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Coronary Artery Disease: HELP
Articles by Amir Lerman
Based on 98 articles published since 2008
(Why 98 articles?)
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Between 2008 and 2019, A. Lerman wrote the following 98 articles about Coronary Artery Disease.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4
1 Guideline Tissue characterisation using intravascular radiofrequency data analysis: recommendations for acquisition, analysis, interpretation and reporting. 2009

García-García, Héctor M / Mintz, Gary S / Lerman, Amir / Vince, D Geoffrey / Margolis, M Paulina / van Es, Gerrit-Anne / Morel, Marie-Angèle M / Nair, Anuja / Virmani, Renu / Burke, Allen P / Stone, Gregg W / Serruys, Patrick W. ·Thoraxcenter, Erasmus Medical Center, Rotterdam, The Netherlands. ·EuroIntervention · Pubmed #20449928.

ABSTRACT: This document suggests standards for the acquisition, measurement, and reporting of radiofrequency data analysis (virtual histology - VH) intravascular ultrasound (IVUS) studies. Readers should view this document as the authors' best attempt in an area of rapidly evolving investigation, an area where rigorous evidence is not yet available or widely accepted. Nevertheless, this document is based on known pathologic data as well as previously reported imaging data; where practical, this data is summarised in the current document, a document which will also include recommendations for future evolution of the technology.

2 Editorial MicroRNAs: small molecule, big potential for coronary artery disease. 2016

Widmer, R Jay / Lerman, Lilach O / Lerman, Amir. ·Division of Cardiovascular Disease, Mayo Clinic, Rochester, MN, USA. · Division of Cardiovascular Disease, Mayo Clinic, Rochester, MN, USA lerman.amir@mayo.edu. ·Eur Heart J · Pubmed #26994151.

ABSTRACT: -- No abstract --

3 Review Targeting the dominant mechanism of coronary microvascular dysfunction with intracoronary physiology tests. 2017

Mejía-Rentería, Hernán / van der Hoeven, Nina / van de Hoef, Tim P / Heemelaar, Julius / Ryan, Nicola / Lerman, Amir / van Royen, Niels / Escaned, Javier. ·Hospital Clínico Universitario San Carlos, 28040, Madrid, Spain. · Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain. · VU University Medical Centre, Amsterdam, The Netherlands. · AMC Heart Centre, Academic Medical Centre, Amsterdam, The Netherlands. · Mayo Clinic, Rochester, MN, USA. · Hospital Clínico Universitario San Carlos, 28040, Madrid, Spain. escaned@secardiologia.es. · Universidad Complutense de Madrid (UCM), Madrid, Spain. escaned@secardiologia.es. · Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain. escaned@secardiologia.es. ·Int J Cardiovasc Imaging · Pubmed #28501910.

ABSTRACT: The coronary microcirculation plays a key role in modulating blood supply to the myocardium. Several factors like myocardial oxygen demands, endothelial and neurogenic conditions determine its function. Although there is available evidence supporting microvascular dysfunction as an important cause of myocardial ischaemia, with both prognostic and symptomatic implications, its diagnosis and management in clinical practice is still relegated to a second plane. Both diagnostic and therapeutic approaches are hampered by the broadness of the concept of microvascular dysfunction, which fails addressing the plurality of mechanisms leading to dysfunction. Normal microcirculatory function requires both structural integrity of the microcirculatory vascular network and preserved signalling pathways ensuring adequate and brisk arteriolar resistance shifts in response to myocardial oxygen demands. Pathological mechanisms affecting these requirements include structural remodelling of microvessels, intraluminal plugging, extravascular compression or vasomotor dysregulation. Importantly, not every diagnostic technique provides evidence on which of these pathophysiological mechanisms is present or predominates in the microcirculation. In this paper we discuss the mechanisms of coronary microvascular dysfunction and the intracoronary tools currently available to detect it, as well as the potential role of each one to unmask the main underlying mechanism.

4 Review Cardiac shock-wave therapy in the treatment of coronary artery disease: systematic review and meta-analysis. 2017

Burneikaitė, Greta / Shkolnik, Evgeny / Čelutkienė, Jelena / Zuozienė, Gitana / Butkuvienė, Irena / Petrauskienė, Birutė / Šerpytis, Pranas / Laucevičius, Aleksandras / Lerman, Amir. ·Clinic of Cardiac and Vascular Diseases, Faculty of Medicine, Vilnius University, Vilnius, Lithuania. gburneikaite@gmail.com. · Centre of Cardiology and Angiology, Vilnius University Hospital Santariskiu Klinikos, Vilnius, Lithuania. gburneikaite@gmail.com. · , Room No A311, Santariskiu str. 2, 08661, Vilnius, Lithuania. gburneikaite@gmail.com. · Moscow State University of Medicine and Dentistry, Moscow, Russia. · Yale- New Haven Health Bridgeport Hospital, Connecticut, United States of America. · Clinic of Cardiac and Vascular Diseases, Faculty of Medicine, Vilnius University, Vilnius, Lithuania. jelena.celutkiene@santa.lt. · Centre of Cardiology and Angiology, Vilnius University Hospital Santariskiu Klinikos, Vilnius, Lithuania. jelena.celutkiene@santa.lt. · Clinic of Cardiac and Vascular Diseases, Faculty of Medicine, Vilnius University, Vilnius, Lithuania. · Centre of Cardiology and Angiology, Vilnius University Hospital Santariskiu Klinikos, Vilnius, Lithuania. · Centre of Innovative Medicine, Vilnius, Lithuania. · Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, United States of America. ·Cardiovasc Ultrasound · Pubmed #28403861.

