Author + information
- Carlos G. Santos-Gallego, MD and
- Juan Badimon, PhD∗ ()
- ↵∗Atherothrombosis Research Unit, Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, Box 1030, New York, New York 10029
We appreciate the interest by Dr. Gavrillaki and colleagues in our editorial and their insightful comments.
First of all, Dr. Gavrillaki and colleagues indicate that we support the infection hypothesis for atherosclerosis. We do not support such hypothesis, and thus, this affirmation was not stated in our editorial. We do believe the role of inflammatory processes (not necessarily infective) in the genesis and progression of atherosclerosis (1). In fact, a variety of systemic proinflammatory conditions increase the risk of atherosclerotic cardiovascular events, including rheumatoid arthritis, systemic lupus erythematosus, or psoriatic arthritis (2). Furthermore, atherosclerosis is aggravated by systemic inflammation of any etiology, as the one seen after myocardial infarction (MI) (3). It is in this context of atherosclerosis as a systemic inflammatory disease (but never of atherosclerosis as caused by microorganisms) where our comments about the pathophysiological link between community-acquired pneumonia (CAP) and MI should be placed. It is the systemic inflammatory response originated by CAP and influenza infection (and not the microorganism per se) that most likely aggravates atherosclerosis burden and contribute to the destabilization of atheroma plaques, thus increasing the risk of MI. In fact, we do agree with Dr. Gavrillaki and colleagues in the microorganism theory having been refuted long ago (4).
Second, Dr. Gavrillaki and colleagues consider the increased platelet activation in CAP patients developing MI because of the comorbidities of those patients, and thus already present even before the CAP. Notwithstanding, Cangemi et al. (5) adjust in the multivariate analysis for those baseline (i.e., pre-CAP) comorbidities (age, sex, body mass index, diabetes, hypertension, renal failure, previous MI or stroke, peripheral artery disease), and they also test for collinearity, so we can conclude that enhanced platelet reactivity in CAP patients is independently associated with MI even after adjusting for those baseline comorbidities. That platelet aggregation is a risk marker or a risk factor is a different story that cannot be demonstrated statistically, only by trial evidence, demonstrating that altering the risk factor (platelet aggregation in CAP) changes the prognosis (MI).
Finally, we do agree with Dr. Gavrillaki and colleagues regarding that platelet reactivity, not aggregation, was assessed in the study by Cangemi et al. (5). As they suggest, the monocyte–platelet aggregates (MPA) are one marker of platelet activation that could shed additional information on the link between platelet activation in CAP and MI. However, heterotypic platelet aggregation (of which MPA is the prime example) is not the only parameter to assess/study platelet activation. Other markers such as homotypic platelet aggregation (by light-transmission aggregometry) or soluble serum markers (such as the P-Selectin, CD40L, or TXB2 that Cangemi et al.  used) are universally established/accepted, so the choice of a specific marker does not change the hypothesis-generating message of this article. Future studies will undoubtedly analyze additional markers of platelet activation (including MPA) to profile in depth the postulated mechanistic role of increased platelet reactivity in MI incidence among CAP patients.
- American College of Cardiology Foundation
- Mason J.C.,
- Libby P.
- Cangemi R.,
- Casciaro M.,
- Rossi E.,
- et al.,
- for the SIXTUS Study Group