The relationship between proteinuria and coronary risk: a systematic review and meta-analysis - PubMed (original) (raw)

Meta-Analysis

. 2008 Oct 21;5(10):e207.

doi: 10.1371/journal.pmed.0050207.

Christine Verdon, Toshiharu Ninomiya, Federica Barzi, Alan Cass, Anushka Patel, Meg Jardine, Martin Gallagher, Fiona Turnbull, John Chalmers, Jonathan Craig, Rachel Huxley

Affiliations

Meta-Analysis

The relationship between proteinuria and coronary risk: a systematic review and meta-analysis

Vlado Perkovic et al. PLoS Med. 2008.

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The authors had full access to the data. JC has received research grants from Servier, administered through the University of Sydney, as co-principal investigator for PROGRESS and ADVANCE. VP, AP, and JC have received honoraria from Servier for speaking about these studies at scientific meetings.

Figures

Figure 1

Figure 1. Identification Process for Eligible Studies

Figure 2

Figure 2. Summary Risk Ratio (95% Confidence Intervals) for the Association of Proteinuria with the Risk of Coronary Heart Disease in Population-Based Cohort Studies

The black squares are inversely proportional to the variance of the study and the horizontal lines represent the 95% CIs. Footnotes: Four studies reported estimates separated according to subgroups including (a) female, (b) male, (c) people without diabetes, (d) people with diabetes, (e) people with type 1 diabetes, and (f) people with type 2 diabetes. References: Culleton 2000 [22]; Fuller 2001 [24]; Irie 2006 [26]; Leelawattana 2003 [30]; Madison 2006 [32]; Miettinen 1996 [34]; Muntner 2002 [35]; Sasaki 1995 [36]; Shimozato 1996 [37]; Wagener 1994 [42].

Figure 3

Figure 3. Examination of Potential Sources of Heterogeneity between Studies of Proteinuria and CHD According to Study or Participant Characteristics

Conventions as in Figure 2. Footnote: (a) One study reported both risk estimates for individuals with and without diabetes.

Figure 4

Figure 4. Summary Risk Ratio (95% Confidence Intervals) for the Association of Albuminuria with the Risk of Coronary Heart Disease in Population-Based Cohort Studies

(A) Studies reporting risk estimate of microalbuminuria compared to normoalbuminuria. (B) Studies reporting risk estimate of macroalbuminuria compared to normoalbuminuria. (C) Studies reporting risk estimate of any level of albuminuria compared to normoalbuminuria. Conventions as in Figure 2. Footnotes: Three studies reported separated estimates according to subgroups including (a) female, (b) male, (c) non-Asian people, and (d) Asian people. References: Beilin 1996 [20]; Borch-Johnsen 1999 [21]; Corona 2005 [45]; Florkowski 2001 [23]; Hu 2002 [25]; Jensen 2000 [27]; Klausen 2004 [28]; Lee 2006 [29]; Lempiainen 1999 [31]; Mattock 1998 [33]; Soedarnah-Muthu 2004 [38]; Tillin 2005 [39]; Torffvit 2005 [40]; Valmadrid 2000 [41]; Wang 2005 [43]; Yuyun 2004 [44].

Figure 5

Figure 5. Subgroup Analysis of Comparisons within Studies Reporting Associations of Proteinuria and Albuminuria with Coronary Heart Disease Risk

Conventions as in Figure 2. Studies reporting both risk estimates for individuals with and without risk factor were included for the analysis. Footnotes: (a) Studies reporting both risk estimates for individuals with and without diabates were included for the analysis. (b) Studies reporting both risk estimates for individuals with microalbuminuria and those with macroalbuminuria were included for the analysis. (c) Studies reporting both age-adjusted estimates and multivariate-adjusted estimates were included for the analysis.

Similar articles

Cited by

References

    1. Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004;364:937–952. - PubMed
    1. Zhang X, Patel A, Horibe H, Wu Z, Barzi F, et al. Cholesterol, coronary heart disease, and stroke in the Asia Pacific region. Int J Epidemiol. 2003;32:563–572. - PubMed
    1. Woodward M, Zhang X, Barzi F, Pan W, Ueshima H, et al. The effects of diabetes on the risks of major cardiovascular diseases and death in the Asia-Pacific region. Diabetes Care. 2003;26:360–366. - PubMed
    1. Woodward M, Lam TH, Barzi F, Patel A, Gu D, et al. Smoking, quitting, and the risk of cardiovascular disease among women and men in the Asia-Pacific region. Int J Epidemiol. 2005;34:1036–1045. - PubMed
    1. Ni Mhurchu C, Rodgers A, Pan WH, Gu DF, Woodward M. Body mass index and cardiovascular disease in the Asia-Pacific Region: an overview of 33 cohorts involving 310 000 participants. Int J Epidemiol. 2004;33:751–758. - PubMed

Publication types

MeSH terms

LinkOut - more resources