ABSTRACT: AIM: To systematically review currently available cardiac shock-wave therapy (CSWT) studies in humans and perform meta-analysis regarding anti-anginal efficacy of CSWT. METHODS: The Cochrane Controlled Trials Register, Medline, Medscape, Research Gate, Science Direct, and Web of Science databases were explored. In total 39 studies evaluating the efficacy of CSWT in patients with stable angina were identified including single arm, non- and randomized trials. Information on study design, subject's characteristics, clinical data and endpoints were obtained. Assessment of publication risk of bias was performed and heterogeneity across the studies was calculated by using random effects model. RESULTS: Totally, 1189 patients were included in 39 reviewed studies, with 1006 patients treated with CSWT. The largest patient sample of single arm study consisted of 111 patients. All selected studies demonstrated significant improvement in subjective measures of angina symptoms and/or quality of life, in the majority of studies left ventricular function and myocardial perfusion improved. In 12 controlled studies with 483 patients included (183 controls) angina class, Seattle Angina Questionnaire (SAQ) score, nitrates consumption were significantly improved after the treatment. In 593 participants across 22 studies the exercise capacity was significantly improved after CSWT, as compared with the baseline values (in meta-analysis standardized mean difference SMD = -0.74; 95% CI, -0.97 to -0.5; p < 0.001). CONCLUSIONS: Systematic review of CSWT studies in stable coronary artery disease (CAD) demonstrated consistent improvement of clinical variables. Meta-analysis showed a moderate improvement of exercise capacity. Overall, CSWT is a promising non-invasive option for patients with end-stage CAD, but evidence is limited to small sample single-center studies. Multi-center adequately powered randomised double blind studies are warranted.

5 Review Use of fractional flow reserve in patients with coronary artery disease: The right choice for the right outcome. 2017

Park, Jae Yoon / Lerman, Amir / Herrmann, Joerg. ·Department of Cardiovascular Diseases, Mayo Clinic, 200 First St. SW, Rochester, MN 55905. · Department of Cardiovascular Diseases, Mayo Clinic, 200 First St. SW, Rochester, MN 55905. Electronic address: herrmann.joerg@mayo.edu. ·Trends Cardiovasc Med · Pubmed #27461526.

ABSTRACT: Despite advances in therapy, coronary artery disease (CAD) remains the leading cause of morbidity and mortality worldwide. Over the past years, the utilization of revascularization procedures has been refined, and in the best interest of the patient and to reduce the healthcare burden of CAD, it is paramount that patients are appropriately selected for therapies aiming at improving their symptoms and prognosis. Fractional flow reserve (FFR) is the current invasive standard test to identify hemodynamically significant coronary artery stenoses with resultant implications for revascularization and clinical outcomes. In this review, we discuss the current evidence behind the use of FFR as well as new trends in the application of this technique to help guide clinicians in making the best management decisions for patients with CAD.

6 Review Clinical implications of intracoronary imaging in cardiac allograft vasculopathy. 2015

Guddeti, Raviteja R / Matsuo, Yoshiki / Matsuzawa, Yasushi / Aoki, Tatsuo / Lerman, Lilach O / Kushwaha, Sudhir S / Lerman, Amir. ·From the Division of Cardiovascular Diseases, Mayo College of Medicine, Rochester, MN (R.R.G., Y.M., Y.M., T.A., S.S.K., A.L.) · and Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN (L.O.L.). ·Circ Cardiovasc Imaging · Pubmed #25596140.

ABSTRACT: -- No abstract --

7 Review Endothelial dysfunction and coronary artery disease: assessment, prognosis, and treatment. 2014

Matsuzawa, Yasushi / Lerman, Amir. ·Department of Internal Medicine, Division of Cardiovascular Diseases, Mayo College of Medicine, Rochester, Minnesota, USA. ·Coron Artery Dis · Pubmed #25365643.

ABSTRACT: Progress in the modification of conventional coronary risk factors and lifestyle behavior has reduced the incidence of atherosclerotic coronary artery disease; nonetheless, it continues to be the leading cause of mortality in the world. This might be attributed to the defective risk stratifying and prevention strategy for coronary artery disease. In the current clinical setting, atherosclerotic coronary artery disease risk is estimated on the basis of identifying and quantifying only traditional risk factors; it does not take into consideration nontraditional risk factors. In addition, most of the prevailing therapies for atherosclerosis are targeted toward traditional risk factors rather than atherosclerosis itself. It is desirable to develop a method that can directly assess the activity of atherogenesis at every moment. Endothelial function is an integrated index of all atherogenic and atheroprotective factors present in an individual including nontraditional factors and heretofore unknown factors, and it is reported to have additional predictive value for future cardiovascular events to traditional risk factors. Moreover, endothelial function has a pivotal role in all phases of atherosclerosis, from initiation to atherothrombotic complication, and is reversible at every phase, indicating that endothelial function-guided therapies might be effective and feasible in cardiovascular practice. Thus, the introduction of endothelial function testing into clinical practice might enable us to innovate individualized cardiovascular medicine. In this review, we summarize the current knowledge on the contribution of endothelial dysfunction to atherogenesis and review the methods that assess endothelial function. Finally, we focus on the effects of major antiatherosclerotic disease therapies on endothelial function and argue the possibility of noninvasive assessment of endothelial function aiming at individualized cardiovascular medicine.

8 Review Endothelial dysfunction over the course of coronary artery disease. 2013

Gutiérrez, Enrique / Flammer, Andreas J / Lerman, Lilach O / Elízaga, Jaime / Lerman, Amir / Fernández-Avilés, Francisco. ·Servicio de Cardiología, Instituto de Investigación Sanitaria, Hospital General Universitario Gregorio Marañón, Madrid, Spain. ·Eur Heart J · Pubmed #24014385.

ABSTRACT: The vascular endothelium regulates blood flow in response to physiological needs. Endothelial dysfunction is closely related to atherosclerosis and its risk factors, and it constitutes an intermediate step on the progression to adverse events throughout the natural history of coronary artery disease (CAD), often affecting clinical outcomes. Understanding the relation of endothelial function with CAD provides an important pathophysiological insight, which can be useful both in clinical and research management. In this review, we summarize the current knowledge on endothelial dysfunction and its prognostic influence throughout the natural history of CAD, from early atherosclerosis to post-transplant management.

9 Review Lipoprotein-associated phospholipase A2: a risk marker or a risk factor? 2008

Lerman, Amir / McConnell, Joseph P. ·Division of Cardiovascular Diseases, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. lerman.amir@mayo.edu ·Am J Cardiol · Pubmed #18549867.

