Biomedical subjects

P Raggi

Publications and source records attributed to P Raggi.

At least 19 recordsLinked to original sources

PubMed2007

Mortality effect of coronary calcification and phosphate binder choice in incident hemodialysis patients.

The risk of death in hemodialysis patients treated with calcium-containing phosphate binders or sevelamer is not known. We assessed all-cause mortality in 127 patients new to hemodialysis assigned to calcium-containing binders or sevelamer after a median follow-up of 44 months from randomization. This was a predetermined secondary end point of a randomized clinical trial designed to assess progression of coronary artery calcium (CAC) scores in the two treatment arms. Thirty-four deaths occurred during the follow-up period: 23 in subjects randomized to calcium-containing phosphate binders and 11 in subjects randomized to sevelamer. Baseline CAC score was a significant predictor of mortality after adjustment for age, race, gender, and diabetes with increased mortality proportional to baseline score (P=0.002). Mortality was borderline significantly lower in subjects randomized to sevelamer (5.3/100 patient years, confidence interval (CI) (2.2-8.5) compared to those randomized to calcium-containing binders (10.6/100 patient years, CI 6.3-14.9) (P=0.05). The greater risk of death for patients treated with calcium-containing phosphate binders persisted after full multivariable adjustment (P=0.016, hazard ratio 3.1, CI 1.23-7.61). In subjects new to hemodialysis baseline CAC score was a significant predictor of all-cause mortality. Treatment with sevelamer was associated with a significant survival benefit as compared to the use of calcium-containing phosphate binders.

Adult↗

PubMed2006

Correlation of simple imaging tests and coronary artery calcium measured by computed tomography in hemodialysis patients.

Vascular calcification is associated with an adverse prognosis in end-stage renal disease. It can be accurately quantitated with computed tomography but simple in-office techniques may provide equally useful information. Accordingly we compared the results obtained with simple non-invasive techniques with those obtained using electron beam tomography (EBT) for coronary artery calcium scoring (CACS) in 140 prevalent hemodialysis patients. All patients underwent EBT imaging, a lateral X-ray of the lumbar abdominal aorta, an echocardiogram, and measurement of pulse pressure (PP). Calcification of the abdominal aorta was semiquantitatively estimated with a score (Xr-score) of 0-24 divided into tertiles, echocardiograms were graded as 0-2 for absence or presence of calcification of the mitral and aortic valve and PP was divided in quartiles. The CACS was elevated (mean 910+/-1657, median 220). The sensitivity and specificity for CACS > or = 100 was 53 and 70%, for calcification of either valve and 67 and 91%, respectively, for Xr-score > or = 7. The area under the curve for CACS > or = 100 associated with valve calcification and Xr-score was 0.62 and 0.78, respectively. The likelihood ratio (95% confidence interval) of CACS > or = 100 was 1.79 (1.09, 2.96) for calcification of either valve and 7.50 (2.89, 19.5) for participants with an Xr-score > or = 7. In contrast, no association was present between PP and CACS. In conclusion, simple measures of cardiovascular calcification showed a very good correlation with more sophisticated measurements obtained with EBT. These methodologies may prove very useful for in-office imaging to guide further therapeutic choices in hemodialysis patients.

Adult↗

PubMed2006

Cardiovascular risk scores and the presence of subclinical coronary artery atherosclerosis in women with systemic lupus erythematosus.

The Framingham risk score is widely used to identify patients at increased cardiovascular risk, and women with systemic lupus erythematosus (SLE) have a marked increased prevalence of cardiovascular events. Thus, we examined the hypothesis that cardiovascular risk scores would identify women with SLE who had asymptomatic coronary atherosclerosis. Ninety-three women with SLE and 65 control subjects were studied. The Framingham score and a score for younger populations developed from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study were compared in both groups. Coronary atherosclerosis was ascertained by electron beam computed tomography. There were no significant differences in the median (interquartile range) Framingham [5 (2-10) compared to 7 (0-10), P = 0.88] and PDAY [15 (14-18) compared to 16 (13-18), P = 0.99] scores in patients with SLE and controls, respectively. Coronary atherosclerosis was associated with higher Framingham [12 (3-15) compared to 4 (1-8), P = 0.008] and PDAY [17 (15-19 compared to 15 (12-18), P = 0.03)] scores in patients with SLE; however, 99% of patients were classified as low-risk with a 10-year predicted risk of 1% (<1-3%). Our data indicate that cardiovascular risk scores are not adequate for risk stratification in women with SLE. Measurement of coronary calcification may add information to identify asymptomatic women with lupus who might benefit from aggressive preventive measures.

Adult↗

PubMed2006

Novel agents to manage dyslipidemias and impact atherosclerosis.

