Addition Of Coronary Artery Calcium Research Articles

Value of addition of coronary artery calcium to risk scores in the prediction of major cardiovascular events in patients with type 2 diabetes

BackgroundThe increased risk for cardiovascular events in diabetics is heterogeneous and contemporary clinical risk score calculators have limited predictive value. We therefore examined the additional value of coronary artery calcium score (CACS) in outcome prediction in type 2 diabetics without clinical coronary artery disease (CAD).MethodsThe study examined a population-based cohort of type 2 diabetics (n = 735) aged 55–74 years, recruited between 2006 and 2008. Patients had at least one additional risk factor and no history or symptoms of CAD. Risk assessment tools included Pooled Cohort Equations (PCE) and Multi-Ethnic Study of Atherosclerosis (MESA) 10-year risk score calculators and CACS. The occurrence of myocardial infarction (MI), stroke or cardiovascular death (MACE) was assessed over 10-years.ResultsRisk score calculators predicted MACE and MI and cardiovascular death individually but not stroke. Increasing levels of CACS predicted MACE and its components independently of clinical risk scores, glycated hemoglobin and other baseline variables: hazard ratio (95% confidence interval) 2.92 (1.06–7.86), 6.53 (2.47–17.29) and 8.3 (3.28–21) for CACS of 1–100, 101–300 and > 300 Agatston units respectively, compared to CACS = 0. Addition of CACS to PCE improved discrimination of MACE [AUC of PCE 0.615 (0.555–0.676) versus PCE + CACS 0.696 (0.642–0.749); p = 0.0024]. Coronary artery calcium was absent in 24% of the study population and was associated with very low event rates even in those with high estimated risk scores.ConclusionsCACS in asymptomatic type 2 diabetics provides additional prognostic information beyond that obtained from clinical risk scores alone leading to better discrimination between risk categories.

Added value of cardiovascular calcifications for prediction of recurrent cardiovascular events and cardiovascular interventions in patients with established cardiovascular disease

The purpose is to investigate the added prognostic value of coronary artery calcium (CAC), thoracic aortic calcium (TAC), and heart valve calcium scores for prediction of a combined endpoint of recurrent major cardiovascular events and cardiovascular interventions (MACE +) in patients with established cardiovascular disease (CVD). In total, 567 patients with established CVD enrolled in a substudy of the UCC-SMART cohort, entailing cardiovascular CT imaging and calcium scoring, were studied. Five Cox proportional hazards models for prediction of 4-year risk of MACE + were developed; traditional CVD risk predictors only (model I), with addition of CAC (model II), TAC (model III), heart valve calcium (model IV), and all calcium scores (model V). Bootstrapping was performed to account for optimism. During a median follow-up of 3.43 years (IQR 2.28–4.74) 77 events occurred (MACE+). Calibration of predicted versus observed 4-year risk for model I without calcium scores was good, and the c-statistic was 0.65 (95%CI 0.59–0.72). Calibration for models II–V was similar to model I, and c-statistics were 0.67, 0.65, 0.65, and 0.68 for model II, III, IV, and V, respectively. NRIs showed improvement in risk classification by model II (NRI 15.24% (95%CI 0.59–29.39)) and model V (NRI 20.00% (95%CI 5.59–34.92)), but no improvement for models III and IV. In patients with established CVD, addition of the CAC score improved performance of a risk prediction model with classical risk factors for the prediction of the combined endpoint MACE+ . Addition of the TAC or heart valve score did not improve risk predictions.

Abstract 17236: Coronary Artery Calcification Scoring Stratifies Risk of Sudden Cardiac Death: The CAC Consortium

