Biomedical subjects
Publications and source records attributed to Paolo Raggi.
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The cardiovascular risk of patients undergoing dialysis is 20-30 times higher than that of individuals of the same age, without abnormal renal function, from the general population. Observational studies of patients with normal and abnormal renal function have shown that there is an association between bone disease, vascular calcification and cardiovascular outcome and that worsening of these conditions happens in parallel. Basic science studies are elucidating several mechanisms that could explain the interaction between bone disease, vascular calcification and cardiovascular outcome. For example, the expression of osteoprotegerin-a protein that regulates bone resorption by binding receptor activator of nuclear factor kappaB (RANK) ligand (RANKL), thus preventing interaction with the receptor RANK and the stimulation of osteoclast maturation-is regulated by several cytokines. Additionally, osteoprotegerin seems involved in the genesis of atherosclerosis. Imbalances of bone mineral metabolism, bone matrix secretion and vascular smooth-muscle-cell apoptosis seem involved in the ossification of the arterial wall in chronic kidney disease, and could explain some of the complex interactions between bone and vascular disease in renal failure. In this article we present a brief review of some of the basic mechanisms involved in vascular calcification and the clinical evidence of an association of vascular and bone disease.
Cardiovascular calcification poses an increased risk for cardiovascular events in advanced phases of chronic kidney disease. This evidence has brought many investigators to focus their attention on the importance of detection of calcification and avoidance of further development of it with appropriate therapeutic choices. Physicians can use a variety of noninvasive imaging tools to identify cardiovascular calcification, some with merely qualitative and others with both qualitative and quantitative capabilities. Plain x-rays and ultrasonography can be used to identify macroscopic calcification of aorta and peripheral arteries, echocardiography is helpful for assessment of valvular calcification, and computed tomography technologies constitute the gold standard for quantification of cardiovascular calcification. The latter is also useful to monitor calcification progression and to assess the effect of different therapeutic strategies directed at modifying calcification progression. In this article, we review the clinical significance of vascular calcification and some of the evidence surrounding the most commonly employed noninvasive imaging techniques.
BACKGROUND: Coronary artery calcification (CAC) is highly prevalent in haemodialysis patients and is associated with cardiovascular outcomes. Though cardiac computed tomography (CCT) is accurate, it is not widely available. METHODS: We developed a cardiovascular calcification index (CCI) to predict the presence of CAC for haemodialysis patients using simple in-office techniques. Prevalent haemodialysis patients (n = 140) underwent CCT imaging for CAC, a lateral abdominal X-ray for calcification of the abdominal aorta, an echocardiogram for valvular calcification, and pulse pressure measurement. A CCI was derived by weighting the prevalence rate ratios of CAC > or =1000. Using bootstrap techniques, validation was performed using receiver operator characteristic curves and likelihood ratios. RESULTS: Points were assigned for patients' age (60-69 and > or =70 years, 1 and 2 points, respectively), dialysis vintage > or =2 years (1 point), aortic and mitral valve calcification (3 and 1 points, respectively), and abdominal aorta X-ray scores of 1-6 and > or =7 (2 and 4 points, respectively). Race, sex and pulse pressure did not contribute to the CCI. The CCI ranged from 0 to 11 points. The likelihood ratio of CAC > or =1000 associated with CCI scores of 2-4, 5, 6-8 and 9-11 were 1.28, 2.03, 2.94 and 3.83, respectively. Given the prevalence of CAC > or =1000 of 21% in the current study, the probability of having CAC > or =1000 was 26%, 38%, 43% and 50% for participants with CCI scores of 2-4, 5, 6-8, and > or =9, respectively. CONCLUSIONS: Although refinement is needed, the CCI developed in the current study provides an alternative for predicting CAC when CCT is not available.
