Table 4– Bradford Hill [108] criteria for causality and the evidence so far

Criterion	Evidence
Strength of association	Strong association depicted in the study by Corrales-Medina et al. [96] Patients were eight times more likely than controls to have a cardiac event 15 days after hospital admission with CAP
Consistency of results in a variety of settings	Studies in both primary and secondary care of a variety of study designs, including case–control and cohort, have shown an increased risk of cardiovascular events following acute respiratory infection
Specificity	Both pneumonia and cardiovascular disease are multifactorial and share common risk factors; therefore, this is difficult to confirm
Temporality	Primary care database studies showed risk of myocardial infarction decreasing with time following infection [82–84]
Biological gradient	In the study by Ramirez et al. [94], a positive association between pneumonia severity score and AMI was noted
Plausibility	Experimental evidence, as highlighted in this review, supports a role for infection in cardiovascular events
Coherence	Laboratory, epidemiological and clinical evidence is consistent in supporting a role for infection in cardiovascular events
Experimental evidence	In vitro/animal model studies specific to pneumonia are awaited Vaccination studies to date are not consistent enough to satisfy this criterion [101–104]
Analogy	The effect of other established cardiovascular risk factors could be considered analogous to that of pneumonia