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Biomedical subjects

Peter H Stone

Publications and source records attributed to Peter H Stone.

At least 37 records · Page 2Linked to original sources
PubMed2004

Vascular basis for the treatment of myocardial ischemia study: trial design and baseline characteristics.

BACKGROUND: Increased low-density lipoprotein (LDL) and oxidized LDL cholesterol levels adversely affect endothelial function in patients with stable coronary artery disease (CAD). Statin drugs are efficacious in primary and secondary prevention of clinical CAD events, but they have not been extensively studied as a treatment for ischemia during routine daily activities or during exercise, indicators of high-risk in patients with stable CAD. The purpose of the Vascular Basis for the Treatment of Myocardial Ischemia study is to determine whether aggressive lowering of LDL cholesterol level with atorvastatin, with or without supplemental antioxidant vitamins C and E, can improve endothelial function and ischemia during ambulatory electrocardiogram (AECG) monitoring and exercise treadmill testing (ETT). METHODS: Patients are eligible when they have ischemia during an ETT and AECG monitoring and when their fasting total cholesterol level is < or =250 mg/dL. Eligible patients are randomized to receive 1 of 3 treatments: intensive atorvastatin to reduce LDL cholesterol level to < or =80 mg/dL, intensive atorvastatin to reduce LDL cholesterol level to < or =80 mg/dL plus antioxidant vitamins C and E, and control of diet and low-dose lovastatin, when needed, to reduce LDL cholesterol level < or = to 130 mg/dL. Patients undergo endothelial function testing, 48-hour AECG monitoring, and ETT at randomization and at 6 and 12 months. RESULTS: A total of 300 patients have been randomized: 101 to receive atorvastatin alone, 103 to receive atorvastatin plus antioxidant vitamins, and 96 to receive placebo. Baseline characteristics are similar across treatment groups. CONCLUSIONS: The Vascular Basis study will provide important insight on the effects of aggressive management of dyslipidemia with statin drugs and antioxidant vitamins in patients with stable but high-risk CAD.

Adult↗
PubMed2003

From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part II.

Atherosclerotic cardiovascular disease results in >19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of opportunity in the field of cardiovascular medicine. This consensus document concludes the following. (1) Rupture-prone plaques are not the only vulnerable plaques. All types of atherosclerotic plaques with high likelihood of thrombotic complications and rapid progression should be considered as vulnerable plaques. We propose a classification for clinical as well as pathological evaluation of vulnerable plaques. (2) Vulnerable plaques are not the only culprit factors for the development of acute coronary syndromes, myocardial infarction, and sudden cardiac death. Vulnerable blood (prone to thrombosis) and vulnerable myocardium (prone to fatal arrhythmia) play an important role in the outcome. Therefore, the term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future. (3) A quantitative method for cumulative risk assessment of vulnerable patients needs to be developed that may include variables based on plaque, blood, and myocardial vulnerability. In Part I of this consensus document, we cover the new definition of vulnerable plaque and its relationship with vulnerable patients. Part II of this consensus document will focus on vulnerable blood and vulnerable myocardium and provide an outline of overall risk assessment of vulnerable patients. Parts I and II are meant to provide a general consensus and overviews the new field of vulnerable patient. Recently developed assays (eg, C-reactive protein), imaging techniques (eg, CT and MRI), noninvasive electrophysiological tests (for vulnerable myocardium), and emerging catheters (to localize and characterize vulnerable plaque) in combination with future genomic and proteomic techniques will guide us in the search for vulnerable patients. It will also lead to the development and deployment of new therapies and ultimately to reduce the incidence of acute coronary syndromes and sudden cardiac death. We encourage healthcare policy makers to promote translational research for screening and treatment of vulnerable patients.

Animals↗
PubMed2003

From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part I.

