 |
|
Coronary Artery Calcium Score Combined With Framingham Score for Risk Prediction in Asymptomatic Individuals
Philip Greenland, MD;
Laurie LaBree, MS;
Stanley P. Azen, PhD;
Terence M. Doherty, BA;
Robert C. Detrano, MD, PhD
JAMA. 2004;291:210-215.
ABSTRACT
| |
Context Guidelines advise that all adults undergo coronary heart disease (CHD) risk assessment to guide preventive treatment intensity. Although the Framingham Risk Score (FRS) is often recommended for this, it has been suggested that risk assessment may be improved by additional tests such as coronary artery calcium scoring (CACS).
Objectives To determine whether CACS assessment combined with FRS in asymptomatic adults provides prognostic information superior to either method alone and whether the combined approach can more accurately guide primary preventive strategies in patients with CHD risk factors.
Design, Setting, and Participants Prospective observational population-based study, of 1461 asymptomatic adults with coronary risk factors. Participants with at least 1 coronary risk factor (>45 years) underwent computed tomography (CT) examination, were screened between 1990-1992, were contacted yearly for up to 8.5 years after CT scan, and were assessed for CHD. This analysis included 1312 participants with CACS results; excluded were 269 participants with diabetes and 14 participants with either missing data or had a coronary event before CACS was performed.
Main Outcome Measure Nonfatal myocardial infarction (MI) or CHD death.
Results During a median of 7.0 years of follow-up, 84 patients experienced MI or CHD death; 70 patients died of any cause. There were 291 (28%) participants with an FRS of more than 20% and 221 (21%) with a CACS of more than 300. Compared with an FRS of less than 10%, an FRS of more than 20% predicted the risk of MI or CHD death (hazard ratio [HR], 14.3; 95% confidence interval [CI]; 2.0-104; P = .009). Compared with a CACS of zero, a CACS of more than 300 was predictive (HR, 3.9; 95% CI, 2.1-7.3; P<.001). Across categories of FRS, CACS was predictive of risk among patients with an FRS higher than 10% (P<.001) but not with an FRS less than 10%.
Conclusion These data support the hypothesis that high CACS can modify predicted risk obtained from FRS alone, especially among patients in the intermediate-risk category in whom clinical decision making is most uncertain.
INTRODUCTION
The Framingham Risk Score (FRS) is a multivariable statistical model that uses age, sex, smoking history, blood pressure, cholesterol, high-density lipoprotein cholesterol (HDL-C), and blood glucose levels or history of diabetes to estimate coronary event risk among individuals without previously diagnosed coronary heart disease (CHD).1 Although coronary risk stratification is widely recommended,2-4 prediction models based on CHD risk factors, such as the FRS, have limitations in their ability to discriminate individuals who will or will not experience CHD.1, 5 Given the uncertainty of current predictive models,5 the search for new strategies to discriminate patients who would benefit most from intensive primary prevention efforts is a clinically important objective.3, 6 One suggested approach to improve risk prediction over the FRS is the quantification of coronary artery calcium score (CACS), most commonly using computed tomography (CT).7-13
The objective of this study was to determine whether CACS assessment combined with FRS among asymptomatic adults provides prognostic information superior to either method alone and whether the combined approach can more accurately guide primary preventive strategies for patients with CHD risk factors.
METHODS
Design and Study Cohort
The design of the South Bay Heart Watch, a prospective observational study, and the demographics of participants have been described. 9, 14-16 The original cohort consisted of 1461 asymptomatic participants (>45 years) with at least 1 abnormal coronary risk factors (>10% estimated 8-year risk of developing CHD by an earlier version of the Framingham risk equation17). Participants with electrocardiographic (ECG) evidence of myocardial infarction (MI) or clinical history of MI, coronary revascularization, or angina were excluded. Thirty months after enrollment, 1312 surviving participants underwent a second evaluation including fasting phlebotomy concurrent with CT examination for measurement of CACS. Participants gave written informed consent at both examinations. The Harbor UCLA Research and Education Institute Human Subjects Committee approved this study.
We excluded patients with diabetes because CACS has not been found to have prognostic value for such patients in this cohort16 and because patients with diabetes are considered to be at high risk of future coronary events based on the presence of diabetes.3 Participants were classified as having diabetes if they had a history of keeping a diet or taking medication for diabetes, had been diagnosed as having diabetes during a hospital admission and had been discharged with insulin or oral hypoglycemic medications or had a random plasma glucose level of at least 200 mg/dL (11.1 mmol/L) at the time of recruitment.16
Risk Factors and CACS Measurements
Risk factors for CHD (smoking; sex; family history of CHD; blood pressure; total cholesterol, HDL-C, and low-density lipoprotein cholesterol [LDL-C] levels; triglycerides; and body mass index as a measure of obesity) and ECG results were routinely obtained at both examinations by previously described methods.9 Computed tomographic scans were performed within 2 (±2) days after the second risk factor evaluation using a 6-mm slice thickness acquisition protocol, which has high rescan reliability and similar predictive capacity compared with the commonly used 3-mm slice thickness.18-19 Although we have found 6-mm slice scores to be equivalent to 3-mm slice scores in predicting future CHD events,18-19 CACS by the former method are slightly lower than 6-mm scan scores. A regression equation has been developed for comparing these 2 types of measurements.18
Quality control included periodic checks of the scanner by a radiation physicist, use of a phantom to calibrate and evaluate noise artifact, and determination of retest reproducibility of the scanning protocol. A single cardiologist blinded to all clinical data interpreted the scans using scoring software identical to that used for the Multi-Ethnic Study of Atherosclerosis (MESA),20 with CACS calculated by the Agatston method.21
Clinical Follow-up
We contacted participants yearly for up to 8.5 years after CT examination (median, 7.0 years) and assessed cardiovascular events using questions about intervening hospital admissions. We reviewed medical records for hospitalizations related to a complaint of chest discomfort, dyspnea, vascular or cardiac problems, or any major surgery. A follow-up attempt was considered successful when surviving participants either returned to the clinic or completed a telephone interview, and all relevant medical records were obtained. For deceased participants, we defined successful follow-up as the procurement of relevant medical records, transcribed conversation with the next of kin, death certificate, or autopsy report. Overall, 99% of the participants completed the questionnaire at least once following the baseline CT scan. During the last contact attempt (2000-2002), with subsequent acquisition and adjudication of relevant medical records, the follow-up rate was 87.5%.
