Coronary Artery Disease: Budoff M

Bluemke DA, Achenbach S, Budoff M, Gerber TC, Gersh B, Hillis LD, Hundley WG, Manning WJ, Printz BF, Stuber M, Woodard PK. · No affiliation provided · Circulation. · Pubmed #18586979 links to  free full text

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Burgstahler C, Budoff M. · No affiliation provided · J Cardiovasc Comput Tomogr. · Pubmed #19083886 No free full text.

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Foster G, Shah H, Sarraf G, Ahmadi N, Budoff M. · Cardiology Section, Department of Medicine, Veterans Affairs Loma Linda Health Care System, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA. · Expert Rev Cardiovasc Ther. · Pubmed #19105767 No free full text.

Abstract: New tomographic cardiovascular imaging tests, such as intravascular ultrasonography and coronary computed tomography angiography, can be used to assess atherosclerotic plaques for the characterization and early staging of coronary artery disease (CAD). Although intravascular ultrasonography provides high-resolution images that are capable of revealing early preclinical CAD, it is a highly invasive technique used clinically only in conjunction with coronary interventions. Multidetector computed tomography angiography, which is noninvasive and corresponds well with plaque histology, shows promise as a diagnostic method for CAD and can provide general evaluation of noncalcified and mixed plaque composition. The current generation of 64-slice computed tomography scanners have high accuracy for detection of lesions obstructing more than 50% of the lumen, with sensitivity, specificity, and positive and negative predictive values all over 90% in patients without known CAD. They may have an important role in characterizing high-risk noncalcified and mixed plaques. Review of the currently available literature suggests that tissue density measured by multidetector computed tomography can be used to accurately characterize coronary atherosclerotic plaque composition. With further advances in tomographic angiography, the goal will be to detect plaques earlier in the development of CAD and to characterize the plaques most likely to generate a clinical event.

Butt AA, Xiaoqiang W, Budoff M, Leaf D, Kuller LH, Justice AC. · VA Pittsburgh Healthcare System, University of Pittsburgh School of Medicine, Center for Health Equity Research and Promotion, Pittsburgh, Pennsylvania, USA. · Clin Infect Dis. · Pubmed #19508169 No free full text.

Abstract: BACKGROUND: The association between hepatitis C virus (HCV) infection and coronary artery disease (CAD) is controversial. We conducted this study to determine and quantify this association. METHODS: We used an established, national, observational cohort of all HCV-infected veterans receiving care at all Veterans Affairs facilities, the Electronically Retrieved Cohort of HCV Infected Veterans, to identify HCV-infected subjects and HCV-uninfected control subjects. We used the Cox proportional-hazards model to determine the risk of CAD among HCV-infected subjects and control subjects. RESULTS: We identified 82,083 HCV-infected and 89,582 HCV-uninfected subjects. HCV-infected subjects were less likely to have hypertension, hyperlipidemia, and diabetes but were more likely to abuse alcohol and drugs and to have renal failure and anemia. HCV-infected subjects had lower mean (+/- standard deviation) total plasma cholesterol (175 +/- 40.8 mg/dL vs. 198 +/- 41.0 mg/dL), low-density lipoprotein cholesterol (102 +/- 36.8 mg/dL vs. 119 +/- 38.2 mg/dL), and triglyceride (144 +/- 119 mg/dL vs. 179 +/- 151 mg/dL) levels, compared with HCV-uninfected subjects ([Formula: see text] for all comparisons). In multivariable analysis, HCV infection was associated with a higher risk of CAD (hazard ratio, 1.25; 95% confidence interval, 1.20-1.30). Traditional risk factors (age, hypertension, chronic obstructive pulmonary disease, diabetes, and hyperlipidemia) were associated with a higher risk of CAD in both groups, whereas minority race and female sex were associated with a lower risk of CAD. CONCLUSIONS: HCV-infected persons are younger and have lower lipid levels and a lower prevalence of hypertension. Despite a favorable risk profile, HCV infection is associated with a higher risk of CAD after adjustment for traditional risk factors.

