PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (680100)

Clipboard (0)
None

Related Articles

1.  Thoracic Aortic Calcification and Coronary Heart Disease Events: the Multi-Ethnic Study of Atherosclerosis (MESA) 
Atherosclerosis  2010;215(1):196-202.
Background
The presence and extent of coronary artery calcium (CAC) is an independent predictor of coronary heart disease (CHD) morbidity and mortality. Few studies have evaluated interactions or independent incremental risk for coronary and thoracic aortic calcification (TAC). The independent predictive value of TAC for CHD events is not well-established.
Methods
This study used risk factor and computed tomography scan data from 6,807 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Using the same images for each participant, TAC and CAC were each computed using the Agatston method. The study subjects were free of incident CHD at entry into the study.
Results
The mean age of the study population (n=6807) was 62±10 years (47% males). At baseline, the prevalence of TAC and CAC was 28 % (1,904/6,809) and 50% (3393/6809), respectively. Over 4.5±0.9 years, a total of 232 participants (3.41%) had CHD events, of which 132 (1.94%) had a hard event (myocardial infarction, resuscitated cardiac arrest, or CHD death). There was a significant interaction between gender and TAC for CHD events (p<0.05). Specifically, in women, the risk of all CHD event was nearly 3-fold greater among those with any TAC (hazard ratio: 3.04, 95% CI; 1.60–5.76). After further adjustment for increasing CAC score, this risk was attenuated but remained robust (HR: 2.15, 95% CI: 1.10–4.17). Conversely, there was no significant association between TAC and incident CHD in men. In women, the likelihood ratio chi square statistics indicate that the addition of TAC contributed significantly to predicting incident CHD event above that provided by traditional risk factors alone (chi square= 12.44, p=0.0004) as well as risk factors + CAC scores (chi square= 5.33, p=0.02) . On the other hand, addition of TAC only contributed in the prediction of hard CHD events to traditional risk factors (chi-square=4.33, p=0.04) in women, without contributing to the model containing both risk factors and CAC scores (chi square=1.55, p=0.21).
Conclusion
Our study indicates that TAC is a significant predictor of future coronary events only in women, independent of CAC. On studies obtained for either cardiac or lung applications, determination of TAC may provide modest supplementary prognostic information in women with no extra cost or radiation.
doi:10.1016/j.atherosclerosis.2010.11.017
PMCID: PMC4110678  PMID: 21227418
atherosclerosis; cardiac CT; coronary calcium; multi-detector CT; prognosis; thoracic atherosclerosis
2.  Cardiovascular events with absent or minimal coronary calcification: the Multi-Ethnic Study of Atherosclerosis (MESA) 
American heart journal  2009;158(4):554-561.
Background
Elevated coronary artery calcium (CAC) is a marker for increase risk of coronary heart disease (CHD). While the majority of CHD events occur among individuals with advanced CAC, CHD can also occur in individuals with little or no calcified plaque. In this study, we sought to evaluate the characteristics associated with incident CHD events in the setting of minimal (score ≤10) or absent CAC (score of zero).
Methods
Asymptomatic participants in the Multi-Ethnic Study of Atherosclerosis (MESA) (N=6,809), were followed for occurrence of all CHD events (including myocardial infarction(MI), angina, resuscitated cardiac arrest, or CHD death) and hard CHD events (MI or CHD death). Time to incident CHD was modeled using age-and gender-adjusted Cox regression.
Results
The final study population consisted of 3,923 MESA asymptomatic participants (mean age: 58±9years,39% males) had with CAC scores of 0-10. Overall no detectable CAC was seen in 3415 individuals, whereas 508 had CAC scores of 1-10. During follow up (median 4.1 years) there were 16 incident hard events, and 28 all CHD events in individuals with absent or minimal CAC. In age, gender, race and CHD risk factors adjusted analysis, minimal CAC (1-10) was associated with an estimated 3-fold greater risk of a hard CHD event (HR: 3.23, 95% CI: 1.17-8.95), or of all CHD event (HR: 3.66, 95% CI 1.71-7.85) compared to those with CAC=0. Former smoking (HR=3.57; 1.08-11.77), current smoking (HR=4.93; 1.20-20.30), and diabetes (HR=3.09; 1.07-8.93) were significant risk factors for events in those with CAC=0.
Conclusion
Asymptomatic persons with absent or minimal CAC are at very low risk of future cardiovascular events. Individuals with minimal CAC (1-10) were significantly increased to three fold increased risk for incident CHD events relative to those with CAC scores of zero.
doi:10.1016/j.ahj.2009.08.007
PMCID: PMC2766514  PMID: 19781414
Computed Tomography; Prognosis; Coronary Artery Calcification; Atherosclerosis; Coronary Calcium Score; Cardiac Events
3.  Calcium Density of Coronary Artery Plaque and Risk of Incident Cardiovascular Events 
Importance
Coronary artery calcium (CAC), measured by computed tomography (CT), has strong predictive value for incident cardiovascular disease (CVD) events. The standard CAC score is the Agatston, which is weighted upward for greater calcium density. However, some data suggest increased plaque calcium density may be protective for CVD.
Objective
To determine the independent associations of CAC volume and CAC density with incident CVD events.
Design, Setting, and Participants
Multicenter, prospective observational MESA study (Multi-Ethnic Study of Atherosclerosis), conducted at 6 US field centers of 3398 men and women from 4 race/ethnicity groups; non-Hispanic white, African American, Hispanic, and Chinese. Participants were aged 45-84 years, free of known CVD at baseline, had CAC greater than 0 on their baseline CT, and were followed up through October 2010.
Main Outcomes and Measures
Incident coronary heart disease (CHD) and all CVD events
Results
During a median of 7.6 years of follow-up, there were 175 CHD events and an additional 90 other CVD events for a total of 265 CVD events. With both lnCAC volume and CAC density scores in the same multivariable model, the lnCAC volume score showed an independent association with incident CHD, with a hazard ratio (HR) of 1.81 (95% CI, 1.47-2.23) per standard deviation (SD = 1.6) increase, absolute risk increase 6.1 per 1000 person-years, and for CVD an HR of 1.68 (95% CI, 1.42-1.98) per SD increase, absolute risk increase 7.9 per 1000 person-years. Conversely, the CAC density score showed an independent inverse association, with an HR of 0.73 (95% CI, 0.58-0.91) per SD (SD = 0.7) increase for CHD, absolute risk decrease 5.5 per 1000 person-years, and an HR of 0.71 (95% CI, 0.60-0.85) per SD increase for CVD, absolute risk decrease 8.2 per 1000 person years. Area under the receiver operating characteristic curve analyses showed significantly improved risk prediction with the addition of the density score to a model containing the volume score for both CHD and CVD. In the intermediate CVD risk group, the area under the curve for CVD increased from 0.53 (95% CI, 0.48-0.59) to 0.59 (95% CI, 0.54-0.64), P = .02.
