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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 9  |  Issue : 2  |  Page : 65-70

Microalbuminuria and serum CRP: potential biomarkers for cardiovascular risk among stable COPD


Department of Respiratory Medicine, Institute of Respiratory Diseases, SMS Medical College, Jaipur, India

Date of Submission01-Jul-2019
Date of Acceptance01-Jun-2020
Date of Web Publication4-Aug-2021

Correspondence Address:
Dr. Ajith Kumar M S
Department of Respiratory Medicine, Institute of Respiratory Diseases, SMS Medical College, Room no-205, H. no-71/1, Cozy homes, Jhakareshwar Marg, Bani Park, Jaipur-302016
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jacp.jacp_2_21

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  Abstract 


Background: Cardiovascular disease is one of the major causes of mortality in chronic obstructive pulmonary disease (COPD) patients. Both microalbuminuria (MAB) and raised serum C-reactive protein (CRP) levels have strong association with cardiovascular events as they reflect generalized endothelial vascular dysfunction. The objectives of the study are (i) to assess the prevalence of MAB and serum CRP levels in stable COPD patients and (ii) to find out the relationship of MAB and serum CRP with clinical and physiological parameters in COPD patients. Methods: This comparative cross-sectional study was carried out on COPD patients attending OPD at Institute of Respiratory Diseases, Jaipur during the year from 2019 to 2020. Forty stable COPD patients and 40 healthy controls were enrolled in the study. Spot urinary albumin/creatinine ratio, serum CRP levels, smoking history, spirometry, blood gases, body mass index, and BMI, Obstruction (FEV1% predicted), Dyspnea (mMRC grading), Exercise Capacity (6 MWD) (BODE) index were assessed. Results: Out of 40 cases, 23(56%) had MAB and 38 (95%) had serum CRP levels >3 mg/L. There was a negative correlation between forced expiratory volume in one second (FEV1), partial pressure of oxygen in arterial blood (PaO2) levels and 6 MWD with both MAB levels and S.CRP levels respectively. There was a positive correlation between BODE Index and modified British Medical Research Council grading with both MAB levels and serum C reactive protein (S.CRP) levels respectively. There was a positive correlation between BODE index and modified British Medical Research Council grading with both MAB and S.CRP levels. Conclusion: COPD patients of varying severity should be screened regularly with MAB and serum CRP levels to determine the risk and progression of cardiovascular consequences so that adequate decision of interventional strategies can be taken out to prolong survival in COPD patients.

Keywords: Cardiovascular events, chronic obstructive pulmonary disease, C-reactive protein, microalbuminuria


How to cite this article:
Kumar M S A, Gaur JK, SP A. Microalbuminuria and serum CRP: potential biomarkers for cardiovascular risk among stable COPD. J Assoc Chest Physicians 2021;9:65-70

How to cite this URL:
Kumar M S A, Gaur JK, SP A. Microalbuminuria and serum CRP: potential biomarkers for cardiovascular risk among stable COPD. J Assoc Chest Physicians [serial online] 2021 [cited 2021 Dec 1];9:65-70. Available from: https://www.jacpjournal.org/text.asp?2021/9/2/65/323088




  Introduction Top


Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the world but is expected to be the third leading cause of death by 2020.[1] The pathological mechanisms and clinical manifestations of COPD are not only restricted to pulmonary inflammation and airway remodeling, but also over the last decade it has been increasingly recognized as a systemic disease.[2] The best recognized systemic manifestations of COPD include systemic inflammation, cardiovascular comorbidities, cachexia, muscle dysfunction, osteoporosis, anemia, depression, and anxiety.

