Sex-related differences in plaque characteristics and endothelial shear stress related plaque-progression in human coronary arteries

Abstract Background Atherosclerosis manifests itself differently in women compared to men. Since the pathophysiology of atherosclerotic plaques is known to be related to endothelial shear stress (ESS), it was hypothesized that female compared to male coronary arteries demonstrate a different i) ESS and ii) ESS related plaque progression. Methods 1183 coronary arteries (male/female:944/239) from the PREDICTION trial were studied for differences in vessel geometry (plaque area (PA) and lumen area (LA)), hemodynamic parameters (flow, minimal ESS over 90 degree arc (minESS) and maximal ESS over 90 degree arc (maxESS)) and ESS related plaque progression (1 year follow up) measured as change in maximal plaque thickness and plaque burden comparing female to male arteries. Arterial geometry and ESS measures were derived from IVUS-based vascular profiling and reported per 3 mm segments. For plaque progression studies minESS was subdivided into low, mid and high (<1,1–1.7,>1.7 Pa). To test statistical differences univariate anova or linear mixed models were used. Results 13030 3mm-segments (m/f: 10.465/2565) were analyzed. Female compared to male coronary arteries were smaller and presented with less plaque area (Table I). No differences in average ESS, minESS and maxESS were found for male versus female coronary arteries, partly explained by the lower flows in female arteries (Table I). The ESS-related plaque growth showed for both sexes an significant inverse relationship between maximal wall thickness (Figure, left) and plaque burden (Figure, right) and the three minESS categories. However, ESS-related plaque growth was not different for male vs females. Conclusion Our data demonstrated that vessel and plaque size are smaller in female compared to male coronary arteries. However, ESS and ESS related plaque progression were not different. Shear stress related plaque progression Funding Acknowledgement Type of funding source: None

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P3588The synergistic effect of NIRS-detected lipid-rich plaque and 5 different multidirectional wall shear stress metrics on human coronary plaque growth

European Heart Journal ◽

10.1093/eurheartj/ehz745.0448 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

E M J Hartman ◽

A M Kok ◽

A Hoogendoorn ◽

F J H Gijsen ◽

A F W Steen ◽

...

Keyword(s):

Shear Stress ◽

Wall Shear Stress ◽

Synergistic Effect ◽

Coronary Arteries ◽

Wall Thickness ◽

Plaque Progression ◽

Lipid Rich Plaque ◽

Plaque Growth ◽

Wall Shear ◽

The Impact

Abstract Introduction Local wall shear stress (WSS) metrics, high local lipid levels (as detected by near-infrared spectroscopy (NIRS)), as well as systemic lipid levels, have been individually associated with atherosclerotic disease progression. However, a possible synergistic effect remains to be elucidated. This study is the first study to combine WSS metrics with NIRS-detected local lipid content to investigate a potential synergistic effect on plaque progression in human coronary arteries. Methods The IMPACT study is a prospective, single centre study investigating the relation between atherosclerotic plaque progression and WSS in human coronary arteries. Patients with ACS treated with PCI were included. At baseline and after 1-year follow-up, patients underwent near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) imaging and intravascular doppler flow measurements of at least one non-culprit coronary artery. After one month, a CT angiography was made. CT derived centreline combined with IVUS lumen contours resulted in a 3D reconstruction of the vessel. The following WSS metrics were computed using computational fluid dynamics applying the vessel specific invasive flow measurements: time-average wall shear stress (TAWSS), relative residence time (RRT), cross-flow index, oscillatory shear index and transverse wall shear stress. Low TAWSS is known as pro atherogenic, in contrast to all the other shear stress metrics, at which a high magnitude is pro-atherogenic. The arteries were divided into 1.5mm/45° sectors. Based on NIRS-IVUS, wall thickness change over time was determined and NIRS positive sectors detected. Furthermore, per vessel the shear stress was divided into tertiles (low, intermediate, high). To investigate the synergistic effect of local lipids on shear stress related plaque growth, wall thickness change over time was related to the different shear stress metrics comparing the NIRS-positive with the NIRS-negative sectors. Results 15 non-culprit coronary arteries from the first 14 patients were analyzed (age 62±10 years old and 92.9% male). A total of 2219 sectors were studied (5.2%, N=130, NIRS-positive) for wall thickness changes. After studying all five shear stress metrics, we found for TAWSS and RRT that presence of lipids, as detected by NIRS, amplified the effect of shear stress on plaque progression (see figure). Sectors presenting with lipid-rich plaque, compared to NIRS-negative sectors, showed more progression when they were exposed to low TAWSS (p=0.07) or high RRT (p=0.012) and more regression in sectors exposed to high TAWSS (p=0.10) or low RRT (p=0.06). Delta wall thickness vs shear stress Conclusion We presented the first preliminary results of the IMPACT study, showing the synergistic effect of lipid rich plaque and shear stress on plaque progression. Therefore, intravascular lipid-rich plaque (NIRS) assessment has added value to shear stress profiling for the prediction of plaque growth, leading to improved risk stratification. Acknowledgement/Funding ERC starting grant 310457