ABSTRACT: Multiple cardiovascular biomarkers are associated with increased cardiovascular disease (CVD) risk. Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) appears to be relatively unique in its high specificity for and the causal pathway of plaque inflammation. In both primary and secondary prevention study populations, Lp-PLA(2) was consistently associated with higher cardiovascular risk, and the risk estimate appears to be relatively unaffected by adjustment for conventional CVD risk factors. Risk ratios were similar, whether the mass concentration or activity of the enzyme was measured. The purpose of this article is to review the evidence for the clinical utility of Lp-PLA(2), both as a risk marker and as a risk factor involved in the causal pathway of plaque inflammation and the formation of rupture-prone plaque.

10 Clinical Trial Chronic inhibition of lipoprotein-associated phospholipase A 2018

Prasad, Megha / Lennon, Ryan / Barsness, Gregory W / Prasad, Abhiram / Gulati, Rajiv / Lerman, Lilach O / Lerman, Amir. ·Mayo Clinic, Department of Cardiovascular Diseases, Rochester, MN, United States. · Mayo Clinic, Department of Health Sciences Research, Rochester, MN, United States. · Mayo Clinic, Department of Cardiovascular Diseases, Rochester, MN, United States. Electronic address: lerman.amir@mayo.edu. ·Int J Cardiol · Pubmed #29306475.

ABSTRACT: AIMS: Lipoprotein-associated phospholipase A METHODS AND RESULTS: Fifty-four patients with CED were enrolled in a double-blinded randomized placebo-controlled trial, and were randomized to receive oral darapladib, 160mg daily, or placebo. Coronary angiography and invasive coronary endothelial function assessment were performed at baseline and post-6months of treatment. Primary endpoints were change in coronary artery diameter and coronary blood flow in response to acetylcholine. Additionally, Lp-PLA DISCUSSION: Lp-PLA GOV IDENTIFIER: NCT01067339.

11 Clinical Trial Long-term darapladib use does not affect coronary plaque composition assessed using multimodality intravascular imaging modalities: a randomized-controlled study. 2018

Choi, Woong Gil / Prasad, Megha / Lennon, Ryan / Gulati, Rajiv / Prasad, Abhiram / Lerman, Lilach O / Lerman, Amir. ·Department of Cardiovascular Diseases. · Division of Cardiology, Department of Internal Medicine, Konkuk University College of Medicine, Chungbuk, Korea. · Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA. ·Coron Artery Dis · Pubmed #29135482.

ABSTRACT: BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) may play a role in plaque progression and vulnerability. We aimed to define plaque characteristics on multimodality intravascular imaging in patients with coronary endothelial dysfunction in response to long-term inhibition of Lp-PLA2 by darapladib. PATIENTS AND METHODS: This is a double-blinded, randomized study screening 70 patients, and enrolling 54 patients with suspected ischemia, without obstructive disease on angiography and with coronary endothelial dysfunction by invasive assessment. Patients were randomized to receive darapladib or placebo for 6 months. Forty patients underwent multimodality intravascular imaging at baseline and after 6 months of therapy. Several parameters of plaque vulnerability were measured, including maximum value of lipid core burden index for any of the 4-mm segment (maxLCBI4 mm) by near-infrared spectroscopy. Microchannels and macrophages were assessed using optical coherence tomography and necrotic core volume by virtual histology intravascular ultrasound. RESULTS: There was no significant difference in maxLCBI4 mm [64.56 (7.74, 128.56) vs. 22.43 (0, 75.63), P=0.522] or in macrophage images angle [-9.5° (-25.53°, 12.68°) vs. -16.7° (-28.6°, -4.8°), P=0.489] between groups. There was a trend toward shorter microchannel length in the darapladib arm [0, (-4.4, 0.2) mm vs. 0.8 (-0.15, 1.9) mm, P=0.08]. Percentage of necrotic core volume was not significantly different. CONCLUSION: Thus, long-term inhibition of endogenous Lp-PLA2 activity with darapladib was not associated with a change in plaque progression and vulnerability indices after 6 months of therapy, and the endogenous Lp-PLA2 pathway may not play a direct role in the progression of early atherosclerosis in humans.

12 Article Coronary microvascular dysfunction is associated with poor glycemic control amongst female diabetics with chest pain and non-obstructive coronary artery disease. 2019

Sara, Jaskanwal D / Taher, Riad / Kolluri, Nikhil / Vella, Adrian / Lerman, Lilach O / Lerman, Amir. ·Division of Cardiovascular Diseases and Department of Internal Medicine, Mayo College of Medicine, 200 First Street SW, Rochester, MN, 55905, USA. · Internal Medicine Department and Department of Endocrinology, Rambam HealthCare Campus, Haifa, Israel. · Division of Internal Medicine, Mayo College of Medicine, Rochester, MN, USA. · Division of Diabetes and Endocrinology, Mayo Clinic, Rochester, MN, USA. · Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA. · Division of Cardiovascular Diseases and Department of Internal Medicine, Mayo College of Medicine, 200 First Street SW, Rochester, MN, 55905, USA. lerman.amir@mayo.edu. ·Cardiovasc Diabetol · Pubmed #30819191.

