Amount Of Coronary Artery Calcium Research Articles

Associations of Serum Uric Acid With Markers of Inflammation, Metabolic Syndrome, and Subclinical Coronary Atherosclerosis

We examined the associations of serum uric acid (UA) with indices of coronary heart disease (CHD) risk, including the 10-year probability of CHD (10y-CHDr), metabolic syndrome (MS), inflammation (C-reactive protein [CRP] and fibrinogen), and the presence and quantity of coronary artery calcium (CAC). Subjects (n = 1107, mean age 58 years, 59% women) belonged to sibships with > or =2 individuals with hypertension diagnosed before age 60 years. UA was measured by a colorimetric method, CAC by electron beam computed tomography, and CAC score calculated using the method of Agatston. The correlation of UA with 10y-CHDr, MS components, log CRP, and fibrinogen was assessed after adjustment for age and gender. Multivariable regression was used to assess whether UA was associated with CAC presence and quantity after (1) adjustment for age and gender, and (2) additional adjustment for CHD risk factors. Most subjects (71%) had hypertension and 14% had diabetes. Mean (+/- SD) UA level was 5.97 +/- 1.6 mg/dL, and CAC was detectable in 63% of patients. After adjustment for age and gender, UA was significantly correlated with 10y-CHDr, number of MS components, log CRP, and fibrinogen. UA was associated with CAC presence and quantity after adjustment for age and gender but not after further adjustment for systolic blood pressure (BP), diabetes, total and HDL-cholesterol, smoking, and body mass index (BMI). Serum UA was significantly correlated with several indices of CHD risk. UA was associated with presence and quantity of CAC, but not independently of conventional risk factors.

Calcium Scoring and Contrast-Enhanced CT Angiography

Computed tomography (CT) technology has emerged as the most promising imaging modality for the noninvasive evaluation of the coronary circulation. Of the CT-based approaches, multidetector-row computed tomography (MDCT) and to a lesser extent electron beam computed tomography offer the potential of providing not only data on the spatial extent and burden of coronary calcium content, but also angiographic data, and plaque composition characteristics with the potential for prediction of susceptibility to future cardiovascular events. A number of studies have now confirmed that CT-based assessment of the presence and amount of coronary artery calcium provides incremental prognostic information over traditional risk factors in patients with coronary artery disease and can be employed to refine risk stratification in both asymptomatic and symptomatic subjects. With the advent of several recent advances in CT imaging, it is now possible to provide high resolution (sub-millimeter, isotropic voxels) images of the coronary arteries obtained rapidly with iodinated contrast injected peripherally. MDCT is currently the preferred modality for noninvasive contrast angiography of the coronary arteries by most groups, with a new generation of 64-slice scanners promising to further improve the results of this technique. MDCT-derived angiographic information in conjunction with coronary calcium scoring and plaque characterization has the potential of replacing invasive angiography, as it potentially could provide better global assessment of risk.

Association of Plasma Homocysteine With Coronary Artery Calcification in Different Categories of Coronary Heart Disease Risk

To Investigate the association of plasma homocystelne with coronary artery calcification (CAC) in strata based on 10-year risk of coronary heart disease (CHD) in a cohort enriched in persons with hypertension. Fasting plasma homocystelne was measured by liquid chromatography electrospray tandem mass spectrometry. Coronary artery calcification was measured noninvasively by electron beam computed tomography and CAC score calculated using the method of Agatston et al. The 10-year CHD risk was calculated based on the Framingham risk score. The association of homocysteine with log-transformed CAC score was assessed in the pooled sample and within each risk stratum by linear regression after adjustment for conventional risk factors. In the 1071 participants studied, homocysteine was associated with CAC quantity (P = .01) after adjustment for CHD risk factors (age, male sex, total and high-density lipoproteln cholesterol, diabetes, history of smoking, body mass Index, and systolic blood pressure), serum creatinine, and statin and hypertension medication use. When the association was assessed in strata based on 10-year CHD risk, homocysteine was significantly (P = .003) associated with CAC quantity in participants at Intermediate 10-year risk of CHD (6%-20%) independent of other risk factors but not in those at lower risk or higher risk. Plasma homocysteine is associated with quantity of CAC Independent of CHD risk factors. When studied in categories of 10-year CHD risk, the association was significant in participants at intermediate risk but not in those at low or high risk. Plasma homocysteine levels may have clinical utility as a marker of CHD risk in such individuals.

