Understanding How Blood Flow Forces Affect Heart Artery Plaque: A Patient's Guide to New Research

Table of Contents

• Key Points
• Why This Research Matters: The Basics of Heart Artery Plaque
• How the Study Was Conducted: Patients, Imaging, and Computer Models
• Key Findings: Changes in Artery Wall Thickness
• Key Findings: Changes in Plaque Composition
• What This Means for Patients: Clinical Implications
• Study Limitations: What This Research Could Not Prove
• Recommendations for Patients: What You Can Do
• Frequently Asked Questions
• Source Information

Key Points

• In a 12-month study of 34 patients, higher mechanical wall stress from blood pressure was linked to new plaque growth in previously clear coronary artery segments.
• Higher wall shear stress and mechanical wall stress were each associated with greater plaque shrinkage, likely due to statin therapy, in a study of 34 patients.
• Across all patients, lipid-rich necrotic core inside plaques shrank by 54% on average, and 85% of plaque areas improved while taking statins.
• The combination of low mechanical wall stress and high wall shear stress was linked to increasing lipid core, a potentially dangerous plaque change.
• Patients are advised to take blood pressure medications and statins, control other risk factors, and talk with their cardiologist about plaque and treatment goals.

Why This Research Matters: The Basics of Heart Artery Plaque

Atherosclerosis—the buildup of plaque inside the coronary arteries that supply blood to the heart—is the leading cause of heart attacks worldwide. But plaque doesn't form uniformly throughout the arteries. Some spots develop dangerous blockages while neighboring areas remain clear. This patchy distribution has puzzled researchers for decades.

The answer may lie in local biomechanical forces—the physical stresses that blood flow and blood pressure exert on the artery walls. Two forces in particular have captured researchers' attention, and a new study from Erasmus Medical Center in the Netherlands investigated how these forces work together to influence plaque behavior.

The first force is wall shear stress (WSS), which is the frictional force created by blood flowing over the endothelial cells—the delicate inner lining of the artery. Think of it like the drag you feel when holding your hand out of a moving car window. The second force is mechanical wall stress (MWS), the structural stress inside the artery wall itself caused by blood pressure. This is like the tension you feel in a balloon's rubber as you inflate it—the pressure from inside stretches and strains the material.

While wall shear stress has been extensively studied, mechanical wall stress has received surprisingly little attention in relation to plaque development. Most previous MWS research focused only on late-stage plaque rupture, which is what triggers heart attacks. This study, published in the journal Atherosclerosis, took a broader approach: it examined how both forces, individually and in combination, influence plaque initiation, growth, and regression over time.

How the Study Was Conducted: Patients, Imaging, and Computer Models

Study Design and Patient Population

The study was embedded within a prospective, single-center observational cohort study at Erasmus University Medical Center in Rotterdam, the Netherlands. Initially, 53 patients were enrolled. All had experienced acute coronary syndrome (a condition that includes heart attacks and unstable angina), were hemodynamically stable, and had at least one non-stented, non-culprit coronary artery suitable for invasive imaging and physiology measurements.

Patients with certain conditions were excluded from the study. These included:

• Prior coronary artery bypass graft (CABG) surgery
• Three-vessel coronary disease
• Renal insufficiency (kidney failure)
• Left ventricular ejection fraction below 30% (significantly reduced heart pumping function)
• Atrial fibrillation (an irregular heart rhythm)

Of the 53 patients initially included, 19 were excluded from the final analysis due to consent withdrawal or missing/low-quality imaging or pressure data. The final analysis included 34 coronary arteries from 34 patients. The average age was 62 years (plus or minus 8.9 years), and 91.2% were men. The average body mass index (BMI) was 27 (plus or minus 4.6)—technically in the overweight range.

Cardiovascular risk factors were common in this group:

• Diabetes mellitus: 17.6% (6 patients)
• Hypertension: 23.5% (8 patients)
• Hypercholesterolemia: 44.1% (15 patients)
• Current smoking: 17.6% (6 patients)
• Positive family history: 38.2% (13 patients)
• Previous heart attack (myocardial infarction): 21.6% (7 patients)
• Previous angioplasty (PCI): 24.3% (8 patients)

Their average LDL cholesterol (the "bad" cholesterol) was 2.6 mmol/L (ranging from 2.1 to 3.2 mmol/L). Notably, 17 patients were already taking statins at the start of the study, another 15 started statin therapy within one month, and the remaining two began statin treatment at the sixth and eleventh months after their first coronary imaging. By the 12-month follow-up, all patients were on statin therapy.

