Ali Choukair describes for SIIC his article published in Journal of the Hong Kong College of Cardiology 23(2):68-74, October 2015

Beirut, Líbano (special for SIIC)
In the last two decades many research articles published suggested for a possible relation between development of coronary artery disease (CAD) and some infectious diseases, mainly infections that can cause long term inflammatory state. This hypothesis was later referred to as “the pathogen burden”. We wanted to test the validity of such hypothesis in our local population and for this aim we chose Brucella as our target pathogen since it's a common infectious organism in our area (402 cases of brucellosis reported in 2016 as per the Ministry of Public Health in Lebanon) and it's also known to be able to cause long term sub-clinical infectious state noted by elevated CRP level in some cases. There is current evidence that Brucella species can infect and survive within the endothelial cells of infected individuals and can induce a pro-inflammatory response, which may be responsible for the pathogenesis of the damage in the vascular system. Our targeted population were patients admitted for coronary angiogram in our medical center. A total of 424 patients were recruited over a period of 4 years (between January 2006 until February 2009). Medical records of enrolled patients were reviewed for demographics, the presence of known risk factors for CAD including family history, diabetes mellitus, hypertension, hypercholesterolemia, obesity, smoking, and dietary habits. Also blood tests (for Brucella titers and CRP level) from the patients where obtained and were compared against the result of their coronary angiograms. All those who experienced myocardial infarction within the previous 6 months, valvular heart disease, or non-atherosclerotic cardiomyopathy were excluded from the study. Subjects were categorized into two groups; those with greater than 75% stenosis in at least one coronary artery and those with normal or less than 75% stenosis. Male to female ratio was almost 3:1, almost 75% of our subjects had significant CAD, 75% had elevated CRP (CRP > 3), more than 50% were smokers, Brucella titer was positive in almost 12% of them. Our study showed that there was a strong association between elevated CRP levels (CRP > 3) and risk for having significant CAD (p-value = 0.01), as well there was a significant association between positive Brucella titers and high CRP levels (p-value = 0.016), but it failed to show any association between Brucella titers and the development of significant CAD. In our study there were no difference between patients who had significant CAD and those who didn't in regard to Brucella titer (p-value = 0.514). Factors that were associated with significant CAD were male gender (p = 0.004), smoking (p = 0.001), hypercholesterolemia (p = 0.008), diabetes mellitus (p = 0.010), statin therapy (p = 0.001) and CRP >3 (p = 0.010). Males were twice as likely to develop occlusive CAD as compared to females. Meanwhile patients with diabetes had a two-fold increased risk and patient with dyslipidemia had 2.4 fold increased risk. Despite some reports which suggested that Brucella species can infect and survive within endothelial cells, and can induce a pro-inflammatory response that might be involved in the vascular manifestations of brucellosis, and despite the findings in our study that showed patients with elevated CRP (CRP > 3) were more likely to have positive anti-Brucella titers than those with low CRP (14.9% vs. 5.8%), it was difficult to prove the presence of any significant association for Brucella as a contributory factor to occlusive CAD. Some published data have suggested that the aggregate effect of co-infection with multiple organisms rather than one organism may be responsible for the atherosclerotic role. This has been eluded to as the "infectious burden" or "pathogen burden". In one study, over 75% of CAD patients had been exposed to at least three of five pathogens tested, suggesting a possible link between increased pathogen burden and the risk of CAD irrespective of traditional risk factors. Thus, the contribution of infectious organisms to atherosclerosis pathogenesis is likely to involve simultaneous direct and indirect mechanisms involving multiple organisms. Regarding limitations in this study, the authors recognize the selection bias inherent in enrolling subjects from a patient population that is undergoing an invasive cardiovascular procedure and that the results obtained may not be necessarily applicable to the population as a whole. Another important limitation is attempting to categorize the study population into those with and without significant occlusive disease (more than 75% stenosis) irrespective of the presence of lumen-limiting CAD or not. Authors concluded that the current study failed to show an association between positive Brucella serology and the development of significant occlusive CAD, despite the presence of a significant correlation between Brucella antibody positivity and elevated CRP. Further studies would be needed to explore any relationship between Brucella infection and CAD including acute versus chronic infection, co-infection with other pathogens, and the interaction with other known risk factors.