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 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 5  |  Issue : 2  |  Page : 167-171

Effect of atorvastatin on high sensitivity c-reactive protein, pulmonary function, and quality of life in chronic obstructive pulmonary disease - an open-labeled randomized control trial


1 Department of Pharmacology, AIIMS, Rishikesh, Uttarakhand, India
2 Department of Pulmonary Medicine, SGRRI of Medical and Health Sciences, Dehradun, Uttarakhand, India

Date of Web Publication15-Dec-2017

Correspondence Address:
Manisha Bisht
Department of Pharmacology, AIIMS, Virbhadra Road, Rishikesh - 249 201, Uttarakhand
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/amhs.amhs_124_16

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  Abstract 

Objective: Beneficial effects of statins on chronic obstructive pulmonary disease (COPD) have been projected in many retrospective studies, but prospective studies were lacking. Hence, this study was done to study the efficacy of atorvastatin in improving the high-sensitivity C-reactive protein (hs-CRP levels), pulmonary functions, and quality of life in COPD patients. Materials and Methods: This was an open-labeled interventional study conducted on sixty stable COPD patients who were having abnormal lipid profile. The patients were randomized into two groups of thirty patients each – one receiving medications for COPD and another receiving 20 mg atorvastatin along with other medications for COPD. The outcome measures were change in hs-CRP levels, pulmonary function test, and health-related quality of life after 12 weeks. Results: A total of sixty participants with COPD were enrolled for the study and divided into two equal groups of thirty patients. There were two and one drop outs in atorvastatin and without atorvastatin group. After 12 weeks follow-up in the atorvastatin group, there was a significant improvement in the levels of hs-CRP levels from 4.82 ± 0.77 to 2.81 ± 0.73 (P < 0.05) as compared to other group without atorvastatin (4.34 ± 0.97–4.04 ± 0.63). Mean force expiratory value in 1 s as a percent of predicted value was similar in the atorvastatin and group without atorvastatin after 12 weeks: 54.2 ± 18.1–55.6 ± 17.9 (P = 0.54) and 55.7 ± 19.1–56.1 ± 18.1 (P = 0.58), respectively. Both treatments had similar improvement in St. George Respiratory Questionnaire total score. No adverse effect was observed in the atorvastatin group. Conclusion: Atorvastatin at a daily dose of 20 mg for 12 weeks has a significant beneficial effect on the levels of hs-CRP in COPD patient in comparison with the other group not receiving atorvastatin. There was no effect on the pulmonary function test and quality of life scores.

Keywords: Chronic obstructive pulmonary disease, C-reactive protein, statins


How to cite this article:
Bisht M, Rawat J. Effect of atorvastatin on high sensitivity c-reactive protein, pulmonary function, and quality of life in chronic obstructive pulmonary disease - an open-labeled randomized control trial. Arch Med Health Sci 2017;5:167-71

How to cite this URL:
Bisht M, Rawat J. Effect of atorvastatin on high sensitivity c-reactive protein, pulmonary function, and quality of life in chronic obstructive pulmonary disease - an open-labeled randomized control trial. Arch Med Health Sci [serial online] 2017 [cited 2018 Jan 23];5:167-71. Available from: http://www.amhsjournal.org/text.asp?2017/5/2/167/220819




  Introduction Top


Chronic obstructive pulmonary disease (COPD) is a common disease worldwide with a high burden to the society. It is characterized by repeated episodes of dyspnea that require frequent hospitalization, thereby decreasing the quality of life of patient and increasing the cost of care. Even though it is affecting a large magnitude of population, there is a lack of effectual therapies for the treatment or limitation of disease process. The study into the pathogenesis of COPD revealed the fact that it involves inflammatory processes.[1] Recently, statins have emerged as a potential disease-modifying agent in COPD.[2] Statins are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors that are widely used for their lipid-lowering effects. They also possess many pleiotropic effects, one of which is an anti-inflammatory effect, which may impart beneficial effect in COPD.[3] This postulate is supported by animal studies showing that statins inhibit the progression of emphysema in mice models.[4] Various retrospective studies indicate that statins may have a beneficial role in decreasing morbidity and mortality in COPD patients.[5] However, there is a lack of information on the effects of specific statins in most of the reviewed observational studies. There are studies to support that high-sensitivity C-reactive protein (hs-CRP) levels are a predictor of COPD morbidity and mortality,[6] and statins have been shown to reduce serum levels of CRP.[7] Lipophilic statins such as simvastatin and atorvastatin have additional anti-inflammatory potential.[8] Since most of the available data of effect of statin on COPD are based on observational studies, interventional studies were needed to evaluate the therapeutic effect of specific statins in COPD.