Douglas PS, Budoff M, Tunis S, Woodard PK, Justman RA, Honigberg R. · Duke University Medical Center, Durham, NC, USA. · JACC Cardiovasc Imaging. · Pubmed #19356455 No free full text.

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Williams M, Shaw LJ, Raggi P, Morris D, Vaccarino V, Liu ST, Weinstein SR, Mosler TP, Tseng PH, Flores FR, Nasir K, Budoff M. · Emory University School of Medicine, Atlanta, Georgia 30306, USA. · JACC Cardiovasc Imaging. · Pubmed #19356407 No free full text.

Abstract: OBJECTIVES: This study sought to evaluate the long-term prognostic value of the number and sites of calcified coronary lesions and to compare the accuracy of number of calcified lesions with the extent of total calcium score. BACKGROUND: There is a strong relationship between mortality and total coronary artery calcium (CAC) score. It is not known whether the number of calcified lesions or their location influences outcome. METHODS: A total of 14,759 asymptomatic patients were referred for evaluation of CAC scanning using electron beam tomography. Univariable and multivariable Cox proportional hazards models were developed to estimate time to all-cause mortality at, on average, 6.8 years (n = 281). RESULTS: Risk-adjusted annual mortality was 0.19% (95% confidence interval 0.18% to 0.21%) for patients without any calcified lesions. For patients with >20 lesions, annual risk-adjusted mortality exceeded 2% per year. Mortality rates were significantly higher for left main lesions as compared to other coronary arteries with annual mortality rates of 1.3%, 2.1%, 9.2%, and 13.6% for 1 to 2, 3 to 5, and > or =6 lesions, respectively (p < 0.0001). For left main CAC scores of 0 to 10, 11 to 100, 101 to 399, and 400 to 999, annual risk-adjusted mortality was 0.33%, 0.81%, 1.73%, and 7.71%, respectively (p < 0.0001). All 4 patients with a CAC score of > or =1,000 in the left main died during follow-up. However, patients with more frequent calcified lesions also had higher CAC scores. Specifically, > or =81% of patients with >10 calcified lesions also had a CAC score > or =100. With exception, for patients with CAC scores > or =1,000, annual mortality was dramatically higher at 3.0% to 4.5% for those with 1 to 5 calcified lesions as compared with 1.1% to 2.0% for those with 6 or more lesions (p < 0.0001). CONCLUSIONS: We report that mortality rates increased proportionally with the number of calcified lesions. Although predictive information is contained in the number of calcified lesions, its added statistical value is minimal. With exception, patients with frequent lesions in the left main or those with a few large calcified lesions have a particularly high mortality risk.

Ahmadi N, Usman N, Shim J, Nuguri V, Vasinrapee P, Hajsadeghi F, Wang Z, Foster GP, Nasir K, Hecht H, Naghavi M, Budoff M. · Los Angeles Biomedical Research Institute, Harbor UCLA Medical Center, 1124 W. Carson Street, RB2, Torrance, CA 90502, USA. · J Nucl Cardiol. · Pubmed #19125310 No free full text.

