doi: 10.1161/CIRCULATIONAHA.107.752386
(Circulation. 2008;117:e170.)
© 2008 American Heart Association, Inc.
Correspondence |
Response to Letter Regarding Article, "Plasminogen Activator Inhibitor-1 as a Predictor of Postoperative Atrial Fibrillation After Cardiopulmonary Bypass"
Department of Anesthesiology, Vanderbilt University Medical School, Nashville, Tenn
Department of Biostatistics, Vanderbilt University Medical School, Nashville, Tenn
Department of Cardiac Surgery, Vanderbilt University Medical School, Nashville, Tenn
Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Vanderbilt University Medical School, Nashville, Tenn
We are thankful to Drs Roldán, Marín, and Lip for their interest in our study.1 We agree that the pathophysiology of postoperative atrial fibrillation (AF) is complex and likely involves interactions among surgical trauma, activation of the inflammatory response, preexisting atrial pathology, and specific triggers. Elevated plasminogen activator inhibitor-1 (PAI-1) levels may reflect augmented transcriptional activation and secretion by many molecules, including insulin, proinsulin-like molecules, glucose, very-low-density lipoprotein, and angiotensin II.2 In our study, PAI-1 significantly correlated with age and body mass index. PAI-1 remained an independent predictor of postoperative AF even after we controlled for possible confounding factors, including body mass index and history of diabetes. We do not claim a direct causal role for PAI-1 in the development of postoperative AF, but we hypothesize that an important action of elevated preoperative PAI-1 may be to promote fibrosis through a decrease in extracellular matrix degradation. Matrix metalloproteinase-9 was measured immediately after cardiopulmonary bypass in our study and may not reflect matrix metalloproteinase-9 concentrations at other time points. That elevated PAI-1 predicted postoperative AF raised the hypothesis that drugs that decrease PAI-1 could influence the risk of postoperative AF. One such class of drugs is the angiotensin-converting enzyme inhibitors, which decrease the risk of AF in patients with left ventricular dysfunction.3 Statins also decrease PAI-14 and have been shown to reduce postoperative AF.5 Thus, we agree that the finding that elevated PAI-1 predicts postoperative AF merits further mechanistic study with a view to improved prophylaxis.
 |
Acknowledgments |
|---|
Disclosures
None.
|
References |
|---|
 Top References |
|---|
1. Pretorius M, Donahue BS, Yu C, Greelish JP, Roden DM, Brown NJ. Plasminogen activator inhibitor-1 as a predictor of postoperative atrial fibrillation after cardiopulmonary bypass. Circulation. 2007; 116 (suppl I): I-1–I-7.[Medline] [Order article via Infotrieve]
2. Kohler HP, Grant PJ. Plasminogen-activator inhibitor type 1 and coronary artery disease. N Engl J Med. 2000; 342: 1792–1801.
3. Pedersen OD, Bagger H, Kober L, Torp-Pedersen C. Trandolapril reduces the incidence of atrial fibrillation after acute myocardial infarction in patients with left ventricular dysfunction. Circulation. 1999; 100: 376–380.
4. Dangas G, Badimon JJ, Smith DA, Unger AH, Levine D, Shao JH, Meraj P, Fier C, Fallon JT, Ambrose JA. Pravastatin therapy in hyperlipidemia: effects on thrombus formation and the systemic hemostatic profile. J Am Coll Cardiol. 1999; 33: 1294–1304.
5. Patti G, Chello M, Candura D, Pasceri V, D’Ambrosio A, Covino E, Di Sciascio G. Randomized trial of atorvastatin for reduction of postoperative atrial fibrillation in patients undergoing cardiac surgery: results of the ARMYDA-3 (Atorvastatin for Reduction of Myocardial Dysrhythmia After Cardiac Surgery) Study. Circulation. 2006; 114: 1455–1461.
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||