_{AUTHOR: Sean Delaney} 

A greater number of traditional cardiovascular risk factors is strongly associated with increased coronary plaque vulnerability in patients with acute coronary syndrome (ACS), particularly in culprit lesions, according to a new analysis published in JACC.¹ The study provides a direct morphological link between the cumulative burden of risk factors and the high-risk plaque features that precipitate adverse clinical events.

The study utilised optical coherence tomography (OCT), a high-resolution intravascular imaging modality that allows for detailed in-vivo characterisation of coronary artery plaques. OCT can identify specific features of vulnerability, such as a thin fibrous cap, lipid content, and inflammatory cell infiltration, which are associated with a higher risk of plaque rupture.

This retrospective analysis investigated the association between the number of cardiovascular risk factors and plaque vulnerability as defined by OCT. The study included patients with ACS who were divided into five groups based on their number of traditional risk factors: diabetes, hypertension, hyperlipidemia, and smoking. For further analysis, patients were also categorised into two groups: those with 0–1 risk factor and those with two or more.

Investigators analysed a total of 2,187 plaques, comprising 1,581 culprit and 606 non-culprit plaques. The presence of vulnerable plaque features, including lipid-rich plaques, thin-cap fibroatheromas (TCFAs), macrophages, microvessels, and cholesterol crystals, was assessed in relation to the patient's risk factor burden.

In culprit plaques, the analysis revealed a significant dose-response relationship between the number of risk factors and plaque instability. The prevalence of lipid-rich plaques (p-trend=0.027), TCFAs (p-trend=0.006), macrophages (p-trend<0.001), microvessels (p-trend<0.001), and cholesterol crystals (p-trend=0.032) all increased as the number of risk factors increased. The presence of two or more risk factors was independently associated with all these vulnerable features, with the exception of lipid-rich plaques.

Furthermore, the mechanism of ACS was influenced by risk factor burden. Plaque rupture showed an increasing prevalence with a higher number of risk factors (p-trend=0.015), whereas plaque erosion demonstrated a decreasing trend (p-trend<0.001). In non-culprit plaques, the association was less pronounced, with only macrophages, cholesterol crystals, and the cumulative number of vulnerable features showing a significant positive association with the risk factor count.

These findings provide a clear mechanistic explanation for the well-established link between traditional risk factors and adverse clinical outcomes.² The study highlights that a higher burden of risk factors directly translates to more inflamed and unstable coronary plaques. According to the study authors, led by Dr Ik-Kyung Jang, “In patients with ACS, an increasing number of cardiovascular risk factors were strongly associated with greater plaque vulnerability, especially for culprit lesions. These findings may explain the relationship between traditional risk factors and adverse clinical outcomes.”¹ The opposing trends for plaque rupture and erosion suggest different underlying pathophysiological pathways depending on the patient's risk profile. This underscores the critical importance of aggressive and comprehensive risk factor management in both primary and secondary prevention of ACS. While this study provides crucial insights into plaque morphology, the findings reinforce the need for proactive clinical strategies that target modifiable risk factors to mitigate plaque vulnerability and prevent future cardiovascular events.

References

1. Covani M, Niccoli G, Fujimoto D, et al. Plaque Vulnerability and Cardiovascular Risk Factor Burden in Acute Coronary Syndrome: An Optical Coherence Tomography Analysis. JACC. 2025;86(2):77–89. https://doi.org/10.1016/j.jacc.2025.04.070

2. Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004;364:937-952. https://doi.org/10.1016/S0140-6736(04)17018-9

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