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Published in: Critical Care 4/2012

Open Access 01-08-2012 | Research

The impact of statin use on pneumonia risk and outcome: a combined population-based case-control and cohort study

Authors: Anders Gunnar Nielsen, Rikke Beck Nielsen, Anders Hammerich Riis, Søren Paaske Johnsen, Henrik Toft Sørensen, Reimar Wernich Thomsen

Published in: Critical Care | Issue 4/2012

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Abstract

Introduction

The impact of statin use on pneumonia risk and outcome remains unclear. We therefore examined this risk in a population-based case-control study and did a 5-year update of our previous 30-day mortality analyses.

Methods

We identified 70,953 adults with a first-time hospitalization for pneumonia between 1997 and 2009 in Northern Denmark. Ten age- and sex-matched population controls were selected for each pneumonia patient. To control for potential confounders, we retrieved individual-level data on other medications, comorbidities, recent surgery, socioeconomic indicators, influenza vaccination, and other markers of frailty or health awareness from medical databases. We followed all pneumonia patients for 30 days after hospital admission.

Results

A total of 7,223 pneumonia cases (10.2%) and 64 523 controls (9.1%) were statin users before admission, corresponding to an age- and sex-matched odds ratio (OR) of 1.17 (95% confidence interval [CI]: 1.14-1.21). After controlling for higher comorbidity and a wide range of other potential confounders, the adjusted OR for pneumonia associated with current statin use dropped to 0.80 (95% CI: 0.77-0.83). Previous statin use was not associated with decreased pneumonia risk (adjusted OR = 0.97, 95% CI: 0.91-1.02). Decreased risk remained significant after further adjustment for frailty and health awareness markers.
The prevalence of statin use among Danish pneumonia patients increased from 1% in 1997 to 24% in 2009. Thirty-day mortality following pneumonia hospitalization was 11.3% among statin users versus 15.1% among nonusers. This corresponded to a 27% reduced mortality rate (adjusted hazard ratio = 0.73, 95% CI: 0.67-0.79), corroborating our earlier findings.