Atherosclerotic cardiovascular disease results in >19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of opportunity in the field of cardiovascular medicine. This consensus document concludes the following. (1) Rupture-prone plaques are not the only vulnerable plaques. All types of atherosclerotic plaques with high likelihood of thrombotic complications and rapid progression should be considered as vulnerable plaques. We propose a classification for clinical as well as pathological evaluation of vulnerable plaques. (2) Vulnerable plaques are not the only culprit factors for the development of acute coronary syndromes, myocardial infarction, and sudden cardiac death. Vulnerable blood (prone to thrombosis) and vulnerable myocardium (prone to fatal arrhythmia) play an important role in the outcome. Therefore, the term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future. (3) A quantitative method for cumulative risk assessment of vulnerable patients needs to be developed that may include variables based on plaque, blood, and myocardial vulnerability. In Part I of this consensus document, we cover the new definition of vulnerable plaque and its relationship with vulnerable patients. Part II of this consensus document focuses on vulnerable blood and vulnerable myocardium and provide an outline of overall risk assessment of vulnerable patients. Parts I and II are meant to provide a general consensus and overviews the new field of vulnerable patient. Recently developed assays (eg, C-reactive protein), imaging techniques (eg, CT and MRI), noninvasive electrophysiological tests (for vulnerable myocardium), and emerging catheters (to localize and characterize vulnerable plaque) in combination with future genomic and proteomic techniques will guide us in the search for vulnerable patients. It will also lead to the development and deployment of new therapies and ultimately to reduce the incidence of acute coronary syndromes and sudden cardiac death. We encourage healthcare policy makers to promote translational research for screening and treatment of vulnerable patients.

Acute Disease↗
PubMed2003

Economic consequences of routine coronary angiography in low- and intermediate-risk patients with unstable angina pectoris.

In low- and intermediate-risk patients with unstable angina pectoris (UAP) and non-ST-elevation acute myocardial infarction (NSTEAMI), routine early invasive management with coronary angiography does not decrease the risk of death or AMI. The economic consequences of this strategy in low- and intermediate-risk patients are unknown. We applied a risk prediction rule to a multihospital practice database and to the population of the Thrombolysis In Myocardial Ischemia trial, phase IIIB (TIMI 3B), which compared early invasive with conservative therapy for UAP and NSTEAMI. We then analyzed the effect of an early invasive strategy with regard to the composite end point of death, AMI, or rehospitalization for ischemia at rest. A logistic regression model was used to compare outcomes in patients with high versus low or intermediate risk scores. The costs and benefits of early invasive management in low- or intermediate-risk patients were assessed. In the practice database, 56% of patients with UAP and NSTEAMI who had low or intermediate risk scores underwent early cardiac catheterization, although early invasive management of these lower risk patients has not been associated with a reduction in the rate of death or MI. In TIMI 3B, when rehospitalization for ischemia at rest was added to the composite end point, invasive management was superior to conservative management at 42 days (p = 0.005) and at 1 year (p = 0.03). If all low- or intermediate-risk patients randomized to conservative therapy in that trial had been treated instead with an early invasive strategy, an estimated 5.4% of rehospitalizations would have been avoided. Within TIMI 3B, such a routine invasive strategy would have resulted in an additional cost of 2,695,700 US dollars with no effect on death or AMI, but it would have led to 34 fewer rehospitalizations. This expenditure of 79,285 US dollars per hospitalization prevented far exceeds the monetary cost of rehospitalization (14,000 US dollars). Although common in clinical practice, routine early invasive management of low- or intermediate-risk patients with UAP generates substantial health-care costs without a mortality benefit or decrease in the risk of AMI. Unless the incremental benefit in quality of life from prevented rehospitalizations for UAP is judged to be worth the large incremental cost (79,285 US dollars per hospitalization prevented), such a strategy is unlikely to be cost effective.

Aged↗
PubMed2003

Effect of endothelial shear stress on the progression of coronary artery disease, vascular remodeling, and in-stent restenosis in humans: in vivo 6-month follow-up study.

BACKGROUND: Native atherosclerosis and in-stent restenosis are focal and evolve independently. The endothelium controls local arterial responses by transduction of shear stress. Characterization of endothelial shear stress (ESS) may allow for prediction of progression of atherosclerosis and in-stent restenosis. METHODS AND RESULTS: By using intracoronary ultrasound, biplane coronary angiography, and measurement of coronary blood flow, we represented the artery in accurate 3D space and determined detailed characteristics of ESS and arterial wall/plaque morphology. Patients who underwent stent implantation and who had another artery with luminal obstruction <50% underwent intravascular profiling initially and after 6-month follow-up. Twelve arteries in 8 patients were studied: 6 native and 6 stented arteries. In native arteries, regions of abnormally low baseline ESS exhibited a significant increase in plaque thickness and enlargement of the outer vessel wall, such that lumen radius remained unchanged (outward remodeling). Regions of physiological ESS showed little change. Regions with increased ESS exhibited outward remodeling with normalization of ESS. In stented arteries, there was an increase in intima-medial thickness, a decrease in lumen radius, and an increase in ESS at all levels of baseline ESS. CONCLUSIONS: The present study represents the first experience in humans relating ESS to subsequent outcomes in native and stented arteries. Regions of low ESS develop progressive atherosclerosis and outward remodeling, areas of physiological ESS remain quiescent, and areas of increased ESS exhibit outward remodeling. ESS may have a limited role in in-stent restenosis. This technology can predict areas of minor plaque likely to exhibit progression of atherosclerosis.

