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Primary and Secondary Prevention of Cardiovascular Disease in Patients with Chronic Kidney Disease

  • Coronary Heart Disease (S. Virani and S. Naderi, Section Editors)
  • Published:
Current Atherosclerosis Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Non-dialysis-dependent chronic kidney disease (NDD-CKD) patients are at an increased risk of cardiovascular disease (CVD)–related deaths in comparison with the general population. This review summarizes recent guideline recommendations and studies on primary and secondary prevention of traditional cardiovascular (CV) risk factors in those with NDD-CKD.

Recent Findings

The use of antiplatelet agents for primary prevention in CKD is not supported by clinical trial evidence; however, they offer potential benefits when used for secondary prevention of CVD in the absence of an elevated bleeding risk. Lipid-lowering therapy reduces CV risk and is recommended for all NDD-CKD patients. In light of recent clinical trial findings, current clinical practice guidelines recommend a blood pressure (BP) goal < 130/80 mmHg and support the use of renin-angiotensin-aldosterone system inhibitors. Evidence supporting intensive glycemic control is limited in those with diabetes and CKD. Newer oral glycemic agents such as sodium-glucose co-transporter type 2 (SGLT2) inhibitors and glucagon-like-peptide-1 (GLP-1) receptor agonists reduce urinary albumin excretion, slow kidney disease progression, and reduce CV events. Despite the absence of dedicated clinical trials in the CKD population, lifestyle modifications including smoking cessation, intentional weight loss, and regular physical activity should be recommended to those with CKD.

Summary

Patients with NDD-CKD should be treated with statins and a BP target of 130/80 mmHg should be aimed for. Limited data exists for interventions targeting other CV risk factors in CKD patients. Future studies examining the impact of various interventions targeting different primary and secondary CV prevention strategies are needed to fill knowledge gaps and improve CV outcomes.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. United States Renal Data System. 2018 USRDS annual data report: epidemiology of kidney disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. 2018.

  2. Navaneethan SD, Schold JD, Arrigain S, Jolly SE, Nally JV Jr. Cause-specific deaths in non-dialysis-dependent CKD. J Am Soc Nephrol. 2015;26(10):2512–20.

    Article  CAS  Google Scholar 

  3. Gregg LP, Hedayati SS. Management of traditional cardiovascular risk factors in CKD: what are the data? Am J Kidney Dis. 2018;72(5):728–44.

    Article  Google Scholar 

  4. Jardine MJ, Ninomiya T, Perkovic V, Cass A, Turnbull F, Gallagher MP, et al. Aspirin is beneficial in hypertensive patients with chronic kidney disease: a post-hoc subgroup analysis of a randomized controlled trial. J Am Coll Cardiol. 2010;56(12):956–65. https://doi.org/10.1016/j.jacc.2010.02.068.

    Article  CAS  PubMed  Google Scholar 

  5. Saito Y, Morimoto T, Ogawa H, Nakayama M, Uemura S, Doi N, et al. Low-dose aspirin therapy in patients with type 2 diabetes and reduced glomerular filtration rate: subanalysis from the JPAD trial. Diabetes Care. 2011;34(2):280–5.

    Article  CAS  Google Scholar 

  6. Levine GN, Bates ER, Bittl JA, Brindis RG, Fihn SD, Fleisher LA, et al. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines: an update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention, 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease, 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction, 2014 AHA/ACC Guideline for the Management of Patients With Non-ST-Elevation Acute Coronary Syndromes, and 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery. Circulation. 2016;134(10):e123–55.

  7. Bhatt DL, Fox KA, Hacke W, Berger PB, Black HR, Boden WE, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med. 2006;354(16):1706–17.

    Article  CAS  Google Scholar 

  8. • Palmer SC, Di Micco L, Razavian M, Craig JC, Perkovic V, Pellegrini F, et al. Antiplatelet agents for chronic kidney disease. Cochrane Database Syst Rev. 2013(2):CD008834. This systematic review examined the effects of various platelet agents in those with CKD. Data from primary and secondary prevention has been presented separately.

  9. Palmer SC, Di Micco L, Razavian M, Craig JC, Perkovic V, Pellegrini F, et al. Effects of antiplatelet therapy on mortality and cardiovascular and bleeding outcomes in persons with chronic kidney disease: a systematic review and meta-analysis. Ann Intern Med. 2012;156(6):445–59.

