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      Poor Lung Function Has Inverse Relationship with Microalbuminuria, an Early Surrogate Marker of Kidney Damage and Atherosclerosis: The 5 th Korea National Health and Nutrition Examination Survey

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          Abstract

          Background

          Despite epidemiological evidences of relationship between poor lung function and atherosclerosis, the relationship between poor lung function and microalbuminuria (MAU), an early surrogate marker of both kidney damage and atherosclerosis, is not well understood. Hence, we plan to investigate the relationship between poor lung function and MAU using multivariate models to adjust for other atherogenic risk factors.

          Methods

          We used data from the 5 th Korean National Health and Nutrition Examination Survey. Poor lung function is determined by spirometric measurement, primarily through estimation of the forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1). Declines in the percent predicted FVC (<80%) and in the FEV 1/FVC ratio (<0.7) are defined as restrictive and obstructive patterns, respectively. Urine albumin to urine creatinine levels ratio (UACR) were measured in spot urine samples. MAU was defined as UACR >30 mg/g.

          Results

          Inverse relationship was observed between lung function and UACR. In an age-adjusted regression model, the regression coefficient (B) of 10% lower FVC was 11.09 in men ( P = 0.002), which remained significant after adjustment for SBP, FBG, triglyceride level, BMI, smoking history, and heavy alcohol consumption (B = 7.52, P = 0.043). When the restrictive pattern was compared to the normal pattern, the odds ratios (OR) (95% confidence interval, 95%CI) for MAU were 1.90 (1.32–2.72) in men, after adjustment for age, hypertension, diabetes mellitus, triglyceride level, obesity, smoking history, physical activity, and heavy alcohol consumption.

          Conclusions

          Our study, the first investigation in Asia, demonstrated that the restrictive pattern is related to MAU in men. Furthermore, there was linear relationship between lower FVC and UACR. Thus, our current study suggests that poor lung function, particularly the restrictive pattern, is related to kidney damage as well as atherosclerosis.

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          Most cited references24

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          Prevalence and outcomes of diabetes, hypertension and cardiovascular disease in COPD.

          Chronic obstructive pulmonary disease (COPD) is associated with important chronic comorbid diseases, including cardiovascular disease, diabetes and hypertension. The present study analysed data from 20,296 subjects aged > or =45 yrs at baseline in the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS). The sample was stratified based on baseline lung function data, according to modified Global Initiative for Obstructive Lung Disease (GOLD) criteria. Comorbid disease at baseline and death and hospitalisations over a 5-yr follow-up were then searched for. Lung function impairment was found to be associated with more comorbid disease. In logistic regression models adjusting for age, sex, race, smoking, body mass index and education, subjects with GOLD stage 3 or 4 COPD had a higher prevalence of diabetes (odds ratio (OR) 1.5, 95% confidence interval (CI) 1.1-1.9), hypertension (OR 1.6, 95% CI 1.3-1.9) and cardiovascular disease (OR 2.4, 95% CI 1.9-3.0). Comorbid disease was associated with a higher risk of hospitalisation and mortality that was worse in people with impaired lung function. Lung function impairment is associated with a higher risk of comorbid disease, which contributes to a higher risk of adverse outcomes of mortality and hospitalisations.
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            Microalbuminuria as an early marker for cardiovascular disease.