CHD End Point
A committee of 3 board-certified cardiologists reviewed medical records and transcripts of conversations with next of kin, without knowledge of other data, and applied majority rule to determine the occurrence of study end points. For this report, we focused only on "hard" CHD end points to minimize bias related to procedures that may ensue after coronary calcium detection. The study end point included nonfatal MI or CHD death.9 We defined MI as the presence of 2 or 3 of the following: prolonged chest pain prompting hospital admission, diagnostic evolutionary ECG changes, and elevation of serum creatine kinase levels to twice the upper limits of normal or a positive serum creatine kinase-MB fraction or troponin. Death due to CHD was assigned by the adjudication committee if death proved to be due to coronary atherosclerosis at autopsy, had occurred within 1 hour after onset of prolonged severe chest pain, had occurred suddenly in the absence of another known cause, or had occurred during hospitalization for MI.
Statistical Analysis
Analyses were conducted using P<.05 as the significance level and SAS statistical software version 9.0 (SAS Inc, Cary, NC). For Cox regression analyses, CACS was grouped into the following preselected categories: 0, 1 to 100, 101 to 300, and 301 or more. The FRS 10-year risk was calculated by age and risk factors at the time of CT scanning using the score derived from the third National Cholesterol Education Program report3 and grouped into the following preselected 10-year risk prediction categories: 0% to 9%, 10% to 15%, 16% to 20%, and 21% or higher. Univariate Cox regression analysis was used to assess the risk of CHD death or nonfatal MI for baseline CACS or FRS. Tests for trend across FRS and CACS (as continuous and categorical variables) were also conducted. Bivariate Cox regression analysis was used to assess risk for CHD death or nonfatal MI based on the joint relationship between the baseline CACS and FRS.
Finally, revised risk probabilities (FRS + CACS) were obtained using bivariate Cox regression with time to death or nonfatal MI as the dependent variable and FRS and CACS as continuous independent variables. The predicted survival probabilities at the median follow-up time were calculated for each participant. The FRS plus CACS for each participant was then calculated as (1 – predicted survival probability). The average FRS plus CACS was then computed for the 4 CACS groups within each of the 4 FRS groups. A 2-way factorial analysis of variance (factors = FRS, CACS, and FRS x CACS) was conducted to test for differences between CACS groups within each FRS group. Pairwise t tests were used to compare the highest CACS level (>300) with each of the lower CACS levels. To accommodate multiple comparisons within each FRS group, the significance level was set at .05/3 = .017 (Bonferroni adjustment). Receiver operating characteristic curves were then plotted, and the areas under the curves were compared for the FRS plus CACS score vs FRS alone as indexes of the discriminative ability of the FRS plus CACS vs FRS alone.
A secondary analysis was also conducted to assess predictive capability of CACS or FRS for all-cause mortality.
RESULTS
Of the 1312 participants with CT scan results, 269 had diabetes, an additional 12 had coronary events prior to the CT scan, and 2 participants had missing risk factor data. Thus, the study cohort consisted of 1029 participants. Characteristics of these participants stratified by CACS groups are shown in Table 1. Overall, the mean (SD) age at the time of the CT scan was 65.7 (7.8) years; 53 (5.2%) were Asian; 55 (5.3%), black; 46 (4.5%), Hispanic; 1 (0.1%), Native American; and 874 (84.9%), white. Over an average (SD) follow-up period of 75.9 (18.4) months (range, 1.4-101.9), 84 individuals experienced either a nonfatal MI (n = 68) or CHD death (n = 16).
|
|
|
|
Table 1. Baseline Characteristics Stratified by Coronary Artery Calcium Score (N = 1029)
|
|
|
Univariate Analyses
Table 2 presents event rates for CHD death or nonfatal MI and the results of the univariate Cox regression analyses relating likelihood of the CHD death or nonfatal MI end point according to increasing levels of CACS or increasing levels of FRS. The risk (hazard ratio [HR]) of a CHD death or nonfatal MI for participants with a CACS higher than 300 was 3.9 times that of participants with a CACS of zero (P<.001). The risk of a CHD death or nonfatal MI for participants in the highest FRS group (>20%) was 14.3 times that of participants with an FRS of less than 10% (P = .009). The risk of a CHD death or nonfatal MI across increasing categories of CACS was 1.6 (P<.001) and 1.7 across increasing categories of FRS (P<.001). When analyzed as continuous variables in univariate Cox regression models, the risk of a CHD death or nonfatal MI per 1-SD increase in CACS (399) and FRS (7.1) was 1.4 (P<.001) and 1.6 (P<.001), respectively.
|
|
|
|
Table 2. Univariate Cox Regression Analyses Predicting Coronary Death or Nonfatal Myocardial Infarction Based on Baseline CACS and FRS*
|
|
|
Bivariate Analyses
Table 3 presents the bivariate Cox regression analyses relating the likelihood of a CHD death or nonfatal MI according to increasing levels of CACS and also increasing levels of FRS. Shown are the distribution of coronary events and the HRs of CHD death or nonfatal MI across the 16 categories defined by CACS x FRS. The referent group has the lowest FRS (0%-9%) and a CACS of 300 or less or a low intermediate FRS (10%-15%) and a CACS of zero. These groups were chosen as the referents due to similar event rates. For FRS from 0% through 9%, there was no significant increased risk with a CACS of 301 or higher. For an FRS from 10% through 15%, the risk was significantly greater than 1.0 for a CACS of more than 100 (P<.05). The risk of FRS from 10% through 15% and a CACS of more than 300 (HR, 17.6) was comparable with the risk of an FRS of more than 20% and a CACS of more than 300 (HR, 19.1; P<.001). For an FRS from 16% through 20%, the risk was significantly greater than 1.0 for the upper 3 CACS groups (P<.05). When analyzed as continuous variables in a bivariate model, the adjusted risk of a CHD death or nonfatal MI per 1-SD increase in the CACS was 1.3 (95% confidence interval [CI], 1.2-1.5; P<.001) and in the FRS was 1.5 (95% CI, 1.2-1.9; P<.001).
