Noncoronary Measures Enhance the Predictive Value of Cardiac CT Above Traditional Risk Factors and CAC Score in the General Population.
The aim of this study was to determine whether noncoronary measures from cardiac computed tomography (CT) may enhance the prognostic value of this imaging technology.
When cardiac CT is performed for quantification of coronary artery calcium (CAC) score, information on other cardiac and thoracic structures is available.
Participants without known cardiovascular disease from the prospective population based Heinz Nixdorf Recall study underwent noncontrast cardiac CT for CAC score quantification. From CT, epicardial adipose tissue (EAT) volume, left ventricular and left atrial (LA) axial area index, ascending and descending aortic diameters, as well as aortic valve, mitral ring, and thoracic aortic calcification (TAC) were assessed. Incident cardiovascular events included myocardial infarction, stroke, and cardiovascular death. The prognostic value of CT-derived parameters was assessed by Cox regression analysis, receiver operating characteristics, and net reclassification improvement.
From 3,630 subjects (59 ± 8 years of age, 46% male), 241 (6.6%) developed a cardiovascular event during 9.9 ± 2.6 years of follow-up. In multivariable Cox regression analysis including Framingham Risk Score, CAC (as log[CAC + 1]), and CT parameters, LA index (hazard ratio [HR]: 1.22 [95% confidence interval [CI]: 1.05 to 1.41] per SD; p = 0.010) and EAT volume (HR: 1.15 [95% CI: 1.01 to 1.30] per SD; p = 0.031) were significantly associated with incident events. In addition, presence of TAC showed an elevated event rate (HR: 1.33 [95% CI: 0.97 to 1.81]; p = 0.08), whereas all other CT-derived parameters showed no relevant association. The LA index, EAT volume, and presence of TAC together improved the prediction of events over Framingham Risk Score and CAC in receiver operating characteristics analysis (area under the curve: 0.749 to 0.764; p = 0.011), and let to a significant net reclassification improvement (HR: 38.0%; 95% CI: 25.1% to 50.8%).
Assessment of LA index, EAT volume, and TAC from non-contrast-enhanced cardiac CT improves the prediction of incident hard cardiovascular events above CAC and established risk factors, indicating that quantification of these noncoronary measures may improve the prognostic value of this imaging technology.
Mahabadi AA
，Lehmann N
，Möhlenkamp S
，Pundt N
，Dykun I
，Roggenbuck U
，Moebus S
，Jöckel KH
，Erbel R
，Kälsch H
，Heinz Nixdorf Investigative Group
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Computed tomography-derived cardiovascular risk markers, incident cardiovascular events, and all-cause mortality in nondiabetics: the Multi-Ethnic Study of Atherosclerosis.
We assess the improvement in discrimination afforded by the addition of the computed tomography risk markers thoracic aorta calcium (TAC), aortic valve calcification (AVC), mitral annular calcification (MAC), pericardial adipose tissue volume (PAT), and liver attenuation (LA) to the Framingham risk score (FRS) + coronary artery calcium (CAC) for incident coronary heart disease (CHD) and incident cerebrovascular disease (CVD) in a multiethnic cohort.
A total of 5745 participants were enrolled, with 2710 at intermediate Framingham risk, 210 CVD events, and 155 CHD events). Over 9 years of follow up, 251 had adjudicated CHD, 346 had CVD events, and 321 died. The data were analysed using 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, incident CHD, and mortality, and CAC had the strongest association. When added to the FRS, CAC had the highest area under the curve (AUC) for the prediction of incident CVD and incident CHD; 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.
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 CVD and incident CHD. Compared with FRS + CAC, the addition of TAC, AVC, MAC, PAT, or LA individually to FRS + CAC worsens the discrimination for incident CVD and incident CHD. These risk markers are unlikely to be useful for improving cardiovascular risk prediction.
Yeboah J
，Carr JJ
，Terry JG
，Ding J
，Zeb I
，Liu S
，Nasir K
，Post W
，Blumenthal RS
，Budoff MJ
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Coronary artery calcification outperforms thoracic aortic calcification for the prediction of myocardial infarction and all-cause mortality: the Heinz Nixdorf Recall Study.