Strong epidemiological evidence linked elevated levels of low-density lipoprotein cholesterol (LDL-C) to risk of atherosclerotic heart disease. As a consequence, LDL-C lowering has been the main goal of therapy to reduce cardiovascular risk for the past few decades and hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have become some of the most commonly prescribed drugs. In spite of the proven efficacy of these drugs, statins reduce cardiovascular events by only 30-40%. Epidemiological analyses clearly indicate that a significant portion of risk is linked to other particles such as low high-density lipoprotein cholesterol (HDL-C), high triglycerides and others. Furthermore, several quantitative coronary angiography studies showing regression of atherosclerosis and reduction in subsequent events utilized a combination of drugs effective on LDL-C as well as other lipoproteins. Hence, several new drugs are being investigated that affect more than the traditional LDL-C pathways. In this article, we review lipoprotein-modifying agents that have either been recently released, or are still in various phases of development. They include agents that reduce LDL-C levels by mechanisms other than HMG-CoA inhibition (such as cholesterol absorption inhibitors, Acyl-CoA cholesterol acyl transferase inhibitors, sterol-regulating binding protein cleavage activating protein ligands, microsomal triglyceride transfer protein inhibitors, LDL-C receptor activators and farnesoid X receptor antagonists) and agents that raise HDL-C cholesterol or improve cholesterol efflux (such as cholesterol ester transfer protein inhibitors, retinoid X receptor selective agonists, specific peroxisome proliferator-activated receptor (PPAR) agonists and estrogen like compounds).

Animals↗

PubMed2004

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.

Arteriosclerosis↗

PubMed2004

Long-term comparison of a calcium-free phosphate binder and calcium carbonate--phosphorus metabolism and cardiovascular calcification.

BACKGROUND: Calcium carbonate used as a phosphate binder may contribute to cardiovascular calcification. Long-term comparisons of sevelamer, a non-calcium polymeric phosphate binder, and calcium carbonate (CC) are lacking. METHODS: 114 adult hemodialysis patients were randomly assigned to open label sevelamer or CC for 52 weeks. Study efficacy endpoints included changes in serum phosphorus, calcium, calcium-phosphorus product, and lipids. In addition, initial and sequential electron beam computerized tomography scans were performed to assess cardiovascular calcification status and change during follow-up. Safety endpoints were serum biochemistry, blood cell counts and adverse events. RESULTS: Patients receiving sevelamer had a similar reduction in serum phosphorus as patients receiving CC (sevelamer -0.58 +/- 0.68 mmol/l, CC -0.52 +/- 0.50 mmol/l; p = 0.62). Reductions in calcium-phosphorus product were not significantly different (sevelamer -1.4 +/- 1.7 mmol2/l2, CC -0.9 +/- 1.2 mmol2/l2; p = 0.12). CC produced significantly more hypercalcemia (> 2.8 mmol/l in 0% sevelamer and 19% CC patients, p < 0.01) and suppressed intact parathyroid hormone below 150 pg/ml in the majority of patients. Sevelamer patients experienced significant (p < 0.01) reductions in total (-1.2 +/- 0.9 mmol/l, -24%) and LDL cholesterol (-1.2 +/- 0.9 mmol/l, -30%). CC patients had significant increases in coronary artery (median +34%, p < 0.01) and aortic calcification (median +32%, p < 0.01) that were not observed in sevelamer-treated patients. Patients on sevelamer required more grams of binder (sevelamer 5.9 g vs. CC 3.9 g) and experienced more dyspepsia than patients on calcium carbonate. CONCLUSIONS: Sevelamer is an effective phosphate binder that unlike calcium carbonate is not associated with progressive cardiovascular calcification in hemodialysis patients.

Adult↗

PubMed2001

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.

Adult↗

PubMed2001

The HCA National Disease Management Program for coronary disease detection and treatment in women.

The diagnosis and treatment of heart disease in women continues to be one of the greatest challenges facing cardiovascular medicine today. Marked reductions in mortality rates during the past 2 decades did not result in improved outcomes for women. A major rate-limiting step to improving mortality rates for women is early diagnosis and initiation of effective lifesaving therapies for women. In 1999, HCA Healthcare Systems, Inc, Nashville, TN, initiated a coordinated effort among 208 hospitals in 26 states to improve the diagnosis of coronary disease and to target women who should receive aggressive risk factor modification and referral to cardiologists. We describe the initial phases of program development, including employee risk factor screening; citywide health risk assessment; nationwide educational programs for clinicians, staff, and consumers; and a dedicated outcomes assessment program for tracking women at risk for coronary disease. We believe that these efforts provide a venue for optimal care and improved outcomes for women served by HCA facilities.

Coronary Disease↗

PubMed2001

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.

Bayes Theorem↗

PubMed2001

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.

Calcinosis↗

PubMed2001

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.

Calcinosis↗

PubMed2001

Prognostic implications of absolute and relative calcium scores.