    Article  Google Scholar 

  10. Xie X, Liu Y, Perkovic V, Li X, Ninomiya T, Hou W, et al. Renin-angiotensin system inhibitors and kidney and cardiovascular outcomes in patients with CKD: a Bayesian network meta-analysis of randomized clinical trials. Am J Kidney Dis. 2016;67(5):728–41.

    Article  CAS  Google Scholar 

  11. Palmer SC, Craig JC, Navaneethan SD, Tonelli M, Pellegrini F, Strippoli GF. Benefits and harms of statin therapy for persons with chronic kidney disease: a systematic review and meta-analysis. Ann Intern Med. 2012;157(4):263–75.

    Article  Google Scholar 

  12. Group KCW. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int Suppl. 2012;1–150.

  13. Best PJ, Steinhubl SR, Berger PB, Dasgupta A, Brennan DM, Szczech LA, et al. The efficacy and safety of short- and long-term dual antiplatelet therapy in patients with mild or moderate chronic kidney disease: results from the Clopidogrel for the Reduction of Events During Observation (CREDO) trial. Am Heart J. 2008;155(4):687–93.

    Article  CAS  Google Scholar 

  14. •• Prof Colin Baigent F, Martin J Landray F, Christina Reith M, Jonathan Emberson P, David C Wheeler F, Charles Tomson D, et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet. 2011;377(9784):2181–92 This the largest clinical trial which demonstrated the cardiovascular benefits of statins plus ezetimibe in those with different stages of chronic kidney disease.

    Article  Google Scholar 

  15. Cholesterol Treatment Trialists C, Herrington WG, Emberson J, Mihaylova B, Blackwell L, Reith C, et al. Impact of renal function on the effects of LDL cholesterol lowering with statin-based regimens: a meta-analysis of individual participant data from 28 randomised trials. Lancet Diabetes Endocrinol. 2016;4(10):829–39.

    Article  Google Scholar 

  16. KDIGO clinical practice guideline for lipid management in chronic kidney disease. Kidney Int Suppl. 2013:259–305.

  17. Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the management of blood cholesterol: executive summary 0(0):CIR.0000000000000624.

  18. Robinson JG, Farnier M, Krempf M, Bergeron J, Luc G, Averna M, et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372(16):1489–99.

    Article  CAS  Google Scholar 

  19. Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376(18):1713–22.

    Article  CAS  Google Scholar 

  20. Kereiakes DJ, Robinson JG, Cannon CP, Lorenzato C, Pordy R, Chaudhari U, et al. Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: the ODYSSEY COMBO I study. Am Heart J. 2015;169(6):906–15 e13.

    Article  CAS  Google Scholar 

  21. Cannon CP, Cariou B, Blom D, McKenney JM, Lorenzato C, Pordy R, et al. Efficacy and safety of alirocumab in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia on maximally tolerated doses of statins: the ODYSSEY COMBO II randomized controlled trial. Eur Heart J. 2015;36(19):1186–94.

    Article  CAS  Google Scholar 

  22. Mafham M, Haynes R. PCSK9 inhibition: ready for prime time in CKD? Kidney Int. 2018;93(6):1267–9.

    Article  CAS  Google Scholar 

  23. Chronic Kidney Disease Prognosis C, Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, et al. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet. 2010;375(9731):2073–81.

    Article  Google Scholar 

  24. Group SR, Wright JT Jr, Williamson JD, Whelton PK, Snyder JK, Sink KM, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373(22):2103–16.

    Article  Google Scholar 

  25. ACCORD Study Group, Cushman WC, Evans GW, Byington RP, Goff DC Jr, Grimm RH Jr, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1575–85.

    Article  Google Scholar 

  26. •• Cheung AK, Rahman M, Reboussin DM, Craven TE, Greene T, Kimmel PL, et al. Effects of intensive BP control in CKD. J Am Soc Nephrol. 2017;28(9):2812–23 This study reported the cardiovascular benefits of intensive blood pressure control in those with non-dialysis-dependent CKD.

    Article  Google Scholar 

  27. Beddhu S, Rocco MV, Toto R, Craven TE, Greene T, Bhatt U, et al. Effects of intensive systolic blood pressure control on kidney and cardiovascular outcomes in persons without kidney disease: a secondary analysis of a randomized trial. Ann Intern Med. 2017;167(6):375–83.

    Article  Google Scholar 

  28. James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507–20.

    Article  CAS  Google Scholar 

  29. Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines. Hypertension. 2018;71(6):1269–324.

