Infections as Novel Risk Factors of Atherosclerotic Cardiovascular Diseases: Pathophysiological Links and Therapeutic Implications

Abstract

Atherosclerotic cardiovascular diseases (ASCVD) are the major cause of mortality worldwide. Despite the continuous progress in ASCVD therapy, the residual risk persists beyond the management of traditional risk factors. Several infections including Helicobacter pylori infection, periodontal disease, and viral infections are associated with the increased risk of ASCVD, both directly by damage to the heart muscle and vasculature, and indirectly by triggering a systemic proinflammatory state. Hence, beyond the optimal management of the traditional ASCVD risk factors, infections should be considered as an important non-classical risk factor to enable early diagnosis and appropriate treatment. Here, we summarized the currently available evidence regarding the role of inflammation in ASCVD and the association between the particular infections and pathogens (Helicobacter pylori, periodontal disease, pneumonia, Cytomegalovirus, Human immunodeficiency virus, Herpes simplex virus, and severe acute respiratory syndrome coronavirus 2) on the development and progression of ASCVD. We also speculated about the potential therapeutic implications of the anti-inflammatory and anti-infective drugs on ASCVD outcomes, including drugs routinely administered in patients with ASCVD (statins, P2Y12 receptor inhibitors, and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers) and novel strategies aiming at residual risk reduction (colchicine, anti-cytokine drugs, and methotrexate). Considering the emerging association between infections and ASCVD, it is crucial to determine the possible advantages of infection prevention and treatment in patients with ASCVD.

Unexpected Relationships: Periodontal Diseases: Atherosclerosis–Plaque Destabilization? From the Teeth to a Coronary Event

“…It is worth noting that not only periodontal pathogens contribute to the development of atherosclerosis, but also infections with such pathogens as: H. pylori , pneumonia pathogens, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), cytomegalovirus (CMV), herpes simplex virus (HSV), hepatitis-C virus (HCV) and HIV [ 155 ].…”

The Role of CMV Infection in Primary Lesions, Development and Clinical Expression of Atherosclerosis

“…Hepatitis C virus increases the expression of cardiac and inflammatory biomarkers. Streptococcus pneumoniae, Chlamydia pneumoniae, and Mycoplasma pneumoniae may induce persistent pro-inflammatory state and platelet activation with subsequent plaque instability [7]. Among the plethora of bacteria and viruses, CMV was frequently detected in both atherosclerotic plaques and in healthy arteries, and its persistence is related to development overtime of atherosclerosis [8].…”

Increased Risk to Develop Hypertension and Carotid Plaques in Patients with Long-Lasting Helicobacter pylori Gastritis

“…Among microorganisms, Helicobacter pylori (H. pylori) is one of the most studied pathogens [11]. Helicobacter pylori is still responsible for widespread chronic bacterial infections [12,13], and its relevance promoting atheroma development is believed to be mediated by a chronic low-grade inflammation, triggered by the release of pro-inflammatory molecules, increased fibrinogen, C reactive protein, triglycerides, and low-density lipoprotein, which participate in the atherosclerotic process and promote a prothrombotic state [11,[14][15][16].…”