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Paolo Raggi

Publications and source records attributed to Paolo Raggi.

At least 37 records · Page 2Linked to original sources
PubMed2005

Aggressive versus moderate lipid-lowering therapy in hypercholesterolemic postmenopausal women: Beyond Endorsed Lipid Lowering with EBT Scanning (BELLES).

BACKGROUND: Women have been underrepresented in statin trials, and few data exist on the effectiveness and safety of statins in this gender. We used sequential electron-beam tomography (EBT) scanning to quantify changes in coronary artery calcium (CAC) as a measure of atherosclerosis burden in patients treated with statins. METHODS AND RESULTS: In a double-blind, multicenter trial, we randomized 615 hyperlipidemic, postmenopausal women to intensive (atorvastatin 80 mg/d) and moderate (pravastatin 40 mg/d) lipid-lowering therapy. Patients also submitted to 2 EBT scans at a 12-month interval (mean interval 344+/-55 days) to measure percent change in total and single-artery calcium volume score (CVS) from baseline. Of the 615 randomized women, 475 completed the study. Mean+/-SD percent LDL reductions were 46.6%+/-19.9% and 24.5%+/-18.5 in the intensive and moderate treatment arms, respectively (P<0.0001), and National Cholesterol Education Program Adult Treatment Panel III LDL goal was reached in 85.3% and 58.8% of women, respectively (P<0.0001). The total CVS% change was similar in the 2 treatment groups (median 15.1% and 14.3%, respectively; P=NS), and single-artery CVS% changes and absolute changes were also similar (P=NS). In both arms, there was a trend toward a greater CVS progression in patients with prior cardiovascular disease, diabetes mellitus, and hypertension, whereas hormone replacement therapy had no effect on progression. CONCLUSIONS: In postmenopausal women, intensive statin therapy for 1 year caused a greater LDL reduction than moderate therapy but did not result in less progression of coronary calcification. The limitations of this study (too short a follow-up period and the absence of a placebo group) precluded determination of whether progression of CVS was slowed in both arms or neither arm compared with the natural history of the disease.

Aged↗
PubMed2005

On the prediction and prevention of myocardial infarctions: models based on retrospective and doubly censored prospective data.

Early detection of coronary heart disease (CHD) in its pre-clinical stages may offer a way to reduce the impact of this endemic disease on society. Coronary calcification accompanies the development of an atherosclerotic plaque, the pathological substrate of CHD, and its identification is currently possible by means of electron beam tomography (EBT). This is a non-invasive imaging test that quantifies the extent of coronary artery plaque calcification by means of a calcium score. In this study, we show that an age-sex based calcium score percentile (CS%) provides an invaluable predictor for myocardial infarction (MI), and examine how CS% is related to traditional risk factors. We study two separate groups of patients: 172 patients who underwent EBT screening after surviving an MI (retrospective group); and 676 asymptomatic subjects who were screened and followed for several years for the occurrence of an MI (prospective group). We use CS% with traditional risk factors in logistic regression models to: (1) compare patients in the retrospective and prospective groups, and (2) develop a mortality model for MIs that occurred in the prospective group. These logistic regressions are used to develop a joint model for the relative log-odds of an MI, which is non-linear in the covariates of the mortality model. We also use baseline covariates in the prospective group to fit an event-time regression model and estimate probabilities for 2 and 3 year exposure periods. The event-time regression provides independent estimates of the relative odds that are associated with risk factors. CS%, smoking, and their interaction were preeminent as predictors in the joint model for the relative odds of an MI and in the event-time regression, although the effects of smoking and CS% were generally subadditive. These models provide important information on the risks associated with elevated CS% levels.

Coronary Disease↗
PubMed2005

Role of electron-beam computed tomography and nuclear stress testing in cardiovascular risk assessment.

Although it is well recognized that stenotic coronary artery lesions carry a significant risk for cardiac events, the importance of nonstenotic lesions is generally underappreciated. However, many acute myocardial infarctions are caused by lesions that cause <50% stenosis. Coronary artery calcification is being increasingly studied as a marker of risk for cardiac events. Measurement of coronary artery calcium using electron-beam computed tomography is emerging as a useful tool to further risk-stratify patients who are otherwise at intermediate risk for events. Coronary calcium scores have been shown to add independent predictive value to traditional risk assessment.

