Change In Coronary Artery Calcification Score Research Articles

Abstract 9379: Higher Levels of Plasminogen-Activator Inhibitor 1 Are Associated with Progression of Coronary Artery Calcification in Middle-Aged Women: The Study of Women’s Health Across the Nation (SWAN) Heart Study

Introduction: Relationships of inflammatory and hemostatic biomarkers with progression of coronary artery calcification (CAC) in asymptomatic women are unknown. Hypothesis: We assessed the hypothesis that C-reactive protein (CRP), fibrinogen, plasminogen-activator inhibitor 1 (PAI-1), and tissue plasminogen activator antigen (tPA-ag) were associated with CAC progression in women free of known coronary heart disease (CHD) and stroke. Methods: CRP, fibrinogen, PAI-1, and tPA-ag were measured in SWAN Heart participants from the Pittsburgh and Chicago sites at baseline. CAC was obtained by CT scans and quantified by the Agatston score at baseline and after 2.3±0.5 years of follow-up. Significant CAC progression was defined as present if 1) CAC score was >0 at follow-up in subjects with CAC score = 0 at baseline, 2) annualized change in CAC score was ≥10 in subjects with 0<CAC score<100 at baseline, and 3) annualized percent change in CAC score was ≥10% in subjects with CAC score ≥100 at baseline. Univariable and multivariable logistic regression were used for statistical analyses. The novel biomarkers were log-transformed. Baseline CAC was transformed as log(CAC+1). Results: The study included 252 women (32.5% black, 67.5% white; 56.4% pre- and early perimenopausal, 30.6% late peri- and postmenopausal, and 13.1% hormone therapy users) with a mean age of 51.2±2.6 years at baseline. In unadjusted analyses, log(PAI-1) and log(tPA-ag) were positively and significantly associated with CAC progression (p<0.05), but log(CRP) and log(fibrinogen) were not. Adjusted analyses included the following covariates: baseline CAC, age, site, race, menopausal status, income, education, systolic blood pressure, body mass index, Homeostasis Model Assessment insulin resistance index, family history of cardiovascular (CV) disease, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides, CV medication use, and current smoking. Only log(PAI-1) was significantly associated with CAC progression (OR: 1.91; 95% CI: 1.24-2.93; p=0.003). Conclusions: In conclusion, PAI-1 is associated with the presence of CAC progression in middle-aged women. Targeting PAI-1 may decrease atherogenesis beyond conventional CHD risk factors.

Prospective analysis of coronary calcium in patients on dialysis undergoing a near-total parathyroidectomy

Patients with secondary hyperparathyroidism and on dialysis are more likely to die of cardiovascular disease than the general population; and we have reported that near-total parathyroidectomy (NTPTX) reduces that mortality rate. Patients on dialysis experience an average of a 15% increase in coronary calcification yearly, contributing to cardiovascular death. Cardiac computed tomography (CT) enables objective measuring of coronary calcium. The purpose of our study was to determine the impact of NTPTX on coronary artery calcium score (CACS). CACS measurement was performed in patients with stage 5 chronic kidney disease before and after NTPTX from 2001 to 2008. Demographics, morbidities, CACS, outcomes, intact parathyroid hormone (PTH) measurements in follow-up (mean, 5.1 years) were maintained in an institutional review board-approved prospective database. Of 31 patients, 19 (61%) returned for a follow-up coronary CT. Preoperative mean PTH level and CACS were 1,794 ± 943 pg/mL and 979 ± 079, respectively; postoperatively, PTH and CACS were 321 ± 244 pg/mL (P < .001) and 1,285 ± 1,577 (P = .044), respectively. CACS was stable or reduced (<10% per year) in 6 of 19 patients (32%), and 42% of patients (n = 8) had nearly undetectable (<1% per year) change in CACS after NTPTX. In patients with stable CACS, mean postoperative PTH was 251 versus 516 pg/mL in patients with increasing CACS (P = .02). In patients with recurrent hyperparathyroidism (PTH > 400) compared with patients with stable postoperative PTH, CACS increased by 804 ± 1082 versus 16 ± 84 (P = .02). Successful NTPTX with stable postoperative PTH levels is associated with stabilization of CACS in patients with severe secondary hyperparathyroidism undergoing hemodialysis, which could contribute to the improved survival seen after NTPTX.

