filho R. Lindholm B. Stenvinkel P. The malnutrition, inflammation, and atherosclerosis (MIA) syndrome—The heart of the matter.Nephrol Dial Transplant. 2002; 17: 28-31Crossref PubMed Scopus (326) Google Scholar. Anemia is an independent predictor for renal disease progression because it may reflect progressive erythropoietin deficiency and the negative influence of increasing uremic factors upon erythropoiesis with renal decline40.Foley R.N. Parfrey P.S. Anemia in predialysis chronic renal failure: What are we treating?.J Am Soc Nephrol. 1998; 9: S82-S84PubMed Google Scholar. Chronic anemia has been demonstrated to be an independent risk factor for adverse CV outcomes, particularly in patients with kidney disease and in patients with heart failure41.Hegarty J. Foley R.N. Anaemia, renal insufficiency and cardiovascular outcome.Nephrol Dial Transplant. 2001; 16: 102-104Crossref PubMed Scopus (9) Google Scholar. Anemia is associated with left ventricular (LV) dilatation, left ventricular hypertrophy (LVH), and death in patients with CKD41.Hegarty J. Foley R.N. Anaemia, renal insufficiency and cardiovascular outcome.Nephrol Dial Transplant. 2001; 16: 102-104Crossref PubMed Scopus (9) Google Scholar. The mechanism for this association is unclear; however, it has been postulated that the presence of anemia may be signifying an acute phase response and systemic inflammatory activity rather than a direct effect, per se41.Hegarty J. Foley R.N. Anaemia, renal insufficiency and cardiovascular outcome.Nephrol Dial Transplant. 2001; 16: 102-104Crossref PubMed Scopus (9) Google Scholar, in addition to the augmentation in cardiac workload. Several retrospective and prospective studies have consistently demonstrated that worsening albuminuria is paralleled by increasing cardiovascular complications42.Borch-Johnsen K. Feldt-Rasmussen B. Strandgaard S. et al.Urinary albumin excretion. An independent predictor of ischemic heart disease.Arterioscler Thromb Vasc Biol. 1999; 19: 1992-1997Crossref PubMed Scopus (365) Google Scholar, 43.Deckert T. Kofoed-Enevoldsen A. Norgaard K. et al.Microalbuminuria. Implications for micro- and macrovascular disease.Diabetes Care. 1992; 15: 1181-1191Crossref PubMed Scopus (181) Google Scholar, 44.Hillege H.L. Fidler V. Diercks G.F. et al.Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population.Circulation. 2002; 106: 1777-1782Crossref PubMed Scopus (1287) Google Scholar. A plausible explanation for these findings is that albuminuria not only reflects glomerular damage, but is also a sensitive indicator of generalized atherosclerotic-mediated capillary vasculopathy43.Deckert T. Kofoed-Enevoldsen A. Norgaard K. et al.Microalbuminuria. Implications for micro- and macrovascular disease.Diabetes Care. 1992; 15: 1181-1191Crossref PubMed Scopus (181) Google Scholar,44.Hillege H.L. Fidler V. Diercks G.F. et al.Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population.Circulation. 2002; 106: 1777-1782Crossref PubMed Scopus (1287) Google Scholar. Albuminuria has been shown to cluster with a number of vascular risk factors inclusive of hypertension, renal dysfunction, dyslipidemia, hyperhomocysteinemia, and several inflammatory markers42.Borch-Johnsen K. Feldt-Rasmussen B. Strandgaard S. et al.Urinary albumin excretion. An independent predictor of ischemic heart disease.Arterioscler Thromb Vasc Biol. 1999; 19: 1992-1997Crossref PubMed Scopus (365) Google Scholar. After adjustment for these factors, albuminuria is an independent predictor for adverse CV events, and this risk increases in a continuous fashion45.Gerstein H.C. Mann J.F. Yi Q. et al.Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals.JAMA. 2001; 286: 421-426Crossref PubMed Scopus (1925) Google Scholar. The precise mechanism underlying this is currently unknown; several derangements in the fibrinolysis and coagulation systems have been noted favoring a thrombogenic state45.Gerstein H.C. Mann J.F. Yi Q. et al.Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals.JAMA. 2001; 286: 421-426Crossref PubMed Scopus (1925) Google Scholar. Individuals with CKD are noted to have evidence of reduced vascular compliance46.Safar M.E. London G.M. Plante G.E. Arterial stiffness and kidney function.Hypertension. 2004; 43: 163-168Crossref PubMed Scopus (233) Google Scholar. Reduced vascular compliance, as evidenced by elevated aortic pulse wave velocities, has been demonstrated to be a significant predictor for adverse CV events47.Raggi P. Boulay A. Chasan-Taber S. et al.Cardiac calcification in adult hemodialysis patients. A link between end-stage renal disease and cardiovascular disease?.J Am Coll Cardiol. 2002; 39: 695-701Abstract Full Text Full Text PDF PubMed Scopus (951) Google Scholar,48.Safar M.E. Henry O. Meaume S. Aortic pulse wave velocity: An independent marker of cardiovascular risk.Am J Geriatr Cardiol. 