|Year : 2019 | Volume
| Issue : 1 | Page : 206-211
Can C-reactive protein predict metabolic syndrome in chronic obstructive pulmonary disease patients?
Ahmad A Ali1, Nourane Y Azab1, Sami S Eldahdouh1, Eman M. S. Abdelsalam2
1 Department of Pulmonology, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia, Egypt
2 Department of Chest, Shebin El-Kom Chest Hospital, Shebin El-Kom, Menoufia, Egypt
|Date of Submission||27-Feb-2017|
|Date of Acceptance||18-Apr-2017|
|Date of Web Publication||17-Apr-2019|
Eman M. S. Abdelsalam
5 Al Fath Street, Berket El Sabaa, Menoufia
Source of Support: None, Conflict of Interest: None
The aims of this study were to assess whether metabolic syndrome (MetS) is more common in chronic obstructive pulmonary disease (COPD) patients and to elucidate the role of C-reactive protein (CRP) as a marker of MetS in COPD patients.
MetS is closely related to COPD as proved in many previous studies. This association is attributed to the presence of systemic inflammation in both conditions. CRP may play a role as a predictor of MetS in COPD patients.
Patients and methods
This case–control study included 30 COPD patients and 20 controls recruited from the Chest Department, Faculty of Medicine, Menoufia University and Shebin El-Kom Chest Hospital between August 2014 and August 2016. All participants underwent clinical, spirometric, and laboratory assessments. Patients were staged according to Global initiative for Obstructive Lung Disease classification, and MetS was diagnosed according to International Diabetes Federation criteria.
Patients had significantly higher systolic and diastolic blood pressures, cholesterol, low-density lipoprotein, fasting blood glucose, CRP, and serum uric acid compared with controls (P < 0.001, 0.002, <0.001, 0.007, <0.001, <0.001, and < 0.001, respectively). High-density lipoprotein was significantly lower in controls. MetS in patients (60%) was more common compared with controls (30%) (P = 0.03). CRP levels were higher in COPD patients with MetS compared with COPD patients without MetS (P < 0.001). CRP more than 14 mg/l predicts the presence of MetS in COPD patients with specificity of 83.33% and sensitivity of 88.89%.
MetS is a common comorbidity associated with COPD. CRP can be a useful predictor of MetS in COPD patients.
Keywords: chronic obstructive pulmonary disease, C-reactive protein, metabolic syndrome
|How to cite this article:|
Ali AA, Azab NY, Eldahdouh SS, Abdelsalam EM. Can C-reactive protein predict metabolic syndrome in chronic obstructive pulmonary disease patients?. Menoufia Med J 2019;32:206-11
|How to cite this URL:|
Ali AA, Azab NY, Eldahdouh SS, Abdelsalam EM. Can C-reactive protein predict metabolic syndrome in chronic obstructive pulmonary disease patients?. Menoufia Med J [serial online] 2019 [cited 2019 Jul 17];32:206-11. Available from: http://www.mmj.eg.net/text.asp?2019/32/1/206/256085
| Introduction|| |
Chronic obstructive pulmonary disease (COPD) is a major respiratory disease that is responsible for many cases of disability and death all over the world . The main feature of COPD is partially reversible limitation to airflow that follows pathological inflammatory reaction of the lungs to noxious particles or gases, especially cigarette smoke. Diagnosis of COPD can be established by spirometry when there is a fixed ratio of postbronchodilator forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC)  below 0.7 .
Systemic inflammation associated with COPD causes several nonrespiratory consequences. Severity of COPD is determined by spirometry and by the associated nonrespiratory conditions .
Abdominal obesity, increased resistance to insulin, abnormal lipid profile, and hypertension are the constituents of metabolic syndrome (MetS) . The aims of the present study were to assess whether MetS is more common in COPD patients and to elucidate the role of C-reactive protein (CRP) as a marker of MetS in COPD patients.
| Patients and Methods|| |
This study was a prospective, case–control study. After obtaining approval of the ethics committee, 30 patients with stable COPD and 20 healthy participants as controls were recruited. COPD was diagnosed using Global initiative for Obstructive Lung Disease (GOLD) criteria: the postbronchodilator FEV1/FVC ratio was less than 70%.
The included COPD patients were aged 40–60 years, and had a stable disease state (no exacerbations and no medication change in the last 6 weeks).
Controls were aged 40–60 years, and all of them were not current smokers. Controls were selected after COPD was excluded by history taking, clinical examination, and spirometry.
Patients on systemic steroids or suffering from other respiratory diseases, coronary artery disease, and/or heart failure, infections, inflammatory diseases (e.g., lupus erythematosus) were excluded.
Informed consent was obtained from all participants before they were subjected to history taking, examination, and anthropometry [waist circumference (WC), height (m), weight (kg), and BMI].
Fasting blood samples (10 ml) were obtained for measuring complete blood count, plasma glucose, complete liver and kidney tests, serum uric acid (sUA), triglycerides (TG), total cholesterol, and high-density lipoprotein (HDL): BIOSYSTEMS (S.A, BARCELONA, Spain) SPINREACT (Sant Esteve de Bas, Girona, Spain) and SPINREACT kits (Spain) for enzymatic calorimetric assay were used. For CRP, slide agglutination test (Biomedical Systems Corp., St Louis, Missouri, USA) was used. Abnormal CRP was defined as CRP levels of at least 10 mg/l.
