Michael Kutner

Michael Kutner
Emory University | EU · Department of Biostatistics and Bioinformatics

PhD

About

259
Publications
25,253
Reads
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48,394
Citations
Citations since 2017
45 Research Items
8573 Citations
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Introduction
Collaborate, mentor and write research grants
Skills and Expertise
Additional affiliations
August 1971 - present
Emory University
Position
  • Rollins Professor
Description
  • former Associate Dean for Faculty Affairs (1990-1993) and Department Chair(1990-1991: 2004-2009); co-author of Applied Linear Regression Models, 4th ed. & Applied Linear Statistical Models, 5th ed.
August 1971 - September 1990
Emory University
Position
  • Professor (Full); statistical consultation; clinical trialist
Description
  • Biostatistician for General Clinical Research Center(1974-1993); teach linear models and biostatistical methods courses

Publications

Publications (259)
Article
Full-text available
Unlabelled: The Centers for Disease Control has well-established surveillance programs to monitor preventable conditions in patients supported by mechanical ventilation (MV). The aim of the study was to develop a data-driven methodology to examine variations in the first tier of the ventilator-associated event surveillance definition, described as...
Article
Background Early life trauma has been associated with increased cardiovascular risk, but the arrhythmic implications are unclear. We hypothesized that in patients with coronary artery disease, early life trauma predicts increased arrhythmic risk during mental stress, measured by elevated microvolt T‐wave alternans (TWA), a measure of repolarization...
Article
Importance Mental stress–induced myocardial ischemia is a recognized phenomenon in patients with coronary heart disease (CHD), but its clinical significance in the contemporary clinical era has not been investigated. Objective To compare the association of mental stress–induced or conventional stress–induced ischemia with adverse cardiovascular ev...
Article
The combined treatments with multiple drugs are very common in the contemporary medicine, especially for medical oncology. Therefore, we developed a Bayesian adaptive Phase I clinical trial design entitled escalation with overdoing control using normalized equivalent toxicity score for estimating maximum tolerated dose (MTD) contour of two drug com...
Article
Background: Noninvasive ventilation (NIV), a form of positive airway pressure (PAP) therapy, is the standard of care for various forms of acute respiratory failure (ARF). Communication impairment is a side effect of NIV, impedes patient care, contributes to distress and intolerance, and potentially increases intubation rates. This study aimed to e...
Article
High sensitive cardiac troponin I (hs-cTnI) increases with inducible myocardial ischemia in patients with coronary artery disease (CAD). We aimed to assess if the change in hs-cTnI levels with exercise stress testing is associated with major adverse cardiac events (MACE). A cohort of 365 (age 62 ± 9 years, 77% men) patients with stable CAD underwen...
Article
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Background Lower extremity peripheral arterial disease (PAD) is a public health problem and many patients with PAD experience claudication despite adequate medical and/or surgical management. Mobilization of endogenous progenitor cells using Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) is a novel therapeutic option that has shown promi...
Article
Importance Stem and progenitor cells mobilize from the bone marrow in response to myocardial ischemia. However, the association between the change in circulating progenitor cell (CPC) counts and disease prognosis among patients with ischemia is unknown. Objective To investigate the association between the change in CPC counts during stress testing...
Article
Importance Acute mental stress can result in transient endothelial dysfunction, but the prognostic relevance of this phenomenon is unknown. Objective To determine the association between mental stress–induced impairment in endothelium-dependent relaxation as assessed by brachial artery flow-mediated vasodilation and adverse cardiovascular outcomes...
Article
Leukocyte telomere length (LTL) may be sensitive to psychosocial stressors such as discrimination. An inclusive examination of experiences of discrimination on LTL across racial/ethnic and sex groups is currently lacking. Baseline data were obtained from 369 White and African American patients with coronary artery disease (CAD) in the Mental Stress...
Article
Full-text available
Background: The autonomic response to acute emotional stress can be highly variable, and pathological responses are associated with increased risk of adverse cardiovascular events. We evaluated the autonomic response to stress reactivity of young healthy subjects and aging subjects with coronary artery disease to understand how the autonomic stress...