            Excretion of albumin in the urine is highly variable, ranging from nondetectable quantities to milligrams of albumin and even grams of albumin. Microalbuminuria is defined as low levels of urinary albumin excretion of 30 to 300 mg/d. Microalbuminuria is highly prevalent; in hypertensive and diabetic populations, its prevalence varies from 10 to 40%. It is interesting that microalbuminuria also is found frequently in seemingly healthy individuals (5 to 7%). The variable excretion of albumin in the urine is related to the risk for the individual to develop cardiovascular (CV) disease: Absence or very low levels of albuminuria is associated with low CV risk, whereas the CV risk increases markedly with increasing amount of albumin in the urine (even within the now considered normal range). The predictive power of urinary albumin levels for CV risk is independent of other CV risk factors and not only is present in individual with diabetes and/or hypertension but also in healthy individuals. Treatments that lower albuminuria are associated with CV protection, as demonstrated in randomized, controlled trials of patients with diabetes as well as in patients with hypertension. There is preliminary evidence that albuminuria lowering is CV protective in healthy individuals with an elevated albumin excretion rate. Differences between individuals in their level of albumin excretion are already observed at a very early age (just after birth). In fact, the interindividual variability seems to be relatively constant in the first 5 decades of life, indicating that microalbuminuria is not necessarily a consequence of vascular damage at later age. Higher levels of urinary albumin seem to reflect the ordinary interindividual variability in (renal and systemic) endothelial function. Experimental data show that between strains and even within strains, rats at young age show a remarkable difference in individual endothelial function, and this is strongly related to the susceptibility of that rat to organ damage. In conclusion, albuminuria seems to be a sensitive marker very early in life for the susceptibility of an individual to CV disease. It therefore may be an ideal target for early primary prevention using CV-protective therapy regimens.
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              Inflammation, Atherosclerosis and Coronary Artery Disease