Conclusions

Current statin use was associated with both a decreased risk of hospitalization for pneumonia and lower 30-day mortality following pneumonia.
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Literature
1.
go back to reference Terblanche M, Almog Y, Rosenson RS, Smith TS, Hackam DG: Statins and sepsis: multiple modifications at multiple levels. Lancet Infect Dis. 2007, 7: 358-368. 10.1016/S1473-3099(07)70111-1.PubMedCrossRef Terblanche M, Almog Y, Rosenson RS, Smith TS, Hackam DG: Statins and sepsis: multiple modifications at multiple levels. Lancet Infect Dis. 2007, 7: 358-368. 10.1016/S1473-3099(07)70111-1.PubMedCrossRef
2.
go back to reference Niessner A, Steiner S, Speidl WS, Pleiner J, Seidinger D, Maurer G, Goronzy JJ, Weyand CM, Kopp CW, Huber K, Wolzt M, Wojta J: Simvastatin suppresses endotoxin-induced upregulation of toll-like receptors 4 and 2 in vivo. Atherosclerosis. 2006, 189: 408-413. 10.1016/j.atherosclerosis.2005.12.022.PubMedCrossRef Niessner A, Steiner S, Speidl WS, Pleiner J, Seidinger D, Maurer G, Goronzy JJ, Weyand CM, Kopp CW, Huber K, Wolzt M, Wojta J: Simvastatin suppresses endotoxin-induced upregulation of toll-like receptors 4 and 2 in vivo. Atherosclerosis. 2006, 189: 408-413. 10.1016/j.atherosclerosis.2005.12.022.PubMedCrossRef
3.
go back to reference McGown CC, Brookes ZL: Beneficial effects of statins on the microcirculation during sepsis: the role of nitric oxide. Br J Anaesth. 2007, 98: 163-175. 10.1093/bja/ael358.PubMedCrossRef McGown CC, Brookes ZL: Beneficial effects of statins on the microcirculation during sepsis: the role of nitric oxide. Br J Anaesth. 2007, 98: 163-175. 10.1093/bja/ael358.PubMedCrossRef
4.
go back to reference Yunoki K, Nakamura K, Miyoshi T, Enko K, Kubo M, Murakami M, Hata Y, Kohno K, Morita H, Kusano KF, Ito H: Impact of hypertriglyceridemia on endothelial dysfunction during statin +/- ezetimibe therapy in patients with coronary heart disease. Am J Cardiol. 2011, 108: 333-339. 10.1016/j.amjcard.2011.03.049.PubMedCrossRef Yunoki K, Nakamura K, Miyoshi T, Enko K, Kubo M, Murakami M, Hata Y, Kohno K, Morita H, Kusano KF, Ito H: Impact of hypertriglyceridemia on endothelial dysfunction during statin +/- ezetimibe therapy in patients with coronary heart disease. Am J Cardiol. 2011, 108: 333-339. 10.1016/j.amjcard.2011.03.049.PubMedCrossRef
5.
go back to reference Chalmers JD, Short PM, Mandal P, Akram AR, Hill AT: Statins in community acquired pneumonia: Evidence from experimental and clinical studies. Respir Med. 2010, 104: 1081-1091. 10.1016/j.rmed.2010.04.005.PubMedCrossRef Chalmers JD, Short PM, Mandal P, Akram AR, Hill AT: Statins in community acquired pneumonia: Evidence from experimental and clinical studies. Respir Med. 2010, 104: 1081-1091. 10.1016/j.rmed.2010.04.005.PubMedCrossRef
6.
go back to reference Janda S, Young A, Fitzgerald JM, Etminan M, Swiston J: The effect of statins on mortality from severe infections and sepsis: a systematic review and meta-analysis. J Crit Care. 2010, 25: 656.e7-656.e22. 10.1016/j.jcrc.2010.02.013.CrossRef Janda S, Young A, Fitzgerald JM, Etminan M, Swiston J: The effect of statins on mortality from severe infections and sepsis: a systematic review and meta-analysis. J Crit Care. 2010, 25: 656.e7-656.e22. 10.1016/j.jcrc.2010.02.013.CrossRef
7.
go back to reference Kopterides P, Falagas ME: Statins for sepsis: a critical and updated review. Clin Microbiol Infect. 2009, 15: 325-334. 10.1111/j.1469-0691.2009.02750.x.PubMedCrossRef Kopterides P, Falagas ME: Statins for sepsis: a critical and updated review. Clin Microbiol Infect. 2009, 15: 325-334. 10.1111/j.1469-0691.2009.02750.x.PubMedCrossRef
8.
