Showing papers by "Leslee J. Shaw published in 2009"
TL;DR: It is hypothesize that women experience more adverse outcomes compared with men because obstructive CAD remains the current focus of therapeutic strategies and antianginal and anti-ischemic therapies can improve symptoms, endothelial function, and quality of life.
619 citations
TL;DR: It is concluded that the absence of CAC is associated with a very low risk of future cardiovascular events, with modest incremental value of other diagnostic tests in this very low-risk group.
Abstract: Objectives In this study, we systematically assessed the diagnostic and prognostic value of absence of coronary artery calcification (CAC) in asymptomatic and symptomatic individuals Background Presence of CAC is a well-established marker of coronary plaque burden and is associated with a higher risk of adverse cardiovascular outcomes Absence of CAC has been suggested to be associated with a very low risk of significant coronary artery disease, as well as minimal risk of future events Methods We searched online databases (eg, PubMed and MEDLINE) for original research articles published in English between January 1990 and March 2008 examining the diagnostic and prognostic utility of CAC Results A systematic review of published articles revealed 49 studies that fulfilled our criteria for inclusion These included 13 studies assessing the relationship of CAC with adverse cardiovascular outcomes in 64,873 asymptomatic patients In this cohort, 146 of 25,903 patients without CAC (056%) had a cardiovascular event during a mean follow-up period of 51 months In the 7 studies assessing the prognostic value of CAC in a symptomatic population, 180% of patients without CAC had a cardiovascular event Overall, 18 studies demonstrated that the presence of any CAC had a pooled sensitivity and negative predictive value of 98% and 93%, respectively, for detection of significant coronary artery disease on invasive coronary angiography In 4,870 individuals undergoing myocardial perfusion and CAC testing, in the absence of CAC, only 6% demonstrated any sign of ischemia Finally, 3 studies demonstrated that absence of CAC had a negative predictive value of 99% for ruling out acute coronary syndrome Conclusions On the basis of our review of more than 85,000 patients, we conclude that the absence of CAC is associated with a very low risk of future cardiovascular events, with modest incremental value of other diagnostic tests in this very low-risk group
602 citations
TL;DR: Women with symptoms and signs suggestive of ischemia but without obstructive CAD are at elevated risk for cardiovascular events compared with asymptomatic community-based women.
Abstract: Symptoms of angina in the absence of clinically significant coronary artery disease (CAD) constitute a relatively common clinical scenario in women and remain a challenge for physicians caring for such patients. Until recently, the prognosis of women with signs and symptoms suggestive of myocardial ischemia in the absence of obstructive CAD was thought to be benign,1–3 and such women have been offered little more than reassurance that they do not have heart disease, despite signs and symptoms that have required them to undergo coronary angiography.4 More recently, the notion of its benign nature has been challenged, with evidence showing that women with chest pain in the setting of normal or nonobstructive coronary arteries have a high risk of future cardiac events.5–9 To our knowledge, there have been no prospective studies examining the implications of chest pain in the absence of obstructive CAD in women, relative to a population of asymptomatic women.
Chest pain and other equivalent cardiac symptoms that are suggestive of myocardial ischemia, even in the absence of obstructive CAD, have important functional and economic implications to women and society. A recent retrospective study of men and women with suspected ischemia resulting in referral for angiography showed that women were more often found to have angiographically normal coronary arteries. These same women were 4 times more likely to be readmitted for chest pain or for acute coronary syndrome within the next 180 days.9 Data from the Women’s Ischemia Syndrome Evaluation (WISE) study estimate that, among the approximately 500 000 US women who undergo coronary angiography annually, half will have no obstructive lesions (where obstruction is considered ≥50% narrowing in any coronary artery) in contrast to 7% to 17% of men who undergo angiography.9–13
Given this high rate of nonobstructive coronary angiograms, until recently such women were usually offered little in terms of treatment, despite recurrent symptoms requiring hospitalization, repeated procedures, functional disabilities, and future cardiac events that translate to a heavy economic burden with average lifetime costs estimated to be greater than $750 000.14 Despite being a common clinical scenario with important public health consequences, the prevalence of chest pain in the absence of obstructive CAD has not declined since it was first reported.15–18
We sought to investigate the prognostic implications of cardiac symptoms in women with nonobstructive CAD compared with community-dwelling women without cardiac symptoms. We investigated this prospectively in a cohort of symptomatic women referred for clinically indicated coronary angiography and compared them with a cohort of asymptomatic women free of known CAD at baseline.