Conclusions and Relevance
CAC volume was positively and independently associated with CHD and CVD risk. At any level of CAC volume, CAC density was inversely and significantly associated with CHD and CVD risk. The role of CAC density should be considered when evaluating current CAC scoring systems.
doi:10.1001/jama.2013.282535
PMCID: PMC4091626  PMID: 24247483
4.  Coronary Artery Calcium Score and Risk Classification for Coronary Heart Disease Prediction: The Multi-Ethnic Study of Atherosclerosis 
Context
Coronary artery calcium score (CACS) has been shown to predict future coronary heart disease (CHD) events. However, the extent to which adding CACS to traditional CHD risk factors improves classification of risk is unclear.
Objective
To determine whether adding CACS to a prediction model based on traditional risk factors improves classification of risk.
Design, Setting and Participants
CACS was measured by computed tomography on 6,814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based cohort without known cardiovascular disease. Recruitment spanned July 2000 to September 2002; follow-up extended through May 2008. Participants with diabetes were excluded for the primary analysis. Five-year risk estimates for incident CHD were categorized as 0-<3%, 3-<10%, and ≥10% using Cox proportional hazards models. Model 1 used age, gender, tobacco use, systolic blood pressure, antihypertensive medication use, total and high-density lipoprotein cholesterol, and race/ethnicity. Model 2 used these risk factors plus CACS. We calculated the net reclassification improvement (NRI) and compared the distribution of risk using Model 2 versus Model 1.
Main Outcome Measures
Incident CHD events
Results
Over 5.8 years median follow-up, 209 CHD events occurred, of which 122 were myocardial infarction, death from CHD, or resuscitated cardiac arrest. Model 2 resulted in significant improvements in risk prediction compared to Model 1 (NRI=0.25, 95% confidence interval 0.16-0.34, P<0.001). With Model 1, 69% of the cohort was classified in the highest or lowest risk categories, compared to 77% with Model 2. An additional 23% of those who experienced events were reclassified to high risk, and an additional 13% without events were reclassified to low risk using Model 2.
Conclusions
In the MESA cohort, addition of CACS to a prediction model based on traditional risk factors significantly improved the classification of risk and placed more individuals in the most extreme risk categories.
doi:10.1001/jama.2010.461
PMCID: PMC3033741  PMID: 20424251
5.  Comparison of Novel Risk Markers for Improvement in Cardiovascular Risk Assessment in Intermediate Risk Individuals. The Multi-Ethnic Study of Atherosclerosis 
Context
Risk markers including coronary artery calcium (CAC), carotid intima-media thickness (CIMT), ankle-brachial Index (ABI), brachial flow-mediated dilation (FMD), high sensitivity C -reactive protein (hs-CRP) and family history (FH) of coronary heart disease (CHD) have been reported to improve on the Framingham risk score (FRS) for prediction of CHD. However, there are no direct comparisons of these markers for risk prediction in a single cohort.
Objective
We compared improvement in prediction of incident CHD/cardiovascular disease (CVD) of these 6 risk markers within intermediate risk participants (5 % < FRS < 20%) in the Multi-Ethnic Study of Atherosclerosis (MESA).
Design, Setting and Participants
Of 6814 MESA participants from 6 US field centers, 1330 were intermediate risk, without diabetes mellitus, and had complete data on all 6 markers. Recruitment spanned July 2000 to September 2002; follow-up extended through May 2011. Probability- weighted Cox proportional hazard models were used to estimate hazard ratios (HR). Area under the receiver operator characteristic curve (AUC) and net reclassification improvement (NRI) were used to compare incremental contributions of each marker when added to the FRS + race/ethnicity.
Main Outcome Measures
Incident CHD defined as MI, angina followed by revascularization, resuscitated cardiac arrest or CHD death. Incident CVD additionally included stroke or CVD death.
Results
After median follow-up of 7.6 years (IQR 7.3 – 7.8 years), 94 CHD and 123 CVD events occurred. CAC, ABI, hs-CRP and FH were independently associated with incident CHD in multivariable analyses [HR (95%CI: 2.60(1.94-3.50), 0.79(0.66-0.95), 1.28(1.00-1.64) and 2.18(1.38-3.42) respectively]. CIMT and FMD were not associated with incident CHD in multivariable analyses [HR (95%CI) 1.17(0.95- 1.45) and 0.95(0.78 −1.14) respectively]. Although the addition of the markers individually to the FRS +race/ethnicity improved the AUC, CAC afforded the highest increment (0.623 vs. 0.784) while FMD afforded the least [0.623 vs. 0.639]. For incident CHD, the NRI with CAC was 0.659, FMD 0.024, ABI 0.036, CIMT 0.102, FH 0.160 and hs-CRP 0.079. Similar results were obtained for incident CVD.
Conclusion
CAC, ABI, hs-CRP and FH are independent predictors of incident CHD/CVD in intermediate risk individuals. CAC provides superior discrimination and risk reclassification compared with other risk markers.
doi:10.1001/jama.2012.9624
PMCID: PMC4141475  PMID: 22910756
6.  The Association of Framingham and Reynolds Risk Scores with Incidence and Progression of Coronary Artery Calcification in the Multi-Ethnic Study of Atherosclerosis 
Objectives
To compare the association of the Framingham Risk Score (FRS) and Reynolds Risk Score (RRS) with subclinical atherosclerosis, assessed by incidence and progression of coronary artery calcium (CAC).
Background
The comparative effectiveness of competing risk algorithms for indentifying subclinical atherosclerosis is unknown.
Methods
The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective cohort study of 6,814 participants free of baseline CVD. All participants underwent risk factor assessment, as well as baseline and follow-up CAC testing. We assessed the performance of the FRS and RRS to predict CAC incidence and progression using relative risk and robust linear regression.
Results
The study population included 5,140 individuals (61±10 years, 47% males, mean follow-up: 3.1±1.3 years). Among 53% of subjects (n=2,729) with no baseline CAC, 18% (n=510) developed incident CAC. Both the FRS and RRS were significantly predictive of incident CAC [RR 1.40 (95% CI 1.29 – 1.52), and RR 1.41 (95% CI 1.30 – 1.54) per 5% increase in risk, respectively] and CAC progression [mean CAC score change 6.92 (95% CI 5.31 – 8.54) and 6.82 (95% CI 5.51 – 8.14) per 5% increase]. Discordance in risk category classification (< or > 10% 10-year CHD risk) occurred in 13.7%, with only the RRS consistently adding predictive value for incidence and progression of CAC. These subclinical atherosclerosis findings are supported by a CHD events analysis over 5.6±0.7 year follow-up.