Adult↗
PubMed2003

Reproducibility of coronary lumen, plaque, and vessel wall reconstruction and of endothelial shear stress measurements in vivo in humans.

The purpose of this study was to assess the reproducibility of an in vivo methodology to reconstruct the lumen, plaque, and external elastic membrane (EEM) of coronary arteries and estimate endothelial shear stress (ESS). Ten coronary arteries without significant stenoses (five native and five stented arteries) were investigated. The 3D lumen and EEM boundaries of each coronary artery were determined by fusing end-diastolic intravascular ultrasound images with biplane coronary angiograms. Coronary flow was measured. Computational fluid dynamics was used to calculate local ESS. Complete data acquisition was then repeated. Analysis was performed on each data set in a blinded manner. The intertest correlation coefficients for all arteries for the two measurements of lumen radius, EEM radius, plaque thickness, and ESS were r = 0.96, 0.96, 0.94, 0.91, respectively (all P values < 0.0001). The 3D anatomy and ESS of human coronary arteries can be reproducibly estimated in vivo. This methodology provides a tool to examine the effect of ESS on atherogenesis, remodeling, and restenosis; the contribution of arterial remodeling and plaque growth to changes in the lumen; and the impact of new therapies.

Adult↗
PubMed2003

Prediction of sites of coronary atherosclerosis progression: In vivo profiling of endothelial shear stress, lumen, and outer vessel wall characteristics to predict vascular behavior.

PURPOSE OF REVIEW: Native atherosclerosis and in-stent restenosis are focal and evolve independently. The endothelium regulates arterial behavior by responding to its local environment of hemodynamic stresses, in particular, shear stress. Identification of endothelial shear stress and arterial wall characteristics may allow for the prediction of the progression of atherosclerosis. Accurate identification of arterial segments at high risk for progression may permit preemptive intervention strategies to avoid adverse coronary events. RECENT FINDINGS: In vitro studies indicate that low endothelial shear stress upregulates the genetic and molecular responses leading to the initiation and progression of atherosclerosis, and promotes inflammation and formation of other features characteristic of vulnerable plaque. Physiologic endothelial shear stress is vasculoprotective and fosters quiescence of the endothelium and vascular wall. High endothelial shear stress promotes platelet aggregation. Recent studies have now provided evidence that endothelial shear stress and vascular wall morphology along the course of human coronary arteries can be characterized in vivo, and, in serial studies, may actually predict the focal areas in which atherosclerosis progression occurs. SUMMARY: Rapidly evolving methodologies are able to characterize the arterial wall and the local hemodynamic environmental factors likely responsible for progression of coronary disease in humans. These new diagnostic modalities allow for identification of plaque progression. Future studies need to identify the factors responsible for vulnerable plaque formation. The current availability of drug-eluting stents with a low risk of restenosis allows for consideration of preemptive intervention strategies for these high-risk vascular sites such that future adverse coronary events can be averted.

Coronary Artery Disease↗
PubMed2002

Prognosis in the thrombolysis in myocardial ischemia III registry according to the Braunwald unstable angina pectoris classification.