Evidence for lower variability of coronary artery calcium mineral mass measurements by multi-detector computed tomography in a community-based cohort—Consequences for progression studies

Purpose To compare the measurement variability for coronary artery calcium (CAC) measurements using mineral mass compared with a modified Agatston score (AS) or volume score (VS) with multi-detector CT (MDCT) scanning, and to estimate the potential impact of these methods on the design of CAC progression studies. Materials and methods We studied 162 consecutive subjects (83 women, 79 men, mean age 51 ± 11 years) from a general Caucasian community-based cohort (Framingham Heart Study) with duplicate runs of prospective electrocardiographically-triggered MDCT scanning. Each scan was independently evaluated for the presence of CAC by four experienced observers who determined a “modified” AS, VS and mineral mass. Results Of the 162 subjects, CAC was detected in both scans in 69 (42%) and no CAC was detected in either scan in 72 (45%). Calcium scores were low in the 21/162 subjects (12%) for whom CAC was present in one but not the other scan (modified AS <20 in 20/21 subjects, mean AS 4.6 ± 1.9). For all three quantification algorithms, the inter- and intraobserver correlation were excellent ( r > 0.96). However, the mean interscan variability was significantly different between mineral mass, modified AS, and VS (coefficient of variation 26 ± 19%, 41 ± 28% and 34 ± 25%, respectively; p < 0.04), with significantly smaller mean differences in pair-wise comparisons for mineral mass compared with modified AS ( p < 0.002) or with VS ( p < 0.03). The amount of CAC but not heart rate was an independent predictor of interscan variability ( r = −0.638, −0.614 and −0.577 for AS, VS, and mineral mass, respectively; all p < 0.0001). The decreased interscan variability of mineral mass would allow a sample size reduction of 5.5% compared with modified AS for observational studies of CAC progression and for randomized clinical trials. Conclusion There is significantly reduced interscan variability of CAC measurements with mineral mass compared with the modified AS or VS. However, the measurement variability of all quantification methods is predicted by the amount of CAC and is inversely correlated to the extent of partial volume artifacts. Moreover, the improvement of measurement reproducibility leads to a modest reduction in sample size for observational epidemiological studies or randomized clinical trials to assess the progression of CAC.

Aortic Pulse Wave Velocity Is Associated With the Presence and Quantity of Coronary Artery Calcium

We investigated the relationship of aortic pulse wave velocity (aPWV), a measure of central arterial stiffness, with the presence and quantity of coronary artery calcium (CAC) in a community-based sample of adults without prior history of heart attack or stroke (n=401, mean age 59.8 years, 53% men). ECG-gated waveforms of the right carotid and right femoral artery were obtained by applanation tonometry, and aPWV was calculated using established methods. CAC was measured noninvasively by electron beam computed tomography, and CAC score was calculated. aPWV was significantly correlated with log(CAC +1; r=0.41; P<0.0001) and pulse pressure (r=0.47; P<0.0001). Multivariable logistic and linear regression models were used to identify independent predictors of the presence and quantity of CAC, respectively. In multivariable logistic regression analyses, aPWV was associated with the presence of CAC (P=0.011) after adjustment for age, male sex, total cholesterol, high-density lipoprotein cholesterol, diabetes, history of smoking, systolic blood pressure, body mass index, and use of hypertension and statin medications. In multivariable linear regression analyses, aPWV was significantly associated with log(CAC +1) after adjustment for the covariates enumerated above (P<0.0001). aPWV remained significantly associated with both the presence and quantity of CAC even after the additional adjustment for diastolic blood pressure. We conclude that aPWV is related to subclinical coronary atherosclerosis independent of conventional risk factors (including indices of blood pressure) and may be a biomarker of cardiovascular risk in asymptomatic individuals.