Introduction: Sudden cardiac death (SCD) commonly presents as the initial manifestation of coronary heart disease in the general population. Coronary artery calcium (CAC), a sub-clinical marker of atherosclerosis, is a strong predictor of cardiovascular events. We assessed the ability of CAC to stratify risk of SCD. Methods: We studied 66,636 adults from the CAC Consortium, a large multi-center cohort of asymptomatic patients free of clinical CVD at baseline. We categorized participants into 4 CAC score groups—CAC=0, CAC 1-99, CAC 100-399, and CAC≥400. The primary outcome was defined by identifying accepted International Classification of Diseases codes for SCD on official death certificates obtained for all deaths from the National Death Index. Predictive value of CAC for SCD was assessed using Cox proportional hazards regression models adjusted for age, sex and traditional risk factors. We performed standard area under receiver operating curve (AUC) analyses from fully adjusted logistic regression models, with and without CAC. All analyses were also repeated among participants aged 45-75 years. Results: Mean age of the study population was 54.4 years, and 33% were females and 89% were Whites. Over a mean follow up of 12.3±3.9 years, there were 211 SCD events. Participants with CAC=0 had lower absolute SCD rates compared to those with CAC≥400 (0.05 vs 1.28 per 1000 person-years, respectively). Increasing CAC scores (reference CAC=0) were associated with increasing SCD risk [CAC 100-399: HR (95% CI) 2.8(1.6-5.0), CAC≥400: 4.3(2.4-7.7)]. Addition of CAC to the fully adjusted model (vs without CAC) improved AUC for SCD among the whole study population (0.88 vs 0.86, P <0.001) and more so among 45-75 year-olds (0.82 vs 0.76, P <0.001). Conclusions: We demonstrate the predictive value of CAC for SCD. CAC could be a cost-effective risk-stratification tool that can be used to help identify individuals at high risk of SCD who could undergo additional screening and management.

Arterial calcification in the prediction of atherosclerotic cardiovascular disease among women and men

Abstract Background The Coronary Artery Calcium (CAC) Score has emerged as a valuable tool in atherosclerotic cardiovascular disease (ASCVD) risk stratification. However, data on the relevance of arterial calcification in different vascular territories for ASCVD risk prediction is lacking. Purpose First, to assess the sex-specific distribution of arterial calcification in different vessel beds across ASCVD risk categories. Second, to determine the added value of arterial calcification in different vascular territories for ASCVD risk prediction. Methods From a large population-based study, 2,139 participants (mean age 69 years, 55% women) underwent non-contrast computed tomography to quantify CAC, aortic arch calcification (AAC), extracranial- (ECAC) and intracranial carotid artery calcification (ICAC), and vertebrobasilar artery calcification (VBAC). The outcome measure, incident ASCVD, composed of fatal and nonfatal myocardial infarction (MI), other coronary heart disease (CHD) mortality, and stroke. We fitted sex-specific prediction models according to the Pooled Cohort Equations (PCE), and categorized participants into low- (<5%), borderline- (5% to 7.5%), intermediate- (7.5% to 20%), and high ASCVD risk (≥20%), based on the American College of Cardiology (ACC) and American Heart Association (AHA) guideline. Subsequently, we determined the distribution of calcifications in different vascular territories across the risk categories. Next, we extended the PCE prediction model with calcification volumes and calculated the c-statistic and the net reclassification improvement for events (NRIe) and non-events (NRIne). Results The median follow-up for ASCVD was 9.3 years. Among women, 38% was classified as low-risk, 19% as borderline risk, 31% as intermediate risk, and 12% as high risk. Among men, 2% was classified as low-risk, 10% as borderline risk, 60% as intermediate risk, and 28% as high risk. With increasing risk of ASCVD, a larger burden of calcification was observed. In women, simultaneously adding calcification volumes in all vessel beds led to the largest increase in c statistic (from 0.71 to 0.75) for the prediction of ASCVD and the most beneficial reclassification (NRIe: 11%, NRIne: 2%). Among men, the addition of CAC alone most substantially improved the prediction of ASCVD (c statistic improved from 0.65 to 0.68, NRIe and NRIne were 4% and 14%, respectively). Conclusions Our findings suggest a potential role for comprehensive assessment of calcification in different vessel beds for ASCVD risk stratification in particular among women. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): The Rotterdam Study is supported by Erasmus MC and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly; the Netherlands Genomics Initiative; the Ministry of Education, Culture, and Science; the Ministry of Health, Welfare, and Sports; European Commission; and the Municipality of Rotterdam. Dr. Kavousi is supported by the VENI grant (91616079) from ZonMw. Dr. Bos was supported by a fellowship of the BrightFocus Foundation (A2017424F). Oscar L. Rueda-Ochoa receives a scholarship from COLCIENCIAS-Colombia and support from Universidad Industrial de Santander,UIS-Colombia. None of the funders had any role in study design; study conduct; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the article.

