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ORIGINAL ARTICLE
Year : 2020  |  Volume : 23  |  Issue : 4  |  Page : 450-455

Could monocyte level/HDL cholesterol ratio predict cardiovascular diseases in patients with COPD?


Department of Pulmonology, Faculty of Medicine, Tokat Gaziosmanpasa University, Tokat, Turkey

Date of Submission27-Jan-2019
Date of Acceptance26-Dec-2019
Date of Web Publication4-Apr-2020

Correspondence Address:
Dr. H I Yakar
Department of Pulmonology, Faculty of Medicine, Tokat Gaziosmanpasa University, Tokat
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/njcp.njcp_54_19

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   Abstract 


Objective: The role of monocytes and high-density lipoprotein (HDL) levels in the pathophysiology of cardiovascular disease (CVD) is well known. However, the relationship between monocytes to HDL-cholesterol ratio (MHR) and CVD in chronic obstructive pulmonary disease (COPD) patients has not been investigated previously. We, therefore, aimed to investigate the predictor role of MHR in the development of CVD in subjects with COPD. Methods: 185 COPD patients and 89 control subjects were enrolled. Demographic data and laboratory parameters were recorded and MHR was calculated for all participants. CVDs were defined if hypertension, ischemic heart disease, congestive heart failure, or stroke present. MHR levels were compared between the two groups in terms of CVD. Receiver operating characteristic analysis was used to determine the MHR cutoff value that predicts CVD in COPD patients. Results: We found positive correlation between MHR and COPD (r = 0.24, P = 0.001). However, there was no statically significant association between MHR and severity of COPD defined by the Global Initiative for Chronic Obstructive Lung Disease criteria (P = 0.78). MHR was significantly higher in COPD patients with CVD compared to without CVD (P = 0.007). In subgroups' analysis, COPD patients with CVD, MHR was significantly higher in COPD patients with ischemic heart diseases (P < 0001). Similarly, MHR was higher in subjects with CVD compared to the subjects without CVD, but it was not statistically significant (P = 0.68). In the ROC analysis, the MHR cutoff value that predicts CVD in COPD patients was found to be 12.50 (sensitivity of 64.9% and specificity of 65.4%) (area under the receiver operating characteristic curve [AUC] = 0.73, P = 0.001). Conclusion: MHR is significantly associated with CVD in COPD patients. Further prospective studies are warranted to elucidate the predictive value of MHR in COPD patients.

Keywords: Cardiovascular diseases, chronic obstructive pulmonary disease, monocyte/HDL ratio


How to cite this article:
Yakar H I, Kanbay A. Could monocyte level/HDL cholesterol ratio predict cardiovascular diseases in patients with COPD?. Niger J Clin Pract 2020;23:450-5

How to cite this URL:
Yakar H I, Kanbay A. Could monocyte level/HDL cholesterol ratio predict cardiovascular diseases in patients with COPD?. Niger J Clin Pract [serial online] 2020 [cited 2020 Sep 28];23:450-5. Available from: http://www.njcponline.com/text.asp?2020/23/4/450/281930




   Introduction Top


Chronic obstructive pulmonary disease (COPD) is a systemic disease characterized by persistent respiratory symptoms and airflow limitation that is usually associated with inflammation resulting from significant exposure to harmful particles or gases.[1] Chronic inflammation causes comorbidities such as osteoporosis and diabetes mellitus.[2],[3] The cells involved in chronic inflammation are inflammatory cells such as monocytes, macrophages, neutrophils, and T lymphocytes in the lung and the blood.

Monocytes and macrophages circulate in the blood, bone marrow, and spleen. They are active members of inflammation in systemic diseases and play an important role in the pathophysiology of COPD.[4] They produce inflammatory mediators, proteases, and they are found to be increased in the airways, lung parenchyma, and bronchoalveolar lavage fluid.[5]

High-density lipoprotein cholesterol (HDL-C) has also an indirect role in inflammation. HDL-C molecules counteract the migration of macrophages and promote the efflux of cholesterol from these cells. In an experimental study, it has been shown that HDL-C exhibits an anti-inflammatory effect on human monocytes by inhibiting activation of CD11b.[6] HDL-C levels were also shown to be lower in smokers and in those having a sedentary lifestyle.[7],[8],[9],[10] In COPD patients, the HDL-C level is thought to be lower than healthy humans due to smoking history and having a sedentary lifestyle.

