JIANG Jiajia1,, FENG Jing1, DAI Rong1, YANG Yuan2, LIANG Yi1, WANG Yang1, ZHANG Fan1,
1.Research Center for Medicine and Social Development, Innovation Center for Social Risk Governance in Health,School of Public Health and Management, Chongqing Medical University,Chongqing 400016, China
2.Department of Cardiovascular Medicine, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
Objective To systematically review the effectiveness and safety of statins for chronic obstructive pulmonary diseases (COPD) combining with pulmonary hypertension (PH). Methods The electronic searches in databases of PubMed, EMbase, the Cochrane Library, Web of Science, CBM, CNKI, VIP and Wanfang Data were conducted from the date of their establishment to January 2016 and the references of the include studies were also retrieved for collecting randomized controlled trials (RCTs) or quasi-RCTs on statins treating COPD combining with PH. Two researchers independently screened the literature according to the inclusion and exclusion criteria, extracted the data, assessed the quality of the included studies by adopting the Cochrane collaboration’s tool for assessing risk of bias, and performed Meta-analysis by using RevMan 5.3 software. Results A total of 24 studies involving 1 587 cases were included. The results of Meta-analysis showed that: compared with the control group, simvastatin significantly improved FEV1 [MD=0.23, 95%CI: 0.16-0.31,P<0.000 01], FEV1% [MD=6.73, 95%CI: 1.34-12.12,P=0.01], FVC [MD=0.39, 95%CI: 0.34-0.45,P<0.000 01], 6 minutes walk distance (6MWD) [MD=59.09,95%CI: 54.24-63.93,P<0.000 01] and decreased mPAP [MD=6.73, 95%CI: 1.34-12.12,P=0.01], SPAP [MD=-4.53,95%CI=-8.87--0.19,P=0.04]. Atorvastatin significantly improved FEV1 [MD=6.22, 95%CI: 2.51-9.93,P=0.001] and 6MWD [MD=24.10, 95%CI: 12.98-35.23,P<0.000 1] and decreased sPAP [MD=-6.44, 95%CI: -7.95--4.93,P<0.000 01] and mPAP [MD=-3.51,95%CI: -5.81--1.22,P=0.003]. But no significant difference was found in the improvement of FEV1,FVC or FEV1/FVC. Fluvastatin significantly decreased sPAP [MD=-5.89, 95%CI: -6.99--4.79,P<0.000 01]. There was a significant decrease in the Borg dyspnoea score in statins group [MD=-3.37, 95%CI: -4.61--2.14,P<0.000 01] as compared with the controls. In addition, the incidence of adverse drug reactions (ADRs) was similar between statins and the control group.Conclusion Current evidence suggests that statins may decrease pulmonary hypertension in patients with COPD combining with PH. However, high-quality clinical trials with large sample size are needed to verify whether the improvement of pulmonary function, 6MWD and Borg dyspnoea score are the class effect or the incidence of ADRs is disparate among different statins.
该公式出自Cochrane Handbook for Systematic Reviews of Interventions (Version 5.1.0) 16.1.3.2 “Imputing standard deviations for changes from baseline”,通过查阅相关文献[10],将Corr值设定为0.5代入公式进行计算。
LOPEZ AD, SHIBUYAK, RAOC, et al.Chronic obstructive pulmonary disease: current burden and future projections[J]. Eur Respir J,2006,27(2): 397-412.
ABSTRACT Summary Information about the comparative magnitude of the burden from various diseases and injuries is a critical input into building the evidence base for health policies and programmes. Such informa- tion should be based on a critical evaluation of all available epidemiological data using standard and comparable procedures across diseases and injuries, including information on the age at death and the incidence, duration and severity of cases who do not die prematurely from the disease. A summary measure, disability-adjusted life yrs (DALYs), has been developed to simulta- neously measure the amount of disease burden due to premature mortality and the amount due to the nonfatal consequences of disease. Approximately 2.7 million deaths from chronic obstructive pulmonary disease (COPD) occurred in 2000, half of them in the Western Pacific Region, with the majority of these occurring in China. About 400,000 deaths occur each year from COPD in industrialised countries. The increase in global COPD deaths between 1990 and 2000 (0.5 million) is likely to be partly real, and partly due to better methods and more extensive data availability in 2000. The regional (adult) prevalence in 2000 varied from 0.5% in parts of Africa to 3-4% in North America.
HALCOX JP,DEANFIELD JE.Beyond the laboratory: clinical implications for statin pleiotropy[J]. Circulation,2004,109(21 Suppl 1): 42-48.
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ITO MK,TALBERT RL,TSIMIKASS.Statin-associated pleiotropy: possible beneficial effects beyond cholesterol reduction[J]. Pharmacotherapy,2006,26(7 Pt 2): 85S-97S.