Adding Coronary Calcium Score to Exercise Treadmill Test: An Alternative to Refine Coronary Artery Disease Risk Stratification in Patients with Intermediate Risk Chest Pain

Introduction:Chest pain is a common symptom for cardiology referrals. The ACC-AHA guidelines recommend exercise stress electrocardiography (TMX) as the initial diagnostic test. However, the TMX only has moderate sensitivity and non-diagnostic cases may require further stress imaging studies. In this study we aimed to look at the feasibility of combining coronary artery calcium (CAC) score with TMX to refine risk stratification. This may be an alternative to stress imaging in cases of non low-risk TMX, with the added advantage of short time turnaround time and low radiation dose.Methods:A total of 145 patients who presented consecutively to the National Heart Centre Singapore with chest pain were included in this study. These were intermediate risk patients with an average Duke Clinical Score of 38.8%. All patients underwent both TMX and computed tomography scan of the coronary arteries (CTCA) which also includes CAC. The primary outcome was defined as obstructive coronary artery disease i.e. >50% left main artery stenosis and/or >70% stenosis in other epicardial arteries.Results:The combination of TMX and CAC was comparable to stress imaging in detecting obstructive coronary artery disease. When added to TMX, CAC has an integrated discriminative improvement of 74.1%, achieved an area under the curve of 0.974 and adjusted R2 of 0.670 in detecting the primary outcome.Conclusion:The strategy of combining TMX and CAC is feasible in clinical practice to refine risk stratification in outpatients with intermediate risk chest pain. The calcium score readout also further guides therapy for primary prevention.Highlights:Treadmill exercise is one of the first line tests for cardiac chest pain work up.Non diagnostic test treadmill results requires further adjunctive tests.Downstream stress imaging causes delay in time to diagnosis.Coronary artery calcium scoring needs minimal preparation with fast turnaround time.Addition of coronary artery calcium to treadmill performs comparably to stress imaging.This is a feasible alternative to risk stratify non diagnostic treadmill tests and guide therapy for primary prevention.

Revised Framingham Stroke Risk Score, Nontraditional Risk Markers, and Incident Stroke in a Multiethnic Cohort.

Limited data exist on the performance of the revised Framingham Stroke Risk Score (R-FSRS) and the R-FSRS in conjunction with nontraditional risk markers. We compared the R-FSRS, original FSRS, and the Pooled Cohort Equation for stroke prediction and assessed the improvement in discrimination by nontraditional risk markers. Six thousand seven hundred twelve of 6814 participants of the MESA (Multi-Ethnic Study of Atherosclerosis) were included. Cox proportional hazard, area under the curve, net reclassification improvement, and integrated discrimination increment analysis were used to assess and compare each stroke prediction risk score. Stroke was defined as fatal/nonfatal strokes (hemorrhagic or ischemic). After mean follow-up of 10.7 years, 231 of 6712 (3.4%) strokes were adjudicated (2.7% ischemic strokes). Mean stroke risks using the R-FSRS, original FSRS, and Pooled Cohort Equation were 4.7%, 5.9%, and 13.5%. The R-FSRS had the best calibration (Hosmer-Lemeshow goodness-of-fit, χ2=6.55; P=0.59). All risk scores were predictive of incident stroke. C statistics of R-FSRS (0.716) was similar to Pooled Cohort Equation (0.716), but significantly higher than the original FSRS (0.653; P=0.01 for comparison with R-FSRS). Adding nontraditional risk markers individually to the R-FSRS did not improve discrimination of the R-FSRS in the area under the curve analysis, but did improve category-less net reclassification improvement and integrated discrimination increment for incident stroke. The addition of coronary artery calcium to R-FSRS produced the highest category-less net reclassification improvement (0.36) and integrated discrimination increment (0.0027). Similar results were obtained when ischemic strokes were used as the outcome. The R-FSRS downgraded stroke risk but had better calibration and discriminative ability for incident stroke compared with the original FSRS. Nontraditional risk markers modestly improved the discriminative ability of the R-FSRS, with coronary artery calcium performing the best.

