Advanced Coronary Artery Calcium Research Articles

Abstract 16481: Comparative Measures of Physical Performance in Healthy Subjects and Patients With Subclinical Heart Failure or Coronary Artery Calcium in the Project Baseline Health Study

Introduction: While exercise stress test is the traditional method for assessing cardiorespiratory fitness, 6-minute walk test (6MWT) and 10-meter walk test (10MWT) can be inexpensive alternatives for physical activity and fitness evaluation. We aim to identify conditions where 6MWT and 10MWT show comparable diagnostic yield to metabolic equivalents of task (MET). Methods: All participants in the Project Baseline Health Study (PBHS) with no missing data were included. Participants were assigned a heart failure (HF) stage according to the 2022 AHA/ACC HF guidelines. Mean and standard deviation (SD) were described for each measurement by HF stages: 0 (healthy), A (presence of risk factors (RF)), and B (presence of RF and LVEF<50%, diastolic dysfunction or LVH); and by coronary artery calcium (CAC) score subgroups: 0, 1-99, ≥100 Agatson units (AU). Multinomial regression was applied to estimate the association of each measurement with HF stage and CAC subgroups adjusted for relevant covariates. Results: 2,181 (87%) of 2,502 PBHS participants had complete data on METs, 6MWT, and 10MWT. The mean (SD) age was 50.1 (17.1) years, with 1224 (56.1%) females. The cohort consisted of participants with Stage 0, A, B (n=711, 742, 372) and CAC = 0, 1-99, ≥ 100 (n=1275, 471, 348). The overall mean (SD) for 6MWT, 10MWT, and METs were 479.8 (79.1) m, 2.0 (0.5) m/s, and 11.6 (4.3), respectively. Each SD decrease of METs was significantly associated with increased odds for more advanced HF stages and CAC subgroups ( Figure A1-B2 ). The 10MWT and 6MWT were also able to differentiate significantly between subclinical stages of HF and compare CAC subgroups 1-99 and ≥100 to CAC=0, although with smaller odds ratios (Figure A1, A2, B1). Conclusions: METs, as measured in a graded exercise test, demonstrated the strongest association with HF stage or CAC subgroup. Based on our findings, there is potential for utilizing the simpler assessments of 10MWT and 6MWT to differentiate between subclinical HF stages.

Distribution of calcium volume, density, number, and type of coronary vessel with calcified plaque in South Asians in the US and other race/ethnic groups: The MASALA and MESA studies

Background and aimsSouth Asians (SA) experience disproportionately higher rates of atherosclerotic cardiovascular disease (ASCVD) events than non-Hispanic whites (NHW) and several other Asian groups. The coronary artery calcium (CAC) Agatston score may not capture the unique characteristics of coronary plaque in SA. We therefore evaluated the prevalence and patterns of advanced CAC measures (specific coronary vessel involvement, CAC volume and density) in SA versus other race/ethnicities. MethodsWe combined data from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) and Multi-Ethnic Study of Atherosclerosis (MESA) cohorts. We used multivariable-adjusted linear regression models to compare advanced CAC measures between SA and other ethnicities. ResultsOur analyses included 7,625 individuals (810 SA, 2,622 whites, 1,893 African Americans, 1,496 Hispanics, 803 Chinese Americans) with mean (SD) age 62 (10) years and 48% men. In adjusted analyses, compared to NHW, SA had lower overall CAC volume [beta coefficient (95% CI)] [-0.46 (−0.62,-0.29)] but higher overall CAC density [0.14 (0.11,0.18)]. These trends were similar when SA were compared to non-whites (Hispanics, Chinese Americans, and African Americans). SA had higher overall [0.07 (0.03,0.12)] and right coronary artery [0.09 (0.03,0.16)] CAC density compared to non-whites, while CAC volume was not significantly different between these two groups. ConclusionsSA have lower CAC volume compared to NHW but similar compared to non-whites. Overall CAC density is higher among SA compared to NHW and non-whites. Future longitudinal studies of ASCVD events are required to confirm the prognostic significance of these findings among SA.