Abstract: BACKGROUND: Previous studies have shown that vascular dysfunction measured by digital thermal monitoring (DTM) during an arm-cuff reactive hyperemia procedure correlates with the severity of coronary artery disease measured by coronary artery calcium in asymptomatic patients. Current study investigates the correlation between DTM and abnormal myocardial perfusion imaging (MPI). METHODS: About 116 consecutive patients with chest discomfort, age 57 +/- 10 years, underwent MPI, DTM and Framingham Risk Score (FRS) assessment. Fingertip temperature rebound (TR), DTM index of vascular reactivity, was assessed after a 2-minute arm-cuff reactive hyperemia test. The extent of myocardial perfusion defect was measured by summed stress score (SSS). RESULTS: TR decreased from SSS < 4 (1.61 +/- 0.15) to 4 < or = SSS < or = 8 (0.5 +/- 0.22) to 9 < or = SSS < or = 13 (0.26 +/- 0.15) to SSS > 13 (-0.37 +/- 0.19) (P = .0001). After adjusting for cardiac risk factors, the odds ratio of the lowest versus two upper tertiles of TR was 3.93 for SSS > or = 4 and 9.65 for SSS > or = 8 compared to SSS < 4. TR correlated well with SSS (r = -0.88, P = .0001). Addition of TR to FRS increased the area under the ROC curve to predict abnormal MPI, SSS > or = 4, from 0.65 to 0.84 (P < .05). CONCLUSION: Vascular dysfunction measured by DTM is associated with the extent of myocardial perfusion defect independent of age, gender, and cardiac risk factors.

McClelland RL, Nasir K, Budoff M, Blumenthal RS, Kronmal RA. · Department of Biostatistics, University of Washington, Seattle, Washington, USA. · Am J Cardiol. · Pubmed #19101230 No free full text.

Abstract: It has been proposed that coronary artery calcium (CAC) can be used to estimate arterial age in adults. Supporting this concept is that chronologic age, as used in cardiovascular risk assessment, is a surrogate for atherosclerotic burden. This measure can provide patients with a more understandable version of their CAC scores (e.g., "You are 55 years old, but your arteries are more consistent with an arterial age of 65 years"). The aim of this study was to describe a method of calculating arterial age by equating estimated coronary heart disease (CHD) risk for observed age and CAC. Arterial age is then the risk equivalent of CAC. Data from the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort study of 6,814 participants free of clinical cardiovascular disease and followed for an average of 4 years, were used. Estimated arterial age was obtained as a simple linear function of log-transformed CAC. In a model for incident CHD risk controlling for age and arterial age, only arterial age was significant, indicating that observed age does not provide additional information after controlling for arterial age. Framingham risk calculated using this arterial age was more predictive of short-term incident coronary events than Framingham risk on the basis of observed age (area under the receiver-operating characteristic curve 0.75 for Framingham risk on the basis of observed age and 0.79 using arterial age, p = 0.006). In conclusion, arterial age provides a convenient transformation of CAC from Agatston units to a scale more easily appreciated by patients and treating physicians.

Ahmadi N, Hajsadeghi F, Gul K, Vane J, Usman N, Flores F, Nasir K, Hecht H, Naghavi M, Budoff M. · Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center, 1124 West Carson Street, RB2, Torrance, CA 90502, USA. · J Cardiovasc Comput Tomogr. · Pubmed #19083982 No free full text.

Abstract: BACKGROUND: Digital thermal monitoring (DTM) of vascular function was shown to correlate with the presence of known coronary artery disease (CAD). OBJECTIVE: We evaluated whether DTM can identify at-risk, asymptomatic patients with significant coronary artery calcium (CAC) or increased Framingham risk score (FRS). METHODS: Two hundred thirty-three consecutive asymptomatic subjects (58 +/- 11 years; 62% men) without known CAD underwent DTM, CAC, and FRS calculation. DTM measurements were obtained during and after a 5-minute suprasystolic arm-cuff occlusion. After cuff-deflation temperature rebound (TR) and area under the temperature curve (AUC) were measured and correlated with FRS and CAC. RESULTS: TR was lower in patients with FRS > 20% and CAC >or= 100 as compared with FRS < 10% and CAC < 10, respectively (P < 0.05). After adjustment for age, sex, and traditional cardiac risk factors, the odds ratio of the lowest compared with the upper 2 tertiles of TR was 3.96 for FRS >or= 20% and 2.37 for CAC >or= 100 compared with low-risk cohorts. The area under the receiver operating characteristic (ROC) curve to predict CAC >or= 100 increased significantly from 0.66 for FRS to 0.79 for TR to 0.89 for TR + FRS. CONCLUSIONS: Vascular dysfunction measured by DTM strongly correlates with FRS and CAC independent of age, sex, and traditional cardiac risk factors and was superior to FRS for the prediction of significant CAC.