488 citations
TL;DR: In appropriately selected asymptomatic patients, the absence of CAC predicts excellent survival with 10-year event rates of approximately 1%, which might be used as a rationale to emphasize lifestyle therapies rather than pharmacotherapy and to forgo repeated imaging studies.
Abstract: Objectives We sought to quantify the mortality rates associated with absent and low positive (CAC 1 to 10) coronary artery calcium (CAC). Background There is increasing interest in the absence of CAC as a “negative” cardiovascular risk factor. However, published event rates for individuals with no CAC vary, likely owing to differences in baseline risk, follow-up period, and outcome ascertainment. The prognostic significance of low CAC (CAC 1 to 10) is not well described. Methods Annualized all-cause mortality rates were assessed in 44,052 consecutive asymptomatic patients referred for CAC testing. Mean follow-up of the cohort was 5.6 ± 2.6 years (range 1 to 13 years). Results A total of 19,898 patients (45%) had no CAC on screening electron beam tomography, whereas 5,388 (12%) had low levels of CAC (CAC 1 to 10), and 18,766 (43%) had CAC >10. There were 104 deaths in those with no CAC (0.52%), 58 deaths in those with CAC 1 to 10 (1.06%), and 739 deaths in those with CAC >10 (3.96%). Annualized all-cause mortality rates for CAC = 0, CAC 1 to 10, and CAC >10 were 0.87, 1.92, and 7.48 deaths/1,000 person-years, respectively. The hazard ratio (HR) for all-cause mortality among CAC 1 to 10 versus CAC = 0 after adjustment for traditional risk factors was 1.99 (95% confidence interval [CI]: 1.44 to 2.75). Smoking (HR: 3.97, 95% CI: 2.75 to 5.41) and diabetes mellitus (HR: 3.36, 95% CI: 2.09 to 5.41) were associated with few events observed in CAC = 0 group. Conclusions In appropriately selected asymptomatic patients, the absence of CAC predicts excellent survival with 10-year event rates of approximately 1%. A finding of 0 CAC might be used as a rationale to emphasize lifestyle therapies rather than pharmacotherapy and to forgo repeated imaging studies. Individuals with low CAC score (CAC 1 to 10) are at increased risk above individuals with a 0 score and could be considered a distinct risk group by physicians and investigators.
417 citations
TL;DR: In stable patients having serial SPECT MPI, quantification is more reproducible than visual for magnitude of perfusion abnormality, suggesting its superiority for use in randomized clinical trials and monitoring the effects of therapy in an individual patient.
139 citations
TL;DR: CAC, but not TAC, is strongly related to CHD and CVD events, and TAC does not further improve event prediction over CAC.
Abstract: Objectives This study compared the ability of coronary artery calcium (CAC) and thoracic aortic calcium (TAC) to predict coronary heart disease (CHD) and cardiovascular disease (CVD) events. Background Coronary artery calcium has been shown to strongly predict CHD and CVD events, but it is unknown whether TAC, also measured within a single cardiac computed tomography (CT) scan, is of further value in predicting events. Methods A total of 2,303 asymptomatic adults (mean age 55.7 years, 38% female) with CT scans were followed up for 4.4 years for CHD (myocardial infarction, cardiac death, or late revascularizations) and CVD (CHD plus stroke). Cox regression, adjusted for Framingham risk score (FRS), examined the relation of Agatston CAC and TAC categories, and log-transformed CAC and TAC with the incidence of CHD and CVD events and receiver-operator characteristic (ROC) curves tested whether TAC improved prediction of events over CAC and FRS. Results A total of 53% of subjects had Agatston CAC scores of 0; 8% 1 to 9; 19% 10 to 99; 12% 100 to 399; and 8% ≥400. For TAC, proportions were 69%, 5%, 12%, 8%, and 7%, respectively; 41 subjects (1.8%) experienced CHD and 47 (2.0%) CVD events. The FRS-adjusted hazard ratios (HR) across increasing CAC groups (relative to Conclusions This study found that CAC, but not TAC, is strongly related to CHD and CVD events. Moreover, TAC does not further improve event prediction over CAC.