Calcinosis↗
PubMed2005

Two year comparison of sevelamer and calcium carbonate effects on cardiovascular calcification and bone density.

BACKGROUND: Calcium-based phosphate binders may induce tissue calcification, and little is known about their effects on bone density. We compared the effects of a calcium with a non-calcium phosphate binder on both arterial calcification and bone density measured by computed tomography. METHODS: Seventy-two adult haemodialysis patients were randomized to treatment with calcium carbonate (CC) or sevelamer (SEV) for 2 years. Electron beam CT scans were performed at baseline and at 6, 12 and 24 months. Serum phosphorus, calcium, calcium x phosphorus product and intact parathyroid hormone (iPTH) were measured and other routine laboratory tests were also carried out. RESULTS: The average calcium x phosphorus product was similar in the two treatment groups. However, patients receiving CC had significantly lower average iPTH (P<0.01), were more likely to have hypercalcaemic episodes (P = 0.03) and had significantly greater increases in coronary artery (CC median 484, P<0.0001, SEV median 37, P = 0.3118, between-group P = 0.0178) and aortic (CC median 610, P = 0.0003, SEV median 0, P = 0.5966, between-group P = 0.0039) calcification scores. The CC group also had a significant decrease in trabecular bone density (CC median -6%, P = 0.0049, SEV median +3%, P = 0.0296, between-group P = 0.0025). However, there was no significant difference in cortical bone density between the two groups. CONCLUSIONS: This 2 year study shows that calcium carbonate use is continuously associated with progressive arterial calcification in haemodialysis patients. In addition, it suggests that it is also associated with decreased trabecular bone density. However, this latter finding requires confirmation by a study specifically devoted to this issue.

Adult↗
PubMed2005

Progression of coronary artery calcium and occurrence of myocardial infarction in patients with and without diabetes mellitus.

Progression of coronary artery calcium, a marker of atherosclerosis, can be slowed with statins, and continued progression of calcium is associated with an increased risk of myocardial infarction. However, it is not known whether statins are effective in slowing calcium progression in diabetes mellitus. In a retrospective study, we examined 1153 nondiabetic and 157 diabetic subjects who underwent sequential electron beam tomography scans at a minimum 1-year interval to assess progression of coronary calcium. A yearly score increase >15% was considered evidence of true progression. The use of statins and occurrence of myocardial infarction were recorded. There was no difference in baseline calcium score between diabetic and nondiabetic patients. Diabetic patients with no coronary calcium on the baseline scans developed it more often than nondiabetic subjects (42% versus 25%; P=0.046) during follow-up. Calcium progression was 33% greater in diabetic patients than nondiabetic subjects (P<0.001) if no statin therapy was provided and 17.7% greater when statins were used (P<0.001). Among the 49 subjects who experienced a myocardial infarction, the calcium score increased on average 20% more in diabetic than nondiabetic patients (P<0.001). In logistic models, diabetes mellitus and systemic hypertension were the best predictors of calcium progression (odds ratio, 3.1 and 1.9, respectively), whereas baseline calcium score percentile and statin therapy were the best predictors of infarction. These findings support the notion that diabetes mellitus causes accelerated atherosclerosis, even in the presence of statin therapy, and provide evidence that coronary calcium monitoring is an effective method to assess treatment efficacy.

Adult↗
PubMed2005

Effects of sevelamer and calcium-based phosphate binders on uric acid concentrations in patients undergoing hemodialysis: a randomized clinical trial.

