Prevalence, pathogenesis, therapy, and prevention of cardiovascular events in patients with community-acquired pneumonia

Abstract

It is now well recognised that cardiac events occur relatively commonly in patients with acute community-acquired pneumonia. While these events are more frequent in patients with underlying risk factors—such as those with underlying chronic cardiovascular and respiratory comorbidities, the elderly, and in nursing home residents—they also occur in patients with no underlying risks other than severe pneumonia. Recent research elucidating the underlying pathogenic mechanisms related to these cardiac events has indicated a probable role for platelet activation, which is possibly exacerbated by pneumolysin in the case of pneumococcal infections. This, in turn, has resulted in the identification of possible therapeutic strategies targeting platelet activation, as well as the cardio-toxic activity of pneumolysin. These issues represent the primary focus of the current review.

Cardiovascular Events after Community-Acquired Pneumonia: A Global Perspective with Systematic Review and Meta-Analysis of Observational Studies

“…Whilst the baseline comorbidities may share the same approach and in a way merely denote a sicker patient, different microbes may pose an opportunity for influencing patient outcomes by improving time to diagnosis and starting pathogen specific interventions. For pneumococcal pneumonia, bacterial exotoxin pneumolysin has been identified as key effector of cell and organ damage in murine models [101,102] and could theoretically become a target for macrolides (or macrolide-like antibiotics), statins or cholesterol rich liposomes [103]. If influenza is being considered, prompt detection may allow the early initiation of neuraminidase inhibitors.…”

The Role of Streptococcus pneumoniae in Community-Acquired Pneumonia

“…These have also been covered in a recent review, 122 and this topic is extended and updated here. Ply-directed therapeutic strategies which have demonstrated protective efficacy in murine models of experimental IPD include (1) intravenous administration of a cocktail of three murine monoclonal antibodies directed against different epitopes on the Ply molecule 140 ; (2) intravenous administration of cholesterol/ sphingomyelin-enriched, Ply-neutralizing liposomes 141 ; (3) intracutaneous administration of liposomes enriched with the phytosterol, β-sitosterol, which mimics the Ply-binding activity of cholesterol 142 ; and (4) verbascoside, a plant-derived phenylpropanoid glycoside, which also targets Ply and, when administered subcutaneously, protects mice against lethal infection with the pneumococcus.…”

“…Some aspects of this section of the current review have recently been described elsewhere 122 and these are updated here. Notwithstanding its role in the pathogenesis of ALI, evidence, largely derived from experimental studies, is also consistent with the involvement of Ply in the pathogenesis of the well-recognized occurrence of cardiac damage and dysfunction associated with IPD described above.…”

“…148 Notwithstanding secondary, immunomodulatory properties, these inhibitory effects of macrolides on the synthesis of Ply by the pneumococcus are also likely to contribute to the utility of these agents in the adjunctive therapy of severe CAP. 122 On a cautionary note, however, some concerns have been raised in relation to the inclusion of macrolides in the antimicrobial/adjunctive therapy of CAP due to the existence of data linking these agents to an increased risk of cardiovascular disease, albeit by poorly characterized mechanisms. 149 These concerns may, however, be "overstated" according to the findings of a very recent population-based, retrospective cohort study conducted in Canada 150 over the period 2002 to 2013.…”

Pathogenesis and prevention of risk of cardiovascular events in patients with pneumococcal community‐acquired pneumonia

“…Subsequently, Seedat et al documented the occurrence of significant electrographic changes in patients with community-CAP, in association with cardiac enzyme leaks [creatinine kinase (CK), including the cardiac fraction (CK-MB)], which were associated with the severity of infection [9]. More recently, a number of other investigators have documented the occurrence of a variety of CVEs in patients with CAP [10][11][12]. These findings were in agreement with those of an earlier systematic review and meta-analysis of complications in patients with CAP, which had indicated that significant cardiac complications occurred in a considerable number of cases [13].…”