110 citations
TL;DR: Development of regional training centers of excellence can guide utilization of nuclear cardiology through the application of guideline- and appropriateness-driven testing, training, continuing education, and quality assurance programs aiding developing nations to confront the epidemics of CVD.
66 citations
TL;DR: This study suggests persons with both increased levels of both MPO and CAC are at an increased risk of CVD events.
Abstract: Objectives We evaluated whether myeloperoxidase (MPO) predicts future cardiovascular disease (CVD) events in asymptomatic adults and whether subclinical atherosclerosis may affect this relation. Background Myeloperoxidase is a leukocyte-derived enzyme-generating reactive oxidant species that has been shown to predict risk of CVD in selected populations. Methods We studied 1,302 asymptomatic adults (mean age 59 years, 47% women) without known CVD who were followed for 3.8 years. We measured MPO by the use of immunoassay. Coronary artery calcium (CAC), a measure of subclinical atherosclerosis, was measured by computed tomography with the Agatston score categorized as none/minimal (0 to 9), mild (10 to 99), and moderate/significant (≥100). Cox regression, adjusted for age, sex, and other risk factors, examined the relation of CAC and/or MPO with incident CVD events. Results Persons with MPO levels at or above compared with below the median (257 pM) were more likely (p Conclusions Our study suggests persons with both increased levels of both MPO and CAC are at an increased risk of CVD events. Imaging of subclinical atherosclerosis combined with assessment of biomarkers of plaque vulnerability may help improve CVD risk stratification.
65 citations
TL;DR: Compared with an initial management strategy of OMT alone, addition of PCI did not decrease the incidence of major cardiovascular outcomes including cardiac death or the composite of cardiac death/MI/ACS/stroke in patients with stable coronary artery disease.
Abstract: The main results of the Clinical Outcomes Utilizing Revascularization and Aggressive DruG Evaluation (COURAGE) trial revealed no significant differences in the primary end point of all-cause mortality or nonfatal myocardial infarction [MI] or major secondary end points (composites of death/MI/stroke; hospitalization for acute coronary syndromes [ACSs]) during a median 4.6-year follow-up in 2,287 patients with stable coronary artery disease randomized to optimal medical therapy (OMT) with or without percutaneous coronary intervention (PCI). We sought to assess the impact of PCI when added to OMT on major prespecified tertiary cardiovascular outcomes (time to first event), namely cardiac death and composites of cardiac death/MI, cardiac death/MI/hospitalization for ACS, cardiac death/MI/stroke, MI/stroke, or cardiac death/MI/ACS/stroke, during study follow-up. There were no significant differences between treatment arms for the composite of cardiac death or MI (15% in PCI + OMT group vs 14.2% in OMT group, hazard ratio 1.07, 95% confidence interval 0.86 to 1.33, p = 0.62) or in any of the major prespecified composite cardiovascular events during long-term follow-up, even after excluding periprocedural MI as an outcome of interest. Overall, cause-specific cardiovascular outcomes paralleled closely the primary and secondary composite outcomes of the trial as a whole. In conclusion, compared with an initial management strategy of OMT alone, addition of PCI did not decrease the incidence of major cardiovascular outcomes including cardiac death or the composite of cardiac death/MI/ACS/stroke in patients with stable coronary artery disease.