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An assessment of intra-patient variability on observed relationships between wall shear stress and plaque progression in coronary arteries

BioMedical Engineering OnLine ◽

10.1186/1475-925x-14-s1-s2 ◽

2015 ◽

Vol 14 (Suppl 1) ◽

pp. S2 ◽

Cited By ~ 12

Author(s):

David S Molony ◽

Lucas H Timmins ◽

Olivia Y Hung ◽

Emad Rasoul-Arzrumly ◽

Habib Samady ◽

...

Keyword(s):

Shear Stress ◽

Wall Shear Stress ◽

Coronary Arteries ◽

Plaque Progression ◽

Wall Shear

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Abstract 12063: High-risk Plaque Co-localizes With Low Endothelial Shear Stress and Expansive Remodeling in Human Coronary Arteries: A 3D Optical Coherence Tomography Study

Circulation ◽

10.1161/circ.132.suppl_3.12063 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Yiannis S Chatzizisis ◽

Konstantinos Toutouzas ◽

Andreas A Giannopoulos ◽

Maria Riga ◽

Antonios P Antoniadis ◽

...

Keyword(s):

Optical Coherence Tomography ◽

Shear Stress ◽

High Risk ◽

Coronary Arteries ◽

Vascular Remodeling ◽

Pool Size ◽

Optical Coherence ◽

Fibrous Cap ◽

Endothelial Shear Stress

Background: High risk plaque accounts for the majority of acute coronary events. Low endothelial shear stress (ESS) is a key factor of the natural history of atherosclerosis. The role of ESS in high risk plaque formation is not well studied in man. Hypothesis: To explore the association of low ESS with high risk plaque and to identify the ESS milieu and vascular remodeling response in high risk vs. non high risk plaque. Methods: 35 coronary arteries from 30 patients were 3D reconstructed with fusion of coronary angiography and optical coherence tomography (Fig A-D) . ESS was calculated in the 3D reconstructed arteries using computational fluid dynamics (Fig E) and classified into low, moderate and high in 3 mm long segments. In each segment: i) fibroatheromas were classified into high risk and non high risk based on fibrous cap thickness and lipid pool size ii) vascular remodeling was classified into constrictive, compensatory and expansive. Results: Fibroatheromas in low ESS segments had significantly thinner fibrous cap compared to high ESS segments (89±84 vs.138±83 μm, p<0.05). Lipid pool size was comparable across all ESS categories. The majority of low ESS segments co-localized with high risk plaques (29 vs. 9%, p<0.05), whereas the majority of high ESS co-localized with non high risk plaques (24 vs. 9%, p<0.05, Fig F ). Compensatory and expansive remodeling was the predominant remodeling response in low ESS segments containing high risk plaques. In non-stenotic fibroatheromas (expansive or compensatory remodeling) low ESS was predominantly associated with high risk plaques (29 vs. 3%, p<0.05) whereas high ESS was associated with non high risk plaques (Fig F) . Conclusions: Novel combined anatomic and functional imaging with 3D OCT showed that low ESS and non-constrictive remodeling are associated with high risk plaque in man. Further studies are needed to assess the role of ESS and vascular remodeling in high risk plaque rupture and precipitation of clinical outcomes.