Cardiovascular disease is a major cause of mortality in COPD, particularly in patients with mild to moderate severity.[3] Cardiovascular conditions that have been reported to occur with a greater frequency in patients with COPD are coronary artery disease, heart failure, peripheral vascular disease, and arrhythmias. The discovery of novel biomarkers helps identify the cardiovascular risk in patients with COPD. Ideally, the biomarker should be inexpensive, noninvasive, and easily assessable. Microalbuminuria (MAB) and serum CRP (C-reactive protein) are such biomarkers. Both have been associated with an increased risk of adverse cardiovascular events such as congestive heart failure, acute coronary syndrome, myocardial infarction, stroke, and so on because of their proatherogenic property.

MAB is a sensitive marker of cardiovascular risk.[4] In COPD, hypoxia induces endothelial cells to release a number of different vasoactive agents including endothelin-1, platelet derived growth factor (PDGF), and nitric oxide that cause endothelial injury and lead to MAB. Serum CRP is another biomarker of cardiovascular risk that is synthesized in liver in response to a number of stimuli involving tissue damage. CRP levels of 1 mg/l, 1 to 3 mg/l and > 3 mg/l are associated with lower, moderate and higher cardiovascular risks respectively. In COPD patients, CRP levels are reported to be associated with increased cardiovascular morbidity. A limited number of studies have investigated the presence of both MAB and serum CRP levels among COPD patients. In the present study, we aimed to investigate an association between MAB and serum CRP levels with clinical and physiological parameters in COPD patients apart from assessing the prevalence of MAB and serum CRP levels in stable COPD patients.


  Materials and methods Top


The present study consisted of 40 stable COPD patients and 40 healthy controls of either sex, aged between 40 to 80 years, who attended the outpatient department of the Respiratory Medicine, IRD, SMS Medical College, Jaipur from July 2019 to June 2020. Both COPD patients and healthy controls for this study were randomly selected.

Patients were excluded based on the following criteria: (i) preexisting renal disease, (ii) acute exacerbation of COPD, (iii) presence of macroalbuminuria [urine albumin creatinine ratio (UACR) >300 mg/g], (iv) diabetes mellitus, (v) cardiovascular disease, (vi) other respiratory diseases such as asthma, interstitial lung diseases, acute lung infections, lung malignancy, and (vii) urinary tract infections. The control group consisted of apparently healthy volunteers with normal spirometry. Approval of the Institutional Ethical Committee was taken prior to the study.

Patients were examined clinically and radiologically to establish the diagnosis of COPD as per Global initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. Routine blood investigations, serum protein, serum albumin and urine microscopy, chest X-ray, spirometry, electrocardiogram, 6-minute walk distance (6MWD), and arterial blood gas analysis were done in all the participants. Body mass index (BMI) was calculated by measuring weight and height. Exercise capacity was assessed by 6MWD test according to American Thoracic Society guidelines.[5] Dyspnea was assessed based on modified British Medical Research Council (mMRC) dyspnea scale.[6] The multidimensional BMI, Obstruction (FEV1% predicted), Dyspnea (mMRC grading), Exercise Capacity (6 MWD) (BODE) (BMI, airflow obstruction, dyspnea, and exercise) index was calculated.

Laboratory methods

The microalbumin (MALB) detection method is an in vitro diagnostic test based on a particle enhanced turbidimetric inhibition immunoassay that allows direct quantitation of albumin in urine samples. MALB Flex reagent cartridge contains a particle reagent consisting of synthetic particles with human albumin bound to surface and aggregates of these particles are formed when a monoclonal antibody (Ab) to human albumin is introduced. Albumin present in sample competes with particle for antibody, thereby decreasing the rate of aggregation. Hence, the rate of aggregation is inversely proportional to the concentration of albumin present in the sample, and the rate of aggregation was measured using bichromatic turbidimetric reading at 340 and 700 nm. Creatinine levels were determined by Jaffe method and were adjusted for sex and race using published formulae.

Urinary albumin/creatinine ratio was defined as [urine albumin (mg)]/k [urine creatinine (g)], where k represents a sex- and race-dependent correction factor. Presence of MAB was defined as UACR between 20 and 299 mg/g in men and 30 and 299 mg/g in women.[7]

Measurement of serum C-reactive protein levels

Venous blood samples (5 mL) were collected from all patients and healthy controls and centrifuged to analyze levels of CRP in serum. The obtained serum was kept at −80°C until time of the analysis. CRP level was assessed in serum by Elisa method according to manufacturer’s protocol.