63 citations
TL;DR: Data from the COURAGE trial support adherence to American College of Cardiology/American Heart Association clinical practice guidelines that advocate OMT as an appropriate initial management strategy, regardless of age.
60 citations
TL;DR: Risk stratification for patients with acute myocardial infarction should incorporate an assessment of renal function with estimated GFR values rather than absolute serum creatinine levels as done in the currently utilized risk scoring algorithms.
Abstract: Age and chronic kidney disease are major risk factors for poor cardiovascular outcome; however, renal function is often estimated on the basis of serum creatinine levels, and advanced renal impairment may be hidden behind near normal creatinine levels We assessed the impact of estimated glomerular filtration rate (GFR) on in-hospital mortality in young (
TL;DR: CAC scanning appears to foster efficient selective testing patterns among asymptomatic individuals at risk for CVD, and is associated with a marked differential in downstream frequency of medical tests and costs.
TL;DR: This study establishes ECG-gated MDCT reference values for right-sided great vessel dimensions derived from a healthy population of individuals free of cardiovascular disease, hypertension, and obesity.
University of British Columbia1, University of Michigan2, Vanderbilt University3, Hartford Hospital4, Université de Montréal5, University of Western Ontario6, New York University7, Emory University8, University of California, Los Angeles9, Geisinger Medical Center10, University of Missouri–Kansas City11, University of Calgary12, Saint Louis University13, University of Texas Health Science Center at San Antonio14, Christiana Care Health System15, McMaster University16, University at Albany, SUNY17
TL;DR: PCI success and completeness of revascularization did not differ significantly by health care system or gender and were similar to contemporary practice.
Abstract: Background— COURAGE compared outcomes in stable coronary patients randomized to optimal medical therapy plus percutaneous coronary intervention (PCI) versus optimal medical therapy alone. Methods and Results— Angiographic data were analyzed by treatment arm, health care system (Veterans Administration, US non–Veterans Administration, Canada), and gender. Veterans Administration patients had higher prevalence of coronary artery bypass graft surgery and left ventricular ejection fraction ≤50%. Men had worse diameter stenosis of the most severe lesion, higher prevalence of prior coronary artery bypass graft surgery, lower left ventricular ejection fraction, and more 3-vessel disease that included a proximal left anterior descending lesion (P<0.0001 for all comparisons versus women). Failure to cross rate (3%) and visual angiographic success of stent procedures (97%) were similar to contemporary practice in the National Cardiovascular Data Registry. Quantitative angiographic PCI success was 93% (residual lesi...
Vanderbilt University1, University of Missouri–Kansas City2, University of British Columbia3, Veterans Health Administration4, University of Michigan5, London Health Sciences Centre6, Hartford Hospital7, Cedars-Sinai Medical Center8, Emory University9, Saint Louis University10, McMaster University11, Murphy Oil12, Christiana Care Health System13, State University of New York System14
TL;DR: An initial strategy of OMT alone for high-risk patients in the COURAGE trial did not result in increased death or myocardial infarction at 4.6 years or worse angina at 1 year, but it was associated with a high rate of crossover to revascularization.
Abstract: We explored the safety and quality-of-life consequences of treating patients with stable coronary disease and high-risk features initially with optimal medical therapy (OMT) alone compared to OMT plus percutaneous coronary intervention. This was a post hoc analysis of Clinical Outcomes Utilizing Revascularization and Aggressive DruG Evaluation (COURAGE) trial patients. We defined high risk as the onset of Canadian Cardiovascular Society class III angina within 2 months or stabilized acute coronary syndrome within 2 weeks of enrollment. The primary end point was death or myocardial infarction after 4.6 years. Of the 2,287 patients enrolled in the COURAGE trial, 264 (12%) were high risk and had a relative risk of 1.56 for death or myocardial infarction (p = 0.0008) compared to those with non-high-risk features. A total of 35 primary events occurred in the OMT group and 32 in the percutaneous coronary intervention plus OMT group (hazard ratio 1.11, 95% confidence interval 0.69 to 1.79; p = 0.68). No significant difference was found in the prevalence of angina between the 2 groups at 1 year. During the first year of follow-up, 30% of the OMT patients crossed over to the revascularization group. In conclusion, an initial strategy of OMT alone for high-risk patients in the COURAGE trial did not result in increased death or myocardial infarction at 4.6 years or worse angina at 1 year, but it was associated with a high rate of crossover to revascularization.