Kingsley LA, Cuervo-Rojas J, Muñoz A, Palella FJ, Post W, Witt MD, Budoff M, Kuller L. · Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA. · AIDS. · Pubmed #18670218 No free full text.

Abstract: OBJECTIVE: To evaluate the association of HIV infection and cumulative exposure to highly active antiretroviral therapy (HAART) with the presence and extent of coronary artery calcification (CAC). DESIGN: A cross-sectional study of 947 male participants (332 HIV-seronegative, 84 HAART-naive and 531 HAART-experienced HIV-infected) from the Multicenter AIDS Cohort Study. METHODS: The main outcome was CAC score calculated as the geometric mean of the Agatston scores of two computed tomography replicates. Presence of CAC was defined as calcification score above 10, and extent of CAC by the score for those with CAC present. Multivariable regression was used to evaluate the association between HIV infection and HAART and presence and extent of calcification. RESULTS: Increasing age was most strongly associated with both prevalence and extent of CAC for all study groups. After adjustment for age, race, family history, smoking, high-density lipoprotein-C, low-density lipoprotein-C and hypertension, HIV infection (odds ratio, 1.35; 95% confidence interval, 0.70, 2.61) and long-term HAART use (odds ratio, 1.33; 95% confidence interval, 0.87, 2.05) increased the odds for presence of CAC. In contrast, after adjustment for these covariates, the extent of CAC was lower among HAART users. Among those not taking lipid-lowering therapy, HAART usage of at least 8 years was associated with significantly reduced CAC scores (relative CAC score, 0.43; 95% confidence interval, 0.24, 0.79). CONCLUSION: HAART use may have different effects on the presence and extent of coronary calcification. Although prevalence of calcification was marginally increased among long-term HAART users, the extent of calcification was significantly reduced among HAART users compared with HIV-seronegative controls.

Raggi P, Gongora MC, Gopal A, Callister TQ, Budoff M, Shaw LJ. · Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA. · J Am Coll Cardiol. · Pubmed #18582630 No free full text.

Abstract: OBJECTIVES: We sought to study the prognostic utility of coronary artery calcium (CAC) in the elderly. BACKGROUND: The prognostic significance of CAC in the elderly is not well known. METHODS: All-cause mortality was assessed in 35,388 patients (3,570 were >or=70 years old at screening, and 50% were women) after a mean follow-up of 5.8 +/- 3 years. RESULTS: In older patients, risk factors and CAC were more prevalent. Overall survival was 97.9% at the end of follow-up. Mortality increased with each age decile with a relative hazard of 1.09 (95% confidence interval: 1.08 to 1.10, p < 0.0001), and rates were greater for men than women (hazard ratio: 1.53; 95% confidence interval: 1.32 to 1.77, p < 0.0001). Increasing CAC scores were associated with decreasing survival across all age deciles (p < 0.0001). Survival for a <40-year and >or=80-year-old man with a CAC score >or=400 was 88% and 19% (95% and 44% for a woman, p < 0.0001), respectively. Among the 20,562 patients with no CAC, annual mortality rates ranged from 0.3% to 2.2% for patients age 40 to 49 years or >or=70 years (p < 0.0001). The use of CAC allowed us to reclassify more than 40% of the patients >or=70 years old more often by excluding risk (i.e., CAC <400) in those with >3 risk factors. CONCLUSIONS: Despite their limited life expectancy, the use of CAC discriminates mortality risk in the elderly. Furthermore, the use of CAC allows physicians to reclassify risk in the elderly.

Qunibi W, Moustafa M, Muenz LR, He DY, Kessler PD, Diaz-Buxo JA, Budoff M, Anonymous00177. · Department of Medicine, Division of Nephrology, University of Texas Health Sciences Center, San Antonio, TX 78229-3900, USA. · Am J Kidney Dis. · Pubmed #18423809 No free full text.