Abstract MP70: Ten Year Coronary Heart Disease Risk Prediction Using Coronary Artery Calcium and Traditional Risk Factors: Results from the Multi-Ethnic Study of Atherosclerosis (MESA)

Objectives: In the modern era existing risk scores are not well calibrated, and may overestimate or underestimate risk in different populations. Several studies have demonstrated the added value of coronary artery calcium (CAC) over and above traditional risk factors for risk prediction. Our goal was to develop a risk score to estimate 10-year CHD risk using CAC and traditional risk factors. Methods: The MESA study is a cohort of 6814 participants aged 45-84 and free of clinical heart disease at baseline (2000-2002) in which CAC (Agatston score) was measured. Incident coronary heart disease (CHD) events included myocardial infarction, CHD death, and angina when accompanied by revascularization. Penalized Cox regression models (“shrinkage” models) were used to perform variable selection and estimate the risk score coefficients. Covariates which were considered for inclusion in the risk score model were: age, gender, race/ethnicity, HDL and total cholesterol, lipid lowering medication use, systolic blood pressure (SBP), anti-hypertensive medication use, body mass index (BMI), current smoking, family history of heart attack, diabetes, and CAC. Pre-specified interactions considered included: age, gender, race/ethnicity and CAC with all other predictors; anti-hypertensive medications-by-SBP; and lipid lowering medications-by- total cholesterol. Bootstrapping was used to establish the internal validity of the model to avoid over-optimism. Results: Participants were followed for a median of 10.2 years, and 393 CHD events were observed. With the exception of BMI and diastolic blood pressure, all the risk factors were included in the risk score. The risk score demonstrates good discrimination and calibration, with survival adapted area under the ROC curve (AUC) of 0.81 and discrimination slope of 0.91. The model exhibits improved performance compared to existing risk scores, even after recalibration of traditional risk scores to the MESA population, which have yield an AUC for Framingham risk score of 0.72, and an AUC for traditional risk factors fit to MESA of 0.76. The improvement reflects both the addition of CAC and a tuning of the parameter estimates for the traditional risk factors. The MESA 10-year CHD risk calculator will be available online to facilitate clinical use. Conclusions: An accurate estimate of 10-year CHD risk can be obtained using traditional cardiovascular risk factors and CAC.

Abstract 18536: Performance of Framingham Risk Function With Coronary Artery Calcium in Predicting Major Coronary Events in an Asian Cohort

Background: In non-White populations, the original Framingham risk functions (FRF) overestimates coronary heart disease (CHD) risk and requires recalibration. We tested whether the inclusion of coronary artery calcium (CAC) can improve the performance of the FRF in CHD prediction in an asymptomatic Asian cohort. Methods: We determined risk factors, CAC burden and CV outcomes in a sample of 4502 asymptomatic South Koreans (from the registry-based ESCORT Study) and in 3141 asymptomatic Caucasian participants from the Framingham Heart Study (FHS). Primary endpoint was a composite of cardiovascular death, myocardial infarction, and unstable angina with revascularization. We assessed both the discriminatory value of the original FRF before and after the addition of CAC using area under the receiver operator characteristic (AUC) and the calibration/predictive ability using the D’Agostino-Nam Chi squared test for survival data, where a chi-square statistic > 20 indicates poor calibration. Results: There were 95 hard CHD events (45 ESCORT, 50 FHS) over a 55 month (ESCORT) and 60 month (FHS) follow-up period. For the FRF, the AUROC was 0.82, and the D’Agostino-Nam chi-squared statistic was 22.59 (p = 0.007) for predicting MACE in the ESCORT cohort. After the addition of CAC, the AUC improved to 0.85 and the D’Agostino-Nam chi-squared statistic improved to 16.14 (p = 0.064). The Caucasian-derived FRF model had poor predictive ability/calibration and consistently overestimated event rates in the Asian ESCORT cohort over all risk categories. For instance, in the 10th decile of risk, the predicted event rate using the FRF was 6% compared to an actual rate of 3.5% in the ESCORT cohort (Figure 1a) Conclusion: Addition of CAC to the classic Framingham risk functions significantly improves its performance in terms of discrimination and calibration in the prediction of major adverse CHD events in an Asian (South Korean) population.

