Background

The coronary artery calcium (CAC) score is an independent predictor of coronary heart disease. We sought to combine information from the CAC score with information from conventional cardiac risk factors to produce post-test risk estimates, and to determine whether the score may add clinically useful information.

Methods

We measured the independent cross-sectional associations between conventional cardiac risk factors and the CAC score among asymptomatic persons referred for non-contrast electron beam computed tomography. Using the resulting multivariable models and published CAC score-specific relative risk estimates, we estimated post-test coronary heart disease risk in a number of different scenarios.

Results

Among 9341 asymptomatic study participants (age 35-88 years, 40% female), we found that conventional coronary heart disease risk factors including age, male sex, self-reported hypertension, diabetes and high cholesterol were independent predictors of the CAC score, and we used the resulting multivariable models for predicting post-test risk in a variety of scenarios. Our models predicted, for example, that a 60-year-old non-smoking non-diabetic women with hypertension and high cholesterol would have a 47% chance of having a CAC score of zero, reducing her 10-year risk estimate from 15% (per Framingham) to 6-9%; if her score were over 100, however (a 17% chance), her risk estimate would be markedly higher (25-51% in 10 years). In low risk scenarios, the CAC score is very likely to be zero or low, and unlikely to change management.

Conclusion

Combining information from the CAC score with information from conventional risk factors can change assessment of coronary heart disease risk to an extent that may be clinically important, especially when the pre-test 10-year risk estimate is intermediate. The attached spreadsheet makes these calculations easy.

Background

Cardiovascular screening of women using traditional risk factors has been challenging, with results often classifying a majority of women as lower risk than men. The aim of this report was to determine the long-term prognosis of asymptomatic women and men classified at low-intermediate risk undergoing screening with coronary artery calcium (CAC) scoring.

Methods and results

A total of 2363 asymptomatic women and men with traditional risk factors aggregating into a low-intermediate Framingham risk score (6%-9.9%; 10-year predicted risk) underwent CAC scanning. Individuals were followed up for a median of 14.6 years. We estimated all-cause mortality using Cox proportional hazards models; hazard ratios with 95% confidence intervals were calculated. The area under the curve from a receiver operating characteristics curve analysis was calculated. There were 1072 women who were older (55.6 years) when compared with the 1291 men (46.7 years; P<0.0001), resulting in a greater prevalence and extent of CAC; 18.8% of women and 15.1% of men had a CAC score ≥100 (P=0.029). This older group of women had a 1.44-fold higher 15-year adjusted mortality hazard when compared with men (P=0.022). For women, the 15-year mortality ranged from 5.0% for those with a CAC score of 0 to 23.5% for those with a CAC score ≥400 (P<0.001). For men, the 15-year mortality ranged from 3.5% for those with a CAC score of 0 to 18.0% for those with a CAC score ≥400 (P<0.001). Women with CAC scores >10 had a higher mortality risk when compared with men.

Conclusions

Our findings extend previous work that CAC effectively identifies high-risk women with a low-intermediate risk factor burden. These data require validation in external cohorts but lend credence to the use of CAC in women to improve risk detection algorithms that are currently based on traditional risk factors.

Objective

Minimal data are available regarding the long-term mortality risk of subclinical atherosclerosis using coronary artery calcium (CAC) scoring among patients with a family history (FH) of coronary artery disease (CAD). The aim of the present analysis was to assess the prognostic utility of CAC scoring among cohorts of young and older patients with and without a FH of CAD.

Methods

A total of 9715 consecutive asymptomatic patients, free of known CAD, underwent CAC scoring for cardiovascular risk assessment. The primary end point was all-cause mortality, with a median follow-up of 14.6 years. Unadjusted and risk-factor adjusted Cox proportional hazard modelling was employed. We calculated the area under the curve (AUC) from receiver operating characteristics analysis.

