Cardiovascular Disease and CKD: Core Curriculum 2010

Abstract

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). Patients with CKD not only have a high prevalence of traditional CVD risk factors, but also are exposed to other nontraditional uremia-related CVD risk factors. In this Core Curriculum, we describe the epidemiologic characteristics and pathophysiologic process of CVD in patients with CKD and focus on several CVD risk factors. We then discuss manifestations and presentations of CVD in patients with CKD and review diagnostic and therapeutic options. As described next, many recommendations in CKD are based on extrapolation of data from the general population. However, we emphasize several of the important published trials on CVD in CKD (Table 1, Table 2). We do not focus on CVD in kidney transplant recipients.Table 1Selected Randomized Clinical Trials in Dialysis Patients With Focus on Clinical CVD Outcomes/MortalityInterventionTrial NamePopulationNPrimary OutcomeaComposite CVD outcome may include all-cause mortality, and each trial may have different cardiovascular events.ResultbResults reported are for primary outcome of the study: + indicates benefit of intervention, − indicates no significant benefit.CommentsCompleted TrialsHigh vs standard dose; high- vs low-flux membraneHEMOHD1,846All-cause mortality−High- vs low-flux membraneMPOIncident HD738All-cause mortality−Benefit in those with albumin ≤4 g/dLCarvedilol vs placeboHD & dilated cardiomyopathy114Change in LVEDV, LVESV, EF, clinical status+Decreased morbidity & mortalityAmlodipine vs placeboHD & hypertension251All-cause mortality−Beneficial effect on CVD outcomesCandesartan vs placeboHD & no CVD80Composite CVD+Fosinopril vs placeboFOSIDIALHD & LVH397Composite CVD−N-Acteylcysteine vs placeboHD134Composite CVD+Vitamin E vs placeboSPACEHD & prevalent CVD196Composite CVD+Atorvastatin vs placebo4DHD & diabetes1,255Composite CVD−Rosuvastatin vs placeboAURORAHD2,776Composite CVD−Folic acid + pyridoxine + cyanocobalamin vs placeboHOSTHD or PD & hyperhomocysteinemia751All-cause mortality−Folic acid, 15 vs 5 vs 1 mgHD or PD510Composite CVD−Sevelamer vs calcium-containing phosphate bindersDCORHD + phosphate-binder therapy2,103All-cause mortality−Epoetin to target Hct of 42% vs 30%HD & HF or IHD1,233Composite CVD−Trend toward worse outcomes in higher HCT groupOngoing TrialsCinacalcet vs placeboEVOLVEHD & PTH ≥300 pg/mL3,883Composite CVDNASimvastatin + ezetimibe vs placeboSHARPHD component of SHARP6,000Composite CVDNAGrowth hormone vs placeboOPPORTUNITYHD & hypoalbuminemia2,500All-cause mortalityNAAbbreviations: AURORA, Assessment of Survival and Cardiovascular Events; CVD, cardiovascular disease; 4D, Die Deutsche Diabetes Dialyse Studie; DCOR, Dialysis Clinical Outcomes Revisited; EF, ejection fraction; EVOLVE, Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events; FOSIDIAL, Fosinopril in Dialysis Study; Hct, hematocrit; HD, hemodialysis; HEMO, Hemodialysis Study; HF, heart failure; HOST, Homocysteinemia in Kidney and Endstage Renal Disease; IHD, ischemic heart disease; LVEDV, left ventricular end-diastolic volume; LVESV, left ventricular end-systolic volume; LVH, left ventricular hypertrophy; MPO, Membrane Permeability Outcome; NA, not available; PD, peritoneal dialysis; PTH, parathyroid hormone; SHARP, Study of Heart and Renal Protection; SPACE, Secondary Prevention With Antioxidants of Cardiovascular Disease in Endstage Renal Disease.References not included in other portions of the Core Curriculum:Eknoyan G, Beck GJ, Cheung AK, et al. Effect of dialysis dose and membrane flux in maintenance hemodialysis. N Engl J Med. 2002;347(25):2010-2019.Kopple JD, Cheung AK, Christiansen JS, et al. OPPORTUNITY: a randomized clinical trial of growth hormone on outcome in hemodialysis patients. Clin J Am Soc Nephrol. 2008;3(6):1741-1751.Locatelli F, Martin-Malo A, Hannedouche T, et al. Effect of membrane permeability on survival of hemodialysis patients. J Am Soc Nephrol. 