OBJECTIVE: Gout affects a large fraction of persons with advanced chronic kidney disease, and hyperuricemia may increase the risk of cardiovascular disease. Several hypouricemic agents are contraindicated in patients with end-stage renal disease. Sevelamer is a nonabsorbed hydrogel that binds phosphorus and bile acids in the intestinal tract. Results of short-term and open-label studies suggest that sevelamer might lower the concentration of uric acid, another organic anion. We undertook this study to test our hypothesis that the reduction in serum uric acid concentration induced by sevelamer would be confirmed in a long-term, randomized, clinical trial comparing sevelamer with calcium-based phosphate binders. METHODS: Two hundred subjects undergoing maintenance hemodialysis were randomly assigned to receive either sevelamer or calcium-based phosphorus binders in an international, multicenter, clinical trial. Data on baseline and end-of-study uric acid concentrations were available in 169 subjects (85%); the change in uric acid concentration from baseline to the end of the study was the outcome of interest. RESULTS: Baseline clinical characteristics, including mean uric acid concentrations, were similar in subjects randomly assigned to receive sevelamer and calcium-based phosphate binders. The mean change in uric acid concentration (from baseline to the end of the study) was significantly larger in sevelamer-treated subjects (-0.64 mg/dl versus -0.26 mg/dl; P = 0.03). The adjusted mean change in uric acid concentration was more pronounced when the effects of age, sex, diabetes, vintage (time since initiation of dialysis), dialysis dose, and changes in blood urea nitrogen and bicarbonate concentrations were considered (-0.72 mg/dl versus -0.15 mg/dl; P = 0.001). Twenty-three percent of sevelamer-treated subjects experienced a study-related reduction in the concentration of uric acid equal to -1.5 mg/dl or more, compared with 10% of calcium-treated subjects (P = 0.02). CONCLUSION: In a randomized clinical trial comparing sevelamer and calcium-based phosphate binders, treatment with sevelamer was associated with a significant reduction in serum uric acid concentrations.

Aged↗
PubMed2005

Increased coronary-artery atherosclerosis in rheumatoid arthritis: relationship to disease duration and cardiovascular risk factors.

OBJECTIVE: To compare the prevalence and severity of coronary-artery atherosclerosis in patients with early and established rheumatoid arthritis (RA) and controls. METHODS: Electron-beam computed tomography was used to measure the extent of coronary-artery calcification in 227 subjects, of whom 70 had early RA, 71 had established RA, and 86 were controls. Coronary-artery calcification calculated according to the Agatston calcium score was compared in patients and controls, and its relationship to clinical characteristics was examined. Adjusted odds ratios (ORs) were obtained with the use of proportional odds logistic regression models to determine independent associations of early and established RA and coronary-artery calcification. RESULTS: Calcium scores were higher in patients with established RA (median 40.2, interquartile range [IQR] 0-358.8) compared with those with early disease (median 0, IQR 0-42.6) and controls (median 0, IQR 0-19.2) (P = 0.001). Coronary-artery calcification occurred more frequently in patients with established RA (60.6%) than in patients with early RA (42.9%) and control subjects (38.4%) (P = 0.016) The OR for the likelihood of having more severe coronary-artery calcification (defined as an Agatston score >109) in patients with established disease was 3.42 (P = 0.002) after adjusting for cardiovascular risk factors. Among patients with RA, smoking (OR 1.02, P = 0.04) and an elevated erythrocyte sedimentation rate (OR 1.02, P = 0.05) were associated with more severe coronary-artery calcification after adjustment for age and sex. CONCLUSION: The prevalence and severity of coronary calcification is increased in patients with established RA and is related, in part, to smoking and an increased erythrocyte sedimentation rate.

Adult↗
PubMed2005

Potential antiatherogenic and anti-inflammatory properties of sevelamer in maintenance hemodialysis patients.

BACKGROUND: Patients affected by end-stage renal disease (ESRD) demonstrate a very high cardiovascular risk mediated by traditional cardiovascular risk factors as well as abnormal mineral metabolism and a state of chronic inflammation. Sevelamer is a nonabsorbable non-calcium-based hydrogel with potential antiatherosclerotic properties. METHOD AND RESULTS: One hundred eight patients undergoing maintenance hemodialysis were randomized to sevelamer or calcium acetate as treatment for hyperphosphatemia. A coronary artery calcium score, as a measure of plaque burden, was calculated at baseline and 1 year, along with serial measurements of serum lipoproteins, beta2-microglobulin, and high-sensitivity C-reactive protein (hs-CRP). At 1 year, coronary artery calcium score progressed significantly from baseline in calcium acetate-treated subjects ( P < .001) but not in sevelamer-treated patients (P = NS). Total cholesterol (P < .0001), low-density lipoprotein cholesterol (P < .0001), apolipoprotein B (P < .0001), beta2-microglobulin (P = .018), and hs-CRP (P < .002) decreased, and high-density lipoprotein increased significantly (P = .036) from baseline in the sevelamer-treated subjects but not in subjects treated with calcium acetate despite the more frequent use of statins in the latter group (46% vs 22%, P < .05). The changes in total and low-density lipoprotein cholesterol, apolipoprotein B, and hs-CRP were significantly different between treatment groups (all P < .01). CONCLUSIONS: Sevelamer leads to favorable changes in lipids and inflammatory markers with potentially useful antiatherogenic effects in hemodialysis patients.