The relationship between C-reactive protein and subclinical cardiovascular disease in the Diabetes Heart Study (DHS)

Epidemiological studies suggest that levels of C-reactive protein (CRP) predict cardiovascular disease (CVD). We have evaluated the relationship between CRP and subclinical CVD in a study cohort at high risk of CVD. The DHS is a single-center, family-based study of the genetic and environmental components of CVD in type 2 diabetes mellitus (T2DM). We evaluated 666 subjects (551 T2DM affected and 115 unaffected) with an average age of 61 years. Measures of coronary artery calcium (CAC), intimal-medial thickness (IMT) of the common carotid artery, and CRP were obtained on all subjects. C-reactive protein is positively and significantly associated with female sex, body mass index, and smoking and is negatively and significantly associated with age and statin use. Generalized estimating equations were used to test whether CRP was associated with each subclinical CVD measure (presence/absence of CAC, quantity of CAC, and IMT) adjusting for covariates and correlation among siblings. Stratified analyses were conducted to examine whether these associations differed across sex and statin use. In the overall analysis, CRP was not significantly associated with IMT or presence of CAC but was negatively and significantly associated with quantity of CAC (P = .01). When covariates were added, the relationship was no longer significant. Similar patterns were observed in stratified analyses based on sex, statin use, and diabetes status: weak but negative association of CAC with CRP, which became nonsignificant with adjustment for covariates. In a population at high risk for CVD, there was no evidence of incremental association of CRP levels with measures of subclinical CVD.

Racial/Ethnic Differences in Subclinical Atherosclerosis Among Adults With Diabetes

Recent findings from the Multi-ethnic Study of Atherosclerosis (MESA) (1) are consistent with previous reports that non-Hispanic white (white) adults have a greater presence and quantity of coronary artery calcium (CAC) than non-Hispanic black (black), Hispanic, and Chinese-American (Chinese) adults (2,3,4,5). It is not known whether previously reported racial/ethnic differences in atherosclerosis persist in the presence of type 1 or type 2 diabetes, an established risk factor for cardiovascular disease (CVD). Further, it is not known whether previously reported racial/ethnic differences in markers of atherosclerosis in the carotid and peripheral arteries (6,7) are also present among persons with diabetes. We assessed whether racial/ethnic differences in CAC, common and internal carotid intimal medial thickness (IMT), and the ankle brachial index (ABI) were evident in persons with diabetes in the MESA cohort and whether these differences persisted following adjustment for measured cardiovascular disease risk factors. MESA is a multicenter study of 6,814 men and women aged 45–84 who were free from clinical CVD in 2000–2002 (8). From the cohort of 6,814 participants, we excluded 25 participants without glucose measurements and 5,761 without diabetes. Our final analysis sample included 204 whites, 387 blacks, 311 Hispanics, and 126 Chinese with diabetes. The prevalence of diabetes in the cohort by race/ethnicity is comparable to …

Early Subclinical Coronary Artery Calcification in Young Adults Who Were Pediatric Kidney Transplant Recipients

Coronary artery disease (CAD) is the leading cause of death in adults after successful kidney transplantation. Children who have undergone successful kidney transplantation are entering young adulthood; however, the prevalence and extent of CAD in this population is unknown. We conducted a pilot study in young adults with stable allograft function, who received kidney transplants as children to measure coronary artery calcification (CAC), a marker of coronary artery atherosclerosis and CAD. We evaluated 19 young adults after successful pediatric kidney transplantation for known CAD risk factors; these patients underwent noninvasive imaging with electron-beam computed tomography (EBCT) for measurement of CAC. Prevalence and quantity of CAC were then compared to asymptomatic individuals from the community. All patients had multiple risk factors for CAD. Mean age at evaluation was 32 years (range: 21-48 years). CAC is uncommon in individuals in the community in this age range; however, nearly half of our patients had CAC detected with the quantity of CAC comparable to asymptomatic individuals from the community 10-40 years older. These data suggest young adults who received pediatric kidney transplants are at increased risk for developing early CAC and need close monitoring to detect early CAD so as to prevent premature cardiac morbidity and mortality.