2009;20(3):645-654.a Composite CVD outcome may include all-cause mortality, and each trial may have different cardiovascular events.b Results reported are for primary outcome of the study: + indicates benefit of intervention, − indicates no significant benefit. Open table in a new tab Table 2Selected Randomized Clinical Trials in Patients with CKD Stages 1-4 With Focus on Clinical CVD Outcomes/MortalityInterventionTrial NamePopulationNPrimary OutcomeaComposite CVD outcome may include all-cause mortality, and each trial may have different cardiovascular events.ResultbResults reported are for primary outcome of the study. + indicates benefit of intervention, − indicates no significant benefit.CommentCompleted TrialsFosinopril vs placebo; pravastatin vs placeboPREVEND ITMicroalbuminuria864Composite CVD−Trend to decrease in CVD events in fosinopril groupEpoetin alfa to target Hb of 13.5 vs 11.3 g/dLCHOIRCKD, GFR of 15-50 mL/min/1.73 m2, Hb <11 g/dL1,432Composite CVDIncreased risk of primary outcome in higher Hb groupEpoetin beta to target Hb of 13-15 vs 10.5-11.5 g/dLCREATEGFR of 15-35 mL/min/1.73 m2, Hb of 11-12.5 g/dL603Composite CVD−Darbepoetin alfa vs placeboTREATDM, CKD, & anemia4,038Composite CVD−Increased risk of stroke in higher Hb groupVitamin B6 + B9 + B12 vs placeboHOSTCKD stage 4 & hyperhomocysteinemia1,305All-cause mortality−Ongoing TrialsSimvastatin + ezetimibe vs placeboSHARPCKD component of SHARP3,000Composite CVDNAACEi + ARB vs ACEi vs ARBLIRICOMicro-/macroalbuminuria2,100Composite CVD & kidney outcomesNASBP <120 vs SBP <140 mm HgSPRINTCKD component of SPRINT (GFR of 30-59 mL/min/1.73 m2)(∼3,000 with CKD)Composite CVDNAAbbreviations: ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; CHOIR, Correction of Hemoglobin Outcomes in Renal Insufficiency; CKD, chronic kidney disease; CREATE, Cardiovascular Risk Reduction by Early Anemia Treatment With Epoetin Beta; CVD, cardiovascular disease; DM, diabetes mellitus; GFR, glomerular filtration rate; Hb, hemoglobin; HOST, Homocysteinemia in Kidney and Endstage Renal Disease; LIRICO, Long-term Impact of RAS Inhibition on Cardiorenal Outcomes; NA, not available; PREVEND IT, Prevention of Renal and Vascular Endstage Disease Intervention Trial; SBP, systolic blood pressure; SHARP, Study of Heart and Renal Protection; SPRINT, Systolic Blood Pressure Intervention Trial; TREAT, Trial to Reduce Cardiovascular Events With Aranesp Therapy.Reference not included in other parts of this article:Maione A, Nicolucci A, Craig JC, et al. Protocol of the Long-term Impact of RAS Inhibition on Cardiorenal Outcomes (LIRICO) randomized trial. J Nephrol. 2007;20(6):646-655.a Composite CVD outcome may include all-cause mortality, and each trial may have different cardiovascular events.b Results reported are for primary outcome of the study. + indicates benefit of intervention, − indicates no significant benefit. Open table in a new tab Abbreviations: AURORA, Assessment of Survival and Cardiovascular Events; CVD, cardiovascular disease; 4D, Die Deutsche Diabetes Dialyse Studie; DCOR, Dialysis Clinical Outcomes Revisited; EF, ejection fraction; EVOLVE, Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events; FOSIDIAL, Fosinopril in Dialysis Study; Hct, hematocrit; HD, hemodialysis; HEMO, Hemodialysis Study; HF, heart failure; HOST, Homocysteinemia in Kidney and Endstage Renal Disease; IHD, ischemic heart disease; LVEDV, left ventricular end-diastolic volume; LVESV, left ventricular end-systolic volume; LVH, left ventricular hypertrophy; MPO, Membrane Permeability Outcome; NA, not available; PD, peritoneal dialysis; PTH, parathyroid hormone; SHARP, Study of Heart and Renal Protection; SPACE, Secondary Prevention With Antioxidants of Cardiovascular Disease in Endstage Renal Disease. References not included in other portions of the Core Curriculum: Eknoyan G, Beck GJ, Cheung AK, et al. Effect of dialysis dose and membrane flux in maintenance hemodialysis. N Engl J Med. 2002;347(25):2010-2019. Kopple JD, Cheung AK, Christiansen JS, et al. OPPORTUNITY: a randomized clinical trial of growth hormone on outcome in hemodialysis patients. Clin J Am Soc Nephrol. 2008;3(6):1741-1751. Locatelli F, Martin-Malo A, Hannedouche T, et al. Effect of membrane permeability on survival of hemodialysis patients. J Am Soc Nephrol. 