Conclusion
Both the RRS and FRS predict onset and progression of subclinical atherosclerosis. However, the RRS may provide additional predictive information when discordance between the scoring systems exists.
doi:10.1016/j.jacc.2011.08.022
PMCID: PMC4079464  PMID: 22051329
coronary artery calcium progression; subclinical atherosclerosis; risk prediction; Reynolds Risk Score; Framingham Risk Score
7.  A comparison of outcomes with coronary artery calcium scanning in Unselected Populations - The Multi-Ethnic Study of Atherosclerosis (MESA) and Heinz Nixdorf Recall Study (HNR) 
Background
The Multi-Ethnic Study of Atherosclerosis (MESA) and the Heinz Nixdorf Recall Study (HNR)) differed in regards to informing physicians and patients of the results of their subclinical atherosclerosis.
Objective
This study investigates whether the association of coronary artery calcium (CAC) with incident non-fatal and fatal cardiovascular (CVD) events is different among these two large, population-based observational studies.
Methods
All Caucasian subjects aged 45–75 years, free of baseline cardiovascular disease were included (n=2232 in MESA, n=3119 HNR participants). We studied the association between CAC and event rates at 5 years, including hard cardiac events (MI, cardiac death, resuscitated cardiac arrest), and separately added revascularizations, and strokes (fatal and non-fatal) to determine adjusted hazard ratios (HR).
Results
Both cohorts demonstrated very low CHD (including revascularization) rates with zero calcium (1.13 and 1.16% over 5 years in MESA and HNR respectively) and increasing significantly in both groups with CAC 100–399 (6.71 and 4.52% in MESA and HNR) and CAC >400 (12.5 and 13.54% in MESA and HNR respectively) and demonstrating strong independent predictive values for scores of 100–399 and >400, despite multivariable adjustment for risk factors. Risk factor adjusted five year revascularization rates were nearly identical for HNR and MESA, and generally low for both studies (1.4% [45/3119] for HNR and 1.9% [43/2232] for MESA) over 5 years.
Conclusions
Across two culturally diverse populations, CAC >400 is a strong predictor of events. High CAC did not determininistically result in revascularization and knowledge of CAC did not increase revascularizations.
doi:10.1016/j.jcct.2013.05.009
PMCID: PMC3732186  PMID: 23849491
coronary artery calcification; subclinical atherosclerosis; Multi-Ethnic Study of Atherosclerosis (MESA); Heinz Nixdorf Recall Study (HNR)
8.  Coronary calcium predicts events better with absolute calcium scores than age-gender-race percentiles – The Multi-Ethnic Study of Atherosclerosis (MESA) 
Background
The presence and extent of coronary artery calcium (CAC) correlates with the overall magnitude of coronary atherosclerotic plaque burden and with the development of subsequent coronary events. In this study we aim to establish whether age-gender specific percentiles of CAC predict cardiovascular outcomes better than the actual (absolute) CAC score.
Methods
MESA is a prospective cohort study of asymptomatic 6814 participants, followed for coronary heart disease (CHD) events including myocardial infarction, angina, resuscitated cardiac arrest, or CHD death. Time to incident CHD was modeled using Cox regression, and we compared models using percentiles based on age, gender and/or race/ethnicity to categories commonly used(0, 1-100, 101-400, 400+ Agatston units).
Results
There were 163(2.4%) incident CHD events (median follow-up 3.75 years). Expressing CAC in terms of age and gender specific percentiles had significantly lower area under the ROC curve(AUC) than using absolute scores (women: AUC 0.73 versus 0.76,p=0.044; men: AUC 0.73 versus 0.77,p<0.001). Akaike’s information criterion (AIC) indicated better model fit using the overall score. Both methods robustly predicted events(>90th percentile associated with a hazard ratio(HR) of 16.4(95% c.i. 9.30,28.9), and score >400 associated with HR of 20.6(95% c.i. 11.8, 36.0). Within groups based on age/gender/race/ethnicity specific percentiles there remains a clear trend of increasing risk across levels of the absolute CAC groups. In contrast, once absolute CAC category is fixed, there is no increasing trend across levels of age/gender/race/ethnicity specific categories. Patients with low absolute scores are low risk, regardless of age-gender-ethnicity percentile rank. Persons with an absolute CAC score of >400 are high risk, regardless of percentile rank.
Conclusion
Using absolute CAC in standard groups performed better than age-gender-ethnicity percentiles in terms of model fit and discrimination. We recommend using cut-points based on the absolute CAC amount and the common CAC cutpoints of 100 and 400 appear to perform well.
doi:10.1016/j.jacc.2008.07.072
PMCID: PMC2652569  PMID: 19161884
prognosis; atherosclerosis; cardiac CT; coronary calcium
9.  Progression of Coronary Calcium and Incident Coronary Heart Disease Events: The Multi-Ethnic Study of Atherosclerosis 
Background
Coronary artery calcium (CAC) predicts coronary heart disease (CHD) events and serial measurement of CAC has been proposed to evaluate atherosclerosis progression. We examined whether progression of CAC is a predictor of future CHD events.
Methods and Results
We studied 6,778 persons (52.8% female) aged 45–84 years from the Multi-Ethnic Study of Atherosclerosis. 5,682 persons had baseline and follow-up CAC scans approximately 2.5 ± 0.8 years apart; multiple imputation was used to account for the remainder (n=1,096) missing follow-up scans. Median follow-up duration from the baseline was 7.6 (max=9.0) years. CAC change was assessed by absolute change between baseline and follow-up CAC. Cox proportional hazards regression providing hazard ratios (HR) examined the relation of change in CAC with CHD events, adjusting for age, gender, ethnicity, baseline calcium score, and other risk factors. 343 total and 206 hard CHD events occurred. The annual change in CAC averaged 24.9 ± 65.3 units. Among persons without CAC at baseline (n=3,396), a 5 unit annual change in CAC was associated with an adjusted HR of 1.4 (1.0–1.9) for total and 1.5 (1.1–2.1) for hard CHD. Among those with CAC>0 at baseline HR’s (per 100 unit annual change) were 1.2 (1.1–1.4) and 1.3 (1.1–1.5), respectively. Among participants with baseline CAC, those with annual progression of ≥300 units had adjusted HR’s of 3.8 (1.5–9.6) for total and 6.3 (1.9–21.5) for hard CHD compared to those without progression.