Prevalence of Coronary Artery Calcium in Patients With Atrial Fibrillation With and Without Cardiovascular Risk Factors

The burden of coronary artery atherosclerosis in patients with atrial fibrillation (AF) is unknown. We aimed to assess the coronary artery calcium (CAC) in AF patients. We retrospectively analyzed 324 consecutive patients with AF who had CT angiogram before AF ablation and their cardiovascular risk were prospectively collected. Mean age of the cohort was 66 years and 71% were male. The previous history of coronary artery disease (CAD) was present in 19% (n = 63) and CAC was positive in all. In patients without known CAD (n = 261), CAC was present in 70% (n = 182) with a comparable prevalence between men and women, which raised the prevalence of coronary atherosclerosis to 76% (n = 245) for the entire cohort. The median CAC score was 170 (range 1 to 6,157) and largely in multivessel distribution in patients without known CAD. Presence of CAC increased with an increasing number of cardiovascular risk factors. Nevertheless, CAC was present in 58% (n = 40) of patients without conventional cardiovascular risk factors. If CAC score >100 was considered as CAD equivalent as 10-year risk of incident atherosclerotic cardiovascular diseases is >7.5% it would have resulted in higher CAD prevalence of 52% and significant reclassification of CHA2DS2-VASc score in 41% of patients without known CAD. In conclusion, coronary calcium is highly prevalent in AF patients, including those without cardiovascular risk factors. Advanced CAC can potentially shift CHA2DS2-VASc score in many AF patients. Our findings suggest that characterizing CAC in AF may be clinically valuable in thromboembolic risk stratification and management of preventive cardiac therapies.

THE ASSOCIATION OF CARDIOVASCULAR RISK FACTORS AND CALCIUM VOLUME, DENSITY, NUMBER, AND TYPE OF CORONARY VESSEL WITH CALCIFIED PLAQUE IN SOUTH ASIANS LIVING IN THE US AND OTHER RACIAL/ETHNIC GROUPS: COMPARING MASALA AND MESA STUDIES

South Asians (SA) experience disproportionately higher rates of atherosclerotic cardiovascular disease (ASCVD). We evaluated prevalence, patterns, and determinants of advanced coronary artery calcium (CAC) measures (specific coronary vessel involvement, plaque volume and density) in SA versus other

Genotype-driven identification of a molecular network predictive of advanced coronary calcium in ClinSeq\xae and Framingham Heart Study cohorts

BackgroundOne goal of personalized medicine is leveraging the emerging tools of data science to guide medical decision-making. Achieving this using disparate data sources is most daunting for polygenic traits. To this end, we employed random forests (RFs) and neural networks (NNs) for predictive modeling of coronary artery calcium (CAC), which is an intermediate endo-phenotype of coronary artery disease (CAD).MethodsModel inputs were derived from advanced cases in the ClinSeq®; discovery cohort (n=16) and the FHS replication cohort (n=36) from 89th-99th CAC score percentile range, and age-matched controls (ClinSeq®; n=16, FHS n=36) with no detectable CAC (all subjects were Caucasian males). These inputs included clinical variables and genotypes of 56 single nucleotide polymorphisms (SNPs) ranked highest in terms of their nominal correlation with the advanced CAC state in the discovery cohort. Predictive performance was assessed by computing the areas under receiver operating characteristic curves (ROC-AUC).ResultsRF models trained and tested with clinical variables generated ROC-AUC values of 0.69 and 0.61 in the discovery and replication cohorts, respectively. In contrast, in both cohorts, the set of SNPs derived from the discovery cohort were highly predictive (ROC-AUC ≥0.85) with no significant change in predictive performance upon integration of clinical and genotype variables. Using the 21 SNPs that produced optimal predictive performance in both cohorts, we developed NN models trained with ClinSeq®; data and tested with FHS data and obtained high predictive accuracy (ROC-AUC=0.80-0.85) with several topologies. Several CAD and “vascular aging" related biological processes were enriched in the network of genes constructed from the predictive SNPs.ConclusionsWe identified a molecular network predictive of advanced coronary calcium using genotype data from ClinSeq®; and FHS cohorts. Our results illustrate that machine learning tools, which utilize complex interactions between disease predictors intrinsic to the pathogenesis of polygenic disorders, hold promise for deriving predictive disease models and networks.