Statistical analysis

Correlation of different parameters of severity of COPD, like forced expiratory volume in one second (FEV1%), BODE index, mMRC dyspnea grading, 6MWD and partial pressure of oxygen in arterial blood (PaO2) values with UACR (microalbumin) and Serum CRP levels were carried out using Spearman correlation analysis on Statistical Package for Social Sciences version 16.0 software. One-way analysis of variance (ANOVA) was used to compare the mean values of >2 subgroups. P < 0.05 was considered statistically significant in all analyses.


  Results Top


Out of 40 cases, 35 were males. Majority of cases (26) were seen over 50 years age contributing to 65% of the patients in case group. Out of 40 controls, 36 were males.

Our study showed MAB was present in 23 (57.5%) cases out of 40 in cases group, while in controls it was in four (10%) only. This association was statistically significant between two groups in our study. In our study, abnormal CRP levels (>3 mg/L) are seen more in case group than control group, contributing to 95% and 15% cases in case and control groups, respectively, which was statistically significant.

[Table 1] gives the comparison of mean value of PaO2, PaCO2, FEV1% predicted, FEV1/FVC (forced vital capacity) ratio, BODE index, 6MWD (meter), UACR (mg/g), and serum CRP levels, which were statistically significant, whereas the mean value of PaCO2 was statistically not significant.
Table 1 Comparison of cases with COPD and controls

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[Table 2] shows the distribution of MAB with severity of COPD. Majority of the cases had MAB in severe and very severe COPD subgroups contributing to 71.4% cases among case group.
Table 2 Distribution of MAB with severity of COPD (GOLD criteria) in cases

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[Table 3] depicts that abnormal serum CRP level (>3 mg/L) was present in all the cases in moderate, severe, and very severe COPD groups.
Table 3 Serum CRP levels (>3 mg/L) with severity of COPD

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[Table 4] shows that a majority of cases (19) were seen with FEV1 from 50% to 80% subgroup, out of which eight had MAB with two (10.5%) in the range from 51 to 100 mg/g, four (21.0%) in the range from 101 to 150 mg/g, and two (10.5%) in the range from 151 to 200 mg/g. Similarly, 25 cases were seen with BODE index 0-3 subgroup, out of which 12 had MAB with two (8%) in the range from 51 to 100 mg/g, five (20%) in the range from 101 to 150 mg/g, and five (20%) in the range from 151 to 200 mg/g. Likewise 14 cases were seen in PaO2 levels between 61 and 70 mmHg subgroup, out of which all 14 had MAB with four (28.57%) in the range from 101 to 150 mg/g, eight (57.14%) in the range from 151 to 200 mg/g, and two (14.2%) in the range from 201 to 300 mg/g. In the same manner, 21 cases were seen in dyspnea grade 2 mMRC subgroup, out of which 11 had MAB with two (9.5%) in the range from 51 to 100 mg/g, four (19.04%) in range from 101 to 150 mg/g, and five (23.80%) in the range from 151 to 200 mg/g. Similarly, 19 cases were seen in 6MWD of >500 m subgroup, out of which eight had MAB with two (10.5%) in the range from 51 to 100 mg/g, four (21.05%) had it between 101 and 150 mg/g, and two (10.5%) had in range between 151 and 200 mg/g. There was a negative correlation between FEV1%, PaO2 levels, and 6MWD with MAB levels, and there was a positive correlation between BODE index and mMRC grading with MAB levels among the 40 cases. The difference in mean MAB levels on one-way ANOVA among subgroups of cases with FEV1 (50–80%, 30–50%, and <30%), BODE index (0–3, 4–6, and 7–10), PaO2 (>80 mmHg, 71–80 mmHg, 61–70 mmHg, and 51–60 mmHg), mMRC (grade 2, grade 3, and grade 4), 6MWD (>500 m, 401–500 m, 301–400 m, and 201–300 m) were statistically significant.
Table 4 Association of MAB with FEV1, BODE index, PaO2, mMRC grade, and 6MWD

