Independent association of subclinical coronary artery disease and emphysema in HIV-infected patients.

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) and coronary artery disease are inflammatory states with a significant clinical impact. The relationship between them has not been investigated in patients with HIV infection. We assessed the presence of subclinical emphysema and coronary artery disease using chest computed tomography (CT) imaging in a cohort of HIV-infected patients receiving antiretroviral therapy. METHODS: Gated chest CT scans were performed in 1446 consecutive patients to assess the presence and severity of coronary artery calcium (CAC) (classified as a score of 0, 1-100 or > 100) and emphysema (classified using a visual semiquantitative scale: 0, absent; 1-4, mild to moderate; > 4, severe). Univariable and multivariable logistic regression analyses were performed to identify factors independently associated with CAC and emphysema. RESULTS: The emphysema score was significantly higher in patients with CAC scores of 1-100 and > 100 compared with those with a CAC score of 0. After adjustments for age, sex, smoking status, pack-years of smoking, visceral adiposity and duration of HIV infection, the presence of any emphysema was significantly associated with a CAC score > 0 [odds ratio (OR) 1.43; 95% confidence interval (CI) 1.08-1.88; P = 0.012]. The association persisted after adjustment for the Framingham risk score (OR 1.52; 95% CI 1.16-1.99; P = 0.002). There was a dose-dependent effect in the association between emphysema score and CAC score. CONCLUSIONS: In this cross-sectional study of HIV-infected patients, there was an independent association between emphysema and CAC, after adjustment for traditional cardiovascular risk factors, suggesting a common pathogenesis of these chronic inflammatory conditions in a chronic inflammatory disease such as HIV infection.

GlycA, a novel marker of inflammation, is elevated in systemic lupus erythematosus.

BACKGROUND: GlycA is a novel marker of systemic inflammation detected by nuclear magnetic resonance (NMR) spectroscopy. In the general population, GlycA is correlated with inflammatory markers such as C-reactive protein (CRP) and associated with coronary heart disease and diabetes. The utility of GlycA in patients with systemic lupus erythematosus (SLE) has not been defined. Therefore, we tested the hypothesis that GlycA concentrations are elevated in patients with SLE and associated with other markers of inflammation and coronary atherosclerosis. METHODS: We compared concentrations of GlycA, detected by NMR, in 116 patients with SLE and 84 control subjects frequency-matched for age, sex, and race. SLE disease activity index (SLEDAI) and the SLE Collaborating Clinics damage index (SLICC) were calculated. Acute phase reactants, a panel of cytokines, and a lipid panel were measured. Electron beam computer tomography (EBCT) was used to quantify coronary artery calcification, a measure of coronary artery atherosclerosis. RESULTS: Patients with SLE had higher concentrations of GlycA (398 (350-445)) than control subjects (339 (299-391)) µmol/L, p < 0.001. In patients with SLE, concentrations of GlycA were significantly associated with sedimentation rate (rho = 0.43), C-reactive protein (rho = 0.59), e-selectin (rho = 0.28), intracellular adhesion molecule-1 (rho = 0.30), triglycerides (rho = 0.45), all p < 0.0023 to account for multiple comparisons, but not with creatinine, SLEDAI, SLICC, or coronary calcium scores. CONCLUSIONS: Concentrations of GlycA are higher in patients with SLE than control subjects and associated with markers of inflammation but not with SLE disease activity or chronicity scores or coronary artery calcification.

Genetic variation and coronary atherosclerosis in patients with systemic lupus erythematosus.

Coronary artery disease is the major cause of mortality in patients with systemic lupus erythematosus (SLE). Increased cardiovascular risk in SLE is not explained by traditional risk factors. We examined the hypothesis that genetic variation contributes to the presence of coronary atherosclerosis in patients with SLE. The genotypes of single-nucleotide polymorphisms (SNP) in 152 candidate genes linked with autoimmune or cardiovascular risk were determined in 125 patients with SLE. Coronary artery calcium (CAC), a measure of coronary atherosclerosis, was detected in 32 patients (26%) by electron-beam computed tomography. Polymorphism in 20 of the candidate genes (ADAM33, ADIPOQ, CCL5, CCR7, CDKN2B, CSF1, IL4, IL12A, IL23R, INS, IRF5, MIF, MS4A1, PTGS1, PTPN22, RETN, SELE, TNFSF4, TNFRSF11B, and VCAM1) were nominally associated with the presence of CAC (p-values = 0.001-0.047 after adjustment for age, sex and race). Some of these are known susceptibility genes for SLE and others have been implicated in cardiovascular disease in other populations. No association withstood false discovery rate adjustment. Replication studies in additional cohorts of patients with SLE may be informative.

