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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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Cardiovascular Risk and Resilience Among Black Adults: Rationale and Design of the MECA Study
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Self-citationPargaonkar, V. S., Lee, J., Chow, E. K. H., Nishi, T., Ball, R. L., Kobayashi, Y., Kimura, T., Lee, D. P., Stefanick, M. L., Fearon, W. F., et al. (2020) · Circulation Cardiovascular Interventions · doi:10.1161/circinterventions.119.008587 · Cited by 23
“(3) Incremental dosing of Ach, starting at 20 μg and increasing to 100 μg, appears to improve the diagnostic utility of identifying a clinically significant MLD constriction during endothelial function testing.”
BackgroundObesity-Related Inflammation and Endothelial Dysfunction in COVID-19: Impact on Disease Severity
Lorenzo, A. D., Estato, V., Castro-Faria-Neto, H. C., & Tibiriçá, E. V. (2021) · Journal of Inflammation Research · doi:10.2147/jir.s282710 · Cited by 24
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Self-citationTetrahydrobiopterin Improves Endothelial Function in Cardiovascular Disease: A Systematic Review
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“Furthermore, endothelial function was demonstrated to serve as a predictor of cardiovascular events [6, 7].”
BackgroundPeripheral vascular endothelial function correlates with exercise capacity in women
Patel, A. R., Kuvin, J. T., Sliney, K. A., Rand, W. M., Pandian, N. G., & Karas, R. H. (2005) · Clinical Cardiology · doi:10.1002/clc.4960280909 · Cited by 23
Health behaviors and endothelial function
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“Studies in patients with CVD (Halcox et al. 2002; Schachinger et al. 2000; Suwaidi et al. 2000) or CVD risk factors (Gokce et al.”
BackgroundFeng, J., Wang, A., Gao, C., Zhang, J., Chen, Z., Hou, L., Luo, C., Jiang, Y., & Pan, J. (2014) · The Anatolian Journal of Cardiology · doi:10.5152/akd.2014.5642 · Cited by 24
“Other studies have shown that dysfunction of autonomic nerve system may be effective in development of atherosclerosis (9), but this theory remains controversial, especially for among patients with stable angina (10).”
BackgroundMontorsi, P., Ravagnani, P. M., Galli, S., Alì, S. G., Briganti, A., Salonia, A., & Montorsi, F. (2008) · European Urology Supplements · doi:10.1016/j.eursup.2008.10.010 · Cited by 23
“Moreover, impairment of the endothelium-dependent dilation has been found to predict long-term coronary events [18,19] in patients with or without obstructive CAD.”
BackgroundIs reversal of endothelial dysfunction still an attractive target in modern cardiology?
Mordi, I. R. (2014) · World Journal of Cardiology · doi:10.4330/wjc.v6.i8.824 · Cited by 22
Mitchell, A. J., Misialek, J. R., Folsom, A. R., Duprez, D. A., Alonso, Á., Jerosch‐Herold, M., Sanchez, O. A., Watson, K. E., Sallam, T., & Konety, S. (2015) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2015.02.040 · Cited by 22
EL-Mesallamy, H. O., Hamdy, N. Μ., Salman, T. M., & Ibrahim, S. M. (2011) · Angiology · doi:10.1177/0003319711408587 · Cited by 22
“01 HDL-C (mg/dL) 39 + 2 (36-41) 25 + 2 (22-29) 27 + 2 (22-29) .”
Naidu, O. A., Rajasekhar, D., & Latheef, S. A. A. (2011) · Cardiovascular Ultrasound · doi:10.1186/1476-7120-9-40 · Cited by 22
“A single measurement of endothelial function in both the coronary and peripheral circulation can be of prognostic value in both normal and coronary heart disease patients [16,20,21].”