MetS was defined as visceral obesity (i.e., WC >95 cm in males and > 80 cm in females) and when two out of the following four criteria were met: (a) increased blood pressure (≥130/85 mmHg), (b) fasting plasma glucose of at least 100 mg/dl), (c) increased TG (≥150 mg/dl), and (d) reduced HDL (<40 mg/dl for men and <50 mg/dl for women).
Use of antihypertensive or hypoglycemic medications fulfilled the first two criteria.
Pulmonary function tests
- Spirolab II (Mir Medical International Research Srl, Rome, Italy) was used to measure FEV1, FVC, and the FEV1/FVC ratio
- GOLD classification (2014) was used for COPD staging (1–4).
Mean values and SDs were used to describe continuous variables, and percentages were used to describe categorical variables. Categorical variables were compared using the χ2-test and Fisher's exact test. If distribution was normal, a t-test was considered to assess differences between groups, and the Mann–Whitney U-test was used for variables with abnormal distribution. Differences between variables in the four stages of COPD were examined by analysis of variance. The area under the receiver operating characteristics (ROC) curve was used to test the ability of CRP to predict the presence of MetS in COPD patients. SPSS for Windows (SPSS Inc., Chicago, Illinois, USA), version 22 was used for analyses.
A minimum sample size of 24 patients and 17 controls was estimated on the basis of Firouzjahi et al.'s  data obtained by comparing CRP values between COPD and controls. Type I error of 5% and power of 95% were assumed. The numbers were increased to 30 patients and 20 controls to obtain round figures.
| Results|| |
There was no statistically significant difference between both patients and controls regarding age (51.23 ± 5.00 and 50.45 ± 5.41 years, P = 0.5, respectively). All patients were males, and the pack-year index of the patients was 43.75 ± 19.75. Patients had significantly higher systolic and diastolic blood pressures, CRP, sUA, cholesterol, and low-density lipoprotein (LDL) levels. However, FEV1% predicted, FVC% predicted, FEV1/FVC, and serum HDL were significantly lower in patients compared with controls [Table 1].
|Table 1: Clinical, spirometric, and laboratory characteristics of patients and controls|
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The number of COPD patients in each GOLD stage was 5, 10, 8, and 7 for stages 1, 2, 3, and 4, respectively.
MetS was found in 18 (60%) COPD patients, whereas in controls MetS was found in only six (30%) patients. MetS, abdominal obesity, hypertension, and hyperglycemia were significantly higher in frequency in patients than in controls [Table 2].
|Table 2: Distribution of metabolic syndrome and its individual components among patients and controls|
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CRP level was significantly higher in COPD patients with MetS than in those without MetS [Table 3].
|Table 3: Smoking and C-reactive protein levels in chronic obstructive pulmonary disease patients with and without metabolic syndrome|
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Distribution of normal (<10 mg/l) and abnormal (≥10 mg/l) CRP in COPD patients with and without MetS according to GOLD stages was not significant as shown in [Table 4].
|Table 4: Distribution of normal (<10 mg/l) and abnormal (≥10 mg/l) C-reactive protein in chronic obstructive pulmonary disease patients with and without metabolic syndrome according to Global initiative for Obstructive Lung Disease stages|
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The ROC curve for CRP to predict the presence of MetS in patients with COPD demonstrated that a cutoff point for CRP more than 14 mg/l can detect the presence or absence of MetS in patients with COPD with a specificity of 83.33% and sensitivity of 88.89% [Figure 1].
| Discussion|| |
Age of patients and controls did not vary significantly [Table 1]. In this study, all patients were males. COPD is more frequent in males as they are exposed to smoking and occupational risks more than females.
BMI and WC were also not different statistically in patients and controls [Table 1]. In patients with COPD, breathing usually requires effort unlike normal individuals who breathe unconsciously and effortlessly. This added effort for breathing increases resting energy expenditure, and thus COPD patients can lose weight if they do not increase their calorie intake .
Patients compared with controls had higher systolic and diastolic blood pressures [Table 1]. Hypertension and cardiovascular disease in COPD patients can be attributed to arterial stiffness that increases in such patients because of systemic inflammation . Acharyya et al.  reported a near-significant difference in systolic blood pressure (P < 0.063) between COPD and control groups.
LDL and total cholesterol were elevated in the studied patients and HDL decreased significantly when compared with controls [Table 1]. This is in agreement with Mitra et al.  who reported similar findings. Smoking per se can cause major changes in serum lipid profile; nicotine increases free fatty acids by increasing cortical adrenaline release, increasing liver synthesis and secretion of cholesterol and very LDL, and therefore increasing TG levels. Smoking decreases HDL indirectly by decreasing estrogen. Smoking also decreases tissue sensitivity to insulin with a decrease in lipoprotein lipase activity increasing the levels of harmful lipids .
FBG was significantly higher in patients than in controls [Table 1]. Acharyya et al.  also found similar results.