Dyslipidemia and progression of cardiovascular calcification (CVC) in patients with end-stage renal disease (ESRD)

Dyslipidemia and progression of cardiovascular calcification (CVC) in patients with end-stage renal disease (ESRD). Cardiovascular calcification (CVC) is commonly encountered both in the general population as well as in patients with end-stage renal disease (ESRD). The etiology of CVC in patients with ESRD is multifactorial. Despite that, current debate remains narrowly focused on the role of calcium loading from calcium-based phosphate binders (CBPB) in the pathogenesis and progression of CVC. Yet, the alleged link between these binders and CVC has not been substantiated in well-designed controlled trials. In contrast, the purported role of sevelamer, a non-calcium-based phosphate binder, in slowing the progression of CVC in dialysis patients has attracted widespread attention. The beneficial effect of sevelamer on progression of calcification was thought to be due to lower calcium loading during its use. However, an alternative and possibly more likely mechanism involves sevelamer-induced lowering of LDL cholesterol. In this context, previous studies in individuals with normal renal function have documented amelioration of coronary artery calcification (CAC) with reduction of LDL-cholesterol by treatment with HMG-CoA reductase inhibitors (statins). Given that CAC is a well-accepted marker of atherosclerosis, and that high plasma cholesterol concentration is one of the main risk factors for atherosclerosis, then it is not unreasonable to suspect that CAC may be halted or even reversed by lowering of LDL cholesterol level with statin therapy. Unfortunately, the effect of lowering the LDL-cholesterol level on CAC has not been studied in patients with ESRD. Therefore, conclusions about this important topic should await the results of well-designed clinical studies that control for all factors potentially implicated in the CVC burden of patients with ESRD. In this review, I will discuss the role of various potential mechanisms involved in the pathogenesis of CVC in patients with ESRD, and emphasize the role of dyslipidemia and its treatment in this important clinical entity.

Progression of Subclinical Coronary Atherosclerosis

Obesity is associated with coronary artery calcification (CAC), a marker of the presence and extent of subclinical coronary atherosclerosis. Obesity adds incremental information in identifying those at higher risk of coronary heart disease to traditional risk factor assessment. The present study examined associations between obesity measures and progression of CAC in those at higher (> or =10%) and lower (<10%) 10-year coronary heart disease risk according to the Framingham risk equation. In this study, 443 asymptomatic white individuals >30 years of age (243 men) had baseline and follow-up CAC measurements an average of 8.9 years apart. Multivariable linear regression models were fit to determine associations of obesity measures at baseline with progression of CAC defined as log(e) of the difference between follow-up and baseline CAC area plus 1 divided by time (in years) between examinations, adjusting for baseline CAC quantity, age, sex, baseline hypertension status, and baseline cholesterol level. Among 329 participants (74.3%) in the lower-risk group, waist circumference (P=0.024), waist-to-hip ratio (P<0.001), body mass index (P=0.036), and being overweight compared with being underweight or of normal weight (P=0.008) were each significantly positively associated with progression of CAC. Among those at higher coronary heart disease risk, no baseline obesity measures were associated with CAC progression. Various measures of obesity were associated with increased progression of CAC in those at lower risk of coronary heart disease. Future studies examining the effectiveness of weight reduction strategies in reducing CAC progression among those with an otherwise favorable risk factor profile may be warranted.

Association between metabolic syndrome and subclinical coronary atherosclerosis in asymptomatic adults

Metabolic syndrome was associated with the presence and quantity of coronary artery calcium, a marker of subclinical coronary atherosclerosis, in 1,129 asymptomatic adults, ages 20 to 79 years, from a community-based study. The association was independent of 10-year risk of coronary heart disease based on the Framingham risk score.