The ratio of monocytes to HDL-C-cholesterol (MHR) is considered to be a strong indicator of inflammation as monocytes play a role in inflammation and HDL cholesterol has also an anti-inflammatory role.[11],[12] Thus, it is believed to be used to predict systemic diseases.

There are many studies showing that MHR predicts cardiovascular disease (CVD) in various patient groups.[13],[14],[15] Nevertheless, the relationship between COPD and MHR has not been addressed previously. In addition, the effect of MHR in predicting CVD in COPD patients has not been investigated previously. With this background in mind, we aimed to investigate the significance of MHR for predicting CVD in COPD patients and to compare the MHR according to the severity of COPD defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria and healthy control subjects.


   Methods Top


In this prospective cohort study, patients with COPD who were admitted to Istanbul Medeniyet University (IMU) Goztepe Training and Research Hospital Chest Diseases outpatient clinic between July 2017 and December 2017 and healthy control group were included. Local ethics committee approval was obtained from the clinical research ethics committee of the IMU Goztepe Training and Research Hospital (protocol no. 2017/0163, 20.06.2017) prior to the study. Written informed consent was obtained from all subjects before enrollment.

According to the GOLD 2017 criteria; the patients over 40 years of age, had >10 years of smoking history or biomass history or occupational exposure and diagnosed with COPD were included in the COPD group. COPD patients were divided into ABCD groups according to the GOLD 2017 report. Volunteers who were admitted to the outpatient clinic with nonspecific symptoms and who had no known pulmonary disease were included in the healthy control group.

Patients with a structural disease (bronchiectasis, KF, etc.), COPD exacerbation in the last month, acute infection, any hematological diseases, hyperlipidemia or on lipid-lowering treatment and patients who did not want to participate were not included in the study. CVDs were defined if hypertension, ischemic heart disease, congestive heart failure, or stroke were present.

Baseline characteristics and laboratory parameters regarding age, gender, smoking history (pack/year), body mass index (BMI), pulmonary function test, comorbidities, whole blood count, C-reactive protein (CRP), monocyte, HDL-C, low-density lipoprotein cholesterol (LDL-C), triglyceride, and total cholesterol levels were recorded. The monocyte level was calculated by measuring in the routine hemogram with the Pentra 120 Retic Hematology Analyzer (ABX, France). In our laboratory, the monocyte reference range is 2–10%. MHR was calculated by dividing the monocyte level into the HDL-C level. The study population was divided into COPD and control groups.

Statistical analyses

The Kolmogorov-Smirnov test was used to test the distribution model of the variables. Parametric data were presented as mean ± standard deviation (SD). The comparison of multiple mean values was performed using variance analysis (ANOVA). Categorical variables were summarized as the percentage and were compared using Chi-square tests. Pearson's correlation coefficient was calculated to analyze the relationship between MHR and COPD. Receiver operating characteristic (ROC) analysis was used to determine the MHR cutoff value that predicts CVD in COPD patients. Statistical analyses were performed using SPSS version 20.0 (SPSS, Inc. Chicago, Illinois). A P value of <0.05 was considered statistically significant.


   Results Top


The study consisted of 185 patients (162 men (87.5%), mean age = 60.4 ± 8.2 years) who were diagnosed with COPD and 89 control group (55 men (61.7%), mean age = 56.7 ± 9.7 years). The demographic and clinical characteristics of the study groups are shown in [Table 1]. BMI was similar in both groups (P = 0.86). 53% of COPD patients and 28% of the control group were smoking. The rates of the active smoker and ex-smoker patients were similar [Table 1]. 27 (14.6%) of those had occupational exposure and 18 (9.7%) of those had biomass exposure. The rates of CVD were similar in both groups (P = 0.08) [Table 1]. The pulmonary function test findings were significantly higher in the control group as expected [Table 1].
Table 1: Demographic and clinical characteristics of the study groups

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Hematologic and biochemical parameters (leukocyte, monocyte, hemoglobin, C-reactive protein, total cholesterol, triglyceride, LDL-C, and HDL-C) were similar in both groups [Table 2] meanwhile MHR was statistically higher in COPD patients than the control group (P < 0.001). Correlation analysis revealed a significant positive correlation between MHR and COPD (r = 0.24, P = 0.001). However, the relationship between MHR and COPD stage by GOLD subgroups were not reached statically significance (f = 0.35, P = 0.78) [Figure 1]a.
Table 2: Biochemical parameters