go back to reference Falagas ME, Makris GC, Matthaiou DK, Rafailidis PI: Statins for infection and sepsis: a systematic review of the clinical evidence. J Antimicrob Chemother. 2008, 61: 774-785. 10.1093/jac/dkn019.PubMedCrossRef Falagas ME, Makris GC, Matthaiou DK, Rafailidis PI: Statins for infection and sepsis: a systematic review of the clinical evidence. J Antimicrob Chemother. 2008, 61: 774-785. 10.1093/jac/dkn019.PubMedCrossRef
9.
go back to reference Tleyjeh IM, Kashour T, Hakim FA, Zimmerman VA, Erwin PJ, Sutton AJ, Ibrahim T: Statins for the prevention and treatment of infections: a systematic review and meta-analysis. Arch Intern Med. 2009, 169: 1658-1667. 10.1001/archinternmed.2009.286.PubMedCrossRef Tleyjeh IM, Kashour T, Hakim FA, Zimmerman VA, Erwin PJ, Sutton AJ, Ibrahim T: Statins for the prevention and treatment of infections: a systematic review and meta-analysis. Arch Intern Med. 2009, 169: 1658-1667. 10.1001/archinternmed.2009.286.PubMedCrossRef
10.
go back to reference van de Garde EM, Hak E, Souverein PC, Hoes AW, van den Bosch JM, Leufkens HG: Statin treatment and reduced risk of pneumonia in patients with diabetes. Thorax. 2006, 61: 957-961. 10.1136/thx.2006.062885.PubMedPubMedCentralCrossRef van de Garde EM, Hak E, Souverein PC, Hoes AW, van den Bosch JM, Leufkens HG: Statin treatment and reduced risk of pneumonia in patients with diabetes. Thorax. 2006, 61: 957-961. 10.1136/thx.2006.062885.PubMedPubMedCentralCrossRef
11.
go back to reference Schlienger RG, Fedson DS, Jick SS, Jick H, Meier CR: Statins and the risk of pneumonia: a population-based, nested case-control study. Pharmacotherapy. 2007, 27: 325-332. 10.1592/phco.27.3.325.PubMedCrossRef Schlienger RG, Fedson DS, Jick SS, Jick H, Meier CR: Statins and the risk of pneumonia: a population-based, nested case-control study. Pharmacotherapy. 2007, 27: 325-332. 10.1592/phco.27.3.325.PubMedCrossRef
12.
go back to reference Myles PR, Hubbard RB, McKeever TM, Pogson Z, Smith CJ, Gibson JE: Risk of community-acquired pneumonia and the use of statins, ace inhibitors and gastric acid suppressants: a population-based case-control study. Pharmacoepidemiol Drug Saf. 2009, 18: 269-275. 10.1002/pds.1715.PubMedCrossRef Myles PR, Hubbard RB, McKeever TM, Pogson Z, Smith CJ, Gibson JE: Risk of community-acquired pneumonia and the use of statins, ace inhibitors and gastric acid suppressants: a population-based case-control study. Pharmacoepidemiol Drug Saf. 2009, 18: 269-275. 10.1002/pds.1715.PubMedCrossRef
13.
go back to reference Vinogradova Y, Coupland C, Hippisley-Cox J: Risk of pneumonia in patients taking statins: population-based nested case-control study. Br J Gen Pract. 2011, 61: e742-748. 10.3399/bjgp11X606654.PubMedPubMedCentralCrossRef Vinogradova Y, Coupland C, Hippisley-Cox J: Risk of pneumonia in patients taking statins: population-based nested case-control study. Br J Gen Pract. 2011, 61: e742-748. 10.3399/bjgp11X606654.PubMedPubMedCentralCrossRef
14.
go back to reference Dublin S, Jackson ML, Nelson JC, Weiss NS, Larson EB, Jackson LA: Statin use and risk of community acquired pneumonia in older people: population based case-control study. BMJ. 2009, 338: b2137-10.1136/bmj.b2137.PubMedPubMedCentralCrossRef Dublin S, Jackson ML, Nelson JC, Weiss NS, Larson EB, Jackson LA: Statin use and risk of community acquired pneumonia in older people: population based case-control study. BMJ. 2009, 338: b2137-10.1136/bmj.b2137.PubMedPubMedCentralCrossRef
15.
go back to reference Thomsen RW, Riis A, Kornum JB, Christensen S, Johnsen SP, Sorensen HT: Preadmission use of statins and outcomes after hospitalization with pneumonia: population-based cohort study of 29,900 patients. Arch Intern Med. 2008, 168: 2081-2087. 10.1001/archinte.168.19.2081.PubMedCrossRef Thomsen RW, Riis A, Kornum JB, Christensen S, Johnsen SP, Sorensen HT: Preadmission use of statins and outcomes after hospitalization with pneumonia: population-based cohort study of 29,900 patients. Arch Intern Med. 2008, 168: 2081-2087. 10.1001/archinte.168.19.2081.PubMedCrossRef