Abstract: BACKGROUND: Previous clinical trials showed that progression of coronary artery calcification (CAC) may be slower in hemodialysis patients treated with sevelamer than those treated with calcium-based phosphate binders. Because sevelamer decreases low-density lipoprotein cholesterol (LDL-C) levels, we hypothesized that intensive lowering of LDL-C levels with atorvastatin in hemodialysis patients treated with calcium acetate would result in CAC progression rates similar to those in sevelamer-treated patients. STUDY DESIGN: Randomized, controlled, open-label, noninferiority trial with an upper bound for the noninferiority margin of 1.8. SETTING & PARTICIPANTS: 203 prevalent hemodialysis patients at 26 dialysis centers with serum phosphorus levels greater than 5.5 mg/dL, LDL-C levels greater than 80 mg/dL, and baseline CAC scores of 30 to 7,000 units assessed by means of electron-beam computed tomography. INTERVENTIONS: 103 patients were randomly assigned to calcium acetate, and 100 patients to sevelamer for 12 months to achieve phosphorus levels of 3.5 to 5.5 mg/dL. Atorvastatin was added to achieve serum LDL-C levels less than 70 mg/dL in both groups. OUTCOMES & MEASUREMENTS: The primary end point was change in CAC score assessed by means of electron-beam computed tomography. RESULTS: After 12 months, mean serum LDL-C levels decreased to 68.8 +/- 22.0 mg/dL in the calcium-acetate group and 62.4 +/- 23.0 mg/dL in the sevelamer group (P = 0.3). Geometric mean increases in CAC scores were 35% in the calcium-acetate group and 39% in the sevelamer group, with a covariate-adjusted calcium acetate-sevelamer ratio of 0.994 (95% confidence interval, 0.851 to 1.161). LIMITATIONS: Treatment assignment was not blinded. The 1.8 a priori margin is large, CAC is a surrogate outcome, duration of treatment was short, and dropout rate was high. CONCLUSIONS: With intensive lowering of LDL-C levels for 1 year, hemodialysis patients treated with either calcium acetate or sevelamer experienced similar progression of CAC.

Mehrotra R, Kermah D, Budoff M, Salusky IB, Mao SS, Gao YL, Takasu J, Adler S, Norris K. · Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA. · Clin J Am Soc Nephrol. · Pubmed #18417740 links to  free full text

Abstract: BACKGROUND AND OBJECTIVES: Recent studies show high prevalence of suboptimal 25-hydroxyvitamin D levels in chronic kidney disease patients. This study sought to test the hypothesis that the prevalence of 25-hydroxyvitamin D deficiency is significantly higher in chronic kidney disease patients and, in diabetic nephropathy, low serum 25-hydroxyvitamin D is associated with abnormal serum parathyroid hormone, bone mineral density, and coronary artery calcification. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Study A used data from the Third National Health and Nutrition Examination Survey. Study B was a post hoc analysis of an observational study of coronary artery calcification in non-dialysis-dependent diabetic nephropathy. RESULTS: In study A, the adjusted odds for 25-hydroxyvitamin D deficiency were 32% higher in chronic kidney disease patients. This higher prevalence of 25-hydroxyvitamin D deficiency, however, could not be explained by differences in total vitamin D intakes. The consequences of suboptimal 25-hydroxyvitamin D levels were analyzed in 146 patients with diabetic nephropathy. The significant, inverse relationship between serum 25-hydroxyvitamin D and parathyroid hormone levels was attenuated to a nonsignificant level on multivariate adjustment. There was a significant, inverse relationship between bone mineral density and coronary artery calcification scores; neither was independently associated with serum 25-hydroxyvitamin D. The serum 25-hydroxyvitamin D levels declined modestly in 72 patients studied after 12.4 +/- 0.4 mo. CONCLUSIONS: 25-Hydroxyvitamin D deficiency is more common in chronic kidney disease, but this higher prevalence is unlikely to be a result of lower vitamin D intakes. The consequences of suboptimal 25-hydroxyvitamin D levels remain to be definitively elucidated.