ABSTRACT: BACKGROUND: Patients with type 2 diabetes mellitus are at an increased risk of adverse cardiovascular events compared to those without diabetes. The timing, relative to disease onset, and degree of glycemic control that reduces the risk of adverse cardiovascular events remains uncertain. Coronary microvascular dysfunction is prevalent in patients with type 2 diabetes mellitus and is linked to adverse cardiovascular events. We assessed the association between endothelial-dependent and endothelial-independent coronary microvascular dysfunction and glycemic control in patients presenting with chest pain and nonobstructive coronary disease at angiography. METHODS: Patients presenting with chest pain and found to have non-obstructive CAD (stenosis < 40%) at angiography underwent an invasive assessment of endothelial-independent and endothelial -dependent microvascular function. Endothelial-independent microvascular function was assessed by comparing the coronary flow velocity, measured using a Doppler guidewire, in response to intracoronary infusion of adenosine to calculate the coronary flow reserve ratio in response to adenosine (CFRAdn Ratio). A CFRAdn Ratio ≤ 2.5 was considered abnormal. Endothelial-dependent microvascular function was assessed by measuring the percent change in coronary blood flow in response to intracoronary infusions of acetylcholine (%ΔCBFAch), and microvascular endothelial dysfunction defined as a %ΔCBFAch of ≤ 50%. Patients were classified by normal versus abnormal CFRAdn Ratio and %ΔCBFAch. Measurements of HbA1c and fasting serum glucose were obtained prior to catheterization and compared between groups. RESULTS: Between 1993 and 2012, 1469 patients (mean age 50.4 years, 35% male) underwent coronary angiography and invasive testing for coronary microvascular dysfunction, of which 129 (8.8%) had type 2 diabetes. Fifty-one (39.5%) had an abnormal %ΔCBFAch and 49 (38.0%) had an abnormal CFRAdn Ratio. Conventional cardiovascular risk factors and cardiovascular or diabetic medication use did not vary significantly between groups. Females with an abnormal CFRAdn Ratio or abnormal %ΔCBFAch had a significantly higher HbA1c compared to patients with a normal CFRAdn Ratio or %ΔCBFAch respectively: HbA1c % (standard deviation) 7.4 (2.1) vs. 6.5 (1.1), p = 0.035 and 7.3 (1.9) vs. 6.4 (1.2), p = 0.022, respectively. Female patients with an abnormal CFRAdn Ratio had significantly higher fasting serum glucose concentrations compared to those with a normal CFRAdn Ratio: fasting serum glucose mg/dL (standard deviation) 144.4 (55.6) vs. 121.9 (28.1), p = 0.035. This was not observed in men. Amongst female diabetics, a higher HbA1c was significantly associated with any coronary microvascular dysfunction both in a univariate and multivariate analysis: odds ratio (95% confidence interval) 1.69 (1.01-2.86) p = 0.049; and a fasting serum glucose > 140 mg/dL was significantly associated with an abnormal CFRAdn Ratio, 4.28 (1.43-12.81). CONCLUSION: Poor glycemic control is associated with coronary microvascular dysfunction amongst female diabetics presenting with chest pain and non-obstructive CAD. These findings highlight the importance of sex specific risk stratification models and treatment strategies when managing cardiovascular risk amongst diabetics. Further studies are required to identify additional risk prevention tools and therapies targeting microvascular dysfunction as an integrated index of cardiovascular risk.

13 Article Voice Signal Characteristics Are Independently Associated With Coronary Artery Disease. 2018

Maor, Elad / Sara, Jaskanwal D / Orbelo, Diana M / Lerman, Lilach O / Levanon, Yoram / Lerman, Amir. ·Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN. · Department of Otorhinolaryngology, Mayo Clinic, Rochester, MN. · Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN. · Beyond Verbal Communications, Tel Aviv, Israel. · Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN. Electronic address: Lerman.Amir@mayo.edu. ·Mayo Clin Proc · Pubmed #29656789.

ABSTRACT: OBJECTIVE: Voice signal analysis is an emerging noninvasive diagnostic tool. The current study tested the hypothesis that patient voice signal characteristics are associated with the presence of coronary artery disease (CAD). METHODS: The study population included 138 patients who were enrolled between January 1, 2015, and February 28, 2017: 37 control subjects and 101 subjects who underwent planned coronary angiogram. All subjects had their voice signal recorded to their smartphone 3 times: reading a text, describing a positive emotional experience, and describing a negative emotional experience. The Mel Frequency Cepstral Coefficients were used to extract prespecified voice features from all 3 recordings. Voice was recorded before the angiogram and analysis was blinded with respect to patient data. RESULTS: Final study cohort included 101 patients, of whom 71 (71%) had CAD. Compared with subjects without CAD, patients with CAD were older (median, 63 years; interquartile range [IQR], 55-68 years vs median, 53 years; IQR, 42-66 years; P=.003) and had a higher 10-year atherosclerotic cardiovascular disease (ASCVD) risk score (9.4%; IQR, 5.0-18.7 vs 2.7%; IQR, 1.6-11.8; P=.005). Univariate binary logistic regression analysis identified 5 voice features that were associated with CAD (P<.05 for all). Multivariate binary logistic regression with adjustment for ASCVD risk score identified 2 voice features that were independently associated with CAD (odds ratio [OR], 0.37; 95% CI, 0.18-0.79; and 4.01; 95% CI, 1.25-12.84; P=.009 and P=.02, respectively). Both features were more strongly associated with CAD when patients were asked to describe an emotionally significant experience. CONCLUSION: This study suggests a potential relationship between voice characteristics and CAD, with clinical implications for telemedicine-when clinical health care is provided at a distance.

14 Article [ENDOTHELIAL DYSFUNCTION: A POSITION PAPER OF THE ISRAEL HEART SOCIETY]. 2018

Shechter, Michael / Amir, Ofer / Lerman, Amir / Shemesh, Joseph / Maor, Elad / Rubinshtein, Ronen. ·Israel Heart Society. ·Harefuah · Pubmed #29484870.

ABSTRACT: INTRODUCTION: Prediction of cardiovascular adverse events is challenging. It became apparent that traditional coronary artery disease (CAD) risk factors are the cornerstones of the European 10-year CAD risk SCRORE and the Framingham score. However, despite their importance, the prediction value of general assessment tools such as the SCORE and Framingham options in an individual subject is limited, especially in young adults and women. The trend toward personalized medicine and individualized risk assessment during recent years is growing strong and various functional and imaging screening tests, including endothelial function studies, have been suggested to improve accuracy and provide the functional implications of these risk factors. Endothelial dysfunction is an early stage of atherosclerosis and has been associated with adverse cardiovascular outcome events, including myocardial infarction, stroke and death. The purpose of this position paper is to review the scientific background, methods available for assessment of endothelial function and the interpretation of test results. The current manuscript also suggest some meaningful clinical guidelines on potential integration of these tests into our practice.