Free fatty acids are associated with metabolic syndrome and insulin resistance but not inflammation in systemic lupus erythematosus.

Free fatty acids (FFAs) are implicated in the pathogenesis of insulin resistance and atherosclerosis. Inflammatory cytokines promote lipolysis and increase FFAs, a cause of endothelial dysfunction and increased atherosclerosis risk. We hypothesized that increased inflammation is associated with increased FFAs, resulting in insulin resistance and atherosclerosis in patients with systemic lupus erythematosus (SLE). We measured clinical variables, serum FFAs, homeostasis model assessment for insulin resistance (HOMA), inflammatory cytokines, markers of endothelial activation, cholesterol concentrations and coronary artery calcium in 156 patients with SLE and 90 controls. We compared FFAs in patients with SLE and controls using Wilcoxon rank sum tests and further tested for the independent association between FFAs and disease status with adjustment for age, race and sex using multivariable regression models. We assessed the relationship between FFAs and continuous variables of interest using Spearman correlation and multivariable regression analysis. Levels of FFAs were higher in patients with SLE than controls (0.55 mmol/l (0.37-0.71) vs 0.44 mmol/l (0.32-0.60), P = 0.02). Levels of FFAs remained significantly higher among patients with SLE after adjustment for age, race and sex (P = 0.03) but not after further adjustment for body mass index (P = 0.13). FFA levels did not differ according to the usage of current immunosuppressive medications in univariate and adjusted analysis (all P > 0.05). Among patients with SLE, concentrations of FFAs were higher among those with metabolic syndrome compared to those without (0.66 mmol/l (0.46-0.81) vs 0.52 mmol/l (0.35-0.66), P < 0.001). FFAs were positively correlated with insulin resistance (HOMA) (rho = 0.23, P = 0.004, P adjusted = 0.006) and triglyceride levels (rho = 0.22, P = 0.01, P adjusted = 0.004). FFAs were not associated with inflammatory cytokines (IL-6, TNF-α) (all P > 0.05) but were positively associated with levels of E-selectin (rho = 0.33, P = < 0.001, P adjusted = 0.001) and ICAM-1 (rho = 0.35, P < 0.001, P adjusted = 0.001). FFAs were correlated with coronary artery calcium score (rho = 0.20, P = 0.01) but this was attenuated after adjustment for age, race and sex (P = 0.33). From our study we concluded that FFAs are elevated in patients with SLE, particularly those with metabolic syndrome. FFAs in patients with SLE are not associated with markers of generalized inflammation but are associated with insulin resistance and markers of endothelial activation.

Cystatin C is associated with inflammation but not atherosclerosis in systemic lupus erythematosus.

BACKGROUND: Even mild renal impairment is associated with increased atherosclerosis and cardiovascular mortality. Cystatin C, a novel measure of renal function, is more sensitive than conventional creatinine-based measures for the detection of subtle renal impairment. Increased cystatin concentrations are also associated with cardiovascular risk, independently of conventional measures of renal function. This study examined the hypothesis that cystatin C is elevated in systemic lupus erythematosus (SLE) and is associated with coronary atherosclerosis. METHODS: Serum cystatin C, creatinine, tumor necrosis factor (TNF)-α, interleukin (IL)-6, coronary artery calcium score (CACS), Framingham risk score (FRS), Modified Diet in Renal Disease estimated glomerular filtration rate (MDRD-eGFR), and other clinical parameters were measured in 118 patients with SLE and 83 control subjects. The independent association between concentrations of cystatin C and SLE was evaluated using multivariable linear regression models, and the relationship between renal measures and coronary calcium was assessed with multivariable proportional odds logistic regression models. RESULTS: Cystatin C, but not other measures of renal function, was significantly higher in patients with SLE than in controls (1.09 [interquartile range, IQR: 0.85-1.28] mg/l vs. 0.89 [IQR: 0.76-0.99] mg/l; p < 0.001 after adjustment for age, race, sex and MDRD-eGFR). Cystatin C was significantly associated with SLICC (p = 0.04), erythrocyte sedimentation rate (ESR) (p = 0.02), TNF-α (p = 0.008) and IL-6 (p = 0.01) after adjustment for age, race, and sex. Cystatin C was not significantly correlated with coronary calcium score in SLE (rho=0.096, p = 0.31) and the association remained non-significant after adjustment for age, race, sex, and Framingham risk score (p = 0.99). CONCLUSIONS: Cystatin C was higher in patients with SLE than in control subjects even after adjustment for conventional measures of renal function. Cystatin C was significantly correlated with several markers of inflammation in SLE but was not associated with coronary atherosclerosis. Subtle renal dysfunction does not appear to be directly associated with accelerated atherosclerosis in SLE.