Tong LL, Mehrotra R, Shavelle DM, Budoff M, Adler S. · Division of Nephrology and Hypertension, Los Angeles Biomedical Research Institute at Harbor, UCLA Medical Center, Torrance, California, U.S.A. · Hemodial Int. · Pubmed #18271835 No free full text.

Abstract: Vascular calcification is highly prevalent and often severe in patients with chronic kidney disease. Arterial calcification in patients with chronic kidney disease can result from the deposition of mineral along the intimal layer of arteries in conjunction with atheromatous plaques or from calcium deposition in the medial wall of arteries, also known as Monckeberg's sclerosis. Whether coronary artery calcium scores as measured by electron beam computed tomography correlate with occlusive atherosclerotic disease in the dialysis population is uncertain. Here we report a case of an asymptomatic patient with diabetes mellitus and end-stage renal disease undergoing maintenance hemodialysis, who was found to have extremely elevated coronary artery calcium scores on electron beam computed tomography, but varied degrees of atherosclerotic plaque in her coronary arteries on coronary angiography. This suggests that in addition to the calcification anticipated in a remodeled intima, a proportion of the calcification is also likely to be in the arterial media. Thus, this case demonstrates that even an extremely high coronary calcium score may not be a satisfactory surrogate marker for obstructive atherosclerosis in elderly diabetic dialysis patients.

Budoff M. · Division of Cardiology, Harbor-UCLA Medical Center, Torrance, CA, USA. · J Nutr. · Pubmed #16484554 links to  free full text

Abstract: Prospective epidemiologic studies have identified several risk factors for heart disease, and most can be the target of risk reduction interventions. The most widely recognized risk factors for atherosclerotic cardiovascular disease (ASCVD) include age, gender, cigarette smoking, sedentary lifestyle, elevated LDL, reduced HDL, hypertension, and diabetes. The consistency of associations between these factors and ASCVD risk across populations is substantial. Our understanding of the pathogenesis and etiology of coronary ASCVD, as well as its clinical implications, has grown tremendously over the past 20 y. The role garlic might play in treating ASCVD has been postulated for many years, but until recently no studies on garlic's ability to inhibit the atherosclerotic process have been reported. A pilot study evaluating coronary artery calcification and the effect of garlic therapy in a group of patients who were also on statin therapy suggested incremental benefits. The implications of this study must be put in context of the potential importance of early atherosclerosis detection and prevention.

Mehrotra R, Budoff M, Hokanson JE, Ipp E, Takasu J, Adler S. · Division of Nephrology and Hypertension, Harbor-UCLA Medical Center, Torrance, California 90502, USA. · Kidney Int. · Pubmed #16105059 No free full text.

Abstract: BACKGROUND: Rapid progression of coronary artery calcification (CAC) has been reported among individuals with end-stage renal disease (ESRD). There is limited information on the progression of CAC during earlier stages of diabetic chronic kidney disease (CKD). METHODS: In a prospective, cohort study of type 2 diabetic individuals (N = 90; normoalbuminuric diabetic controls, 30; diabetic nephropathy, DN, 60), electron-beam computed tomography (EBCT) was repeated at an average interval of 19 months. All scan images were acquired at end-systole to minimize interscan variability. In order to eliminate the dependence of the residual error from interscan variability on baseline CAC scores, square root transformed CAC scores were used for analyses of progression of coronary calcification. RESULTS: Repeat EBCT scans were completed in 68 subjects (diabetic controls: 23; DN: 45). There was a highly significant relationship between the proportion of subjects with progressive CAC and renal disease-DN who progressed to ESRD, 80%; DN who did not progress to ESRD, 30%; and diabetic controls, 13% (P < 0.001). Similarly, the magnitude of change was significantly related to renal disease (DN who progressed to ESRD > DN who did not progress to ESRD > diabetic controls, P < 0.001). Using logistic regression and controlling for non-dialyzed DN, ESRD and inter-scan interval, advanced age was the only significant variable associated with progression of CAC. Finally, serum creatinine and baseline CAC score emerged as independent predictors for the magnitude of increase in CAC. CONCLUSION: Progression of CAC is apparent among individuals with DN both before and after ESRD. However, the risk factors associated with progression of CAC may differ at different stages of CKD.