2009;20(3):645-654. Abbreviations: ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; CHOIR, Correction of Hemoglobin Outcomes in Renal Insufficiency; CKD, chronic kidney disease; CREATE, Cardiovascular Risk Reduction by Early Anemia Treatment With Epoetin Beta; CVD, cardiovascular disease; DM, diabetes mellitus; GFR, glomerular filtration rate; Hb, hemoglobin; HOST, Homocysteinemia in Kidney and Endstage Renal Disease; LIRICO, Long-term Impact of RAS Inhibition on Cardiorenal Outcomes; NA, not available; PREVEND IT, Prevention of Renal and Vascular Endstage Disease Intervention Trial; SBP, systolic blood pressure; SHARP, Study of Heart and Renal Protection; SPRINT, Systolic Blood Pressure Intervention Trial; TREAT, Trial to Reduce Cardiovascular Events With Aranesp Therapy. Reference not included in other parts of this article: Maione A, Nicolucci A, Craig JC, et al. Protocol of the Long-term Impact of RAS Inhibition on Cardiorenal Outcomes (LIRICO) randomized trial. J Nephrol. 2007;20(6):646-655. •CVD is the leading cause of mortality, accounting for nearly 45% of deaths at all ages; the high mortality is due to both a high prevalence of CVD and a high case fatality rate in those with heart failure or acute myocardial infarction•Of all deaths, 25%-30% (50%-60% of cardiovascular deaths) are classified as cardiac arrest/cause unknown or arrhythmia•There are conflicting data about whether peritoneal dialysis or hemodialysis patients are at higher risk of CVD∘Results of studies vary depending on the study population, statistical method used to adjust for case mix, country where the study is performed, incident versus prevalent patients, and dialysis vintage•Observational studies suggest that daily dialysis and nocturnal hemodialysis may be associated with improved blood pressure control, decreased left ventricular hypertrophy (LVH), and better control of mineral metabolism abnormalities∘In a small randomized controlled trial (n = 52), frequent nocturnal dialysis was associated with improved left ventricular mass (using cardiovascular magnetic resonance imaging) in comparison to standard of care•The Frequent Hemodialysis Network has 2 ongoing parallel randomized trials∘Both studies have 2 primary outcomes■Composite of mortality with change in the 36-Item Short Form Health Survey (SF-36) RAND physical health composite■Change in left ventricular mass∘Daily trial: 250 patients will be randomly assigned to either conventional hemodialysis 3 days per week or frequent hemodialysis 6 days per week∘Nocturnal trial: 150 patients will be randomly assigned to either conventional home hemodialysis 3 days per week or nocturnal home hemodialysis 6 times per week •High prevalence of CVD in incident dialysis patients suggests that CVD develops before the onset of kidney failure•Higher prevalence of coronary artery disease (CAD), heart failure, and CVD risk factors than in the general population•Graded and independent relationship between estimated glomerular filtration rate (GFR) and CVD outcomes, particularly in individuals with estimated GFR <45 mL/min/1.73 m2 (<0.75 mL/s/1.73 m2; Fig 1) •Independent association between microalbuminuria and clinical CVD in cross-sectional analysis•Higher prevalence of surrogates of CVD in those with microalbuminuria, such as∘LVH in patients with hypertension∘Carotid arterial intima-media thickening in patients with diabetes∘Brain white matter hyperintensity volume in older adults•Microalbuminuria is independently associated with CVD outcomes and all-cause mortality in those with and without diabetes•Albuminuria, even with albumin excretion less than the microalbuminuria range, is associated independently with CVD outcomes; no threshold has been defined, and in some studies, the risk extends to <10 μg/mg•Microalbuminuria may represent kidney disease itself or be a manifestation of systemic endothelial disease burden•In PREVEND IT (Prevention of Renal and Vascular End Stage Disease Intervention Trial), treatment with angiotensin-converting enzyme (ACE) inhibitors in patients with microalbuminuria showed a trend to reducing CVD outcomes ≫ Asselbergs FW, Diercks GF, Hillege HL, et al. Effects of fosinopril and pravastatin on cardiovascular events in subjects with microalbuminuria. Circulation. 