Conclusions
Progression of CAC is associated with an increased risk for future hard and total CHD events.
doi:10.1016/j.jacc.2012.12.035
PMCID: PMC4148074  PMID: 23500326
coronary calcification; atherosclerosis; imaging; coronary heart disease
10.  Interpretation of the Coronary Artery Calcium Score in Combination with Conventional Cardiovascular Risk Factors: The Multi-Ethnic Study of Atherosclerosis (MESA) 
Circulation  2013;128(10):10.1161/CIRCULATIONAHA.113.002598.
Background
The coronary artery calcium (CAC) score predicts coronary heart disease (CHD) events, but methods for interpreting the score in combination with conventional CHD risk factors have not been established.
Methods and Results
We analyzed CAC scores and CHD risk factor measurements from 6757 Black, Chinese, Hispanic and white men and women aged 45–84 years in the Multi-Ethnic Study of Atherosclerosis (MESA). CAC was associated with age, sex, race-ethnicity, and all conventional CHD risk factors. Multivariable models using these factors predicted the presence of CAC (C-statistic = 0.789) and degree of elevation (16% of variation explained), and can be used to update a “pre-test” CHD risk estimate, such as the 10-year Framingham Risk Score, that is based on an individual’s conventional risk factors. In scenarios where a high CAC score is expected, a moderately elevated CAC score of 50 is reassuring (e.g., reducing risk from 10% to 6% in a healthy older white man); but when a low/zero CAC score is expected, even with identical pre-test CHD risk, the same CAC score of 50 may be alarmingly high (e.g., increasing risk from 10% to 20% in a middle-aged black woman with multiple risk factors). Both the magnitude and direction of the shift in risk varied markedly with pre-test CHD risk and with the pattern of risk factors.
Conclusions
Knowing what CAC score to expect for an individual patient, based on their conventional risk factors, may help clinicians decide when to order a CAC test and how to interpret the results.
doi:10.1161/CIRCULATIONAHA.113.002598
PMCID: PMC3840900  PMID: 23884352
coronary disease; calcium; imaging; epidemiology
11.  Arterial Age as a Function of Coronary Artery Calcium (From the Multi-Ethnic Study of Atherosclerosis [MESA]) 
It has been proposed that coronary artery calcium (CAC) can be used to estimate an arterial age in adults. Supporting this concept is that chronologic age, as used in cardiovascular risk assessment, is a surrogate for atherosclerotic burden. This measure can provide the patient with a more understandable version of their CAC score (e.g. you are 55 years old, but your arteries are more consistent with an arterial age of 65). We describe a method of estimating arterial age by equating estimated coronary heart disease (CHD) risk for observed age and coronary artery calcium (CAC). Arterial age is then the risk-equivalent of coronary artery calcium. We use data from the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort study of 6814 participants free of clinical cardiovascular disease, followed for an average of 4 years. Estimated arterial age is obtained as a simple linear function of log-transformed CAC. In a model for incident CHD risk controlling for both age and arterial age, only arterial age was significant, indicating that observed age does not provide additional information after controlling for arterial age. Framingham risk calculated using this arterial age is more predictive of short-term incident coronary events than Framingham risk based on observed age (area under the ROC curve 0.75 for Framingham risk based on observed age, 0.79 using arterial age, p=0.006). In conclusion, arterial age provides a convenient transformation of CAC from Agatston units to a scale more easily appreciated by both patients and treating physicians.
doi:10.1016/j.amjcard.2008.08.031
PMCID: PMC2621006  PMID: 19101230
12.  Associations of Inflammatory Markers with Coronary Artery Calcification: Results from the Multi-Ethnic Study of Atherosclerosis 
Atherosclerosis  2009;209(1):226-229.
Objective
Inflammatory markers predict coronary heart disease (CHD). However, associations with coronary artery calcium (CAC), a marker of subclinical CHD, are not established.
Methods
We examined cross-sectional associations of C-reactive protein (CRP), interleukin-6 (IL-6) and fibrinogen with CAC presence (Agatston score > 0 by computed tomography) in 6,783 Multi-Ethnic Study of Atherosclerosis (MESA) participants.
Results
In all participants, those in the highest, compared to lowest, quartile of CRP had a relative risk (RR, 95% confidence interval) of 1.13 (1.06-1.19; p<0.01) for CAC in age, sex and ethnicity adjusted models. For highest versus lowest quartiles, relative risks were 1.22 (1.15-1.30; p<0.01) for IL-6 and 1.18 (1.11-1.24; p<0.01) for fibrinogen. Adjusting for CHD risk factors (smoking, diabetes, blood pressure, obesity and dyslipidemia) attenuated RRs. RRs for CAC were 1.05 (0.99-1.12; p=0.63) for CRP, 1.12 (1.06-1.20; p<0.01) for IL-6 and 1.09 (1.02-1.16; p=0.01) for fibrinogen in multivariable adjusted models. Results were similar for men and women and across ethnic groups.
Conclusion
Inflammatory markers were weakly associated with CAC presence and burden in MESA. Our data support the hypothesis that inflammatory biomarkers and CAC reflect distinct pathophysiology.
doi:10.1016/j.atherosclerosis.2009.08.037
PMCID: PMC2830357  PMID: 19766217
Atherosclerosis; Calcium; Inflammation; Population
13.  Impact of Subclinical Atherosclerosis on Cardiovascular Disease Events in Individuals With Metabolic Syndrome and Diabetes 
Diabetes Care  2011;34(10):2285-2290.
OBJECTIVE
While metabolic syndrome (MetS) and diabetes confer greater cardiovascular disease (CVD) risk, recent evidence suggests that individuals with these conditions have a wide range of risk. We evaluated whether screening for coronary artery calcium (CAC) and carotid intimal-medial thickness (CIMT) can improve CVD risk stratification over traditional risk factors (RFs) in people with MetS and diabetes.
RESEARCH DESIGN AND METHODS
We assessed CAC and CIMT in 6,603 people aged 45–84 years in the Multi-Ethnic Study of Atherosclerosis (MESA). Cox regression examined the association of CAC and CIMT with coronary heart disease (CHD) and CVD over 6.4 years in MetS and diabetes.