|
|
|
|
Table 3. Bivariate Cox Regression Analyses Predicting Coronary Death or Nonfatal Myocardial Infarction Based on the Joint Relationship Between Baseline Coronary Artery Calcium Score (CACS) and the Baseline Framingham Risk Score (FRS)*
|
|
|
Predicted Event Rates
Figure 1 shows the mean predicted event rates (FRS + CACS) for CHD death or nonfatal MI stratified by CACS groups within FRS groups. Pairwise comparisons revealed a statistically significant difference between a CACS of more than 300 and each of the other 3 CACS groups for an FRS of 10% or more (P<.001), and between a CACS of more than 300 and a CACS of zero for an FRS of less than 10% (P = .01). Figure 2 displays receiver operating characteristic curves for prediction of CHD death or nonfatal MI. The mean (SD) area under the curve for the receiver operating characteristic curve for FRS plus CACS was 0.68 (0.03), significantly greater than that of the FRS alone (0.63 [0.03]; P<.001).
|
|
|
|
Figure 1. Predicted 7-Year Event Rates From COX Regression Model for CHD Death or Nonfatal Myocardial Infarction for Categories of FRS or CACS
The rates are stratified by 4 levels of Framingham Risk Score (FRS) and 4 levels of the coronary artery calcium score (CACS). Pairwise analyses compared the highest CACS level (>300) with each of the lower levels of CACS within each FRS group. Analysis of variance with pairwise comparisons revealed a statistically significant difference between a CACS of >300 and each of the other 3 CACS groups for an FRS of >10% (P<.001) and between a CACS of >300 and a CACS of zero for an FRS of <10% (P = .01).
|
|
|
|
|
|
|
Figure 2. Predicting Coronary Death or Nonfatal Myocardial Infarction for Framingham Risk Scores (FRS)
The receiver operating characteristic curves illustrate FRS alone or plus coronary artery calcium score (CACS). Areas under the curves are 0.63 for FRS alone, 0.68 for FRS plus CACS. P<.001 for the comparison between the 2 areas.
|
|
|
All-Cause Mortality
A univariate Cox regression analysis was performed to determine whether the CACS and the FRS predicted all-cause mortality (Table 4). Hazard ratios for all levels of CACS greater than zero were not significantly greater than 1.0. In contrast, the risk of all-cause mortality for an FRS of more than 20% was significantly greater than 1.0 (P = .03).
|
|
|
|
Table 4. Univariate Cox Regression Analyses Predicting All-Cause Mortality
|
|
|
COMMENT
In this report from a large prospective study with a median follow-up of 7 years, we found that in asymptomatic participants without diabetes and at least 1 risk factor for CHD but no prior clinical CHD, the FRS alone was able to rank participants according to CHD event risk in a graded fashion, as expected. Coronary artery calcium scores alone were also able to rank CHD event risk independently of the FRS. The CACS significantly modified the risk prediction in all categories of an FRS of at least 10% but not when the FRS was less than 10%. The increment in predicted risk was equal to a 3% to 9% increase in 10-year event risk compared with FRS alone for every category of FRS estimate when the CACS was more than 300. Additionally, among the 316 participants with a CACS of zero, 14 coronary events were observed (4.4%); thus, absence of CACS did not preclude risk of a CHD event as has been reported in some other studies.7
Comparison With Previous Studies
Studies comparing the prognostic accuracy of coronary calcium measurement by CT vs the FRS alone, or risk factors alone, have yielded somewhat conflicting results.8, 10-13 For example, in an earlier report based on the 3-year follow-up from the South Bay Heart Watch,9 CACS results added little overall predictive capability for definite coronary events beyond that available by the FRS. However, other studies found that CACS results added to risk prediction beyond that attributable to traditional risk factors.8, 10-13
Variability in study results may be related to differences in patient characteristics, lengths of follow-up, numbers and types of defined CHD events, or differences in measurement of CHD risk factors. The purpose of this study was to reevaluate the additive predictive capability of CACS in the South Bay Heart Watch in light of the availability of a median follow-up of 7 years, the routine availability of measured coronary risk factors, and the occurrence of a considerable number of definite coronary events (MI or coronary death) during the follow-up period.
Study Strengths
This report is unique in several ways in comparison with other studies on the prognostic value of CT-derived coronary calcium scores in asymptomatic people. Previous reports10-13 included participants who were either self-referred or both self-referred and physician-referred, suggesting the possibility that these patients represented a biased group. In contrast, all participants in the South Bay Heart Watch were recruited and assessed to be asymptomatic before enrollment, suggesting that they may be more representative of the general population of asymptomatic individuals with CHD risk factors. Also, in other studies, coronary risk factors were not actually measured but were estimated based on patient self-report.10-13 Self-reported risk factors are less accurate and precise than measured risk factors; therefore, it is likely that the predictive value of risk factors was artifactually limited in other studies. This methodological issue would also tend to overestimate the incremental effect of coronary calcium scores since CACS was the only directly measured risk marker in the previous studies, rendering comparison of CACS with FRS hazardous. In 4 previously published reports, average follow-up was less than 4 years, and definite coronary events were often few.10-13 Earlier reports also typically included revascularizations among the coronary events counted to increase study power.10-13 This practice could also lead to overestimation of the value of CACS since the calcium score may have influenced the likelihood of a patient seeking revascularization.22
Therefore, the current data derive from the only prospective study to measure all risk factors required to calculate the FRS in addition to measuring the CACS. Based on these unique aspects of the South Bay Heart Watch, it may be considered the only study to demonstrate conclusively that CACS can add to coronary event risk prediction over and above that determined by the FRS. Alexopoulus et al23 measured the coronary risk factors of 435 research patients and determined clinical outcomes following coronary calcium estimation using digital cinefluoroscopy. However, there were too few definite MI and coronary deaths to ascertain whether coronary calcium measurement by this non-CT technique added to the FRS prediction. Shaw et al24 demonstrated the ability of CACS to predict all-cause mortality in a study of 10 377 asymptomatic people referred for CT scanning by primary care physicians; however, that study did not include direct measurement of risk factors included in the FRS.