Results

15-year all-cause mortality rates ranged from 4.7% to 25.0% for FH patients and from 5.0% to 38.0% for non-FH patients with CAC scores of 0 to >400 (p<0.0001). Effect modification by age altered the mortality risk of CAC among FH patients. For patients aged >60 years with FH of CAD, there was a significant improvement in the AUC with CAC over CAD risk factors (AUC: 0.539 vs 0.725, p<0.001). No such improvement was observed in FH patients aged <60 years (AUC: 0.636 vs 0.626, p=0.67).

Conclusion

CAC effectively stratified mortality risk of patients with and without FH of CAD. However, for younger and lower-risk FH cohorts, CAC screening did not provide additive prognostic information beyond that of the traditional cardiac risk factors.

Objective

It is unclear whether coronary artery calcium (CAC) is effective for risk stratifying patients with diabetes in whom treatment decisions are uncertain.

Research design and methods

Of 44,052 asymptomatic individuals referred for CAC testing, we studied 2,384 individuals with diabetes. Subjects were followed for a mean of 5.6 ± 2.6 years for the end point of all-cause mortality.

Results

There were 162 deaths (6.8%) in the population. CAC was a strong predictor of mortality across age-groups (age <50, 50-59, ≥60), sex, and risk factor burden (0 vs. ≥1 additional risk factor). In individuals without a clear indication for aspirin per current guidelines, CAC stratified risk, identifying patients above and below the 10% risk threshold of presumed aspirin benefit.

Conclusions

CAC can help risk stratify individuals with diabetes and may aid in selection of patients who may benefit from therapies such as low-dose aspirin for primary prevention.

Objectives

The purpose of this study was to examine sex-specific associations, if any, between per-vessel coronary artery disease (CAD) extent and the risk of major adverse cardiovascular events (MACE) over a 5-year study duration.

Background

The presence and extent of CAD diagnosed by coronary computed tomography angiography (CTA) is associated with increased short-term mortality and MACE. Nevertheless, some uncertainty remains regarding the influence of sex on these findings.

Methods

5,632 patients (mean age 60.2 ± 11.8 years, 36.5% women) from the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry were followed for 5 years. Obstructive CAD was defined as ≥50% luminal stenosis in a coronary vessel. Using Cox proportional hazards models, we calculated the hazard ratio (HR) for incident MACE among women and men, defined as death or myocardial infarction.

Results

Obstructive CAD was more prevalent in men (42% vs. 26%; p < 0.001), whereas women were more likely to have normal coronary arteries (43% vs. 27%; p < 0.001). There were a total of 798 incident MACE events. After adjustment, there was a strong association between increased MACE risk and nonobstructive CAD (HR: 2.16 for women, 2.56 for men; p < 0.001 for both), obstructive 1-vessel CAD (HR: 3.69 and 2.66; p < 0.001), 2-vessel CAD (HR: 3.92 and 3.55; p < 0.001), and 3-vessel/left main CAD (HR: 5.94 and 4.44; p < 0.001). Further exploratory analyses of atherosclerotic burden did not identify sex-specific patterns predictive of MACE.

Conclusions

In a large prospective coronary CTA cohort followed long-term, we did not observe an interaction of sex for the association between MACE risk and increased per-vessel extent of obstructive CAD. These findings highlight the persistent prognostic significance of anatomic CAD subsets as detected by coronary CTA for the risk of MACE in both women and men.

Objective

We sought to examine the risk of mortality associated with nonobstructive coronary artery disease (CAD) and to determine the impact of baseline statin and aspirin use on mortality.