2002; 11: 295-298Crossref PubMed Scopus (61) Google Scholar, and several studies have also shown that widened pulse pressure is also an independent predictor for cardiovascular and all cause mortality, both of which have been shown to progressively worsen with renal decline49.Safar M. Pulse pressure and cardiovascular risk.J Med Liban. 2000; 48: 354-355PubMed Google Scholar. In a study involving 1290 untreated hypertensive patients with mild to moderate CKD, an inverse correlation with renal function independent of blood pressure and other traditional coronary risk factors was seen with aortic pulse wave velocity50.Mourad J.J. Pannier B. Blacher J. et al.Creatinine clearance, pulse wave velocity, carotid compliance and essential hypertension.Kidney Int. 2001; 59: 1834-1841Abstract Full Text Full Text PDF PubMed Scopus (214) Google Scholar. The effect of calcium on CV risk in individuals with ESRD has been studied and contributes to reduced vascular compliance51.Block G.A. Port F.K. Re-evaluation of risks associated with hyperphosphatemia and hyperparathyroidism in dialysis patients: Recommendations for a change in management.Am J Kidney Dis. 2000; 35: 1226-1237Abstract Full Text Full Text PDF PubMed Scopus (554) Google Scholar. Elevations in the calcium-phosphate product associated with secondary hyperparathyroidism lead to vascular calcification51.Block G.A. Port F.K. Re-evaluation of risks associated with hyperphosphatemia and hyperparathyroidism in dialysis patients: Recommendations for a change in management.Am J Kidney Dis. 2000; 35: 1226-1237Abstract Full Text Full Text PDF PubMed Scopus (554) Google Scholar; this has not been demonstrated in individuals with CKD, who usually have normal calcium/phosphate homeostasis. Mechanisms as to why vascular compliance is reduced and/or arterial stiffness progressively increases with worsening renal function are still being elucidated. The metabolism of homocysteine and other sulfur-containing amino acids has been shown to be abnormal with renal decline52.Friedman A.N. Bostom A.G. Selhub J. et al.The kidney and homocysteine metabolism.J Am Soc Nephrol. 2001; 12: 2181-2189Crossref PubMed Google Scholar. Among patients with severe CKD, every 1 μmol increase in plasma homocysteine levels has been shown to be independently associated with a 1% risk for vascular events52.Friedman A.N. Bostom A.G. Selhub J. et al.The kidney and homocysteine metabolism.J Am Soc Nephrol. 2001; 12: 2181-2189Crossref PubMed Google Scholar. The mechanism by which elevated homocysteine levels cause vascular disease is unknown; it may be related to endothelial dysfunction, platelet hyper-reactivity, and/or abnormalities involving the coagulation cascade3.Luft F.C. Renal disease as a risk factor for cardiovascular disease.Basic Res Cardiol. 2000; 95: I72-I76Crossref PubMed Google Scholar. Among individuals with hyperhomocysteinemia and vascular events, but without CKD, lowering of homocysteine levels is associated with reduced risk for further CV events. However, the same relationship does not seem to hold true among those with severe CKD; in particular, these patients seem to be resistant to conventional homocysteine-lowering therapies, and among those where the level is reduced, only marginal benefits in reducing CV events have been noted3.Luft F.C. Renal disease as a risk factor for cardiovascular disease.Basic Res Cardiol. 2000; 95: I72-I76Crossref PubMed Google Scholar. Despite the higher risk of major CV events and death, the proportion of individuals with CKD receiving appropriate risk factor modification and/or interventional strategies is lower than the general population, a concept termed “therapeutic nihilism”2.McCullough P.A. Cardiorenal risk: An important clinical intersection.Rev Cardiovasc Med. 2002; 3: 71-76Abstract Full Text PDF PubMed Google Scholar. This reduced use of proven therapies must be considered as a significant iatrogenic factor contributing to their increased CV risk. Several databases and registries have consistently observed a reduced use of proven therapies with worsening renal function12.Gibson C.M. Pinto D.S. Murphy S.A. et al.Association of creatinine and creatinine clearance on presentation in acute myocardial infarction with subsequent mortality.J Am Coll Cardiol. 2003; 42: 1535-1543Abstract Full Text Full Text PDF PubMed Scopus (222) Google Scholar, 53.Beattie J.N. Soman S.S. Sandberg K.R. et al.Determinants of mortality after myocardial infarction in patients with advanced renal dysfunction.Am J Kidney Dis. 2001; 37: 1191-1200Abstract Full Text PDF PubMed Scopus (193) Google Scholar, 54.Best P.J. Lennon R. Gersh B.J. et al.Safety of abciximab in patients with chronic renal insufficiency who are undergoing percutaneous coronary interventions.Am Heart J. 2003; 146: 345-350Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar. In patients with severe CKD who are known to be at extreme CV risk, less than 50% are on the combination of aspirin, β-blocker, ACE inhibitors, and statins55.French W.J. Wright R.S. Renal insufficiency and worsened prognosis with STEMI: A call for action.J Am Coll Cardiol. 