CHADS2 score and C-reactive protein

SALT LAKE CITY, UTAH. Several studies have observed a direct correlation between atrial fibrillation and elevated value for the inflammation marker hs-CRP (high-sensitivity C-reactive protein). This correlation applies to both lone afibbers and afibbers with underlying heart disease. There is also evidence that permanent afibbers tend to have higher CRP values than persistent afibbers who, in turn, have higher values than paroxysmal afibbers.

A study of 5000 healthy individuals without afib found that CRP values varied between 0.01 mg/dL (0.1 mg/L) and 0.38 mg/dL (3.8 mg/L) with a median of 0.16 mg/dL (1.6 mg/L). A CRP value above 0.38 mg/dL (3.8 mg/L) is generally considered a sign of a systemic inflammation. There is also evidence that a high CRP value increases the risk of ischemic stroke.

Researchers at the Mayo Clinic and the University of Utah School of Medicine have now quantified the relationship between CRP and stroke risk. They correlated CRP results from 2340 patients with suspected coronary artery disease (CAD) with the patientsí CHADS2 score. The CHADS2 score is an estimate of the risk of ischemic stroke in which congestive heart failure, hypertension, age over 75 years, and diabetes are each assigned a point score of 1, while having experienced a stroke or a transient ischemic attack (TIA) is assigned a point score of 2.

The study group included 3288 patients who underwent coronary angiography for suspected CAD. Of these, 61% did indeed have CAD, 56% had hypertension, 19% diabetes, 15% congestive heart failure, and 2% had suffered a prior stroke or TIA. Ten percent of the group had atrial fibrillation (AF) who, on average, had a higher CRP level (14.0 mg/L or 1.4 mg/dL) than did study participants without AF (9.1 mg/L or 0.9 mg/dL). A higher CHADS2 score was found to be associated with a higher CRP value.

CHADS2 Score
hs-CRP, mg/L
0
1.99 (0.2 mg/dL)
1
2.91 (0.29 mg/dL)
2
3.49 (0.35 mg/dL)
3
3.89 (0.39 mg/dL)
4 - 5
4.82 (0.48 mg/dL)

Patients with AF tended to have higher CRP values for equivalent CHADS2 scores, but this increase was only statistically significant for a CHADS2 score of 2 indicating that afib, on its own, does not increase CRP in patients with a low risk of ischemic stroke (0 or 1 risk factor).

Crandall, MA, et al. Atrial fibrillation and CHADS2 risk factors are associated with highly sensitive C-reactive protein incrementally and independently. PACE, Vol. 32, May 2009, pp. 648-52

Editorís comment: The authors of the study conclude that the presence of AF increases hs-CRP across the CHADS2 score strata and that this means AF is an inflammatory process and may convey an independent risk of ischemic stroke. It is indeed unfortunate that their data does not support this conclusion, i.e. patients with AF and a CHADS2 score of 0 or 1 (none or one risk factor) do not have a statistically significant higher level of CRP than do patients without AF. Furthermore, the CRP levels associated with CHADS2 scores of 0 and 1 (2 mg/L and 2.9 mg/L) are not generally considered a sign of systemic inflammation, but are within the range observed in healthy people. It would seem that the conclusions drawn from this study are flawed, but as the headlines reporting the results in the mainstream media will no doubt read ďAF is an independent risk factor for strokeĒ, I thought it useful to debunk this study before its results attain the status of dogma.