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Differential role of central and peripheral arterial stiffness in determining brachial artery resting retrograde flow in patients with ischemic heart disease vs healthy subjects


Retrograde flow in endothelial cell cultures has been shown to induce a pro-atherogenic phenotype. Despite its potential role as a pathophysiological link between cardiovascular risk factors and atherosclerotic disease, resting retrograde flows between patients with cardiovascular disease and healthy subjects have not been compared. Further, the vascular characteristics governing retrograde flow in human arteries have not been systematically investigated. Association of central and peripheral vascular characteristics with retrograde flow profile was investigated in 32 healthy subjects and 47 patients with ischemic heart disease. Endothelial dysfunction was assessed by brachial ultrasound-based calculation of flow-mediated dilation (FMD) and sub-clinical atherosclerosis was estimated from carotid-intima media thickness (CIMT). Retrograde blood flow velocity (RBFV) and shear rate were comparable between the two groups (RBFV 1.82(0.97–3.32) vs 1.78(1.24–2.65) cm/s p  =  0.79). Augmentation index was a significant determinant of retrograde flow in both patients and healthy subjects. Carotid artery incremental elastic modulus was an independent determinant of retrograde flow patterns in healthy subjects while ejection fraction, cf/cr PWV ratio and forearm vascular conductance emerged as independent determinants in patients. Retrograde flow patterns were also associated with FMD (RBFV r  =  −0.43, p  =  0.004) and CIMT (r  =  0.30, p  =  0.041) in patients. The results of the study suggest a difference in the determinants of retrograde flow in patients and healthy subjects, with central arterial stiffness being a major contributor in healthy subjects while interaction between central, peripheral, and cardio-arterial factors influence retrograde flow in patients with ischemic heart disease.

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Fig. 1: Comparison of central stiffness and retrograde flow profile between the two groups.
Fig. 2: Association of retrograde and oscillatory flow profile with central and peripheral vascular factors in healthy subjects and patients.
Fig. 3: Association of retrograde flow profile with endothelial function and sub-clinical atherosclerosis in healthy subjects (A) and patients (B, C).
Fig. 4: Summary of the central, peripheral, and composite vascular factors associated with retrograde flow.

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Data generated and analysed for the study is available from the corresponding author upon request.


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This study was supported by Indian Council of Medical Research Grant No. 3/1/2 (2)/CVD/2018-NCD-II.

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Authors and Affiliations



SB contributed to conception and design of the study, data acquisition, analysis, and interpretation, drafting and final approval of the submitted manuscript. DSC contributed to conception and design of the study, interpretation of data, revising and final approval of the submitted manuscript. AKJ contributed to conception and design of the study, revising and final approval of the submitted manuscript. RN contributed to conception and design of the study, revising the article, and final approval of the submitted manuscript. CP contributed to conception and design of the study, acquisition, analysis and interpretation of data, revising the article, and final approval of the submitted manuscript. KKP contributed to conception and design of the study, revising the article, and final approval of the submitted manuscript.

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Correspondence to Dinu S. Chandran.

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The authors declare no competing interests.

Ethical approval

The study was approved by the All India Institute of Medical Sciences, New Delhi, Institute Ethics Committee for Post Graduate Research for Clinical Science, for research on human subjects (Ref No. IECPG/288/27.04.2016,RT-37/29.06.2016) and the investigations conformed to the Declaration of Helsinki.

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Badhwar, S., Chandran, D.S., Jaryal, A.K. et al. Differential role of central and peripheral arterial stiffness in determining brachial artery resting retrograde flow in patients with ischemic heart disease vs healthy subjects. J Hum Hypertens (2022).

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