Cardiovascular diseases (CVDs) consist of various complex and multifactorial disorders of the heart and circulatory system. Inflammatory pathways are implicated in this suite of diseases that are a leading cause of death worldwide, accounting for 17.9 million deaths annually (1).

Cardiovascular Disease Pathways

CVDs include coronary heart disease, heart attack, rheumatic heart disease, heart failure, heart valve problems, congenital heart disease, cardiomyopathy, peripheral artery disease, and cerebrovascular disease (2). The pathogenesis of these diseases is complex and poorly understood. Mounting evidence points to inflammation as a significant causative and contributing factor in the initiation, development, and complication of CVDs (3).

Inflammation is a series of regulated events that occur as a protective immune system response to an irritant. It is a vital defense mechanism against foreign invaders (4). However, when it persists—described as chronic inflammation—it becomes maladaptive, causing progressive tissue damage. When the tissues involved are the heart and blood vessels, inflammation causes pathological changes that lead to CVDs (5).

Inflammatory mediators involved in the development of CVDs include cytokines such as interleukins (IL)-1β, IL-16, and IL-18, pentraxin 3 (PTX3), cellular adhesion molecules (CAM), and C-Reactive protein (CRP) (6). These mediators and their interactions with one another—in some cases, working in a feedback loop—play complex regulatory roles in inflammatory responses and cardiac remodeling (changes in the heart’s shape, size, or internal structure that occurs after injury to it and is tied to poor prognosis). (7, 8).

CRP has been recognized as an “active mediator” in the pathogenesis of cardiovascular disease, with raised levels being a strong predictor for adverse cardiovascular events and death (3, 9). CRP may also promote the release of problematic proinflammatory cytokines like TNF-α, IL-1β, and IL-6 that are also involved in CVDs. Similarly, these pro-inflammatory cytokines, IL-1β and TNFα, stimulate the release of PTX3. Meanwhile, a rise in PTX3 levels may indicate atherosclerosis, acute myocardial infarction, heart failure, and cardiac arrest and predict mortality risk (10).

Taken together, targeting inflammation pathways of CVDs is a promising therapeutic approach to effectively treating cardiovascular diseases. The efficacy of this approach has been successfully demonstrated in experimental models but less in clinical practice (11).

Molecular changes that occur during the initiation and progression of CVDs can be observed in altered gene expression in smooth muscle cells, cardiac fibroblasts, cardiomyocytes, endothelial cells, and inflammatory cells (12).  Some of these differentially expressed genes related to CVDs have been identified by microarray studies that have characterized gene expression signatures to distinguish between healthy and diseased patients (13). For example, a 2022 study observed that the upregulated genes G0S2, CXCL1, ACKR3, and PTPRD are active in CVDs and risk factors like hypertension and aging (14).

The risk of CVDs is multifactorial and is determined by the complex interplay between genetic and environmental factors. The exact contribution of genes and the environment to the development of CVDs is unclear. However, behavioral and environmental factors such as exposure to noise, air pollutants, and artificial light at night, tobacco and alcohol use, secondhand smoke exposure, stress, a sedentary lifestyle, and an unhealthy diet, seem to show a greater influence on the likelihood of CVDs and their progression and manifestation over a person’s genetic makeup (11). In addition, lifestyle risk factors may contribute to the likelihood of developing health conditions like obesity, high blood pressure, and high low-density lipoprotein (LDL) cholesterol, all of which raise the risk of CVDs (1).

Evidence also suggests that as a person’s modifiable risk factors decline, so does their genetic predisposition to CVDs, further grounding the predominance of environmental and lifestyle factors to CVD risk (15).

Regarding genetic contribution to the risk of CVDs, it has been observed that CVDs run in families as a family history of CVDs makes a person susceptible to developing these conditions. But researchers emphasize that family history takes into account that family members follow similar lifestyles and live in shared environments (16). It is, however, also worth noting that high-risk genetic conditions and monogenic CVDs like familial hypercholesterolemia (FH), hypertrophic cardiomyopathy (HCM), and arrhythmias exist and although rare, are likely underdiagnosed (17).



1. World Health Organization (Accessed June 26, 2023)

2. Frąk W, Wojtasińska A, Lisińska W, Młynarska E, Franczyk B, Rysz J. Pathophysiology of Cardiovascular Diseases: New Insights into Molecular Mechanisms of Atherosclerosis, Arterial Hypertension, and Coronary Artery Disease. Biomedicines. 2022;10(8):1938.

3. Kosmas CE, Silverio D, Sourlas A, Montan PD, Guzman E, Garcia MJ. Anti-inflammatory therapy for cardiovascular disease. Ann Transl Med. 2019;7(7):147.

4. Alfaddagh A, Martin SS, Leucker TM, et al. Inflammation and cardiovascular disease: From mechanisms to therapeutics. Am J Prev Cardiol. 2020;4:100130.

5. Wang X, Zhang M, Wang X. Editorial: Chronic inflammation and pharmacological interventions in cardiovascular diseases. Front Pharmacol. 2022;13:993569. 

6. Lubrano V, Balzan S. Consolidated and emerging inflammatory markers in coronary artery disease. World J Exp Med. 2015;5(1):21-32.

7. Cucu, I. Signaling Pathways in Inflammation and Cardiovascular Diseases: An Update of Therapeutic Strategies. Immuno. 2022,2, 630–650