Moderately Increased Albuminuria Is an Independent Risk Factor of Cardiovascular Events in the General Japanese Population under 75 Years of Age: The Watari Study

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Abstract

Background

Moderately increased albuminuria (formerly called microalbuminuria) is widely recognized as a predictor of cardiovascular disease. However, it is not clear whether this observation is applicable to the Asian population, as studies leading to this conclusion were conducted on Western populations. The aim of this study was to examine the hypothesis if moderately increased albuminuria could be an independent predictor of cardiovascular mortality and morbidity in the Japanese population.

Methods and Results

The study population consisted of 3093 inhabitants of Watari, Miyagi Prefecture, who participated in an annual health check-up in 2009. We examined anthropometry, sitting blood pressure, fasting blood sample, and urine albumin-to-creatinine ratio (UACR). After baseline assessment, subjects were followed prospectively for up to 60 months. The incidence of major cardiovascular events (stroke, myocardial infarction, revascularization, and cardiovascular death) was determined based on death certificate records or medical claims sent to the National Health Insurance of Japan. Follow-up was discontinued for those who reached 75 years of age because they were moved to a different medical insurance system. We observed 57 cardiovascular events during a mean follow-up period of 47.8 months. The cumulative incidence rate for major cardiovascular events was significantly higher in patients with moderately increased albuminuria (UACR 30–299 mg/gCr) than in those with normoalbuminuria (UACR <30 mg/gCr) (6.4% vs. 2.2%, p = 0.0002 by log-rank test). Multivariate Cox proportional hazards analyses have revealed that moderately increased albuminuria is an independent predictor of cardiovascular events (HR 2.386, 95% CI: 1.120–4.390).

Conclusions

Moderately increased albuminuria is an independent predictor of cardiovascular events in the general Japanese population under 75 years of age.

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Most cited references 13

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Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population.

Hans Hillege, Vaclav Fidler, Gilles F. H. Diercks … (2002)

For the general population, the clinical relevance of an increased urinary albumin excretion rate is still debated. Therefore, we examined the relationship between urinary albumin excretion and all-cause mortality and mortality caused by cardiovascular (CV) disease and non-CV disease in the general population. In the period 1997 to 1998, all inhabitants of the city of Groningen, the Netherlands, aged between 28 and 75 years (n=85 421) were sent a postal questionnaire collecting information about risk factors for CV disease and CV morbidity and a vial to collect an early morning urine sample for measurement of urinary albumin concentration (UAC). The vital status of the cohort was subsequently obtained from the municipal register, and the cause of death was obtained from the Central Bureau of Statistics. Of these 85 421 subjects, 40 856 (47.8%) responded, and 40 548 could be included in the analysis. During a median follow-up period of 961 days (maximum 1139 days), 516 deaths with known cause were recorded. We found a positive dose-response relationship between increasing UAC and mortality. A higher UAC increased the risk of both CV and non-CV death after adjustment for other well-recognized CV risk factors, with the increase being significantly higher for CV mortality than for non-CV mortality (P=0.014). A 2-fold increase in UAC was associated with a relative risk of 1.29 for CV mortality (95% CI 1.18 to 1.40) and 1.12 (95% CI 1.04 to 1.21) for non-CV mortality. Urinary albumin excretion is a predictor of all-cause mortality in the general population. The excess risk was more attributable to death from CV causes, independent of the effects of other CV risk factors, and the relationship was already apparent at levels of albuminuria currently considered to be normal.

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Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes.