2004;110(18):2809-2816. ≫ Culleton BF, Walsh M, Klarenbach SW, et al. Effect of frequent nocturnal hemodialysis vs conventional hemodialysis on left ventricular mass and quality of life: a randomized controlled trial. JAMA. 2007;298(11):1291-1299. ≫ Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351(13):1296-1305. ≫ Herzog CA, Ma JZ, Collins AJ. Poor long-term survival after acute myocardial infarction among patients on long-term dialysis. N Engl J Med. 1998;339(12):799-805. ≫ Romundstad S, Holmen J, Kvenild K, Hallan H, Ellekjaer H. Microalbuminuria and all-cause mortality in 2,089 apparently healthy individuals: a 4.4-year follow-up study. The Nord-Trondelag Health Study (HUNT), Norway. Am J Kidney Dis. 2003;42(3):466-473. ≫ Sarnak MJ, Levey AS, Schoolwerth AC, 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. Circulation. 2003;108(17):2154-2169. ≫ Suri RS, Garg AX, Chertow GM, et al. Frequent Hemodialysis Network (FHN) randomized trials: study design. Kidney Int. 2007;71(4):349-359. ≫ Tonelli M, Wiebe N, Culleton B, et al. Chronic kidney disease and mortality risk: a systematic review. J Am Soc Nephrol. 2006;17(7):2034-2047. ≫ US Renal Data System. USRDS 2008 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2008. ≫ Wachtell K, Ibsen H, Olsen MH, et al. Albuminuria and cardiovascular risk in hypertensive patients with left ventricular hypertrophy: the LIFE Study. Ann Intern Med. 2003;139(11):901-906. ≫ Weiner D, Sarnak MJ. Cardiovascular disease in patients with kidney disease. In: Chronic Kidney Disease, Dialysis, & Transplantation: A Companion to Brenner & Rector's The Kidney. 3rd ed. In press. There are 3 primary forms of CVD in patients with CKD: atherosclerosis, arteriosclerosis, and cardiomyopathy. Each of the risk factors described next may predispose to one form of CVD in particular or combinations thereof. •Occlusive disease of the vasculature•Focal process of plaque formation resulting in luminal narrowing•Manifestation of risk factors that are prevalent as kidney disease progresses, including a highly atherogenic lipid profile •Nonocclusive remodeling of the vasculature•Characterized by diffuse dilatation and hypertrophy of large arteries with loss of arterial elasticity and reduced arterial compliance•Risk factors include volume overload and mineral metabolism abnormalities•Manifestations of arteriosclerosis include∘LVH∘Decreased coronary perfusion∘Increased systolic blood pressure and pulse pressure LVH resulting from either pressure or volume overload reflects appropriate adaptation by the heart to these forces. As workload increases over time, increased oxygen demands by the hypertrophied left ventricle ultimately may exceed its perfusion, resulting in ischemia and eventual myocyte death. The end stage of this process is cardiomyopathy. •Leads to concentric thickening of the left ventricular wall to allow for generation of greater intraventricular pressure from∘Increased cardiac afterload from hypertension and aortic stenosis∘Reduced arterial compliance from arteriosclerosis •Leads to eccentric hypertrophy secondary to the addition of new sarcomeres in series and may be related to∘Anemia∘Increased extracellular volume∘Arteriovenous fistula with high blood flow Initial physiology often is consistent with diastolic dysfunction, but as this process progresses, myocardial fibrosis may ensue, and with sustained maladaptive forces, dilated cardiomyopathy may develop. ≫ London GM, Marchais SJ, Guerin AP, Metivier F. Impairment of arterial function in chronic renal disease: prognostic impact and therapeutic approach. Nephrol Dial Transplant. 2002;17(suppl 1):S113-115. ≫ Middleton RJ, Parfrey PS, Foley RN. Left ventricular hypertrophy in the renal patient. J Am Soc Nephrol. 2001;12(5):1079-1084. ≫ Parfrey PS, Foley RN. The clinical epidemiology of cardiac disease in chronic renal failure. J Am Soc Nephrol. 1999;10(7):1606-1615. CVD risk factors are defined as characteristics, both modifiable and nonmodifiable, that increase the risk of developing CVD. The risk factors shown in the left-hand side of Box 1 were defined in the Framingham Heart Study.