2003; 42: 1544-1546Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar. Potential explanations, whether justified or not, include concerns of worsening existing renal function, and/or therapy-related toxic effects due to low clearance rates2.McCullough P.A. Cardiorenal risk: An important clinical intersection.Rev Cardiovasc Med. 2002; 3: 71-76Abstract Full Text PDF PubMed Google Scholar,56.Levin A. Stevens L. McCullough P.A. Cardiovascular disease and the kidney. Tracking a killer in chronic kidney disease.Postgrad Med. 2002; 111: 53-60Crossref PubMed Scopus (34) Google Scholar. Bleeding concerns with the use of platelet inhibitors and anticoagulants are especially important with reduced renal function and appear to contribute to the decreased likelihood of patients with severe CKD to receive aspirin and/or clopidrogrel54.Best P.J. Lennon R. Gersh B.J. et al.Safety of abciximab in patients with chronic renal insufficiency who are undergoing percutaneous coronary interventions.Am Heart J. 2003; 146: 345-350Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar. However, several studies have shown that when appropriately titrated and monitored, cardiovascular medications and coronary revascularization used in the general population can be safely administered to those with renal impairment, and with similar benefits55.French W.J. Wright R.S. Renal insufficiency and worsened prognosis with STEMI: A call for action.J Am Coll Cardiol. 2003; 42: 1544-1546Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar,57.Ruggenenti P. Perna A. Remuzzi G. ACE inhibitors to prevent end-stage renal disease: When to start and why possibly never to stop: A post hoc analysis of the REIN trial results. Ramipril Efficacy in Nephropathy.J Am Soc Nephrol. 2001; 12: 2832-2837PubMed Google Scholar. Chronic kidney disease is a potent harbinger for adverse cardiovascular outcomes, incorporating both conventional and nonconventional cardiovascular risk factors. Ironically, although awareness of this high risk is being appreciated, application of strategies for reducing their cardiovascular morbidity and mortality seem to be limited when compared with non-CKD cohorts. CKD patients seem to derive as much, if not more, benefit from such established cardiovascular therapies and strategies. Greater efforts are needed to reduce this therapeutic gap." @default.
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• W2047195246 cites W1975435286 @default.
• W2047195246 cites W1985992748 @default.
• W2047195246 cites W1991923231 @default.
• W2047195246 cites W1994057975 @default.
• W2047195246 cites W2011862587 @default.
• W2047195246 cites W2018901137 @default.
• W2047195246 cites W2028021654 @default.
• W2047195246 cites W2029785070 @default.
• W2047195246 cites W2032748094 @default.
• W2047195246 cites W2040504617 @default.
• W2047195246 cites W2049428559 @default.
• W2047195246 cites W2052644196 @default.
• W2047195246 cites W2060451901 @default.
• W2047195246 cites W2064303862 @default.
• W2047195246 cites W2069557492 @default.
• W2047195246 cites W2073258103 @default.
• W2047195246 cites W2082069148 @default.
• W2047195246 cites W2085058703 @default.
• W2047195246 cites W2089151124 @default.
• W2047195246 cites W2094341345 @default.
• W2047195246 cites W2095963691 @default.
• W2047195246 cites W2100124500 @default.
• W2047195246 cites W2102080772 @default.
• W2047195246 cites W2105581950 @default.
• W2047195246 cites W2107031719 @default.
• W2047195246 cites W2108985466 @default.
• W2047195246 cites W2114693066 @default.
• W2047195246 cites W2115276193 @default.
• W2047195246 cites W2120309051 @default.
• W2047195246 cites W2122821137 @default.
• W2047195246 cites W2123831918 @default.
• W2047195246 cites W2124764590 @default.
• W2047195246 cites W2127636733 @default.
• W2047195246 cites W2128722360 @default.
• W2047195246 cites W2129352623 @default.
• W2047195246 cites W2131334318 @default.
• W2047195246 cites W2139468731 @default.
• W2047195246 cites W2140766694 @default.
• W2047195246 cites W2143147344 @default.
• W2047195246 cites W2146311281 @default.
• W2047195246 cites W2149734505 @default.
• W2047195246 cites W2154761934 @default.
• W2047195246 cites W2159087408 @default.
• W2047195246 cites W2165222873 @default.
• W2047195246 cites W2169272593 @default.
• W2047195246 cites W2203491484 @default.
• W2047195246 cites W2488868277 @default.
• W2047195246 cites W4245250897 @default.
• W2047195246 cites W75460707 @default.
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