Correspondence

Markers of Myocardial Damage and Inflammation in Unstable Coronary Artery Disease

N Engl J Med 2001; 344:688-689March 1, 2001

Article

To the Editor:

Lindahl and colleagues (Oct. 19 issue)1 report that elevated levels of troponin T and C-reactive protein are predictors of the long-term risk of death from cardiac causes in patients with unstable coronary artery disease. They specify the use of cardiac medications at admission in Table 1 but do not mention any concurrent treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). The statins do more than just lower cholesterol levels.2 Recent evidence demonstrates that they appear to be potent and effective cardioprotective agents that inhibit leukocyte–endothelial cell interactions, possibly through enhanced endothelial release of nitric oxide,3 which itself has been shown to have a cardioprotective role in ischemia–reperfusion injury.4

We would appreciate it if the authors could provide the details of such treatment, in view of the potential impact of their findings on future preventive strategies to reduce long-term mortality in patients with coronary artery disease.

Thomas Engelhardt, M.D.
Brian H. Cuthbertson, M.D.
University of Aberdeen, Aberdeen AB25 9ZD, United Kingdom

4 References

1. 1

   Lindahl B, Toss H, Siegbahn A, Venge P, Wallentin L. Markers of myocardial damage and inflammation in relation to long-term mortality in unstable coronary artery disease. N Engl J Med 2000;343:1139-1147
   Full Text | Web of Science | Medline

2. 2

   Vaughan CJ, Murphy MB, Buckley BM. Statins do more than just lower cholesterol. Lancet 1996;348:1079-1082
   CrossRef | Web of Science | Medline

3. 3

   Lefer AM, Campbell BA, Shin YK, Scalia R, Hayward R, Lefer DJ. Simvastatin preserves the ischemic-reperfused myocardium in normocholesterolemic rat hearts. Circulation 1999;100:178-184
   Web of Science | Medline

4. 4

   Jones SP, Girod WG, Palazzo AJ, et al. Myocardial ischemia-reperfusion injury is exacerbated in absence of endothelial cell nitric oxide synthase. Am J Physiol 1999;276:H1567-H1573
   Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: Drs. Engelhardt and Cuthbertson point out that statins might have other cardioprotective effects besides lowering cholesterol levels — for example, antiinflammatory effects — and request information about the use of statins in our study. We agree that this information would have been valuable, especially since it has been shown that long-term treatment with statins decreases inflammatory activity as measured by C-reactive protein levels1 and that statin treatment might decrease the risk associated with elevation of C-reactive protein.2 However, the use of statins at admission or during follow-up was not included in the case-report form in our study.

The study was begun in April 1992, before the results of the first large-scale trial of statins were presented.3 At that time, treatment with statins was very uncommon in clinical practice in Sweden. Even in 1995 and 1996, only 9 percent and 17 percent, respectively, of patients with myocardial infarction in Sweden were receiving statins at discharge (data from the Swedish register of cardiac intensive care). Therefore, one can assume that the influence of treatment with statins on the results of the present study was quite limited. Nevertheless, since the use of statins is now part of the standard treatment for coronary artery disease, the question of whether treatment with statins will influence the predictive value of markers of myocardial damage and inflammation is important. We hope to be able to answer that question as soon as we have the results of the Fragmin during Instability in Coronary Artery Disease inflammation substudy (FRISC II), which will include detailed information about statin use, inflammatory markers, markers of myocardial damage, and long-term outcome.

Bertil Lindahl, M.D., Ph.D.
Lars Wallentin, M.D., Ph.D.
University Hospital, S-751 85 Uppsala, Sweden

3 References

1. 1

   Ridker PM, Rifai N, Pfeffer MA, Sacks F, Braunwald E. Long-term effects of pravastatin on plasma concentration of C-reactive protein. Circulation 1999;100:230-235
   Web of Science | Medline

2. 2

   Ridker PM, Rifai N, Pfeffer MA, et al. Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Circulation 1998;98:839-844
   Web of Science | Medline

3. 3

   Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344:1383-1389
   Web of Science | Medline