Acetates↗
PubMed2005

Tracking atherosclerosis regression: a clinical tool in preventive cardiology.

Progression of coronary artery disease was initially evaluated using quantitative coronary angiography with ensuing evidence indicating a strong relationship to adverse cardiovascular outcomes. Since then, several other atherosclerosis imaging techniques have emerged as new tools in cardiovascular medicine to evaluate the effectiveness of preventive therapies through serial monitoring of changes in atherosclerosis burden. Conducting large randomized trials to test new approaches for the medical management of atherosclerosis, with the goal of showing a reduction in event rates, may often be impractical in an era of cost containment and reduced societal resources. Recent evidence has unfolded that investigates alternative ways of assessing therapeutic results such as the attainment of surrogate goals with substantial outcome relevance. Atherosclerosis imaging modalities such as coronary computed tomography, carotid ultrasound, cardiovascular magnetic resonance imaging, and intravascular ultrasound each possess specific imaging abilities and inter-test characteristics that enable their serial use as intermediate endpoints in clinical trials and, increasingly, in individual patient management. The current review focuses on the application of these modalities as emerging tools in cardiovascular prevention.

Coronary Artery Disease↗
PubMed2005

Diagnostic and prognostic value of coronary artery calcium screening.

PURPOSE OF REVIEW: Algorithms and equations to calculate risk of cardiovascular events, though very useful as an in-office tool to conduct a preliminary assessment demonstrate a limited ability to predict risk in the individual patient. This has favored the development of several imaging modalities for subclinical atherosclerosis such as imaging of coronary calcium by computed tomography. RECENT FINDINGS: Arterial wall calcification is intimately associated with atherosclerosis development and is therefore an optimal marker of the presence of disease. The paradigm underlying the use of imaging technologies to identify subclinical disease is that the quantification of plaque burden may provide a better risk stratification approach for the individual patient than the currently available tools. SUMMARY: The most recent evidence supports this approach as will be discussed in the current review.

Calcinosis↗
PubMed2005

Effects of sevelamer and calcium on coronary artery calcification in patients new to hemodialysis.

BACKGROUND: Hemodialysis patients are at increased risk for progressive coronary artery calcification; however, the development and progression of this disease process in patients new to hemodialysis is unknown. METHOD: One hundred and twenty-nine patients new to hemodialysis were randomized to receive calcium containing phosphate binders or the noncalcium phosphate binder sevelamer hydrochloride. Subjects underwent electron beam computed tomography scanning (EBCT) at entry into the study and again at 6, 12, and 18 months. RESULTS: One hundred and nine patients underwent baseline and at least one additional assessment of coronary calcification. At baseline, 37% of sevelamer treated and 31% of calcium treated patients had no evidence of coronary calcification. No subject with a zero coronary artery calcium score (CACS) at baseline progressed to a CACS >30 over 18 months. Subjects with a CACS > 30 at baseline showed progressive increases in CACS in both treatment arms (P < 0.05 for each time point in both groups). Subjects treated with calcium containing phosphate binders showed more rapid and more severe increases in CACS when compared with those receiving sevelamer hydrochloride (P= 0.056 at 12 months, P= 0.01 at 18 months). CONCLUSION: New hemodialysis patients with no evidence of coronary calcification showed little evidence of disease development over 18 months independent of phosphate binder therapy. However, subjects with evidence of at least mild coronary calcification had significant progression at 6, 12, and 18 months. Use of calcium containing phosphate binders resulted in more rapid progression of coronary calcification than did use of sevelamer hydrochloride.

Adult↗
PubMed2005

Cardiovascular calcification in end stage renal disease.