One-Year Outcomes After Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction With Varying Quantities of Coronary Artery Calcium (from a 13-Year Registry)

Coronary artery calcium (CAC) is associated with poor angiographic results and higher rates of complications after percutaneous coronary intervention (PCI). Limited data are available regarding the impact of angiographically evident CAC on long-term outcomes after primary PCI in patients presenting with ST-segment elevation myocardial infarction (STEMI). In this single-center, registry-based retrospective cohort analysis, we analyzed 2,143 consecutive patients presenting with STEMI who underwent primary PCI within 12 hours of symptom onset. Patients were divided based on degree of CAC (determined by visual inspection of angiograms) as follows: (1) moderate-to-severe CAC (n= 306; 14.3%) and (2) minimal-to-none CAC (n= 1,837; 85.7%). The primary end point was all-cause mortality at 1-year after PCI. Patients with moderate-to-severe CAC were older, women, and had higher rates of hypertension, chronic kidney disease, and peripheral vascular disease. Moderate-to-severe CAC was associated with higher rates of anterior myocardial infarction, advanced Killip class, and poor final angiographic results. At 1-year follow-up, rates of all-cause mortality were higher in the moderate-to-severe CAC cohort than those in the minimal-to-none CAC cohort (8.5% vs 4.7%; p= 0.008). However, after accounting for major clinical and angiographic characteristics, moderate-to-severe CAC on presenting STEMI angiogram was no longer predictive of 1-year all-cause mortality. In conclusion, advanced CAC burden occurs in ∼15% of patients undergoing primary PCI for STEMI and reflects a marker of adverse prognosis late into follow-up after PCI.

Subclinical Vascular Disease and Subsequent Erectile Dysfunction: The Multiethnic Study of Atherosclerosis (MESA).

The association between subclinical cardiovascular disease and subsequent development of erectile dysfunction (ED) remains poorly described. Among multiple subclinical atherosclerosis and vascular dysfunction measurements, coronary artery calcium (CAC) score best predicts ED. After excluding participants taking ED medications at baseline, we studied 1862 men age 45 to 84 years free of known cardiovascular disease from the Multi-Ethnic Study of Atherosclerosis (MESA) with comprehensive baseline subclinical vascular disease phenotyping and ED status assessed at MESA visit 5 (9.4 ± 0.5 years after baseline) using a standardized question on ED symptoms. Multivariable logistic regression was used to assess the associations between baseline measures of vascular disease (atherosclerosis domain: CAC, carotid intima-media thickness, carotid plaque, ankle-brachial index; vascular stiffness/function domain: aortic stiffness, carotid stiffness, brachial flow-mediated dilation) and ED symptoms at follow-up. Mean baseline age was 59.5 ± 9 years, and 839 participants (45%) reported ED symptoms at follow-up. Compared with symptom-free individuals, participants with ED had higher baseline prevalence of CAC score >100 (36.4% vs 17.2%), carotid intima-media thickness Z score >75th percentile (35.3% vs 16.6%), carotid plaque score ≥2 (39% vs 21.1%), carotid distensibility <25th percentile (34.6% vs 17.1%), aortic distensibility <25th percentile (34.2% vs 18.7%), and brachial flow-mediated dilation <25th percentile (28.4% vs 21.3%); all P < 0.01. Only CAC >100 (odds ratio: 1.43, 95% confidence interval: 1.09-1.88) and carotid plaque score ≥2 (odds ratio: 1.33, 95% confidence interval: 1.02-1.73) were significantly associated with ED. Subclinical vascular disease is common in men who later self-report ED. Early detection of subclinical atherosclerosis, particularly advanced CAC and carotid plaque, may provide opportunities for predicting the onset of subsequent vascular ED.

