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Prognostic Value of Coronary Vascular Endothelial Dysfunction
Abstract
Background — Whether patients at increased risk can be identified from a relatively low-risk population by coronary vascular function testing remains unknown. We investigated the relationship between coronary endothelial function and the occurrence of acute unpredictable cardiovascular events (cardiovascular death, myocardial infarction, stroke, and unstable angina) in patients with and without coronary atherosclerosis (CAD). Methods and Results — We measured the change in coronary vascular resistance (ΔCVR) and epicardial diameter with intracoronary acetylcholine (ACh, 15 μg/min) to test endothelium-dependent function and sodium nitroprusside (20 μg/min) and adenosine (2.2 mg/min) to test endothelium-independent vascular function in 308 patients undergoing cardiac catheterization (132 with and 176 without CAD). Patients underwent clinical follow-up for a mean of 46±3 months. Acute vascular events occurred in 35 patients. After multivariate analysis that included CAD and conventional risk factors for atherosclerosis, ΔCVR with ACh ( P =0.02) and epicardial constriction with ACh ( P =0.003), together with increasing age, CAD, and body mass index, were independent predictors of adverse events. Thus, patients in the tertile with the best microvascular responses with ACh and those with epicardial dilation with ACh had improved survival by Kaplan-Meier analyses in the total population, as did those in the subset without CAD. Similar improvement in survival was also observed when all adverse events, including revascularization, were considered. Endothelium-independent responses were not predictive of outcome. Conclusions — Epicardial and microvascular coronary endothelial dysfunction independently predict acute cardiovascular events in patients with and without CAD, providing both functional and prognostic information that complements angiographic and risk factor assessment.
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“Endothelial dysfunction occurs early in the pathogenesis of atherosclerosis, and predicts future cardiovascular events.”
From The Vasculature in Prediabetes (2018) · cites this paper as [32]
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Päivärinta, J., Koivuviita, N. S., Oikonen, V., Iida, H., Liukko, K. E., Manner, I., Löyttyniemi, E., Nuutila, P., & Metsarinne, K. P. (2018) · EJNMMI Research · doi:10.1186/s13550-018-0395-3 · Cited by 15
“There has been high hopes that RFR (renal flow reserve), the difference between stress and basal flow, would be a good marker of microvascular function as CFR (coronary flow reserve) which is a strong predictor of future cardiovascular events [9].”
BackgroundLiu, L., Wu, Q., Yan, H., Chen, B., Zheng, X., & Zhou, Q. (2020) · Disease Markers · doi:10.1155/2020/6659166 · Cited by 15
“Recently, studies that dysfunction of the cardiac autonomic system may be effective in the development of vascular atherosclerosis have been well documented [6, 7].”
BackgroundGram-Kampmann, E.-M., Olesen, T. B., Hansen, C. D., Hugger, M. B., Jensen, J. M., Handberg, A., Beck‐Nielsen, H., Krag, A. A., Olsen, M. H., & Højlund, K. (2023) · Cardiovascular Diabetology · doi:10.1186/s12933-023-01956-8 · Cited by 16
Epigenetic clock in the aorta and age-related endothelial dysfunction in mice
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“Age-dependent decline of endothelial function predicts CVD-related morbidity and mortality [6, 7], but the mechanisms responsible for the ageing of vasculature are far from well-understood [6].”
BackgroundThe Long-Term Effect of Coronary Stenting on Epicardial and Microvascular Endothelial Function
Lim, S., Flammer, A. J., Yoon, M., Lennon, R. J., Gulati, R., Mathew, V., Rihal, C. S., Lerman, L. O., & Lerman, A. (2012) · Circulation Cardiovascular Interventions · doi:10.1161/circinterventions.112.970111 · Cited by 15
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OBSTRUCTIVE CORONARY ATHEROSCLEROSIS AND ISCHEMIC HEART DISEASE: AN ELUSIVE LINK!
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Postprandial endothelial function does not differ in women by race: an insulin resistance paradox?