Extensive atherosclerosis and heavy vascular and valvular calcifications are common complications of end stage chronic kidney disease (CKD-V) and are related to a high incidence of cardiovascular events. In CKD-V vascular calcifications occur both in the subintimal space and in the runica media. Intimal calcification is associated with atherosclerosis and is therefore a universal finding. On the contrary, medial calcification is characteristically associated with advanced CKD and diabetes mellitus. Numerous metabolic and endocrine abnormalities, primarily involving calcium and phosphorus metabolism, are found in CKD. Furthermore, CKD-V is believed to be a state of heightened inflammation and oxidative stress. All of these dysfunctions occur early in the course of the renal failure and likely contribute to the development and progression of vascular calcification and atherosclerosis. This review is centred on the pathobiology of vascular calcification in CKD-V, its detection with modern imaging modalities and the therapeutic approaches currently available to slow its progression.

Calcinosis↗
PubMed2005

Ethiopathogenesis, diagnosis and prevention of vascular calcification in end stage renal disease.

Extensive atherosclerosis and heavy vascular and valvular calcifications are common complications of end stage renal disease (ESRD) and are very likely related to the high incidence of cardiovascular disease in these patients. The greatly increased incidence of cardiovascular disease is only partly explained by traditional risk factors for atherosclerosis. In ESRD, vascular calcification occurs both in the vascular intima layer and in the tunica media. Intimal calcification is disseminated and is characteristically associated with damaged and abnormally functioning endothelium, and macrophage and vascular smooth muscle cell (VSMC) infiltration typical of atherosclerosis. On the contrary, medial calcification occurs in patchy distribution and the most frequent cell types found in its vicinity are the VSMC and macrophage. The uremic state is associated with numerous metabolic abnormalities and endocrine disturbances primarily involving calcium and phosphorus metabolism. Furthermore, chronic kidney disease and dialysis are considered states of active and strong inflammatory response. These dysfunctions occur early in the course of renal failure and likely contribute to the development and progression of vascular calcification and atherosclerosis. For many years, vascular calcification was considered solely the result of a passive deposition of hydroxyapatite crystals in the arterial wall due to elevated calcium-phosphate ion product. However, a large body of evidence has now shown that this is a highly regulated process governed by factors that closely resemble calcium deposition in bone tissue. In fact, vascular calcification requires changes in the phenotype of VSMC and the expression of several proteins normally involved in bone metabolism. This review is centered on the etiopathogenesis of vascular calcification in ESRD, its detection with modern imaging modalities and the therapeutic approaches currently available to slow its progression.

Calcinosis↗
PubMed2005

Ischemia imaging and plaque imaging in diabetes: complementary tools to improve cardiovascular risk management.

Cardiovascular disease is the most frequent cause of death and disability in diabetes, and the morbidity and mortality for coronary artery disease (CAD) in this population is two to four times higher than in nondiabetic subjects. Traditional risk factors do not fully explain the level of cardiovascular risk, and coronary disease events are often silent in diabetic patients. Thus, research has recently focused on improving the risk assessment of an individual patient with new tools in an effort to better identify subjects at highest risk and in need of aggressive management. Cardiovascular imaging has proven very helpful in this regard. Traditional methods to assess CAD are based on detection of obstructive luminal disease responsible for myocardial ischemia. However, acute coronary syndromes often occur in the absence of luminal stenoses. Hence, the utilization of imaging methodologies to visualize atherosclerosis in its presymptomatic stages has received mounting attention in recent years. In this article, we review the current literature on the utility of traditional imaging modalities for obstructive CAD (nuclear and echocardiographic stress testing) as well as atherosclerosis plaque imaging with carotid intima-media thickness and coronary artery calcium for risk stratification of diabetic patients.

Cardiovascular Diseases↗
PubMed2005

[Atherosclerosis imaging to assess plaque progression].

Cardiovascular disease is the first cause of morbidity and mortality for both men and women in developed countries. Tracking the progression of the atherosclerotic plaque appears to be an effective way to predict modification of risk in individual patients. Quantitative coronary angiography was initially proposed as a method of choice to assess coronary disease progression. With this methodology it was possible to demonstrate a strong association of plaque regression with reduction in adverse cardiovascular outcomes. More recently, the focus of research has turned to the development of noninvasive modalities to image the atherosclerotic plaque in its preclinical stages and to evaluate the effectiveness of preventive therapies with sequential imaging. The ease of performance of these tests enabled their use as intermediate endpoints in clinical trials to test new strategies to treat atherosclerosis. If proven successful, these imaging tools may allow a reduction in size and duration of clinical trials with a substantial cost benefit for society.