Progression of coronary artery calcification is associated with long-term cadiovascular events in hypertensive adults

Coronary artery calcification (CAC) is an independent predictor of cardiovascular (CV) events in hypertensive adults. However, the additive value of serial CAC measurements for risk stratification is unclear. The aim of the present study was to find whether CAC progression predicts long-term CV events in hypertensive patients. The study group included 210 patients (mean age 64 ± 5.6 years, 54% men), a subgroup of 544 participants in the calcification side arm of the INSIGHT (International Nifedipine Study Intervention as Goal for Hypertension Therapy). All were free of symptoms or known CV disease, had at least two CT scans 1 year apart, and had available long-term follow-up. Progression of CAC was defined as the absolute change in CAC score between maximal score during follow-up and baseline score. The endpoint was the first CV event after the last CT scan. Three categories of CAC progression were defined. Zero progression was defined as 'nonprogressors', and progression below and above the median of maximal progression were defined as 'slow progressors' and 'rapid progressors', respectively. During 15 years of follow-up (mean 11.4 ± 4.4), 83 patients experienced a first CV event. The rate of events was higher in rapid (29/59, 49%), and slow (36/78 46%) than in nonprogressors (18/73 25%); (P=0.005). Compared with nonprogressors, the adjusted hazard ratio for CV events was 1.91 [95% confidence interval (95% CI); 1.05-3.47] in the slow, and 2.13 (95% CI; 1.12-4.03) in the rapid progressors. In hypertensive patients, progression of CAC is associated with long-term CV events.

Abstract MP056: Subclinical Coronary Artery Disease is Present in 28% of Adults 43-55 Years of Age: Recent Findings of the CARDIA Study

Background: Coronary artery disease (CAD) starts in childhood and progresses to advanced lesions in adult life. The coronary artery calcium (CAC) score is a measure of subclinical CAD that indicates advanced coronary atheroma and independently predicts future clinical events. Our objective was to document the prevalence and amount of subclinical CAD among black and white adults in early adult life. Methods: The Coronary Artery Risk Development in Young Adults (CARDIA) study is a U.S. population-based, prospective, observational study of black and white men and women. Initially 5,115 participants age of 18-30 yrs were recruited in 1985-6. CAC was measured using non-contrast cardiac CT and reported as the Agatston score at three exams 15, 20 &amp; 25 years after the baseline visit. Results: CAC prevalence was 10.1%(309/3046), 18.6%(583/3140) and 28.1%(890/3160) when the returning cohort was between 33-45 yrs, 38-50 yrs, and 43-55 yrs, respectively (see figure). Prevalence of CAC at all time points was greater in men than women and highest in white men. In the most recent exam, black men had a lower prevalence of CAC (34.3% vs 47.7%) compared to white men but similar distribution of CAC amount. Quartiles of CAC among men with any CAC were: black men 10, 48, 183 and white men 14, 42, 173 (Q1, Q2(median) and Q3 respectively). Change in CAC score among participants in the two most recent CT exams was observed in 29.8% (774/2600). Of those participants, 89.3%(691/774) had any increase in CAC score and 66.7%(516/774) an increase of 10 units or greater. Prevalence of CAC was highly correlated with age and no period effect was observed. Conclusions: 28% of adults less than 55 years of age have advanced plaque in their coronary arteries indicating significant subclinical disease burden. Prevalence is highest in white men, followed by black men and then women in these age ranges. Black men, given CAC, have a comparable amount of CAC to white men. Subclinical CAD is prevalent in early adulthood and once initiated appears to progress in the vast majority of adults.

Study design and subject baseline characteristics in the ADVANCE Study: effects of cinacalcet on vascular calcification in haemodialysis patients