15 Article Downregulation of circulating MOTS-c levels in patients with coronary endothelial dysfunction. 2018

Qin, Qing / Delrio, Silvia / Wan, Junxiang / Jay Widmer, R / Cohen, Pinchas / Lerman, Lilach O / Lerman, Amir. ·Department of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA; Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University, Shanghai 200032, China. · Università Vita-Salute San Raffaele, via Olgettina 58, 20132 Milan, Italy. · Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA. · Department of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. · Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. · Department of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. Electronic address: Lerman.amir@mayo.edu. ·Int J Cardiol · Pubmed #29242099.

ABSTRACT: BACKGROUND: MOTS-c is one of the newly identified mitochondrial-derived peptides which play a role in regulating metabolic homeostasis. The current study aimed to investigate whether circulating MOTS-c levels are also associated with endothelial dysfunction(ED) in patients without significant structural coronary lesions. METHODS: Forty patients undergoing coronary angiography and endothelial function testing for clinical indications of recurrent angina with no structural coronary lesions were included in the study. They were divided into two groups based on coronary blood flow response to intracoronary acetylcholine (ACh) as normal endothelial function (≥ 50% increase from baseline) or ED, (n=20 each). Aortic plasma samples were collected at the time of catheterization for analysis of circulating MOTS-c levels by ELISA. The effect of MOTS-c on vascular reactivity was assessed in organ chambers using aortic rings collected from rats and renal artery stenosis (RAS) mice. RESULTS: Baseline characteristics were similar between the two groups. MOTS-c plasma levels were lower in patients with ED compared with patients with normal endothelial function (p=0.007). Furthermore, plasma MOTS-c levels were positively correlated with microvascular (p=0.01) and epicardial (p=0.02) coronary endothelial function. Although MOTS-c did not have direct vasoactive effects, pretreating aortic rings from rats or RAS mice with MOTS-c (2μg/ml) improved vessel responsiveness to ACh compared with vessels without MOTS-c treatment. CONCLUSION: Lower circulating endogenous MOTS-c levels in human subjects are associated with impaired coronary endothelial function. In rodents, MOTS-c improves endothelial function in vitro. Thus, MOTS-c represents a novel potential therapeutic target in patients with ED.

16 Article Mitoprotection attenuates myocardial vascular impairment in porcine metabolic syndrome. 2018

Yuan, Fang / Hedayat, Ahmad F / Ferguson, Christopher M / Lerman, Amir / Lerman, Lilach O / Eirin, Alfonso. ·Division of Nephrology and Hypertension, Mayo Clinic , Rochester, Minnesota. · Department of Cardiology, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital , Henan , People's Republic of China. · Department of Cardiovascular Diseases, Mayo Clinic , Rochester, Minnesota. ·Am J Physiol Heart Circ Physiol · Pubmed #29196345.

ABSTRACT: Metabolic syndrome (MetS) leads to cardiac vascular injury, which may reflect in increased retention of endothelial progenitor cells (EPCs). Coronary endothelial cell (EC) mitochondria partly regulate vascular function and structure. We hypothesized that chronic mitoprotection would preserve EC mitochondria and attenuate coronary vascular injury and dysfunction in swine MetS. Pigs were studied after 16 wk of diet-induced MetS, MetS treated for the last 4 wk with the mitochondria-targeted peptide elamipretide (ELAM; 0.1 mg/kg sc once daily), and lean controls ( n = 6 each). Cardiac remodeling and function were assessed in vivo by multidetector-computed tomography (CT), and coronary artery and sinus blood samples were collected. EC mitochondrial density, apoptosis, oxidative stress, endothelial nitric oxide synthase immunoreactivity, myocardial microvascular density (three-dimensional microcomputed tomography), and coronary endothelial function (organ bath) were assessed ex vivo. The number and arteriovenous gradient of CD34

17 Article Mental stress peripheral vascular reactivity is elevated in women with coronary vascular dysfunction: Results from the NHLBI-sponsored Cardiac Autonomic Nervous System (CANS) study. 2018

Mehta, Puja K / Hermel, Melody / Nelson, Michael D / Cook-Wiens, Galen / Martin, Elizabeth A / Alkhoder, Ayman A / Wei, Janet / Minissian, Margo / Shufelt, Chrisandra L / Marpuri, Sailaja / Hermel, David / Shah, Amit / Irwin, Michael R / Krantz, David S / Lerman, Amir / Noel Bairey Merz, C. ·Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA, United States. Electronic address: pkmehta@emory.edu. · Barbra Streisand Women's Heart Center, Cedars-Sinai Heart Institute, Los Angeles, CA, United States. · Biostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, Los Angeles, CA, United States. · Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA, United States. · Department of Epidemiology, Rollins School of Public Health, Emory University, United States. · Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience, David Geffen SOM at UCLA, United States. · Department of Medical and Clinical Psychology, Uniformed Services University, Bethesda, MD, United States. · Cardiovascular Diseases, Mayo Clinic, Rochester, MN, United States. ·Int J Cardiol · Pubmed #29103858.

ABSTRACT: BACKGROUND: Women with chest pain, ischemia, and no obstructive coronary artery disease often have coronary vascular dysfunction (CVaD). Peripheral vascular reactivity to mental stress may contribute mechanistic understanding of stress-induced ischemia in women with CVaD. METHODS: 62 women (41 CVaD and 21 controls) underwent mental stress testing (MST) with anger recall, mental arithmetic, and forehead cold pressor (COP) challenge. Emotional arousal was measured (Likert scale). Reactive hyperemia index (RHI) was calculated before and after MST by peripheral arterial tonometry (PAT). Stress PAT ratio (SPR) of pulse amplitude during stress to rest was obtained to measure vasoconstriction. Wilcoxson rank sum test was used for analysis. RESULTS: Mean age of CVaD and control groups was 58±9 and 55±10years (p=0.73). Baseline RHI correlated with coronary endothelial function (r=0.36, p=0.03) and inversely with RHI change post-MST (r=-0.51, p<0.001). During MST, 10% of controls reported chest pain vs. 41% of CVaD subjects (p=0.01). RHI did not change significantly after MST in either group. CVaD subjects had lower SPR vs. controls during mental arithmetic (0.54 [0.15, 1.46] vs. 0.67 [0.36, 1.8], p=0.039), not evident in the other tasks. Vasoconstriction inversely correlated with anxiety (r=-3.4, p=0.03), frustration (r=-0.37, p=0.02), and feeling challenged (r=-0.37, p=0.02) in CVaD but not controls. CONCLUSIONS: Mental stress peripheral vascular reactivity is elevated in women with CVaD compared to controls. Elevated vascular reactivity may be one contributor to stress-induced chest pain in CVaD. Interventions that modulate vasoconstrictive responses may be of benefit and should be tested in clinical trials in women with CVaD.