Imaging Procedures

The researchers imaged one non-culprit artery per patient—meaning an artery that was not responsible for the original heart event. These included 13 left anterior descending arteries (LAD), 11 right coronary arteries (RCA), and 10 left circumflex arteries (LCX).

Two sophisticated imaging techniques were used at both baseline and after 12 months:

• Near-infrared spectroscopy with intravascular ultrasound (NIRS-IVUS): This combined technique uses sound waves to create detailed cross-sectional images of the artery wall and simultaneously uses light spectroscopy to detect the chemical signature of lipid-rich necrotic cores (LRNC)—the dangerous, cholesterol-filled core of atherosclerotic plaques.
• Optical coherence tomography (OCT): A high-resolution imaging technique that uses light waves to produce extremely detailed images of the artery's inner structures, like an "optical biopsy" of the blood vessel.

Additionally, one month after the initial procedure, patients underwent a coronary computed tomography angiogram (CCTA)—a specialized CT scan of the heart arteries. All arterial segments studied were at least 30 mm long. Blood flow and pressure were measured within each segment using a special guidewire called a ComboWire.

Computational Modeling

This study's technology-heavy approach involved creating patient-specific computer models of each coronary artery. Researchers used the imaging data to build three-dimensional reconstructions of the artery geometry—including the inner lumen (the blood-carrying channel) and the vessel wall, which consists of the intima/media layer and the adventitia (the outer supportive layer). A 0.15 mm uniform layer was added around the external elastic lamina to account for the mechanical contribution of the adventitia.

For wall shear stress (WSS), the team used computational fluid dynamics (CFD)—computer simulations of blood flow. Blood was modeled as an incompressible, homogeneous Carreau fluid (a mathematical model that captures how blood thickens at low flow rates), and the artery walls were assumed to be rigid. Patient-specific flow measurements from the ComboWire were used to set the inlet and outlet conditions. Time-averaged wall shear stress values were calculated for the entire cardiac cycle.

For mechanical wall stress (MWS), the researchers used finite element (FE) modeling—a computer technique that breaks a complex structure into tiny elements to calculate stress and strain. Since the arteries were imaged while under blood pressure (not at zero pressure), a special "backward incremental method" was used to compute the initial stresses that existed at the time of imaging. Artery-specific blood pressure measurements were incorporated into the models. The tissues were modeled as isotropic, nonlinear, hyperelastic, and incompressible materials, using approximately 5,000 finite elements per cross-section. The researchers reported both the maximum luminal MWS (stress at the inner surface of the artery) and the average MWS within the vessel wall.

Sector Analysis and Statistics

To study local effects, each coronary artery was divided into small sectors measuring 1.5 mm in length and 45 degrees in circumference. Cross-sections at side-branch locations were excluded because the artery circumference wasn't complete at those points. This yielded 6,527 individual sectors for analysis.

Sectors were categorized as either plaque-free (mean wall thickness less than 0.5 mm) or plaque sectors (mean wall thickness greater than 0.5 mm). Plaque sectors were further divided into those with LRNC (NIRS positive percentage greater than 50%) or without LRNC (NIRS positive percentage less than 50%).

The researchers then calculated how much each sector's wall thickness changed over the year (ΔWT) and how the lipid-rich necrotic core percentage changed (ΔLRNC). For statistical analysis, baseline WSS and MWS values were divided into tertiles—low, mid, and high—with specific threshold values for each sector type. A statistical method called linear mixed models was used to account for the fact that multiple sectors from the same artery are not fully independent of each other. All analyses corrected for baseline wall thickness, statin treatment, and cardiovascular risk factors including diabetes, hypertension, hypercholesterolemia, smoking, obesity, and family history. A p-value below 0.05 was considered statistically significant.

Key Findings: Changes in Artery Wall Thickness

Baseline Characteristics

At the start of the study, 63% of sectors (n = 4,112) were plaque-free, meaning they had a wall thickness under 0.5 mm. The median baseline wall thickness in these plaque-free sectors was 0.23 mm (ranging from 0.02 to 0.49 mm). The remaining 2,415 sectors (37%) contained plaque, with a median wall thickness of 0.70 mm (ranging from 0.50 to 2.06 mm). Of these plaque sectors, 22% contained LRNC tissue. Plaque sectors with LRNC had a median baseline wall thickness of 0.76 mm, while those without LRNC had a median of 0.67 mm.