Lack of Association Between Lipoprotein(a) and Coronary Artery Calcification in the Genetic Epidemiology Network of Arteriopathy (GENOA) Study

To investigate the relationship between lipoprotein(a) [Lp(a)] levels and the extent of coronary atherosclerosis in a cohort that consisted predominantly of hypertensive patients. Patients were ascertained through sibships that contained at least 2 individuals with essential hypertension diagnosed before the age of 60 years. The 10-year coronary heart disease (CHD) risk was estimated on the basis of the Framingham risk equation. Serum Lp(a) was measured by an immunoturbidimetric assay. Coronary artery calcification (CAC) was measured noninvasively by electron beam computed tomography and CAC score calculated using the Agatston score. Patients included 765 non-Hispanic, white individuals (59% women) participating in the Genetic Epidemiology Network of Arteriopathy study. The mean +/- SD age of the patients was 62 +/- 8 years, and 77% had hypertension. The prevalence of detectable CAC was 87% in men and 60% in women. The CAC scores did not differ significantly across quintiles of Lp(a) levels in either men or women. In a multiple regression model that included conventional risk factors, Lp(a) levels were not related to CAC quantity in either sex. No significant interactions were noted between Lp(a) levels and the conventional risk factors in the prediction of CAC quantity. When stratified on the basis of the 10-year CHD risk, 26.5% of the patients were low risk (< 6%), 60.5% were intermediate risk (6%-20%), and 12.9% were high risk (> 20%). Lipoprotein(a) was not associated with CAC quantity within subgroups based on 10-year CHD risk. In this cohort enriched with hypertensive patients, the estimated 10-year CHD risk did not appear to modify the lack of an association between Lp(a) levels and CAC.

Noninvasive detection of coronary lesions using 16-detector multislice spiral computed tomography technologyInitial clinical results

The aim of our study was to evaluate the feasibility of detecting coronary artery lesions using a new computed tomography (CT) scanner with 16 detectors and faster gantry rotation. Computed tomography angiography of the coronaries permits assessment of the coronaries; however, image quality is still impaired by motion artifacts and calcifications. Sixty patients scheduled for conventional coronary angiography (CCA) were additionally studied by multislice spiral computed tomography (MSCT).Calcium scores and a contrast-enhanced visualization of the coronaries were performed and analyzed regarding evaluability, presence of coronary artery lesions, and correct clinical diagnosis. Calcium scoring was successful in all patients; 58 of 60 patients had a diagnostic contrast-enhanced scan. Mean calcium score was 506 ± 743 Agatston score equivalent (ASE); 13 of 58 (22%) patients had an ASE ≥1,000, 46 of 58 (78%) patients <1,000. In 763 coronary segments, CCA detected a total of 75 lesions ≥50%. The MSCT correctly assessed 54 of these. Twenty-one lesions were missed or incorrectly underestimated. Sensitivity was 72%, specificity 97%. When restricting analysis to patients with an ASE <1,000, 40 significant lesions ≥50% were seen on CCA, and MSCT correctly detected 39 lesions (sensitivity 98%, specificity 98%). Regardless of any threshold, the correct clinical diagnosis could be obtained in 58 of 60 (97%) of all patients. In individuals with low-to-moderate amounts of coronary artery calcium, 16-detector CT coronary angiography has high sensitivity and specificity for the diagnosis of significant coronary artery stenosis.

Noninvasive detection of coronary lesions using 16-detector multislice spiral computed tomography technology: Initial clinical results

The aim of our study was to evaluate the feasibility of detecting coronary artery lesions using a new computed tomography (CT) scanner with 16 detectors and faster gantry rotation. Computed tomography angiography of the coronaries permits assessment of the coronaries; however, image quality is still impaired by motion artifacts and calcifications. Sixty patients scheduled for conventional coronary angiography (CCA) were additionally studied by multislice spiral computed tomography (MSCT). Calcium scores and a contrast-enhanced visualization of the coronaries were performed and analyzed regarding evaluability, presence of coronary artery lesions, and correct clinical diagnosis. Calcium scoring was successful in all patients; 58 of 60 patients had a diagnostic contrast-enhanced scan. Mean calcium score was 506 +/- 743 Agatston score equivalent (ASE); 13 of 58 (22%) patients had an ASE >or=1,000, 46 of 58 (78%) patients <1,000. In 763 coronary segments, CCA detected a total of 75 lesions >or=50%. The MSCT correctly assessed 54 of these. Twenty-one lesions were missed or incorrectly underestimated. Sensitivity was 72%, specificity 97%. When restricting analysis to patients with an ASE <1,000, 40 significant lesions >or=50% were seen on CCA, and MSCT correctly detected 39 lesions (sensitivity 98%, specificity 98%). Regardless of any threshold, the correct clinical diagnosis could be obtained in 58 of 60 (97%) of all patients. In individuals with low-to-moderate amounts of coronary artery calcium, 16-detector CT coronary angiography has high sensitivity and specificity for the diagnosis of significant coronary artery stenosis.