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“161 Annals of Pediatric Cardiology 2012 Vol 5 Issue 2 coronary vascular endothelial dysfunction is also an independent factor for coronary atherosclerosis.[11]”
Association of genetic polymorphisms of CYP 2C19 with hypertension in a Chinese Han population
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“Previous study indicated that endothelial dysfunction is associated with increased risk of cardiovascular events (23), and is typically manifested by impairment in endothelial-dependent vasodilation (24).”
BackgroundMicrovascular Angina: an Update On Diagnosis and Treatment
Titterington, J. S., Hung, O. Y., & WENGER, N. K. (2015) · Future Cardiology · doi:10.2217/fca.14.79 · Cited by 15
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A Short History of Vasospastic Angina
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“Importantly, in patients with CRFs, endothelial dysfunction is associated with an increased risk of future cardiovascular events[7].”
BackgroundThe assessment of vascular function during dietary intervention trials in human subjects
McCall, D. O., McKinley, M. C., Noad, R., McKeown, P. P., McCance, D. R., Young, I. S., & Woodside, J. V. (2011) · British Journal Of Nutrition · doi:10.1017/s0007114511002996 · Cited by 14
Weggen, J. B., Darling, A. M., Autler, A. S., Hogwood, A. C., Decker, K., Imthurn, B., Tuzzolo, G., & Garten, R. S. (2021) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00054.2021 · Cited by 14
Qiu, Z., Wang, Y., Liu, Y., Zhou, Z., & Wang, Z. (2024) · Medicine · doi:10.1097/md.0000000000037022 · Cited by 14
“Other studies [33,34] have also demonstrated an association between coronary microvascular dysfunction and an increased risk of adverse outcomes in patients with non-obstructive CAD (Coronary Artery Disease).”
BackgroundEndothelial function and risk of hypertension and blood pressure progression
Lytsy, P., Lind, L., & Sundström, J. (2013) · Journal of Hypertension · doi:10.1097/hjh.0b013e32835ed5a0 · Cited by 14
“Hence, the repeatedly observed associations between impaired endothelial function and risk of cardiovascular events [1–4] must be mediated through other physiological pathways, such as development of atherosclerosis [15], increased oxidative stress [16], impaired fibrinolytic capacity [17] or, as shown in participants…”
BackgroundAhmadi, N., Hajsadeghi, F., Nabavi, V., Olango, G., Molla, M., Budoff, M. J., Vaidya, N. A., Quintana, J., Pynoos, R. S., Hauser, P., et al. (2018) · Psychosomatic Medicine · doi:10.1097/psy.0000000000000565 · Cited by 14
“Family history of MHD 25% (49) 30% (15) .”
Metadata
- Authors
- Halcox, J. P. J., Schenke, W. H., Zalos, G., Mincemoyer, R., Prasad, A., Waclawiw, M. A., Nour, K. R. A., & Quyyumi, A. A.
- Affiliations
- National Institutes of Health (US)
- Venue
- Circulation
- Published
- 2002-08-06
- Volume
- 106
- Issue
- 6
- Pages
- 653-658
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2019338486
- Cited by
- 1,385
- References
- 24
- Citations by year
- 2026: 12 · 2025: 13 · 2024: 25 · 2023: 33 · 2022: 21 · 2021: 33 · 2020: 49 · 2019: 50 · 2018: 56 · 2017: 51 · 2016: 51 · 2015: 70 · 2014: 87 · 2013: 59 · 2012: 70
- FWCI
- 51.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Cardiac Imaging and Diagnostics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Keywords
- coronary endothelial dysfunction, coronary artery disease, acetylcholine provocation test, sodium nitroprusside, adenosine, coronary vascular resistance, cardiovascular events, prognosis, myocardial infarction, unstable angina, stroke, cardiovascular mortality, revascularization
- MeSH terms
- Angina, Unstable, Coronary Artery Disease, Coronary Circulation, Coronary Vessels, Endothelium, Vascular, Female, Follow-Up Studies, Humans, Male, Microcirculation, Middle Aged, Myocardial Infarction, Pericardium, Prognosis, Vascular Resistance, Vasodilator Agents, Disease-Free Survival, Stroke
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