Association of coronary shear stress with endothelial function and vascular remodeling in patients with normal or mildly diseased coronary arteries

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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Restoration of Vitamin D Levels Improves Endothelial Function and Increases TASK-Like K+ Currents in Pulmonary Arterial Hypertension Associated with Vitamin D Deficiency

Biomolecules ◽

10.3390/biom11060795 ◽

2021 ◽

Vol 11 (6) ◽

pp. 795

Author(s):

Maria Callejo ◽

Daniel Morales-Cano ◽

Gema Mondejar-Parreño ◽

Bianca Barreira ◽

Sergio Esquivel-Ruiz ◽

...

Keyword(s):

Vitamin D ◽

Pulmonary Arterial Hypertension ◽

Endothelial Function ◽

Arterial Hypertension ◽

Vascular Remodeling ◽

Standard Diet ◽

Pulmonary Vascular Remodeling ◽

Vitamin D Levels ◽

Pulmonary Arterial ◽

K Currents

Background: Vitamin D (vitD) deficiency is highly prevalent in patients with pulmonary arterial hypertension (PAH). Moreover, PAH-patients with lower levels of vitD have worse prognosis. We hypothesize that recovering optimal levels of vitD in an animal model of PAH previously depleted of vitD improves the hemodynamics, the endothelial dysfunction and the ionic remodeling. Methods: Male Wistar rats were fed a vitD-free diet for five weeks and then received a single dose of Su5416 (20 mg/Kg) and were exposed to vitD-free diet and chronic hypoxia (10% O2) for three weeks to induce PAH. Following this, vitD deficient rats with PAH were housed in room air and randomly divided into two groups: (a) continued on vitD-free diet or (b) received an oral dose of 100,000 IU/Kg of vitD plus standard diet for three weeks. Hemodynamics, pulmonary vascular remodeling, pulmonary arterial contractility, and K+ currents were analyzed. Results: Recovering optimal levels of vitD improved endothelial function, measured by an increase in the endothelium-dependent vasodilator response to acetylcholine. It also increased the activity of TASK-1 potassium channels. However, vitD supplementation did not reduce pulmonary pressure and did not ameliorate pulmonary vascular remodeling and right ventricle hypertrophy. Conclusions: Altogether, these data suggest that in animals with PAH and severe deficit of vitD, restoring vitD levels to an optimal range partially improves some pathophysiological features of PAH.

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Exploring wall shear stress spatiotemporal heterogeneity in coronary arteries combining correlation-based analysis and complex networks with computational hemodynamics

Proceedings of the Institution of Mechanical Engineers Part H Journal of Engineering in Medicine ◽

10.1177/0954411920923253 ◽

2020 ◽

Vol 234 (11) ◽

pp. 1209-1222 ◽

Cited By ~ 2

Author(s):

Karol Calò ◽

Giuseppe De Nisco ◽

Diego Gallo ◽

Claudio Chiastra ◽

Ayla Hoogendoorn ◽

...

Keyword(s):

Shear Stress ◽

Wall Shear Stress ◽

Complex Networks ◽

Coronary Arteries ◽

Early Stage ◽

Flow Direction ◽

Computational Hemodynamics ◽

Time Histories ◽

Wall Shear

Atherosclerosis at the early stage in coronary arteries has been associated with low cycle-average wall shear stress magnitude. However, parallel to the identification of an established active role for low wall shear stress in the onset/progression of the atherosclerotic disease, a weak association between lesions localization and low/oscillatory wall shear stress has been observed. In the attempt to fully identify the wall shear stress phenotype triggering early atherosclerosis in coronary arteries, this exploratory study aims at enriching the characterization of wall shear stress emerging features combining correlation-based analysis and complex networks theory with computational hemodynamics. The final goal is the characterization of the spatiotemporal and topological heterogeneity of wall shear stress waveforms along the cardiac cycle. In detail, here time-histories of wall shear stress magnitude and wall shear stress projection along the main flow direction and orthogonal to it (a measure of wall shear stress multidirectionality) are analyzed in a representative dataset of 10 left anterior descending pig coronary artery computational hemodynamics models. Among the main findings, we report that the proposed analysis quantitatively demonstrates that the model-specific inlet flow-rate shapes wall shear stress time-histories. Moreover, it emerges that a combined effect of low wall shear stress magnitude and of the shape of the wall shear stress–based descriptors time-histories could trigger atherosclerosis at its earliest stage. The findings of this work suggest for new experiments to provide a clearer determination of the wall shear stress phenotype which is at the basis of the so-called arterial hemodynamic risk hypothesis in coronary arteries.

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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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