OAK BROOK, Ill. (June 3, 2025) – A new study published today in Radiology, the journal of the Radiological Society of North America (RSNA), reveals that carotid artery plaques—which may exist quietly in patients with no symptoms—can evolve into dangerous lesions over time. Researchers from the Erasmus MC, University Medical Center Rotterdam, and collaborators analyzed data from the long-running Rotterdam Study in the Netherlands and found that even calcified plaques once considered stable can develop internal bleeding, dramatically increasing the risk of plaque rupture and subsequent stroke.
Understanding Atherosclerotic Plaque: From Fatty Deposits to Calcification
Atherosclerosis begins when fatty substances, cholesterol, and other materials accumulate in the arterial wall, forming a plaque. Over time, some plaques become more fibrous and develop calcifications—deposits of calcium that often appear as bright, dense regions on imaging studies. Historically, calcification was thought to stabilize the plaque by “capping” the fatty core. However, Dr. Daniel Bos, the study’s lead author and an associate professor of Clinical Epidemiology and Neurovascular Imaging, cautions that calcification may not guarantee safety. “Calcified plaques may not be as harmless as once believed,” he said. “Our findings demonstrate that these lesions can still undergo intraplaque hemorrhage, which is the primary driver of plaque rupture and stroke.”
Why Carotid Plaque Matters: Linking Silent Lesions to Stroke Risk
The carotid arteries—one on each side of the neck—supply oxygenated blood to the brain. When atherosclerotic plaques form within these vessels, they can narrow the arterial lumen and reduce blood flow. More critically, ruptured plaques can dislodge debris or trigger the formation of a blood clot. If a clot travels to the brain or obstructs the carotid artery entirely, it can cause an ischemic stroke. Approximately 15 to 20 percent of all ischemic strokes are attributed to carotid artery disease.
Traditionally, physicians rely on symptoms—such as transient ischemic attacks (TIAs) or minor strokes—and duplex ultrasound measurements of stenosis (narrowing) to decide which patients require surgical intervention (carotid endarterectomy or stenting). This approach, however, overlooks patients with subclinical or asymptomatic plaques that may nonetheless be vulnerable to rupture. The new Radiology study underscores the importance of monitoring plaque composition in asymptomatic individuals.
Study Design: Leveraging the Rotterdam Cohort to Track Plaque Evolution
The Rotterdam Study is a large, population-based cohort study launched in 1990 to investigate the determinants of cardiovascular, neurological, ophthalmological, and other age-related diseases. For this carotid plaque analysis, researchers selected 802 participants aged 45 and older who exhibited subclinical atherosclerosis on initial imaging but had no history of stroke or TIA. All underwent high-resolution magnetic resonance imaging (MRI) of the carotid arteries at baseline and again six years later.
MRI was chosen because it can characterize plaque components—such as lipid-rich necrotic cores, fibrous tissue, calcification, and intraplaque hemorrhage—far better than ultrasound or computed tomography. Each plaque was categorized by its dominant feature at baseline (e.g., non-calcified, calcified, hemorrhagic) and then re-evaluated six years later to document changes. The researchers also collected participants’ demographic data, medical histories, and cardiovascular risk factor profiles (hypertension, hyperlipidemia, smoking status, diabetes) to assess predictors of plaque progression.
Key Findings: Calcification No Longer a Safe Harbor
By the end of the six-year follow-up, 57 percent of participants had plaques that evolved from simple, single-component lesions into more complex, multicomponent plaques. While all plaques could potentially worsen, those that already contained calcification at baseline were particularly prone to developing intraplaque hemorrhage. Specifically:
- Risk Doubling with Calcification: Participants with calcified plaques at baseline were twice as likely to exhibit intraplaque hemorrhage after six years compared to those with non-calcified plaques.
- Sex Differences in Plaque Progression: Plaque progression was more common in men than in women; 62 percent of male participants showed increased plaque complexity versus 52 percent of female participants.
- Projected 30-Year Evolution: Using computational modeling, researchers simulated plaque changes over a 30-year horizon. By age 70, more than half of those with initially simple plaques (single-component) would develop complex, multicomponent plaques—heightening their long-term stroke risk.
Dr. Bos elaborated on these findings: “We expected calcification to be a marker of stability. Instead, our data show that calcified plaques remain vulnerable to intraplaque hemorrhage. This is clinically significant because hemorrhage within a plaque dramatically increases the likelihood of rupture and can lead to an acute stroke.”
Clinical Implications: Rethinking Screening and Management Strategies
The study challenges existing dogma that treats calcified plaques as benign and suggests a need for closer surveillance of all plaque types, even in asymptomatic patients. According to Dr. Bos, “Physicians should consider regular imaging follow-up for patients with known carotid plaque, regardless of whether the plaque appears calcified or non-calcified. Detecting intraplaque hemorrhage early could identify individuals at high risk of stroke before symptoms arise.”
Current guidelines recommend carotid endarterectomy primarily based on the degree of stenosis (usually 70 percent or greater in asymptomatic patients). However, plaque composition—rather than stenosis alone—may more accurately predict risk. Dr. Sara Klein, a vascular neurologist unaffiliated with the study, observes: “Intraplaque hemorrhage is like a ticking time bomb. Even a modestly stenotic plaque with hemorrhage can be more dangerous than a heavily stenotic but stable plaque. This research underscores the need to integrate advanced imaging into routine vascular risk assessments.”