The unstable angina pectoris (UAP) classification proposed by Braunwald in 1989, although often used, has never been validated in a large, prospective multicenter study in which all subgroups of patients were included. Patients with UAP or non-ST-elevation myocardial infarction (NSTEMI) were enrolled in the Thrombolysis In Myocardial Ischemia III Registry and classified according to the Braunwald classification for UAP. Clinical end points were compared at 6 weeks and 1 year. Of 3,318 patients, those with primary UAP had lower rates of recurrent myocardial infarction (MI) or death when compared with patients with secondary UAP and post-MI UAP at 6 weeks (4.1% vs 6.4% vs 13.4%, respectively; p <0.001) and 1 year (9.7% vs 16.7% vs 19.7%; p <0.001). Recurrent ischemia at 6 weeks followed the same gradient (13.2% vs 18.5% vs 20.8%; p <0.001). Patients with secondary UAP had similar extent of disease at angiography as primary UAP. Patients with nonresting UAP had lower rates of death or MI than patients with UAP at rest (3.0% vs 5.6%, p = 0.011 at 6 weeks, and 8.2% vs 12.5%, p = 0.004 at 1 year). Patients with ST-segment deviation and those who had received prior antianginal medical treatment also had worse outcomes. Thus, the Braunwald classification of UAP predicts prognosis with secondary UAP, post-MI UAP, and patients with pain at rest who have a higher risk for death or recurrent cardiac events. Given their high risk for adverse events, patients with secondary UAP should be treated aggressively.

Aged↗
PubMed2002

Mental stress-induced ischemia and all-cause mortality in patients with coronary artery disease: Results from the Psychophysiological Investigations of Myocardial Ischemia study.

BACKGROUND: Ischemia during laboratory mental stress tests has been linked to significantly higher rates of adverse cardiac events. Previous studies have not been designed to detect differences in mortality rates. METHODS AND RESULTS: To determine whether mental stress-induced ischemia predicts death, we evaluated 196 patients from the Psychophysiological Investigations of Myocardial Ischemia (PIMI) study who had documented coronary artery disease and exercise-induced ischemia. Participants underwent bicycle exercise and psychological stress testing with radionuclide imaging. Cardiac function data and psychological test results were collected. Vital status was ascertained by telephone and by querying Social Security records 3.5+/-0.4 years and 5.2+/-0.4 years later. Of the 17 participants who had died, new or worsened wall motion abnormalities during the speech test were present in 40% compared with 19% of survivors (P=0.04) and significantly predicted death (rate ratio=3.0; 95% CI, 1.04 to 8.36; P=0.04). Ejection fraction changes during the speech test were similar in patients who died and in survivors (P=0.9) and did not predict death even after adjusting for resting ejection fraction (P=0.63), which was similar in both groups (mean, 56.4 versus 59.7; P=0.24). Other indicators of ischemia during the speech test (ST-segment depression, chest pain) did not predict death, nor did psychological traits, hemodynamic responses to the speech test, or markers of the presence and severity of ischemia during daily life and exercise. CONCLUSIONS: In patients with coronary artery disease and exercise-induced ischemia, the presence of mental stress-induced ischemia predicts subsequent death.

Coronary Artery Disease↗
PubMed2002

Quantifying uncertainties in climate system properties with the use of recent climate observations.

We derive joint probability density distributions for three key uncertain properties of the climate system, using an optimal fingerprinting approach to compare simulations of an intermediate complexity climate model with three distinct diagnostics of recent climate observations. On the basis of the marginal probability distributions, the 5 to 95% confidence intervals are 1.4 to 7.7 kelvin for climate sensitivity and -0.30 to -0.95 watt per square meter for the net aerosol forcing. The oceanic heat uptake is not well constrained, but ocean temperature observations do help to constrain climate sensitivity. The uncertainty in the net aerosol forcing is much smaller than the uncertainty range for the indirect aerosol forcing alone given in the Intergovernmental Panel on Climate Change Third Assessment Report.

Journal Article↗
PubMed2002

Randomized trial of a medical food for the dietary management of chronic, stable angina.