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Figure 1: (a) Association between MHR and GOLD stages (groups). Notes: Control group (n = 89), GOLD stage 1 (A) (n = 98), GOLD stage 2 (B) (n = 57), GOLD stage 3 (C) (n = 9), GOLD stage 4 (D) (n = 21). Data analyzed with one-way analysis of variance with Tukey post hoc test (F = 0.35, P = 0.78). Error bars represent 95% CIs. Abbreviations: GOLD: Global Obstructive Lung Disease, MHR: monocyte high-density lipoprotein (HDL) ratio. (b) MHR was significantly higher in patients with cardiovascular diseases (CVD) (+) chronic obstructive pulmonary disease (COPD) patients (n = 76) than patients with CVD (-) COPD (n = 109) (16.4 ± 4.2, 12.7 ± 4.9, P = 0.007, respectively). In the control group, CVD (+) patients (n = 23) had higher MHR than CVD (-) patients (n = 66), but not statistically significant (10.7 ± 2.6, 9.3 ± 2.5, P = 0.68, respectively)

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MHR was significantly higher in COPD patients with CVD than those without CVD (16.4 ± 4.2, 12.7 ± 4.9, respectively, P = 0.007) [Figure 1]b. Furthermore, when we divided CVDs into subgroups, MHR was significantly higher in patients with ischemic heart disease (P < 0.001) [Table 3]. MHR was also higher in the control group with CVD than those without CVD, but not reached statistical significance (10.7 ± 2.6, 9.3 ± 2.5, respectively, P = 0.68) [Figure 1]b.
Table 3: MHR levels in COPD patients according to cardiovascular diseases

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In the ROC analysis, the MHR cut-off value that predicts CVD in COPD patients was found to be 12.50 (sensitivity of 64.9% and specificity of 65.4%) (area under the ROC [AUC] =0.73, 95% CI: 0.63-0.84, P < 0.001) [Figure 2].
Figure 2: In receiver operating characteristic (ROC) analysis, the MHR cutoff value that predicts CVD in COPD patients was 12.50 (% 64.9 sensitivity and % 65.4 specificity) (AUC = 0.73, 95% CI: 0.63–0.84, P < 0.001)

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   Discussion Top


In the present study, we showed that MHR is high in COPD patients and there is a significant association between MHR and CVD in COPD patients for the first time in the literature. In light of our study, MHR might be used as a new predictive marker for CVD in COPD patients.

In the literature, BMI is lower in COPD patients than in the control group due to systemic inflammation in COPD.[16],[17] In this study, the mean BMI of the patients was similar in both groups (P = 0.86). The similarity of BMI in both groups was thought to be important for the accurate assessment of MHR between COPD and the control group since obesity may affect the HDL-C level.

In previous studies, the rate of smoking in COPD was 70–90%.[18],[19] However, nearly half of the COPD group had a smoking history in this study. It was considered that this ratio was lower than previous studies because of high exposure to nonsmoking risk factors (biomass, occupational exposure). Although the smoking history and age were known in the control group compared to the COPD group, the percent of CVD was similar in both groups. The similarity of CVD in both groups is important for the accurate assessment of MHR between COPD and the control group since CVD may affect the MHR level.

Previous studies have shown that HDL-C plays a protective role in the lung.[20] However, it has also been revealed that dysfunctional HDL-C plays a role in lung diseases.[21] HDL levels were also shown to be lower in smokers and in those having a sedentary lifestyle.[7],[8],[9],[10] We believed that HDL-C levels are lower in COPD patients due to smoking history and a sedentary lifestyle. In this study, as expected, HDL-C levels were lower in COPD patients but not statistically significant (P = 0.73) [Table 2].

There are many studies in the literature about the effects of MHR on systemic diseases. Kanbay et al. have investigated the relationship between MHR and cardiovascular events in patients with chronic renal failure (CRF).[13] In that study, patients were divided into three groups according to MHR and cardiovascular events were found to be more common in the highest group of MHR. Cetin et al. have evaluated the relationship between coronary artery disease and MHR.[14] The patients were divided into three groups by MHR, and cardiovascular events were found to be more common in the third group of patients who have more severe coronary artery disease. In the other study, Bolayir et al. showed that MHR may be used in predicting mortality in patients with cerebral ischemic stroke.[15] In another study, MHR was found to be associated with cardiac syndrome X, and MHR was shown to predict the presence of CVD with a sensitivity of 78% and a specificity of 70% in one study.[22] In another study, Gunay et al. have investigated that atherogenic indices (including an atherogenic index of plasma, cardiogenic risk ratio, and atherogenic coefficient) could be considered to predict susceptibility to CVD in subjects with COPD.[23] According to the results of our study, we speculate that MHR may be used in predicting CVD in patients with COPD. It is not surprising to us; ischemic heart disease had significantly high MHR in COPD patients with CVD.