Peripheral arterial disease (PAD) is a well-established risk factor for clinical cardiovascular disease (CVD). The impact of a low ankle-brachial index (ABI), higher than the generally recognized 0.9 cutpoint for PAD, on CVD risk is not well characterized. We analyzed data from the 1999 to 2002 National Health and Nutrition Examination Survey (n = 4,895), a nationally representative sample of United States adults, to determine the prevalence of PAD (ABI <0.90), borderline PAD (ABI 0.90 to 0.99), a low-normal ABI (1.00 to 1.09), and a normal ABI (1.10 to 1.29), and the association of these ABI levels with CVD. The prevalence of PAD, borderline PAD, a low-normal ABI, and a normal ABI was 5.0%, 8.7%, 27.8%, and 54.8%, respectively. After age, race/ethnicity, and gender adjustment, the odds ratios of a 10-year coronary heart disease (CHD) risk of >or=20%, CHD, stroke, and CVD were higher at lower ABI levels (each p trend <0.01). After additional adjustment for potential confounders, the odds ratios associated with a low-normal ABI, borderline PAD, and PAD, compared with those with a normal ABI, were 1.24 (95% confidence interval [CI] 0.91 to 1.70), 1.34 (95% CI 0.99 to 1.83), and 1.87 (95% CI 1.29 to 2.73), respectively (p trend <0.001) for CVD and 1.20 (95% CI 0.82 to 1.77), 1.45 (95% CI 0.80 to 2.63), and 2.02 (95% CI 1.20 to 3.39), respectively (p trend = 0.015) for a 10-year risk of CHD of >or=20%. In contrast, a trend was not present for CHD and stroke after multivariate adjustment. In conclusion, subjects with a low-normal ABI or with borderline PAD need screening for CVD risk factors, and interventions may be appropriate to prevent cardiovascular events.
BACKGROUND: The metabolic syndrome is an independent risk factor for ischaemic heart disease. Patients with systemic lupus erythematosus (SLE) have accelerated atherosclerosis; however, there are no controlled studies of the metabolic syndrome in patients with SLE. OBJECTIVE: To compare the prevalence of the metabolic syndrome in patients with SLE and controls and to evaluate its relationship to other cardiovascular risk factors and inflammation. METHODS: 102 patients with SLE and 101 controls were studied. The prevalence of the metabolic syndrome was compared in patients and controls using the National Cholesterol Education Program Adult Treatment Panel III (NCEP) and the World Health Organization (WHO) definitions, and associations with cardiovascular risk factors and lupus characteristics were examined. RESULTS: The metabolic syndrome was present in 32.4% of patients and in 10.9% of controls subjects (p<0.001) using the WHO definition that requires direct determination of insulin resistance, and in 29.4% of patients with SLE and in 19.8% of controls (p = 0.14) using the NCEP definition. Among patients with SLE, both definitions were significantly associated with higher concentrations of C reactive protein (p = 0.001) and the NCEP definition was significantly associated with higher concentrations of homocysteine (p<0.001), lipoprotein (a) (p = 0.02) and cholesterol (p = 0.04). Neither lupus disease activity nor damage scores were associated with the metabolic syndrome. CONCLUSIONS: Patients with SLE have a higher prevalence of insulin resistance and consequently of the WHO-defined metabolic syndrome than controls. In patients with SLE, the metabolic syndrome was associated with higher levels of inflammation and may provide a link between inflammation and increased cardiovascular risk.
BACKGROUND: Vascular calcification and low bone turnover with a relatively low parathyroid hormone (PTH) often coexist in diabetic patients undergoing haemodialysis. Since calcium salts (CaS) are used extensively as primary phosphate binders and have been associated with progressive vascular calcification, we studied the effects of CaS on coronary arteries and parathyroid activity in incident haemodialysis diabetic patients. METHODS: We measured the change in coronary artery calcium scores (CACS) with sequential electron beam computed tomography (EBCT) in 64 diabetic and 45 non-diabetic patients, randomized to CaS or sevelamer within 90 days of starting haemodialysis. CACS measurements were repeated after 6, 12 and 18 months. Serum intact PTH (iPTH), calcium and phosphorus were serially tested. RESULTS: During the study period, serum phosphate was similar in diabetic and non-diabetic patients. Serum calcium levels were similar at baseline (2.3+/-0.25 mmol/l for both) and increased significantly with CaS treatment (P<0.05) both in diabetic and non-diabetic patients but not with sevelamer. Diabetic patients treated with CaS showed a significantly greater CACS progression than sevelamer-treated patients (median increase 177 vs 27; P=0.05). During follow-up, diabetic patients receiving CaS were significantly more likely to develop serum iPTH values<16 pmol/l than diabetic patients treated with sevelamer (33% vs 6%, P=0.005) and had a lower mean iPTH level (24+/-16 vs 31+/-14 pmol/l; P=0.038). CONCLUSIONS: The management of hyperphosphataemia with CaS in haemodialysis diabetic patients is associated with a significantly greater progression of CACS than with sevelamer. These effects are accompanied by iPTH changes suggestive of low bone turnover.