CRP level in the present study was significantly higher in COPD patients compared with controls [Table 1]. Karadag et al.  and Garcia-Rio et al.  also found higher CRP in COPD patients than in controls. More recently, Aksu et al.  and other researchers , found higher CRP levels in COPD patients. CRP production in the liver is enhanced by the cytokine interleukin-6, explaining the elevated CRP levels in COPD patients in whom cytokines (especially interleukin-6) are highly expressed .
On the other hand, Silva et al.  could not demonstrate differences between patients with COPD and controls regarding CRP levels (P = 0.62).
In the present study, CRP levels did not vary significantly at different GOLD stages. Akpinar et al.  found that abnormal CRP level was more prominent in stage II but without statistical significance. Silva et al.  also showed similar results (P = 0.66). In contrast, Lin et al.  found that CRP levels varied significantly between different stages. Their sample was larger in size than the present study.
Smoking (pack-year index) in the present study showed a positive correlation with CRP in the patient group. Abdelsadek et al.  also found similar findings.
sUA increases with hypoxia in COPD exacerbations and in metabolic diseases. Decomposition of purines increases because of hypoxia and increasing uric acid levels . In the present study, patients had higher levels of sUA than controls. Kocak et al.  also showed similar findings.
Several studies have shown an association between COPD and MetS, and the latter is responsible for worsening lung function and respiratory symptoms . Our results show a statistically significant higher rate of MetS in COPD patients than in controls. This is in agreement with Akpinar et al. , Hosny et al. , Breyer et al. , and Lipovec et al. .
MetS was found in 40% of GOLD 1 COPD patients, in 90% of GOLD 2 patients, 37.5% of GOLD 3 patients, and 57.1% of GOLD 4 patients. Similar frequencies were reported by Watz et al.  and Akpinar et al. . Interestingly, in all these studies, including the present one, patients with GOLD stage 2 had the highest prevalence of MetS. However, as in the present study, Kupeli et al.  found that the frequency of MetS between different GOLD stages was not statistically significant. This finding may prove that the underlying inflammatory process is responsible for the association between both diseases and that COPD severity does not cause MetS.
In COPD patients, hypertension was found to be the most frequent component of MetS [Table 2]. This is in agreement with Akpinar et al.  and Watz et al. . In addition, Hosny et al.  found that patients have significantly higher systolic blood pressure than controls.
In contrast, Barr et al.  found a lower frequency of hypertension in COPD patients (55%), and unlike the objective measurement of blood pressure in the present study they used a telephone questionnaire.
Unlike the findings of the present study, Hosny et al.  and Breyer et al.  found that WC was significantly higher in the COPD group compared with controls [Table 1]. They attributed the difference to malnutrition and decreased physical activity. On the other hand, and in agreement with the present study, Acharyya et al.  found no statistically significant difference between COPD patients and controls regarding WC, and thus WC per se is an unreliable marker for predicting MetS in COPD patients.
The results of the present study showed that hyperglycemia was significantly higher in COPD patients than in controls [Table 1]. The findings of Hosny et al.  and Acharyya et al.  were similar. Mirrakhimov  reviewed the associations between COPD and hyperglycemia, diabetes mellitus, and Mets. The pathophysiology of glucose metabolism disturbances in COPD was attributed to several factors including obesity, systemic inflammation and oxidative stress, hypoxia, hormonal dysregulation, reduced lung function, and the effect of COPD treatment such as corticosteroids.
High blood pressure, visceral adiposity, and high fasting blood glucose were the most common MetS components in patients and controls as reviewed by Lipovec et al. .
TG levels did not vary significantly between patients and controls. Hosny et al.  reported similar findings, and there was no significant difference between both groups with regard to HDL. This is also in agreement with Acharyya et al. .
A direct effect of smoking on the development of MetS in patients with COPD was not found, as there was no significant difference between COPD patients with and without MetS with regard to smoking (pack-year index) [Table 3]. This is in agreement with Kupeli et al.'s  findings.
Analysis of CRP levels in COPD patients, considering the presence or absence of MetS, revealed higher CRP levels in MetS patients, suggesting that the degree of underlying inflammation is higher in COPD patients with MetS than in those without. Kupeli et al.  found similar results. Therefore, elevated CRP levels in COPD patients may reflect low-grade inflammation that may be due to associated MetS.
In every GOLD stage, the presence or absence of MetS did not affect CRP levels [Table 4]. Akpinar et al.  found that abnormal CRP (>5 μg/l) was significantly higher in COPD patients with MetS than in those without MetS in GOLD stage II (P < 0.001) and nearly significant in GOLD stage III (P = 0.05).
ROC curve for CRP to predict the presence of MetS in patients with COPD demonstrates that a cutoff point of CRP more than 14 mg/l can detect the presence of MetS in patients with COPD with a sensitivity of 88.89% (95% confidence interval: 65.3–98.6) and a specificity of 83.33% (95% confidence interval: 51.6–97.9). A similar ROC curve analysis with the same aim has not been reported in the literature.
| Conclusion|| |
MetS is a common comorbidity of COPD. CRP can be a useful predictor of MetS in COPD patients.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]