•Many traditional risk factors, such as diabetes and hypertension, are more prevalent in patients with CKD than in the general population•The Framingham coronary risk equation severely underestimates CVD risk in dialysis patients•Individuals with CKD stages 3-4 have higher coronary risk scores using the Framingham prediction equations compared with the general population; however, with poor discrimination and calibration reflecting:∘Greater severity of traditional CVD risk factors∘Role of nontraditional risk factorsBox 1Traditional and Nontraditional Cardiovascular Risk FactorsTabled 1Traditional Risk FactorsNontraditional Factors•Older age•Male sex•Hypertension•Higher LDL cholesterol•Lower HDL cholesterol•Diabetes•Smoking•Physical inactivity•Menopause•Family history of coronary disease•Left ventricular hypertrophy•White raceFactors particular to individuals with kidney disease•Anemia•Volume overload•Abnormal mineral metabolism•Electrolyte imbalances•AlbuminuriaFactors in the general population•Lipoprotein(a) and Apo(a) isoforms & lipoprotein remnants•Homocysteine•Oxidative stress/inflammation•Malnutrition•Thrombogenic factors•Sleep disturbances•High sympathetic tone•Altered nitric oxide/endothelin balance Open table in a new tab Abbreviations: Apo, apolipoprotein; HDL, high-density lipoprotein; LDL, low-density lipoprotein. Tabled 1Traditional Risk FactorsNontraditional Factors•Older age•Male sex•Hypertension•Higher LDL cholesterol•Lower HDL cholesterol•Diabetes•Smoking•Physical inactivity•Menopause•Family history of coronary disease•Left ventricular hypertrophy•White raceFactors particular to individuals with kidney disease•Anemia•Volume overload•Abnormal mineral metabolism•Electrolyte imbalances•AlbuminuriaFactors in the general population•Lipoprotein(a) and Apo(a) isoforms & lipoprotein remnants•Homocysteine•Oxidative stress/inflammation•Malnutrition•Thrombogenic factors•Sleep disturbances•High sympathetic tone•Altered nitric oxide/endothelin balance Open table in a new tab Abbreviations: Apo, apolipoprotein; HDL, high-density lipoprotein; LDL, low-density lipoprotein. The right-hand side of Box 1 shows putative CVD risk factors that increase in prevalence as kidney function decreases, but were not described in the original Framingham Heart Study. ≫ Cheung AK, Sarnak MJ, Yan G, et al. Atherosclerotic cardiovascular disease risks in chronic hemodialysis patients. Kidney Int. 2000;58(1):353-362. ≫ Stenvinkel P, Carrero JJ, Axelsson J, Lindholm B, Heimburger O, Massy Z. Emerging biomarkers for evaluating cardiovascular risk in the chronic kidney disease patient: how do new pieces fit into the uremic puzzle? Clin J Am Soc Nephrol. 2008;3(2):505-521. ≫ Weiner DE, Tighiouart H, Elsayed EF, et al. The Framingham predictive instrument in chronic kidney disease. J Am Coll Cardiol. 2007;50(3):217-224. ≫ Weiner DE, Tighiouart H, Griffith JL, et al. Kidney disease, Framingham risk scores, and cardiac and mortality outcomes. Am J Med. 2007;120(6):552 e551-558. Hypertension is both a cause and a result of kidney disease. Of patients with CKD stages 1-4, a total of 70%-80% have hypertension and the prevalence increases as GFR decreases. •High blood pressure is an independent risk factor for nonfatal CVD events•There is a “U”-shaped relationship between blood pressure and all-cause and CVD mortality, with increased risk at both high and low blood pressures•The relationship between baseline blood pressure and mortality changes over time, with low systolic blood pressure associated with increased mortality in the first 2 years and the adverse effects of high systolic blood pressure apparent after 3 years of dialysis therapy•Increased pulse pressure, a marker of vascular stiffness, is associated with increased mortality in hemodialysis patients•Intradialytic hypotension is a relatively common occurrence during hemodialysis∘Represents inability of the heart or blood vessels to appropriately compensate for decreased blood volume∘Heart failure itself in the absence of overt volume overload•Intradialytic