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ObjectivesThis study sought to quantify and model conversion of a normal coronary artery calcium (CAC) scan to an abnormal CAC scan.BackgroundAlthough the absence of CAC is associated with excellent prognosis, progression to CAC >0 confers increased risk. The time interval for repeated scanning remains poorly defined.MethodsThis study included 3,116 participants from the MESA (Multi-Ethnic Study of Atherosclerosis) with baseline CAC = 0 and follow-up scans over 10 years after baseline. Prevalence of incident CAC, defined by thresholds of CAC >0, CAC >10, or CAC >100, was calculated and time to progression was derived from a Weibull parametric survival model. Warranty periods were modeled as a function of sex, race/ethnicity, cardiovascular risk, and desired yield of repeated CAC testing. Further analysis was performed of the proportion of coronary events occurring in participants with baseline CAC = 0 that preceded and followed repeated CAC testing at different time intervals.ResultsMean participants' age was 58 ± 9 years, with 63% women, and mean 10-year cardiovascular risk of 14%. Prevalence of CAC >0, CAC >10, and CAC >100 was 53%, 36%, and 8%, respectively, at 10 years. Using a 25% testing yield (number needed to scan [NNS] = 4), the estimated warranty period of CAC >0 varied from 3 to 7 years depending on sex and race/ethnicity. Approximately 15% of participants progressed to CAC >10 in 5 to 8 years, whereas 10-year progression to CAC >100 was rare. Presence of diabetes was associated with significantly shorter warranty period, whereas family history and smoking had small effects. A total of 19% of all 10-year coronary events occurred in CAC = 0 prior to performance of a subsequent scan at 3 to 5 years, whereas detection of new CAC >0 preceded 55% of future events and identified individuals at 3-fold higher risk of coronary events.ConclusionsIn a large population of individuals with baseline CAC = 0, study data provide a robust estimation of the CAC = 0 warranty period, considering progression to CAC >0, CAC >10, and CAC >100 and its impact on missed versus detectable 10-year coronary heart disease events. Beyond age, sex, race/ethnicity, diabetes also has a significant impact on the warranty period. The study suggests that evidence-based guidance would be to consider rescanning in 3 to 7 years depending on individual demographics and risk profile.

AimsThe European Society of Cardiology (ESC) guideline on cardiovascular risk assessment considers coronary artery calcium a class B indication for risk assessment. We evaluated the degree to which coronary artery calcium can change the recommendation for individuals based on a change in estimated risk.Methods and resultsWe stratified 5602 MESA participants according to the ESC recommendation as: no lipid-lowering treatment recommended ( N = 2228), consider lipid-lowering treatment if uncontrolled ( N = 1686), or lipid-lowering treatment recommended ( N = 1688). We evaluated the ability of coronary artery calcium to reclassify cardiovascular risk. Among the selected sample, 54% had coronary artery calcium of zero, 25% had coronary artery calcium of 1-100 and 21% had coronary artery calcium greater than 100. In the lipid-lowering treatment recommended group 31% had coronary artery calcium of zero, while in the lipid-lowering treatment if uncontrolled group about 50% had coronary artery calcium of zero. The cardiovascular mortality rate was 1.7%/10 years in the lipid-lowering treatment if uncontrolled, and 7.0%/10 years in the lipid-lowering treatment recommended group. The absence of coronary artery calcium was associated with 1.4%/10 years in the lipid-lowering treatment if uncontrolled group and 3.0%/10 years in the lipid-lowering treatment recommended group. Compared with coronary artery calcium of zero, any coronary artery calcium was associated with significantly higher cardiovascular mortality in the lipid-lowering treatment recommended group (9.0%/10 years), whereas only coronary artery calcium greater than 100 was significantly associated with a higher cardiovascular mortality in the lipid-lowering treatment if uncontrolled group (3.2%/10 years).ConclusionThe absence of coronary artery calcium is associated with a low incidence of cardiovascular mortality or coronary heart disease events even in individuals in whom lipid-lowering therapy is recommended. A significant proportion of individuals deemed to be candidates for lipid-lowering therapy might be reclassified to a lower risk group with the use of coronary artery calcium.

