C-Reactive Protein, Serum Amyloid A Protein, and Coronary Events
To the Editor:
Ridker et al1 examined C-reactive protein (CRP) and serum amyloid A protein (SAA) in patients from CARE, a secondary-prevention study of pravastatin after myocardial infarction. They observed that the median plasma concentrations of CRP (0.31 versus 0.28 mg/dL; P=0.05) and SAA (0.34 versus 0.28 mg/dL; P=0.006) were significantly higher among those in whom coronary events occurred than in age- and sex matched controls. They concluded that the plasma concentrations of CRP and SAA predict the risk of recurrent coronary events among patients with prior myocardial infarction.
However, the matching of the subjects and controls was not complete. The group in whom events occurred contained a significantly higher proportion of diabetic patients (22.3% versus 9.7%; P=0.001), who are known to be at high risk of coronary events.2
We investigated 23 diabetic patients (mean age 62.0 years, SD 10.3, range 42 to 76; 18 men, 5 women) and 33 nondiabetic controls (61.3 years, SD 9.2, range 39 to 86; 31 men, 2 women), all with similar symptoms of stable angina and angiographically confirmed coronary disease. There were no significant differences between the groups in the mean number of affected coronary vessels (2.47 in diabetic and 2.21 in controls) or in history of hypertension, smoking, total cholesterol, cholesterol subfractions, or use of statins and aspirin. However, we found that the diabetic patients had significantly higher plasma concentrations of both CRP (mean, SD of log values 2.78, −0.60, +0.77 versus 1.52, −1.00, +2.92 mg/L, P=0.05) and SAA (mean, SD of log values 2.33, −1.52, +4.38 versus 1.15, −0.86, +3.38 mg/L, P=0.042). The values of these analytes were highly skewed, as usual, but were normalized by log transformation and were then subjected to a 1-way ANOVA.
In view of these findings, it is possible that higher levels of CRP and SAA observed by Ridker et al may have been due to an excess of diabetic patients in the event group. Larger studies will establish the role of CRP and SAA as predictors of future events in diabetic patients. The inflammatory response may be an important factor in the predisposition to atherothrombotic events in diabetes. The stimuli responsible for the acute-phase response in higher-risk atherosclerosis patients may arise from more severe, extensive, or unstable arterial lesions and/or from inflammation or low-grade infection elsewhere.
- Copyright © 1999 by American Heart Association
Ridker PM, Rifai N, Pfeffer MA, Sacks FM, Moye LA, Goldman S, Flaker GC, Braunwald E, for the Cholesterol and Recurrent Events (CARE) Investigators. Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Circulation. 1998;98:839–844.