hypertension also may be associated with adverse outcomes•Absence of clinical trials delineating target blood pressure in dialysis patients•A meta-analysis of 8 randomized controlled trials of blood pressure–lowering medications showed that use of blood pressure–lowering medication was associated with lower risk of CVD events compared with controls; however, there was significant heterogeneity among studies •Increased systolic blood pressure is an independent risk factor for CVD outcomes in both diabetic and nondiabetic patients A summary of the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) grading system for guideline recommendations is shown in Box 2.•In dialysis patients, goal predialysis and postdialysis blood pressures are <140/90 and <130/80 mm Hg, respectively (level C evidence)•ACE inhibitors or angiotensin II receptor blockers (ARBs) should be preferred in patients on dialysis (level C evidence)•In patients with CKD stages 1-4, goal blood pressure is <130/80 mm Hg for prevention of CVD and kidney disease progression (level B evidence)•Dietary sodium intake <2.4 g/d should be recommended in most adults with CKD and hypertension (level A evidence)•Use of ACE inhibitors or ARBs in patients with CKD stages 1-4 as preferred agents in those with either diabetes mellitus or urine protein-creatinine ratio >200 mg/g in a spot urine specimen (level A evidence)Box 2Evidence Grades for KDOQI Guideline RecommendationsGrade AIt is strongly recommended that clinicians routinely follow the guideline for eligible patients. There is strong evidence that the practice improves health outcomes.Grade BIt is recommended that clinicians routinely follow the guideline for eligible patients. There is moderately strong evidence that the practice improves health outcomes.Grade CIt is recommended that clinicians consider following the guideline for eligible patients. This recommendation is based on either weak evidence or on the opinions of the Work Group and reviewers, that the practice might improve health outcomes.Abbreviation: KDOQI, Kidney Disease Outcomes Quality Initiative. Grade A It is strongly recommended that clinicians routinely follow the guideline for eligible patients. There is strong evidence that the practice improves health outcomes. Grade B It is recommended that clinicians routinely follow the guideline for eligible patients. There is moderately strong evidence that the practice improves health outcomes. Grade C It is recommended that clinicians consider following the guideline for eligible patients. This recommendation is based on either weak evidence or on the opinions of the Work Group and reviewers, that the practice might improve health outcomes. Abbreviation: KDOQI, Kidney Disease Outcomes Quality Initiative. ≫ Foley RN, Parfrey PS, Harnett JD, Kent GM, Murray DC, Barre PE. Impact of hypertension on cardiomyopathy, morbidity and mortality in end-stage renal disease. Kidney Int. 1996;49(5):1379-1385. ≫ Heerspink HJ, Ninomiya T, Zoungas S, et al. Effect of lowering blood pressure on cardiovascular events and mortality in patients on dialysis: a systematic review and meta-analysis of randomised controlled trials. Lancet. 2009;373(9668):1009-1015. ≫ Inrig JK, Patel UD, Toto RD, Szczech LA. Association of blood pressure increases during hemodialysis with 2-year mortality in incident hemodialysis patients: a secondary analysis of the Dialysis Morbidity and Mortality Wave 2 Study. Am J Kidney Dis. 2009;54(5):881-890. ≫ Klassen PS, Lowrie EG, Reddan DN, et al. Association between pulse pressure and mortality in patients undergoing maintenance hemodialysis. JAMA. 2002;287(12):1548-1555. ≫ National Kidney Foundation. K/DOQI Clinical Practice Guidelines on Hypertension and Antihypertensive Agents in Chronic Kidney Disease. Am J Kidney Dis. 2004;43(5 suppl 1):S1-290. ≫ National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Cardiovascular Disease in Dialysis Patients. Am J Kidney Dis. 2005;45(4 suppl 3):S1-153. ≫ Stidley CA, Hunt WC, Tentori F, et al. Changing relationship of blood pressure with mortality over time among hemodialysis patients. J Am Soc Nephrol. 