Novel cardiovascular risk prediction models in patients with systemic lupus erythematosus.

Women with systemic lupus erythematosus (SLE) have increased risk for coronary heart disease (CHD) which is underestimated by the Framingham risk score (FRS). We hypothesized that new risk scores that include inflammation or vascular age in the risk calculation would better identify women with SLE at risk for CHD, particularly in those with subclinical coronary atherosclerosis. We calculated the FRS and Reynolds risk score (RRS) in 121 women with SLE and 65 age-matched female controls; coronary age-modified risk scores (camFRS, camRRS) were calculated using coronary age derived from the coronary artery calcium (CAC) score. Risk scores were compared in SLE and controls, and in SLE patients with and without CAC. Although CAC was present in 21 SLE patients (17%) and four controls (6%) (p = 0.033); the FRS, camFRS, RRS, and camRRS, did not differ significantly among SLE and controls (p > 0.05), but were all significantly higher in SLE patients with CAC compared with those without (p < 0.001 for all). The camFRS (8%, p = 0.016) but not camRRS (5%, p = 0.221) assigned significantly more SLE patients to a category of ≥ 10% risk than conventional FRS (1%) and RRS (2%). The RRS was of limited use but coronary age may improve CHD risk prediction in SLE.

Identification of patients at increased risk of first unheralded acute myocardial infarction by electron-beam computed tomography.

BACKGROUND: There is a clear relationship between absolute calcium scores (CS) and severity of coronary artery disease. However, hard coronary events have been shown to occur across all ranges of CS. METHODS AND RESULTS: We conducted 2 analyses: in group A, 172 patients underwent electron-beam CT (EBCT) imaging within 60 days of suffering an unheralded myocardial infarction. In group B, 632 patients screened by EBCT were followed up for a mean of 32+/-7 months for the development of acute myocardial infarction or cardiac death. The mean patient age and prevalence of coronary calcification were similar in the 2 groups (53+/-8 versus 52+/-9 years and 96% each). In group B, the annualized event rate was 0.11% for subjects with CS of 0, 2.1% for CS 1 to 99, 4.1% for CS 100 to 400, and 4.8% for CS >400, and only 7% of the patients had CS >400. However, mild, moderate, and extensive absolute CSs were distributed similarly between patients with events in both groups (34%, 35%, and 27%, respectively, in group A and 44%, 30%, and 22% in group B). In contrast, the majority of events in both groups occurred in patients with CS >75th percentile (70% in each group). CONCLUSIONS: Coronary calcium is present in most patients who suffer acute coronary events. Although the event rate is greater for patients with high absolute CSs, few patients have this degree of calcification on a screening EBCT. Conversely, the majority of events occur in individuals with high CS percentiles. Hence, CS percentiles constitute a more effective screening method to stratify individuals at risk.

Comparison of technetium-99m tetrofosmin and thallium-201 single-photon emission computed tomographic imaging for detection of myocardial perfusion defects in patients with coronary artery disease.