16.
go back to reference Mortensen EM, Restrepo MI, Anzueto A, Pugh J: The effect of prior statin use on 30-day mortality for patients hospitalized with community-acquired pneumonia. Respir Res. 2005, 6: 82-10.1186/1465-9921-6-82.PubMedPubMedCentralCrossRef Mortensen EM, Restrepo MI, Anzueto A, Pugh J: The effect of prior statin use on 30-day mortality for patients hospitalized with community-acquired pneumonia. Respir Res. 2005, 6: 82-10.1186/1465-9921-6-82.PubMedPubMedCentralCrossRef
17.
go back to reference Frost FJ, Petersen H, Tollestrup K, Skipper B: Influenza and COPD mortality protection as pleiotropic, dose-dependent effects of statins. Chest. 2007, 131: 1006-1012. 10.1378/chest.06-1997.PubMedCrossRef Frost FJ, Petersen H, Tollestrup K, Skipper B: Influenza and COPD mortality protection as pleiotropic, dose-dependent effects of statins. Chest. 2007, 131: 1006-1012. 10.1378/chest.06-1997.PubMedCrossRef
18.
go back to reference Mortensen EM, Pugh MJ, Copeland LA, Restrepo MI, Cornell JE, Anzueto A, Pugh JA: Impact of statins and angiotensin-converting enzyme inhibitors on mortality of subjects hospitalised with pneumonia. Eur Respir J. 2008, 31: 611-617. 10.1183/09031936.00162006.PubMedCrossRef Mortensen EM, Pugh MJ, Copeland LA, Restrepo MI, Cornell JE, Anzueto A, Pugh JA: Impact of statins and angiotensin-converting enzyme inhibitors on mortality of subjects hospitalised with pneumonia. Eur Respir J. 2008, 31: 611-617. 10.1183/09031936.00162006.PubMedCrossRef
19.
go back to reference Chalmers JD, Singanayagam A, Murray MP, Hill AT: Prior statin use is associated with improved outcomes in community-acquired pneumonia. Am J Med. 2008, 121: 1002-1007. 10.1016/j.amjmed.2008.06.030. e1001PubMedCrossRef Chalmers JD, Singanayagam A, Murray MP, Hill AT: Prior statin use is associated with improved outcomes in community-acquired pneumonia. Am J Med. 2008, 121: 1002-1007. 10.1016/j.amjmed.2008.06.030. e1001PubMedCrossRef
20.
go back to reference Douglas I, Evans S, Smeeth L: Effect of statin treatment on short term mortality after pneumonia episode: cohort study. BMJ. 2011, 342: d1642-10.1136/bmj.d1642.PubMedPubMedCentralCrossRef Douglas I, Evans S, Smeeth L: Effect of statin treatment on short term mortality after pneumonia episode: cohort study. BMJ. 2011, 342: d1642-10.1136/bmj.d1642.PubMedPubMedCentralCrossRef
21.
go back to reference Vandermeer ML, Thomas AR, Kamimoto L, Reingold A, Gershman K, Meek J, Farley MM, Ryan P, Lynfield R, Baumbach J, Schaffner W, Bennett N, Zansky S: Association between use of statins and mortality among patients hospitalized with laboratory-confirmed influenza virus infections: a multistate study. J Infect Dis. 2012, 205: 13-19. 10.1093/infdis/jir695.PubMedCrossRef Vandermeer ML, Thomas AR, Kamimoto L, Reingold A, Gershman K, Meek J, Farley MM, Ryan P, Lynfield R, Baumbach J, Schaffner W, Bennett N, Zansky S: Association between use of statins and mortality among patients hospitalized with laboratory-confirmed influenza virus infections: a multistate study. J Infect Dis. 2012, 205: 13-19. 10.1093/infdis/jir695.PubMedCrossRef
22.
go back to reference Rothberg MB, Bigelow C, Pekow PS, Lindenauer PK: Association between statins given in hospital and mortality in pneumonia patients. J Gen Intern Med. 2012, 27: 280-286. 10.1007/s11606-011-1826-2.PubMedPubMedCentralCrossRef Rothberg MB, Bigelow C, Pekow PS, Lindenauer PK: Association between statins given in hospital and mortality in pneumonia patients. J Gen Intern Med. 2012, 27: 280-286. 10.1007/s11606-011-1826-2.PubMedPubMedCentralCrossRef