OBJECTIVES: We determined the electrocardiographic, vascular and clinical effects of a medical food bar enriched with L-arginine and a combination of other nutrients known to enhance endothelium-derived nitric oxide (NO) in patients with stable angina. BACKGROUND: Enhancement of vascular NO by supplementation with L-arginine and other nutrients has been shown to have clinical benefits in patients with angina secondary to atherosclerotic coronary artery disease (CAD). However, the amounts and combinations of these nutrients required to achieve a clinical effect make traditional delivery by capsules and pills less suitable than alternative delivery methods such as a specially formulated nutrition bar. METHODS: Thirty-six stable outpatients with CAD and class II or III angina participated in a randomized, double-blind, placebo-controlled, crossover trial with two treatment periods each of two weeks' duration (two active bars or two placebo bars per day). Flow-mediated brachial artery dilation was measured by ultrasound. Electrocardiographic measures of ischemia, exercise capacity and angina onset time were measured by treadmill exercise testing and by Holter monitor during routine daily activities. Quality of life was assessed by SF-36 and Seattle Angina Questionnaires and by diary. RESULTS: The medical food improved flow-mediated vasodilation (from 5.5 +/- 4.5 to 8.0 +/- 4.9, p = 0.004), treadmill exercise time (by 20% over placebo, p = 0.05) and quality-of-life scores (SF-36 summary score; 68 +/- 13 vs. 63 +/- 21 after placebo, p = 0.04, Seattle Angina Questionnaire summary score; 67 +/- 10 vs. 62 +/- 18, p = 0.04) without affecting electrocardiographic manifestations of ischemia or angina onset time. CONCLUSIONS: These findings reveal that this arginine-rich medical food, when used as an adjunct to traditional therapy, improves vascular function, exercise capacity and aspects of quality of life in patients with stable angina.

Adult↗
PubMed2002

Which patients with unstable angina or non-Q-wave myocardial infarction should have immediate cardiac catheterization? A clinical decision rule for predicting who will fail medical therapy.

Unstable angina and non-Q-wave myocardial infarction (MI) are common and costly clinical events, but there is considerable uncertainty about optimal clinical management of these syndromes. We developed a prediction rule to help clinicians determine which patients with unstable angina or non-Q-wave MI are likely to "fail" medical therapy and ultimately require cardiac catheterization within 6 weeks of presentation. Subjects were 733 patients presenting with unstable angina or non-Q-wave MI enrolled in the TIMI IIIB trial and randomized to initial medical management. We developed a prediction rule based on logistic regression analysis of baseline data from history, physical examination, electrocardiogram, and blood studies. The outcome of interest was "failure" of medical therapy, defined as need for coronary catheterization within 42 days. Significant predictors of "failing" medical therapy included ST segment depression >or= .1 mV (odds ratio, OR, = 2.7, 95% confidence interval, CI, 1.8-4.1), accelerated angina in the prior 2 months (OR = 1.8, 95% CI 1.2-2.6), nitrate use in the prior week (OR = 1.6, 95% CI 1.1-2.2), exertional angina in the prior 2 months (OR = 1.6, 95% CI 1.1-2.2), and cardiac troponin I (cTnI) >or= 0.4 ng/mL (OR = 1.4, 95% CI 1.1-1.9). We used these variables to build a risk score by assigning point values based on these ORs. The risk score had a moderate ability to predict which patients would subsequently fail medical therapy and undergo cardiac catheterization (c = 0.682). Out of a total risk score of 13, failure of medical therapy occurred in 86% of patients who had a risk score >or= 8 (n = 111), 78% of patients who had a risk score >or= 6 (n = 240), and 72% of patients who had a risk score >or= 4 (n = 438). At scores of < 2 (n = 88), 40% of patients failed medical therapy. Although the management of unstable angina is in constant evolution, clinicians will always be faced with determining which patients should be managed most invasively. The simple prediction rule we present can be applied to patients with unstable angina or non-Q-wave MI at the time of presentation to predict which patients have a high probability of failing medical therapy. Such a rule may be useful for identifying patients who should be considered for early cardiac catheterization.

Adult↗
PubMed2002

Optimizing ambulatory ECG monitoring of T-wave alternans for arrhythmia risk assessment.

Considerable scientific data support the potential value of T-wave alternans (TWA) as an index of vulnerability to ventricular fibrillation. This chapter summarizes our state of knowledge regarding the use of routine ambulatory ECGs to evaluate TWA and discusses recent methodologic approaches designed to optimize AECG-based TWA analysis for arrhythmia risk stratification. Newer methods, including the nonspectral technique of Modified Moving Average analysis, appear promising in detecting TWA during the changing conditions associated with daily activities. The Modified Moving Average approach does not require specialized electrodes and is not encumbered by the need to achieve target heart rates, as is the case for conventional spectral-based methods. Guidelines are provided for evaluating latent cardiac electrical instability using AECG-based TWA testing. These recent developments make possible the TWA analysis of ambulatory ECGs not only in prospective trials but also in vast stores of archival data.

Arrhythmias, Cardiac↗