Nguyen, M. T., Pham, I., Valensi, P. E., Rousseau, H., Vicaut, É., Laguillier, C., Nitenberg, A., & Cosson, E. (2014) · Cardiovascular Diabetology · doi:10.1186/1475-2840-13-20 · Cited by 23
Genetic loci associated with nonobstructive coronary artery disease in Caucasian women
Weng, L., Taylor, K. D., Chen, Y. I., Sopko, G. S., Kelsey, S. F., Merz, C. N. B., Pepine, C. J., Miller, V. M., Rotter, J. I., Gulati, M., et al. (2015) · Physiological Genomics · doi:10.1152/physiolgenomics.00067.2015 · Cited by 22
“While ischemic heart disease due to obstructive coronary artery disease (CAD) is well studied (29), nonobstructive CAD also contributes to cardiovascular (CV) morbidity and mortality (1, 12, 16) but is less well characterized particularly in women, as nonobstructive CAD risk is often underdiagnosed and underestimated…”
BackgroundHamid, M. A., Bakhoum, S., Sharaf, Y., Sabry, D., El-gengehe, A., & Abdel‐Latif, A. (2016) · Journal of Interventional Cardiology · doi:10.1111/joic.12269 · Cited by 22
“Other findings of a significantly lower FMD in the MACE compared to the non-MACE group confirm the major link between endothelial injury or dysfunction and CV outcome described in many studies.(35-39) vWF is a critical factor for platelet aggregation and adhesion.”
ResultRetinal endothelial function in cardiovascular risk patients: A randomized controlled exercise trial
Streese, L., Kotliar, K. E., Deiseroth, A., Infanger, D., Gugleta, K., Schmaderer, C., & Hanssen, H. (2019) · Scandinavian Journal of Medicine and Science in Sports · doi:10.1111/sms.13560 · Cited by 22
Coronary microvascular function in patients with type 2 diabetes mellitus
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Locati, D., Morandi, S., Cupisti, A., Ghiadoni, L., & Arnoldi, A. (2005) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.2222 · Cited by 22
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Role of quercetin in cardiovascular diseases
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Angina With “Normal” Coronary Arteries
Bugiardini, R., & Merz, C. N. B. (2005) · ACC Current Journal Review · doi:10.1016/j.accreview.2005.04.049 · Cited by 21
“acetylcholine testing, it predicts an unfavorable outcome.(15,32,49-51) Outcomes,”
InfluentialFairbairn, T. A., Motwani, M., Mather, A. N., Biglands, J. D., Larghat, A. M., Radjenovic, A., Greenwood, J. P., & Plein, S. (2013) · Radiology · doi:10.1148/radiol.13122345 · Cited by 21
Coronary endothelial function assessment using self‐gated cardiac cine MRI andk‐tsparse SENSE
Yerly, J., Ginami, G., Nordio, G., Coristine, A. J., Coppo, S., Monney, P. A., & Stuber, M. (2015) · Magnetic Resonance in Medicine · doi:10.1002/mrm.26050 · Cited by 21
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Coronary Exercise Hyperemia Is Impaired in Patients with Peripheral Arterial Disease
Ross, A. J., Gao, Z., Luck, J. C., Blaha, C., Cauffman, A. E., Aziz, F., Radtka, J. F., Proctor, D. N., Leuenberger, U. A., Sinoway, L. I., et al. (2016) · Annals of Vascular Surgery · doi:10.1016/j.avsg.2016.05.135 · Cited by 21
Park, K.-H., Sun, T., Díez‐Delhoyo, F., Liu, Z., Yang, S.-W., Lennon, R. J., Herrmann, J., Gulati, R., Rodriguez-Porcel, M. G., Lerman, L. O., et al. (2016) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2016.08.031 · Cited by 21
Shechter, M., Matetzky, S., Prasad, M., Goitein, O., Goldkorn, R., Naroditsky, M., Koren‐Morag, N., & Lerman, A. (2017) · International Journal of Cardiology · doi:10.1016/j.ijcard.2017.04.101 · Cited by 21
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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