One of the earliest studies documenting the occurrence of cardiac changes in patients with community-acquired pneumonia, was an investigation of the electrocardiographic, echocardiographic, and cardiac biomarker changes in patients between the ages of 15 and 50 years, without evidence of any pre-existing or underlying cardiorespiratory illness, admitted to hospital for community-acquired pneumonia of all-cause aetiology [1]. A variety of electrocardiographic changes were documented to occur in 31% (32/102) of the patients, varying from clockwise rotation through to cardiac arrythmias. These electrocardiographic changes, especially those compatible with acute cor pulmonale and accompanied by a cardiac enzyme leak (creatinine kinase, and cardiac fraction of creatinine kinase [CK-MB] leak), correlated with severity of illness but not mortality and most of these abnormalities returned to normal in survivors within 2 days. In 2007, Musher and colleagues documented the association between acute cardiac changes and pneumococcal pneumonia [2]. These investigators documented the occurrence of myocardial infarction, serious arrythmia or new or worsening congestive heart failure in these patients, with 33 of 170 patients (19.4%) having one or more of these events, and in the study these events were significantly associated with mortality. Thereafter, others continued to document cardiac complications in patients with community-acquired pneumonia, which were noted to be associated with increased short-term mortality (30-days) [3, 4]. In the former study, older age, residents of nursing homes, those with underlying cardiovascular conditions and pneumonia severity were important risk factors. Additional studies documented that these intrahospital cardiac complications, occurring early during the course of pneumonia were also associated with cardiovascular events and death even in long-term follow up after hospital discharge [5, 6]. Among the risk factors for both early and late events following community-acquired pneumonia were age, smoking, severity of pneumonia, infection with S. pneumoniae, as well as hypertension and diabetes mellitus, factors that were also associated with increased risk of mortality [5, 6]. The latter authors also noted that measurement of some of the newer cardiac biomarkers and systemic inflammatory markers (especially interleukin-6) were able to predict those patients at risk for both early and for long-term cardiac events and indicated that these biomarkers may be helpful for use in planning personalised treatment of cases with community-acquired pneumonia [7]. Studies have also evaluated whether people living with HIV were at increased risk of cardiovascular events, or mortality, following hospitalisation for community-acquired pneumonia [8]. In one study, the risk of cardiovascular events was similar in people living with HIV compared to HIV-negative cases; however, after adjusting for known cardiovascular disease risk and severity of CAP, HIV was noted on multivariable analysis to be an independent predictor of mortality at 30-days. Perhaps not surprisingly, cardiovascular complications were noted to occur in 18% of patients hospitalised with severe acute respiratory syndrome (SARS)-CoV-2 pneumonia [9]. Prior comorbidities, older age, male sex, severity of illness and presence of hypoxaemia were associated with the occurrence of cardiovascular complications, and once these occurred the risk of death was extremely high. Much recent research has studied potential mechanisms for these cardiovascular events occurring in association with community-acquired pneumonia, some of which has been reviewed elsewhere [10]. Most interestingly, one group of researchers noted the occurrence of microlesions in the myocardium in association with invasive pneumococcal disease in a variety of animal species, including subsequently, in non-human primates, and even in humans, which housed extracellular S. pneumoniae [11]. The thiol-activated pore forming toxin of the pneumococcus, pneumolysin, was required for the formation of these microlesions and among other factors, platelet activating factor receptor was required for translocation of the microorganisms into the ventricular lesions. Interestingly, administration of antibiotics was associated with a robust immune response to these lesions with subsequent deposition of collagen tissue, associated with long-term scarring in the myocardium, compatible with the long-term cardiovascular events following community-acquired pneumonia. Other researchers have documented additional potential mechanisms of cardiovascular events concentrating their research onto the prothrombotic/proinflammatory mechanisms of pneumococcal mediated myocardial damage [10]. These investigators, in a series of in vitro investigations, noted that pneumococcal virulence factors, particularly pneumolysin, initiate a chain of events leading to platelet activation, with homotypic platelet aggregation, formation of heterotypic neutrophil: platelet aggregates, as well as the formation of neutrophil extracellular traps all of which may pose the risk of intravascular coagulation leading to further myocardial injury. Figure 1 shows the proposed mechanisms involved in the pathogenesis of pneumolysin-mediated cardiac injury in patients with invasive pneumococcal disease. The latter authors further reviewed the concept of persistent antigenaemia and inflammation that may underpin the long-term cardiovascular consequences of community-acquired pneumonia. While it has been known that low-grade endotoxaemia may occur in community-acquired pneumonia, its possible role in these cardiovascular events had until more recently not been elucidated. Cangemi and colleagues studied the occurrence of cardiovascular events in patients with community-acquired pneumonia and noted that there was a progressive increased in these events from the lowest to the highest tertile of lipopolysaccharide [12]. Logistic regression analysis confirmed that the higher tertile of lipopolysaccharide was independently associated with cardiovascular events. These authors recommended further studies to determine the effects of lowering lipopolysaccharide using non-absorbable antibiotics. Clearly, while the occurrence of a cardiovascular event in a patient with community-acquired pneumonia needs to be recognised early, and appropriately managed, the ongoing challenge is how to prevent them from occurring in the first place. In this regard, there have been studies investigating possible options. For example, one study noted that use of aspirin was associated with a reduction in the short-term occurrence of ischaemic stroke and myocardial infarction in participants in primary care who developed pneumonia [13], while a retrospective study documented that patient's hospitalised with community-acquired pneumonia, who were on corticosteroids, has a lower incidence of myocardial infarction [14]. There is also the important consideration that vaccination can prevent many of these infections in the first place, which has several potential benefits both to the individual and to society. The author declares no conflicts of interest.
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