The Relationship between Proteinuria and Coronary Risk: A Systematic Review and Meta-Analysis

English version České info

Background:
Markers of kidney dysfunction such as proteinuria or albuminuria have been reported to be associated with coronary heart disease, but the consistency and strength of any such relationship has not been clearly defined. This lack of clarity has led to great uncertainty as to how proteinuria should be treated in the assessment and management of cardiovascular risk. We therefore undertook a systematic review of published cohort studies aiming to provide a reliable estimate of the strength of association between proteinuria and coronary heart disease.

Methods and Findings:
A meta-analysis of cohort studies was conducted to obtain a summary estimate of the association between measures of proteinuria and coronary risk. MEDLINE and EMBASE were searched for studies reporting an age- or multivariate-adjusted estimate and standard error of the association between proteinuria and coronary heart disease. Studies were excluded if the majority of the study population had known glomerular disease or were the recipients of renal transplants. Two independent researchers extracted the estimates of association between proteinuria (total urinary protein >300 mg/d), microalbuminuria (urinary albumin 30–300 mg/d), macroalbuminuria (urinary albumin >300 mg/d), and risk of coronary disease from individual studies. These estimates were combined using a random-effects model. Sensitivity analyses were conducted to examine possible sources of heterogeneity in effect size. A total of 26 cohort studies were identified involving 169,949 individuals and 7,117 coronary events (27% fatal). The presence of proteinuria was associated with an approximate 50% increase in coronary risk (risk ratio 1.47, 95% confidence interval [CI] 1.23–1.74) after adjustment for known risk factors. For albuminuria, there was evidence of a dose–response relationship: individuals with microalbuminuria were at 50% greater risk of coronary heart disease (risk ratio 1.47, 95% CI 1.30–1.66) than those without; in those with macroalbuminuria the risk was more than doubled (risk ratio 2.17, 1.87–2.52). Sensitivity analysis indicated no important differences in prespecified subgroups.

Conclusion:
These data confirm a strong and continuous association between proteinuria and subsequent risk of coronary heart disease, and suggest that proteinuria should be incorporated into the assessment of an individual's cardiovascular risk.

Vyšlo v časopise: The Relationship between Proteinuria and Coronary Risk: A Systematic Review and Meta-Analysis. PLoS Med 5(10): e207. doi:10.1371/journal.pmed.0050207
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pmed.0050207

Souhrn

Zdroje

1. YusufSHawkenSOunpuuSDansTAvezumA

2004

Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study.

Lancet

364

937

952

2. ZhangXPatelAHoribeHWuZBarziF

2003

Cholesterol, coronary heart disease, and stroke in the Asia Pacific region.

Int J Epidemiol

563

572

3. WoodwardMZhangXBarziFPanWUeshimaH

2003

The effects of diabetes on the risks of major cardiovascular diseases and death in the Asia-Pacific region.

Diabetes Care

360

366

4. WoodwardMLamTHBarziFPatelAGuD

2005

Smoking, quitting, and the risk of cardiovascular disease among women and men in the Asia-Pacific region.

Int J Epidemiol

1036

1045

5. Ni MhurchuCRodgersAPanWHGuDFWoodwardM

2004

Body mass index and cardiovascular disease in the Asia-Pacific Region: an overview of 33 cohorts involving 310 000 participants.

Int J Epidemiol

751

758

6. KengneAPPatelABarziFJamrozikKLamTH

2007

Systolic blood pressure, diabetes and the risk of cardiovascular diseases in the Asia-Pacific region.

J Hypertens

1205

1213

7. DaneshJWheelerJGHirschfieldGMEdaSEiriksdottirG

2004

C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease.

N Engl J Med

350

1387

1397

8. DaneshJWhincupPWalkerMLennonLThomsonA

2001

Fibrin D-dimer and coronary heart disease: prospective study and meta-analysis.

Circulation

103

2323

2327

9. DaneshJLewingtonSThompsonSGLoweGDCollinsR

2005

Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis.

JAMA

294

1799

1809

10. SarnakMJLeveyASSchoolwerthACCoreshJCulletonB

2003

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

108

2154

2169

11. CoreshJAstorBCGreeneTEknoyanGLeveyAS

2003

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

12. ChadbanSJBrigantiEMKerrPGDunstanDWWelbornTA

2003

Prevalence of kidney damage in Australian adults: The AusDiab kidney study.