In this study, it was found to predict the CVD in COPD patients with a sensitivity of 64.9% and a specificity of 65.4%. (AUC = 0.73, 95% CI: 0.63–0.84, P < 0.001) [Figure 2].

In the study of Gunay et al., it was found triglyceride, atherogenic index of plasma, cardiogenic risk ratio, and atherogenic coefficient values were significantly higher in subjects with stable COPD than in control subjects.[23] Similarly, in our study, a significant relationship was found between MHR and COPD. MHR was significantly higher in patients with COPD than the control group (P < 0.001). The reason for the relationship between COPD and MHR could be a common pathological pathway. Systemic inflammatory response and its chronicity are a common reason for the development of these chronic diseases.[24] Increased level of inflammatory cytokines has been investigated in the development of both COPD and CVD. Moreover, the relationship between reduced pulmonary function and carotid intima-media thickness is associated with atherosclerotic changes in subjects with COPD.[24] Thus, these pathways might explain the development of concomitant CVD and COPD diseases.[24],[25]

When we grouped COPD patients according to GOLD criteria, it was found to be higher in group B than group A, in group D than group C, but there was no statistically significant difference. The reason why there is no relationship between GOLD groups and MHR in COPD may be the absence of a linear relationship between the ABCD stages and the severity of inflammation. In addition, the categorization reduces the power of the analysis. If we could enroll more patients in group C and D, we could find more significance between GOLD groups.

In conclusion, MHR is a minimally invasive and easily measurable method because the monocyte level and HDL-C level could be measured in routine blood tests. In this study, we showed that MHR is significantly higher in COPD patients than the control group and significantly higher in COPD patients with CVD than COPD patients without CVD. This study is important because there is no other study in the literature that evaluates the relationship between CVD and MHR in COPD patients. However, further prospective studies with larger sample sizes are required to confirm and explore these results in COPD.

Declaration of patient consent

All participants provided written informed consent prior to participation.

Competing interests

The authors declare that they have no competing interests.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Kocabaş A, Atış S, Çöplü L, Erdinç E, Ergan B, Gürgün A, et al. Kronik obstrüktif akciǧer hastalıǧı, koruma, tanı ve tedavi raporu. Turk Thorac J 2014;15(Ek 2).  Back to cited text no. 1
    
2.
Pickup JC. Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. Diabetes Care 2004;27:813-23.  Back to cited text no. 2
    
3.
Manolagas SC. Birth and death of bone cells: Basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev 2000;21:115-37.  Back to cited text no. 3
    
4.
Auffray C, Sieweke MH, Geissmann F. Blood monocytes: Development, heterogeneity, and relationship with dendritic cells. Annu Rev Immunol 2009;27:669-92.  Back to cited text no. 4
    
5.
MacNee W. Pathology, pathogenesis, and pathophysiology. Br Med J 2006;332:1202-4.  Back to cited text no. 5
    
6.
Murphy AJ, Woollard KJ, Hoang A, Mukhamedova N, Stirzaker RA, McCormick SP, et al. High-density lipoprotein reduces the human monocyte inflammatory response. Arterioscler Thromb Vasc Biol 2008;28:2071-7.  Back to cited text no. 6
    
7.
Takata K, Imaizumi S, Kawachi E, Suematsu Y, Shimizu T, Abe S, et al. Impact of cigarette smoking cessation on high-density lipoprotein functionality. Circ J 2014;78:2955-62.  Back to cited text no. 7
    
8.
He BM, Zhao SP, Peng ZY. Effects of cigarette smoking on HDL quantity and function: Implications for atherosclerosis. J Cell Biochem 2013;114:2431-6.  Back to cited text no. 8
    
9.
Vaisberg M, Bachi AL, Latrilha C, Dioguardi GS, Bydlowski SP, Maranhão RC. Lipid transfer to HDL is higher in marathon runners than in sedentary subjects, but is acutely inhibited during the run. Lipids 2012;47:679-86.  Back to cited text no. 9
    
10.
Pollock RD, Duggal NA, Lazarus NR, Lord JM, Harridge SDR. Cardiorespiratory fitness not sedentary time or physical activity is associated with cardiometabolic risk in active older adults. Scand J Med Sci Sports 2018. doi: 10.1111/sms. 13071.  Back to cited text no. 10
    
