{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:57:35Z","timestamp":1791910655688,"version":"4.3.4"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T00:00:00Z","timestamp":1627344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Heart rate variability (HRV) was proposed as a noninvasive biomarker to stratify the risk of cardiovascular disease. However, it remains to be determined if HRV can be used as a surrogate for coronary artery physiology as analyzed by quantitative flow ratio (QFR) in patients with new-onset unstable angina pectoris (UAP).<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> A total of 129 consecutive patients with new-onset UAP who underwent 24-h long-range 12-channel electrocardiography from June 2020 to December 2020 were included in this study. HRV, coronary angiography, and QFR information was retrieved from patient medical records, the severity of coronary lesions was evaluated using the Gensini score (GS), and total atherosclerotic burden was assessed using the three-vessel contrast QFR (3V-cQFR) calculated as the sum of cQFR in three vessels.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Multivariate logistic analysis showed that low-frequency power (LF) and high-sensitivity C-reactive protein (hs-CRP) were directly correlated with functional ischemia of target vessel, which were inversely correlated with total atherosclerotic burden as assessed by 3V-cQFR. Moreover, incorporation of the increase in LF into the existing model that uses clinical risk factors, GS, and hs-CRP significantly increased the discriminatory ability for evaluating coronary artery physiology of target vessel.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> LF and hs-CRP are independently associated with functional ischemia in patients with new-onset UAP. The relative increase of LF and hs-CRP could add value to the use of classical cardiovascular risk factors to predict the functional severity of coronary artery stenosis. Our results suggest a potential association between the autonomic nervous system, inflammation, and coronary artery physiology.<\/jats:p>","DOI":"10.3389\/fcvm.2021.700943","type":"journal-article","created":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T05:57:27Z","timestamp":1627365447000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["Novel Insights Into the Interaction Between the Autonomic Nervous System and Inflammation on Coronary Physiology: A Quantitative Flow Ratio Study"],"prefix":"10.3389","volume":"8","author":[{"given":"Jun","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaqiang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengzhe","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huixin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongyang","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoupeng","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilei","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1001\/jama.290.7.898","article-title":"Prevalence of conventional risk factors in patients with coronary heart disease","volume":"290","author":"Khot","year":"2003","journal-title":"JAMA"},{"key":"B2","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1001\/jama.290.7.891","article-title":"Major risk factors as antecedents of fatal and nonfatal coronary heart disease events","volume":"290","author":"Greenland","year":"2003","journal-title":"JAMA"},{"key":"B3","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1016\/0735-1097(93)90174-Y","article-title":"Independent and incremental prognostic value of exercise single-photon emission computed tomographic (SPECT) thallium imaging in coronary artery disease","volume":"22","author":"Iskandrian","year":"1993","journal-title":"J Am Coll Cardiol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1161\/hc0702.103973","article-title":"Value of stress myocardial perfusion single photon emission computed tomography in patients with normal resting electrocardiograms: an evaluation of incremental prognostic value and cost-effectiveness","volume":"105","author":"Hachamovitch","year":"2002","journal-title":"Circulation"},{"key":"B5","doi-asserted-by":"publisher","first-page":"3312","DOI":"10.1093\/eurheartj\/ehv235","article-title":"Fundamentals in clinical coronary physiology: why coronary flow is more important than coronary pressure","volume":"36","author":"van de Hoef","year":"2015","journal-title":"Eur Heart J"},{"key":"B6","doi-asserted-by":"publisher","first-page":"180","DOI":"10.4244\/EIJ-D-18-00896","article-title":"Prognostic implication of three-vessel contrast-flow