J Am Soc Nephrol

S131

138

13. WhiteSLCassAAtkinsRCChadbanSJ

2005

Chronic kidney disease in the general population.

Adv Chronic Kidney Dis

14. LindnerACharraBSherrardDScribnerB

1974

Accelerated atherosclerosis in prolonged maintenance haemodialysis.

New Engl J Med

290

701

15. de ZeeuwDParvingHHHenningRH

2006

Microalbuminuria as an early marker for cardiovascular disease.

J Am Soc Nephrol

2100

2105

16. StroupDFBerlinJAMortonSCOlkinIWilliamsonGD

2000

Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group.

JAMA

283

2008

2012

17. HigginsJPThompsonSGDeeksJJAltmanDG

2003

Measuring inconsistency in meta-analyses.

BMJ

327

557

560

18. HigginsJPThompsonSG

2002

Quantifying heterogeneity in a meta-analysis.

Stat Med

1539

1558

19. DuvalSTweedieR

2000

Trim and fill: A simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis.

Biometrics

455

463

20. BeilinJStantonKGMcCannVJKnuimanMWDivitiniML

1996

Microalbuminuria in type 2 diabetes: An independent predictor of cardiovascular mortality.

Aust N Z J Med

519

525

21. Borch-JohnsenKFeldt-RasmussenBStrandgaardSSchrollMJensenJS

1999

Urinary albumin excretion: An independent predictor of ischemic heart disease.

Arterioscler Thromb Vasc Biol

1992

1997

22. CulletonBFLarsonMGParfreyPSKannelWBLevyD

2000

Proteinuria as a risk factor for cardiovascular disease and mortality in older people: A prospective study.

Am J Med

109

23. FlorkowskiCMScottRSCoopePAMoirCL

2001

Predictors of mortality from type 2 diabetes mellitus in Canterbury, New Zealand; a ten-year cohort study.

Diabetes Res Clin Pract

113

120

24. FullerJHStevensLKWangSLLeeETKeenH

2001

Risk factors for cardiovascular mortality and morbidity: The WHO multinational study of vascular disease in diabetes.

Diabetologia

S54

S64

25. HuDJablonskiKASparlingYHRobbinsDCLeeET

2002

Accuracy of lipoprotein lipids and apoproteins in predicting coronary heart disease in diabetic American Indians: the Strong Heart Study.

Ann Epidemiol

26. IrieFIsoHSairenchiTFukasawaNYamagishiK

2006

The relationships of proteinuria, serum creatinine, glomerular filtration rate with cardiovascular disease mortality in Japanese general population.

Kidney Int

1264

1271

27. JensenJSFeldt-RasmussenBStrandgaardSSchrollMBorch-JohnsenK

2000

Arterial hypertension, microalbuminuria, and risk of ischemic heart disease.

Hypertension

898

903

28. KlausenKBorch-JohnsenKFeldt-RasmussenBJensenGClausenP

2004

Very low levels of microalbuminuria are associated with increased risk of coronary heart disease and death independently of renal function, hypertension, and diabetes.

Circulation

110

29. LeeYTFujitaTShimamotoKWuZZhuJ

2006

Other health matters to be considered for the Asian population: Hypertensive patients at high risk.

Int J Clin Pract

30. LeelawattanaRRattarasarnCLimASoonthornpunSSetasubanW

2003

Causes of death, incidence and risk factors of cardiovascular diseases in Thai type 2 diabetic patients: A 5-year follow-up study.

Diabetes Res Clin Pract

183

189

31. LempiainenPMykkanenLPyoralaKLaaksoMKuusistoJ

1999

Insulin resistance syndrome predicts coronary heart disease events in elderly nondiabetic men.

Circulation

100

123

128

32. MadisonJRSpiesCSchatzIJMasakiKChenR

2006

Proteinuria and risk for stroke and coronary heart disease during 27 years of follow-up: The Honolulu Heart Program.

Arch Intern Med

166

884

889

33. MattockMBBarnesDJVibertiGKeenHBurtD

1998

Microalbuminuria and coronary heart disease in NIDDM: an incidence study.

Diabetes

1786

1792

34. MiettinenHHaffnerSMLehtoSRonnemaaTPyoralaK

1996

Proteinuria predicts stroke and other atherosclerotic vascular disease events in nondiabetic and non-insulin-dependent diabetic subjects.