The Role of Coronary Artery Calcium Score and Age in Early Identification of Occult Coronary Artery Disease among Patients Undergoing Liver Transplant Work-up for End-stage Liver Disease

Purpose: Cardiac evaluation is an important component of the liver transplantation work-up in an attempt to achieve higher post-transplant survival rates. Identification of coronary artery disease among asymptomatic candidates is challenging. The addition of coronary artery calcium (Ca) score in conjunction with dobutamine or nuclear stress testing has been recently proposed to improve risk stratification. However, it is unclear if all groups of liver transplant candidates will benefit from Ca score testing. Due to the rise in transplant candidate referrals over the age of 60 years, our aim was to investigate the role of Ca score among older cirrhotic populations. Methods: Following IRB approval, electronic medical records of adult liver transplant candidates (above age 40) evaluated at Johns Hopkins Liver Transplant program between 1/1/2011 and 5/1/2013 were retrospectively reviewed. Patients who had a history of diabetes mellitus, hypertension, or smoking were further evaluated using coronary artery calcium score. Results: Coronary artery calcium (Ca) score was obtained on 66 patients. There were 42 patients less than age 60 (mean age 54 ± SD 5.4), and 24 greater than age 60 (mean age 63 ± SD 2.7). Within the first group, there were 17 females and 25 males; in the latter group, there were nine females and 15 males. The mean Ca scores in patients age <60 was 319 ± 652, while among patients age >60 was 684 ± 616 (p=0.042). Conclusion: Dobutamine or nuclear stress tests are standard tests among patients undergoing liver transplant work-up. The addition of coronary artery calcium (Ca) score can be a very useful tool in the identification of occult CAD, especially among patients with cardiac risk factors (DM, HTN and smoking) and those above age 60.Figure

Markers for Prediction of Cardiovascular Disease Risk

To the Editor: The article by Dr Yeboah and colleagues compared the ability of several risk markers to improve prediction of coronary heart disease (CHD) and cardiovascular disease (CVD) among individuals at intermediate risk. The authors reported that coronary artery calcium (CAC) provided superior reclassification compared with other risk markers and recommended CAC as a tool for refining cardiovascular risk prediction in individuals at intermediate risk. While the added predictive ability of CAC in CHD risk prediction was substantial and confirmed previous findings, we believe that supporting CAC as a candidate for CVD screening based on the results is less grounded. While it is straightforward to define an intermediaterisk group for CHD, this is not the case for CVD because accepted thresholds are lacking. In the study by Yeboah et al, the authors included persons at intermediate risk for CHD and therefore the results might not necessarily apply to persons at intermediate risk for CVD. While CAC has been shown to accurately predict CHD in different populations, CAC has not been proven to be a useful predictor for stroke. In the study by Yeboah et al, addition of CAC to the Framingham risk score provided overall net reclassification improvement of 0.66 for CHD and 0.47 for CVD risk prediction. The percentage net correct reclassification in the group without events hardly changed after adding a non–CAC-related outcome such as stroke (40.4% for CHD and 36.0% for CVD). However, the percentage net correct reclassification for those with events, which reflects the ability to identify persons who will benefit from intensive treatment, dropped from 25.5% for CHD and 10.6% for CVD. The percentage net correct reclassification for persons with CHD events of 25.5% in the current study and 24.0% previously reported imply that adding CAC to risk prediction models moves a substantial proportion of persons initially at intermediate risk to the high-risk group, in which they qualify for more aggressive treatment. This supports the incorporation of CAC in CHD risk assessment. However, whether 10.6% net correct reclassification of persons with CVD events provided by CAC is sufficiently large to warrant recommending CAC as a screening tool for CVD is doubtful. The general trend in developing new guidelines on cardiovascular risk prevention is moving toward focusing on broader CVD risk rather than on CHD risk only. However, before considering new markers for CVD risk prediction, all components of this broad outcome should be considered and limitations for stroke risk prediction should be recognized.

