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.

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.

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.

Adipocytokines in systemic lupus erythematosus: relationship to inflammation, insulin resistance and coronary atherosclerosis.

We tested the hypothesis that concentrations of adipocytokines are altered in SLE and associated with coronary atherosclerosis, insulin resistance and inflammation. Concentrations of resistin, leptin, adiponectin and visfatin were measured in 109 patients with SLE and 78 control subjects. Coronary calcification was measured using electron beam-computed tomography, and insulin resistance was defined by the homeostasis model assessment index. Concentrations of adiponectin (28.7 +/- 17.9 vs 22.0 +/- 15.3 microg/mL, P = 0.003), leptin (41.1 +/- 49.9 vs 19.8 +/- 24.6 ng/mL, P < 0.001) and visfatin (7.5 +/- 10.5 vs 4.5 +/- 2.8 ng/mL, P < 0.001) were higher in patients with SLE than in controls. These differences remained significant after adjustment for age, race, sex and body mass index (BMI; all P values < 0.02). Concentrations of resistin (10.7 +/- 7.6 vs 9.1 +/- 5.1 ng/mL, P = 0.41) did not differ in patients and controls. In patients with SLE, leptin was positively associated with BMI (rho = 0.80, P < 0.001), insulin resistance (rho = 0.46, P < 0.001) and C-reactive protein (CRP) (rho = 0.30, P = 0.002), whereas adiponectin was negatively associated with the same factors (rho = -0.40, P < 0.001; rho = -0.38, P < 0.001; rho = -0.22, P = 0.02, respectively). None of the adipocytokines were associated with coronary atherosclerosis in SLE. In conclusion, patients with SLE have increased concentrations of adiponectin, leptin and visfatin. Lower concentrations of adiponectin and higher concentrations of leptin are associated with insulin resistance, BMI and CRP in patients with SLE.

Markers of vascular disease do not differ in black and white hemodialysis patients despite a different risk profile.

Increased aortic stiffness, as measured by pulse wave velocity (PWV) and augmentation index (Aix), and vascular calcification have been associated with an unfavourable cardiovascular outcome in hemodialysis patients. However, the majority of data have been published in white patients and epidemiological data are discordant on the fate of patients of different races. In this cross sectional study we measured PWV and Aix by applanation tonometry and coronary artery and thoracic aorta calcium score (CAC and AoC) by electron beam tomography (EBT) in 81 Blacks and 61 Whites on maintenance hemodialysis. Vascular stiffness measurements and EBT scans were performed within a week of each other. There was no difference between races in age, systolic blood pressure or gender distribution. Blacks had a more frequent history of hypertension (100% versus 89%; P=0.002), lower prevalence of dyslipidemia (30% versus 66%; P<0.001), higher PTH levels (geometric mean 607 pg/ml versus 245 pg/ml; P=0.039), received calcium based phosphate binders less frequently (37% versus 60%, P=0.007) and calcium antagonists more frequently than Whites (54% versus 28%; P=0.003). Nonetheless, the unadjusted and risk adjusted PWV and Aix, as well as CAC and AoC were not statistically different between races. In this dialysis cohort there was no difference in markers of vasculopathy between black and white patients despite differences in baseline clinical characteristics. Epidemiological data from the general population indicate that Blacks have lower calcium scores and stiffer vessels than Whites. Some studies in the renal populations suggest a better and others a similar survival of Blacks and Whites on hemodialysis. Our findings raise the important question of the prognostic significance of markers of vasculopathy in patients of different races and with different risk profiles.

Association of pulse wave velocity with vascular and valvular calcification in hemodialysis patients.

The recent Kidney Disease: Improving Quality Outcomes (KDIGO) recommendations called for an investigation of the relationship between various radiological methods to assess cardiovascular calcification and measures of arterial stiffness. Accordingly, in 131 adult maintenance hemodialysis patients, we investigated the association of aortic pulse wave velocity (PWV) with calcification of cardiac valves on echocardiography, coronary artery, and thoracic aorta calcium on computed tomography and a calcification score of the abdominal aorta obtained on a plain abdominal X-ray. All tests were performed within a week. Mean PWV increased as the severity of coronary artery, thoracic, and abdominal aorta calcium scores increased (each P<0.05). No trend was present for number of valves with calcification. After multivariable adjustment, abdominal aorta X-ray calcium scores remained associated with PWV (P=0.004), whereas the association of PWV with thoracic aorta and coronary artery calcium scores became marginal (P=0.308 and P=0.083, respectively). No association was found between number of calcified valves and PWV. This study demonstrates a strong association between abdominal aorta calcification on plain X-ray and PWV and a borderline association with thoracic aorta and coronary artery calcification. Sudden death and congestive heart failure, two frequent causes of death in hemodialysis, are likely caused by increased arterial stiffness that can be closely predicted by the presence of aortic calcification on plain X-rays.

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.

Juice powder concentrate and systemic blood pressure, progression of coronary artery calcium and antioxidant status in hypertensive subjects: a pilot study.

Because micronutrients from plants may have beneficial cardiovascular effects, the hypothesis that an encapsulated juice powder concentrate might affect several measures of vascular health was tested in free living adults at low cardiovascular risk. Blood pressure, vascular compliance, lipid and antioxidant markers, and serial electron beam tomography (to calculate a coronary artery calcium score as a measure of atherosclerosis burden), were monitored in 51 pre-hypertensive and hypertensive subjects over 2 years. By the end of follow-up, systolic and diastolic blood pressure decreased significantly (-2.4 +/- 1.0 mmHg, P < 0.05 and -2.2 +/- 0.6 mmHg, P < 0.001), and large artery compliance improved significantly (1.9 +/- 0.6 ml mmHg(-1) x 100, P < 0.01). The progression of coronary artery calcium score was smaller than expected compared with a historical database (P < 0.001). Laboratory testing showed a significant decrease in homocysteine (P = 0.05), HDL cholesterol (P = 0.025) and Apo A (P = 0.004), as well as a significant increase in beta-carotene, folate, Co-Q10 and alpha-tocopherol (all P < 0.001). The phytonutrient concentrate we utilized induced several favorable modifications of markers of vascular health in the subjects. This study supports the notion that plant nutrients are important components of a heart healthy diet.

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.

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).

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.

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.

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.

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.

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.

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.

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.