Stroke

2033

2039

35. MuntnerPHeJHammLLoriaCWheltonPK

2002

Renal insufficiency and subsequent death resulting from cardiovascular disease in the United States.

J Am Soc Nephrol

745

753

36. SasakiAHoriuchiNHasegawaKUeharaM

1995

Mortality from coronary heart disease and cerebrovascular disease and associated risk factors in diabetic patients in Osaka District, Japan.

Diabetes Res Clin Pract

37. ShimozatoMNakayamaTYokoyamaTYoshi-ikeNYamaguchiM

1996

A 15.5-year cohort study on risk factors for possible myocardial infarction and sudden death within 24 hours in a rural Japanese community.

J Epidemiol

38. Soedamah-MuthuSSChaturvediNToellerMFerrissBReboldiP

2004

Risk factors for coronary heart disease in type 1 diabetic patients in Europe: The EURODIAB Prospective Complications Study.

Diabetes Care

530

537

39. TillinTForouhiNMcKeiguePChaturvediN

2005

Microalbuminuria and coronary heart disease risk in an ethnically diverse UK population: a prospective cohort study.

Journal of the American Society of Nephrology: JASN

3702

3710

40. TorffvitOLovestam-AdrianMAgardhEAgardhCD

2005

Nephropathy, but not retinopathy, is associated with the development of heart disease in Type 1 diabetes: A 12-year observation study of 462 patients.

Diabet Med

723

729

41. ValmadridCTKleinRMossSEKleinBEK

2000

The risk of cardiovascular disease mortality associated with microalbuminuria and gross proteinuria in persons with older-onset diabetes mellitus.

Archives Intern Med

160

1093

1100

42. WagenerDKHarrisTMadansJH

1994

Proteinuria as a biomarker: Risk of subsequent morbidity and mortality.

Environ Res

160

172

43. WangZHoyWE

2005

Albuminuria and incident coronary heart disease in Australian Aboriginal people.

Kidney Int

1289

1293

44. YuyunMFKhawKTLubenRWelchABinghamS

2004

A prospective study of microalbuminuria and incident coronary heart disease and its prognostic significance in a British population: The EPIC-Norfolk Study.

Am J Epidemiol

159

284

293

45. CoronaAJMartinezDRAvilaMHHaffnerSWilliamsK

2005

Microalbuminuria as a predictor of myocardial infarction in a Mexican population: the Mexico City Diabetes Study.

Kidney Int Suppl

S34

46. MoscaLBankaCLBenjaminEJBerraKBushnellC

2007

Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update.

Circulation

115

1481

1501

47. GansevoortRTBrinkmanJBakkerSJDe JongPEde ZeeuwD

2006

Evaluation of measures of urinary albumin excretion.

Am J Epidemiol

164

725

727

48. HallanSAstorBRomundstadSAasarodKKvenildK

2007

Association of kidney function and albuminuria with cardiovascular mortality in older vs younger individuals: The HUNT II Study.

Arch Intern Med

167

2490

2496

49. LewisEJHunsickerLGClarkeWRBerlTPohlMA

2001

Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes.

N Engl J Med

345

851

860

50. BrennerBMCooperMEde ZeeuwDKeaneWFMitchWE

2001

Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy.

N Engl J Med

345

861

869

51. YusufSSleightPPogueJBoschJDaviesR

2000

Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators.

N Engl J Med

342

145

153

52. de ZeeuwDRemuzziGParvingHHKeaneWFZhangZ

2004

Proteinuria, a target for renoprotection in patients with type 2 diabetic nephropathy: lessons from RENAAL.

Kidney Int

2309

2320

53. IbsenHOlsenMHWachtellKBorch-JohnsenKLindholmLH

2005

Reduction in albuminuria translates to reduction in cardiovascular events in hypertensive patients: losartan intervention for endpoint reduction in hypertension study.

Hypertension

198

202

54. DeckertTFeldt-RasmussenBBorch-JohnsenKJensenTKofoed-EnevoldsenA

1989

Albuminuria reflects widespread vascular damage. The Steno hypothesis.

Diabetologia

219

226

55. MacMahonSPetoRCutlerJCollinsRSorlieP

1990

Blood pressure, stroke, and coronary heart disease. Part 1, Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias.

Lancet

335

765

774