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[Table 5] shows that majority of cases (19) were seen with FEV1 between 50% and 80% subgroup, out of which 17(89.5%) had abnormal CRP levels. Similarly, 25 cases were seen with BODE index 0-3 subgroup, out of which 23 (92%) had abnormal CRP levels. Likewise 14 cases were seen in PaO2 levels between 61 and 70 mmHg subgroup, out of which all 12 (85.7%) had abnormal CRP levels. In the same manner, 21 cases were seen in dyspnea grade 2 mMRC subgroup, out of which all 21 (100%) had abnormal CRP levels. Similarly, 19 cases were seen in 6MWD of >500 m subgroup, out of which 17 (89.47%) had abnormal CRP levels. There was a negative correlation between FEV1%, PaO2 levels, and 6MWD with serum CRP levels and there was a positive correlation between BODE index and mMRC grading with serum CRP levels among the 40 cases. The differences in mean serum CRP levels on one-way ANOVA among subgroups of cases with FEV1 (50–80%, 30–50%, and <30%), BODE index (0–3, 4–6, and 7–10), PaO2 (>80 mmHg, 71–80 mmHg, 61–70 mmHg, and 51–60 mmHg), mMRC (grade 2, grade 3, and grade 4), 6MWD (>500 m, 401–500 m, 301–400 m, and 201–300 m) were statistically significant.
Table 5 Association of serum CRP with FEV1, BODE index, PaO2, mMRC grade, and 6MWD

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  Discussion Top


COPD is a multicomponent disease in which structural and functional changes are seen in the lungs and extrapulmonary organs. Many different inflammatory markers appear to be increased in the serum of stable COPD patients. Both MAB and serum CRP are sensitive markers of cardiovascular risk and has a stronger association with cardiovascular events and death.

Our study showed that the comparison of the mean value of SPO2, PaO2, UACR (mg/g), CRP (mg/l), 6MWD (meter), BODE index, FEV1% predicted, and FEV1/FVC ratio was statistically significant and was comparable to the study by Kumar et al.[8].

Our study showed that the prevalence of MAB in COPD cases was around 56%, which was quite higher compared to 24% reported by Casanova et al.[9] Bulcun et al.[10] and Sahay and Prasad[11] found MAB prevalence of 39% and 38.27%, respectively, in COPD cases in their studies.

Majority of the COPD cases with prevalence of MAB in our study were from severe and very severe COPD subgroups (71.4%), which was similar to study done by Sahay and Prasad,[11] who reported severe and very severe COPD cases in 51.62% and 22.58% MAB prevalence, respectively.

Our study showed a negative correlation between FEV1%, 6MWD, PaO2, and MAB levels among the 40 cases, which was similar to study done by Kumar et al.,[8] who reported a significant inverse relationship between UACR and PaO2, FEV1%, and 6MWD. Similarly, Casanova et al.[9], Kömürcüoğlu et al.,[12] Mehmood and Sofi[13] reported a negative correlation between PaO2 and MAB levels in their respective studies.Our study showed a positive correlation between MAB levels with BODE index and mMRC grading, which was similar to the study by Kumar et al.,[8] who reported a positive relationship between UACR and BODE index and mMRC grading.

Our study showed that the prevalence of abnormal serum CRP (>3 mg/L) was 95%, which was quite higher compared to the study done by Silva et al.,[14] who reported 56.7%.