Abstract P159: Coronary Artery Calcium Score Improves the Net Reclassification Index of Prevalent Cardiovascular Disease In African Americans: The Jackson Heart Study

Background: Prior studies suggest that African Americans (AA) have lower prevalence of coronary artery calcium (CAC) compared to whites, yet CAC has similar ability to predict coronary heart disease (CHD) events. The role of CAC as a screening tool for CHD risk in AA is unclear. We compared the diagnostic accuracy for CHD prevalence using the CAC score and the Framingham Risk Score (FRS) in an adult population of AA. Methods: CAC was measured in 2944 participants in the Jackson Heart Study, an NHLBI funded study of AA based in Jackson, MS. Approximately 8% of this cohort had known cardiovascular disease (CVD) defined as prior MI, angina, stroke, PTCA, CABG or PVD. Logistic regression, ROC and net reclassification index (NRI) analysis were used adjusting for age, gender, SBP, total and HDL cholesterol, smoking status, DM and BMI. FRS was calculated and those with DM were classified as high risk. Results: The mean age was 60, 65% were females, 26% had DM, 50% were obese and 30% were current or former smokers. Prevalent CVD was associated with older age, higher SBP, lower HDL and total cholesterol, and higher CAC. CAC was independently associated with prevalent CVD in our multivariable model [OR (95% CI): 1.26 (1.17, 1.35), p&lt; 0.0001]. In ROC analysis, CAC improved the diagnostic accuracy (c statistic) of the FRS from 0.617 to 0.757 (p &lt; 0.0001) for prevalent CVD. The FRS classified 30% of the cohort as high risk, 38.5% as intermediate risk and 31.5% as low risk. FRS classfied 51% of subjects with prevalent CVD as high risk. Addition of CAC to FRS resulted in net reclassification improvement of 4% for subjects with known CVD and 28.5% in those without CVD (see figure). Conclusion: In AA, the CAC is independently associated with prevalent CVD and improves the diagnostic accuracy of FRS for prevalent CVD by 14%. Addition of CAC improves the NRI of those with prevalent CVD by 4% and the NRI of individuals without CVD by 28.5%. Determination of CAC in AA may be useful in identifying individuals at risk of CVD and reclassifying individuals with low and intermediate FRS.

Abstract MP054: Coronary Calcification, C-reactive Protein and Prediction of Cardiovascular and All-Cause Mortality in Diabetes: Diabetes Heart Study

Objective: Does coronary artery calcium (CAC) and C-reactive protein (CRP) improve discrimination and risk stratification of cardiovascular (CVD) and all-cause mortality in diabetes. Background: Inflammation is associated in the pathogenesis and progression of atherosclerosis. Since diabetes is characterized by both atherosclerosis and high CRP levels, we hypothesized that CAC and CRP will predict CVD and all-cause mortality in diabetes beyond Framingham risk factors (FRS). Method: A total of 961 participants, ages 39-86, with complete data on diabetes, vascular imaging, and inflammation in the Diabetes Heart Study were followed for an average of 7.4 years. CAC was assessed by CT at baseline. CRP was measured using enzyme-linked immunosorbent assay. Risk estimates for CVD and all-cause mortality were obtained using logistic regression models. Model 1 included FRS; age, gender, smoking, systolic blood pressure, antihypertensive medication use, total and HDL cholesterol, and ethnicity. Model 2 included FRS plus CRP or CAC. Model 3 included FRS plus CRP and CAC. Models for CVD and all-cause mortality were compared using c-statistics. Results: During follow-up there were 183 (19%) deaths of which 80 (8%) were CVD deaths. In FRS adjusted models both CRP and CAC were independently associated with all-cause mortality, however only CAC was associated with CVD mortality. The addition of CAC to a model with FRS and CRP improves discrimination for CVD and all-cause mortality (both p=0.001). However, the addition of CRP to a model with FRS and CAC only improves discrimination in all-cause mortality (p=0.001) ( Table 1 ). Conclusion: In participants with T2DM, measures of CAC and CRP are significantly associated with CVD (CAC only) and all-cause (CAC and CRP) mortality independent of the FRS; however, the improvement in CVD and all-cause mortality prediction was predominantly driven by CAC. Table 1 C-Statistics for the Combined Assessment of Framingham Risk Factors, CAC and CRP in Predicting Cardiovascular and All-Cause Mortality CVD Mortality All-Cause Mortality C-Statistic p-value C-Statistic p-value Model 1 FRS Only 0.715 -- 0.701 -- Model 2 vs. Model 1 Adding CRP to FRS Adding CAC to FRS 0.715 0.768 P=0.737 P=0.001 0.709 0.760 p=0.002 P=0.001 Model 3 vs. Model 2 Adding CAC to FRS + CRP Adding CRP to FRS + CAC 0.769 0.769 P=0.001 P=0.981 0.765 0.765 P=0.001 P=0.001