RESULTS
Of the subjects, 1,686 (25%) had MetS but no diabetes and 881 (13%) had diabetes. Annual CHD event rates were 1.0% among MetS and 1.5% for diabetes. Ethnicity and RF-adjusted hazard ratios for CHD for CAC 1–99 to ≥400 vs. 0 in subjects with neither MetS nor diabetes ranged from 2.6 to 9.5; in those with MetS, they ranged from 3.9 to 11.9; and in those with diabetes, they ranged from 2.9 to 6.2 (all P < 0.05 to P < 0.001). Findings were similar for CVD. CAC increased the C-statistic for events (P < 0.001) over RFs and CIMT in each group while CIMT added negligibly to prediction over RFs.
CONCLUSIONS
Individuals with MetS or diabetes have low risks for CHD when CAC or CIMT is not increased. Prediction of CHD and CVD events is improved by CAC more than by CIMT. Screening for CAC or CIMT can stratify risk in people with MetS and diabetes and support the latest recommendations regarding CAC screening in those with diabetes.
doi:10.2337/dc11-0816
PMCID: PMC3177707  PMID: 21844289
14.  Competing Cardiovascular Outcomes Associated with Subclinical Atherosclerosis (From the Multi-Ethnic Study of Atherosclerosis) 
The American journal of cardiology  2013;111(11):1541-1546.
Subclinical atherosclerosis measured by coronary artery calcium (CAC) is associated with increased risk for multiple cardiovascular disease (CVD) outcomes and non-CVD death simultaneously, and we sought to determine the competing risks of specific cardiovascular disease (CVD) events and non-CVD death associated with varying burdens of subclinical atherosclerosis. We included 3095 men and 3486 women from the Multi-Ethnic Study of Atherosclerosis, aged 45–84 years, and from 4 ethnic groups. Participants were stratified by CAC scores: 0, 1–99, and ≥ 100. We used competing Cox models to determine competing cumulative incidences and hazards ratios within a group (e.g., among those with CAC ≥ 100) and hazards ratios for specific events between groups (e.g., CAC ≥ 100 vs. CAC = 0). We compared risks for specific CVD events and also compared against non-CVD death. In women, during a mean follow up of 7.1 years, the hazards ratios (HR) for any CVD event compared with a non-CVD death occurring first for CAC = 0 and CAC ≥ 100 were 1.40 (95% CI, 0.97–2.04) and 3.07 (2.02–4.67), respectively. CHD was the most common first CVD event type at all levels of CAC, and CHD rates were 9.5% vs. 1.6% (HR 6.24; 3.99–9.75) for women with CAC ≥100 compared with CAC = 0. We observed similar results in men. In conclusion, at all levels of CAC, CHD was the most common first CVD event and this analysis represents a novel approach to understanding the temporal sequence of cardiovascular events associated with atherosclerosis.
doi:10.1016/j.amjcard.2013.02.003
PMCID: PMC3657323  PMID: 23499272
coronary artery calcium; competing risks
15.  Association between hsCRP≥2, Coronary Artery Calcium, and Cardiovascular Events – Implications for the JUPITER Population: Multi-Ethnic Study of Atherosclerosis (MESA) 
Lancet  2011;378(9792):684-692.
Background
The JUPITER trial demonstrated that some patients with LDL-C <130 mg/dL and hsCRP ≥2 mg/L benefit from rosuvastatin, although absolute event rates were low. We sought to determine whether coronary artery calcium (CAC) may further risk stratify a JUPITER-eligible population, and to compare hsCRP vs. CAC for risk prediction in otherwise JUPITER-eligible participants.
Methods
A total of 950 MESA participants met all JUPITER entry criteria. We compared CHD and CVD event rates and multivariable-adjusted hazard ratios after stratifying by both presence and burden of CAC (0, 1–100, >100). We also calculated 5-year number needed to treat (NNT5) by applying the benefit observed in JUPITER to the observed event rates within each CAC strata.
Findings
Median follow-up was 5.8 years. Approximately 47% of the MESA JUPITER population had CAC=0, and CHD event rates in this group were <1 per 1000 person-years. Over 2/3 of all CHD events occurred in the 25% of participants with CAC >100 (20.2 per 1000 person-years). For CHD, the predicted NNT5 for CAC 0, 1–100, and >100 was 549, 94, and 24 respectively. For CVD, the NNT5 was 124, 54, and 19. Amongst otherwise JUPITER-eligible patients, presence of CAC was associated with 4.3-fold increased CHD (95% CI 2.0 – 9.3) and 2.6-fold increased CVD (95% CI 1.5–4.5), while hsCRP was not associated with either CHD or CVD after multivariable adjustment.
Interpretation
Within MESA, approximately half of JUPITER-eligible participants had CAC=0 and experienced an extremely low 6-year event rate. Nearly all events occurred in patients with CAC. CAC appears to further risk stratify JUPITER-eligible patients and may be used to target a subgroup of patients expected to derive the most, and the least, absolute benefit from statin treatment. Focusing treatment on the subset of individuals with measurable atherosclerosis may represent a more appropriate allocation of resources.
Funding
NIH-NHLBI.
doi:10.1016/S0140-6736(11)60784-8
PMCID: PMC3173039  PMID: 21856482
hsCRP; CAC; and Clinical Events
16.  Coronary Artery Calcification and Myocardial Perfusion in Asymptomatic Adults: The MESA (Multi-Ethnic Study of Atherosclerosis) 
OBJECTIVES
This study assessed the cross-sectional association between coronary artery calcification (CAC) and myocardial perfusion in an asymptomatic population.
BACKGROUND
Clinical studies showed that the prevalence of stress-induced ischemia increased with CAC burden among patients with coronary heart disease (CHD). Whether an association between CAC and myocardial perfusion exists in subjects without a history of CHD remains largely unknown.
METHODS
A total of 222 men and women, ages 45 to 84 years old and free of CHD diagnosis, in the Minnesota field center of the MESA (Multi-Ethnic Study of Atherosclerosis) were studied. Myocardial blood flow (MBF) was measured using magnetic resonance imaging during rest and adenosine-induced hyperemia. Perfusion reserve was calculated as the ratio of hyperemic to resting MBF. Agatston CAC score was determined from chest multidetector computed tomography.
RESULTS
Mean values of hyperemic MBF and perfusion reserve, but not resting MBF, were monotonically lower across increasing CAC levels. After adjusting for age and gender, odds ratios (95% confidence intervals) of reduced perfusion reserve (<2.5) for subjects with CAC scores of 0, 0.1 to 99.9, 100 to 399, and ≥400 were 1.00 (reference), 2.16 (0.96 to 4.84), 2.81 (1.04 to 7.58), and 4.99 (1.73 to 14.4), respectively. Further adjustment for other coronary risk factors did not substantially modify the association. However, the inverse association between perfusion reserve and CAC attenuated with advancing age (p for interaction < 0.05).