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Rates of hypertension, high low density lipoprotein (LDL) cholesterol, and diabetes mellitus awareness, treatment, and control for persons with a history of myocardial infarction and stroke were compared by using two nationally representative samples of the US population: the Third National Health and Nutrition Examination Survey in 1988-1994 (n = 1,004) and the National Health and Nutrition Examination Survey in 1999-2002 (n = 512). Estimated numbers of adult myocardial infarction and stroke survivors increased from 6.32 to 6.78 million and from 3.85 to 4.96 million, respectively. Among such survivors, awareness of a previous diagnosis of hypertension and prevalence of self-reported diabetes mellitus remained stable while awareness of high LDL cholesterol increased from 43.3% to 60.2% (p < 0.01). Among those aware of their diagnosis, pharmacologic treatment for high LDL cholesterol increased from 33.1% to 78.4% and pharmacologic treatment for diabetes mellitus increased from 80.0% to 93.6% during this time (each p < 0.01), while pharmacologic treatment for hypertension increased nonsignificantly. Among those receiving pharmacologic treatment, hypertension and high LDL cholesterol control increased from 48.9% to 59.3% (p = 0.05) and from 5.1% to 33.1% (p < 0.01), respectively. In contrast, glycemic control among diabetics decreased from 45.0% to 33.2% (p = 0.20). The number of US myocardial infarction and stroke survivors increased between 1988-1994 and 1999-2002, and substantial improvements occurred in the awareness, treatment, and control of high LDL cholesterol in this population.
OBJECTIVE: . To examine the hypothesis that patients with systemic lupus erythematosus (SLE) have increased concentrations of interleukin-6 (IL-6), IL-8, and monocyte chemoattractant protein-1 (MCP-1) and that these cytokines are associated with coronary risk factors and atherosclerosis. METHODS: Plasma IL-6, MCP-1, and serum IL-8 (pg/ml) concentrations were measured in 74 patients with SLE and in 85 controls. Clinical characteristics, homocysteine, lipids, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and coronary artery calcification as detected by electron beam computed tomography were measured. RESULTS: IL-6 (13.2 +/- 13.8 pg/ml vs 6.7 +/- 3.2 pg/ml, p < 0.001) and MCP-1 (264.2 +/- 581.8 pg/ml vs 131.0 +/- 63.7 pg/ml, p < 0.001) concentrations were higher in patients with lupus than in controls. IL-8 concentrations did not differ between patients and controls (p = 0.86). In patients, IL-6 concentrations were correlated with CRP (p < 0.001), ESR (p < 0.001), SLE disease activity index (SLEDAI, p = 0.003), and body mass index (BMI, p = 0.003). IL-6 concentrations were inversely correlated with HDL cholesterol (p = 0.01). MCP-1 concentrations were correlated with SLEDAI (p = 0.01), ESR (p = 0.04), and triglycerides (p = 0.03). After controlling for age, sex, disease activity, SLICC damage index, smoking status, and systolic blood pressure, IL-6 was associated with coronary calcification (odds ratio, OR = 1.07, p = 0.035). Similar models found no association between MCP-1 or IL-8 with coronary artery calcification. CONCLUSION: Patients with SLE have increased concentrations of IL-6 and MCP-1. These cytokines are associated with increased inflammation, BMI, and adverse lipid profiles. IL-6 is associated with burden of atherosclerosis in SLE.