TL;DR: It is likely that the use of CCTA will continue to expand, particularly for patients with more atypical symptoms and patients with a lower likelihood of CAD.
Abstract: This review highlights and compares risk assessment, predictive accuracy, and economic outcomes for 3 commonly applied cardiac imaging procedures: stress myocardial perfusion SPECT or PET and coronary CT angiography (CCTA). This review highlights an expansive evidence base for stress myocardial perfusion imaging and reveals a decided advantage for higher-risk patients, notably those who have established coronary artery disease (CAD). It is likely that the use of CCTA will continue to expand, particularly for patients with more atypical symptoms and patients with a lower likelihood of CAD. Despite a high level of evidence, comparative research is not available across modalities that could definitively drive utilization of cardiac imaging modalities.
TL;DR: Sixty-four-detector-row coronary computed tomographic angiography identifies patients more likely to have STD and higher risk DTS, while providing incremental diagnostic yield for the detection of obstructive CAD beyond ETT.
Abstract: Sixty-four-detector-row coronary computed tomographic angiography (CCTA) has been proposed for the evaluation of low- to intermediate-risk patients with suspected coronary artery disease (CAD). Historically, exercise treadmill testing (ETT) measures of ST-segment depression (STD) and the Duke treadmill score (DTS) have been used to evaluate myocardial ischemia and functional capacity. The relation of plaque characteristics on CCTA to STD and DTS is unknown. In this study, 156 low- to intermediate-risk patients without known CAD who underwent ETT and CCTA were evaluated. By ETT, 22% (n = 35) had STD and 27% (n = 42) had abnormal DTS. On CCTA, 21% (n = 33) had obstructive CAD (≥70% stenosis) and 49% (n = 77) had nonobstructive CAD (
TL;DR: B-type natriuretic peptide and CAC are independently predictive of CV events in patients with hypertension and in elderly patients beyond the Framingham risk score, in conclusion.
Abstract: B-type natriuretic peptide (BNP) has prognostic implications in patients with acute and chronic cardiac symptoms. Its prognostic role in asymptomatic patients with evidence of subclinical disease remains unclear. The population of this study included 2,458 asymptomatic adults (47% women) with an average Framingham risk score of 8.8 ± 7% who underwent computed tomographic evaluation of coronary artery calcium (CAC). BNP levels were measured using the Triage CardioProfilER panel method. Cox proportional-hazards models were used to estimate time to a cardiovascular (CV) event (n = 84; 16 deaths, 12 myocardial infarctions, 8 cerebrovascular accidents or transient ischemic attacks, and 48 diagnoses of incident symptomatic coronary disease). Relative risk was calculated. The median follow-up time was 3.9 years (25th and 75th percentiles 2.9 and 4.0). The relative hazard for a CV event ranged from 2.2 to 7.5 for BNP values of 40 to 99.9 and ≥100 pg/ml (p
TL;DR: In this article, the optimal non-invasive test for evaluation of ischemic heart disease in women is unknown, although current guidelines support the choice of the exercise tolerance test (ETT) as a first line test for women with a normal baseline ECG and adequate exercise capabilities.
TL;DR: The relative value of anatomical versus functional imaging and their complementary role in different clinical scenarios are reviewed.
TL;DR: Diabetes is a major coronary artery disease (CAD) risk factor which is increasing in prevalence, and commonly associated with asymptomatic CAD, and secondary prevention of CAD is recommended for all adult diabetic patients.
TL;DR: The Detection of Ischemia in Diabetics (DIAD) study represents the only prospective study designed to examine the nonselective application of stress SPECT MPI in asymptomatic diabetic patients.