Abstract 18376: Long-term Atherosclerotic Cardiovascular Disease Outcomes Associated With Coronary Artery Calcium

Introduction: Current risk assessment guidelines focus on prevention of atherosclerotic cardiovascular disease (ASCVD), which includes stroke as a primary outcome variable. The long-term (&gt;10 year) relationship of coronary artery calcium (CAC) scoring with stroke has not been previously reported, a limitation cited by the guidelines. Further, large-scale, long-term outcomes studies following CAC are limited. We sought to define the long-term relationship of CAC for stroke and myocardial infarction (MI) in a large screening cohort. Methods: We retrospectively identified 24,246 subjects (mean age 50±8; 70.5% men) without ASCVD or malignancy who underwent CAC scoring (Agatston) at Walter Reed Medical Center from 1997-2009. Subjects were assessed for the primary outcomes of MI and stroke and the secondary outcome of late (&gt;90 days post CAC) coronary revascularization. Outcomes were extracted from the military data repository, a comprehensive healthcare database that captures care provided within and outside of the military healthcare system, and then analyzed using Cox proportional hazard multivariate stepwise regression controlling for baseline risk factors. Results: With a mean follow-up of 11.3±3.6 years there were 546 MI, 947 strokes and 843 late coronary revascularizations. Compared to subjects with no CAC, the adjusted hazard ratios (aHR) for MI were 2.09 (95% CI, 1.68-2.60), 2.01 (1.78-2.28) and 1.91 (1.72-2.11) for CAC scores of 1-100, 101-400 and &gt;400, respectively. CAC of 1-100 was not predictive of stroke compared to no CAC. The aHRs of incident stroke were 1.15 (1.03-1.28) and 1.23 (1.13-1.33) for CAC scores of 101-400 and &gt;400. CAC was strongly associated with late coronary revascularizations. CAC explained the most variance in models for MI and late revascularization and was the third most important predictor for stroke behind age and hypertension. Conclusion: In patients without ASCVD, CAC was a stronger independent predictor of incident MI and late coronary artery revascularization as compared to stroke over one of the longest follow-up intervals reported to date. Advanced CAC (&gt;100) was a modest independent predictor of stroke during the study period. These results support the role of CAC for the prediction of incident ASCVD outcomes.

Atherosclerosis and Vascular Biology

Atherosclerosis and Vascular Biology

Prevalence of Coronary Atherosclerosis in Asymptomatic Middle-Age Men With High Aerobic Fitness

Good aerobic fitness is associated with favorable cardiovascular outcomes. However, it is not well known whether aerobic fitness correlates to the degree of coronary atherosclerosis, which affects cardiovascular prognosis. The aim of the present study was to investigate the relation between aerobic fitness and coronary atherosclerosis. A total of 8,565 apparently healthy men underwent routine health screening, including both cardiopulmonary function testing and coronary calcium scoring. The subjects with clinical cardiovascular disease or abnormal exercise electrocardiographic findings were excluded. A treadmill exercise test was done using the modified Bruce protocol, and the Agatston coronary artery calcium (CAC) score was measured using multidetector computed tomography. Advanced CAC was defined as a score > 75th percentile according to the age group. The mean age was 51 ± 7 years, the average maximum oxygen uptake was 32 ± 5 ml/kg/min, and 34% had a positive CAC score. On univariate analysis, age, blood pressure, lipid profile, body mass index, hemoglobin A1c, fasting glucose, calculated 10-year risk for coronary disease, and maximum oxygen uptake were significantly associated with advanced CAC. In the multiple logistic regression model, the subjects in the highest quartile of the maximum oxygen uptake for age were less likely to have advanced CAC for age compared to those in the lowest quartile (odds ratio 0.60, 95% confidence interval 0.48 to 0.73), with adjustment for age, hypertension, hemoglobin A1c, current smoking, body mass index, and regular exercise habit. In conclusion, greater aerobic fitness was associated with less prevalent advanced coronary atherosclerosis in an asymptomatic male population. The degree of subclinical coronary artery disease might be 1 of the mechanisms connecting aerobic fitness and cardiovascular outcome.