Thoracic aortic calcification (TAC) is associated with cardiovascular (CV) risk factors and prevalent coronary artery disease. We aimed to investigate whether TAC burden is associated with incident myocardial infarction (MI) and all-cause mortality in subjects without known coronary artery disease and to determine its predictive value for these endpoints.
We used longitudinal data from the population-based prospective Heinz Nixdorf Recall Study. TAC and coronary artery calcification (CAC) scores were quantified from non-contrast enhanced electron beam computed tomography. Cox regression analysis was used to determine the association of TAC with incident MI or all-cause mortality, adjusting for CV risk factors and additionally for CAC-score in a separate step. Predictive value of TAC was assessed using Harrell's C index.
Overall, 4040 participants without known coronary artery disease (59.4 years, 47% male) were included in this analysis. During a mean follow-up of 8.0 ± 1.5 years, we observed 136 coronary events and 304 deaths. In subjects with TAC>0 vs TAC = 0, the incidence of nonfatal MI was 4.2% vs 2.0% (p < 0.001), and all-cause mortality was 8.9% vs 5.2% (p < 0.001). Risks for coronary events and for all-cause mortality increased significantly with increasing TAC-scores (p < 0.001). After adjustment for CV risk factors, body mass index (BMI) and CV medication, a unit increase of TAC on a logarithmic scale (log(TAC + 1)) remained independently associated with coronary events (hazard ratio (HR) (95% confidence interval (CI)): 1.06 (1.00-1.14), p = 0.03) and all-cause mortality (HR 1.06 (1.01-1.12), p < 0.01). After further adjustment for CAC-score (log(CAC + 1)), hazard ratios were attenuated for both endpoints (coronary events: 0.98 (0.91-1.05), p = 0.56, all-cause mortality: 1.03 (0.98-1.08), p = 0.33). When adding log(TAC + 1) to the model containing traditional risk factors and CAC, Harrell's C indices did not increase for coronary events (0.773-0.772, p = 0.66) or for all-cause mortality (0.741-0.743, p = 0.49).
TAC is associated with incident coronary events and all-cause mortality independent of traditional CV risk factors in the general population. TAC fails to improve event prediction over CAC in both coronary events and all-cause mortality.
Kälsch H
，Lehmann N
，Berg MH
，Mahabadi AA
，Mergen P
，Möhlenkamp S
，Bauer M
，Kara K
，Dragano N
，Hoffmann B
，Moebus S
，Schmermund A
，Stang A
，Jöckel KH
，Erbel R
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Cardiovascular Event Prediction and Risk Reclassification by Coronary, Aortic, and Valvular Calcification in the Framingham Heart Study.
We determined whether vascular and valvular calcification predicted incident major coronary heart disease, cardiovascular disease (CVD), and all-cause mortality independent of Framingham risk factors in the community-based Framingham Heart Study.
Coronary artery calcium (CAC), thoracic and abdominal aortic calcium, and mitral or aortic valve calcium were measured by cardiac computed tomography in participants free of CVD. Participants were followed for a median of 8 years. Multivariate Cox proportional hazards models were used to determine association of CAC, thoracic and abdominal aortic calcium, and mitral and aortic valve calcium with end points. Improvement in discrimination beyond risk factors was tested via the C-statistic and net reclassification index. In this cohort of 3486 participants (mean age 50±10 years; 51% female), CAC was most strongly associated with major coronary heart disease, followed by major CVD, and all-cause mortality independent of Framingham risk factors. Among noncoronary calcifications, mitral valve calcium was associated with major CVD and all-cause mortality independent of Framingham risk factors and CAC. CAC significantly improved discriminatory value beyond risk factors for coronary heart disease (area under the curve 0.78-0.82; net reclassification index 32%, 95% CI 11-53) but not for CVD. CAC accurately reclassified 85% of the 261 patients who were at intermediate (5-10%) 10-year risk for coronary heart disease based on Framingham risk factors to either low risk (n=172; no events observed) or high risk (n=53; observed event rate 8%).
CAC improves discrimination and risk reclassification for major coronary heart disease and CVD beyond risk factors in asymptomatic community-dwelling persons and accurately reclassifies two-thirds of the intermediate-risk population.
Hoffmann U
，Massaro JM
，D'Agostino RB Sr
，Kathiresan S
，Fox CS
，O'Donnell CJ
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《Journal of the American Heart Association》
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