The intent of CAD-RADS - Coronary Artery Disease Reporting and Data System is to create a standardized method to communicate findings of coronary CT angiography (coronary CTA) in order to facilitate decision-making regarding further patient management. The suggested CAD-RADS classification is applied on a per-patient basis and represents the highest-grade coronary artery lesion documented by coronary CTA. It ranges from CAD-RADS 0 (Zero) for the complete absence of stenosis and plaque to CAD-RADS 5 for the presence of at least one totally occluded coronary artery and should always be interpreted in conjunction with the impression found in the report. Specific recommendations are provided for further management of patients with stable or acute chest pain based on the CAD-RADS classification. The main goal of CAD-RADS is to standardize reporting of coronary CTA results and to facilitate communication of test results to referring physicians along with suggestions for subsequent patient management. In addition, CAD-RADS will provide a framework of standardization that may benefit education, research, peer-review and quality assurance with the potential to ultimately result in improved quality of care.

The intent of CAD-RADS - Coronary Artery Disease Reporting and Data System is to create a standardized method to communicate findings of coronary CT angiography (coronary CTA) in order to facilitate decision-making regarding further patient management. The suggested CAD-RADS classification is applied on a per-patient basis and represents the highest-grade coronary artery lesion documented by coronary CTA. It ranges from CAD-RADS 0 (Zero) for the complete absence of stenosis and plaque to CAD-RADS 5 for the presence of at least one totally occluded coronary artery and should always be interpreted in conjunction with the impression found in the report. Specific recommendations are provided for further management of patients with stable or acute chest pain based on the CAD-RADS classification. The main goal of CAD-RADS is to standardize reporting of coronary CTA results and to facilitate communication of test results to referring physicians along with suggestions for subsequent patient management. In addition, CAD-RADS will provide a framework of standardization that may benefit education, research, peer-review and quality assurance with the potential to ultimately result in improved quality of care.

AimsPatients with a low lifetime risk of coronary heart disease (CHD) are not completely free of events over 10 years. We evaluated predictors for CHD among "low lifetime risk" participants in the population-based Multi-Ethnic Study of Atherosclerosis (MESA).MethodsMESA enrolled 6814 men and women aged 45-84 years who were free of baseline cardiovascular disease. Using established criteria of non-diabetic, non-smokers with total cholesterol ≤ 200 mg/dL, systolic BP ≤ 139 mmHg, and diastolic BP ≤ 89 mmHg at baseline, we identified 1391 participants with a low lifetime risk for cardiovascular disease. Baseline covariates were age, gender, ethnicity, HDL-C, C-reactive protein, family history of CHD, carotid intima-media thickness and coronary artery calcium (CAC). We calculated event rates and the number needed to scan (NNS) to identify one participant with CAC>0 and > 100.ResultsOver 10.4 years median follow-up, there were 33 events (2.4%) in participants with low lifetime risk. There were 479 participants (34%) with CAC>0 including 183 (13%) with CAC>100. CAC was present in 25 (76%) participants who experienced an event. In multivariable analyses, only CAC>100 remained predictive of CHD (HR 4.6; 95% CI: 1.6-13.6; p = 0.005). The event rates for CAC = 0, CAC>0 and CAC>100 were 0.9/1,000, 5.7/1,000, and 11.0/1000 person-years, respectively. The NNS to identify one participant with CAC>0 and > 100 were 3 and 7.6, respectively.ConclusionsWhile 10-year event rates were low in those with low lifetime risk, CAC was the strongest predictor of incident CHD. Identification of individuals with CAC = 0 and CAC>100 carries significant potential therapeutic implications.