The current results also demonstrated that a CACS of zero does not routinely exclude risk of future CHD events. A previous preliminary analysis from the South Bay Heart Watch similarly reported that coronary events can occur despite low or undetectable CACS.25 Our analysis, with longer follow-up and more coronary events, further supports this observation. Why individuals without detectable coronary calcium might experience coronary events is uncertain, but it appears consistent with the current concept that soft, lipid-filled plaques are most vulnerable, leading to subsequent clinical events.26-27 It might be anticipated that such lesions would contain lower amounts of radiographically detectable calcium.28-29 Therefore, for individuals with no detectable coronary calcium, FRS may be the more prudent guide to clinical management of risk.
Study Limitations
Although this study has unique strengths, it also has limitations. The South Bay Heart Watch comprises predominantly male participants with an average age of 62 years at enrollment. Some have suggested that this cohort is neither heterogeneous nor representative of the general population, thus possibly reducing generalizability of the study's findings.30 However, as shown, the FRS ranged from about a 9% to a more than 21% 10-year risk, suggesting that the cohort was moderately diverse from the perspective of overall risk, within a clinically relevant range. These data may also have limited applicability to women and nonwhite ethnic groups. It should also be noted that the study did not test whether CACS measurement allowed for improved clinical outcomes. Rather, this study examined only whether application of CACS measurements could modify risk estimation.
These results may have been affected by unmeasured variables such as motivation to alter lifestyles that might influence event rates after testing for risk factors or CACS. This concern applies also to all previous studies of the predictive role of CACS.10-13,17 Wong et al22 showed that risk-reducing behaviors are reinforced by awareness of a positive cardiac scan. However, O'Malley et al reported in 2 randomized trials that knowledge of CACS testing did not result in significantly altered coronary risk profiles31 and did not result in smoking cessation.32
Conclusion
In this intermediate to high risk cohort, with coronary risk factors routinely measured for FRS, a CACS of more than 300 was associated with a significant increase in CHD event risk compared with that determined by FRS alone. The data support the hypothesis6 that a high CACS can significantly modify predicted risk and thereby could alter clinical decision making, especially for those in the intermediate-risk category for whom decision making is most uncertain. These data further support evidence that a CACS of zero does not markedly lower risk as predicted by FRS. Thus, these data lend support to a selective strategy that might use CACS when FRS is predicted to be in the range of 10% to 19% in 10 years. A CACS does not appear to change predicted risk substantially enough for people with an FRS of less than 10% or an FRS of 20% or more to modify the overall clinical approach, as currently recommended by the National Cholesterol Education Program.3
AUTHOR INFORMATION
| |
Corresponding Author and Reprints: Robert C. Detrano, MD, PhD, Division of Cardiology, Bldg RB-2, Harbor-UCLA Medical Center, 1135 W Carson St, Torrance, CA 90502 (e mail: rdetrano{at}rei.edu).
This article was corrected on January 14, 2004.
Author Contributions: Dr Detrano had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Greenland, Azen, Doherty, Detrano.
Acquisition of data: Detrano, Doherty.
Analysis and interpretation of data: Greenland, LaBree, Azen, Doherty, Detrano.
Drafting of the manuscript: Greenland, Azen, Doherty, Detrano.
Critical revision of the manuscript for important intellectual content: LaBree, Azen, Doherty, Detrano.
Statistical expertise: LaBree, Azen.
Obtained funding: Azen, Detrano.
Administrative, technical, or material support: Doherty, Detrano.
Funding/Support: This study was supported by grants HL 63963-01A1 and GCRC 009593-00-00 from the National Heart, Lung, and Blood Institute.
Role of the Sponsor: The National Heart, Lung, and Blood Institute provided financial support for clinical visits, salaried personnel, and laboratory maintenance equipment.
Acknowledgment: We thank the National Heart, Lung, and Blood Institute for providing funding for this research project.
Author Affiliations: Departments of Preventive Medicine and Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Ill (Dr Greenland); Statistical Consultation and Research Center, Department of Preventive Medicine, Keck School of Medicine, University of Southern California (Ms LaBree and Dr Azen), Division of Cardiology, Cedars Sinai Medical Center, Los Angeles (Mr Doherty); and Department of Medicine, Harbor UCLA Research and Education Institute (Dr Detrano), Torrance.
REFERENCES
1. Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation. 1998;97:1837-1847.
FREE FULL TEXT
2. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. JAMA. 2003;289:2560-2572.
FREE FULL TEXT
3. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:2486-2497.
FREE FULL TEXT
4. Smith SC Jr, Greenland P, Grundy SM. Beyond secondary prevention: Identifying the high-risk patient for primary prevention: executive summary. Circulation. 2000;101:111-116.
FREE FULL TEXT
5. Diverse Populations Collaborative Group. Prediction of mortality from coronary heart disease among diverse populations. Heart. 2002;88:222-228.
FREE FULL TEXT
6. Greenland P, Smith SC Jr, Grundy SM. Improving coronary heart disease risk assessment in asymptomatic people. Circulation. 2001;104:1863-1867.