What Happened in Plaque-Free Sectors

Over the one-year study period, plaque-free sectors showed a mean increase in wall thickness (ΔWT) of 0.06 mm (95% confidence interval: 0.05 to 0.07 mm). This means these previously clear areas began developing new plaque—a process that 63% of the sectors experienced to some degree.

When analyzing the forces involved, researchers found a striking result: higher baseline mechanical wall stress (MWS) was significantly associated with greater vessel wall growth (p < 0.001). In plain terms, areas of the artery exposed to more stretching stress from blood pressure grew thicker over the year, indicating new plaque formation.

A different pattern emerged for wall shear stress. Sectors exposed to lower WSS tended to show higher wall thickness increase over time, though this association fell just short of statistical significance (p = 0.058). This is consistent with previous research showing that low blood-flow friction promotes plaque initiation.

What Happened in Plaque Sectors

The plaque sectors told the opposite story. These areas showed a mean decrease in wall thickness of -0.07 mm (95% confidence interval: -0.08 to -0.06 mm), with 67% of sectors getting thinner over the year. This regression is likely explained by the statin therapy that all patients were receiving—statins are known to shrink plaques and reduce their lipid content.

Both biomechanical forces influenced how much shrinkage occurred:

• Higher luminal MWS was associated with greater wall thickness reduction (p = 0.02). Areas with more mechanical stretching stress showed more plaque regression.
• Higher WSS was also associated with greater wall thickness reduction (p < 0.001). Areas with more blood-flow friction regressed more.

The combination of forces mattered too. The researchers found a significant combined effect of WSS, luminal MWS, and LRNC presence on wall thickness change (p = 0.02). Specifically:

• The smallest wall thickness reduction occurred in plaque sectors exposed to both low luminal MWS and low WSS—these "double-low" areas were the most sluggish in responding to treatment.
• The highest wall thickness reduction was observed in sectors with both high luminal MWS and high WSS—these "double-high" areas regressed the most.

Interestingly, for any combination of luminal MWS and WSS, plaque sectors without LRNC demonstrated greater wall thickness reduction than sectors with LRNC. This suggests that lipid-rich, necrotic-core-containing plaques may be more resistant to regression than fibrous plaques.

Key Findings: Changes in Plaque Composition

Beyond measuring how thick the artery walls became, the researchers tracked changes in plaque composition—specifically the amount of lipid-rich necrotic core (LRNC), which is the dangerous, inflammation-filled material inside plaques that makes them prone to rupture.

Over the study year, plaque sectors showed an average 54% reduction in LRNC percentage (95% confidence interval: -64% to -43%). An impressive 85% of sectors showed a decrease in LRNC percentage—strong evidence that the statin therapy was effectively "de-fatting" the plaques across the board.

However, biomechanical forces modified this response. Statistical analysis revealed that luminal MWS (p = 0.022), WSS (p = 0.004), and their interaction (p = 0.003) were all significantly associated with LRNC percentage change:

• Luminal MWS showed a negative trend: Higher mechanical wall stress was associated with greater LRNC reduction.
• WSS showed a positive trend: Higher wall shear stress was associated with less LRNC reduction (or even an increase).

The most clinically important finding emerged from combining the two forces: sectors with low MWS combined with high WSS demonstrated the highest LRNC increase (p < 0.01). This "dangerous combination"—low stretching stress plus high blood-flow friction—was associated with a growing lipid core, even in patients receiving statin therapy. Conversely, high MWS combined with low WSS was associated with possible LRNC reduction.

This matters because LRNC is a hallmark of vulnerable plaque—the type most likely to rupture, cause a blood clot, and trigger a heart attack. A growing lipid core may represent transformation into a higher-risk plaque phenotype, even if overall wall thickness is decreasing.

What This Means for Patients: Clinical Implications

This study offers several important insights that could eventually affect how heart disease is monitored and treated.

First, mechanical wall stress deserves more attention. For years, research on biomechanics and atherosclerosis focused almost exclusively on wall shear stress. This study demonstrates that MWS—the structural stress caused by blood pressure—is independently associated with both plaque initiation in clear arteries and plaque regression in diseased ones. The two forces were found to be essentially uncorrelated with each other (R² = 0.015 in plaque-free sectors and R² = 0.006 in plaque sectors), meaning they provide separate, complementary information about plaque risk.