Factors Associated With Presence and Extent of Coronary Calcium in Those Predicted to Be at Low Risk According to Framingham Risk Score (from the Multi-Ethnic Study of Atherosclerosis)

Even among asymptomatic persons at low risk (<10%) according to the Framingham risk score, high coronary artery calcium (CAC) scores signify a greater predicted risk of coronary heart disease events. We sought to determine the noninvasive factors (without radiation exposure) significantly associated with CAC in low-risk, asymptomatic persons. In a cross-sectional analysis, we studied 3,046 participants from the Multi-Ethnic Study of Atherosclerosis at a low 10-year predicted risk (Framingham risk score <10%) of coronary heart disease events. Multivariate logistic regression analysis was used to assess the association of novel markers with the presence of any CAC (CAC >0) and advanced CAC (CAC ≥ 300). A CAC level of >0 and of ≥ 300 was present in 30% and 3.5% of participants, respectively. Factor VIIIc, fibrinogen, and soluble intercellular adhesion molecule were each associated with the presence of CAC (p ≤ 0.02), and C-reactive protein, D-dimer, and the carotid intima-media thickness with advanced CAC (p ≤ 0.03). The base model combining the traditional risk factors had excellent discrimination for advanced CAC (C-statistic 0.808). The addition of the 2 best-fit models combining the biomarkers with or without carotid intima-media thickness improved the c-statistic to 0.822 and 0.820, respectively. All 3 models calibrated well but were similar in estimating the individual risk probabilities for advanced CAC (prevalence 9.97%, 10.63%, and 10.10% in the greatest quartiles of predicted probabilities vs 0.26%, 0.26%, and 0.26% in the lowest quartiles, respectively). In conclusion, in low-risk persons, the traditional risk factors alone predicted advanced CAC with high discrimination and calibration. The biomarker combinations with and without carotid intima-media thickness were also significantly associated with advanced CAC; however, the improvement in the prediction and estimation of the clinical risk were modest compared to the traditional risk factors alone.

General Cardiovascular Risk Profile Identifies Advanced Coronary Artery Calcium and Is Improved by Family History

Background— The General Cardiovascular Risk Profile is a multivariable model that predicts global cardiovascular disease risk. Our goal was to assess the ability of the General Cardiovascular Risk Profile to identify individuals with advanced coronary artery calcification (CAC) and determine whether identification is improved with family history. Methods and Results— Using data from the Multiethnic Study of Atherosclerosis, 3 sex-specific models were developed with ordinal logistic regressions to relate risk factors to CAC scores. Model 1 included covariates in the General Cardiovascular Risk Profile. Then family history was added, defined as having at least 1 first-degree relative with premature coronary heart disease (model 2) or as a weak, moderate, or strong family history based on number of relatives with coronary heart disease, age at onset, and the presence of stroke or diabetes in the family (model 3). For each model, we estimated mathematical CAC risk functions, derived CAC score sheets, evaluated the ability to discriminate persons having positive CAC scores, and assessed reclassification of individuals with low, intermediate, or high probability of CAC &gt;300. Model 1 worked well to identify women and men with positive CAC scores; c-statistics were 0.752 and 0.718 and χ 2 values were 821.2 ( P &lt;0.0001) and 730.6 ( P &lt;0.0001), respectively. Addition of family history improved discrimination and fit of model 1. However, reclassification of participants with advanced CAC was significantly improved with model 3 only. Conclusions— The General Cardiovascular Risk Profile identifies advanced CAC, an emerging indication for aggressive risk factor modification. Incorporation of family history, especially comprehensive familial risk stratification, provides incremental prognostic value.