The ADVANCE (A Randomized Study to Evaluate the Effects of Cinacalcet plus Low-Dose Vitamin D on Vascular Calcification in Subjects with Chronic Kidney Disease Receiving Haemodialysis) Study objective is to assess the effect of cinacalcet plus low-dose active vitamin D versus flexible dosing of active vitamin D on progression of coronary artery calcification (CAC) in haemodialysis patients. We report the ADVANCE Study design and baseline subject characteristics. ADVANCE is a multinational, multicentre, randomized, open-label study. Adult haemodialysis patients with moderate to severe secondary hyperparathyroidism (intact parathyroid hormone [iPTH] >300 pg/mL or bio-intact PTH >160 pg/mL) and baseline CAC score >or=30 were stratified by CAC score (>or=30-399, >or=400-999, >or=1000) and randomized in a 1:1 ratio to cinacalcet (30-180 mg/day) plus low-dose active vitamin D (cinacalcet group) or flexible dosing of active vitamin D alone (control). The study had three phases: screening, 20-week dose titration and 32-week follow-up. CAC scores obtained by cardiac computed tomography were determined at screening and weeks 28 and 52. The primary end point was percentage change in CAC score from baseline to Week 52. Subjects (n = 360) were randomized to cinacalcet or control. Mean age was 61.5 years, 43% were women, and median dialysis vintage was 36.7 months (range, 2.7-351.5 months). The baseline geometric mean CAC score by the Agatston method was 548.7 (95% confidence interval, 480.5-626.6). Baseline CAC score was independently associated with age, sex, dialysis vintage, diabetes and iPTH. Subjects also had extensive aortic and valvular calcification at baseline. Subjects enrolled in ADVANCE have extensive CAC at baseline. The ADVANCE Study should help determine whether cinacalcet attenuates progression of vascular calcification.

Abstract: 1069 ELEVATED LEVELS OF OXIDIZED LIPOPROTEIN(A) ARE ASSOCIATED WITH THE PRESENCE AND SEVERITY OF ACUTE CORONARY SYNDROMES

Results from previous studies support the association of lipoprotein(a) [Lp(a)] levels and coronary artery disease risk. In this study, we analyzed the association between baseline Lp(a) levels and future progression of coronary artery calcification (CAC) in apparently healthy Korean adults.A total of 2611 participants (mean age: 41 years, 92% mend) who underwent a routine health check-up in 2010 and 2014 were enrolled. Coronary artery calcium score (CACS) were measured by multi-detector computed tomography. Baseline Lp(a) was measured by high-sensitivity immunoturbidimetric assay. Progression of CAC was defined as a change in CACS > 0 over four years.Bivariate correlation analyses with baseline Lp(a) and other metabolic parameters revealed age, total cholesterol, HDL-C, LDL-C and CACS to have a significant positive correlation, while body weight, fasting glucose level, blood pressure and triglyceride level were negatively correlated with baseline Lp(a) level. After four years of follow-up, 635 subjects (24.3%) had CAC progression. The participants who had CAC progression were older, composed of more men, more obese, and had higher fasting glucose levels and worse baseline lipid profiles compared to those who did not have CAC progression. The mean serum Lp(a) level was significantly higher in subjects who had CAC progression compared to those who did not (32.5 vs. 28.9 mg/dL, p < 0.01). When the risk for CAC progression according to baseline Lp(a) was calculated, those with Lp(a) level ≥ 50 mg/dL had an odds ratio of 1.333 (95% CI 1.027–1.730) for CAC progression compared to those with Lp(a) < 50 mg/dL after adjusting for confounding factors.In this study, the subjects who had higher Lp(a) were at significantly higher risk for CAC progression after four years of follow-up, suggesting the role of high Lp(a) in CAC progression.

Comparison of coronary artery calcium progression in African American and white men

Although African Americans have a lower prevalence and extent of coronary artery calcium (CAC) than whites, the relationship between ethnicity and CAC progression is unknown. In a prospective rescan substudy of the Prospective Army Coronary Calcium (PACC) Project, we evaluated ethnic differences in the rates of CAC progression over 4 years. Two hundred healthy male PACC Project participants (age, 47.8 +/- 2.8 years) with CAC on their original scan volunteered to undergo a second electron beam tomography (EBT) scan and cardiovascular risk factor assessment (interscan interval, 4.3 +/- 1.2 y). All results were independently examined and blinded to baseline data. A change in CAC score >or=15%/y was defined as clinically significant progression. The relationship between race and CAC progression was evaluated with multivariable linear and logistic regression models controlling for age and other cardiovascular risk factors. African Americans had significantly lower baseline CAC scores (34.3 vs 101.5; P = 0.004); lower follow-up CAC scores (56.6 vs 180.6; P = 0.001); and worse cardiovascular risk profiles. The annualized CAC progression rate was not significantly related to race in the multivariable linear regression model controlling for age, the Framingham risk score, and other cardiovascular risk factors. Significant CAC progression occurred in 43.5% of all participants. The incidence of significant progression of CAC for African American and white men was similar (53.1% vs 52.4%; P = 0.94), even when controlling for age, the Framingham risk score, and other cardiovascular risk factors. Although African American men have less CAC than white men, CAC progression occurs at a comparable rate over 4 years.

