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Published on: January 28, 2020
Inflammatory biomarkers and risk of cardiovascular events in patients undergoing coronary angiography
Reza Mohebi1, Cian P McCarthy1, Hanna K Gaggin1
1Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA.
Insights
Distinct inflammatory biomarker patterns predict cardiovascular events. Identifying these clusters offers new targets for anti-inflammatory therapies to prevent heart disease.
Area of Science:
- Cardiology
- Inflammation Research
- Biomarker Discovery
Background:
- Inflammation is a known risk factor for cardiovascular (CV) events, traditionally measured by biomarkers like C-reactive protein.
- Advancements allow for measuring numerous inflammatory biomarkers, necessitating a comprehensive evaluation.
- A need exists for contemporary analysis of established and novel inflammatory biomarkers in relation to CV disease.
Purpose of the Study:
- To identify distinct patterns of inflammatory biomarkers using unsupervised machine learning.
- To assess the association of these inflammatory biomarker clusters and individual biomarkers with major adverse cardiovascular events (MACE).
- To explore potential new targets for anti-inflammatory treatments in cardiovascular disease.
Main Methods:
- 1,090 individuals undergoing coronary angiography were enrolled.
- Twenty-four inflammatory biomarkers were measured pre-angiography.
- Cox proportional hazard regression analyzed associations between biomarker clusters/individual biomarkers and MACE over a median follow-up of 3.67 years.
Main Results:
- Four distinct inflammatory biomarker clusters were identified, with increasing biomarker levels from cluster 1 to 4.
- Higher inflammatory clusters were associated with significantly increased risk of MACE (HRs ranging from 1.55 to 2.93).
- Several individual biomarkers, including IL-6, IL-8, and hs-CRP, were independently associated with MACE.
Conclusions:
- Distinct clusters of inflammatory biomarkers with prognostic significance can be identified in patients undergoing coronary angiography.
- These findings may highlight novel targets for anti-inflammatory therapies to mitigate cardiovascular disease risk.
Background:
Inflammation, measured by traditional biomarkers such as C-reactive protein, has been linked to cardiovascular (CV) events. Recent technological advancement has allowed for measuring larger numbers of inflammatory biomarkers. A contemporary evaluation with established and novel biomarkers of inflammation is needed.
Methods:
1,090 individuals who underwent coronary angiography were enrolled. Twenty-four inflammatory biomarkers were collected prior to angiography. Unsupervised machine learning cluster analyses determined unique patterns of inflammatory biomarkers. Cox proportional hazard regression assessed both association of inflammatory biomarker clusters and individual biomarker associations with major adverse cardiovascular events (MACE; non-fatal myocardial infarction or stroke, and CV death) during a median follow-up of 3.67 years.
Results:
Four distinct clusters were recognized. Incremental increases in inflammatory biomarkers were observed from cluster 1 to cluster 4. During follow-up, 263 MACE were ascertained. Considering cluster 1 as a reference, study participants with inflammatory cluster 2 (Hazard ratio [HR] 1.55, 95% confidence interval [CI]: 1.01-2.37), cluster 3 (HR 1.89, CI: 1.25-2.85), and cluster 4 (HR 2.93, CI: 1.95-4.42) were at increased risk of MACE. Interleukin (IL)-1α IL-6, IL-8, IL-10, IL-12, Adhesion molecule-1 high-sensitivity C-reactive protein, ferritin, myeloperoxidase, macrophage inflammatory protein (MIP)-1a, MIP 3, and macrophage colony-stimulating factor-1 were independently associated with MACE.
Conclusions:
Among persons undergoing coronary angiography procedures, distinct clusters of inflammatory biomarker distributions with significant prognostic meaning may be identified. These results may identify unique targets for anti-inflammatory treatments aimed at CV disease.
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