Expert Commentary: Weighing the Role of Advanced Imaging
Radiology experts emphasize that routine MRI screening of asymptomatic populations is not without challenges. High-resolution carotid MRI is resource-intensive, time-consuming, and not universally available. Dr. Michael Chu, professor of neuroradiology at Stanford University, notes: “While the evidence for plaque composition as a prognostic marker grows stronger, implementing widespread MRI screening would require significant investment in infrastructure and training. We must balance the potential benefits of early detection with cost-effectiveness and accessibility.”
Other experts point to ultrasound-based technologies—such as contrast-enhanced ultrasound and shear-wave elastography—for noninvasively assessing plaque vulnerability. Nonetheless, MRI remains the gold standard for detailed plaque characterization. Dr. Angela Roberts, a stroke prevention specialist, suggests a tiered approach: “Patients with multiple vascular risk factors—especially older men with a history of hypertension or smoking—might be prioritized for carotid MRI. Meanwhile, ultrasound-based risk scores could help triage lower-risk individuals. Ultimately, a combination of modalities may be the most practical strategy.”
Risk Factor Management: A Cornerstone for Preventing Plaque Progression
Beyond imaging, aggressive control of modifiable risk factors remains paramount. The Rotterdam team emphasizes that blood pressure control, statin therapy, smoking cessation, and glycemic management in diabetics can slow atherosclerosis and potentially reduce plaque vulnerability. In their cohort, participants with well-managed hypertension and lower low-density lipoprotein (LDL) cholesterol levels exhibited less plaque progression overall.
Dr. Bos also highlights emerging pharmacologic interventions. “Newer antiplatelet agents, PCSK9 inhibitors for cholesterol reduction, and anti-inflammatory drugs like colchicine are under investigation for their ability to stabilize plaques. We need clinical trials to determine whether targeting plaque composition—rather than stenosis alone—can improve outcomes.”
Recommendations for Clinicians and Patients
Based on these findings, the researchers and external experts offer several recommendations:
- Periodic Vascular Imaging for High-Risk Patients: Adults over 60 with multiple cardiovascular risk factors (e.g., hypertension, diabetes, hyperlipidemia, smoking history) should undergo baseline vascular imaging. If carotid plaque is present, clinicians may consider MRI follow-up every 3–5 years to monitor plaque composition.
- Broaden Risk Assessment Beyond Stenosis: Incorporate plaque vulnerability markers—such as intraplaque hemorrhage or lipid-rich necrotic core—into decision-making for carotid interventions. Even plaques causing less than 50 percent stenosis may warrant closer observation if imaging reveals hemorrhage or ulceration.
- Intensive Risk Factor Control: Emphasize strict blood pressure targets (<130/80 mm Hg), LDL cholesterol <70 mg/dL (or <55 mg/dL in very high-risk individuals), smoking cessation, and glycemic control (HbA1c <7 percent). Lifestyle interventions—dietary modification, exercise, and weight management—remain foundational.
- Multidisciplinary Collaboration: Involve neurologists, vascular surgeons, radiologists, and primary care providers in a coordinated care model. A multidisciplinary vascular clinic can streamline imaging, risk stratification, and management decisions.
Patient Perspective: The Importance of Awareness and Early Detection
For patients, recognizing that a “silent” carotid plaque can progress without any warning signs is critical. Mr. Johan de Vries, a Rotterdam Study participant whose initial carotid MRI in 2018 disclosed a small, non-calcified plaque, shares his experience: “I felt fine—no dizziness, no TIA. When my physician recommended a follow-up MRI six years later, I was surprised. The new images showed a small area of bleeding inside the plaque. My doctor prescribed higher-dose statins and an antiplatelet agent, and I’ve been more diligent about my blood pressure and diet ever since.” De Vries adds, “Knowing about the plaque’s progression gave me a sense of control. I didn’t want to wait for a stroke to happen.”
READ MORE: Research Unveils Genetic Complexity in Cancer Metastasis
Patients are encouraged to discuss vascular risk screening with their primary care provider, particularly if they have a family history of stroke or heart disease. Understanding individual stroke risk—and that plaque composition matters—can empower patients to adhere to preventive measures.
Future Directions: Unraveling Plaque Dynamics and Therapeutic Targets
The Rotterdam investigators plan to extend their research in two directions:
- Component Interactions: Delve deeper into how different plaque elements—calcification, hemorrhage, lipid cores—interact over time. For instance, does calcification predispose to hemorrhage by altering mechanical stress, or vice versa? Identifying these pathways could reveal novel therapeutic targets.
- Experimental Validation: Conduct longitudinal clinical trials to test whether modifying risk factors or initiating anti-inflammatory therapies at the first sign of intraplaque hemorrhage reduces stroke incidence.
Dr. Bos and his co-authors also propose developing machine-learning algorithms that combine clinical data, blood biomarkers, and imaging features to predict individual plaque trajectories. “If we can anticipate which plaques will become unstable, we can tailor preventive strategies more effectively,” Bos explains.
Conclusion: A Call for Vigilance in Asymptomatic Carotid Atherosclerosis
The Radiology study’s findings underscore a critical paradigm shift: carotid plaques once deemed stable—particularly those with calcification—can transition to high-risk lesions through intraplaque hemorrhage. For clinicians, this means that plaque composition must be weighed as heavily as the degree of arterial narrowing when assessing stroke risk. For patients, the message is clear: even in the absence of symptoms, carotid atherosclerosis can evolve silently, and proactive risk-factor management—alongside advanced imaging when indicated—can be lifesaving.
As Dr. Daniel Bos concludes, “Early detection and vigilant monitoring of plaque changes are essential. We must treat subclinical atherosclerosis not as a static condition, but as a dynamic process that demands ongoing attention. Only then can we hope to prevent the devastating consequences of stroke in patients who never saw it coming.”