A 1-Year Randomized Trial of Calcium Acetate Versus Sevelamer on Progression of Coronary Artery Calcification in Hemodialysis Patients With Comparable Lipid Control: The Calcium Acetate Renagel Evaluation-2 (CARE-2) Study

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. Randomized, controlled, open-label, noninferiority trial with an upper bound for the noninferiority margin of 1.8. 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. 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. The primary end point was change in CAC score assessed by means of electron-beam computed tomography. 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). 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. With intensive lowering of LDL-C levels for 1 year, hemodialysis patients treated with either calcium acetate or sevelamer experienced similar progression of CAC.

Abstract 3573: Higher Soluble Thrombomodulin is Associated with Risk of Coronary Artery Calcification: Longitudinal Analysis of the Multi-Ethnic Study of Atherosclerosis (MESA)

Background. A prior cross sectional study reported that higher soluble thrombomodulin (sTM) was associated with subclinical atherosclerosis only in the presence of higher soluble intercellular adhesion molecule-1, sICAM-1. We evaluated this interaction longitudinally with regard to coronary artery calcium (CAC) in the MESA cohort. Methods: MESA is a multi-center longitudinal study with baseline measurements of endothelial biomarkers in a random sample (n=1000) of the baseline cohort. In the random sample, 374 men and 496 women had CT measurement for CAC (Agatston score) at baseline and a median follow-up of 2.9 years. Among those with no baseline CAC (n=490), we estimated the relative risk of detectable CAC at follow-up using general linear models with Gaussian error and robust standard errors. Among those with detectable baseline CAC (n=380), change in CAC on follow-up was modeled using robust regression that down-weights outliers. Models with log(sTM) as predictor were adjusted for follow-up time, sex, ethnicity and baseline age, BMI, smoking, diabetes, systolic blood pressure, total cholesterol, use of BP or lipid-lowering medications and for hormone replacement (HRT) in women in separate models. Interactions between sTM and sICAM-1, sex and ethnicity was assessed. Results: The median [interquartile range] of sTM was 38 [28 to 47] ng/mL for persons with incident detectable CAC, and 30 [23 to 41] ng/mL in those without (rank sum p &lt;0.001). On adjustment, a 2-fold higher sTM at baseline (e.g., from 23 to 46 ng/mL) was associated with a 1.36-fold increased risk of detectable CAC on follow-up (95% CI: 1.03, 1.79, p=0.031). Among those with baseline detectable CAC, the rank correlation between sTM level and change in CAC score was 0.10 (p = 0.042), however, on adjustment, a 2-fold higher sTM was associated with a non-significant 0.86 Agatston units greater CAC change (p = 0.84). Higher sICAM-1 did not modify the association of sTM with CAC incidence (interaction p = 0.15) or change (interaction p = 0.26). There was no significant heterogeneity by sex, or ethnicity, or confounding by HRT in women. Conclusion: High circulating levels of sTM were independently associated with incident calcification of the coronary arteries.

Progression of calcified coronary atherosclerosis: Relationship to coronary risk factors and carotid intima-media thickness

Background The determinants of coronary artery calcium (CAC) progression are not well understood. Prior studies have shown a limited relationship between CAC progression and traditional coronary risk factors. We hypothesized that the extent of non-calcified atherosclerosis detected using carotid intima-media thickness (CIMT) would predict progression of calcified atherosclerosis. Methods One hundred and eighty healthy male participants (mean age 47.9) with CAC from the Prospective Army Coronary Calcium (PACC) project volunteered to undergo a second EBCT scan, risk factor assessment, lab testing, and CIMT assessment 4.2 ± 1.3 years after their original scan. All results were independently examined, blinded to baseline data. A change in CAC score ≥15% per year was defined as clinically significant progression. Results CAC progression occurred in 60.2%. Compared to participants without progression, those with progression had higher triglycerides, LDL and total cholesterol and Framingham risk scores, but similar blood pressure, HDL cholesterol, blood glucose, C-reactive protein, fibrinogen, and body mass index. CIMT was significantly higher among those with versus without CAC progression (0.660 mm versus 0.603 mm; P = 0.001). Each quintile of increasing CIMT was independently associated with a 35% increase in the odds of CAC progression ( P = 0.01), after controlling for the Framingham risk score and C-reactive protein. Conclusion Among middle-aged men with coronary calcium, increasing extent of non-calcified atherosclerosis is strongly associated with coronary artery calcium progression over 4 years.