Majority of COPD cases showed that the prevalence of abnormal serum CRP in our study were from moderate, severe, and very severe COPD (100%) cases, which was similar to the study by Silva et al.[15]

There was a negative correlation between FEV1% (r = –0.7313), PaO2 (r = –0.2872), 6MWD (r = –0.701), and CRP levels among the 40 cases, and there was a positive correlation between BODE index (r = 0.8091), mMRC grading (r = 0.5402), and CRP levels among the 40 cases. We compared our study of serum CRP with disease severity with the following studies: Pinto-Plata et al.[15] reported that 6MWD, age, and BMI significantly predicted CRP levels in cases with COPD. Most important clinically relevant predictor was 6MWD, which decreased with increasing CRP.

De Torres et al found that CRP levels are elevated in clinically stable COPD cases and that CRP levels correlate best with arterial oxygen tension and 6MWD and also there were no differences in CRP levels between those with cardiovascular risk factors or disease and those without them.


  Conclusion Top


COPD patients should be screened regularly with MAB and serum CRP levels to determine the risk of/and progression of cardiovascular morbidity and mortality so that adequate decision of interventional strategies can be taken to prolong the survival.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Barnes PJ, Celli BR. Systemic manifestations and comorbidities of COPD. Eur Respir J 2009;33:1165-85.  Back to cited text no. 2
    
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Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW et al. TORCH investigators. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med 2007;356:775-89.  Back to cited text no. 3
    
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Diercks GF, Van Boven AJ, Hillege JL, de Jong PE, Rouleau JL, van Gilst WH. The importance of microalbuminuria as a cardiovascular risk indicator: a review. Can J Cardiol 2002;18:525-35.  Back to cited text no. 4
    
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American Thoracic Society. ATS statement: guidelines for six-minute walk test. Am J Respir Crit Care Med 2002;166:111-7.  Back to cited text no. 5
    
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Bestall JC, Paul EA, Garrod R, Garnham R, Jones PW, Wedzicha JA. Usefulness of Medical Research Council (MRC) dyspnoea scale as a measure of disability in patients with chronic obstructive pulmonary disease. Thorax 1999;54:581-6.  Back to cited text no. 6
    
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De Jong PE, Curhan GC. Screening, monitoring and treatment of albuminuria: public health perspectives. J Am Soc Nephrol 2006;17:2120-6.  Back to cited text no. 7
    
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Kumar A, Verma SK, Mehrotra A, Kumar A, Chaudhri S, Verma CM, Prasad R, Surya Kant. A study on microalbuminuria in patients with chronic obstructive pulmonary disease at a tertiary care centre in North India. Indian J Chest Dis Allied Sci 2017;59:17-21.  Back to cited text no. 8
    
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Casanova C, de Torres JP, Navarro J, Aguirre-Jaime A, Toledo P. Microalbuminuria and hypoxemia in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2010;182:1004-10.  Back to cited text no. 9
    
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Bulcun E, Mehmet E, Aydanur E, Ucler K. Microalbuminuria in chronic obstructive pulmonary disease. COPD 2013;10:186-92.  Back to cited text no. 10
    
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Sahay S, Prasad MK. Microalbuminuria and COPD: A Clinical and Physiological Association. Int J Med Res Prof 2018;4:270-2.  Back to cited text no. 11
    
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Komurcuoglu A, Kalenci S, Kalenci D, Komurcuoglu B, Tibet G. Microalbuminuria in chronic obstructive pulmonary disease. Monaldi Arch Chest Dis 2003;59:269-72.  Back to cited text no. 12
    
13.
Mehmood K, Sofi FA. Microalbuminuria and hypoxemia in patients with COPD. J Pulm Respir Med 2015;5:280.  Back to cited text no. 13
    
14.
Silva DR, Gazzana MB, Knorst MM. C-reactive protein levels in stable COPD patients: a case-control study. Int J Chron Obstruct Pulmon Dis 2015;10:1719-25.  Back to cited text no. 14
    
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Pinto-Plata VM, Mullerova H, Toso JF. C-reactive protein in patients with COPD, control smokers and nonsmokers. Thorax 2006;61:23-8.  Back to cited text no. 15
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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