18 Article High-sensitivity C-reactive protein is an independent marker of abnormal coronary vasoreactivity in patients with non-obstructive coronary artery disease. 2017

Sara, Jaskanwal D S / Prasad, Megha / Zhang, Ming / Lennon, Ryan J / Herrmann, Joerg / Lerman, Lilach O / Lerman, Amir. ·Division of Cardiovascular Diseases, Mayo College of Medicine, Rochester, MN. Electronic address: Jaskanwal.sara@mayo.edu. · Division of Cardiovascular Diseases, Mayo College of Medicine, Rochester, MN. Electronic address: Prasad.megha@mayo.edu. · Division of Cardiovascular Diseases, Mayo College of Medicine, Rochester, MN. Electronic address: Zhang.ming@mayo.edu. · Division of Biomedical Statistics and Informatics, Mayo College of Medicine, Rochester, MN. Electronic address: Lennon.ryan@mayo.edu. · Division of Cardiovascular Diseases, Mayo College of Medicine, Rochester, MN. Electronic address: Herrmann.joerg@mayo.edu. · Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN. Electronic address: Lerman.lilach@mayo.edu. · Division of Cardiovascular Diseases, Mayo College of Medicine, Rochester, MN. Electronic address: Lerman.amir@mayo.edu. ·Am Heart J · Pubmed #28760202.

ABSTRACT: BACKGROUND: Coronary endothelial dysfunction (CED) is an early stage of atherosclerosis and is associated with adverse cardiovascular events. Inflammation may play a role in the development of endothelial dysfunction. To date no study has evaluated the relationship between C-reactive protein and CED. We aimed to determine if C-reactive protein is associated with CED. METHODS: In 1016 patients (mean age 50.7±12.3 years, 34% male) presenting to the catheterization laboratory with chest pain and non-obstructive coronary artery disease, coronary vasoreactivity was assessed by measuring the percent change in coronary blood flow (%ΔCBF) and coronary artery diameter (%ΔCAD) in response to intracoronary acetylcholine. Plasma high sensitivity C-reactive protein (hs-CRP) was measured and patients were divided into 2 groups: hs-CRP≤3.0 mg/L (low-intermediate cardiovascular risk n=169) and 3 mg/LHs-CRP is independently associated with and a strong predictor of abnormal coronary vasoreactivity in patients with non-obstructive coronary artery disease.

19 Article Current and Future Use of Robotic Devices to Perform Percutaneous Coronary Interventions: A Review. 2017

Maor, Elad / Eleid, Mackram F / Gulati, Rajiv / Lerman, Amir / Sandhu, Gurpreet S. ·Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN. · Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN sandhu.gurpreet@mayo.edu. ·J Am Heart Assoc · Pubmed #28739860.

ABSTRACT: -- No abstract --

20 Article Multiarterial grafts improve the rate of early major adverse cardiac and cerebrovascular events in patients undergoing coronary revascularization: analysis of 12 615 patients with multivessel disease. 2017

Locker, Chaim / Schaff, Hartzell V / Daly, Richard C / Bell, Malcolm R / Frye, Robert L / Stulak, John M / Said, Sameh M / Dearani, Joseph A / Joyce, Lyle D / Greason, Kevin L / Pochettino, Alberto / Li, Zhuo / Lennon, Ryan J / Lerman, Amir. ·Department of Cardiovascular Surgery, Mayo Clinic, Rochester, MN, USA. · Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA. · Division of Biostatistics, Mayo Clinic, Rochester, MN, USA. ·Eur J Cardiothorac Surg · Pubmed #28595326.

ABSTRACT: OBJECTIVES: Our goal was to compare the rates of in-hospital and 30-day major adverse cardiac and cerebrovascular events (MACCE) including death, stroke, myocardial infarction and repeat revascularization in patients with multivessel disease undergoing multiarterial (MultArt) coronary artery bypass grafting (CABG) with the left internal mammary artery/saphenous vein (LIMA/SV) CABG or percutaneous coronary intervention (PCI). METHODS: From 1 January 1993 to 31 December 2009, 12 615 consecutive patients underwent isolated primary CABG (n = 6667) with LIMA/SV (n = 5712) or MultArt (n = 955) or were treated by PCI (n = 5948) with balloon angioplasty (n = 1020), bare metal stent (n = 3242), and drug-eluting stent (n = 1686). We excluded patients with acute myocardial infarction. We matched the CABG group with the 3 PCI subgroups, and the PCI group with the 2 CABG subgroups. Multivariable analyses were used to evaluate the impact of CABG versus PCI and their subgroups on early MACCE. RESULTS: Unadjusted early MACCE were lower for MultArt (1.5%) than for LIMA/SV (4.5%, P < 0.001) and PCI (8.5%, P < 0.001). In matched analysis, CABG had lower early MACCE versus balloon angioplasty (4.7% vs 13.2%, P < 0.001), bare metal stent (4.3% vs 8.3%, P < 0.001), and drug-eluting stent (2.9% vs 5.5%, P = 0.008), as well as LIMA/SV versus PCI (4.6% vs 9.2%, P < 0.001) and MultArt versus PCI (1.8% vs 7.8%, P < 0.001). Stroke rate was similar in MultArt versus PCI (0.8% vs 0.3%, P = 0.18) but higher with LIMA/SV versus PCI (2.3% vs 0.4%, P < 0.001). In multivariable analysis, PCI (odds ratio 4.53, 95% confidence interval: 2.62-7.83; P < 0.001) and LIMA/SV (odds ratio 2.04, 95% confidence interval: 1.18-3.53; P < 0.011) were strong predictors of early MACCE compared with MultArt. CONCLUSIONS: MultArt confers the lowest rate of early MACCE.