2006;17(2):513-520. ≫ Takahashi A, Takase H, Toriyama T, et al. Candesartan, an angiotensin II type-1 receptor blocker, reduces cardiovascular events in patients on chronic haemodialysis—a randomized study. Nephrol Dial Transplant. 2006;21(9):2507-2512. ≫ Tepel M, Hopfenmueller W, Scholze A, Maier A, Zidek W. Effect of amlodipine on cardiovascular events in hypertensive haemodialysis patients. Nephrol Dial Transplant. 2008;23(11):3605-3612. ≫ Zager PG, Nikolic J, Brown RH, et al. “U” Curve association of blood pressure and mortality in hemodialysis patients. Medical Directors of Dialysis Clinic, Inc. Kidney Int. 1998;54(2):561-569. Although the nature of dyslipidemia can be highly variable, it is common in all stages of CKD. •In hemodialysis patients, high-density lipoprotein (HDL) cholesterol typically is low, low-density lipoprotein (LDL) cholesterol level is normal to low, and triglyceride, lipoprotein(a), and atherogenic oxidized LDL cholesterol levels are high compared with the general population•Peritoneal dialysis patients tend to have lower HDL cholesterol and higher triglyceride, LDL cholesterol, and apolipoprotein levels than hemodialysis patients; may be due to∘Absorption of glucose from the peritoneal dialysis fluid, which provides a substrate for increased lipoprotein synthesis∘Hypoalbuminemia secondary to peritoneal protein losses leading to overproduction of LDL cholesterol∘Loss of HDL across the peritoneum•Lower total cholesterol levels are associated with higher mortality, possibly because low cholesterol level is a surrogate for malnutrition and inflammation•Higher total cholesterol levels are associated with increased CVD risk in patients with preserved nutritional status•Two recent randomized controlled trials have been published about the effect of lipid-lowering therapy on CVD events in hemodialysis patients∘In the 4D Study (Die Deutsche Diabetes Dialyse Studie), although atorvastatin decreased LDL cholesterol levels, it did not decrease the primary composite CVD outcome in patients with type 2 diabetes∘Similarly, in the AURORA (Assessment of Survival and Cardiovascular Events) Study, rosuvastatin decreased LDL cholesterol levels, but had no significant effect on the composite primary end point of death from CVD causes, nonfatal myocardial infarction, or nonfatal stroke compared with placebo •Higher prevalence of increased LDL cholesterol and triglyceride and low HDL cholesterol levels compared with the general population•Nephrotic-range proteinuria can exacerbate dyslipidemia•Post hoc analyses of secondary prevention trials of statins in the general population show similar benefits in patients with and without CKD∘In the CARE (Cholesterol and Recurrent Events) Study, participants with decreased GFR (creatinine clearance <75 mL/min [<1.25 mL/s]) receiving pravastatin had a lower incidence of death from coronary disease or symptomatic nonfatal myocardial infarction than those receiving placebo∘In a pooled analysis using data from 3 randomized trials, pravastatin decreased CVD events compared with placebo in patients with CKD•In a meta-analysis of secondary prevention of CVD, statins significantly decreased lipid concentrations and CVD end points in patients with CKD, but had no benefit on all-cause mortality•In a primary prevention study, atorvastatin decreased CVD events, but not all-cause mortality, in a post hoc analysis of the CKD subgroup of CARDS (Collaborative Atorvastatin Diabetes Study) •All patients with CKD, even in the absence of known CVD, should be considered at high risk of CVD outcomes•Goal lipid levels are LDL cholesterol <100 mg/dL (<2.59 mmol/L) and non-HDL cholesterol <130 mg/dL (<3.36 mmol/L) (level B evidence) •The KDOQI guidelines potentially are still valid for CKD stage 3, but likely do not apply to dialysis patients, given results of the 4D Study and AURORA, particularly in individuals with an expected remaining lifespan less than 5 years•SHARP (Study of Heart and Renal Protection), a randomized trial of a combination of simvastatin and ezetimibe, will offer additional guidance in individuals with CKD stages 4-5 ≫ Baigent C, Landry M. Study of Heart and Renal P