Abstract Because elevated serum cholesterol levels are strongly associated with coronary heart disease, cholesterol reduction by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (or statins) has been assumed to be the predominant, if not the only, mechanism underlying the beneficial effects of these drugs in cardiovascular diseases. Subgroup analyses of large clinical trials, however, have suggested that the beneficial effects of statins may extend to mechanisms beyond cholesterol reduction. Indeed, recent experimental and clinical evidence indicates that some of the cholesterol-independent or "pleiotropic" effects of statins may be mediated through improving or restoring endothelial function, enhancing the stability of atherosclerotic plaques, and decreasing oxidative stress and vascular inflammation.
LIAO JK.Clinical implications for statin pleiotropy[J]. Curr Opin Lipidol,2005,16(6): 624-629.
PURPOSE OF REVIEW: is a multi-factorial condition involving that can result in . are potent inhibitors of , and in clinical trials, have been shown to be beneficial in the primary and secondary prevention of . However, the overall benefits observed with appear to occur much earlier and to be greater than what might be expected from changes in levels alone, suggesting effects beyond cholesterol lowering.: Recent studies indicate that some of the cholesterol-independent or 'pleiotropic' effects of involve improving endothelial function, enhancing the stability of atherosclerotic plaques, decreasing oxidative stress and inflammation, and inhibiting the thrombogenic response. Many of these pleiotropic effects are mediated by inhibition of , which serve as attachments for signaling molecules. In particular, inhibition of small , , , and , whose proper and function are dependent upon isoprenylation, may play an important role in mediating the pleiotropic effects of .: The potential clinical implications of pleiotropy suggests that perhaps other biomarkers, in addition to levels, should be used to gauge the full efficacy of therapy in patients with cardiovascular risks or that therapy may be effective in disease states, such as inflammatory conditions, or , where levels have not been shown to be a strong epidemiological risk for these diseases.
MOOSAVI SA,RAJIH,FAGHANKHANIM,et al.Evaluation of the effects of atorvastatin on the treatment of secondary pulmonary hypertension due to chronic obstructive pulmonary diseases: a randomized controlled trial[J]. Iran Red Crescent Med J,2013, 15(8): 649-654.
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LEE TM,CHEN CC,SHEN HN,et al.Effects of pravastatin on functional capacity in patients with chronic obstructive pulmonary disease and pulmonary hypertension[J]. Clin Sci (Lond),2009,116(6): 497-505.
PH () often complicates the disease course of patients with COPD () and is an indication of a worse prognosis. In the present study, we assessed whether administration was effective in improving PH and exercise capacity in COPD patients with PH, and whether the pulmonary protection was mediated by inhibiting () production. In a double-blind parallel design, 53 COPD patients with PH were randomly assigned to receive either placebo or (40 mg/day) over a period of 6 months at a medical centre. Baseline characteristics were similar in both groups. The exercise time remained stable throughout the study in the placebo group. After 6 months, the exercise time significantly increased 52% from 660+/-352 to 1006+/-316 s (P<0.0001) in -treated patients. With , echocardiographically derived systolic (pulmonary artery pressure) decreased significantly from 47+/-8 to 40+/-6 mmHg. There was significant improvement in the Borg dyspnoea score after administering . Despite unchanged plasma levels throughout the study, urinary of the was decreased and significantly correlated with an improvement in exercise time in -treated patients (r=-0.47, P=0.01). In conclusion, significantly improved exercise tolerance, and decreased PH and dyspnoea during exercise in COPD patients with PH, probably by inhibiting .
ALEXEEFF SE,LITONJUA AA,SPARROWD,et al.Statin use reduces decline in lung function:VA Normative Aging Study[J].Am J RespirCrit Care Med,2007,176(8): 742-747.
ABSTRACT Decreased lung function has been linked to increased inflammation and oxidative stress. Statins have demonstrated antiinflammatory and antioxidant properties. We investigated the effect of statin use on decline in lung function in the elderly, and whether smoking modified this effect. Our study population included 2,136 measurements on 803 elderly men from the Normative Aging Study whose lung function (FVC and FEV(1)) was measured two to four times between 1995 and 2005. Subjects indicated statin use and smoking history at each visit. We used mixed linear models to estimate the effects of each covariate, adjusting for subject and possible confounders. For those not using statins, the estimated decline in FEV(1) was 23.9 ml/year (95% confidence interval [CI], -27.8 to -20.1 ml/yr), whereas those taking statins had an estimated 10.9-ml/year decline in FEV(1) (95% CI, -16.9 to -5.0 ml/yr). We also examined the effect of statins with smoking by dividing the cohort into four groups: never-smokers, longtime quitters (quit >or= 10 yr ago), recent quitters (quit < 10 yr ago), and current smokers. We found a significant three-way interaction between time since first visit, statin use, and smoking status (P < 0.001). Within each smoking category, the effect of statins was always estimated to be beneficial, but the size of the improvement in the decline rate varied among smoking groups. We found similar results for FVC decline. Our results indicate that statin use attenuates decline in lung function in the elderly, with the size of the beneficial effect modified by smoking status.