11.
Libby P. Inflammation in atherosclerosis. Arterioscler Thromb Vasc Biol 2012;32:2045-51.  Back to cited text no. 11
    
12.
Canpolat U, Çetin EH, Cetin S, Aydin S, Akboga MK, Yayla C, et al. Association of monocyte-to-HDL cholesterol ratio with slow coronary flow is linked to systemic inflammation. Clin Appl Thromb Hemost 2016;22:476-82.  Back to cited text no. 12
    
13.
Kanbay M, Solak Y, Unal HU, Kurt YG, Gok M, Cetinkaya H, et al. Monocyte count/HDL cholesterol ratio and cardiovascular events in patients with chronic kidney disease. Int Urol Nephrol 2014;46:1619-25.  Back to cited text no. 13
    
14.
Kundi H, Kiziltunc E, Cetin M, Cicekcioglu H, Cetin ZG, Cicek G, et al. Association of monocyte/HDL-C ratio with SYNTAX scores in patients with stable coronary artery disease. Herz 2016;41:523-9.  Back to cited text no. 14
    
15.
Bolayir A, Gokce SF, Cigdem B, Bolayir HA, Yildiz OK, Bolayir E, et al. Monocyte/high-density lipoprotein ratio predicts the mortality in ischemic stroke patients. Neurol Neurochir Pol 2017. pii: S0028-384330104-4. doi: 10.1016/j.pjnns. 2017.08.011.  Back to cited text no. 15
    
16.
Menezes AM, Perez-Padilla R, Jardim JR, Muiño A, Lopez MV, Valdivia G, et al. Chronic obstructive pulmonary disease in five Latin American cities (the PLATINO study): A prevalence study. Lancet 2005;366:1875-81.  Back to cited text no. 16
    
17.
Zhong N, Wang C, Yao W, Chen P, Kang J, Huang S, et al. Prevalence of chronic obstructive pulmonary disease in China: A large, population-based survey. Am J Respir Crit Care Med 2007;176:753-60.  Back to cited text no. 17
    
18.
Eisner MD, Anthonisen N, Coultas D, Kuenzli N, Perez-Padilla R, Postma D, et al. An official American Thoracic Society public policy statement: Novel risk factors and the global burden of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2010;182:693-718.  Back to cited text no. 18
    
19.
Marie-Louise Koniski, Hocine Salhi, Aïcha Lahlou et al. Distribution of body mass index among subjects with COPD in the Middle East and North Africa region: Data from the BREATHE study. Int J Chron Obstruct Pulmon Dis 2015;10:1685-94.  Back to cited text no. 19
    
20.
Cirillo DJ, Agrawal Y, Cassano PA. Lipids and pulmonary function in the third national health and nutrition examination survey. Am J Epidemiol 2002;155:842-8.  Back to cited text no. 20
    
21.
Burkart KM, Manichaikul A, Wilk JB, Ahmed FS, Burke GL, Enright P, et al. ApoM and high-density lipoprotein cholesterol are associated with lung function and per cent emphysema. Eur Respir J 2014;43:1003-17.  Back to cited text no. 21
    
22.
Alizade E, Avcı A, Güner A, Tabakcı MM, Zehir R, Güler A, et al. Association of monocyte-to-HDL cholesterol ratio with cardiac syndrome X is linked to systemic inflammation. Kosuyolu Heart J 2016;19. doi: 10.5578/khj. 20996.  Back to cited text no. 22
    
23.
Gunay S, Sariaydin M, Acay A. New predictor of atherosclerosis in subjects with COPD: Atherogenic indices. Respir Care 2016;61:1481-7.  Back to cited text no. 23
    
24.
Corbi G, Bianco A, Turchiarelli V, Cellurale M, Fatica F, Daniele A, et al. Potential mechanisms linking atherosclerosis and increased cardiovascular risk in COPD: Focus on sirtuins. Int J Mol Sci 2013;14:12696-713.  Back to cited text no. 24
    
25.
Iwamoto H, Yokoyama A, Kitahara Y, Ishikawa N, Haruta Y, Yamane K, et al. Airflow limitation in smokers is associated with subclinical atherosclerosis. Am J Respir Crit Care Med 2009;179:35-40.  Back to cited text no. 25
    


    Figures

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    Tables

  [Table 1], [Table 2], [Table 3]



 

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