    Article  CAS  Google Scholar 

  30. Group KC. KDIGO clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int Suppl. 2012:337–414.

  31. Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006;355(3):251–9.

    Article  CAS  Google Scholar 

  32. Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345(12):861–9.

    Article  CAS  Google Scholar 

  33. Mann JF, Gerstein HC, Pogue J, Bosch J, Yusuf S. Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: the HOPE randomized trial. Ann Intern Med. 2001;134(8):629–36.

    Article  CAS  Google Scholar 

  34. Tobe SW, Clase CM, Gao P, McQueen M, Grosshennig A, Wang X, et al. Cardiovascular and renal outcomes with telmisartan, ramipril, or both in people at high renal risk: results from the ONTARGET and TRANSCEND studies. Circulation. 2011;123(10):1098–107.

    Article  CAS  Google Scholar 

  35. Fried LF, Emanuele N, Zhang JH, Brophy M, Conner TA, Duckworth W, et al. Combined angiotensin inhibition for the treatment of diabetic nephropathy. N Engl J Med. 2013;369(20):1892–903.

    Article  CAS  Google Scholar 

  36. Rahman M, Ford CE, Cutler JA, Davis BR, Piller LB, Whelton PK, et al. Long-term renal and cardiovascular outcomes in antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT) participants by baseline estimated GFR. Clin J Am Soc Nephrol. 2012;7(6):989–1002.

    Article  Google Scholar 

  37. Saruta T, Hayashi K, Ogihara T, Nakao K, Fukui T, Fukiyama K, et al. Effects of candesartan and amlodipine on cardiovascular events in hypertensive patients with chronic kidney disease: subanalysis of the CASE-J study. Hypertens Res. 2009;32(6):505–12.

    Article  CAS  Google Scholar 

  38. Blood Pressure Lowering Treatment Trialists C, Ninomiya T, Perkovic V, Turnbull F, Neal B, Barzi F, et al. Blood pressure lowering and major cardiovascular events in people with and without chronic kidney disease: meta-analysis of randomised controlled trials. BMJ. 2013;f5680:347.

    Google Scholar 

  39. ADVANCE collaborative group, Patel A, MacMahon S, Chalmers J, Neal B, Billot L, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358(24):2560–72.

  40. National Kidney F. KDOQI clinical practice guideline for diabetes and CKD: 2012 update. Am J Kidney Dis. 2012;60(5):850–86.

    Article  Google Scholar 

  41. Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377(7):644–57.

    Article  CAS  Google Scholar 

  42. •• Wanner C, Inzucchi SE, Lachin JM, Fitchett D, von Eynatten M, Mattheus M, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016;375(4):323–34 Data from large clinical trial demonstrating benefits of SGLT2 inhibitors on renal outcomes.

    Article  CAS  Google Scholar 

  43. Xia J, Wang L, Ma Z, Zhong L, Wang Y, Gao Y, et al. Cigarette smoking and chronic kidney disease in the general population: a systematic review and meta-analysis of prospective cohort studies. Nephrol Dial Transplant. 2017;32(3):475–87.

    Article  CAS  Google Scholar 

  44. Staplin N, Haynes R, Herrington WG, Reith C, Cass A, Fellstrom B, et al. Smoking and adverse outcomes in patients with CKD: the Study of Heart and Renal Protection (SHARP). Am J Kidney Dis. 2016;68(3):371–80.

    Article  Google Scholar 

  45. Ricardo AC, Anderson CA, Yang W, Zhang X, Fischer MJ, Dember LM, et al. Healthy lifestyle and risk of kidney disease progression, atherosclerotic events, and death in CKD: findings from the Chronic Renal Insufficiency Cohort (CRIC) study. Am J Kidney Dis. 2015;65(3):412–24.

    Article  Google Scholar 

  46. Sawicki PT, Didjurgeit U, Muhlhauser I, Bender R, Heinemann L, Berger M. Smoking is associated with progression of diabetic nephropathy. Diabetes Care. 1994;17(2):126–31.

    Article  CAS  Google Scholar 

  47. Gambaro G, Bax G, Fusaro M, Normanno M, Manani SM, Zanella M, et al. Cigarette smoking is a risk factor for nephropathy and its progression in type 2 diabetes mellitus. Diabetes Nutr Metab. 2001;14(6):337–42.

    CAS  PubMed  Google Scholar 

  48. Chuahirun T, Simoni J, Hudson C, Seipel T, Khanna A, Harrist RB, et al. Cigarette smoking exacerbates and its cessation ameliorates renal injury in type 2 diabetes. Am J Med Sci. 2004;327(2):57–67.