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Synergistic effect of local endothelial shear stress and systemic hypercholesterolemia on coronary atherosclerotic plaque progression and composition in pigs

International Journal of Cardiology ◽

10.1016/j.ijcard.2013.10.021 ◽

2013 ◽

Vol 169 (6) ◽

pp. 394-401 ◽

Cited By ~ 21

Author(s):

Konstantinos C. Koskinas ◽

Yiannis S. Chatzizisis ◽

Michail I. Papafaklis ◽

Ahmet U. Coskun ◽

Aaron B. Baker ◽

...

Keyword(s):

Shear Stress ◽

Synergistic Effect ◽

Atherosclerotic Plaque ◽

Plaque Progression ◽

Coronary Atherosclerotic Plaque ◽

Endothelial Shear Stress

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Shear stress related plaque progression in human coronary arteries is dependent on sex and age

Atherosclerosis ◽

10.1016/j.atherosclerosis.2021.06.276 ◽

2021 ◽

Vol 331 ◽

pp. e94-e95

Author(s):

J.J. Wentzel ◽

M. Papafaklis ◽

A. Antoniadis ◽

S. Takahashi ◽

N.V. Cefalo ◽

...

Keyword(s):

Shear Stress ◽

Coronary Arteries ◽

Plaque Progression

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Association of Remodeling With Endothelial Shear Stress, Plaque Elasticity, and Volume in Coronary Arteries

Angiology ◽

10.1177/0003319713483543 ◽

2013 ◽

Vol 65 (5) ◽

pp. 413-419 ◽

Cited By ~ 5

Author(s):

Sotirios A. Katranas ◽

Anastasios L. Kelekis ◽

Antonios P. Antoniadis ◽

Yiannis S. Chatzizisis ◽

George D. Giannoglou

Keyword(s):

Shear Stress ◽

Coronary Arteries ◽

Endothelial Shear Stress

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Estimation of endothelial shear stress in atherosclerotic lesions detected by intravascular ultrasound using computational fluid dynamics from coronary CT scans with a pulsatile blood flow and an individualized blood viscosity

Clinical Hemorheology and Microcirculation ◽

10.3233/ch-201025 ◽

2021 ◽

pp. 1-14

Author(s):

Adrian Curta ◽

Ahmad Jaber ◽

Johannes Rieber ◽

Holger Hetterich

Keyword(s):

Fluid Dynamics ◽

Computational Fluid Dynamics ◽

Shear Stress ◽

Coronary Arteries ◽

Blood Viscosity ◽

Flow Profile ◽

Cfd Simulations ◽

Coronary Ct ◽

Endothelial Shear Stress

INTRODUCTION: Endothelial shear stress (ESS) is a local hemodynamic factor that is dependent on vessel geometry and influences the process of atherogenesis. As in vivo measurements of ESS are not possible, it must be calculated using computational fluid dynamics (CFD). In this feasibility study we explore CFD-models generated from coronary CT-angiography (CCTA) using an individualised blood viscosity and a pulsatile flow profile derived from in vivo measurements. MATERIALS AND METHODS: We retrospectively recruited 25 consecutive patients who received a CCTA followed by a coronary angiography including intravascular ultrasound (IVUS) and generated 3D models of the coronary arteries from the CT-datasets. We then performed CFD-simulations on these models. Hemodynamically non-relevant stenosis were identified in IVUS. They were isolated in the CFD-model and separated longitudinally into a half with atherosclerotic lesion (AL) and one without (NAL). ESS was measured and compared for both halves. RESULTS: After excluding vessels with no IVUS data or relevant stenosis we isolated 31 hemodynamically non-relevant excentric AL from a total of 14 vessels. AL segments showed consistently significantly lower ESS when compared to their corresponding NAL segments when regarding minimum (0.9 Pa, CI [0.6, 1.2] vs. 1.3 Pa, CI [0.9, 1.8]; p = 0.004), mean (5.0 Pa, CI [3.4, 6.0] vs. 6.7 Pa, CI [5.5, 8.4]; p = 0.008) and maximum ESS values (12.4 Pa, CI [8.6, 14.6] vs. 19.6 Pa, CI [12.4, 21.0]; p = 0.005). Qualitatively ESS was lower on the inside of bifurcations and curvatures. CONCLUSION: CFD simulations of coronary arteries from CCTA with an individualised flow profile and blood viscosity are feasible and could provide further prognostic information and a better risk stratification in coronary artery disease. Further prospective studies are needed to investigate this claim.

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