Raggi P, Cooil B, Ratti C, Callister TQ, Budoff M. · Tulane University School of Medicine, 1430 Tulane Ave, SL-48, New Orleans, LA 70112, USA. · Hypertension. · Pubmed #15851627 links to  free full text

Abstract: 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.

Mehrotra R, Westenfeld R, Christenson P, Budoff M, Ipp E, Takasu J, Gupta A, Norris K, Ketteler M, Adler S. · Division of Nephrology and Hypertension, Harbor-UCLA Medical Center, Torrance, California 90502, USA. · Kidney Int. · Pubmed #15698447 No free full text.

Abstract: BACKGROUND: Fetuin-A is the most potent circulating inhibitor of calcium phosphorus precipitation and, possibly, an important mediator of insulin resistance. METHODS: In order to determine the role of fetuin-A in the high coronary artery calcification (CAC) burden seen in nondialyzed individuals with diabetic nephropathy (DN), post-hoc analyses of data collected from a cross-sectional study of 88 patients with type 2 diabetes mellitus was done [age, 40-65 years; normoalbuminuria, N= 30 (Latinos); DN, N= 58 (Latinos and African Americans)]. RESULTS: The serum levels of fetuin-A were significantly higher among Latinos with DN when compared to either African Americans with DN or Latino diabetics with normoalbuminuria. Upon adjusting the data for race/ethnicity, there was a strong, direct relationship between serum fetuin-A levels and the CAC score (r= 0.22, P= 0.038) in the study cohort; however, a strong interaction between the nephropathy status and relationship of serum fetuin-A levels with CAC score was present (DN: r= 0.36, P= 0.006; diabetic controls, r= 0.0, P= 0.98). Among individuals with DN, the significance of the association persisted even after controlling the data for other predictors of CAC (partial r= 0.33, P= 0.018). Furthermore, there was a significant direct relationship between serum fetuin-A and serum triglycerides (partial r= 0.27, P= 0.01) and albumin (partial r= 0.30, P= 0.005), and an inverse relationship with glomerular filtration rate (r=-0.24, P= 0.03). CONCLUSION: This first study in early stages of diabetic chronic kidney disease shows that the role of serum fetuin-A may be far more complex than previously described. During predialysis stage of DN, there is a direct relationship between serum fetuin-A levels and CAC score. The reasons for this association in the presence of nephropathy are unclear, but may be secondary to proatherogenic insulin resistance.

Mehrotra R, Budoff M, Christenson P, Ipp E, Takasu J, Gupta A, Norris K, Adler S. · Division of Nephrology and Hypertension, Harbor-UCLA Medical Center, Torrance, California 90502, USA. · Kidney Int. · Pubmed #15496175 No free full text.