AIMS: To determine the extent and prognostic significance of coronary artery calcium in asymptomatic smokers and non-smokers. Population data are available on the prognostic impact of smoking on atherosclerotic imaging measurements of the carotid and peripheral arteries. Limited data are available on the impact of cigarette smoking on the prognostic value of coronary calcium. METHODS AND RESULTS: A referred patient registry of 10,377 asymptomatic individuals (40% were current smokers) was followed for death from all-causes at 5 years. Univariable and multivariable Cox proportional hazard models were calculated to estimate time to all-cause mortality. Cumulative 5-year survival was 96.9 and 98.4% for smokers when compared with non-smokers (P < 0.0001). Using a stratified Cox proportional hazards survival analysis, survival for non-smokers ranged from 99.7 to 89.6% with calcium score of 0-10 and >1000 (P < 0.0001). In comparison, smokers had survival rates ranging from 99.5 to 81.4% for calcium score of 0-10 to >1000 (P < 0.0001). When further evaluating the effect of age on prognosis by coronary calcium, there was an additive relationship between age and calcium that was exacerbated with smoking, resulting in higher relative risk ratios for older smokers with coronary calcium (P < 0.0001). For smokers <50 years of age, a calcium score >1000 was associated with a relative risk ratio that was elevated 8.9-fold (P = 0.029). Thus, resulting in an expected reduction in life expectancy of 4.8 years for smokers <50 years of age with a calcium score >400 (P < 0.0001). CONCLUSION: The prognostic value of coronary artery calcium scoring was accurate in identifying a high-risk cohort of asymptomatic smokers and non-smokers. Young smokers with high-risk calcium scores have a four- to nine-fold increased risk of dying when compared with similarly aged non-smokers. When prospectively applied, evidence of a high-risk calcium score may be useful in educating patients as to their expected risk of dying over the next 5 years.
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The prevalence of ischemic heart disease and atherosclerosis is increased in patients with rheumatoid arthritis (RA). In the general population, but not in patients with systemic lupus erythematosus, the Framingham risk score identifies patients at increased cardiovascular risk and helps determine the need for preventive interventions. We examined the hypothesis that the Framingham score is increased and associated with coronary-artery atherosclerosis in patients with RA. The Framingham score and the 10-year cardiovascular risk were compared among 155 patients with RA (89 with early disease, 66 with long-standing disease) and 85 control subjects. The presence of coronary-artery calcification was determined by electron-beam computed tomography. The Framingham score was compared in patients with RA and control subjects, and the association between the risk score and coronary-artery calcification was examined in patients. Patients with long-standing RA had a higher Framingham score (14 [11 to 18]) (median [interquartile range]) compared to patients with early RA (11 [8 to 14]) or control subjects (12 [7 to 14], P < 0.001). This remained significant after adjustment for age and gender (P = 0.015). Seventy-six patients with RA had coronary calcification; their Framingham risk score was higher (14 [12 to 17]) than that of 79 patients without calcification (10 [5 to 14]) (P < 0.001). Furthermore, a higher Framingham score was associated with a higher calcium score (odds ratio [OR] = 1.20, 95% confidence interval [CI] 1.12 to 1.29, P < 0.001), and the association remained significant after adjustment for age and gender (OR = 1.15, 95% CI 1.02 to 1.29, P = 0.03). In conclusion, a higher Framingham risk score is independently associated with the presence of coronary calcification in patients with RA.
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Coronary artery disease imaging has traditionally been based on luminal angiography, but it has become evident that this tool, although extremely useful in diagnosing obstructive disease, is insufficient to define the presence and extent of atherosclerotic disease in the vessel wall. Progression of coronary artery disease was also initially evaluated using quantitative coronary angiography, and evidence soon accumulated that minor regression or nonprogression of luminal disease was associated with a favorable cardiovascular outcome. In recent years, however, several other techniques have been developed to image atherosclerosis and are emerging as useful tools in preventive cardiovascular medicine. These techniques provide new methods to assess the burden of atherosclerosis, gauge the risk of cardiovascular events, and offer a means to test the efficacy of therapeutic approaches to atherosclerosis. Furthermore, noninvasive coronary angiography can be performed with some of the new imaging modalities, potentially reducing the number of unnecessary invasive tests. This review focuses on techniques such as cardiac computed tomography, carotid artery intima-media thickness, cardiovascular magnetic resonance imaging, and intravascular ultrasonography as emerging tools in cardiovascular disease prevention.