Second, the combination of forces matters more than either alone. The finding that low MWS combined with high WSS was associated with increased lipid-rich necrotic core—the most dangerous plaque component—suggests that using both biomechanical measurements together could identify "hot spots" at higher risk of progressing to vulnerable plaques.

Third, these findings may help explain why some plaque areas respond better to statin therapy than others. Even with all patients on statins, certain sectors showed plaque regression while others continued to develop. The biomechanical environment—specifically, how much stress and friction a given artery segment experiences—appears to influence how responsive that segment is to lipid-lowering treatment.

Fourth, this could eventually lead to more personalized monitoring strategies. If computational models can identify high-risk coronary segments based on biomechanical forces, doctors might focus imaging follow-up on specific "at-risk" regions of the coronary tree rather than assessing the whole artery uniformly. This is still years away from routine clinical practice, but the foundation is now being laid.

For patients, the most actionable takeaway is straightforward: controlling blood pressure matters at the local level. The MWS experienced by the coronary arteries is directly driven by blood pressure. Keeping blood pressure well-controlled may reduce the damaging mechanical stress on artery walls—not just globally, but in the precise locations where plaques are forming.

Study Limitations: What This Research Could Not Prove

Like all scientific studies, this research has important limitations that patients should understand.

Calcified segments were excluded. The presence of calcium in artery cross-sections made it impossible to visualize the outer vessel wall layer (the external elastic lamina) on imaging. This meant the study was limited to non-calcified cross-sections only. Since calcification is common in advanced atherosclerosis, the findings may not apply equally to heavily calcified arteries.

Side-branch segments were excluded. Cross-sections exactly at side-branch locations could not be analyzed because the finite element models required complete intactness of the artery circumference. Side branches are known to be sites of disturbed blood flow and plaque formation, so their exclusion may have removed some biologically important areas.

LRNC borders were reconstructed, not directly measured. The outer edge of the lipid-rich necrotic core was not fully visible on either NIRS-IVUS or OCT imaging. Instead, the researchers used a previously validated algorithm to reconstruct the LRNC outer edges. While the authors argue this likely has minimal effect on luminal MWS calculations (since the reconstructed edge is far from the lumen), some inaccuracy is possible.

All patients were on statins. This was actually a major confounder. Statins lower LDL cholesterol and reduce vascular inflammation, which hinders the "natural" development of atherosclerosis. The observed plaque regression in many sectors likely reflects statin effects rather than biomechanical forces alone. However, the statistical models did correct for statin treatment, and the fact that biomechanical associations persisted even after this correction strengthens the findings.

Sample size was modest. The study included 34 patients and 6,527 sectors, but the patient-level sample is relatively small. The generalizability to broader populations—including women (who made up only 8.8% of participants) and people with different risk profiles—remains uncertain.

Follow-up was only 12 months. Atherosclerosis develops over decades. A one-year window, while sufficient to detect changes in wall thickness and LRNC content, cannot capture long-term plaque behavior or clinical outcomes like heart attacks or death.

This is an observational association study, not a cause-and-effect experiment. While the statistical models corrected for many potential confounders, the association between biomechanical forces and plaque changes does not definitively prove that one causes the other. A randomized controlled trial would be needed to establish causality.

Recommendations for Patients: What You Can Do

While this research is still early-stage, its findings reinforce several well-established principles that patients can apply right now to protect their heart health:

1. Take your blood pressure medication as prescribed. This study shows that blood-pressure-related mechanical stress on artery walls is linked to plaque development. Keeping blood pressure in a healthy range directly reduces the mechanical stretch and strain on your coronary arteries.
2. Stay on your statin therapy. The study vividly demonstrates the power of statins: 85% of plaque sectors showed reduced lipid-rich necrotic core over one year, with an average 54% reduction in LRNC percentage. If you've been prescribed a statin, staying consistent with it is one of the most effective ways to stabilize and shrink plaque.
3. Control your other risk factors. Diabetes, hypertension, smoking, and high cholesterol were all present in this patient population and were corrected for in the analysis. Managing these risk factors remains foundational for reducing both biomechanical stress and the biological processes that drive plaque formation.
4. Maintain a heart-healthy lifestyle. Regular exercise, a Mediterranean-style diet, stress reduction, and weight management all contribute to better blood pressure control, healthier blood vessels, and reduced inflammation—all of which are relevant to the forces studied here.
5. Have informed conversations with your cardiologist. If you have known coronary artery disease, ask your doctor about the state of your plaque and your treatment goals. Advanced imaging techniques like IVUS and OCT are increasingly used in research settings to characterize plaque, and understanding your personal risk factors can help guide treatment decisions.