Approach and results

Coronary computed tomographic angiography permits direct visualization of nonobstructive CAD. To date, the prognostic implications of nonobstructive CAD and the potential benefit of directing therapy based on nonobstructive CAD have not been carefully examined. A total of 27 125 consecutive patients who underwent computed tomographic angiography (12 enrolling centers and 6 countries) were prospectively entered into the COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter (CONFIRM) registry. Patients, without history of previous CAD or obstructive CAD, for whom baseline statin and aspirin use was available were analyzed. Each coronary segment was classified as normal or nonobstructive CAD (1%-49% stenosis). Patients were followed up for a median of 27.2 months for all-cause mortality. The study comprised 10 418 patients (5712 normal and 4706 with nonobstructive CAD). In multivariable analyses, patients with nonobstructive CAD had a 6% (95% confidence interval, 1%-12%) higher risk of mortality for each additional segment with nonobstructive plaque (P=0.021). Baseline statin use was associated with a reduced risk of mortality (hazard ratio, 0.44; 95% confidence interval, 0.28-0.68; P=0.0003), a benefit that was present for individuals with nonobstructive CAD (hazard ratio, 0.32; 95% confidence interval, 0.19-0.55; P<0.001) but not for those without plaque (hazard ratio, 0.66; 95% confidence interval, 0.30-1.43; P=0.287). When stratified by National Cholesterol Education Program/Adult Treatment Program III, no mortality benefit was observed in individuals without plaque. Aspirin use was not associated with mortality benefit, irrespective of the status of plaque.

Conclusions

The presence and extent of nonobstructive CAD predicted mortality. Baseline statin therapy was associated with a significant reduction in mortality for individuals with nonobstructive CAD but not for individuals without CAD.

Clinical trial registration

URL: http://clinicaltrials.gov/. Unique identifier NCT01443637.

Aims

Coronary computed tomographic angiography (CCTA) has become an important tool for non-invasive diagnosis of coronary artery disease (CAD). Coronary dominance can be assessed by CCTA; however, the predictive value of coronary dominance is controversially discussed. The aim of this study was to evaluate the prevalence and prognosis of coronary dominance in a large prospective, international multicentre cohort of patients undergoing CCTA.

Methods and results

The study population consisted of 6382 patients with or without CAD (47% females, 53% males, mean age 56.9 ± 12.3 years) who underwent CCTA and were followed over a period of 60 months. Right or left coronary dominance was determined. Right dominance was present in 91% (n = 5817) and left in 9% (n = 565) of the study population. At the end of follow-up, outcome in patients with obstructive CAD (>50% luminal stenosis) and right dominance was similar compared with patients with left dominance [hazard ratio (HR) 0.46, 95% CI 0.16-1.32, P = 0.15]. Furthermore, no differences were observed for the type of coronary dominance in patients with non-obstructive CAD (HR 0.95, 95% CI 0.41-2.21, P = 0.8962) or normal coronary arteries (HR 1.04, 95% CI 0.68-1.59, P = 0.9). Subgroup analysis in patients with left main disease revealed an elevated hazard of the combined endpoint for left dominance (HR 6.45, 95% CI 1.66-25.0, P = 0.007), but not for right dominance.

Conclusion

In our study population, survival after 5 years of follow-up did not differ significantly between patients with left or right coronary dominance. Thus, assessment of coronary vessel dominance by CCTA may not enhance risk stratification in patients with normal coronary arteries or obstructive CAD, but may add prognostic information for specific subpopulations.

Aim

Prior evidence observed no predictive utility of coronary CT angiography (CCTA) over the coronary artery calcium score (CACS) and the Framingham risk score (FRS), among asymptomatic individuals. Whether the prognostic value of CCTA differs for asymptomatic patients, when stratified by CACS severity, remains unknown.

Methods and results

From a 12-centre, 6-country observational registry, 3217 asymptomatic individuals without known coronary artery disease (CAD) underwent CACS and CCTA. Individuals were categorized by CACS as: 0-10, 11-100, 101-400, 401-1000, >1000. For CCTA analysis, the number of obstructive vessels-as defined by the per-patient presence of a ≥50% luminal stenosis-was used to grade the extent and severity of CAD. The incremental prognostic value of CCTA over and above FRS was measured by the likelihood ratio (LR) χ(2), C-statistic, and continuous net reclassification improvement (NRI) for prediction, discrimination, and reclassification of all-cause mortality and non-fatal myocardial infarction. During a median follow-up of 24 months (25th-75th percentile, 17-30 months), there were 58 composite end-points. The incremental value of CCTA over FRS was demonstrated in individuals with CACS >100 (LRχ(2), 25.34; increment in C-statistic, 0.24; NRI, 0.62, all P < 0.001), but not among those with CACS ≤100 (all P > 0.05). For subgroups with CACS >100, the utility of CCTA for predicting the study end-point was evident among individuals whose CACS ranged from 101 to 400; the observed predictive benefit attenuated with increasing CACS.