FREE FULL TEXT
7. O'Rourke RA, Brundage BH, Froelicher VF, et al. American College of Cardiology/American Heart Association Expert Consensus document on electron-beam computed tomography for the diagnosis and prognosis of coronary artery disease. Circulation. 2000;102:126-140.
FREE FULL TEXT
8. O'Malley PG, Taylor AJ, Jackson JL, Doherty TM, Detrano RC. Prognostic value of coronary electron-beam computed tomography for coronary heart disease events in asymptomatic populations. Am J Cardiol. 2000;85:945-948.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
9. Detrano RC, Wong ND, Doherty TM, et al. Coronary calcium does not accurately predict near-term future coronary events in high-risk adults. Circulation. 1999;99:2633-2638.
FREE FULL TEXT
10. Kondos GT, Hoff JA, Sevrukov A, et al. Electron-beam tomography coronary artery calcium and cardiac events. Circulation. 2003;107:2571-2576.
FREE FULL TEXT
11. Raggi P, Cooil B, Callister TQ. Use of electron beam tomography data to develop models for prediction of hard coronary events. Am Heart J. 2001;141:375-382.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
12. Wong ND, Hsu JC, Detrano RC, et al. Coronary artery calcium evaluation by electron beam computed tomography and its relation to new cardiovascular events. Am J Cardiol. 2000;86:495-498.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
13. Arad Y, Spadaro LA, Goodman K, Newstein D, Guerci AD. Prediction of coronary events with electron beam computed tomography. J Am Coll Cardiol. 2000;36:1253-1260.
FREE FULL TEXT
14. Park R, Detrano R, Xiang M, et al. Combined use of computed tomography coronary calcium scores and C-reactive protein levels in predicting cardiovascular events in nondiabetic individuals. Circulation. 2002;106:2073-2077.
FREE FULL TEXT
15. Doherty TM, Tang W, Detrano RC. Racial differences in the significance of coronary calcium in asymptomatic black and white subjects with coronary risk factors. J Am Coll Cardiol. 1999;34:787-794.
FREE FULL TEXT
16. Qu W, Le TT, Azen SP, et al. Value of coronary artery calcium scanning by computed tomography for predicting coronary heart disease in diabetic subjects. Diabetes Care. 2003;26:905-910.
FREE FULL TEXT
17. Anderson KM, Wilson PW, Odell PM, Kannel WB. An updated coronary risk profile: a statement for health professionals. Circulation. 1991;83:356-362.
FREE FULL TEXT
18. Wang S, Detrano RC, Secci A. Detection of coronary calcification with electron-beam computed tomography. Am Heart J. 1996;132:550-558.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
19. Secci A, Wong N, Tang W, Wang S, Doherty T, Detrano R. Electron beam computed tomographic coronary calcium as a predictor of coronary events. Circulation. 1997;96:1122-1129.
FREE FULL TEXT
20. Bild DE, Bluemke DA, Burke GL, et al. Multi-ethnic study of atherosclerosis: objectives and design. Am J Epidemiol. 2002;156:871-881.
FREE FULL TEXT
21. Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol. 1990;15:827-832.
ABSTRACT
22. Wong ND, Detrano RC, Diamond G, et al. Does coronary artery screening by electron beam computed tomography motivate potentially beneficial lifestyle behaviors? Am J Cardiol. 1996;78:1220-1223.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
23. Alexopoulus D, Toulgaridis T, Davlouros P, et al. Prognostic significance of coronary artery calcium in asymptomatic subjects with usual cardiovascular risk. Am Heart J. 2003;145:542-548.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
24. Shaw LJ, Raggi P, Schisterman E, Berman DS, Callister TQ. Prognostic value of cardiac risk factors and coronary artery calcium screening for all-cause mortality. Radiology. 2003;228:826-833.
FREE FULL TEXT
25. Doherty TM, Wong ND, Shavelle RM, et al. Coronary heart disease deaths and infarctions in people with little or no coronary calcium. Lancet. 1999;353:41-42.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
26. Forrester JS. Prevention of plaque rupture. Ann Intern Med. 2002;137:823-833.
FREE FULL TEXT
27. Shah PK. Pathophysiology of coronary thrombosis. Prog Cardiovasc Dis. 2002;44:357-368.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
28. Doherty TM, Detrano RC, Mautner SL, Mautner GC, Shavelle RM. Coronary calcium: the good, the bad, and the uncertain. Am Heart J. 1999;137:806-814.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
29. Doherty TM, Detrano RC. Coronary arterial calcification as an active process: a new perspective on an old problem. Calcif Tissue Int. 1994;54:224-230.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
30. Hecht H, Rumberger JA, Budoff MJ. C-reactive protein and electron beam tomography [letter]. Circulation. 2003;107:e123-e124.
FREE FULL TEXT
31. O'Malley PG, Feuerstein IM, Taylor AJ. Impact of electron beam tomography, with or without case management, on motivation, behavioral change, and cardiovascular risk profile: a randomized controlled trial. JAMA. 2003;289:2215-2223.
FREE FULL TEXT
32. O'Malley PG, Rupard EJ, Jones DL, et al. Does the diagnosis of coronary calcification with electron beam computed tomography motivate behavioral change in smokers? Mil Med. 2002;167:211-214.
WEB OF SCIENCE
| PUBMED
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter
What's this?
RELATED LETTERS
Use of Coronary Calcification Scores to Predict Coronary Heart Disease
Anthony S. Wierzbicki, Patrick J. Twomey, and Timothy M. Reynolds
JAMA. 2004;291(15):1831.
EXTRACT
| FULL TEXT
Use of Coronary Calcification Scores to Predict Coronary Heart Disease
Mark J. Pletcher, Jeffrey A. Tice, and Michael Pignone
JAMA. 2004;291(15):1831-1832.
EXTRACT
| FULL TEXT
Use of Coronary Calcification Scores to Predict Coronary Heart Disease
Matthew J. Budoff, James Ehrlich, Harvey S. Hecht, and John A. Rumberger
JAMA. 2004;291(15):1832.