23.
go back to reference Majumdar SR, McAlister FA, Eurich DT, Padwal RS, Marrie TJ: Statins and outcomes in patients admitted to hospital with community acquired pneumonia: population based prospective cohort study. BMJ. 2006, 333: 999-10.1136/bmj.38992.565972.7C.PubMedPubMedCentralCrossRef Majumdar SR, McAlister FA, Eurich DT, Padwal RS, Marrie TJ: Statins and outcomes in patients admitted to hospital with community acquired pneumonia: population based prospective cohort study. BMJ. 2006, 333: 999-10.1136/bmj.38992.565972.7C.PubMedPubMedCentralCrossRef
24.
go back to reference Yende S, Milbrandt EB, Kellum JA, Kong L, Delude RL, Weissfeld LA, Angus DC: Understanding the potential role of statins in pneumonia and sepsis. Crit Care Med. 2011, 39: 1871-1878. 10.1097/CCM.0b013e31821b8290.PubMedPubMedCentralCrossRef Yende S, Milbrandt EB, Kellum JA, Kong L, Delude RL, Weissfeld LA, Angus DC: Understanding the potential role of statins in pneumonia and sepsis. Crit Care Med. 2011, 39: 1871-1878. 10.1097/CCM.0b013e31821b8290.PubMedPubMedCentralCrossRef
25.
go back to reference Dormuth CR, Patrick AR, Shrank WH, Wright JM, Glynn RJ, Sutherland J, Brookhart MA: Statin adherence and risk of accidents: a cautionary tale. Circulation. 2009, 119: 2051-2057. 10.1161/CIRCULATIONAHA.108.824151.PubMedPubMedCentralCrossRef Dormuth CR, Patrick AR, Shrank WH, Wright JM, Glynn RJ, Sutherland J, Brookhart MA: Statin adherence and risk of accidents: a cautionary tale. Circulation. 2009, 119: 2051-2057. 10.1161/CIRCULATIONAHA.108.824151.PubMedPubMedCentralCrossRef
26.
go back to reference Thomsen RW: The lesser known effects of statins: benefits on infectious outcomes may be explained by 'healthy user' effect. BMJ. 2006, 333: 980-981. 10.1136/bmj.39024.513218.BE.PubMedPubMedCentralCrossRef Thomsen RW: The lesser known effects of statins: benefits on infectious outcomes may be explained by 'healthy user' effect. BMJ. 2006, 333: 980-981. 10.1136/bmj.39024.513218.BE.PubMedPubMedCentralCrossRef
29.
go back to reference Charlson ME, Pompei P, Ales KL, MacKenzie CR: A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987, 40: 373-383. 10.1016/0021-9681(87)90171-8.PubMedCrossRef Charlson ME, Pompei P, Ales KL, MacKenzie CR: A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987, 40: 373-383. 10.1016/0021-9681(87)90171-8.PubMedCrossRef
30.
go back to reference de Groot V, Beckerman H, Lankhorst GJ, Bouter LM: How to measure comorbidity: a critical review of available methods. J Clin Epidemiol. 2003, 56: 221-229. 10.1016/S0895-4356(02)00585-1.PubMedCrossRef de Groot V, Beckerman H, Lankhorst GJ, Bouter LM: How to measure comorbidity: a critical review of available methods. J Clin Epidemiol. 2003, 56: 221-229. 10.1016/S0895-4356(02)00585-1.PubMedCrossRef
31.
go back to reference Deyo RA, Cherkin DC, Ciol MA: Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol. 1992, 45: 613-619. 10.1016/0895-4356(92)90133-8.PubMedCrossRef Deyo RA, Cherkin DC, Ciol MA: Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol. 1992, 45: 613-619. 10.1016/0895-4356(92)90133-8.PubMedCrossRef
32.
go back to reference Rothman KJ: Modern Epidemiology. 1998, Philadelphia, PA: Lippincott Williams & Wilkins Rothman KJ: Modern Epidemiology. 1998, Philadelphia, PA: Lippincott Williams & Wilkins
33.
go back to reference Austin PC, Anderson GM, Cigsar C, Gruneir A: Comparing the cohort design and the nested case-control design in the presence of both time-invariant and time-dependent treatment and competing risks: bias and precision. Pharmacoepidemiol Drug Saf. 2012, 21: 714-724. 10.1002/pds.3299.PubMedPubMedCentralCrossRef Austin PC, Anderson GM, Cigsar C, Gruneir A: Comparing the cohort design and the nested case-control design in the presence of both time-invariant and time-dependent treatment and competing risks: bias and precision. Pharmacoepidemiol Drug Saf. 2012, 21: 714-724. 10.1002/pds.3299.PubMedPubMedCentralCrossRef
