Community-Acquired Pneumonia: Pathogenesis of Acute Cardiac Events and Potential Adjunctive Therapies

doi:10.1378/chest.15-0484

Chest

Volume 148, Issue 2, August 2015, Pages 523-532

https://doi.org/10.1378/chest.15-0484 Get rights and content

Despite advances in antimicrobial chemotherapy and access to sophisticated intensive care facilities, bacterial community-acquired pneumonia (CAP) continues to carry an unacceptably high mortality rate of 10% to 15% in hospitalized cases. CAP, considered by many to be the most underestimated disease worldwide, poses a particular threat to the elderly whose numbers are steadily increasing in developed countries. Indeed, elderly patients with severe CAP, as well as those with other risk factors, are at significant risk for development of inflammationmediated acute cardiac events that may undermine the success of antimicrobial therapy. Adjunctive antiinflammatory strategies are, therefore, of considerable potential benefit in this setting. Currently, the most promising of these are the macrolides, corticosteroids, and, more recently, statins, all of which target immune/inflammatory cells. In addition, recent insights into the immunopathogenesis of acute coronary events in patients with CAP have revealed a probable pivotal role of platelet activation, potentially modifiable by agents that possess antiinflammatory or platelet-targeted activities or both. Statins, which not only possess antiinflammatory activity but also appear to target several pathways involved in platelet activation, seem particularly well suited as adjuncts to antibiotic therapy in bacterial CAP. Following a brief consideration of the immunopathogenesis of bacterial CAP, this review is focused on mechanisms of platelet activation by CAP pathogens, as well as the pharmacologic control thereof, with emphasis on statins. CHEST 2015;148(2):523-532

Section snippets

Pathogenesis of CAP

The three most common causes of bacterial CAP are Streptococcus pneumoniae (the pneumococcus), Haemophilus influenzae, and Moraxella catarrhalis. Collectively, these organisms account for > 80% of cases of CAP, the pneumococcus being the predominant cause (> 60% of cases). Colonization of the upper airways by these organisms is mediated via the interaction of bacterial surface adhesins with respiratory epithelium which is a prerequisite for development of invasive disease. During this phase,

CAP, Acute Cardiac Events, and Platelet Activation

With respect to CAP-associated cardiovascular disorders, the increased risk for cardiac events in hospitalized patients may be as high as eightfold in the 15-day period following admission and greatest (100-fold increased risk) within the first 2 to 3 days.⁶ Incident cardiac complications associated with increased morbidity and mortality include myocardial infarction (predominantly silent) and new or worsening heart failure or arrhythmias, with the major risk factors being older age, nursing

Alternative Mechanisms of CAP-Associated Cardiac Events

Experimental studies in mice and macaques have revealed that invasive pneumococcal disease leads to translocation of the pneumococcus into the myocardium resulting in the formation of “unique microlesions that disrupt cardiac function.”²² Bacterial translocation into the heart and formation of microlesions was found to be dependent on the pneumococcal adhesin, choline-binding protein A, and the cholesterol-binding pore-forming cytotoxin, pneumolysin, respectively.²² In this context, it is

Therapeutic Implications

Among the myriad of adjunctive therapies that have been studied, the three major options are the macrolides, corticosteroids, and statins, all of which have been documented to possess antiinflammatory activities, targeting various cell types and their mediators and, to a greater or lesser extent, to have antiplatelet effects.

Conclusions

Despite all advances in medical care, patients with CAP still have considerable morbidity and mortality. It has been suggested that adjunctive therapy, with the addition of agents that target aspects of disease pathogenesis may be helpful in improving outcome and to this end a number of agents have been considered. Recent research indicating the relatively frequent occurrence of cardiac events in patients with CAP, which has been documented to be associated with a poorer prognosis, has

Acknowledgments

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Feldman has received honoraria for lectures and for participating in advisory boards from pharmaceutical companies manufacturing or marketing macrolide antibiotics (Abbott Laboratories, Aspen Pharmacare, Pfizer Inc, Sandoz). Dr Anderson has reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

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