  Materials and Methods Top


The study was conducted in the Department of Pulmonary Medicine in tertiary care teaching hospital in Uttarakhand, over a period of 6 months from December 2012 to May 2013. It was an open-label interventional study conducted on chronic stable COPD patients. Approval for the study was obtained from the hospital's Institutional Research Committee and Institutional Ethical Committee. Patients suffering with COPD in stable condition for ≥3 months, aged between 40 and 80 years, and having abnormal lipid profile (low-density lipoprotein [LDL] - 130–160 mg/dl) were included in the study. The exclusion criteria were a history of bronchial asthma, prior exposure to statins, acute exacerbation of COPD for ≥3 months, any active infection, renal disease, hepatic dysfunction, and pregnant and nursing females.

After taking written informed consent, sixty patients were randomized into two groups – Group I receiving only the medications for COPD and Group II receiving 20 mg atorvastatin along with other medications for COPD. At baseline, the patients were evaluated with physical examination, pulmonary function test, blood test, and health-related quality of life questionnaire. The pulmonary function test included total lung capacity, inspiratory lung capacity, and force expiratory value in 1 s (FEV1). The hematological and biochemical investigation included serum hemoglobin, complete lipid profile, and serum hs-CRP (done by ELISA). The quality of life was assessed with COPD-related St. George's Respiratory Questionnaire (SGRQ).[9] It is a validated self-administered questionnaire which provides an overall measure for quality of life with subscale scores in three areas: symptom, activity, and impact of disease on daily life. SGRQ scores range from 0 to 100, a score of zero represents no quality of life impairment whereas 100 mean maximal impairment. The questionnaire was interpreted in the local language of the patient to facilitate the understanding while administering it. The minimum clinically important difference was four points in SGRQ total score.[10] The patients were followed up monthly and again reevaluated after 12 weeks. The patients were actively monitored for any adverse effects with the help of checklist.

Statistical methods

GraphPad InStat 3 was used for statistical analysis. All statistical calculations were done by paired t-test and unpaired t-test. P < 0.05 was considered statistically significant.


  Results Top


A total of 69 patients were screened for the study. Seven patients were excluded due to prior use of statins and two other were having renal disease [Figure 1]. The demographic and baseline clinical characteristics of the participants in both the groups are shown in [Table 1]. Out of sixty patients, 25% were women. The patients had a mean age of 60.5 ± 8.4 years and FEV1 that was 41.95 ± 11.5% of the predicted value, and a smoking history of 34.44 ± 17.73 pack-years. There were no significant differences between the two groups with respect to any characteristics at baseline. Follow-up visit information was not available for 3 of the 60 participants (5%), so 28 patients in the atorvastatin group and 29 in the no atorvastatin group were included in the primary analysis.
Figure 1: Consort flow chart for the study

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Table 1: Demographic profile and baseline characteristic of the patients assigned to both the grou

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[Figure 2] shows the change in the hs-CRP levels at weeks 0 and 12 in both treatment groups. In Group I, there was no significant change in hs-CRP levels after 12 weeks (4.34 ± 0.97–4.04 ± 0.63). In the Group II (atorvastatin group), there was a significant change in the levels of hs-CRP from 4.82 ± 0.77 to 2.81 ± 0.73 (P < 0.05).
Figure 2: Serum in high-sensitivity C-reactive protein levels

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Both the groups had similar significant improvement in SGQR quality of life score as shown in [Figure 3]. In Group I, the scores were reduced from 46 ± 16.1 to 40 ± 15.2 (P < 0.05), and in Group II, the scores were reduced from 47 ± 14.8 to 40 ± 15.1 (P < 0.05) which indicates improvement in quality of life. [Figure 3] shows the change in the FEV1 (% predicted value) at weeks 0 and 12 in both treatment groups. In Group I, the increase in the FEV1 (% predicted value) was from 54.2 ± 18.1 to 55.6 ± 17.9, whereas in Group II, it was 55.7 ± 19.1 to 56.1 ± 18.1. The change in FEV1 was not significant in the intragroup and intergroup comparison.
Figure 3: St. George's Respiratory Questionnaire quality of life score in patients with chronic obstructive pulmonary disease

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There was a significant reduction in the serum levels of LDL in Group II (receiving atorvastatin) after 12 weeks (142.7 ± 10.19–101 ± 30.4; P < 0.01) as compared to Group I (140.3 ± 9.19–141.5 ± 10.19; P = 0.863). There was no adverse effect reported in both the groups.