quantitative flow ratio in patients with stable coronary artery disease","volume":"15","author":"Hamaya","year":"2019","journal-title":"EuroIntervention"},{"key":"B7","doi-asserted-by":"publisher","first-page":"2850","DOI":"10.1161\/01.CIR.94.11.2850","article-title":"Impact of reduced heart rate variability on risk for cardiac events. The framingham heart study","volume":"94","author":"Tsuji","year":"1996","journal-title":"Circulation"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2143","DOI":"10.2337\/dc19-0993","article-title":"Heart rate variability and cardiac autonomic dysfunction: prevalence, risk factors, and relationship to arterial stiffness in the treatment options for type 2 diabetes in adolescents and youth (TODAY) study","volume":"42","author":"Shah","year":"2019","journal-title":"Diabetes Care"},{"key":"B9","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.diabres.2003.10.009","article-title":"Low heart rate variability is a risk factor for sudden cardiac death in type 2 diabetes","volume":"64","author":"Kataoka","year":"2004","journal-title":"Diabetes Res Clin Pract"},{"key":"B10","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1016\/S0002-8703(98)70269-8","article-title":"Depressed heart rate variability is associated with events in patients with stable coronary artery disease and preserved left ventricular function. REGRESS Study Group","volume":"135","author":"van Boven","year":"1998","journal-title":"Am Heart J"},{"key":"B11","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1161\/01.HYP.32.2.293","article-title":"Reduced heart rate variability and new-onset hypertension: insights into pathogenesis of hypertension: the Framingham Heart Study","volume":"32","author":"Singh","year":"1998","journal-title":"Hypertension"},{"key":"B12","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1136\/heartjnl-2011-300033","article-title":"Five-minute heart rate variability can predict obstructive angiographic coronary disease","volume":"98","author":"Kotecha","year":"2012","journal-title":"Heart"},{"key":"B13","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1007\/s00392-010-0236-5","article-title":"Heart rate variability and biomarkers of systemic inflammation in patients with stable coronary heart disease: findings from the Heart and Soul Study","volume":"100","author":"von","year":"2011","journal-title":"Clin Res Cardiol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1016\/j.jacc.2017.12.015","article-title":"Environmental noise and the cardiovascular system","volume":"71","author":"M\u00fcnzel","year":"2018","journal-title":"J Am Coll Cardiol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1038\/nature11260","article-title":"Myocardial infarction accelerates atherosclerosis","volume":"487","author":"Dutta","year":"2012","journal-title":"Nature"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1687","DOI":"10.1093\/eurheartj\/ehy913","article-title":"Depression and coronary heart disease: 2018 position paper of the ESC working group on coronary pathophysiology and microcirculation","volume":"41","author":"Vaccarino","year":"2020","journal-title":"Eur Heart J"},{"key":"B17","doi-asserted-by":"publisher","first-page":"3077","DOI":"10.1016\/j.jacc.2017.10.035","article-title":"Diagnostic accuracy of angiography-based quantitative flow ratio measurements for online assessment of coronary stenosis","volume":"70","author":"Xu","year":"2017","journal-title":"J Am Coll Cardiol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1617","DOI":"10.1016\/j.jcin.2020.04.040","article-title":"The impact of coronary physiology on contemporary clinical decision making","volume":"13","author":"Kogame","year":"2020","journal-title":"JACC Cardiovasc Interv"},{"key":"B19","doi-asserted-by":"publisher","first-page":"10289","DOI":"10.1002\/jcp.27945","article-title":"Relationship between serum high sensitivity C-reactive protein with angiographic severity of coronary artery disease and traditional cardiovascular risk factors","volume":"234","author":"Tajfard","year":"2019","journal-title":"J Cell Physiol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1093\/ije\/dyq165","article-title":"Wodd Health Organization definition of myocardial infarction:2008\u201309 revision","volume":"40","author":"Mendis","year":"2011","journal-title":"Int J Epidemiol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"364","DOI":"10.3389\/fphys.2013.00364","article-title":"Short-term vs. long-term heart rate variability in ischemic cardiomyopathy risk stratification","volume":"4","author":"Voss","year":"2013","journal-title":"Front Physiol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.bjpt.2019.02.006","article-title":"Heart rate variability: are you using it properly? Standardisation checklist of procedures","volume":"24","author":"Catai","year":"2020","journal-title":"Braz J Phys Ther"},{"key":"B23","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1515\/folmed-2015-0036","article-title":"Heart rate variability asa method for assessment of the autonomic nervous system and the adaptations to different physiological and pathological conditions","volume":"57","author":"Taralov","year":"2015","journal-title":"Folia Med."