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Inflammation is a critical biological response that helps the body protect itself against infections, injuries, and toxins. However, when inflammation becomes chronic, it can contribute to the development and progression of cardiometabolic disease (CMD) such as atherosclerosis, diabetes, and metabolic syndrome. Keep reading to learn about the role of inflammation in CMD.

The connection between inflammation and cardiometabolic disease

Inflammation is the body's immediate response to harmful stimuli, involving immune cells, blood vessels, and molecular mediators. Acute inflammation is short-term and generally beneficial, aiding in healing and defense. In contrast, chronic inflammation is prolonged and can become detrimental, leading to tissue damage and contributing to various diseases, including CMD. 

Chronic inflammation is a significant factor in the pathogenesis of CMD, resulting from persistent infections, autoimmune reactions, environmental factors, and lifestyle choices. It promotes the development of insulin resistance, endothelial dysfunction, and lipid abnormalities, all of which are critical in CMD. (Chen 2017)

Diet can play a major role in preventing or promoting inflammation. Encouraging a diet rich in fruits and vegetables for their anti-inflammatory properties. (Kurowska 2023)

Causes of chronic inflammation in cardiometabolic disease

Several factors can lead to chronic inflammation in CMD. 

Chronic stress

Psychological stress can activate the hypothalamic-pituitary-adrenal (HPA) axis, increasing cortisol levels and promoting inflammation. (Stephens 2012)

Diet

Diets high in refined sugars, trans fats, and processed foods can promote inflammation. (Ma 2022) Conversely, diets rich in fruits, vegetables, and omega-3 fatty acids have anti-inflammatory properties. (Kurowska 2023)

Obesity

Excess adipose tissue, especially visceral fat, secretes pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), contributing to systemic inflammation. (Ellulu 2017)

Physical inactivity

Sedentary lifestyles are associated with increased inflammatory markers and higher CMD risk. (Allison 2012)

Sleep disorders

Poor sleep quality and duration can increase inflammatory markers and the risk of CMD. (Dzeirzewski 2020)

Smoking

Tobacco smoke contains numerous pro-inflammatory substances that damage the endothelium and promote atherosclerosis. (Ardiana 2023)

How inflammation contributes to cardiometabolic disease

Inflammation plays a central role in the development and progression of conditions such as atherosclerosis, diabetes, and metabolic syndrome, linking various risk factors and mediating the damage that leads to these diseases.

Atherosclerosis

Atherosclerosis, a leading cause of cardiovascular disease, is driven by chronic inflammation. When an endothelial injury occurs, low-density lipoprotein (LDL) accumulates in the arterial wall. Oxidized LDL (oxLDL) triggers an inflammatory response, recruiting immune cells like macrophages. These macrophages engulf oxLDL, forming foam cells and contributing to plaque formation. Chronic inflammation perpetuates plaque growth and instability, increasing the risk of plaque rupture and thrombosis. (Zhong 2020)(Stark 2021)(Gusev 2023)

Diabetes

Chronic inflammation is a hallmark of type 2 diabetes. Inflammatory cytokines like TNF-α and IL-6 impair insulin signaling pathways, leading to insulin resistance. Adipose tissue inflammation in obese patients exacerbates insulin resistance, promoting hyperglycemia and the development of diabetes. Additionally, chronic inflammation can damage pancreatic β-cells, reducing insulin production. (Wondmkun 2020)

Inflammation plays a key role in the development of diabetes.

Metabolic syndrome

Metabolic syndrome comprises a cluster of conditions, including central obesity, hypertension, dyslipidemia, and insulin resistance. Chronic inflammation links these conditions, with pro-inflammatory cytokines playing a central role. (Van Den Brink 2019) Visceral adipose tissue inflammation contributes to dysregulated lipid metabolism and hypertension, both key components of metabolic syndrome. (Chait 2020)

Key inflammatory markers in cardiometabolic disease testing

Accurate assessment of inflammation and CMD risk involves several biomarkers.

Inflammatory markers

Inflammatory markers are critical in assessing the extent of inflammation and its role in CMD, offering valuable insights for diagnosis and management.

Erythrocyte sedimentation rate 

Erythrocyte sedimentation rate (ESR) is a foundational but nonspecific marker of inflammation. Elevated ESR levels indicate systemic inflammation and are often seen in chronic inflammatory conditions. (National Library of Medicine n.d.) ESR is less specific to cardiovascular disease and more reflective of general inflammatory activity but can still guide recommendations for addressing inflammation. (Tishkowski 2023)

Fibrinogen

Fibrinogen is an acute-phase protein involved in clot formation. High fibrinogen levels are associated with increased cardiovascular risk and inflammation. (Surma 2021)

High-sensitivity C-reactive protein

C-reactive protein (CRP) is produced by the liver in response to inflammation in the body and serves as a general marker of inflammation. CRP levels rise when there’s inflammation due to infections, chronic diseases, or other inflammatory conditions. (Nehring 2023) On the other hand, high-sensitivity CRP (hs-CRP) is a more sensitive marker of systemic inflammation. Elevated hs-CRP levels are associated with an increased risk of cardiovascular events and can predict CMD progression. (Banait 2022)

Interleukin-6

IL-6 is a pro-inflammatory cytokine involved in the acute phase response. Elevated IL-6 levels are linked to obesity, insulin resistance, and cardiovascular risk. (Qu 2014)

Tumor necrosis factor-alpha 

TNF-α is a key mediator of inflammation and is elevated in obesity and insulin resistance, contributing to endothelial dysfunction and atherosclerosis. (Kwaifa 2020)

Lipid profile

A lipid profile is essential for evaluating dyslipidemia and its contribution to inflammation and CMD risk.