BackgroundThe transition from no coronary artery calcium (CAC) to detectable CAC is important, as even mild CAC is associated with increased cardiovascular events. We sought to characterize the anatomic distribution and burden of newly detectable CAC over 10-year follow-up.MethodsWe evaluated 3112 participants (mean age, 58 years; 64% female) with baseline CAC = 0 from the Multi-Ethnic Study of Atherosclerosis. Participants underwent repeat CAC testing at different time intervals (between 2-10 years after baseline) per the Multi-Ethnic Study of Atherosclerosis protocol. Among participants who developed CAC on a follow-up scan, we used logistic regression and marginal probability modeling to describe the coronary distribution and burden of new CAC by age, sex, and race after adjustment for cardiovascular risk factors and time to detection.ResultsA total of 1125 participants developed detectable CAC during follow-up with a mean time to detection of 6.1 ± 3 years. New CAC was most commonly isolated to 1 vessel (72% of participants), with the left anterior descending artery (44% of total) most commonly affected followed by the right coronary (12%), left circumflex (10%), and left main (6%). These patterns were similar across age, sex, and race. In multivariate models, residual predictors of multivessel CAC (28% of total) included male sex, African American or Hispanic race, hypertension, obesity, and diabetes. At the first detection of CAC >0, burden was usually low with median Agatston CAC score of 7.1 and 100.ConclusionNew-onset CAC most commonly involves just 1 vessel, occurs in the left anterior descending artery, and has low CAC burden. New CAC can be detected at an early stage when aggressive preventive strategies may provide benefit.

BackgroundA subgroup has emerged within the obese that do not display the typical metabolic disorders associated with obesity and are hypothesized to have lower risk of complications. The purpose of this review was to analyze the literature which has examined the burden of cardiovascular disease (CVD) and all-cause mortality in the metabolically healthy obese (MHO) population.MethodsPubmed, Cochrane Library, and Web of Science were searched from their inception until December 2012. Studies were included which clearly defined the MHO group (using either insulin sensitivity and/or components of metabolic syndrome AND obesity) and its association with either all cause mortality, CVD mortality, incident CVD, and/or subclinical CVD.ResultsA total of 20 studies were identified; 15 cohort and 5 cross-sectional. Eight studies used the NCEP Adult Treatment Panel III definition of metabolic syndrome to define "metabolically healthy", while another nine used insulin resistance. Seven studies assessed all-cause mortality, seven assessed CVD mortality, and nine assessed incident CVD. MHO was found to be significantly associated with all-cause mortality in two studies (30%), CVD mortality in one study (14%), and incident CVD in three studies (33%). Of the six studies which examined subclinical disease, four (67%) showed significantly higher mean common carotid artery intima media thickness (CCA-IMT), coronary artery calcium (CAC), or other subclinical CVD markers in the MHO as compared to their MHNW counterparts.ConclusionsMHO is an important, emerging phenotype with a CVD risk between healthy, normal weight and unhealthy, obese individuals. Successful work towards a universally accepted definition of MHO would improve (and simplify) future studies and aid inter-study comparisons. Usefulness of a definition inclusive of insulin sensitivity and stricter criteria for metabolic syndrome components as well as the potential addition of markers of fatty liver and inflammation should be explored. Clinicians should be hesitant to reassure patients that the metabolically benign phenotype is safe, as increased risk cardiovascular disease and death have been shown.

AimsWe sought to evaluate the impact of coronary artery calcium (CAC) in individuals at the extremes of risk factor (RF) burden.Methods and results6698 individuals from the Multi-Ethnic Study of Atherosclerosis (MESA) were followed for coronary heart disease (CHD) events over mean 7.1 ± 1 years. Annualized CHD event rates were compared among each RF category (0, 1, 2, or ≥3) after stratification by CAC score (0, 1-100, 101-300, and >300). The following traditional modifiable RFs were considered: cigarette smoking, LDL cholesterol ≥3.4 mmol/L, low HDL cholesterol, hypertension, and diabetes. There were 1067 subjects (16%) with 0 RFs, whereas 1205 (18%) had ≥3 RFs. Among individuals with 0 RFs, 68% had CAC 0, whereas 12 and 5% had CAC >100 and >300, respectively. Among individuals with ≥3 RFs, 35% had CAC 0, whereas 34 and 19% had CAC >100 and >300, respectively. Overall, 339 (5.1%) CHD events occurred. Individuals with 0 RFs and CAC >300 had an event rate 3.5 times higher than individuals with ≥3 RFs and CAC 0 (10.9/1000 vs. 3.1/1000 person-years). Similar results were seen across categories of Framingham risk score.ConclusionAmong individuals at the extremes of RF burden, the distribution of CAC is heterogeneous. The presence of a high CAC burden, even among individuals without RFs, is associated with an elevated event rate, whereas the absence of CAC, even among those with many RF, is associated with a low event rate. Coronary artery calcium has the potential to further risk stratify asymptomatic individuals at the extremes of RF burden.