BACKGROUND: The continuing epidemic of cardiovascular disease underscores the need for more effective atherosclerosis detection and prevention. In fact, though the mortality rate decreased during the past decades, the morbidity rate continued to climb. The use of conventional risk factors is helpful to assess the median risk of a population, but it is unsatisfactory to estimate the actual risk of an individual patient. MODERN IMAGING TECHNOLOGIES: As a consequence, modern imaging technologies able to detect silent atherosclerotic disease have elicited a strong interest in the medical community with the hope that they may render risk stratification more accurate. Technologies such as electron beam tomography (EBT) are expected to bridge the gap between the mere presence of risk factors for disease development and assessment of the actual individual risk of events based on the visualization and quantification of silent disease. CONCLUSION: The medical literature is currently pervaded by a vivacious debate regarding the ability of EBT to provide such information as some investigators still hold concerns about the cost and effectiveness of a preventive approach driven by technology.

Adult↗

PubMed2001

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.

Calcinosis↗

PubMed2001

Use of electron beam tomography data to develop models for prediction of hard coronary events.

BACKGROUND: Prediction of hard cardiac events (myocardial infarction and coronary death) remains difficult in spite of the identification of several relevant risk factors for the development of coronary artery disease (CAD). New indicators of risk might add to our predictive ability. We used measures of coronary artery calcification (CAC) found by electron beam tomography (EBT) imaging to develop prediction models for hard cardiac events alone and in association with traditional risk factors for CAD. METHODS: Two groups of patients were studied: group A, 676 asymptomatic patients (mean age 52 years, 51% men) prospectively followed up for 32 +/- 7 months after being referred by primary care physicians for a screening EBT, and group B, 10,122 asymptomatic patients screened by EBT at one center and used as controls for calculation of calcium score nomograms. RESULTS: The occurrence of hard events in group A patients was related to traditional risk factors for CAD, presence of CAC (score >0), Ln (1 + absolute calcium score [CS]), and age- and sex-specific CS percentiles (CS%). Univariate analyses showed that age, smoking, diabetes mellitus, presence of CAC, Ln (1 + absolute CS), and CS% were predictive of hard events (all P <.05). Multiple logistic regression analyses demonstrated that CS% was the only significant predictor of events and provided incremental prognostic value when added to traditional risk factors for CAD (chi-square, P <.001). In a comparison of receiver-operator characteristic curves for prediction of hard events, the area under the curve for CS% plus conventional risk factors and age was significantly larger than that obtained by use of traditional risk factors and age separately as predictors (0.84 vs 0.71, respectively, P <.001). Furthermore, the area under the curve of CS% alone was significantly larger than that of traditional risk factors and age combined (0.82 vs 0.71, P =.028). CONCLUSIONS: Patients are usually selected for EBT screening on the basis of the presence of conventional risk factors for CAD. However, an age- and sex-specific calcium score provides the best predictive model for the occurrence of hard coronary events and adds incremental prognostic information to conventional risk factors for CAD.

Aged↗

PubMed2001

Aggressive versus moderate lipid-lowering therapy in postmenopausal women with hypercholesterolemia: Rationale and design of the Beyond Endorsed Lipid Lowering with EBT Scanning (BELLES) trial.

BACKGROUND: Electron beam tomography (EBT) is a noninvasive technique that allows the study of the entire coronary artery tree during a brief imaging session without the injection of any contrast media. Atherosclerosis is identified vicariously through the visualization of coronary calcific deposits. Quantitative assessments of calcium burden, such as calcium volume scores, have been shown to be a useful means to assess treatment-related changes in the extent of atherosclerotic plaques. Historically, the elderly female population has received less medical recognition regarding the risk and severity of coronary heart disease (CHD). METHODS: In the BELLES (Beyond Endorsed Lipid Lowering with EBT Scanning) trial, the presence of asymptomatic CHD in 600 postmenopausal women will be assessed by EBT. In this 1-year, multicenter, randomized, double-blind, parallel-group study, aggressive lipid-lowering treatment will be compared with moderate lipid-lowering treatment in postmenopausal women with hypercholesterolemia. The hypothesis we will test is that aggressive lipid-lowering therapy with 80 mg/d atorvastatin can produce greater reductions in atherosclerotic plaque burden as assessed by volumetric calcium scores than a moderate treatment with 40 mg/d pravastatin. The primary outcome measure will be the percent change from baseline in total CVS determined by EBT at 12 months. CONCLUSIONS: The results of the BELLES trial will help assess the actual incidence of CHD in postmenopausal women and the relative ability of two different lipid-lowering therapies to halt its progression.

Aged↗

PubMed2000

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.

Adult↗

PubMed2000

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.

Adult↗

PubMed2000

Regression of calcified coronary artery plaque assessed by electron beam computed tomography.

Lipid lowering therapies and aggressive life style modifications can induce regression of coronary artery disease as demonstrated by several angiographic studies. Such regression has also been associated with greatly reduced cardiovascular event rates. However, coronary angiography is invasive and expensive and other non-invasive diagnostic approaches would be preferable. Electron beam computed tomography imaging is used to detect coronary artery calcification, it is non-invasive and considerably less expensive than angiography. This tool provides an opportunity to serially monitor the effectiveness of medical therapy for coronary artery disease via the follow-up of a surrogate marker of disease such as vascular calcification. We review the current status of the literature on the use of electron beam computed tomography as a tool to follow progression of disease.

Adult↗