EXTRACT
| FULL TEXT
Use of Coronary Calcification Scores to Predict Coronary Heart Disease—Reply
Robert C. Detrano, Philip Greenland, Terence M. Doherty, Stanley P. Azen, and Laurie LaBree
JAMA. 2004;291(15):1832-1833.
EXTRACT
| FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
X-ray computed tomography of the heart
Wijesekera et al.
Br Med Bull 2009;0:ldp043v1-ldp043.
ABSTRACT
| FULL TEXT
The coronary artery calcium score and stress myocardial perfusion imaging provide independent and complementary prediction of cardiac risk.
Chang et al.
J Am Coll Cardiol 2009;54:1872-1882.
ABSTRACT
| FULL TEXT
The heart of patients with aortic aneurysms: evidence from cardiac computed tomography
Stolzmann et al.
ICVTS 2009;9:769-773.
ABSTRACT
| FULL TEXT
Incremental prognostic value of multi-slice computed tomography coronary angiography over coronary artery calcium scoring in patients with suspected coronary artery disease
van Werkhoven et al.
Eur Heart J 2009;30:2622-2629.
ABSTRACT
| FULL TEXT
Mis-SHAPEing Public Health Policy
Spatz and Ross
Circ Cardiovasc Qual Outcomes 2009;2:681-683.
FULL TEXT
Using Nontraditional Risk Factors in Coronary Heart Disease Risk Assessment: U.S. Preventive Services Task Force Recommendation Statement
U.S. Preventive Services Task Force
ANN INTERN MED 2009;151:474-482.
ABSTRACT
| FULL TEXT
Emerging Risk Factors for Coronary Heart Disease: A Summary of Systematic Reviews Conducted for the U.S. Preventive Services Task Force
Helfand et al.
ANN INTERN MED 2009;151:496-507.
ABSTRACT
| FULL TEXT
Relationship Between Baseline Coronary Calcium Score and Demonstration of Coronary Artery Stenoses During Follow-Up: MESA (Multi-Ethnic Study of Atherosclerosis)
Rosen et al.
J Am Coll Cardiol Img 2009;2:1175-1183.
ABSTRACT
| FULL TEXT
Should Coronary Calcium Screening Be Used in Cardiovascular Prevention Strategies?
Bonow
NEJM 2009;361:990-997.
FULL TEXT
Myeloperoxidase, Subclinical Atherosclerosis, and Cardiovascular Disease Events
Wong et al.
J Am Coll Cardiol Img 2009;2:1093-1099.
ABSTRACT
| FULL TEXT
Do Socioeconomic Gradients in Subclinical Atherosclerosis Vary According to Acculturation Level? Analyses of Mexican-Americans in the Multi-Ethnic Study of Atherosclerosis
Gallo et al.
Psychosom. Med. 2009;71:756-762.
ABSTRACT
| FULL TEXT
Inflammation Imaging in Atherosclerosis
Rudd et al.
Arterioscler. Thromb. Vasc. Bio. 2009;29:1009-1016.
ABSTRACT
| FULL TEXT
Lesions without calcium: lessons from CT angiography
Schuijf et al.
Heart 2009;95:1038-1040.
FULL TEXT
Clinical characteristics of patients with obstructive coronary lesions in the absence of coronary calcification: an evaluation by coronary CT angiography
Marwan et al.
Heart 2009;95:1056-1060.
ABSTRACT
| FULL TEXT
Diagnosis and treatment of acquired coronary artery disease in adults
Wilson
Postgrad. Med. J. 2009;85:364-365.
ABSTRACT
| FULL TEXT
Diagnostic and Prognostic Value of Absence of Coronary Artery Calcification
Sarwar et al.
J Am Coll Cardiol Img 2009;2:675-688.
ABSTRACT
| FULL TEXT
An Ounce of Prevention With a Calcium Score Scan?
Garcia and Fuster
J Am Coll Cardiol Img 2009;2:689-691.
FULL TEXT
Fibroblast Growth Factor 23 and Left Ventricular Hypertrophy in Chronic Kidney Disease
Gutierrez et al.
Circulation 2009;119:2545-2552.
ABSTRACT
| FULL TEXT
Thoracic aortic calcium versus coronary artery calcium for the prediction of coronary heart disease and cardiovascular disease events.
Wong et al.
J Am Coll Cardiol Img 2009;2:319-326.
ABSTRACT
| FULL TEXT
Atherosclerosis Imaging: Prognostically Useful or Merely More of What We Know?
Kaul and Douglas
Circ Cardiovasc Imaging 2009;2:150-160.
FULL TEXT
Cardiac radionuclide imaging in stable coronary artery disease and acute coronary syndromes
Stirrup et al.
Br Med Bull 2009;89:63-78.
ABSTRACT
| FULL TEXT
Carotid Intima-Media Thickness and Coronary Artery Calcium Score as Indications of Subclinical Atherosclerosis
Lester et al.
Mayo Clin Proc. 2009;84:229-233.
ABSTRACT
| FULL TEXT
Prognostic value of multislice computed tomography and gated single-photon emission computed tomography in patients with suspected coronary artery disease.
van Werkhoven et al.
J Am Coll Cardiol 2009;53:623-632.
ABSTRACT
| FULL TEXT
Prognostic utility of 64-slice computed tomography in patients with suspected but no documented coronary artery disease
Carrigan et al.
Eur Heart J 2009;30:362-371.
ABSTRACT
| FULL TEXT
Are you as old as your arteries or as old as your coronary artery calcification score?
Schiele and Meneveau
J Am Coll Cardiol 2009;53:353-354.
FULL TEXT
Heart Disease and Stroke Statistics--2009 Update: A Report From the American Heart Association Statistics Committee and Stroke Statistics Subcommittee
WRITING GROUP MEMBERS et al.
Circulation 2009;119:e21-e181.