Data
Effects of a behavioral intervention using biofeedback on myocardial blood flow changes during mental stress in patients with coronary artery disease. Protocol document provides detailed description of each intervention applied to patients with CAD. (PDF)
Data
R-squared values and 95% CI for stress reactivity and Gensini scores. R-squared values and 95% CI (lower bound, upper bound) values from the linear models derived from the change in each physiological measure and the corresponding Gensini score. The changes were assessed as the difference between stress and rest values for each physiological measur...
Data
Consolidated Standards of Reporting Trials (CONSORT) checklist of the manuscript. (DOC)
Data
Lists the physiological outcomes for each young, heathy and aging subject with CAD, each are in separate sheets. (XLSX)
Data
Statistical analyses on the CAD group’s baseline, first minute of stress, and overall stress on HR, SBP, DBP, PP. Baseline, first minute of stress, overall stress values represent mean (SD). P-values were calculated from ANOVA (for normal data) or Kruskal-Wallis (for non-normal data) on the three intervals (baseline, first minute of stress, overall...
Article
Full-text available
Background: Many patients with coronary artery disease (CAD) are routinely referred for surveillance stress testing despite recommendations against it. Objective: To determine whether low levels of resting high-sensitivity cardiac troponin I (hs-cTnI) can identify persons without inducible myocardial ischemia. Design: Observational study. Set...
Article
Full-text available
Among various Phase I clinical trial designs, rule-based standard 3 + 3 designs are the most widely utilized for their simplicity and robustness. It is necessary to define crucial operating characteristics of a Phase I clinical trial before it starts. Based on the assumed probability of dose limiting toxicity (DLT) at each tested dose level, Lin an...
Article
Full-text available
Living in neighborhoods characterized by poverty may act as a chronic stressor that results in physiological dysregulation of the sympathetic nervous system. No previous study has assessed neighborhood poverty with hemodynamic, neuroendocrine, and immune reactivity to stress. We used data from 632 patients with coronary artery disease. Patients’ re...
Article
Full-text available
The influence of acute psychological stress on cardiovascular disease is an emerging public health concern. Identification of brain mechanisms underlying this may aid in the discovery of possible treatments. Acute psychological stress may induce arteriolar vasoconstriction and reduce blood flow to vital organs. We hypothesized that functional chang...
Article
1 Background Definition of response is critical when seeking to establish valid predictors of treatment success. However, response at the end of study or endpoint only provides one view of the overall clinical picture that is relevant in testing for predictors. The current study employed a classification technique designed to group subjects based o...
Data
Table S1. Hemodynamic and Intracoronary Doppler Measurements During the Individual Steps of the Study Protocol Figure S1. Intracoronary Doppler tracing and respective hemodynamic measurements of a subject during the study protocol. Baseline (A) was the reference for acetylcholine (B) and adenosine (C). Pre‐MS (D) was the reference for MS (E), and...
Article
Full-text available
Background Coronary microvascular dysfunction may contribute to myocardial ischemia during mental stress (MS). However, the role of coronary epicardial and microvascular function in regulating coronary blood flow (CBF) responses during MS remains understudied. We hypothesized that coronary vasomotion during MS is dependent on the coronary microvasc...
Article
Full-text available
Objective: Coronary artery disease (CAD) is a major cause of morbidity and mortality, and despite important advances in our understanding of this disorder, the underlying mechanisms remain under investigation. Recently, increased attention has been placed to the role of behavioral factors like emotional stress on CAD risk. Brain areas involved in...
Article
Background: Exposure to psychological stress has been associated with the development of sustained arrhythmias. Acute changes in atrial electrophysiology may serve as intermediate phenotypes for stress-induced arrhythmia. The relationship between atrial electrical changes and stress related changes in heart rate and myocardial ischemia is unknown....
Article
Ischemia results from an imbalance between myocardial oxygen supply and demand. Ischemia associated with mental stress (MS) has been associated with adverse outcomes in patients with coronary artery diseases (CAD). Higher heart rate (HR) and blood pressure responses to MS are associated with a greater likelihood of MS-induced ischemia. Although mul...