KEDDISSI JI,YOUNIS WG,CHBEIR EA,et al.The use of statins andlung function in current and fomer smokers[J]. Chest,2007,132(6): 1764-1771.
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NISHIMURAT,FAUL JL,BERRY GJ,et al.Simvastatin attenuates smooth muscle neointimal proliferation and pulmonary hypertension in rats[J]. Am J Respir Crit Care Med, 2002,166(10): 1403-1408.
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LEE JH,LEE DS,KIM EK,et al.Simvastatin inhibits cigarette smoking-induced emphysema and pulmonary hypertension in rat lungs[J]. Am J Respir Crit Care Med, 2005, 172(8):987-993.
ABSTRACT In cigarette smoking-induced chronic obstructive pulmonary disease, structural and functional derangements are characterized by parenchymal destruction and pulmonary hypertension. Statins are 3-hydroxy-3-methyl-glutaryl-coenzyme-A reductase inhibitors that have been used as lipid-lowering agents. These drugs also have additional pharmacologic properties, including antiinflammation, scavenging reactive oxygen species, restoring endothelial function, and antithrombogenesis, all of which can counteract the harmful effects of cigarette smoking. We performed assays to determine whether simvastatin could attenuate lung damage induced by chronic cigarette smoking in rats. In Sprague-Dawley rats exposed to cigarette smoke for 16 weeks, morphologic changes in the lungs and pulmonary arterial pressure were examined. Simvastatin inhibited lung parenchymal destruction and development of pulmonary hypertension, and also inhibited peribronchial and perivascular infiltration of inflammatory cells and induction of matrix metalloproteinase-9 activity in lung tissue. Simvastatin additionally prevented pulmonary vascular remodeling and the changes in endothelial nitric oxide synthase expression induced by smoking. In human lung microvascular endothelial cells, simvastatin increased expression of endothelial nitric oxide synthase mRNA. Simvastatin ameliorated the structural and functional derangements of the lungs caused by cigarette smoking, partly by suppressing inflammation and matrix metalloproteinase-9 induction and preventing pulmonary vascular abnormality. These findings indicate that statins may play a role in the treatment of cigarette smoking-induced chronic obstructive pulmonary disease.
REED RM, IACONOA,DEFILIPPISA,et al.Statin therapy is associated with decreased pulmonary vascular pressures in severe COPD[J]. COPD,2011,8(2): 96-102.
Background: Pulmonary hypertension (PH) in COPD carries a poor prognosis. Statin therapy has been associated with numerous beneficial clinical effects in COPD, including a possible improvement in PH. We examined the association between statin use and pulmonary hemodynamics in a well-characterized cohort of patients undergoing evaluation for lung transplantation. Methods: We conducted a cross-sectional analysis of 112 subjects evaluated for lung transplant with a diagnosis of COPD. Clinical characteristics, pulmonary function, cardiac catheterization findings and medical comorbidities were compared between statins users and non-users. Results: Thirty-four (30%) subjects were receiving statin therapy. Statin users were older and had an increased prevalence of systemic hypertension and coronary artery disease (CAD). Mean pulmonary arterial pressure (mPAP) in the statin group was lower [26 +/- 7 vs 29 +/- 7 mmHg, p = 0.02], as was pulmonary artery wedge pressure (PAWP) [12 +/- 5 vs. 15 +/- 6 mmHg, p = 0.02]. Pulmonary vascular resistance did not differ between the groups. In multiple regression analysis, statin use was associated with a 4.2 mmHg (95% CI: 2 to 6.4, p = < 0.001) lower PAWP and a 2.6 mmHg (95% CI: 0.3 to 4.9, p = 0.03) reduction in mPAP independent of PAWP. Conclusions: In patients with severe COPD, statin use is associated with significantly lower PAWP and mPAP. These finding should be evaluated prospectively.
MIYAMOTO SL,NAGAYAN,SATOHT,et al.Clinical correlates and prognostic significance of six-minute walk test in patients with primary pulmonary hypertension. Comparison with cardiopulmonary exercise testing[J]. Am J Respir Crit Care Med,2000, 161(2 Pt 1): 487-492.
... 该公式出自Cochrane Handbook for Systematic Reviews of Interventions (Version 5.1.0) 16.1.3.2 “Imputing standard deviations for changes from baseline”,通过查阅相关文献[10],将Corr值设定为0.5代入公式进行计算. ...
Evaluation of the effects of atorvastatin on the treatment of secondary pulmonary hypertension due to chronic obstructive pulmonary diseases: a randomized controlled trial
Clinical correlates and prognostic significance of six-minute walk test in patients with primary pulmonary hypertension. Comparison with cardiopulmonary exercise testing
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