OBJECTIVES: We compared dipyridamole technetium-99m (Tc-99m) tetrofosmin and thallium-201 (Tl-201) single-photon emission computed tomographic (SPECT) imaging with respect to the detection rate of perfusion abnormalities in 26 patients with angiographic coronary artery disease (CAD). BACKGROUND: Experimental studies have shown that myocardial extraction of Tc-99m tetrofosmin is lower than that of Tl-201 at high flow rates, resulting in less severe defects with vasodilator stress. It is uncertain whether this results in a lower sensitivity than Tl-201 for detecting coronary stenoses with vasodilator stress in patients. METHODS: Twenty-six patients with CAD underwent both dipyridamole Tl-201 and Tc-99m tetrofosmin SPECT. Tomographic images were scored for initial defects and the presence of reversibility. Defect magnitude was computer quantitated. RESULTS: Of the 26 patients, 25 had defects on both Tl-201 and Tc-99m tetrofosmin SPECT images. Of 340 segments analyzed, 102 had defects by Tl-201 and 92 by Tc-99m tetrofosmin (p = NS). Whereas Tl-201 detected 27 fixed defects in 12 patients, Tc-99m tetrofosmin identified 37 fixed defects in 14 patients (p = NS). In contrast, Tl-201 identified more reversible and partially reversible defects than did Tc-99m tetrofosmin (89 vs. 55, p = 0.002). The average defect magnitude (percent normal) was similar for defects concordantly graded as fixed (38 +/- 3.0% for Tl-201 vs. 42 +/- 4% [mean +/- SEM] for Tc-99m tetrofosmin, p = NS). The average defect magnitude for defects concordantly graded as completely reversible was significantly more severe on Tl-201 than on Tc-99m tetrofosmin (49 +/- 3% vs. 58 +/- 3%) SPECT images. A significantly greater defect magnitude for Tl-201 was also found for defects concordantly classified as partly reversible (30 +/- 4% for Tl-201 vs. 45 +/- 5% for Tc-99m tetrofosmin). CONCLUSIONS: With dipyridamole stress, 1) at least one defect was seen on both Tl-201 and Tc-99m tetrofosmin SPECT images; 2) Tc-99m tetrofosmin SPECT identified fewer reversible defects than did Tl-201, but showed a similar number of fixed defects; 3) the magnitude of reversible defects seen on Tc-99m tetrofosmin images was less, whereas fixed defects were similar for both tracers; 4) reversible defects seen on Tl-201 and not on Tc-99m tetrofosmin SPECT images were predominantly regions perfused by mild coronary stenoses.

The use of electron-beam computed tomography as a tool for primary prevention.

Coronary artery disease (CAD) is the most common cause of death in the United States, and most acute CAD events occur unexpectedly in patients unaware of their condition. Consequently, attention has recently focused on the development of new technologies for the early detection of CAD, such as electron-beam computed tomography (EBCT). With EBCT imaging, the coronary artery tree is visualized noninvasively and vascular calcification, a marker of atherosclerotic disease, is easily detected and its extent quantified. Current research suggests that the presence of coronary artery calcification on a screening EBCT image provides relevant prognostic information for the development of future coronary events. Furthermore, preliminary evidence suggests that the use of EBCT to observe the progression of disease, as demonstrated by changes in the coronary calcium burden on sequential studies, is a viable and exciting new application. The Beyond Endorsed Lipid Lowering with EBCT Scanning (BELLES) trial will use EBCT to compare the effects of 12 months of treatment with aggressive or moderate statin therapy on the progression of coronary atherosclerosis.

Coronary calcium on electron beam tomography imaging as a surrogate marker of coronary artery disease.

Although currently recognized risk factors for coronary artery disease are helpful to predict the development of atherosclerosis, their ability to identify individual patients at risk of events is limited. Therefore, surrogate markers are being investigated to identify disease in its early phases in an attempt to decrease cardiovascular morbidity and mortality. Coronary artery calcification is a useful surrogate marker of coronary artery disease, and it can be visualized and measured noninvasively by means of electron beam tomography (EBT) imaging. Atherosclerosis starts to infiltrate the arterial intima layer much before luminal stenosis develops. Calcium is present in the large majority of mature atherosclerotic plaques, although, in rare cases, it may be absent. Recent research indicates that in selected patient subsets, coronary calcium may add incremental prognostic value to conventional risk factors for coronary artery disease and should therefore be used in association with such factors. EBT imaging for detection of arterial calcification is best employed in asymptomatic individuals at intermediate risk of coronary artery disease, symptomatic patients at low risk of coronary artery disease, and to track disease progression.

Electron-beam computed tomography: a Bayesian approach to risk assessment.