  Discussion Top


This randomized controlled open-labeled study was conducted to evaluate the effect of 20 mg atorvastatin on FEV1, hs-CRP, and quality of life in patients with COPD. Our results demonstrated that 20 mg of daily atorvastatin had no effect on the lung function and disease-specific quality of life in patients with moderate-to-severe COPD. However, there was a statistically significant decrease in the hs-CRP levels with the use of atorvastatin. There was no difference in the adverse drug reaction in both the groups. These data clearly indicate that daily use of 20 mg atorvastatin for the duration of 3 months has no role in the improvement of pulmonary function and health-related quality of life but has a significant improvement of hs-CRP levels.

We preferred to use atorvastatin in our study as it is easily accessible and affordable in India. Moreover, being a lipophilic agent, it is postulated to have greater anti-inflammatory potential.[8] It has a dose-dependent anti-inflammatory effect ranging from 10 to 80 mg dose [11] and therefore a dose of 20 mg atorvastatin was selected to minimize dose-related adverse effects.[12] In our study, there was no effect on the pulmonary function with the use of 20 mg atorvastatin. This was in concurrence with other randomized controlled trials where similar results were demonstrated with the use of statins.[13],[14] Randomized control trials failed to reciprocate the inverse relationship of hs-CRP and pulmonary function as postulated by many cross-sectional studies. The most plausible reason for this could be that the shorter duration of follow-up in these studies as compared to the longitudinal trials where the patients were followed up till 8–9 years.[15],[16],[17],[18] Other factor which could contribute to the lack of effect can be a relatively lower dose of 20 mg used in this study. Moreover, in our study, only moderate-to-severe COPD patients were included, and therefore, the feasibility of the beneficial effect of statins in a patient with less severe impairment could not be evaluated.

Our study has revealed that there was a significant decrease in the levels of hs-CRP with 3 months of 20 mg/day atorvastatin therapy. These findings were consistent with few other studies which have demonstrated a decrease in hs-CRP levels in patients with COPD with the use of statins.[13],[19],[20] In contrast to our study one study has reported a statistically nonsignificant change in hs-CRP levels after the use of 40 mg/day simvastatin for 3 months in patients with COPD.[21] Similarly, two other studies also reported no effect on the serum levels of inflammatory markers including hs-CRP with simvastatin.[22],[23] This could be attributed to small sample size and short treatment period in these studies.

In our study, SGRQ scores had similar improvement in both Group I not receiving atorvastatin and Group II receiving atorvastatin (decrease of 7 points vs. 5 points; P > 0.05). These results are in contrast of a recent study which reported a significant improvement in SGRQ with mean SGRQ decreased by 12 points after treatment with 40 mg/day atorvastatin for 12 weeks (P = 0.012) as compared with placebo.[20] The major limitation of this study was a small sample of patient (n = 18) as compared to our study sample. Similarly, another study has also reported improved asthma quality of life with short-term treatment with atorvastatin in mild asthmatic smokers.[24] Since ambiguous results are available for the effect of atorvastatin on SGRQ scores in COPD patients, further research on larger groups and the effects of long-term intervention on clinical outcomes are needed.


  Conclusion Top


Our study demonstrated a significant decrease in serum hs-CRP levels in COPD patient with the use of 20 mg/day atorvastatin for 12 weeks. However, our study did not reveal any significant effect on other clinical outcomes such as pulmonary functions or quality of life. The major limitation of our study was that it was an open-labeled study, had small sample size, and was of short duration. Since many other studies have demonstrated a favorable effect on the clinical outcomes such as pulmonary functions and quality of life, further large-scale randomized placebo control clinical trials are required to assess the beneficial effect of statins on COPD.

Financial support and sponsorship

The study was financially funded by Himalayan Institute of Medical Sciences, Dehradun.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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