Different acute phase response to a standardized stimulus in patients with history of stable or unstable coronary heart disease

The basis of the relationship between inflammation and atherosclerosis are not fully understood. We speculated that the characteristics of the innate immune response may influence the development and expression of CHD. Thus, we compared the C-reactive protein (CRP) and serum amyloid A (SAA) responses to a standardized inflammatory stimulus in patients with history of stable or unstable CHD Methods: Adjuvanted influenza subcutaneous vaccination (lnflexal v®) was given to 60 adult male non-diabetic and non-current smoker patients with quiescent CHD and well controlled cardiovascular (CV) risk factors who had presented at onset of CHD as silent or inducible ischemia (group 1, n=26) or as acute coronary syndromes (group 2; n=34 ). CRP and SAA were determined by ELISA on plasma samples collected at baseline and 48 hours after vaccination, according to the results of a pilot time-course study performed in 5 healthy subjects. Results: The patients were immunocompetent and free of inflammatory conditions. Both groups were similar at baseline in terms of risk factor control, use of CV drugs including aspirin (1 00%) and statins (90%), and median [25-75th perc] CRP and SAA levels. Vaccination significantly augmented CRP in both groups (group 1: 0.47 [0.21-0.86] to 0.56 [0.32-1.17] µg/ml, p=0.005; group 2: 0.64 [0.21-1.09] to 0.75 [0.33-1.48] µg/ml, p=0.003), without significant differences between groups in terms of absolute or percent changes. Conversely, SAA did not change after vaccination in group 1 (14.4 [8.9-19.5] to 14.8 [10.3- 18.8] µg/ml , p=0.88) whereas it augmented significantly in group 2 (16.9 [1 0.0-21.5] to 19.2 [11.3-29.1] µg/ml , p=0.002), with significant differences between groups in terms of absolute and percent changes (p=0.015 and 0.019, respectively). Use of statins significantly interacted with changes induced by vaccination in CRP levels (p=0.05) but not in SAA levels (p=0.47). Conclusion: CHD patients with a history of stable or unstable disease respond differently to a defined standardized inflammatory stimulus (influenza vaccination) in terms of SAA changes, suggesting that individual features of the innate immune response may influence the clinical expression of CHD, presumably by determining attributes of atherosclerotic lesions. Lack of significant differences in terms of CRP changes may be related to interference by statins.