The epidemic of coronary artery disease continues to affect a large number of individuals who often experience sudden and unexpected events. This underscores the need to develop more effective programs to detect silent atherosclerosis, with the ultimate goal of preventing coronary events. The use of conventional risk factors is helpful in assessing the median risk of a population, but it is often unsatisfactory in estimating the actual risk of an individual patient. As a consequence, newer imaging modalities are being developed to detect atherosclerosis in its early developmental phases. Technologies such as electron-beam computed tomography (EBCT) may render risk stratification more accurate if used in the appropriate patient populations and with the right diagnostic approach. Several studies have already demonstrated the power of coronary calcification as a strong predictor of future cardiovascular events. Nonetheless, the medical literature is currently pervaded by an animated debate, as some investigators still have concerns about the effectiveness of a preventive approach driven by technology. The use of Bayesian models to interpret data acquired with EBCT screening may provide practitioners with valuable evidence to aid in their decision making.

Coronary artery disease progression assessed by electron-beam computed tomography.

The ability to observe changes in atherosclerotic plaque burden over time should provide an accurate measure of efficacy for different cardiovascular therapies. Electron-beam computed tomography (EBCT), by quantification of coronary artery calcification, is a noninvasive measure of atherosclerosis burden. This article summarizes data from abstracts and publications related to coronary artery calcium measurement and its use in progression studies. The issues related to interscan variability and reproducibility of this measure are detailed. The limitations of multidetector spiral computed tomography (high radiation dose and poor reproducibility) are also addressed. Several studies of progression using 2 scans, administered > or =1 year apart, demonstrate significant annual progression (22% to 52% per year). All studies demonstrate that therapy with cholesterol-lowering agents slows the atherosclerotic process, and that it may lead to regression of coronary calcium over time. There are 2 small prognostic studies that demonstrate that coronary events predominantly occur in those patients who exhibit significant progression of coronary artery calcium. Large multicenter trials are underway to evaluate the prognostic significance of coronary artery calcium progression. The progression of coronary artery atherosclerosis can be observed noninvasively by monitoring the progression of coronary calcification with EBCT. With annual progression rates of 22% to 52% and a median interscan variability of only 5% to 8%, this technology provides an opportunity to noninvasively monitor patients to assess the clinical efficacy of medical therapies in studies as short as 1 year.

Doppler echocardiographic methods to estimate severity of aortic stenosis.

The continuity equation should be regarded as the Doppler echocardiographic gold standard for estimation of valve area in patients with aortic stenosis, but a quick, easy, and inexpensive screening test may be desirable in an era of medical cost containment. Aortic valve leaflet separation could be used as such a test. In fact, it could prove especially useful in cases where calculations using the continuity equation or the fractional shortening-velocity ratio are problematic.

Detection of coronary vasospasm by posthyperventilation technetium-99m sestamibi single-photon emission computed tomography imaging in patients with coronary artery disease.

Forced hyperventilation is simple, safe to perform, and can be used as a provocative test for coronary vasospasm. This study assesses whether a vasospastic component of angina might be detected in patients with angiographically "nonobstructive" coronary artery disease by posthyperventilation technetium-99m (Tc-99m) sestamibi single-photon emission computed tomography (SPECT) cardiac imaging. Eleven patients with angiographically nonobstructive coronary artery disease underwent Tc-99m sestamibi SPECT imaging at rest and after forced hyperventilation. Vessel diameters were measured by quantitative angiography before and after forced hyperventilation, and posthyperventilation SPECT images were compared with dipyridamole Tc-99m sestamibi stress images. Forced hyperventilation resulted in a 15% reduction in coronary artery diameter in stenotic segments (p <0.01), and a 17% reduction in adjacent nonstenotic segments (p <0.001). Myocardial uptake of Tc-99m sestamibi in segments perfused by vessels with angiographically nonobstructive stenoses was reduced by 24% following forced hyperventilation (p <0.001) compared with only 4% following dipyridamole (p <0.02). These findings suggest that posthyperventilation Tc-99m sestamibi SPECT imaging in patients with angina pectoris and nonobstructive coronary artery disease may be useful in identifying a vasospastic component of angina.

Evaluation of chest pain in patients with low to intermediate pretest probability of coronary artery disease by electron beam computed tomography.