34.
go back to reference Novack V, Eisinger M, Frenkel A, Terblanche M, Adhikari NK, Douvdevani A, Amichay D, Almog Y: The effects of statin therapy on inflammatory cytokines in patients with bacterial infections: a randomized double-blind placebo controlled clinical trial. Intensive Care Med. 2009, 35: 1255-1260. 10.1007/s00134-009-1429-0.PubMedCrossRef Novack V, Eisinger M, Frenkel A, Terblanche M, Adhikari NK, Douvdevani A, Amichay D, Almog Y: The effects of statin therapy on inflammatory cytokines in patients with bacterial infections: a randomized double-blind placebo controlled clinical trial. Intensive Care Med. 2009, 35: 1255-1260. 10.1007/s00134-009-1429-0.PubMedCrossRef
35.
go back to reference Sever PS, Chang CL, Gupta AK, Whitehouse A, Poulter NR: The Anglo-Scandinavian Cardiac Outcomes Trial: 11-year mortality follow-up of the lipid-lowering arm in the UK. Eur Heart J. 2011, 32: 2525-2532. 10.1093/eurheartj/ehr333.PubMedCrossRef Sever PS, Chang CL, Gupta AK, Whitehouse A, Poulter NR: The Anglo-Scandinavian Cardiac Outcomes Trial: 11-year mortality follow-up of the lipid-lowering arm in the UK. Eur Heart J. 2011, 32: 2525-2532. 10.1093/eurheartj/ehr333.PubMedCrossRef
36.
go back to reference Thomsen RW, Riis A, Norgaard M, Jacobsen J, Christensen S, McDonald CJ, Sorensen HT: Rising incidence and persistently high mortality of hospitalized pneumonia: a 10-year population-based study in Denmark. J Intern Med. 2006, 259: 410-417. 10.1111/j.1365-2796.2006.01629.x.PubMedCrossRef Thomsen RW, Riis A, Norgaard M, Jacobsen J, Christensen S, McDonald CJ, Sorensen HT: Rising incidence and persistently high mortality of hospitalized pneumonia: a 10-year population-based study in Denmark. J Intern Med. 2006, 259: 410-417. 10.1111/j.1365-2796.2006.01629.x.PubMedCrossRef
37.
go back to reference Gaist D, Sorensen HT, Hallas J: The Danish prescription registries. Dan Med Bull. 1997, 44: 445-448.PubMed Gaist D, Sorensen HT, Hallas J: The Danish prescription registries. Dan Med Bull. 1997, 44: 445-448.PubMed
38.
go back to reference Larsen J, Andersen M, Kragstrup J, Gram LF: High persistence of statin use in a Danish population: compliance study 1993-1998. Br J Clin Pharmacol. 2002, 53: 375-378. 10.1046/j.1365-2125.2002.01563.x.PubMedPubMedCentralCrossRef Larsen J, Andersen M, Kragstrup J, Gram LF: High persistence of statin use in a Danish population: compliance study 1993-1998. Br J Clin Pharmacol. 2002, 53: 375-378. 10.1046/j.1365-2125.2002.01563.x.PubMedPubMedCentralCrossRef
39.
go back to reference Thomsen RW, Nielsen RB, Nørgaard M, Horsdal HT, Larsen FB, Sørensen HT: Lifestyle profile among statin users. Presented at: 27th International Conference on Pharmacoepidemiology & Therapeutic Risk Management; 14-17. 2011, August ; Chicago, IL. Abstract 258 Thomsen RW, Nielsen RB, Nørgaard M, Horsdal HT, Larsen FB, Sørensen HT: Lifestyle profile among statin users. Presented at: 27th International Conference on Pharmacoepidemiology & Therapeutic Risk Management; 14-17. 2011, August ; Chicago, IL. Abstract 258
Metadata
Title
The impact of statin use on pneumonia risk and outcome: a combined population-based case-control and cohort study
Authors
Anders Gunnar Nielsen
Rikke Beck Nielsen
Anders Hammerich Riis
Søren Paaske Johnsen
Henrik Toft Sørensen
Reimar Wernich Thomsen
Publication date
01-08-2012
Publisher
BioMed Central
Published in
Critical Care / Issue 4/2012
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc11418

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