Article
Full-text available
Background The response of progenitor cells (PCs) to transient myocardial ischemia in patients with coronary artery disease remains unknown. We aimed to investigate the PC response to exercise‐induced myocardial ischemia (ExMI) and compare it to flow mismatch during pharmacological stress testing. Methods and ResultsA total of 356 patients with sta...
Article
Objective: To investigate sex-specific vascular mechanisms for mental stress-induced myocardial ischemia (MSIMI). Approach and results: Baseline data from a prospective cohort study of 678 patients with coronary artery disease underwent myocardial perfusion imaging before and during a public speaking stressor. The rate-pressure product response...
Article
Introduction: Mental Stress-Induced Myocardial Ischemia (MSIMI) can occur in patients with coronary artery disease (CAD) during acute mental stress challenge and is associated with an increased risk of adverse cardiovascular events. Adverse dynamic changes in repolarization with stress may also be particularly important when assessing risk of MSIMI...
Article
Background: Mental stress-induced myocardial ischemia (MSIMI) is associated with increased risk of adverse cardiovascular outcomes, yet the underlying mechanisms are not well understood. We measured the inflammatory response to acute laboratory mental stress in patients with coronary artery disease (CAD) and its association with MSIMI. We hypothes...
Article
Background: Acute stress may trigger atrial fibrillation (AF), but the underlying mechanisms are unclear. We examined if acute mental stress results in abnormal left atrial electrophysiology as detected by more negative deflection of P-wave terminal force in lead V1 (PTFV1 ), a well-known marker of AF risk. Methods and results: We examined this...
Article
Aims Mental stress-induced myocardial ischemia (MSIMI) in patients with coronary artery disease (CAD) is associated with adverse cardiovascular outcomes. We aim to assess hemodynamic, neuro-hormonal, endothelial, vasomotor and vascular predictors of MSIMI. Methods and results We subjected 660 patients with stable CAD to 99mTc sestamibi myocardial...
Article
Background: Acute stress may trigger atrial fibrillation, but the mechanisms are not clear. We hypothesized that acute mental stress results in abnormal atrial remodeling via electrophysiologic effects. Methods: We examined our hypothesis in 168 patients (mean age=63±8.7 years; 74% men; 65% Caucasian) with stable coronary heart disease who underwen...
Article
Rationale: Leukocyte telomere length (LTL) is an indicator of biological aging. Telomere shortening may be sensitive to social stressors such as discrimination, but this has not been previously examined in a biracial cohort of patients with coronary heart disease (CHD). Objective: To explore differences in LTL by race and gender and examine whether...
Article
Objectives This study sought to investigate whether patients with mental stress–induced myocardial ischemia will have high resting and post–mental stress high-sensitivity cardiac troponin I (hs-cTnI). Background Hs-cTnI is a marker of myocardial necrosis, and its elevated levels are associated with adverse outcomes. Hs-cTnI levels may increase wit...
Article
Full-text available
Background Many biomarkers have been shown to be associated with the efficacy of cancer therapy. Estimation of personalized maximum tolerated doses (pMTDs) is a critical step toward personalized medicine, which aims to maximize the therapeutic effect of a treatment for individual patients. In this study, we have established a Bayesian adaptive Phas...
Article
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The W.J. Dixon Award for Excellence in Statistical Consulting is given by the American Statistical Association to “a distinguished individual who has demonstrated excellence in statistical consulting or developed and contributed new methods, software, or ways of thinking that improve statistical practice in general.” In this article, five of the se...
Article
Full-text available
Objective: Mental stress-induced myocardial ischemia (MSIMI) is a common phenomenon in patients with coronary artery disease (CAD), but contemporary studies of its prognostic significance and its underlying pathophysiology are limited. Methods: We prospectively enrolled patients with confirmed CAD in the Mental Stress Ischemia Prognosis Study (M...
Article
Full-text available
Rationale: Leucocyte telomere length (LTL) is a biological marker of aging, and shorter LTL is associated with adverse cardiovascular outcomes. Reduced regenerative capacity has been proposed as a mechanism. Bone marrow-derived circulating progenitor cells (PCs) are involved in tissue repair and regeneration. Objective: To examine the relationsh...