              Supplement Aims and Scope Research into inflammation, atherosclerosis and coronary artery disease, including observational studies, clinical trials, epidemiology, and advances in applied (translational) research. The supplement is intended to include overviews of new concepts in pathophysiology, natural history, diagnostic strategies, and treatment approaches. Articles should focus on vascular disease may include: ■ Diagnosis ■ Prognosis ■ Treatment ■ Screening ■ Prevention ■ Risk factor modification ■ Systematic reviews ■ Risk and safety of medical interventions ■ Epidemiology and statistical methods ■ Evidence-based medicine ■ Evaluation of guidelines ■ Translational medicine Article types include original clinical and basic research articles, case reports, commentaries, meeting reports, methodology, perspectives. Inflammation has been well recognized to play an important role in the development of atherosclerosis.1,2 Since chronic infection may lead to chronic systemic inflammation, many studies have investigated the associations between atherosclerotic diseases, such as coronary artery disease (CAD) and chronic infections by various microorganisms, including Chlamydia pneumoniae, cytomegalovirus, herpes simplex virus, and hepatitis C virus (HCV). However, these associations and precise mechanisms remain controversial. Several studies have suggested that more infectious pathogens, referred to as the infectious burden, rather than any single pathogen, may be involved in the development of atherosclerosis.3 In this supplementary issue of Clinical Medicine Insights: Cardiology, Ishizaka et al.4, reviewed the possible association between atherosclerosis and chronic HCV infection. In 2002, Ishizaka et al.5, first reported the higher prevalence of carotid artery plaques in HCV-positive patients than in control subjects, however, the findings of subsequent studies remain controversial, with some studies showing positive results and others negative. Regarding the associations between inflammatory biomarkers and atherosclerotic diseases, many studies have demonstrated that elevated high sensitivity C-reactive protein (hsCRP) levels, which are one of the biomarkers of systemic inflammation, are a powerful predictor of future cardiovascular events, such as myocardial infarction (MI) and cardiac death.6 However, hsCRP levels vary remarkably among different ethnic populations, and hsCRP levels in East Asian populations are much lower in comparison to those in Western populations.7 In this supplementary issue of Clinical Medicine Insights: Cardiology, Saito et al.8, reported a meta-analysis of 8 prospective studies regarding the association between hsCRP levels and atherosclerotic diseases in East Asians. They demonstrated that East Asians had low hsCRP levels and that, even in East Asians, elevated hsCRP levels were associated with an increased risk of stroke, especially ischemic stroke. Enomoto et al.9, also showed hsCRP levels to be associated with all-cause death in 1920 healthy Japanese subjects. In addition to hsCRP levels, some new inflammatory biomarkers related to both metabolic and atherosclerotic diseases have been reported. In this supplementary issue, Furuhashi et al.10, reviewed the association between atherosclerosis and fatty acid-binding protein 4 (FABP4), one of adipokines, that is mainly expressed in adipocytes and macrophages and may play an important role in the development of insulin resistance and atherosclerosis. Elevated FABP4 levels were reported to be associated with obesity, diabetes mellitus and atherosclerotic diseases.11,12 Notably, there is a male preponderance of death due to atherosclerotic diseases, especially CAD, at a younger age than women, thus suggesting that sex hormones may play a major role in the process of atherosclerotic diseases.13,14 Estrogen has anti-inflammatory effects, and such hormones may alter the immune response during the development of atherosclerosis, thereby leading to different disease processes between men and women. In this supplementary issue, Fairweather et al.15, reviewed sex differences in the inflammatory immune response during atherosclerosis. Moreover, sex hormones are suggested to affect the process of myocardial inflammation and remodeling during myocarditis. Systemic inflammatory responses are considered to play a major role in the destabilization of atherosclerotic plaques. The presence of inflammation in one artery is highly predictive of inflammation in other arteries.16 Imaging modalities are expected to noninvasively evaluate atherosclerotic plaques and inflammation within vessel walls. The glucose analogue 18F-FDG is taken up by metabolically active cells, especially macrophages, thus allowing the detection of inflammatory activity. Using this 18F-FDG tracer, positron emission tomography (PET) has become recognized as a reliable imaging technique for the detection of metabolic activity of atherosclerosis.17 Because the most important disadvantage is its limited spatial resolution, PET/computed tomography (CT) combines the excellent spatial resolution of CT with the high sensitivity of PET for the detection of inflammation. In this supplementary issue, Alie et al.18, reviewed the clinical usefulness of 18F-FDG-PET/CT for the noninvasive evaluation of atherosclerosis and inflammation in the carotid, coronary arteries and aortas. A modern lifestyle with high fat diet and lack of physical activity promotes atherosclerosis. Obesity and high fat diet have been shown to be associated with chronic inflammation in human adipose tissues and arteries.19 Oxidative modification of LDL is an essential mechanism that increases their inflammatory potential, and dietary antioxidants, such as vitamins C and E and polyphenols, are the potential nutrients leading to the prevention of LDL oxidation and atherosclerosis progression. The inverse associations between the consumption of vegetables, fruits and fish and atherosclerotic diseases have been reported in many epidemiological studies, showing a reduced risk of such diseases. However, there are still many unclear points regarding the contribution of these foods to the prevention of atherosclerosis. In this supplementary issue, Saita et al.20, reviewed the preventative effects of antioxidant foods on atherosclerosis and CAD. In addition to vegetables and fruits, antioxidant polyphenols are rich in beverages, such as wine and black and green tea. Recently, a meta-analysis showed green tea consumption to be associated with a reduced risk of CAD.21 Green tea, which is very rich in catechins, is the most popular beverage in Japan. In