CONCLUSIONS
Coronary vasodilatory response was associated inversely with the presence and severity of CAC in asymptomatic adults. Myocardial perfusion could be impaired by or manifest the progression to subclinical coronary atherosclerosis in the absence of clinical CHD.
doi:10.1016/j.jacc.2006.04.089
PMCID: PMC1853335  PMID: 16949496
17.  Polypill Therapy, Subclinical Atherosclerosis, and Cardiovascular Events – Implications for the Use of Preventive Pharmacotherapy: Multi-Ethnic Study of Atherosclerosis (MESA) 
OBJECTIVES
Examine whether the coronary artery calcium score (CAC) can be used to define the target population to treat with a polypill.
BACKGROUND
Prior studies suggested a single polypill to reduce cardiovascular disease (CVD) at the population level.
METHODS
Participants from the Multi-Ethnic Study of Atherosclerosis (MESA) were stratified using the criteria of four polypill studies (TIPS, Poly-Iran, Wald's, and the PILL collaboration). We compared coronary heart disease (CHD) and CVD event rates and calculated 5-year number needed to treat (NNT) after stratification based on the CAC score.
RESULTS
Among MESA participants eligible for the TIPS, Poly-Iran, Wald's and PILL collaboration, a CAC=0 was observed in 58.6%, 54.5%, 38.9% and 40.8%, respectively. The rate of CHD events among those with CAC=0 varied from 1.2 to 1.9 events per 1000 person-years, those with CAC 1- 100 had event rates ranging from 4.1 to 5.5, and in those with CAC>100 the event rate ranged from 11.6 to 13.3. The estimated 5-year NNT to prevent one CVD event ranged from 81 to 130 for individuals with CAC=0, 38 to 54 for those with CAC 1-100, and 18 to 20 for those with CAC>100.
CONCLUSION
Among individuals eligible for treatment with the polypill, the majority of events occurred in those with CAC>100. The group with CAC=0 had a very low event rate and a high projected NNT. The avoidance of treatment in individuals with CAC=0 could allow for significant reductions in the population considered for treatment, with a more selective use of the polypill and as a result, avoiding treatment in those who are unlikely to be benefit
doi:10.1016/j.jacc.2013.08.1640
PMCID: PMC4174413  PMID: 24161320
subclinical atherosclerosis; risk stratification; polypill
18.  Computed Tomography-Derived Cardiovascular Risk Markers, Incident Cardiovascular Events, and All-Cause Mortality in Non- Diabetics. The Multi-Ethnic Study of Atherosclerosis 
AIM
We assess the improvement in discrimination afforded by the addition thoracic aorta calcium (TAC), aortic valve calcification (AVC), mitral annular calcification (MAC), pericardial adipose tissue volume (PAT) and liver attenuation (LA) to Framingham risk score(FRS) + coronary artery calcium (CAC) for incident CHD/CVD in a multi ethnic cohort.
Methods and Results
A total 5745(2710 were intermediate Framingham risk, 210 CVD and 155 CHD events) 251 had adjudicated CHD, 346 had CVD events, 321 died after 9 years of follow-up. Cox proportional hazard, receiver operator curve (ROC) and net reclassification improvement (NRI) analyses.
In the whole cohort and also when the analysis was restricted to only the intermediate risk participants: CAC, TAC, AVC and MAC were all significantly associated with incident CVD/CHD/ mortality; CAC had the strongest association. When added to the FRS, CAC had the highest area under the curve (AUC) for the prediction of incident CHD/CVD; LA had the least. The addition of TAC, AVC, MAC, PAT and LA to FRS + CAC all resulted in a significant reduction in AUC for incident CHD [0.712 vs. 0.646, 0.655, 0.652, 0.648 and 0.569; all p<0.01 respectively] in participants with intermediate FRS. The addition of CAC to FRS resulted in an NRI of 0.547 for incident CHD in the intermediate risk group. The NRI when TAC, AVC, MAC, PAT and LA were added to FRS + CAC were 0.024, 0.026, 0.019, 0.012 and 0.012 respectively, for incident CHD in the intermediate risk group. Similar results were obtained for incident CVD in the intermediate risk group and also when the whole cohort was used instead of the intermediate FRS group.
Conclusion
The addition of CAC to the FRS provides superior discrimination especially in intermediate risk individuals compared with the addition of TAC, AVC, MAC, PAT or LA for incident CHD/CVD. Compared with FRS + CAC, the addition of TAC, AVC, MAC, PAT or LA individually to FRS + CAC worsens the discrimination for incident CHD/CVD. These CT risk markers are unlikely to be useful for improving cardiovascular risk prediction.
doi:10.1177/2047487313492065
PMCID: PMC4150859  PMID: 23689526
cardiac CT derived risk factors; coronary heart disease; cardiovascular events; risk prediction
19.  Coronary Artery Calcification Compared with Carotid Intima-Media Thickness in Prediction of Cardiovascular Disease Incidence: The Multi-Ethnic Study of Atherosclerosis (MESA) 
Archives of internal medicine  2008;168(12):1333-1339.
Context
Coronary artery calcium (CAC) and carotid intima-media thickness (IMT) are noninvasive measures of atherosclerosis that consensus panels have recommended as possible additions to risk factor assessment for predicting the probability of cardiovascular disease (CVD) occurrence.
Objective
To assess whether maximum carotid IMT or CAC (Agatston Score) is the better predictor of incident CVD.
Design, Setting, Patients
Prospective cohort study of 45–84 year-olds initially free of CVD (n = 6,698) in four ethnic groups, with standardized carotid IMT and CAC measures at baseline, in six field centers of the Multi-Ethnic Study of Atherosclerosis (MESA).
Main Outcome Measure(s)
Incident CVD events (coronary heart disease, stroke, and fatal CVD) over a maximum of 5.3 years of follow-up.
Results
There were 222 CVD events during follow-up. CAC was associated more strongly than carotid IMT with risk of incident CVD. After adjustment for each other and traditional CVD risk factors, the hazard of CVD increased 2.1-fold (95% CI 1.8–2.5) for each standard deviation greater level of log-transformed CAC, versus 1.3-fold (95% CI 1.1–1.4) for each standard deviation greater maximum IMT. For coronary heart disease, the hazard ratios per standard deviation increment were 2.5-fold (95% CI 2.1–3.1) for CAC and 1.2-fold (95% CI 1.0–1.4) for IMT. An ROC analysis also suggested that CAC predicted incident CVD better than IMT did.