Despite its limited sensitivity and specificity in patients with low to intermediate probability of coronary artery disease (CAD), exercise treadmill testing (ETT) is frequently used as the initial test for investigation of chest pain. Although myocardial perfusion imaging is a significantly more accurate test, its added cost to ETT is considerable. The cost of a non-contrast electron beam computed tomography (EBCT) scan is comparable to that of ETT and the calcium score (CS) correlates closely with the volume of atherosclerotic plaque. Therefore, we tested the hypothesis that EBCT might be an effective and cost-beneficial technique for the identification of angiographically obstructive CAD (> or = 50% stenosis) in patients with low to intermediate pretest probability of disease. We calculated the theoretic cost of attaining a diagnosis of CAD based on a Bayesian model that utilizes published sensitivity and specificity levels for ETT, EBCT, and stress myocardial perfusion imaging. We then submitted a cohort of 207 patients with low to intermediate probability of disease both to EBCT and ETT in random order, and estimated the cost of achieving a correct diagnosis by either route based on the number of expected further tests. An EBCT calcium score of 150 was chosen as a cut-point with a sensitivity of 74% and a specificity of 89% for the presence of obstructive CAD. The theoretic Bayesian model predicted substantial cost savings when EBCT was used as the initial test instead of ETT, with decreasing benefit as the prevalence of disease increased (44% saving at 0% prevalence; 15% saving at 100% prevalence). In the patient cohort, the diagnostic pathway starting with EBCT provided a 45% to 65% cost saving over the ETT pathway. We conclude that in patients with low to intermediate pretest probability of disease, a pathway based on EBCT as the initial test to investigate presence of obstructive CAD provides a substantial cost benefit over a pathway based on ETT. Such cost advantages decrease as the prevalence of disease increases.

Imaging of cardiovascular calcifications with electron beam tomography in hemodialysis patients.

Cardiovascular disease is the leading cause of death in Western countries and it is especially frequent in dialysis patients. Although for a long time physicians have been mainly focused on the severity of luminal coronary stenosis, atherosclerosis starts and expands in the thickness of the arterial wall much before it extends into the vessel lumen. Indeed, most acute coronary events occur in patients with non-obstructive luminal disease. On pathologic examination, patients with end-stage renal disease (ESRD) show larger and more extensively calcified atherosclerotic lesions than non-dialysis patients. Recent evidence shows that even very young dialysis patients show premature calcification of the coronary arteries. Therefore, early detection of atherosclerotic disease with a non-invasive imaging technology, such as electron beam tomography (EBT), may provide an opportunity to modify the disease course and reduce the related event rate.

Is mitral valve prolapse due to cardiac entrapment in the chest Cavity? A CT view.

BACKGROUND: Mitral valve prolapse (MVP) is the most frequently diagnosed valvular disease, but its pathophysiology remains elusive. Its complete absence in 1,734 neonatal echocardiographic studies suggests that this may be an acquired rather than a congenital disease. We observed several patients with distorted cardiac and valvular anatomies on electron beam CT (EBCT) images of the chest who reported symptoms reminiscent of MVP. In these patients, the heart is compressed between the spine and the anterior chest wall and it appears trapped in a chest cavity that is too small for its size. METHODS: We performed EBCT in 66 patients with echocardiographically proven MVP and no clinical pectus excavatum (group A; 80% were women; mean age, 48 +/- 12 years) and in 96 control patients without MVP by echocardiography (group B; 72% were women; mean age, 49 +/- 10 years). EBCT alone was also performed on 200 patients who had reported atypical chest discomfort and palpitations to their physicians (group C) and on 200 asymptomatic patients (group D). The EBCT measurements included the following: anteroposterior chest diameter (APD); the angle formed by the confluence of the mitral valve ring with the interatrial septum (ANGLE); and the contact area between the posterior surface of the anterior chest wall and the myocardium (CA). Entrapment was considered present if the individual patient's measurements varied by more than two SDs compared to measurements made in control subjects (group B). RESULTS: EBCT images demonstrated cardiac entrapment in 82% of group A patients and in 4.2% of group B patients (p < 0.001). ANGLE and CA were significantly larger in MVP patients than in group B patients (114 +/- 9 degrees vs 91 +/- 5 degrees and 6,230 +/- 2,020 mm(2) vs 476 +/- 1,009 mm(2), respectively; p < 0.001 for both comparisons), while APD was significantly smaller (91 +/- 16 mm vs 128 +/- 17 mm, respectively; p < 0.001). The prevalence of entrapment was significantly greater in group C patients than in group D patients (22% vs 6.5%; p < 0. 001). CONCLUSIONS: MVP may be an acquired condition caused by a growth disproportion between the heart and the chest cavity, with distortion of the mitral valve annulus and subsequent leaflet prolapse. A narrow APD, a wide ANGLE, and a large CA characterize this condition. Similar findings are found in a sizable proportion of patients with atypical chest pain symptoms and palpitations.