FULL TEXT
Prevalence and Progression of Subclinical Atherosclerosis in Younger Adults With Low Short-Term but High Lifetime Estimated Risk For Cardiovascular Disease: The Coronary Artery Risk Development in Young Adults Study and Multi-Ethnic Study of Atherosclerosis
Berry et al.
Circulation 2009;119:382-389.
ABSTRACT
| FULL TEXT
Association of Coronary Artery and Aortic Calcium With Lumbar Bone Density: The MESA Abdominal Aortic Calcium Study
Hyder et al.
Am J Epidemiol 2009;169:186-194.
ABSTRACT
| FULL TEXT
Traditional Clinical Risk Assessment Tools Do Not Accurately Predict Coronary Atherosclerotic Plaque Burden: A CT Angiography Study
Johnson et al.
Am. J. Roentgenol. 2009;192:235-243.
ABSTRACT
| FULL TEXT
The Association of Coronary Artery Calcification and Carotid Artery Intima-Media Thickness With Distinct, Traditional Coronary Artery Disease Risk Factors in Asymptomatic Adults
Rampersaud et al.
Am J Epidemiol 2008;168:1016-1023.
ABSTRACT
| FULL TEXT
Intakes of long-chain n-3 polyunsaturated fatty acids and fish in relation to measurements of subclinical atherosclerosis
He et al.
Am. J. Clin. Nutr. 2008;88:1111-1118.
ABSTRACT
| FULL TEXT
Identifying patterns of atherosclerotic disease manifestation with coronary computed tomography. Impact on clinical management and outcome?
Schoenhagen and Tuzcu
Eur Heart J 2008;29:2323-2324.
FULL TEXT
Hot Flashes and Subclinical Cardiovascular Disease: Findings From the Study of Women's Health Across the Nation Heart Study
Thurston et al.
Circulation 2008;118:1234-1240.
ABSTRACT
| FULL TEXT
Association between non-subcutaneous adiposity and calcified coronary plaque: a substudy of the Multi-Ethnic Study of Atherosclerosis
Ding et al.
Am. J. Clin. Nutr. 2008;88:645-650.
ABSTRACT
| FULL TEXT
Importance of a Patient's Personal Health History on Assessments of Future Risk of Coronary Heart Disease
Mainous et al.
J Am Board Fam Med 2008;21:408-413.
ABSTRACT
| FULL TEXT
Ankle Brachial Index Combined With Framingham Risk Score to Predict Cardiovascular Events and Mortality: A Meta-analysis
Ankle Brachial Index Collaboration
JAMA 2008;300:197-208.
ABSTRACT
| FULL TEXT
Coronary CT Angiography Findings in Patients Without Coronary Calcification
Kelly et al.
Am. J. Roentgenol. 2008;191:50-55.
ABSTRACT
| FULL TEXT
The Use of CT for Screening: A National Survey of Radiologists' Activities and Attitudes
Burger et al.
Radiology 2008;248:160-168.
ABSTRACT
| FULL TEXT
Atherosclerosis Inflammation Imaging with 18F-FDG PET: Carotid, Iliac, and Femoral Uptake Reproducibility, Quantification Methods, and Recommendations
Rudd et al.
JNM 2008;49:871-878.
ABSTRACT
| FULL TEXT
Coronary Calcium Coverage Score: Determination, Correlates, and Predictive Accuracy in the Multi-Ethnic Study of Atherosclerosis
Brown et al.
Radiology 2008;247:669-675.
ABSTRACT
| FULL TEXT
Methods and Limitations of Assessing New Noninvasive Tests: Part II: Outcomes-Based Validation and Reliability Assessment of Noninvasive Testing
Hachamovitch and Di Carli
Circulation 2008;117:2793-2801.
FULL TEXT
Application of the Screening for Heart Attack Prevention and Education Task Force Recommendations to an Urban Population: Observations From the Dallas Heart Study
See et al.
Arch Intern Med 2008;168:1055-1062.
ABSTRACT
| FULL TEXT
Methods and Limitations of Assessing New Noninvasive Tests: Part I: Anatomy-Based Validation of Noninvasive Testing
Hachamovitch and Di Carli
Circulation 2008;117:2684-2690.
FULL TEXT
Cancer risks from diagnostic radiology
HALL and BRENNER
Br. J. Radiol. 2008;81:362-378.
ABSTRACT
| FULL TEXT
Contribution of Bone and Mineral Abnormalities to Cardiovascular Disease in Patients with Chronic Kidney Disease
Raggi and Kleerekoper
CJASN 2008;3:836-843.
ABSTRACT
| FULL TEXT
Incidental Findings on Cardiac Multidetector Row Computed Tomography Among Healthy Older Adults: Prevalence and Clinical Correlates
Burt et al.
Arch Intern Med 2008;168:756-761.
ABSTRACT
| FULL TEXT
How Low-Risk Is a Coronary Calcium Score of Zero?: The Importance of Conditional Probability
Greenland and Bonow
Circulation 2008;117:1627-1629.
FULL TEXT
Coronary Calcium as a Predictor of Coronary Events in Four Racial or Ethnic Groups
Detrano et al.
NEJM 2008;358:1336-1345.
ABSTRACT
| FULL TEXT
Screening High-Risk Patients With Computed Tomography Angiography
Gottlieb and Lima
Circulation 2008;117:1318-1332.
FULL TEXT
All High-Risk Patients Should Not Be Screened With Computed Tomographic Angiography
Kramer
Circulation 2008;117:1333-1339.
FULL TEXT
Impaired coronary vasodilation by magnetic resonance angiography is associated with advanced coronary artery calcification.
Terashima et al.
J Am Coll Cardiol Img 2008;1:167-173.
ABSTRACT
| FULL TEXT
Cardiac CT: Indications and Limitations
Prat-Gonzalez et al.
J. Nucl. Med. Technol. 2008;36:18-24.
ABSTRACT
| FULL TEXT
Incremental predictive value of vascular assessments combined with the Framingham Risk Score for prediction of coronary events in subjects of low-intermediate risk
Lau et al.