This research offers hope. The fact that plaque regresses rather dramatically when patients are on statin therapy—with biomechanical forces modifying that response—suggests that heart disease is not a one-way street. With proper treatment and risk factor control, even established plaques can shrink and become less dangerous.

Frequently Asked Questions

What are the two forces on heart arteries that this research looked at?

The two forces are wall shear stress, the friction from blood flowing over the artery's inner lining, and mechanical wall stress, the stretching from blood pressure. Wall shear stress is like hand drag from a car window; mechanical wall stress is like the tension in a balloon as it inflates.

What did the study find about new plaque formation in clear arteries?

In previously clear artery segments, higher mechanical wall stress from blood pressure was linked to greater wall thickening over one year. This suggests that areas experiencing more stretching stress may be more likely to develop new plaque. Low wall shear stress also showed a link, though this was not statistically significant.

What did the study find about plaque shrinkage?

Plaque areas shrank on average by 0.07 mm over the year, likely due to statin therapy. Higher wall shear stress and higher mechanical wall stress were each linked to greater shrinkage. Plaques with both low forces shrank the least, while those with both high forces regressed the most.

How did the forces affect the dangerous lipid core inside plaques?

Overall, the lipid-rich necrotic core shrank by 54%, and 85% of plaque areas showed improvement. But the combination of low mechanical wall stress plus high wall shear stress was linked to an increase in this dangerous lipid core, even during statin therapy, suggesting a potentially higher-risk plaque.

What are the limitations of this research?

The study was small, with only 34 patients, and most were men. Calcified artery areas and side branches were excluded. Lipid core borders were reconstructed, not directly measured. All patients were on statins, and the follow-up was only 12 months. So this shows associations, not proven cause and effect.

What can patients do based on these findings?

Take blood pressure medications as prescribed to reduce mechanical stress on artery walls. Stay on statin therapy, which shrank plaques in most patients. Control other risk factors like diabetes, smoking, and high cholesterol. Maintain a heart-healthy lifestyle and discuss plaque imaging and treatment goals with your cardiologist.

When should a patient with coronary artery plaque consider a second opinion about using advanced imaging to assess biomechanical forces like wall shear stress and mechanical wall stress?

A second opinion may be helpful for a patient with coronary artery disease who wants to know whether advanced imaging (such as IVUS or OCT) could assess plaque vulnerability based on biomechanical forces like wall shear stress and mechanical wall stress. Even with statin therapy—which reduced lipid-rich necrotic core in 85% of plaque sectors—some areas exposed to low mechanical stress and high shear stress show increased lipid core. A specialist can review imaging and risk factors to clarify monitoring options. Diagnostic Detectives Network provides independent expert second opinions.

Source Information

Original article title: Mechanical wall stress and wall shear stress are associated with atherosclerosis development in non-calcified coronary segments

Author: Aikaterini Tziotzioua, Eline Hartmana, Suze-Anne Kortelanda, Aad van der Lugtc, Antonius F.W. van der Steena, Joost Daemenb, Daniel Bosc,d, Jolanda Wentzela, Ali C. Akyildiza,e,*

Publication: Atherosclerosis, Volume 387 (2023), Article 117387. Published by Elsevier B.V. Available online November 15, 2023.

Funding/affiliations: The research was conducted at the Department of Biomedical Engineering, Erasmus Medical Center, Rotterdam, the Netherlands, with contributions from the Departments of Cardiology, Radiology & Nuclear Medicine, and Epidemiology, as well as the Department of Biomechanical Engineering at Delft University of Technology.

Ethics: The study was approved by the local medical ethics committee of Erasmus University Medical Center (MEC 2015-535, NL54519.078.15) and conducted in accordance with the Declaration of Helsinki and the Dutch Medical Research Involving Human Subject Act (WMO).

Disclosure: This is an open-access article under the CC BY license.

Note: This patient-friendly article is based on peer-reviewed research. It is intended for educational purposes and should not replace professional medical advice. Always consult your healthcare provider before making any changes to your treatment plan.