Low-density lipoprotein particle size and coronary atherosclerosis in subjects belonging to hypertensive sibships

Dyslipidemia in hypertensive sibships may be characterized by atherogenic small low-density lipoprotein (LDL) particles. Whether LDL particle size is associated with the extent of coronary atherosclerosis in hypertensive sibships is unknown. Subjects (n = 792, mean age 62 years, 60% women) were ascertained through sibships containing at least two individuals with essential hypertension diagnosed before age 60 years. The LDL particle size was measured by polyacrylamide gel electrophoresis. Coronary artery calcium (CAC) was measured noninvasively by electron beam computed tomography, and CAC score was calculated using the method of Agatston et al. Sex-specific multiple regression models were used to assess independent predictors of LDL particle size and the association of LDL particle size with CAC. In all, 76% of women and 77% of men were hypertensive. In each sex, independent predictors of smaller LDL particle size were total cholesterol, triglycerides, and lower HDL cholesterol. In women, greater age was an additional predictor of smaller LDL particle size. After adjustment for age and statin use, LDL particle size was significantly associated with the amount of CAC in women but not in men. After further adjustment for HDL cholesterol, triglycerides, diabetes, smoking, and hypertension, LDL particle size was not independently associated with CAC in either sex. After adjustment for age and statin use, LDL particle size was found to be significantly related to CAC quantity in women but not in men belonging to hypertensive sibships. In women, LDL particle size may mediate some of the atherogenic effects of low-HDL cholesterol-high-triglyceride dyslipidemia, but does not appear to be independently associated with the extent of coronary atherosclerosis in either sex.

Age-dependent associations between blood pressure and coronary artery calcification in asymptomatic adults

The age-dependent roles of the components of blood pressure (BP) in the development of coronary artery calcification (CAC) are poorly understood. We examined systolic (SBP), diastolic (DBP), mean arterial pressure (MAP) and pulse pressure (PP) as predictors of CAC in 830 asymptomatic, non-diabetic participants in a community-based study who were aged > or = 30 years and free of antihypertensive therapy or known cardiovascular disease. CAC was measured with electron beam computed tomography. Tobit regression was used in two age groups (< 50 years and > or = 50 years) to evaluate the relationship of BP components with presence and quantity of CAC, adjusting for traditional coronary artery disease (CAD) risk factors. Among those aged < 50 years, CAC was positively associated with SBP, DBP and MAP, considering each pressure individually and DBP was the strongest predictor (P = 0.0088). Among those aged > or = 50 years, CAC was positively associated with SBP (P = 0.0257) and PP (P = 0.0028), considered individually. When SBP and DBP were in the same model, presence and CAC quantity were positively associated with SBP (P = 0.0024) and negatively with DBP (P = 0.0401), favoring PP as the best predictor of CAC. SBP, DBP and PP have age-dependent roles in the prediction of CAC similar to their roles in prediction of future CAD events. These observations provide new evidence supporting the measurement of CAC as a surrogate of target organ disease and subsequently, as a predictor of increased risk of future CAD events.

Polymorphism of the soluble epoxide hydrolase is associated with coronary artery calcification in African-American subjects: The Coronary Artery Risk Development in Young Adults (CARDIA) study.