Article
Full-text available
Background Emerging data suggest that young women with coronary heart disease (CHD) are disproportionally vulnerable to the adverse cardiovascular effects of psychological stress. We hypothesized that younger, but not older, women with stable CHD are more likely than their male peers to develop mental stress‐induced myocardial ischemia (MSIMI). Me...
Article
Introduction: Endothelial dysfunction is associated with short term and long term cardiovascular events. African Americans (AA) have worse cardiovascular outcomes than Non-African Americans (NAA). AAs have higher chronic stress exposure due to socioeconomic deprivation which may affect vascular responses to stress and contribute to health dispariti...
Article
Introduction: Synchronized contraction of left ventricle (LV) is necessary for normal cardiac pump function. Delayed activation of LV segments, known as “dyssynchrony,” can result in systolic and diastolic function deterioration and clinical heart failure. The autonomic nervous system regulates LV conduction and is influenced by psychological stres...
Article
Background: Evidence supports that peripheral vasoconstriction during mental stress predicts mental stress induced ischemia (MSIMI). However, whether a dose response relationship exists with ischemia severity has not been evaluated; additionally, whether peripheral vascular function during the recovery phase is also related to MSIMI is not known. H...
Article
Introduction: Mental stress ischemia (MSI) is an independent risk factor for cardiovascular outcomes and death in CAD patients, but little is known about the mechanisms behind this phenomenon. We hypothesized that alterations in autonomic function before, during, or after mental stress may play a role. We examined whether MSI positive patients with...
Article
Background: Patients with CAD develop varying degrees of microvascular vasoconstriction in response to mental stress, leading to myocardial ischemia. Catecholamine increases during mental stress may explain this effect. We hypothesized, in a cohort of stable CAD patients, that increased epinephrine and norepinephrine levels from rest to peak mental...
Article
Introduction: Depression and posttraumatic stress disorder (PTSD) are associated with impaired baroreflex sensitivity, a risk factor for sudden death. Unlike depression, PTSD is associated with hyperarousal. We hypothesized that, in patients with CAD, depressive and PTSD symptoms associate with different autonomic responses to standing (baroreflex...
Article
Introduction: Previous studies have found that lower resting short-term heart rate variability (HRV), a measure of autonomic dysfunction, predicts adverse cardiac events. Abnormal autonomic function may precipitate myocardial ischemia. Physiologic challenges like Valsalva and deep breathing may also provide important data by modulating preload/afte...
Article
Introduction: Increased hemodynamic responses to psychological stress have been associated with adverse CAD events. African Americans (AA) have worse CAD outcomes than other groups. Heightened hemodynamic responses to stress may play a role. Our hypothesis was that AA would have higher hemodynamic reactivity to a standardized mental stress compared...
Article
Full-text available
Supplemental melatonin may ameliorate metabolic syndrome (MetS) components, but data from placebo-controlled trials are lacking. We conducted a double-blind, placebo-controlled, crossover, Phase II randomized pilot clinical trial to estimate the effects of melatonin supplementation on MetS components and the overall prevalence of MetS. We randomize...
Article
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Pharmacologic treatment options for posttraumatic stress disorder (PTSD) are limited in number and effectiveness. Medications currently in use to treat PTSD were originally approved based on their efficacy in other disorders, such as major depression. Substantial research in PTSD suggests that increased activity of corticotropin releasing hormone (...
Article
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Background Limited controlled data exist to guide treatment choices for clinicians caring for patients with major depressive disorder (MDD). Although many putative predictors of treatment response have been reported, most were identified through retrospective analyses of existing datasets and very few have been replicated in a manner that can impac...
Article
Lonafarnib (LNF) is a protein farnesyl transferase (FTase) inhibitor that has shown synergistic activity with taxanes in preclinical models and early stage clinical trials. Preclinical findings suggested tubulin acetylation and FTase expression levels may be important determinants of drug sensitivity that would help identify patient populations mor...