C E Mogensen (1984)

We studied whether microalbuminuria (30 to 140 micrograms of albumin per milliliter) would predict the later development of increased proteinuria and early mortality in Type II diabetics. During 1973, morning urine specimens of diabetic clinic patients 50 to 75 years of age whose disease had been diagnosed the age of 45 were examined for albumin level by radioimmunoassay. Seventy-six patients with albumin concentrations of 30 to 140 micrograms per milliliter were identified for long-term follow-up. They were compared with normal controls, diabetic patients with lower albumin concentrations (75 patients with concentrations less than 15 micrograms per milliliter and 53 with concentrations of 16 to 29 micrograms per milliliter), and 28 diabetic patients with higher concentrations (greater than 140). Age, duration of diabetes, treatment method, fasting blood glucose level, blood pressure, height, and weight were determined for the four diabetic groups. After nine years the group with albumin concentrations of 30 to 140 micrograms per milliliter was more likely to have clinically detectable proteinuria (greater than 400 micrograms per milliliter) than were the groups with lower concentrations. Mortality was 148 per cent higher in this group than in normal controls--comparable to the increase (116 per cent) in the group with heavy proteinuria (albumin levels greater than 140 micrograms per milliliter). In addition, mortality was increased 76 per cent in the group with albumin levels of 16 to 29 micrograms per milliliter and 37 per cent in the group with levels below 15. We conclude that microalbuminuria in patients with Type II diabetes is predictive of clinical proteinuria and increased mortality.

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HDL and cardiovascular disease: atherogenic and atheroprotective mechanisms.

Mohamad Navab, Srinivasa T. Reddy, Brian Van Lenten … (2011)

The lipoprotein HDL has two important roles: first, it promotes reverse cholesterol transport, and second, it modulates inflammation. Epidemiological studies show that HDL-cholesterol levels are inversely correlated with the risk of cardiovascular events. However, many patients who experience a clinical event have normal, or even high, levels of HDL cholesterol. Measuring HDL-cholesterol levels provides information about the size of the HDL pool, but does not predict HDL composition or function. The main component of HDL, apolipoprotein A-I (apo A-I), is largely responsible for reverse cholesterol transport through the macrophage ATP-binding cassette transporter ABCA1. Apo A-I can be damaged by oxidative mechanisms, which render the protein less able to promote cholesterol efflux. HDL also contains a number of other proteins that are affected by the oxidative environment of the acute-phase response. Modification of the protein components of HDL can convert it from an anti-inflammatory to a proinflammatory particle. Small peptides that mimic some of the properties of apo A-I have been shown in preclinical models to improve HDL function and reduce atherosclerosis without altering HDL-cholesterol levels. Robust assays to evaluate the function of HDL are needed to supplement the measurement of HDL-cholesterol levels in the clinic. © 2011 Macmillan Publishers Limited. All rights reserved

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Author and article information

Contributors

Gianpaolo Reboldi: Role: Academic Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, CA USA )

ISSN (Electronic): 1932-6203

Publication date (Electronic): 7 April 2015

Publication date Collection: 2015

Volume: 10

Issue: 4

Electronic Location Identifier: e0123893

Affiliations

[1 ]Division of Hypertension, Tohoku Rosai Hospital, Sendai, Japan

[2 ]Research Center for Life Style Related Disease, Tohoku Rosai Hospital, Sendai, Japan

University of Perugia, ITALY

Author notes

Competing Interests: The authors have declared that no competing interests exist.

Conceived and designed the experiments: MM. Performed the experiments: SK MM. Analyzed the data: SK. Wrote the paper: SK MM.

* E-mail: munakata@ 123456tohokuh.rofuku.go.jp

Article

Publisher ID: PONE-D-14-43704

DOI: 10.1371/journal.pone.0123893

PMC ID: 4388624

PubMed ID: 25849735

SO-VID: fb622afd-4123-4a04-86af-dd2e0e9af917

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

History

Date received : 29 September 2014

Date accepted : 27 February 2015

Page count

Figures: 2, Tables: 3, Pages: 10

Funding

The Watari study was made possible by Grants-in-Aid from the Japan Labor, Health, and Welfare Organization. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Custom metadata

Data Availability Due to legal restrictions from the local government and identifying patient information, de-identified data for this paper will be available upon request from the Tohoku Rosai Hospital Ethics Committee.

Moderately Increased Albuminuria Is an Independent Risk Factor of Cardiovascular Events in the General Japanese Population under 75 Years of Age: The Watari Study

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Most cited references 13

Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population.

Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes.

HDL and cardiovascular disease: atherogenic and atheroprotective mechanisms.

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