Modulation of endogenous epoxide levels by soluble epoxide hydrolase (sEH) in the endothelium represents an important mechanism in the regulation of cardiovascular function. We examined the relationship between a common, functional polymorphism of the human sEH gene and coronary artery calcification (CAC) in young, largely asymptomatic African-American and non-Hispanic white subjects. Multiple logistic regression and Tobit regression models were used to assess the relationship between the sEH Arg287Gln polymorphism and presence and quantity of CAC. Models adjusting for race (except in race-specific analyses), age, sex, smoking, body mass index, systolic blood pressure, LDL cholesterol, and HDL cholesterol were estimated. Allele and genotype frequency distributions were not significantly different between the 2 ethnic groups (P=0.22; P=0.17, respectively). The Arg287Gln polymorphism of the sEH gene was a significant predictor of CAC status in African-American participants, either alone or after adjusting for other risk factors. African-American subjects with at least 1 copy of the Gln287 allele had a 2-fold greater risk of having CAC compared with those not carrying this allele (95% CI, 1.1 to 2.9; P=0.02). There was no relationship between Arg287Gln polymorphism and the probability of having CAC in white participants (OR, 0.8; 95% CI, 0.5 to 1.3; P=0.49). Inferences from multivariable Tobit regression were similar to those obtained in the logistic regression models, indicating that the Arg287Gln polymorphism was a significant independent predictor of both presence and quantity of CAC in African-American but not white subjects. These data suggest an intriguing and possibly novel role for sEH in the pathogenesis of atherosclerosis, which deserves additional investigation.

Study 1: unexpected high incidence of coronary artery disease and abnormal platelet reactivity in long-term pediatric kidney transplant recipients

L ong-term outcomes of children who undergo renal transplantation are unknown. However, as they enter adulthood, many will have risk factors for developing coronary artery disease (CAD). Certain noninvasive tests may detect early CAD. Electron-beam computed tomography (EBCT) can measure the amount of coronary artery calcification (CAC), which correlates with the presence of atherosclerotic CAD. In addition, abnormal platelet function has been linked to increased risk for atherogenesis and CAD. The purpose of this study was to determine the incidence of CAD by using EBCT in adults who underwent renal transplantation as children and determine whether presence of accelerated atherogenesis is associated with enhanced platelet reactivity. Eight pediatric kidney transplant recipients with good long-term allograft function ( 10 years) underwent evaluation by EBCT. The CAC score was determined by standardized technique. Platelet reactivity was assessed by measures of dense granule secretory rate, metabolic content, and spontaneous microaggregate formation. Results were compared with those in age-matched controls. The mean age at transplantation was 14 years (range, 10-16). Mean age at evaluation was 45 years (range, 23-48). Mean follow-up in this group was 17 years (range, 10-23). All received cyclosporine-based immunosuppression. Seven had 2 or more clinical risk factors for CAD. All were asymptomatic at the time of evaluation. Seven out of 8 patients had significant CAC detected on EBCT. When compared with ageand gender-matched controls, study patients had CAC scores 99% (n 4), 95% to 99% (n 2), and 75% to 95% (n 1). Platelets from those with CAC were significantly more likely to form microaggregates after mild stimulation compared with those without CAC (P .02). Also, they were more likely to form microaggregates (P .03), had slower dense granule secretion (P .04), and had lower metabolic stores (P .03) compared with controls. Conclusion: The incidence of CAC by EBCT in long-term pediatric kidney transplant recipients is much higher than expected compared with the general population. Besides clinical risk factors, it appears that platelets from these patients are more reactive, which may place them at further increased risk for thrombotic complications of atherosclerosis. Our data suggest that measures to decrease risk factors for CAD should be undertaken as children approach young adulthood. From the William J. von Liebig Transplant Center, Mayo Clinic; and the Department of Radiology; and Division of Cardiovascular Medicine, Mayo Clinic, Rochester, MN. © 2004 Elsevier Inc. All rights reserved. 0955-470X/04/1704-0000$30.00/0 doi:10.1016/j.trre.2003.10.006

Comparison of prevalence and severity of coronary calcium determined by electron beam tomography among various ethnic groups