21 Article Uric Acid Is Associated With Inflammation, Coronary Microvascular Dysfunction, and Adverse Outcomes in Postmenopausal Women. 2017

Prasad, Megha / Matteson, Eric L / Herrmann, Joerg / Gulati, Rajiv / Rihal, Charanjit S / Lerman, Lilach O / Lerman, Amir. ·From the Division of Cardiovascular Diseases (M.P., J.H., C.S.R., L.O.L., A.L.) and Division of Rheumatology (E.L.M.), Mayo Clinic, Rochester, MN. · From the Division of Cardiovascular Diseases (M.P., J.H., C.S.R., L.O.L., A.L.) and Division of Rheumatology (E.L.M.), Mayo Clinic, Rochester, MN. lerman.amir@mayo.edu. ·Hypertension · Pubmed #27993955.

ABSTRACT: Uric acid is a risk factor for coronary artery disease in postmenopausal women, but the association with inflammation and coronary endothelial dysfunction (CED) is not well defined. The aim of this study was to determine the relationship of serum uric acid (SUA), inflammatory markers, and CED. In this prospective cohort study, SUA, high-sensitivity C-reactive protein levels, and neutrophil count were measured in 229 postmenopausal women who underwent diagnostic catheterization, were found to have no obstructive coronary artery disease, and underwent coronary microvascular function testing, to measure coronary blood flow response to intracoronary acetylcholine. The average age was 58 years (interquartile range, 52-66 years). Hypertension was present in 48%, type 2 diabetes mellitus in 5.6%, and hyperlipidemia in 61.8%. CED was diagnosed in 59% of postmenopausal women. Mean uric acid level was 4.7±1.3 mg/dL. Postmenopausal women with CED had significantly higher SUA compared with patients without CED (4.9±1.3 versus 4.4±1.3 mg/dL; P=0.02). There was a significant correlation between SUA and percent change in coronary blood flow to acetylcholine (P=0.009), and this correlation persisted in multivariable analysis. SUA levels were significantly associated with increased neutrophil count (P=0.02) and high-sensitivity C-reactive protein levels (P=0.006) among patients with CED, but not among those without CED. SUA is associated with CED in postmenopausal women and may be related to inflammation. These findings link SUA levels to early coronary atherosclerosis in postmenopausal women.

22 Article Circulating osteogenic endothelial progenitor cell counts: new biomarker for the severity of coronary artery disease. 2017

Yang, Shi-Wei / Hennessy, Rebecca R / Khosla, Sundeep / Lennon, Ryan / Loeffler, Darrell / Sun, Tao / Liu, Zhi / Park, Kyoung-Ha / Wang, Fei-Long / Lerman, Lilach O / Lerman, Amir. ·Department of Cardiovascular Diseases, Mayo Clinic and College of Medicine, Rochester, MN 55905, USA; 12(th) Ward, Department of Cardiology, Beijing An Zhen Hospital, Capital Medical University, Beijing 100029, China; Atherosclerosis Research Center, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing 100029, China; The Key Laboratory of Remodeling-related Cardiovascular Disease, Ministry of Education, Beijing 100029, China. · Department of Cardiovascular Diseases, Mayo Clinic and College of Medicine, Rochester, MN 55905, USA. · Department of Endocrinology, Mayo Clinic and College of Medicine, Rochester, MN 55905, USA. · Department of Biomedical Statistics, Mayo Clinic and College of Medicine, Rochester, MN 55905, USA. · Department of Nephrology and Hypertension, Mayo Clinic and College of Medicine, Rochester, MN 55905, USA. · Department of Cardiovascular Diseases, Mayo Clinic and College of Medicine, Rochester, MN 55905, USA. Electronic address: lerman.amir@mayo.edu. ·Int J Cardiol · Pubmed #27836295.

ABSTRACT: BACKGROUND: There is increasing evidence implying that the early and functionally highly active circulating endothelial progenitor cell (CEPC) phenotype (CD34-/CD133+/KDR+) with osteogenic potential (OCN+) might link between vascular atherosclerotic calcification and mechanisms of bone metabolism. We sought to evaluate the early OCN+ CEPC counts as an independent biomarker for the severity of coronary artery disease (CAD). METHODS: Peripheral blood samples were drawn from 593 patients undergoing clinically indicated coronary angiography. CAD severity was assessed by the presence of significant coronary artery stenosis (CAS) as well as an ordinal categorical variable. Subjects were followed for all-cause death over a median follow-up of 40months. RESULTS: OCN+ early CEPC counts (square-root transformed) were independently associated with the presence of significant CAS [odds ratio (OR) per standard deviation (SD) increment: 1.389, 95% confidence interval [CI]: 1.131 to 1.707, p=0.002). Similar association was observed with an increase in levels of CAS (OR: 1.353, 95% CI: 1.157 to 1.582, p<0.001). There was a weak tendency between OCN+ early CEPC counts and all-cause mortality (p=0.090), whereas the highest decile of OCN+ early CEPC counts had a 2.991-fold increased risk of all-cause death (p=0.047). CONCLUSIONS: We demonstrate for the first time an independent, significant, and strong correlation between OCN+ early CEPC counts and CAD severity. Additionally, very high numbers of OCN+ early CEPC tend to be linked to the risk of all-cause mortality.

23 Article Relationship between markers of plaque vulnerability in optical coherence tomography and atherosclerotic progression in adult patients with heart transplantation. 2017

Park, Kyoung-Ha / Sun, Tao / Liu, Zhi / Yang, Shi-Wei / Lennon, Ryan J / Lerman, Lilach O / Kushwaha, Sudhir S / Lerman, Amir. ·Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA; Division of Cardiovascular Disease, Hallym University Medical Center, Anyang, Korea. · Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA. · Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, USA. · Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA. · Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA. Electronic address: lerman.amir@mayo.edu. ·J Heart Lung Transplant · Pubmed #27461884.