Progression of Coronary Artery Calcification in Patients Taking Alendronate for Osteoporosis

Rationale and Objectives As with their actions on bone, bisphosphonates may play a role in coronary artery calcification (CAC) by inhibiting calcium resorption from plaque. The objective of this study was to determine whether the osteoporosis treatment agent alendronate accelerates the rate of CAC. Materials and Methods The study was a pilot comparative analysis of 56 alendronate-treated patients with osteoporosis compared with 56 control subjects matched for age, sex, risk factors, and CAC scores and with a reference cohort that included 213 control subjects. Patients received alendronate sodium (10 mg daily) for a mean of 24 months and underwent annual assessment of CAC with electron-beam computed tomography and bone mineral density with dual x-ray absorptiometry. The principal outcome measure was the rate of change in CAC score in patients and control populations. Results There was significant progression of CAC in both alendronate-treated and matched-control groups (paired t test, P = .004 and .006, respectively) but no difference in the rates of CAC progression between the alendronate-treated patients and either the matched or reference control cohort. Conclusions This small pilot study indicates that oral alendronate administration does not accelerate the rate of CAC, but a larger cohort should be studied to confirm these findings.

Significant association between the progression of coronary artery calcification and dyslipidemia in patients on chronic hemodialysis

Quantification of coronary artery calcification (CAC) determined by electron-beam computed tomography (EBCT), known as the CAC score (CACS), correlates with total plaque amount and coronary risk factors and strongly associates with maximal stenosis in the epicardial arteries. However, data are limited concerning the CACS in chronic dialysis patients, although atherosclerotic vascular disease is the most frequent complication. We examined the relation between coronary risk factors, metabolic factors of calcium and other minerals, and CACS progression in 24 dialysis patients. The mean patient age was 53 ± 14 (SD) years, and mean duration of dialysis was 64 ± 69 months. In each patient, the CACS was measured twice, with a mean interscan period of 17 ± 3 months. The mean CACS progressed from 449 ± 605 to 669 ± 894 overall, and the mean change in CACS (ΔCACS) was 220 ± 78. Patients were divided into two groups: slow progressors, with ΔCACS of 7.5 ± 31 (n = 12), and rapid progressors, with ΔCACS of 432 ± 458 (n = 12). Triglyceride concentrations (198 ± 65 versus 103 ± 50 mg/dL; P < 0.001) were high, and high-density lipoprotein cholesterol (HDL-C) concentrations (46 ± 11 versus 60 ± 18 mg/dL; P < 0.05) were low in rapid progressors. Rapid progression of CAC was associated with high triglyceride and low HDL-C concentrations. The clinical significance of these observations remains to be determined. © 2001 by the National Kidney Foundation, Inc.

Progression of Coronary Artery Calcification: A Pilot Study

To describe individual changes in the quantity of coronary artery calcification (CAC) measured by electron beam computed tomography (CT) and determine the rate of change in the quantity of CAC during a 3.5-year period. Eighty-eight consecutive participants (51 men at least 30 years of age and 37 women at least 40 years of age) from a community-based CAC study were invited for a follow-up examination. Established coronary artery disease risk factors were studied at baseline. CAC score was measured by electron beam CT at baseline and follow-up. Of the 88 invited participants, 82 (93%) returned for a follow-up examination. Considerable variation existed among the participants in the extent of CAC score change. On average, CAC score increased over time by an estimated 24% each year (P<0.05). The relative increase in CAC score over time was significantly lower for older than for younger participants but did not vary significantly by sex. The ability to recruit follow-up participants in this pilot study and to detect significant change in CAC score over time provides evidence that electron beam CT is useful for studying progression of CAC in a sample and may be a valuable procedure for assessing the effectiveness of clinical interventions designed to retard progression of coronary atherosclerosis.