Assessment of Improved Prediction Beyond Traditional Risk Factors

The moderate predictive performance of cardiovascular disease risk models necessitates more studies that investigate the incremental value of novel biomarkers. In recent years, many new biomarkers have been evaluated for their ability to improve prediction of cardiovascular disease beyond traditional risk factors, including C-reactive protein, coronary artery calcium, and single-nucleotide polymorphisms in the 9p21 region.1 The interest in novel biomarkers is propelled, in part, by emerging discoveries from genomewide association studies of genetic variants associated with risk for many common diseases.2 Nonetheless, family history, an “old” tool in clinical practice—crucial for the diagnosis and management of genetic disorders—has not been adequately explored for its value in risk assessment and prevention of common diseases.3 Positive family history is a strong risk factor for cardiovascular diseases,4,5 reflecting the consequences of genetic and nongenetic risk factors that are shared among relatives. From a practical perspective, family history is a strong determinant of disease that is relatively easy to assess. For this reason, family history is advocated as a useful tool for identifying individuals at increased risk of disease and for tailoring preventive interventions.4,6,7 However, the challenge is to show that this knowledge has clinical utility for improving health.8 Article see p 97 In this issue of Circulation: Cardiovascular Genetics , Scheuner et al9 report the incremental value of adding family history information to the General Cardiovascular Risk Profile to improve identification of individuals with advanced coronary artery calcification. The incremental value of family history in disease prediction is assessed in several questions10: 1. Does family history improve prediction beyond traditional risk factors? 2. Does improved prediction change treatment decisions or health recommendations? 3. Do these changes improve health outcomes or have other benefits? 4. Do the incremental benefits outweigh the extra costs? This evaluation is a stepwise …

Cardiovascular events with absent or minimal coronary calcification: The Multi-Ethnic Study of Atherosclerosis (MESA)

Elevated coronary artery calcium (CAC) is a marker for increase risk of coronary heart disease (CHD). Although most 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 <or=10) or absent CAC (score of zero). Asymptomatic participants in the MESA (N = 6,809) were followed for occurrence of all CHD events (including myocardial infarction, angina, resuscitated cardiac arrest, or CHD death) and hard CHD events (myocardial infarction or CHD death). Time to incident CHD was modeled using age-and gender-adjusted Cox regression. The final study population consisted of 3,923 MESA asymptomatic participants (mean age 58 +/- 9 years, 39% males) who had CAC scores of 0 to 10. Overall, no detectable CAC was seen in 3415 individuals, whereas 508 had CAC scores of 1 to 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 factor-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, 95% CI 1.08-11.77), current smoking (HR 4.93, 95% CI 1.20-20.30), and diabetes (HR 3.09, 95% CI 1.07-8.93) were significant risk factors for events in those with CAC = 0. 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 3-fold increased risk for incident CHD events relative to those with CAC scores of zero.

Smoking cessation and subclinical atherosclerosis—Results from the Heinz Nixdorf Recall Study

BackgroundSmoking accounts for more than 5 million years of potential life lost per year in the US alone. Leading causes of smoking attributable mortality are acute atherothrombotic complications of coronary heart disease (CHD). Smoking cessation is a key issue in preventive medicine, but quantitative data on its benefit for the coronary arteries are sparse. MethodsThe Heinz Nixdorf Recall Study is an ongoing population-based, prospective cohort study, with 4814 participants aged 45–74 years (49.8% men). Baseline data of 4078 participants without history of established coronary heart disease or stroke are included in this report. Electron beam-computed tomography allows for non-invasive quantification of coronary artery calcium (CAC). We estimate the risk-related ageing of coronary arteries from multivariable regression of CAC on smoking behavior, sex, age and risk factors. ResultsSmoking 20 cigarettes per day since the age of 16 is associated with a CAC burden which is found in a person 10 years older who has never smoked (both sexes). Smoking cessation at 45, 55 or 65 leads to CAC at the age of 75 that would have been reached 9, 6 or 3 years earlier, respectively, had smoking been continued. ConclusionsIn individuals without overt CHD, present smokers are about 10 years older in ‘coronary artery age’ than never smokers. The accumulation of CAC is accelerated by smoking and slows down after smoking cessation, but advanced CAC is persistent for a long period. These quantitative findings strongly support smoking cessation measures as early as possible, to prevent accelerated arterial ageing.