Postgrad. Med. J. 2008;84:153-157.
ABSTRACT
| FULL TEXT
What Is the Value of Measuring Coronary Artery Calcification?
Wexler
Radiology 2008;246:1-2.
FULL TEXT
Relation of Retinopathy to Coronary Artery Calcification: The Multi-Ethnic Study of Atherosclerosis
Wong et al.
Am J Epidemiol 2008;167:51-58.
ABSTRACT
| FULL TEXT
Can Coronary Calcification Define the Warranty Period of a Normal Myocardial Perfusion Study?
Bax and Schuijf
Mayo Clin Proc. 2008;83:10-12.
FULL TEXT
Are We Getting Nearer to Screening for Atherosclerosis?
Stern
Circulation 2008;117:122-126.
FULL TEXT
Determinants of Progression of Coronary Artery Calcification in Type 2 Diabetes: Role of Glycemic Control and Inflammatory/Vascular Calcification Markers
Anand et al.
J Am Coll Cardiol 2007;50:2218-2225.
ABSTRACT
| FULL TEXT
Comparative performance of subclinical atherosclerosis tests in predicting coronary heart disease in asymptomatic individuals
Simon et al.
Eur Heart J 2007;28:2967-2971.
ABSTRACT
| FULL TEXT
Juice Powder Concentrate and Systemic Blood Pressure, Progression of Coronary Artery Calcium and Antioxidant Status in Hypertensive Subjects: A Pilot Study
Houston et al.
Evid Based Complement Alternat Med 2007;4:455-462.
ABSTRACT
| FULL TEXT
Risk Factors for Development of Coronary Heart Disease in Patients with Acromegaly: A Five-Year Prospective Study
Bogazzi et al.
J. Clin. Endocrinol. Metab. 2007;92:4271-4277.
ABSTRACT
| FULL TEXT
CT-Based Calcium Scoring to Screen for Coronary Artery Disease: Why Aren't We There Yet?
Leontiev and Dubinsky
Am. J. Roentgenol. 2007;189:1061-1063.
ABSTRACT
| FULL TEXT
Estrogen Therapy and Coronary-Artery Calcification
Hodis et al.
NEJM 2007;357:1252-1254.
FULL TEXT
Ethnic Differences in the Prognostic Value of Coronary Artery Calcification for All-Cause Mortality
Nasir et al.
J Am Coll Cardiol 2007;50:953-960.
ABSTRACT
| FULL TEXT
Family History of Premature Coronary Heart Disease and Coronary Artery Calcification: Multi-Ethnic Study of Atherosclerosis (MESA)
Nasir et al.
Circulation 2007;116:619-626.
ABSTRACT
| FULL TEXT
A Comparison of Risk Factors for Calcified Atherosclerotic Plaque in the Coronary, Carotid, and Abdominal Aortic Arteries: The Diabetes Heart Study
Wagenknecht et al.
Am J Epidemiol 2007;166:340-347.
ABSTRACT
| FULL TEXT
Molecular Imaging of Inflammation in Atherosclerosis With Targeted Ultrasound Detection of Vascular Cell Adhesion Molecule-1
Kaufmann et al.
Circulation 2007;116:276-284.
ABSTRACT
| FULL TEXT
Abdominal obesity and coronary artery calcification in young adults: the Coronary Artery Risk Development in Young Adults (CARDIA) Study
Lee et al.
Am. J. Clin. Nutr. 2007;86:48-54.
ABSTRACT
| FULL TEXT
Review: Imaging to assess effect of medical therapy in patients with diabetes mellitus
Raggi and Bellasi
British Journal of Diabetes & Vascular Disease 2007;7:157-164.
ABSTRACT
A 52-Year-Old Woman With Hypertension and Diabetes Who Presents With Chest Pain
Harris
Clin. Diabetes 2007;25:115-118.
FULL TEXT
Estrogen Therapy and Coronary-Artery Calcification
Manson et al.
NEJM 2007;356:2591-2602.
ABSTRACT
| FULL TEXT
Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: full text: The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD)
Authors/Task Force Members et al.
Eur Heart J Suppl 2007;9:C3-C74.
FULL TEXT
Risk Factors for the Progression of Coronary Artery Calcification in Asymptomatic Subjects: Results From the Multi-Ethnic Study of Atherosclerosis (MESA)
Kronmal et al.
Circulation 2007;115:2722-2730.
ABSTRACT
| FULL TEXT
The Prognostic Accuracy of Coronary Calcification
Guerci
J Am Coll Cardiol 2007;49:1871-1873.
FULL TEXT
Long-Term Prognosis Associated With Coronary Calcification: Observations From a Registry of 25,253 Patients
Budoff et al.
J Am Coll Cardiol 2007;49:1860-1870.
ABSTRACT
| FULL TEXT
Primary Prevention of Atherosclerotic Cardiovascular Disease: The High Public Burden of Low Individual Risk
Lauer
JAMA 2007;297:1376-1378.
FULL TEXT
New Technology for Noninvasive Evaluation of Coronary Artery Disease
Di Carli and Hachamovitch
Circulation 2007;115:1464-1480.
FULL TEXT
A Commentary on Lifestyle Medicine Strategies for Risk Factor Reduction, Prevention, and Treatment of Coronary Artery Disease
Greenstone
AMERICAN JOURNAL OF LIFESTYLE MEDICINE 2007;1:91-94.
ABSTRACT
Aortic Valve Calcification: Determinants and Progression in the Population
Messika-Zeitoun et al.
Arterioscler. Thromb. Vasc. Bio. 2007;27:642-648.
ABSTRACT
| FULL TEXT
Challenges in the phenotypic characterisation of patients in genetic studies of coronary artery disease
Luo et al.
J. Med. Genet. 2007;44:161-165.
ABSTRACT
| FULL TEXT
Determinants of Coronary Artery and Aortic Calcification in the Old Order Amish
Post et al.
Circulation 2007;115:717-724.
ABSTRACT
| FULL TEXT
|