},{"key":"B24","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.pcad.2012.09.001","article-title":"Heart rate variability today","volume":"55","author":"Xhyheri","year":"2012","journal-title":"Prog Cardiovasc Dis"},{"key":"B25","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1016\/S0002-9149(83)80105-2","article-title":"A more meaningful scoring system for determining the severity of coronary heart disease","volume":"51","author":"Gensini","year":"1983","journal-title":"Am J Cardiol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"e007107","DOI":"10.1161\/CIRCIMAGING.117.007107","article-title":"Evaluation of coronary artery stenosis by quantitative flow ratio during invasive coronary angiography: the WIFI II study (Wire-Free Functional Imaging II)","volume":"11","author":"Westra","year":"2018","journal-title":"Circ Cardiovasc Imaging"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1623","DOI":"10.1001\/jamainternmed.2017.4772","article-title":"Coronary computed tomography angiography vs functional stress testing for patients with suspected coronary artery disease: a systematic review and meta-analysis","volume":"177","author":"Foy","year":"2017","journal-title":"JAMA Intern Med"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1672","DOI":"10.1016\/j.amjcard.2015.08.038","article-title":"Usefulness of coronary atheroma burden to predict cardiovascular events in patients presenting with acute coronary syndromes (from the PROSPECT study)","volume":"116","author":"Shan","year":"2015","journal-title":"Am J Cardiol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1093\/eurheartj\/ehx458","article-title":"Clinical implications of three-vessel fractional flow reserve measurement in patients with coronary artery disease","volume":"39","author":"Lee","year":"2018","journal-title":"Eur Heart J"},{"key":"B30","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1111\/j.1542-474X.2007.00164.x","article-title":"C-reactive protein is associated with heart rate variability","volume":"12","author":"Madsen","year":"2007","journal-title":"Ann Noninvasive Electrocardiol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"e014540","DOI":"10.1161\/JAHA.119.014540","article-title":"Heart rate variability for risk assessment of myocardial ischemia in patients without known coronary artery disease: the HRV-DETECT (Heart Rate Variability for the Detection of Myocardial Ischemia) study","volume":"8","author":"Goldenberg","year":"2019","journal-title":"J Am Heart Assoc"},{"key":"B32","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.bbi.2019.03.009","article-title":"Heart rate variability and inflammation: a meta-analysis of human studies","volume":"80","author":"Williams","year":"2019","journal-title":"Brain Behav Immun"},{"key":"B33","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.cmpb.2015.08.007","article-title":"Generalized discriminant analysis for congestive heart failure risk assessment based on longterm heart rate variability","volume":"122","author":"Shahbazi","year":"2015","journal-title":"Comput Methods Progr Biomed"},{"key":"B34","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1109\/JBHI.2013.2244902","article-title":"Classifcation tree for risk assessment in patients sufering from congestive heart failure via long-term heart rate variability","volume":"17","author":"Melillo","year":"2013","journal-title":"IEEE J Biomed Health Inform"},{"key":"B35","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1007\/BF02291354","article-title":"Detection of serious bradyarrhythmias in Guillain-Barre syndrome: sensitivity and specifcity of the 24-h heart rate power spectrum","volume":"10","author":"Flachenecker","year":"2000","journal-title":"Clin Auton Res"},{"key":"B36","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1007\/s11517-010-0728-5","article-title":"Discrimination power of long-term heart rate variability measures for chronic heart failure