    Article  Google Scholar 

  49. Wing RR, Lang W, Wadden TA, Safford M, Knowler WC, Bertoni AG, et al. Benefits of modest weight loss in improving cardiovascular risk factors in overweight and obese individuals with type 2 diabetes. Diabetes Care. 2011;34(7):1481–6.

    Article  CAS  Google Scholar 

  50. Chang AR, Grams ME, Ballew SH, Bilo H, Correa A, et al. Adiposity and risk of decline in glomerular filtration rate: meta-analysis of individual participant data in a global consortium. BMJ. 2019;364:k5301.

    Article  Google Scholar 

  51. • Ikizler TA, Robinson-Cohen C, Ellis C, Headley SAE, Tuttle K, Wood RJ, et al. Metabolic effects of diet and exercise in patients with moderate to severe CKD: a randomized clinical trial. J Am Soc Nephrol. 2018;29(1):250–9 This clinical trial demonstrated the feasibility of diet and exercise interventions in those with chronic kidney disease.

    Article  CAS  Google Scholar 

  52. Look ARG. Effect of a long-term behavioural weight loss intervention on nephropathy in overweight or obese adults with type 2 diabetes: a secondary analysis of the Look AHEAD randomised clinical trial. Lancet Diabetes Endocrinol. 2014;2(10):801–9.

    Article  Google Scholar 

  53. Scirica BM, Bohula EA, Dwyer JP, Qamar A, Inzucchi SE, McGuire DK, et al. Lorcaserin and renal outcomes in obese and overweight patients in the CAMELLIA-TIMI 61 trial. Circulation. 2019;139(3):366–75.

    Article  CAS  Google Scholar 

  54. Navaneethan SD. Trials and tribulations in studying kidney outcomes with intentional weight loss. Circulation. 2019;139(3):376–9.

    Article  Google Scholar 

  55. Global Recommendations on Physical Activity for Health. WHO Guidelines Approved by the Guidelines Review Committee. Geneva; 2010.

  56. Physical Activity Guidelines Advisory Committee report, 2008. To the Secretary of Health and Human Services. Part a: executive summary. Nutr Rev. 2009;67(2):114–20.

  57. Mora S, Cook N, Buring JE, Ridker PM, Lee IM. Physical activity and reduced risk of cardiovascular events: potential mediating mechanisms. Circulation. 2007;116(19):2110–8.

    Article  CAS  Google Scholar 

  58. Heiwe S, Jacobson SH. Exercise training in adults with CKD: a systematic review and meta-analysis. Am J Kidney Dis. 2014;64(3):383–93.

    Article  Google Scholar 

  59. WRITING COMMITTEE MEMBERS, Arnett DK, Blumenthal RS, Albert MA, Michos ED, Buroker AB, Miedema MD, Goldberger ZD, Muñoz D, Hahn EJ, Smith Jr SC, Himmelfarb CD, Virani SS, Khera A, Williams Sr KA, Lloyd-Jones D, Yeboah J, McEvoy JW, Ziaeian B, ACC/ AHA TASK FORCE MEMBERS, O’Gara PT, Beckman JA, Levine GN, Chair IP, Al-Khatib SM, Hlatky MA, Birtcher KK, Ikonomidis J, Cigarroa JE, Joglar JA, Deswal A, Mauri L, Fleisher LA, Piano MR, Gentile F, Riegel B, Goldberger ZD, Wijeysundera DN. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease. J Am Coll Cardiol. 2019. https://doi.org/10.1016/j.jacc.2019.03.010.

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Sources of Support

Dr. Navaneethan is supported by a grant from the National Institutes of Health (National Institute of Diabetes and Digestive and Kidney Disease-R01DK101500).

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Correspondence to Sankar D. Navaneethan.

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The authors report no relevant financial interest in the contents of this review. Outside the submitted work, S.D.N. has served on the event adjudication committee for clinical trials sponsored by Bayer and Boehringer Ingelheim, served as a consultant for Tricida, and has received investigator-initiated research support from Keryx Pharmaceuticals.

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Ali, S., Dave, N., Virani, S.S. et al. Primary and Secondary Prevention of Cardiovascular Disease in Patients with Chronic Kidney Disease. Curr Atheroscler Rep 21, 32 (2019). https://doi.org/10.1007/s11883-019-0794-6

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