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LETTER TO THE EDITOR

Beneficial Effects of Statin Therapy on Infection Related Mortality in Patients with Atherosclerotic and Cardiovascular Disease

Assistant Professor; Department of Anaesthesia; ASCOMS; Jammu, J&K; drmahajanr{at}rediffmail.com (Mahajan) Senior Resident; Department of Hepatology; PGIMER; Chandigarh (Gupta) Junior Resident; Department of Anaesthesia; ASCOMS; Jammu, J&K (Sharma)

To the Editor:

The recent editorial by Sethi and Collard described beneficial effects of statins in decreasing surgical morbidity and mortality.1 In addition to direct cholesterol reduction and pleiotropic effects, which include antiatherosclerotic, antithrombotic, antiinflammatory, antioxidant, and endothelial stabilizing properties, statins also reduce the incidence of infection and sepsis, which, in turn, contributes to decreased mortality and morbidity in patients with cardiovascular and atherosclerotic disease.2–4

A pivotal population-based cohort study, the largest of its kind so far, 141,487 patients hospitalized for an acute coronary syndrome, ischemic stroke, or arterial revascularization and survived 3 mo after discharge, found that the incidence of sepsis was substantially lower among patients receiving statin therapy than controls.3 This protective association between statins and sepsis persisted in high risk subgroups, including patients with diabetes mellitus, chronic renal failure, chronic liver disease, malignancy, or those with history of recurrent infections.

Atherosclerosis and sepsis share several pathophysiologic similarities, including immune dysregulation, increased thrombogenesis, and systemic inflammation. Therefore, it is not surprising to find beneficial effects of statins in patients with sepsis.3,4 Pretreatment in animals with statins leads to substantial reductions in inflammatory cytokines and activation of immune cells, findings which have since been replicated in human studies.5–7 Additionally, statins appear to decrease the overproduction of nitric oxide implicated in the vasodilatation and circulatory collapse of septic shock.5,8 Beneficial effects of statins in sepsis have also been attributable to their antioxidant and anticoagulant properties.9,10

Therefore, prevention of sepsis and reduced risk of infection-related mortality in patients with atherosclerotic and cardiovascular disease seems to be a major advantage of statins and should have been discussed by Sethi and Collard in their editorial, an important preamble/ preface to the landmark trial by Le Menach et al.11

Footnotes

Dr. Collard does not wish to respond.

REFERENCES

1. Sethi M, Collard CD. Perioperative statin therapy: are formal and physician education needed? Anesth Analg 2007;104: 1322–4[Free Full Text]
2. Kinlay S, Ganz P. Early statin therapy in acute coronary syndromes. Semin Vasc Med 2003;3:419–24[Medline]
3. Hackam DG, Mamdani M, Li P, Redelmeier DA. Statins and sepsis in patient s with cardiovascular disease: a population based cohort analysis. Lancet 2006;367:413–8[Web of Science][Medline]
4. Amlong Y, Novack V, Eisinger M, Porath A, Novack L, Gilutz H. The effect of statin therapy on infection related mortality in patients with atherosclerotic disease. Crit Care Med 2007;35:327–8[Web of Science][Medline]
5. Merx MW, Liehn EA, Janssens U. HMG-CoA reductase inhibitor, simvastatin profoundly improves survival in a murine model of sepsis. Circulation 2004;109: 2560–5[Abstract/Free Full Text]
6. Steiner S, Speidl WS, Pleiner J, Seidinger D, Zorn G, Kaun C, Wojta J, Huber K, Minar E, Wolzt M, Kopp CW. Simvastatin blunts endotoxin-induced tissue factor in vivo. Circulation 2005;111:1841–6[Abstract/Free Full Text]
7. Pleiner J, Schaller G, Mittermayer F, Zorn S, Marsik C, Polterauer S, Kapiotis S, Wolzt M. Simvastatin prevents vascular hyporeactivity during inflammation. Circulation 2004;110:3349–54[Abstract/Free Full Text]
8. Giusti-Paiva A, Martinez MR, Felix JV, da Rocha MJ, Carnio EC, Elias LL, Antunes-Rodrigues J. Simvastatin decreases nitric oxide overproduction and reverts the impaired vascular responsiveness induced by endotoxic shock in rats. Shock 2004;21:271–5[Web of Science][Medline]
9. Durrant R, Klouche K, Delbosc S, Morena M, Amigues L, Beraud JJ, Canaud B, Cristol JP. Superoxide anion overproduction in sepsis: effects of vitamin E and Simvastatin. Shock 2004;22: 34–9[Web of Science][Medline]
10. Shi J, Wang J, Zheng H, Ling W, Joseph J, Li D, Mehta JL, Ponnappan U, Lin P, Fink LM, Hauer-Jensen M. Statins increase thrombomodulin expression and function in human endothelial cells by nitric oxide-dependent mechanism and counteract tumor necrosis factor alpha-induced thrombomodulin down regulation. Blood Coagul Fibrinolysis 2003;14: 575–85[Web of Science][Medline]
11. Le Manach Y, Godet G, Coriat P, Martinon C, Bertrand M, Fléron MH, Riou B. The impact of postoperative discontinuation or continuation of chronic statin therapy on cardiac outcome after major vascular surgery. Anesth Analg 2007;104:1326–33[Abstract/Free Full Text]

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