ObjectivesThe aim of this study was to evaluate the impact of coronary artery calcium (CAC) burden and regional distribution on the need for and type of future coronary revascularization-percutaneous versus surgical (coronary artery bypass graft [CABG])-among asymptomatic subjects.BackgroundThe need for coronary revascularization and the chosen mode of revascularization are thought to be functions of disease burden and anatomic distribution. The association between the baseline burden and regional distribution of CAC and the risk and type of future coronary revascularization remains unknown.MethodsA total of 6,540 participants in the MESA (Multi-Ethnic Study of Atherosclerosis) (subjects aged 45 to 84 years, free of known baseline cardiovascular disease) with vessel-specific CAC measurements were followed for a median of 8.5 years (interquartile range: 7.7 to 8.6 years). Annualized rates and multivariate-adjusted hazard ratios for revascularization and revascularization type were analyzed according to CAC score category, number of vessels with CAC (0 to 4, including the left main coronary artery), and involvement of individual coronary arteries.ResultsA total of 265 revascularizations (4.2%) occurred during follow-up, and 206 (78% of the total) were preceded by adjudicated symptoms. Revascularization was uncommon when CAC score was 0.0 (0.6%), with a graded increase over both rising CAC burden and increasingly diffuse CAC distribution. The revascularization rates per 1,000 person-years for CAC scores of 1 to 100, 101 to 400, and >400 were 4.9, 11.7, and 25.4, respectively; for 1, 2, 3, and 4 vessels with CAC, the rates were 3.0, 8.0, 16.1, and 24.8, respectively. In multivariate models adjusting for CAC score, the number of vessels with CAC remained predictive of revascularization and mode of revascularization. Independent predictors of CABG versus percutaneous coronary intervention included 3- or 4-vessel CAC, higher CAC burden, and involvement of the left main coronary artery. Risk for CABG was extremely low with

ObjectivesThis study examines whether the coronary artery calcium (CAC) score can be used to define the target population to treat with a polypill.BackgroundPrior studies have suggested a single polypill to reduce cardiovascular disease (CVD) at the population level.MethodsParticipants from MESA (Multi-Ethnic Study of Atherosclerosis) were stratified using the criteria of 4 polypill studies (TIPS [The Indian Polycap Study], Poly-Iran, Wald, and the PILL [Program to Improve Life and Longevity] Collaboration). We compared coronary heart disease (CHD) and CVD event rates and calculated the 5-year number needed to treat (NNT) after stratification based on the CAC score.ResultsAmong MESA participants eligible for TIPS, Poly-Iran, Wald, and the PILL Collaboration, 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 1,000 person-years, those with CAC scores from 1 to 100 had event rates ranging from 4.1 to 5.5, and in those with CAC scores >100 the event rate ranged from 11.6 to 13.3. The estimated 5-year NNT to prevent 1 CVD event ranged from 81-130 for patients with CAC = 0, 38-54 for those with CAC scores from 1 to 100, and 18-20 for those with CAC scores >100.ConclusionsIn MESA, among individuals eligible for treatment with the polypill, the majority of CHD and CVD events occurred in those with CAC scores >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, avoidance of treatment in those who are unlikely to benefit.