Adult↗
PubMed2004

Decrease in thoracic vertebral bone attenuation with calcium-based phosphate binders in hemodialysis.

UNLABELLED: We performed a post hoc analysis of a 52-week randomized trial conducted in adult hemodialysis patients that compared the effects of calcium-based phosphate binders and sevelamer, a nonabsorbable polymer, on parameters of mineral metabolism and vascular calcification by electron beam tomography. In this analysis, we evaluated the relative effects of calcium and sevelamer on thoracic vertebral attenuation by CT and markers of bone turnover. Subjects randomized to calcium salts experienced a significant reduction in trabecular bone attenuation and a trend toward reduction in cortical bone attenuation, in association with higher concentrations of serum calcium, lower concentrations of PTH, and reduced total and bone-specific alkaline phosphatase. INTRODUCTION: In patients with chronic kidney disease, hyperphosphatemia is associated with osteodystrophy, vascular and soft tissue calcification, and mortality. Calcium-based phosphate binders are commonly prescribed to reduce intestinal phosphate absorption and to attenuate secondary hyperparathyroidism. Clinicians and investigators have presumed that, in hemodialysis patients, calcium exerts beneficial effects on bone. MATERIALS AND METHODS: We performed a post hoc analysis of a 52-week randomized trial conducted in adult hemodialysis patients that compared the effects of calcium-based phosphate binders and sevelamer, a nonabsorbable polymer, on parameters of mineral metabolism and vascular calcification by electron beam tomography. In this analysis, we evaluated the relative effects of calcium and sevelamer on thoracic vertebral attenuation by CT and markers of bone turnover. RESULTS AND CONCLUSIONS: The average serum phosphorus and calcium x phosphorus products were similar for both groups, although the average serum calcium concentration was significantly higher in the calcium-treated group. Compared with sevelamer-treated subjects, calcium-treated subjects showed a decrease in thoracic vertebral trabecular bone attenuation (p = 0.01) and a trend toward decreased cortical bone attenuation. More than 30% of calcium-treated subjects experienced a 10% or more decrease in trabecular and cortical bone attenuation. On study, sevelamer-treated subjects had higher concentrations of total and bone-specific alkaline phosphatase, osteocalcin, and PTH (p < 0.001). When used to correct hyperphosphatemia, calcium salts lead to a reduction in thoracic trabecular and cortical bone attenuation. Calcium salts may paradoxically decrease BMD in hemodialysis patients.

Aged↗
PubMed2004

Prognostic value of coronary artery calcium screening in subjects with and without diabetes.

OBJECTIVES: The study was done to determine the interaction of coronary artery calcium and diabetes mellitus for prediction of all-cause death. BACKGROUND: Diabetes is a strong risk factor for coronary artery disease (CAD) and is associated with an elevated overall mortality. Electron beam tomography (EBT) provides information on the presence of subclinical atherosclerosis and may be useful for risk stratification. METHODS: We followed 10,377 asymptomatic individuals (903 diabetic patients) referred for EBT imaging. Primary end point was all-cause mortality, and the average follow-up was 5.0 +/- 3.5 years. Cox proportional hazard models, with and without adjustment for other risk factors, were developed to predict all-cause mortality. RESULTS: Patients with diabetes had a higher prevalence of hypertension and smoking (p < 0.001) and were older. The average coronary calcium score (CCS) for subjects with and for those without diabetes was 281 +/- 567 and 119 +/- 341, respectively (p < 0.0001). Overall, the death rate was 3.5% and 2.0% for subjects with and without diabetes (p < 0.0001). In a risk-factor-adjusted model, there was a significant interaction of CCS with diabetes (p < 0.00001), indicating that, for every increase in CCS, there was a greater increase in mortality for diabetic than for nondiabetic subjects. However, patients suffering from diabetes with no coronary artery calcium demonstrated a survival similar to that of individuals without diabetes and no detectable calcium (98.8% and 99.4%, respectively, p = 0.5). CONCLUSIONS: Mortality from all causes is increased in asymptomatic patients with diabetes in proportion to the screening CCS. Nonetheless, subjects without coronary artery calcium have a low short-term risk of death even in the presence of diabetes mellitus.

Adult↗