ABSTRACT: BACKGROUND: Cardiac allograft vasculopathy (CAV) is an accelerated form of coronary artery disease, and optical coherence tomography (OCT) provides detailed microstructural information. The current study was designed to test the hypothesis that markers of plaque vulnerability derived from OCT could predict CAV progression after heart transplantation (HTx). METHODS: In 34 consecutive patients (median 3.1 years from HTx), intravascular ultrasound (IVUS) and OCT were performed in the left anterior descending artery (LAD) during routine annual coronary angiography. The presence of vulnerability markers, such as lipid pools, thin-cap fibroatheroma, macrophages and microchannels, was assessed in 100 consecutive frames of OCT in 20-mm segments of proximal LAD. The total number of appearances of vulnerable markers was defined as the vulnerability score (VS). Plaque volume (PV) was measured in the same study segment using IVUS at baseline and at 1-year follow-up, and the association between the baseline VS and the subsequent change in percent PV (PV / vessel volume × 100 [%PV]) was evaluated. RESULTS: Follow-up IVUS study was conducted after 12.5 ± 1.3 months. The mean VS was 59.9 ± 44.6. Compared with the initial %PV, the follow-up %PV increased in the study segment (25.6 ± 13.7% to 31.8 ± 17.5%, p < 0.001). The correlations between baseline VS and Δ%PV were significant in the study segment (r = 0.757, p < 0.001). On multivariable analysis, only the VS correlated significantly with Δ%PV. CONCLUSIONS: Our results demonstrate that the markers of plaque vulnerability in OCT can predict the progression of CAV. Therefore, in patients with HTx, OCT may aid in determining prognosis and guiding therapy related to CAV.

24 Article Effect of Low-Dose Rapamycin on Senescence Markers and Physical Functioning in Older Adults with Coronary Artery Disease: Results of a Pilot Study. 2016

Singh, M / Jensen, M D / Lerman, A / Kushwaha, S / Rihal, C S / Gersh, B J / Behfar, A / Tchkonia, T / Thomas, R J / Lennon, R J / Keenan, L R / Moore, A G / Kirkland, J L. ·Mandeep Singh, MD, MPH, 200 First street SW, Mayo Clinic, Rochester, MN 55905, Tel: 507-255-5891, Fax: 507-255-2550, Email: Singh.Mandeep@mayo.edu. ·J Frailty Aging · Pubmed #27883166.

ABSTRACT: Rapamycin, an mTOR inhibitor affects senescence through suppression of senescence-associated secretory phenotype (SASP). We studied the safety and feasibility of low-dose rapamycin and its effect on SASP and frailty in elderly undergoing cardiac rehabilitation (CR). 13 patients; 6 (0.5mg), 6 (1.0mg), and 1 patient received 2mg oral rapamycin (serum rapamycin <6ng/ml) daily for 12 weeks. Median age was 73.9±7.5 years and 12 were men. Serum interleukin-6 decreased (2.6 vs 4.4 pg/ml) and MMP-3 (26 vs 23.5 ng/ml) increased. Adipose tissue expression of mRNAs (arbitrary units) for MCP-1 (3585 vs 2020, p=0.06), PPAR-γ (1257 vs 1166), PAI-1 (823 vs 338, p=0.08) increased, whereas interleukin-8 (163 vs 312), TNF-α (75 vs 94) and p16 (129 vs 169) decreased. Cellular senescence-associated beta galactosidase activity (2.2% vs 3.6%, p=0.18) tended to decrease. We observed some correlation between some senescence markers and physical performance but no improvement in frailty with rapamycin was noted. (NCT01649960).

25 Article Association between coronary microvascular function and the vasa vasorum in patients with early coronary artery disease. 2016

Park, Kyoung-Ha / Sun, Tao / Diez-Delhoyo, Felipe / Liu, Zhi / Yang, Shi-Wei / Lennon, Ryan J / Herrmann, Joerg / Gulati, Rajiv / Rodriguez-Porcel, Martin / Lerman, Lilach O / Lerman, Amir. ·Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA; Division of Cardiovascular Disease, Hallym University Medical Center, Anyang, South Korea. · Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA. · Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA. · Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA. · Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA. Electronic address: lerman.amir@mayo.edu. ·Atherosclerosis · Pubmed #27626971.

ABSTRACT: BACKGROUND AND AIMS: The vasa vasorum (VV) plays a role in the initial phase of atherosclerosis, and abnormalities in microvascular function may be sensitive measures of the early development of atherosclerosis. The current study was designed to access the association between coronary microvascular function and VV density in patients undergoing cardiac catheterization. METHODS: Twenty-four patients with early coronary artery disease underwent endothelium-dependent (coronary blood flow, CBF) and endothelium-independent (coronary flow velocity reserve, CFVR) coronary microvascular function testing, and optical coherence tomography (OCT) imaging of the left anterior descending coronary artery (LAD). Using an intracoronary Doppler guidewire, CBF was examined by evaluating changes in blood flow in response to acetylcholine and CFVR in response to adenosine. VV density (VV volume/vessel volume × 100, %VV) of the proximal 10 mm of the LAD was quantified by OCT. RESULTS: The median values (Q1, Q3) of CFVR, % changes in CBF in response to acetylcholine, and the %VV were 2.70 (2.30, 2.90), -16.82 (-42.34, 54.52), and 2.62 (2.35, 3.35), respectively. %VV correlated inversely with CBF (r = -0.614, p = 0.001) and directly with CFVR (r = 0.423, p = 0.040). Multivariate analysis showed that only %VV was significantly correlated with CBF and the association was independent of other clinical variables, Framingham risk score, body mass index, and a family history of coronary heart disease. CONCLUSIONS: This study demonstrates that VV density has negative correlation with endothelium-dependent microvascular function in patients with early coronary atherosclerosis. These observations link adventitial VV structure and function to microvascular dysfunction in early coronary atherosclerosis.

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