Conclusion

Coronary CT angiography provides incremental prognostic utility for prediction of mortality and non-fatal myocardial infarction for asymptomatic individuals with moderately high CACS, but not for lower or higher CACS.

Extent of coronary atherosclerotic disease (CAD) burden on coronary computed tomography angiography (CCTA) as measured by segment involvement score (SIS) has a prognostic value. We sought to investigate the incremental prognostic value of 'age adjusted SIS' (aSIS), which may be a marker of premature atherosclerosis and vascular age. Consecutive patients were prospectively enrolled into the CONFIRM (Coronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicentre) multinational observational study. Patients were followed for the outcome of all-cause death. aSIS was calculated on CCTA for each patient, and its incremental prognostic value was evaluated. A total of 22,211 patients [mean age 58.5 ± 12.7 years, 55.8% male) with a median follow-up of 27.3 months (IQR 17.8, 35.4)] were identified. After adjustment for clinical factors and presence of obstructive CAD, higher aSIS was associated with increased death on multivariable analysis, with hazard ratio (HR) 2.40 (1.83-3.16, p < 0.001), C-statistic 0.723 (0.700-0.756), net reclassification improvement (NRI) 0.36 (0.26-0.47, p < 0.001), and relative integrated discrimination improvement (IDI) 0.33 (p = 0.009). aSIS had HR 3.48 (2.33-5.18, p < 0.001) for mortality in those without obstructive CAD, compared to HR 1.79 (1.25-2.58, p = 0.02) in those with obstructive CAD. In conclusion, aSIS has an incremental prognostic value to traditional risk factors and obstructive CAD, and may enhance CCTA risk stratification.

Patients with obstructive (≥50% stenosis) left main (LM) coronary artery disease (CAD) are at high risk for adverse events; prior studies have also documented worse outcomes among women than men with severe multivessel/LM CAD. However, the prognostic significance of nonobstructive (1%-49% stenosis) LM CAD, including sex-specific differences, has not been previously examined. In the long-term CONFIRM (Coronary CT Angiography Evaluation For Clinical Outcomes: An International Multicenter) registry, patients underwent elective coronary computed tomographic angiography for suspected CAD and were followed for 5 years. After excluding those with obstructive LM CAD, 5166 patients were categorized as having normal LM or nonobstructive LM (18% of cohort). Cumulative 5-year incidence of death, myocardial infarction, or revascularization was higher among patients with nonobstructive LM than normal LM in both women and men: women (34.3% versus 15.4%; P<0.0001); men (24.6% versus 18.2%; P<0.0001). A significant interaction existed between sex and LM status for the composite outcome (P=0.001). In multivariable Cox regression, the presence of nonobstructive LM plaque increased the risk for the composite outcome in women (adjusted hazard ratio, 1.48; P=0.005) but not in men (adjusted hazard ratio, 0.98, P=0.806). In subgroup analysis, women with nonobstructive LM CAD had a nearly 80% higher risk for events than men with nonobstructive LM CAD (adjusted hazard ratio, 1.78; P=0.017); sex-specific interactions were not observed across other patterns (eg, location or extent) of nonobstructive plaque. Nonobstructive LM CAD was frequently detected on coronary computed tomographic angiography and strongly associated with adverse events among women. Recognizing the sex-specific prognostic significance of nonobstructive LM plaque may augment risk stratification efforts.