High-density lipoprotein 

High-density lipoprotein (HDL) is generally protective due to its role in reverse cholesterol transport and anti-inflammatory properties; however, inflammation can impair HDL functionality. During inflammatory states, HDL can become dysfunctional, losing its protective qualities and potentially becoming pro-inflammatory. (Hima Bindu 2011) 

Furthermore, while higher levels of HDL are generally protective, excessively high HDL levels (over 80 mg/dL) may be dysfunctional and pro-inflammatory. (Bonacina 2021)(Liu 2022)  Therefore, understanding the inflammatory status of a patient is crucial for accurately assessing the impact of HDL on cardiovascular health.

Oxidized low-density lipoprotein 

oxLDL is a form of LDL cholesterol that has undergone oxidative modification, making it more atherogenic and harmful to the arterial walls. Therefore, measuring oxLDL is an important factor in evaluating atherosclerosis risk. Because it triggers inflammation and plaque formation within the artery, elevated oxLDL levels may indicate increased oxidative stress and inflammation within the arterial wall. (Poznyak 2021) Monitoring oxLDL provides insight into the impact of oxidative stress and inflammation, essential for assessing cardiovascular risk and disease progression.

Total cholesterol

Total cholesterol (TC) is already part of a standard lipid panel. It’s well established that elevated TC levels can indicate dyslipidemia and an increased risk of CMD. In the context of inflammation, this is particularly due to an increase in oxLDL and excessively high HDL. (Pappan 2024)

Oxidative stress markers

Oxidative stress markers help in understanding oxidative damage and its relationship with chronic inflammation in CMD.

Malondialdehyde 

Malondialdehyde (MDA) is a byproduct of lipid peroxidation and an indicator of oxidative stress. This oxidative stress can lead to the formation of oxLDL contributing to plaque formation and further increasing cardiovascular risk. (Ito 2019) Therefore, elevated MDA levels reflect increased oxidative damage, contributing to CMD. (Cordiano 2023)

8-hydroxydeoxyguanosine 

8-hydroxydeoxyguanosine (8-OHdG) is a marker of oxidative DNA damage. High 8-OHdG levels indicate increased oxidative stress and are associated with CMD. (Wu 2004) Assessing 8-OHdG levels might be useful for monitoring oxidative stress damage to vascular cells that may contribute to atherosclerosis. (Di Minno 2016)

Glutathione 

Glutathione (GSH) is a key antioxidant that protects cells from oxidative damage. Reduced GSH levels indicate reduced antioxidant capacity and increased CMD risk, making it a beneficial marker in assessing cardiovascular disease (CVD) by providing insight into the body's antioxidant defenses. (Giustarini 2023) By evaluating GSH levels, clinicians can develop more targeted interventions to enhance antioxidant status and potentially reduce the risk of CMD.

Additional relevant markers

There are a few additional markers that provide further insights into other factors that influence inflammation and contribute to CMD risk.

Homocysteine

Homocysteine, an amino acid found in the blood, is a byproduct of methionine metabolism and is metabolized through pathways involving vitamins B6, B12, and folate. High homocysteine levels are a risk factor for atherosclerosis, endothelial dysfunction, and inflammation. (Oudi 2010)(Pushpakumar 2014) Tracking homocysteine can inform strategies to help reduce homocysteine levels and mitigate the associated cardiovascular risks.

Uric acid

Uric acid is a classic marker historically related to gout and kidney function. Additionally, elevated uric acid levels have been linked to hypertension, insulin resistance, endothelial dysfunction, atherosclerosis, and cardiovascular risk. (Di Gioia 2024)

Vitamin D

Vitamin D has anti-inflammatory properties. Deficiency in vitamin D is associated with increased inflammation, insulin resistance, hypertension, and therefore, overall CMD risk. (Ao 2021)(Kheiri 2018)(Sung 2012) Monitoring vitamin D status can help inform clinical decisions and optimize vitamin D levels. 

Magnesium

Magnesium plays a crucial role in modulating inflammation, and low magnesium levels are associated with hypertension and increased inflammatory markers, insulin resistance, and CVD risk. (Fritzen 2023) Assessing RBC magnesium levels provides a more accurate measure of magnesium status, helping clinicians identify deficiencies and develop targeted interventions to modulate CMD risks.

Factoring inflammation into cardiometabolic assessment

Chronic inflammation plays a major role in the development and progression of CMD. Understanding the causes and pathways of inflammation can aid in the prevention, diagnosis, and management of CMD. By addressing modifiable risk factors and monitoring key inflammatory markers, practitioners can help mitigate chronic inflammation and improve cardiometabolic health outcomes.