Article
The objective of the current study was to delineate the optimal cutpoints for depression rating scales during pregnancy and the postpartum period and to assess the perinatal factors influencing these scores. Women participating in prospective investigations of maternal mental illness were enrolled prior to 28 weeks gestation and followed through 6...
Article
The transfusion-transmitted cytomegalovirus (TT-CMV) can cause serious morbidity and mortality in low-birth weight infants (LBWIs). Transfusion-transmitted cytomegalovirus can be minimized in LBWIs born to cytomegalovirus (CMV)-seronegative mothers with the use of CMV-seronegative blood components. Despite evidence that has independently shown that...
Article
Full-text available
Sleep-disordered breathing (SDB) is associated with pathophysiology that may influence the development and progression of frailty. Using data collected in 1995-1996, the authors explored the relation between SDB and components of frailty among 1,042 participants of the Cardiovascular Health Study. Diagnosis of SDB was based on the results of overni...
Article
Full-text available
To examine the association between sleep-disordered breathing (SDB) and 24-hour blood pressure (BP) pattern among community-dwelling older adults. A convenience sample of 70 community-dwelling older adults, recruited from senior housing, community centers, and learning centers, were admitted to General Clinical Research Center, Emory University Hos...
Article
Women experience greater morbidity and mortality than men after conventional coronary artery bypass grafting (CABG) on cardiopulmonary bypass (CPB). The objective of this study was to determine whether off-pump CABG (OPCAB) alters this gender-based disparity. Retrospective review of risk factors and clinical outcomes for 11 413 consecutive patients...
Article
Variceal bleeding refractory to medical treatment with beta-blockers and endoscopic therapy can be managed by variceal decompression with either surgical shunts or transjugular intrahepatic portal systemic shunts (TIPS). This prospective randomized trial tested the hypothesis that patients receiving distal splenorenal shunts (DSRS) would have signi...
Article
Full-text available
Few data exist to evaluate whether Tai Chi (TC) training improves physical performance and hemodynamic outcomes more than a wellness education (WE) program does among older fallers transitioning to frailty. This 48-week randomized clinical trial was provided at 10 matched pairs of congregate living facilities in the Atlanta metropolitan area to 291...
Article
Studies in animals showed that the hippocampus, a brain area involved in learning and memory, is sensitive to stress. Although several MRI studies showed smaller hippocampal volume in adults with chronic PTSD, others did not show significant differences from controls. These studies are typified by small sample sizes which may limit the ability to s...
Article
To test the effects of a rehabilitative intervention directed at continence, mobility, endurance, and strength (Functional Incidental Training (FIT)) in older patients in Department of Veterans Affairs (VA) nursing homes. Randomized, controlled, crossover trial. Four VA nursing homes. All 528 patients in the nursing homes were screened; 178 were el...
Article
To determine whether an intense tai chi exercise program could reduce fear of falling better than a wellness education (WE) program in older adults who had fallen previously and meet criteria for transitioning to frailty. Cluster-randomized, controlled trial of 48 weeks' duration. Ten matched pairs of congregate living facilities in the greater Atl...
Article
The Dialysis Outcomes and Practice Patterns Study (DOPPS) is a prospective, observational study designed to elucidate aspects of hemodialysis practice that are associated with the best outcomes for hemodialysis patients. In DOPPS I, 308 hemodialysis units from 7 countries participated, including 145 facilities from the United States (1996-2001), 62...
Article
Examining gait characteristics in older adults who are transitioning to frailty enhances our understanding of movement control in this fall-prone population and helps to better target preventive interventions. This work presents data on temporal and spatial gait parameters of a group of older adults who have been operationally defined as "transitio...
Article
The objective of this study was to examine the association between psychoactive medications and sleep quality in a sample of nursing home patients. We studied a baseline data collection for a clinical trial of a nonpharmacologic sleep intervention program. This study was conducted at six community nursing homes. We studied 168 nursing home patients...
Article
To investigate the relationship between sleep-disordered breathing (SDB) and nocturia episodes in community-dwelling older adults. A cross-sectional study. Community. Community-dwelling older adults (N=72) recruited from independent living facilities and adult learning centers in Atlanta, Georgia. Three-day voiding diary, ambulatory sleep recording...