Abstract: BACKGROUND: In the general population, including those with diabetes mellitus, coronary artery calcification (CAC) correlates with atherosclerotic plaque burden. On the other hand, accumulating evidence suggests that disordered mineral metabolism significantly contributes to the vascular calcification in individuals with end-stage renal disease (ESRD). METHODS: In order to determine the relative contribution of accelerated atherosclerosis and disordered mineral metabolism to CAC in chronic kidney disease, a pilot study of 90 patients with type 2 diabetes mellitus was done [age, 40-65 years; normoalbuminuria, N= 30; diabetic nephropathy (DN), N= 60]. RESULTS: CAC was more prevalent and severe among individuals with DN compared to diabetic controls (odds ratio for prevalence 8.1, 95% CI 2.3-28.5; median scores, 66 vs. 4, P < 0.001). None of the 4 measures of disordered mineral metabolism evaluated in this study (serum calcium, phosphorus, parathyroid hormone, and 1,25 di-hydroxy vitamin D levels) correlated with the prevalence or severity of CAC, or accounted for the differences seen between DN and diabetic controls. On the other hand, the difference in the severity of hypertension (number of antihypertensive medications) appeared to account for the differences in CAC burden seen between DN and diabetic controls. CONCLUSION: This first such study of nondialyzed individuals with DN suggests that, unlike ESRD patients, the high CAC burden seen at earlier stages of diabetic chronic kidney disease is probably unrelated to disordered mineral metabolism. The relationship between the severity of hypertension and CAC burden provides a probable target for intervention in the predialysis phase of DN.

Raggi P, Cooil B, Shaw LJ, Aboulhson J, Takasu J, Budoff M, Callister TQ. · Tulane University School of Medicine, New Orleans, Lousiana, USA. · Am J Cardiol. · Pubmed #14516885 No free full text.

Abstract: We conducted an observational study relating the occurrence of acute myocardial infarction (MI) to coronary artery calcium progression in 817 asymptomatic subjects referred for sequential electron beam tomographic imaging (average interval 2.2 +/- 1.3 years). A calcium volume score (CVS) was used for plaque quantification. The yearly mean absolute and percent CVS changes in the 45 patients who had a MI were 147 +/- 152 and 47 +/- 50%, respectively, compared with 63 +/- 128 and 26 +/- 32%, respectively (p <0.001, p = 0.01), in patients without events.

Merjanian R, Budoff M, Adler S, Berman N, Mehrotra R. · Division of Nephrology and Hypertension, Department of Pediatrics, Harbor-UCLA Medical Center and Research and Education Institute, Torrance, California 90502, USA. · Kidney Int. · Pubmed #12787418 No free full text.

Abstract: BACKGROUND: Individuals with end-stage renal disease (ESRD) have highly prevalent and severe vascular and valvular calcification. We undertook this study to test the hypothesis that vascular and valvular calcification begins and is often severe long before diabetic renal disease progresses to ESRD. METHODS: A total of 32 nondialyzed individuals with type 2 diabetes mellitus and diabetic renal disease (albumin excretion rate>30 microg/min) [mean glomerular filtration rate (GFR), 49.8 +/- 6.1 mL/min/1.73 m2] were identified and compared with a group of 18 normoalbuminuric diabetics. We used 3:1 matching to identify 95 nondiabetic controls without renal disease, matched for age, gender, ethnicity, and the presence/absence of dyslipidemia, hypertension, and known coronary artery disease (CAD). RESULTS: Using electron beam computed tomography (CT), the prevalence of coronary artery calcification was significantly greater among diabetic renal disease individuals (prevalence, 94% vs. 59%, P < 0.001; median score, 238 vs. 10, P < 0.001) than the nondiabetic controls. The coronary artery calcification scores were significantly more severe among diabetic renal disease individuals than either the diabetic or nondiabetic controls. Among individuals with diabetic renal disease, the coronary artery calcification and aortic wall calcification scores were several-fold greater among those with known CAD than among those without. There was also a significantly greater prevalence of aortic and mitral valve calcification among diabetic renal disease individuals than nondiabetic controls (aortic, 23% vs. 6%, P = 0.03; mitral, 25% vs. 2%, P < 0.001). Multivariate analysis using all three groups reproduced these findings and also consistently identified age and diabetic renal disease as additional predictors for the presence or severity of coronary artery and aortic wall calcification. CONCLUSION: In this first, systematic analysis among nondialyzed individuals with diabetic renal disease, these data demonstrate that vascular and valvular calcification is present and often severe long before the disease progresses to ESRD. The data also suggest that the coronary artery and aortic wall calcification may represent atherosclerosis.