ContextThe internet is gaining popularity as a means of delivering employee-based cardiovascular (CV) wellness interventions though little is known about the cardiovascular health outcomes of these programs. In this review, we examined the effectiveness of internet-based employee cardiovascular wellness and prevention programs.Evidence acquisitionWe conducted a systematic review by searching PubMed, Web of Science and Cochrane library for all published studies on internet-based programs aimed at improving CV health among employees up to November 2012. We grouped the outcomes according to the American Heart Association (AHA) indicators of cardiovascular wellbeing--weight, BP, lipids, smoking, physical activity, diet, and blood glucose.Evidence synthesisA total of 18 randomized trials and 11 follow-up studies met our inclusion/exclusion criteria. Follow-up duration ranged from 6-24 months. There were significant differences in intervention types and number of components in each intervention. Modest improvements were observed in more than half of the studies with weight related outcomes while no improvement was seen in virtually all the studies with physical activity outcome. In general, internet-based programs were more successful if the interventions also included some physical contact and environmental modification, and if they were targeted at specific disease entities such as hypertension. Only a few of the studies were conducted in persons at-risk for CVD, none in blue-collar workers or low-income earners.ConclusionInternet based programs hold promise for improving the cardiovascular wellness among employees however much work is required to fully understand its utility and long term impact especially in special/at-risk populations.

BackgroundWorldwide clinical practice guidelines for dyslipidemia emphasize allocating statin therapy to those at the highest absolute atherosclerotic cardiovascular disease (CVD) risk.Methods and resultsWe examined 5534 Multi-Ethnic Study of Atherosclerosis (MESA) participants who were not on baseline medications for dyslipidemia. Participants were classified by baseline coronary artery calcium (CAC) score (>0, ≥ 100) and the common clinical scheme of counting lipid abnormalities (LA), including low-density lipoprotein cholesterol ≥ 3.36 mmol/L (130 mg/dL), high-density lipoprotein cholesterol

Patients with obstructive sleep apnea (OSA) have a high burden of cardiovascular disease (CVD) but a causal relationship between OSA and atherosclerotic CVD remains unclear. We systematically reviewed the literature analyzing the relationship. A review of the Medline database for studies noninvasively evaluating subclinical CVD in OSA was conducted. A total of fifty-two studies were included in this review.Across the studies the prevalence of atherosclerosis, as assessed by coronary artery calcification, carotid intima-media thickness, brachial artery flow-mediated dilation and pulse wave velocity was higher in patients with OSA and correlated with increasing severity and duration of OSA.This study shows OSA is an independent predictor of subclinical CVD as CVD is more likely to occur in patients with long standing and severe OSA. Further research is however necessary to identify specific OSA populations that would benefit from aggressive screening.

ObjectiveWe sought to determine whether insulin resistance predicts the incidence and progression of coronary artery calcification (CAC).Research design and methodsWe studied 5,464 participants not on hypoglycemic therapy from the Multi-Ethnic Study of Atherosclerosis (MESA). Each had baseline homeostasis model assessment of insulin resistance (HOMA-IR) and baseline and follow-up CAC scores. Incident CAC was defined as newly detectable CAC; progression was defined as advancing CAC volume score at follow-up.ResultsMedian HOMA-IR was 1.2 (0.8-2.0). Across all ethnicities, there was a graded increase in CAC incidence and progression with increasing HOMA-IR. When compared with those in the 1st quartile, participants in the 2nd-4th quartiles had 1.2, 1.5, and 1.8 times greater risk of developing CAC. Median annualized CAC score progression was 8, 14, and 17 higher, respectively. However, HOMA-IR was not predictive after adjustment for metabolic syndrome components.ConclusionsHOMA-IR predicts CAC incidence and progression, but not independently of metabolic syndrome.

Background. Among the obese, the so-called metabolically healthy obese (MHO) phenotype is thought to confer a lower CVD risk as compared to obesity with typical associated metabolic changes. The present study aims to determine the relationship of different subtypes of obesity with inflammatory-cardiometabolic abnormalities. Methods. We evaluated 5,519 healthy, Brazilian subjects (43±10 years, 78% males), free of known cardiovascular disease. Those with