Coronary Artery Calcium Scores and Risk for Cardiovascular Events in Women Classified as “Low Risk” Based on Framingham Risk Score

To assess coronary artery calcium (CAC) score and subsequent risk for coronary heart disease (CHD) and cardiovascular (CVD) events among asymptomatic women judged to be at low risk by the Framingham risk score (FRS), a common approach for determining 10-year absolute risk for CHD. Based on population survey data, 95% of American women are considered at low risk based on FRS. The Multi-Ethnic Study of Atherosclerosis (MESA) included 3601 women aged 45 to 84 years at baseline. The CAC score was measured by coronary computed tomography. Cox proportional hazard models were used to examine the CHD and CVD risk associated with CAC score among women classified as "low risk" based on FRS. Excluding women with diabetes and those older than 79 years, 90% of women in MESA (mean +/- SD age, 60 +/- 9 years) were classified as "low risk" based on FRS. The prevalence of CAC (CAC score > 0) in this low-risk subset was 32% (n = 870). Compared with women with no detectable CAC, low-risk women with a CAC score greater than 0 were at increased risk for CHD (hazard ratio, 6.5; 95% confidence interval, 2.6-16.4) and CVD events (hazard ratio, 5.2; 95% confidence interval, 2.5-10.8). In addition, advanced CAC (CAC score > or = 300) was highly predictive of future CHD and CVD events compared with women with nondetectable CAC and identified a group of low-risk women with a 6.7% and 8.6% absolute CHD and CVD risk, respectively, over a 3.75-year period. The presence of CAC in women considered to be at low risk based on FRS was predictive of future CHD and CVD events. Advanced CAC identified a subset of low-risk women at higher risk based on current risk stratification strategies.

Relation of degree of physical activity to coronary artery calcium score in asymptomatic individuals with multiple metabolic risk factors

Lack of physical activity (PA) increases risk of coronary heart disease. Metabolic risk factors increase the risk of coronary heart disease and development of advanced coronary artery calcium (CAC). We hypothesized that, in a population with multiple metabolic risk factors (> or =2), the degree of PA would be inversely associated with the degree and prevalence of CAC. After excluding subjects who had known diabetes and coronary heart disease, we studied 779 asymptomatic patients referred for electron beam tomography. All patients had > or =2 of the following metabolic risk factors: blood pressure > 130/85 mm Hg, serum triglycerides >150 mg/dl, serum high-density lipoprotein < 40 and < 50 mg/dl in men and women, respectively, and body mass index >30 kg/m(2). Advanced CAC was defined as a calcium score >75th percentile based on gender and age. In the study, 37% patients were sedentary, 26% engaged in moderate-duration (< 30 minutes 1 to 2 times/week) PA, and 37% engaged in long-duration (> or =30 minutes > or =3 times/week) PA. The median CAC scores were 24 (sedentary), 18 (moderate PA), and 11 (long-duration PA; p <0.002). Advanced CAC was prevalent in 26% of sedentary patients, 24% of patients who performed moderate PA, and 16% of patients who engaged in long-duration PA (p <0.05). On logistic regression analysis, long-duration PA had an independent inverse association with advanced CAC. Thus, asymptomatic patients who have > or =2 metabolic risk factors and who regularly engage in long-duration PA have a lower prevalence of CAC than do those who are sedentary or participate in moderate-duration PA.