this supplementary issue, Ohmori et al.22, reported the association between green tea consumption and MI in 725 Japanese patients. Moreover, they demonstrated the inhibitory effect of LDL oxidation and the anti-inflammatory effect of green tea in 22 healthy volunteers. Inflammation is recognized to play an important role in both the initiation and progression of atherosclerotic diseases, such as CAD, however, the aim to prevent or treat atherosclerosis via modulating inflammation remains challenging. The articles in this supplementary issue of Clinical Medicine Insights: Cardiology encompass new research or timely reviews regarding inflammation, atherosclerosis and coronary artery disease. Lead Guest Editor Dr Yukihiko Momiyama Dr Yukihiko Momiyama is the Director of the Department of Cardiology at NHO Tokyo Medical Center in Tokyo. He received his MD from Keio University school of Medicine. He has previously worked at St. George’s Hospital Medical school in London and at the National Defense Medical College in Saitama. His research interests have focused on biomarkers, coronary artery disease, epidemiology, and MRI, especially plaque imaging. His previous studies have been published in a variety of peer-reviewed journals including Journal of the American College of Cardiology; Arteriosclerosis, Thrombosis, and Vascular Biology; Atherosclerosis, American Heart Journal, and American Journal of Cardiology. ymomiyamajp@yahoo.co.jp https://www.researchgate.net/profile/Yukihiko_Momiyama Guest Editors HISASHI ADACHI Dr. Hisashi Adachi is a Professor in the Department of Community Medicine, Kurume University, School of Medicine. He received his MD from Kurume University School of Medicine. He has previously worked at the University of Minnesota in the USA as a research fellow. His research interests have focused on novel risk factors, coronary artery disease, and epidemiology, and he is also interested in trends in nutritional intake shown in the Tanushimaru Study, one of the original cohorts of the Seven Countries Study. His previous studies have been published in a variety of peer-reviewed journals including Hypertension, Journal of Hypertension, American Journal of Hypertension, Atherosclerosis and others. hadac@med.kurume-u.ac.jp https://www.researchgate.net/profile/Hisashi_Adach DELISA FAIRWEATHER Dr. DeLisa Fairweather is an Associate Professor of Cardiovascular Diseases and Director of Translational Research at Mayo Clinic in Jacksonville, Florida. She also has an Adjunct appointment in the Department of Environmental Health Sciences at the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland. Dr. Fairweather was responsible for papers on inflammation, atherosclerosis and coronary artery disease. She completed her PhD at the University of Western Australia and conducted her Postdoctoral Fellowship with Dr. Noel R. Rose at Johns Hopkins University School of Medicine before joining the faculty at the Johns Hopkins Bloomberg School of Public Health. She now works primarily to understand how sex hormones and environmental co-exposures like infections and chemicals increase chronic inflammatory diseases like cardiovascular and autoimmune diseases. Dr. Fairweather has received funding from the national Institutes of Health, the American Heart Association, and industry. She has authored 70 manuscripts and book chapters and has given over 80 national and international presentations. Fairweather.DeLisa@mayo.edu http://mayoweb.mayo.edu/ NOBUKAZU ISHIZAKA Dr. Nobukazu Ishizaka is the Professor of the Faculty of Medicine at the Department of Cardiology, Osaka Medical College in Osaka. He received his MD from University Tokyo. He had previously worked at the Faculty of Medicine of University Tokyo in Tokyo. His previous studies have been published in a variety of peer-reviewed journals including Lancet, Circulation, Arterioscler Thromb Vasc Biol, Hypertension, Atherosclerosis, FEBS Lett, and Am Heart J. ishizaka@poh.osaka-med.ac.jp EMI SAITA Dr Emi Saita is a lecturer of Endowed Research Department “Food for Health” at Ochanomizu University, and was responsible for papers on Anti-inflammatory Diet for Atherosclerosis and Coronary Artery Disease: Antioxidant Foods. She completed her PhD at Ochanomizu University. She now works primarily in developing understanding of inhibitory effects of nutritional factors on atherosclerosis. Her previous studies have been published in a variety of peer-reviewed journals including J Oleo Sci, J Clin Biochem Nutr, and Eur J Nutr. saita.emi@ocha.ac.jp http://www.cf.ocha.ac.jp/food-health/index.html
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                9 April 2014
                : 9
                : 4
                : e94125
                Affiliations
                [1 ]The Institute for Occupational Health, Yonsei University College of Medicine, Seoul, Korea
                [2 ]Department of Preventive Medicine and Public Health, Yonsei University College of Medicine, Seoul, Korea
                [3 ]Graduate School of Public Health, Yonsei University College of Medicine, Seoul, Korea
                [4 ]Department of Occupational and Environmental Medicine, Dongguk University Ilsan Hospital, Goyang, Korea
                CUNY, United States of America
                Author notes

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

                Conceived and designed the experiments: JR JHY. Performed the experiments: JR. Analyzed the data: JHY YSA. Contributed reagents/materials/analysis tools: JHY JUW. Wrote the paper: JHY JUW YSA.

                Article
                PONE-D-14-03487
                10.1371/journal.pone.0094125
                3981770
                24718679
                81680e0e-3b11-4205-9b08-ef262da6ceb8
                Copyright @ 2014

                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
                : 23 January 2014
                : 12 March 2014
                Page count
                Pages: 8
                Funding
                The authors have no support or funding to report.
                Categories
                Research Article
                Medicine and Health Sciences
                Cardiology
                Epidemiology
                Cardiovascular Disease Epidemiology
                Environmental Epidemiology
                Nephrology
                Chronic Kidney Disease
                Pulmonology
                Vascular Medicine
                Atherosclerosis

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                Uncategorized

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