Impact of Coronary Artery Calcium Scanning on Coronary Risk Factors and Downstream Testing: The EISNER (Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) Prospective Randomized Trial

We conducted a prospective randomized trial to compare the clinical impact of conventional risk factor modification to that associated with the addition of coronary artery calcium (CAC) scanning.Although CAC scanning predicts cardiac events, its impact on subsequent medical management and coronary artery disease risk is not known.We assigned 2,137 volunteers to groups that either did undergo CAC scanning or did not undergo CAC scanning before risk factor counseling. The primary end point was 4-year change in coronary artery disease risk factors and Framingham Risk Score. We also compared the groups for differences in downstream medical resource utilization.Compared with the no-scan group, the scan group showed a net favorable change in systolic blood pressure (p = 0.02), low-density lipoprotein cholesterol (p = 0.04), and waist circumference for those with increased abdominal girth (p = 0.01), and tendency to weight loss among overweight subjects (p = 0.07). While there was a mean rise in Framingham Risk Score (FRS) in the no-scan group, FRS remained static in the scan group (0.7 ± 5.1 vs. 0.002 ± 4.9, p = 0.003). Within the scan group, increasing baseline CAC score was associated with a dose-response improvement in systolic and diastolic blood pressure (p < 0.001), total cholesterol (p < 0.001), low-density lipoprotein cholesterol (p < 0.001), triglycerides (p < 0.001), weight (p < 0.001), and Framingham Risk Score (p = 0.003). Downstream medical testing and costs in the scan group were comparable to those of the no-scan group, balanced by lower and higher resource utilization for subjects with normal CAC scans and CAC scores ≥400, respectively.Compared with no scanning, randomization to CAC scanning was associated with superior coronary artery disease risk factor control without increasing downstream medical testing. Further study of CAC scanning, including pre-specified treatment recommendations, to assess its impact of cardiovascular outcomes is warranted.

Coronary artery calcium score improves cardiovascular risk prediction in persons without indication for statin therapy

BackgroundRecent revision to the Canadian Cardiovascular Society (CCS) guidelines on cardiovascular disease (CVD) risk stratification provides expanded recommendations for statin therapy. If CVD risk in the remaining individuals can further be stratified and discriminated by additional risk assessment using coronary artery calcium (CAC) scoring is unknown. Methods and resultsIn a retrospectively analyzed subgroup comprising 1934 participants from the Heinz Nixdorf Recall study, who did not meet criteria for statin therapy based on current CCS guidelines, traditional CVD risk variables and CAC were measured. Between 2000 and 2008, incident CVD events, i.e. coronary deaths, non-fatal myocardial infarction, coronary revascularization, stroke and CV death were determined. Those 43 participants who experienced 55 CVD events (5-year risk to first event: 2.2% (1.6–3.0%)) had higher CAC scores than those who did not (p<0.0001). In multiple Cox regression analysis including age, sex, total-/HDL-cholesterol ratio, and antihypertensive medication, log2(CAC+1) remained an independent predictor of CVD events (HR=1.21 (1.09–1.33), p<0.001). Measures of discrimination improved with the addition of CAC into the model: the incremental discrimination improvement was 0.0167, p=0.014. Net reclassification improvement using risk categories of 0–<3%, 3–10% and >10% was 25.1%, p=0.01, largely driven by a 32.6% correct up-classification in persons with events. Yet, only 38 (2%) of participants were identified being at high risk using CAC imaging in addition to traditional risk factor assessment. ConclusionAdding CAC to traditional risk assessment in persons without indication for statin therapy improves discrimination. However, reclassification to the high risk category and overall event rates seem too low to justify liberal CAC testing in all these individuals.