BACKGROUND: Age is assigned a heavy weight in the calculation of the total cardiovascular risk score but often the atherosclerotic disease burden varies from a patient's chronological age. METHODS: We used measures of coronary artery calcium to estimate the number of life years lost (calcium-adjusted age) in 10,377 asymptomatic individuals referred for electron beam tomography (EBT) screening and followed for 5 years for all-cause mortality. Linear regression was used to calculate predicted age and time to death was estimated via a Cox proportional hazard model. RESULTS: There was a direct relationship between coronary artery calcium and observed age (r = 0.32, p < 0.0001). In linear prediction models, a calcium score < 10 resulted in a reduction in observed age by 10 years in subjects older than 70 years, while a calcium score > 400 added as much as 30 years of age to younger patients. Calcium-adjusted age was a better predictor of mortality (model chi2 = 373, p < 0.0001) than observed age (model chi2 = 355, p < 0.0001). Detectable calcium was noted in 16% of men and 12% of women with an unadjusted low risk Framingham score (p < 0.0001). For those with an intermediate Framingham risk score, calcium scores > 10 were noted in 31 and 43% of men and women (p < 0.0001). Using calcium-adjustments to age, 55% of previously low risk Framingham scores to intermediate risk (p < 0.0001). Similarly, 45% of the unadjusted intermediate Framingham risk scores were re-classified as high risk based upon calcium-adjusted ages (p < 0.0001). CONCLUSIONS: Measures of coronary artery calcium are related to survival and can be used to assess an individual's biological age. Undetected risk based upon current calculations of the Framingham risk may be improved based upon determination of a re-adjustment of a patient's age using the extent of coronary calcification.
We utilized coronary artery calcium scores (CACS) to assess differences in atherosclerosis burden between asymptomatic White populations living in continents with different cardiovascular disease rates. The similarities in the genetic pool between Brazilian and Portuguese Caucasian subjects offered an opportunity to assess the influence of environmental factors on the development of atherosclerosis. We reviewed CACS data from 17,563 individuals (12,378 men and 5169 women) collected in the USA (74% of the subjects), Brazil (15% of the subjects) and Portugal (11% of the subjects). CACS was absent in 80 and 88% of Portuguese men and women, compared with 46 and 62% and 33 and 59% of Brazilian and US counterparts (p<0.0001). Although the US subjects showed the lowest prevalence of risk factors they had a higher median (interquartile range) CACS than the Brazilian and the Portuguese cohorts: 4 (0;87), 1 (0;68) and 0 (0;0), respectively (p<0.0001). After adjusting for differences in age and cardiovascular risk factors, US men showed higher relative risk ratios of having any CACS than either Brazilian or Portuguese men. Brazilian and US women did not differ as far as risk of CACS although they demonstrated a greater risk than Portuguese women. In this study, significant differences in CACS were detected among three nations in different continents. The CACS differences paralleled the respective cardiovascular mortality rates.
OBJECTIVES: The purpose of this study was to investigate the classification of cardiovascular risk in young individuals and women according to the National Cholesterol Education Program (NCEP) guidelines across a continuum of coronary calcium scores (CCS). BACKGROUND: Current NCEP guidelines might underestimate cardiovascular risk in young individuals and women. METHODS: The study population consisted of 1,611 asymptomatic individuals (67% men, mean age: 53 +/- 10 years) who presented to a single electron beam tomography facility for coronary artery calcium screening. Participants were categorized into low-risk (n = 738, 46%), intermediate-risk (n = 583, 36%), moderately high-risk (n = 263, 16%), and high-risk (n = 27, 2%) according to the NCEP Panel III guidelines. RESULTS: Absence of calcium, CCS of 0 to 99 (mild), 100 to 399 (moderate), and > or =400 (severe), was observed in 572 (35%), 707 (44%), 192 (12%), and 140 (9%) of the patients, respectively. A high CCS percentile (> or =75th percentile) was present in 426 (26%) individuals. Overall, 59% and 78% of participants with CCS > or =400 and CCS > or =75th percentile were not identified as high risk and candidates for pharmacotherapy on the basis of NCEP categories. Furthermore, women as well as young individuals were less likely to be considered candidates for pharmacotherapy compared with men and older individuals in each CCS category. CONCLUSIONS: The NCEP guidelines seem to underestimate cardiovascular risk in young asymptomatic individuals and women. For these individuals, assessment of plaque burden might provide incremental value to global risk assessment.