Conclusions
Although whether and how to clinically use bio-imaging tests of subclinical atherosclerosis remains a topic of debate, this study found that CAC predicts subsequent CVD events better than does carotid IMT.
doi:10.1001/archinte.168.12.1333
PMCID: PMC2555989  PMID: 18574091
20.  Age-Related Macular Degeneration and Incident Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis 
Ophthalmology  2011;119(4):765-770.
Objective
To determine whether age-related macular degeneration (AMD) is a risk indicator for coronary heart disease (CHD) and cardiovascular disease (CVD) events independent of other known risk factors in a multi-ethnic cohort.
Design
Population-based prospective cohort study.
Participants
A diverse population sample of 6233 men and women aged 45–84 without known CVD from the Multi-Ethnic Study of Atherosclerosis (MESA).
Methods
Participants in the MESA had retinal photographs taken between 2002 and 2003. Photographs were evaluated for AMD. Incident CHD/CVD events were ascertained during clinical follow-up visits for up to 8 years after the retinal images were taken.
Main Outcome Measures
Incident CHD/CVD events.
Results
Of the 6814 persons at risk of CHD, there were 893 participants with early AMD (13.1%) and 27 (0.5%) at baseline. Over a mean follow-up period of 5.4 years, there was no statistically significant difference in incident CHD or CVD between the AMD and non-AMD groups (5.0%vs. 3.9%, p=0.13 for CHD and 6.6 vs. 5.5%, p=0.19 for CVD, respectively). In Cox regression models adjusting for CVD risk factors, there was no significant relationship between presence of any AMD and any CHD/CVD events (HR=0.99, 95% CI 0.74–1.33, p=0.97). No significant association was found between subgroups of early AMD or late AMD and incident CHD/CVD events.
Conclusions
In persons without a history of cardiovascular disease, AMD was not associated with an increased risk of CHD or CVD.
doi:10.1016/j.ophtha.2011.09.044
PMCID: PMC3314126  PMID: 22197438
21.  Association of Plasma Sphingomyelin levels and Incident Coronary Heart Disease Events in an Adult Population: Multi Ethnic Study of Atherosclerosis 
Objectives
High plasma sphingomyelin level has been associated with subclinical atherosclerosis, coronary artery disease and worse prognosis in subjects with acute coronary syndromes. We assess the predictive value of plasma sphingomyelin levels for incident CHD events in the Multi Ethnic Study of atherosclerosis (MESA).
Method and Results
Plasma sphingomyelin was measured in 6809 out of 6814 subjects with mean age 62.2 ± 10.2 years, participating in the MESA study, a population based cohort study of adults free of clinical CVD at baseline recruited at six clinic sites in USA. The subjects consisted of 52.8% females, 38.5% Caucasian, 11.8% Chinese, 27.8% African Americans and 21.9% Hispanics. Cox proportional hazard analysis was used to examine the association between plasma sphingomyelin and five years of adjudicated incident CHD events including MI, resuscitated cardiac arrest, angina, CHD death and revascularization (CABG or PTCA). Mean (SD) plasma sphingomyelin level was 48 mg/dl (16.0). One hundred and eighty-nine subjects had an adjudicated CHD event during the five years of follow up. In the Kaplan meier analysis, subjects with plasma sphingomyelin level above the sex specific median had similar event free survival rate compared with subjects with plasma sphingomyelin level below or equal to the sex specific median (97.16% vs 97.0%, log rank p= 0.713). In the univariate Cox proportional hazard analysis, plasma sphingomyelin was not a predictor of incident CHD event [hazard ratio 0.992(0.982 – 1.004), p=0.09]. In our multistage multivariable Cox models, higher plasma sphingomyelin had modest negative association with incident CHD events when total cholesterol, HDL and triglycerides were included in the model [hazard ratio 0.985 (0.973 – 0.996), p=0.008] and also in our full model after adjusting for age, gender, total cholesterol, HDL, triglycerides, diabetes, cigarette smoking, systolic BP, diastolic BP, BP medication use, HMG CoA use [hazard ratio 0.984 (0.973 – 0.996), p=0.002]. In other models, plasma sphingomyelin was not associated with incident CHD events.
Conclusion
High plasma sphingomyelin level is not associated with increased risk of incident coronary heart disease in population based adults free of clinical cardiovascular disease at baseline.
doi:10.1161/ATVBAHA.109.199281
PMCID: PMC2862629  PMID: 20032291
Plasma sphingomyelin; prognosis; coronary heart disease events; epidemiology
22.  Associations between Aspirin and other non-steroidal anti-inflammatory drugs and aortic valve or coronary artery calcification: The Multi-Ethnic Study of Atherosclerosis and the Heinz Nixdorf Recall Study 
Atherosclerosis  2013;229(2):310-316.
Background
The association between non-steroidal anti-inflammatory drugs (NSAIDs) and the incidence of valvular and arterial calcification is not well established despite known associations between these drugs and cardiovascular events.
Objective
To compare the association between the baseline use of aspirin with other NSAID class medications with the incidence and prevalence of aortic valve calcification (AVC) and coronary artery calcium (CAC).
Methods
The relationship of NSAID use to AVC and CAC detected by computed tomography was assessed in 6,814 participants within the Multi-Ethnic Study of Atherosclerosis (MESA) using regression modeling. Results were adjusted for age, sex, ethnicity, study site, anti-hypertensive medication use, education, income, health insurance status, diabetes, smoking, exercise, body mass index, blood pressure, serum lipids, inflammatory markers, fasting glucose, statin medication use, and a simple diet score. Medication use was assessed by medication inventory at baseline which includes the use of non-prescription NSAIDs. MESA collects information on both incident and prevalent calcification. The 4,814 participants of the Heinz Nixdorf Recall (HNR) Study, a German prospective cohort study with similar measures of calcification, were included in this analysis to enable replication.
Results
Mean age of the MESA participants was 62 years (51% female). After adjustment for possible confounding factors, a possible association between aspirin use and incident AVC (Relative Risk(RR): 1.60; 95%Confidence Interval (CI): 1.19–2.15) did not replicate in the HNR cohort (RR: 1.06; 95%CI: 0.87–1.28). There was no significant association between aspirin use and incident CAC in the MESA cohort (RR 1.08; 95%CI: 0.91–1.29) or in the HNR cohort (RR 1.24; 95%CI: 0.87–1.77). Non-aspirin NSAID use was not associated with either AVC or CAC in either cohort. There were no associations between regular cardiac dose aspirin and incident calcification in either cohort.