Symptoms of patients with silent ischemia as detected by thallium stress testing.

This study was undertaken to determine whether patients with silent ischemia (SI) (a positive thallium stress test without chest pain) have nonchest-pain symptoms that might serve as "anginal equivalents." Two hundred ninety-four individuals on completing a stress test were requested to score ten symptoms on a questionnaire (0 absent; 3 severe). Forty-three with a positive test had pains (chest, back, arm, and/or jaw) (no SI), whereas 93 with a positive test did not (SI). Patients with SI and patients without SI did not differ as to age, gender, or clinical features (including presence of diabetes or a history of myocardial infarction), but patients with SI were less likely to report a history of effort-related chest pains. Patients with SI exercised longer and had a higher peak heart rate. Patients were comparable with respect to myocardial ischemia (ST segment depression, double product, thallium lung uptake, and positive thallium scintigrams) and severity of coronary disease. Patients with SI complained less of weakness (p < 0.02) and tended to have lower overall symptom scores (4.2 +/- 0.3 vs 5.4 +/- 0.6), but breathlessness was comparable for both groups. On multivariate analysis, no nonanginal symptom was associated with SI. Only absence of a history of chest pain with activity and longer exercise time were related to SI. Patients with SI have similar clinical features as those with angina but tend to be less symptomatic with myocardial ischemia even for symptoms other than chest pain.

Prevalence of patent foramen ovale and its contribution to hypoxemia in patients with obstructive sleep apnea.

STUDY OBJECTIVES: The objectives of this study were (1) to assess the prevalence of patent foramen ovale (PFO) by means of contrast transesophageal echocardiography (TEE) in patients with obstructive sleep apnea, and (2) to determine the potential contribution of right to left interatrial shunting to systemic oxygen desaturation following the performance of Valsalva maneuver. DESIGN: Performance of contrast TEE during Valsalva maneuver with simultaneous measurement of systemic arterial oxygen saturation (SaO2) by means of pulse oximetry in patients with obstructive sleep apnea and a control group. SETTING: Government teaching hospital, university hospital affiliate. PATIENTS: Study group comprised 48 patients with documented obstructive sleep apnea and 24 control subjects. INTERVENTIONS: Sleep studies, contrast TEE, Valsalva maneuver, pulse oximetry. MEASUREMENTS AND RESULTS: Thirty-three of 48 patients with obstructive sleep apnea compared with 4 of 24 control patients had a detectable PFO (69% vs 17%; p < 0.0001). All sleep apnea patients had comparable baseline SaO2 regardless of the presence of a PFO (93.9+/-1.7% vs 95+/-1.2%; p=not significant). After performance of a Valsalva maneuver, however, a significantly greater fall in SaO2 was observed in patients with obstructive sleep apnea and PFO compared with patients with obstructive sleep apnea without PFO (-2.4 +/- 1.5% vs -1.3 +/- 0.6%; p=0.007). A statistically significant fall in SaO2 (defined as > 4 SD of recorded SaO2 values after Valsalva maneuver in patients without PFO) was found in one third of patients with sleep apnea and PFO. CONCLUSION: We conclude that there is an increased prevalence of PFO in patients with obstructive sleep apnea that could contribute to significant hypoxemia after a Valsalva maneuver in approximately one third of these patients.

Electron beam tomography as a non invasive method to monitor effectiveness of antiatherosclerotic therapy.

Coronary artery calcification has long been known to be associated with atherosclerosis and is intimately associated with atherosclerotic plaque development. Similarly, aortic valve degeneration and calcification appears to follow a pathophysiologic process very similar to atherosclerosis. Newer noninvasive technologies such as Electron Beam Tomography (EBT) allow the practicing physician to accurately detect and quantify cardiovascular calcification. It has recently become apparent that coronary calcium is an excellent marker of risk for myocardial infarction and sudden death in an individual patient and that aortic valve sclerosis is associated with high risk of coronary events. Besides identification and quantification of cardiovascular calcification, the EBT technology has also been employed to accurately measure the rate of progression of coronary calcification and it could become a very helpful tool to gauge effectiveness of therapy instituted to halt the progression of atherosclerosis. In this article we present a review of the studies published to date on the use of EBT imaging to gauge the effects of medical therapy on coronary and valvular calcification.