detection","volume":"49","author":"Melillo","year":"2011","journal-title":"Med Biol Eng Comput"},{"key":"B37","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1016\/S0002-9149(97)89199-0","article-title":"Short- and long-term assessment of heart rate variability for risk stratifcation after acute myocardial infarction","volume":"1996","author":"Fei","year":"1996","journal-title":"Am J Cardiol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/s12938-018-0490-8","article-title":"A new approach for analysis of heart rate variability and QT variability in long-term ECG recording","volume":"17","author":"Wu","year":"2018","journal-title":"Biomed Eng Online"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1161\/01.CIR.102.11.1239","article-title":"Low heart rate variability in a 2-minute rhythm strip predicts risk of coronary heart disease and mortality from several causes: the ARIC Study. Atherosclerosis Risk In Communities","volume":"102","author":"Dekker","year":"2000","journal-title":"Circulation"},{"key":"B40","doi-asserted-by":"publisher","first-page":"2171","DOI":"10.1113\/JP270063","article-title":"Differing autonomic responses to dobutamine stress in the presence and absence of myocardial ischaemia","volume":"593","author":"Sharma","year":"2015","journal-title":"J Physiol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.atherosclerosis.2010.01.029","article-title":"Elevated heart rate and cardiovascular outcomes in patients with coronary artery disease: clinical evidence and pathophysiological mechanisms","volume":"212","author":"Lang","year":"2010","journal-title":"Atherosclerosis"},{"key":"B42","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1714\/1820.19824","article-title":"Heart rate modulation in stable ischemic heart disease: what we have learned from the SIGNIFY study?","volume":"16","author":"Perna","year":"2015","journal-title":"G Ital Cardiol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1056\/NEJMoa1707914","article-title":"Antiinflammatory therapy with canakinumab for atherosclerotic disease","volume":"377","author":"Ridker","year":"2017","journal-title":"N Engl J Med"},{"key":"B44","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1172\/JCI88884","article-title":"Therapeutic approaches targeting inflammation for diabetes and associated cardiovascular risk","volume":"127","author":"Goldfine Allison","year":"2017","journal-title":"J Clin Invest"},{"key":"B45","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.jjcc.2018.06.002","article-title":"Clinical impact of high-sensitivity C-reactive protein during follow-up on long-term adverse clinical outcomes in patients with coronary artery disease treated with percutaneous coronary intervention","volume":"73","author":"Shitara","year":"2019","journal-title":"J Cardiol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.ijcard.2018.10.029","article-title":"Clinical utility of circulating interleukin-6 concentrations in the detection of functionally relevant coronary artery disease","volume":"275","author":"Walter","year":"2019","journal-title":"Int J Cardiol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1007\/s00392-018-1387-z","article-title":"Plasma interleukin 6 levels are associated with cardiac function after ST-elevation myocardial infarction","volume":"108","author":"Groot","year":"2019","journal-title":"Clin Res Cardiol"},{"key":"B48","doi-asserted-by":"publisher","first-page":"2654","DOI":"10.1016\/j.jacc.2011.08.055","article-title":"High-sensitivity C-reactive protein is within normal levels at the very onset of first ST-segment elevation acute myocardial infarction in 41% of cases: a multiethnic case-control study","volume":"58","author":"Cristell","year":"2011","journal-title":"J Am Coll Cardiol"},{"key":"B49","doi-asserted-by":"publisher","first-page":"1511","DOI":"10.1016\/j.jcin.2017.04.036","article-title":"Low-level tragus stimulation for the treatment of ischemia and reperfusion injury in patients with ST-segment elevation myocardial infarction: a proof-of-concept study","volume":"10","author":"Yu","year":"2017","journal-title":"JACC-Cardiovasc Interv"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2021.700943\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T16:07:53Z","timestamp":1627402073000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2021.700943\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,27]]},"references-count":49,"alternative-id":["10.3389\/fcvm.2021.700943"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2021.700943","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,27]]},"article-number":"700943"}}