TL;DR: Among women with suspected myocardial ischemia, the combined protective health effects of self-reported high exercise capacity and a negative smoking history remained significant after controlling for preexisting CAD severity and other established risk factors.
Abstract: Background: Although extensive research has been conducted on both smoking and low exercise capacity alone, few studies have examined the joint impact or interaction of these two risk fact...
Journal Article•
Journal Article•
Journal Article•
01 Jan 2009
TL;DR: In order to understand plaque formation and plaque composition it is necessary to have a knowledge of the normal histology.
Abstract: In order to understand plaque formation and plaque composition it is necessary to have a knowledge of the normal histology. In general, arteries contain three concentric layers: the intima, media and adventitia (Fig. 4.1.1). The intima consists of a single layer of endothelial cells with only a small amount of underlying connective tissue. The intima is separated from the media by a thick layer of elastic fibers called the intern elastic lamina. The media is mostly composed of smooth muscle cells. Approximately the inner half of the smooth muscle cell layer receives its nutrients from the lumen via diffusion. The outer half, however, needs nourishment from blood vessels themselves, called the vasa vasorum, which course into the media from the adventitia. Between the media and the adventitia lies the external elastic lamina. The adventitia consists of connective tissue, nerve fibers and the vasa vasorum.
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Fig. 4.1.1.
Micrograph showing a normal muscular artery with a single layer thick intima (I), the media (M, arrows mark the borders) and adventitia (A)
01 Jan 2009
TL;DR: In this chapter, the current evidence surrounding some of the most popular techniques to diagnose coronary artery disease as well as some emerging techniques for detection of subclinical atherosclerosis are discussed.
Abstract: The growing incidence of diabetes mellitus and the continuing epidemic of cardiovascular disease associated with this ailment have induced numerous investigators to seek evidence of pre-clinical disease besides trying to diagnose advanced stages of disease. Although many of the techniques used in the general population to diagnose obstructive coronary artery disease have proven of value, it appears that the overall diagnostic accuracy of these methodologies may be lower in diabetic patients. Furthermore, in the presence of normal results the short-term event rate is considerably higher in a diabetic patient than in the general population. In this chapter, we discuss the current evidence surrounding some of the most popular techniques to diagnose coronary artery disease as well as some emerging techniques for detection of subclinical atherosclerosis.
01 Jan 2009
TL;DR: Cardiac imaging findings from MESA with respect to racial/ethnic differences reveal that the incidence and prevalence of CAD differ among some racial/ ethnic groups in the United States.
Abstract: Over the last decade, the increased research focus on cardiovascular imaging for the identification of patients at risk for and with significant coronary artery disease (CAD) has augmented clinician awareness and ability to properly risk stratify and categorize patients. Cardiac imaging has now become a technique not only for assessing patients with established CAD but also for the identification of patients with subclinical CAD who are at risk for ischemic heart disease and cardiac events of death and myocardial infarction. The Multi-Ethnic Study of Atherosclerosis (MESA) is a 10-year longitudinal study supported by the National Heart, Lung, and Blood Institute with the goals of identifying and quantifying risk factors for subclinical atherosclerosis, and for transition in patients from subclinical disease to clinically apparent events. Cardiac imaging findings from MESA with respect to racial/ethnic differences reveal that the incidence and prevalence of CAD differ among some racial/ethnic groups in the United States. The large number of patients affected by CAD has driven the development of effective, non-invasive methods to identify and risk-stratify patients with and at risk for CAD. When patients are properly identified, the appropriate treatment strategies can be applied to individual patients to prevent future events, such as death or myocardial infarction. Historically, exercise treadmill testing (ETT) with electrocardiogram (ECG) monitoring was the initial test applied to patients suspected of having CAD. Today, non-invasive cardiovascular testing with imaging has become the gold standard for the diagnostic and prognostic assessment of patients with suspected or known cardiovascular disease.