Electron beam tomography (EBT) can accurately and noninvasively quantitate the amount of coronary artery calcium (CAC), thus, providing an index of atherosclerotic burden. We sought to evaluate whether ethnic differences exist in the prevalence and severity of coronary calcium in asymptomatic, highrisk patients.  We evaluated 1,426 minority participants (828 men, 598 women) who underwent EBT scanning. These patients were were age- and gender-matched 3:1 with Caucasians (2,484 men, 1,794 women). We utilized the mean age of the minority participants and percentages of men and women to match to our physician-referred Caucasian population. All participants (minorities and matched Caucasians) were asymptomatic and referred by their primary physician to evaluate the presence and amount of CAC. Physicians referred patients to assess their cardiovascular risk. Data on risk factors for coronary artery disease (CAD) were collected at interview before the EBT procedure. The presence and number of risk factors for a participant were calculated based on the National Cholesterol Education Program guidelines. 1 Risk factors included: men aged 45 years, women aged 55 years, current cigarette smokers, history of premature coronary disease in a first-degree relative (men 55 years, women 65 years), diabetes, hypertension, and hypercholesterolemia. Cigarette smoking was defined as smoking 10 cigarettes/day. Participants currently using insulin or oral hypoglycemic agents, or those with dietcontrolled diabetes were classified as diabetic. Systemic hypertension was defined by current use of antihypertensive medication or known and untreated hypertension; hypercholesterolemia was similarly defined by use of cholesterol-lowering medication or known but untreated serum total cholesterol 240 mg/dl. Participants were excluded from the study if they had documented CAD before entry into the study. The study protocol was approved by the institutional review board of the Harbor-UCLA Research and Education Institute. One thousand four hundred twenty-six minority and 4,278 Caucasian subjects at Harbor-UCLA Medical Center underwent EBT using an Imatron C-150XL Ultrafast computed tomographic scanner (Imatron, Inc., South San Francisco, California). Coronary artery visualization was obtained without contrast medium injection, and 30 consecutive images were obtained at 3-mm intervals beginning 1 cm below the carina and progressing caudally to include the entire coronary tree. Exposure time was 100 ms/image slice, and total skin irradiation dose was 600 mrads/ scan. Electrocardiographic triggering was used and adjusted such that image acquisition occurred at the same point in the cardiac cycle starting in late systole.2,3 A computed tomographic threshold of 2 pixels and 130 Hounsfield units was utilized for identification of a calcific lesion. Each focus exceeding the minimum criteria was scored using the algorithm developed by Agatston et al, 4 calculated by multiplying the lesion area by a density factor derived from the maximal Hounsfield unit within this area. A total coronary calcium score was determined by summing individual lesion scores from each of 4 anatomic sites (left main, left anterior descending, circumflex, and right coronary arteries). EBT scoring was performed by a cardiologist who was blinded to the clinical, electrocardiographic, and angiographic information. Categorical data are presented as number (percentages), and continuous data as mean value SD.

Conventional coronary artery disease risk factors and coronary artery calcium detected by electron beam tomography in 30,908 healthy individuals.

Electron beam tomography (EBT) is a noninvasive measure of coronary artery calcium (CAC), a marker for atherosclerosis. In this study we examined the association between conventional risk factors for coronary artery disease (CAD) and CAC. EBT CAC screening was performed on 30,908 asymptomatic individuals aged 30 to 90 years. Prior to EBT screening, individuals provided demographic and CAD risk factor information. EBT utilized a C-100 EBT scanner, and the amount of CAC was determined using the Agatston scoring method. The results of this study demonstrate that for both men and women, all conventional risk factors were significantly associated with the presence of any detectable CAC, and the mean CAC score increased in proportion to the number of CAD risk factors. In age-adjusted (multivariable) logistic regression analysis, cigarette use, histories of hypercholesterolemia, diabetes, and hypertension were each significantly associated with mild to extensive CAC scores (> or =10.0). CAD risk factors are associated with higher atherosclerotic plaque burden in both men and women. The odds ratios associated with each risk factor relative to the extent of CAC are similar to those reported for the development of clinical CAD, suggesting the existence of an association between CAC (subclinical disease) and CAD (clinical disease).