Beyond Lipids: The Inflammation Connection in Heart Disease Risk Assessment
- Richa Gupta
- 6 days ago
- 3 min read
For decades, cholesterol and lipid profiles have been central to assessing cardiovascular risk. However, a growing body of research highlights that traditional cholesterol tests—while important—are not sufficient to fully capture an individual’s risk of heart disease. Increasingly, inflammatory markers, such as high-sensitivity C-reactive protein (hs-CRP), have emerged as crucial indicators of cardiovascular risk, even among patients with “normal” lipid levels.
Why Lipids Alone Are Not Enough
Lipid panels, which measure cholesterol and triglycerides, provide valuable information about the risk of atherosclerosis and plaque buildup in arteries. However, these metrics do not account for the underlying inflammation that drives the progression of heart disease. Atherosclerosis is not just a cholesterol problem—it is also an inflammatory disease. Inflammation within the vessel walls contributes to plaque instability, rupture, and the formation of blood clots, which can lead to heart attacks and strokes.[1,2]
The Role of Inflammation in Heart Disease
Inflammation is a complex biological response that can be triggered by various factors, including obesity, diabetes, smoking, and even psychological stress. In the context of cardiovascular disease, chronic low-grade inflammation accelerates the formation and destabilization of atherosclerotic plaques. Key inflammatory pathways involve the activation of immune cells, release of cytokines, and upregulation of adhesion molecules on endothelial cells, all of which promote the progression of atherosclerosis.[1,3]
hs-CRP: A Powerful Predictor of Heart Risk
High-sensitivity C-reactive protein (hs-CRP) is a biomarker produced by the liver in response to inflammation. Studies have consistently shown that elevated hs-CRP levels are associated with an increased risk of cardiovascular events—such as heart attack, stroke, and cardiovascular death—even in individuals with normal cholesterol levels. [2,4]
Large-scale studies, including the Women’s Health Study, have demonstrated that each quintile increase in hs-CRP is associated with a 1.5-fold greater risk of cardiovascular events compared to similar increases in LDL cholesterol.[5]
This suggests that hs-CRP may be a stronger predictor of heart disease risk than LDL cholesterol itself in some populations.
Clinical Guidelines and Risk Assessment
Current guidelines, such as those from the American College of Cardiology and American Heart Association, recommend considering hs-CRP testing in patients at intermediate risk for atherosclerotic cardiovascular disease (ASCVD0. [5] An hs-CRP level of 2 mg/L or higher is considered a “risk enhancer,” which may prompt clinicians to initiate or intensify preventive therapies, such as statins or additional lipid-lowering agents, even in patients with seemingly normal lipid profiles.[2]
Practical Implications
Risk Stratification: hs-CRP can help refine risk assessment, particularly in individuals with borderline or intermediate risk based on traditional factors.
Treatment Guidance: Elevated hs-CRP may indicate the need for more aggressive preventive measures, even if cholesterol levels are within target ranges.
Monitoring: Tracking changes in hs-CRP over time can provide insight into the effectiveness of lifestyle modifications and medications aimed at reducing cardiovascular risks.[6]
Beyond hs-CRP: The Future of Inflammatory Biomarkers
While hs-CRP is the most widely used inflammatory biomarker, research is exploring the value of other markers, such as interleukins (IL-6, IL-8, IL-1α), myeloperoxidase, and macrophage colony-stimulating factor-1 (MCSF-1). These biomarkers may provide even greater precision in identifying individuals at highest risk for cardiovascular events, especially when used in combination with traditional risk factors.[3]
Conclusion
Traditional cholesterol tests remain essential, but they do not tell the whole story. Inflammation, as measured by markers like hs-CRP, plays a pivotal role in the development and progression of heart disease. Incorporating inflammatory biomarkers into cardiovascular risk assessment allows for a more comprehensive approach to prevention, enabling clinicians to identify and treat at-risk individuals—even those with “normal” lipid levels.
Sources
Alfaddagh A, Martin SS, Leucker TM, Michos ED, Blaha MJ, Lowenstein CJ, Jones SR, Toth PP. Inflammation and cardiovascular disease: From mechanisms to therapeutics. Am J Prev Cardiol. 2020 Nov 21;4:100130. doi: 10.1016/j.ajpc.2020.100130. PMID: 34327481; PMCID: PMC8315628.
Mohebi R, McCarthy CP, Gaggin HK, van Kimmenade RRJ, Januzzi JL. Inflammatory biomarkers and risk of cardiovascular events in patients undergoing coronary angiography. Am Heart J. 2022 Oct;252:51-59. doi: 10.1016/j.ahj.2022.06.004. Epub 2022 Jun 23. PMID: 35753356; PMCID: PMC9336200.
Bassuk SS, Rifai N, Ridker PM. High-sensitivity C-reactive protein: clinical importance. Curr Probl Cardiol. 2004 Aug;29(8):439-93. PMID: 15258556.
Mehta A, Blumenthal RS, Gluckman TJ, Feldman DI, Kohli P. High-sensitivity C-reactive Protein in Atherosclerotic Cardiovascular Disease: To Measure or Not to Measure? US Cardiol. 2025 Mar 21;19:e06. doi: 10.15420/usc.2024.25. PMID: 40171210; PMCID: PMC11959579.
https://www.thecardiologyadvisor.com/ddi/high-sensitivity-crp/
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