Conclusion
Baseline NSAID use, as assessed by medication inventory, appears to have no protective effect regarding the onset of calcification in either coronary arteries or aortic valves.
doi:10.1016/j.atherosclerosis.2013.05.002
PMCID: PMC3724227  PMID: 23880181
Non-steroidal anti-inflammatory drugs; aspirin; aortic valve calcification; coronary artery calcification; Multi-Ethnic Study of Atherosclerosis; Heinz Nixdorf Recall Study
23.  Eligibility of Individuals with Subclinical Coronary Artery Calcium and Intermediate Coronary Heart Disease Risk for Reclassification (from the Framingham Heart Study) 
The American journal of cardiology  2009;103(12):1710-1715.
Coronary artery calcium (CAC) predicts risk for coronary heart disease (CHD) events and it is possible that CAC testing may further stratify risk in individuals at intermediate CHD risk. We sought to determine the percentage of individuals at intermediate CHD risk who could potentially be reclassified as high CHD risk based on the presence of a high CAC score as well as the prevalence, treatment, and control of CHD risk factors in this group. Framingham Heart Study Offspring and Third Generation cohort participants underwent multidetector CT (n=3,529; mean age=51 years; 48% women). High CAC was defined as either ≥90th age- and sex-specific percentiles based on a healthy reference group or by an absolute modified Agatston score of 100 Hounsfield units (HU). The prevalence of CHD risk factors (hypertension, hypercholesterolemia, high low-density lipoprotein cholesterol, low high-density lipoprotein cholesterol, smoking, and obesity), and their treatment, and control was compared between non-diabetic subjects with and without high CAC. Of the 595 participants at intermediate CHD risk, 22% had CAC ≥90th percentile and 39% had CAC ≥100 and could be eligible for reclassification as high CHD risk based on the presence of a high CAC score. There were no statistically significant differences in prevalence, treatment, and control of risk factors between those with and without high CAC. In conclusion, the prevalence of CHD risk factors did not differ between intermediate risk individuals with and without high CAC. Approximately 25% of intermediate risk persons have high CAC scores and may be eligible for reclassification into a higher risk category.
doi:10.1016/j.amjcard.2009.02.020
PMCID: PMC3042246  PMID: 19539080
coronary artery calcium; coronary heart disease; Framingham risk score; reclassification
24.  Metabolic Syndrome, Diabetes, and Incidence and Progression of Coronary Calcium: The Multiethnic Study of Atherosclerosis (MESA) 
Jacc. Cardiovascular Imaging  2012;5(4):358-366.
Objectives
The purpose of the study was to examine and compare the incidence and progression of coronary artery calcium (CAC) among persons with metabolic syndrome (MetS) and diabetes mellitus (DM), compared to those with neither condition.
Background
MetS and DM are associated with subclinical atherosclerosis as evidenced by coronary artery calcium (CAC).
Methods
The Multiethnic Study of Atherosclerosis included 6,814 African-American, Asian, Caucasian, and Hispanic adults aged 45–84 free of cardiovascular disease at baseline. 5,662 subjects (51% female, mean age 61.0 ± 10.3 years) received baseline and follow-up (mean 2.4 years) cardiac CT scans. We compared the incidence of CAC in 2,927 subjects without CAC at baseline and progression of CAC in 2,735 subjects with CAC at baseline in those with MetS without DM (25.2%), DM without MetS (3.5%), or both DM and MetS (9.0%), compared to neither MetS nor DM (58%). Progression of CAC was also examined in relation to coronary heart disease events over an additional 4.9 years.
Results
Relative to those with neither MetS nor DM, adjusted relative risks (95% confidence intervals) for incident CAC were 1.7 (1.4–2.0), 1.9 (1.4–2.4), and 1.8 (1.4–2.2) (all p<0.01) and absolute differences in mean progression (volume score) were 7.8 (4.0–11.6; p<0.01), 11.6 (2.7–20.5; p<0.05), and 22.6 (17.2–27.9; p<0.01) for those with MetS without DM, DM without MetS, and both DM and MetS, respectively. Similar findings were seen in analysis using Agatston calcium score. In addition, progression predicted CHD events in those with MetS without DM (adjusted hazard ratio 4.1, 95% CI=2.0–8.5, p<0.01) and DM (4.9 [1.3–18.4], p<0.05) among those in highest tertile of CAC increase vs. no increase).
Conclusions
Individuals with MetS and DM have a greater incidence and absolute progression of CAC compared to individuals without these conditions, with progression also predicting CHD events in those with MetS and DM.
doi:10.1016/j.jcmg.2011.12.015
PMCID: PMC3327555  PMID: 22498324
atherosclerosis; diabetes; risk factors; calcification
25.  Prediction of Coronary Artery Calcium Progression in Individuals with Low Framingham Risk Score: The Multi-Ethnic Study of Atherosclerosis (MESA) 
Jacc. Cardiovascular Imaging  2012;5(2):144-153.
Objectives
We sought to determine whether novel markers not involving ionizing radiation could predict CAC progression in a low-risk population.
Background
Increase in coronary artery calcium (CAC) scores over time (CAC progression) improves prediction of coronary heart disease (CHD) events. Due to radiation exposure, CAC measurement represents an undesirable method for repeated risk assessment, particularly in low predicted risk individuals (Framingham Risk Score [FRS] <10%).
Methods
From 6814 MESA participants, 2620 individuals were classified as low risk for CHD events (FRS <10%), and had follow-up CAC measurement. In addition to traditional risk factors [(RFs) - base model], various combinations of novel-marker models were selected based on data-driven, clinical, or backward stepwise selection techniques.
Results
Mean follow-up was 2.5 years. CAC progression occurred in 574 participants (22% overall; 214 of 1830 with baseline CAC =0, and 360 of 790 with baseline CAC >0). Addition of various combinations of novel markers to the base model (c-statistic =0.711), showed improvements in discrimination of approximately only 0.005 each (c-statistics 0.7158, 0.7160 and 0.7164) for the best-fit models. All 3 best-fit novel-marker models calibrated well but were similar to the base model in predicting individual risk probabilities for CAC progression. The highest prevalence of CAC progression occurred in the highest compared to the lowest probability quartile groups (39.2–40.3% versus 6.4–7.1%).
Conclusions
In individuals at low predicted risk by FRS, traditional RFs predicted CAC progression in the short term with good discrimination and calibration. Prediction improved minimally when various novel markers were added to the model.
doi:10.1016/j.jcmg.2011.11.008
PMCID: PMC3310187  PMID: 22340820
coronary calcium; Framingham risk score; risk factors; progression

Results 1-25 (680100)