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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Comparing coronary artery calcium and thoracic aorta calcium for prediction of all-cause mortality and cardiovascular events on low-dose non-gated computed tomography in a high-risk population of heavy smokers.
Coronary artery calcium (CAC) and thoracic aorta calcium (TAC) can be detected simultaneously on low-dose, non-gated computed tomography (CT) scans. CAC has been shown to predict cardiovascular (CVD) and coronary (CHD) events. A comparable association between TAC and CVD events has yet to be established, but TAC could be a more reproducible alternative to CAC in low-dose, non-gated CT. This study compared CAC and TAC as independent predictors of all-cause mortality and cardiovascular events in a population of heavy smokers using low-dose, non-gated CT.
Within the NELSON study, a population-based lung cancer screening trial, the CT screen group consisted of 7557 heavy smokers aged 50-75 years. Using a case-cohort study design, CAC and TAC scores were calculated in a total of 958 asymptomatic subjects who were followed up for all-cause death, and CVD, CHD and non-cardiac events (stroke, aortic aneurysm, peripheral arterial occlusive disease). We used Cox proportional-hazard regression to compute hazard ratios (HRs) with adjustment for traditional cardiovascular risk factors.
A close association between the prevalence of TAC and increasing levels of CAC was established (p<0.001). Increasing CAC and TAC risk categories were associated with all-cause mortality (p for trend=0.01 and 0.001, respectively) and CVD events (p for trend <0.001 and 0.03, respectively). Compared with the lowest quartile (reference category), multivariate-adjusted HRs across categories of CAC were higher (all-cause mortality, HR: 9.13 for highest quartile; CVD events, HR: 4.46 for highest quartile) than of TAC scores (HR: 5.45 and HR: 2.25, respectively). However, TAC is associated with non-coronary events (HR: 4.69 for highest quartile, p for trend=0.01) and CAC was not (HR: 3.06 for highest quartile, p for trend=0.40).
CAC was found to be a stronger predictor than TAC of all-cause mortality and CVD events in a high-risk population of heavy smokers scored on low-dose, non-gated CT. TAC, however, is stronger associated with non-cardiac events than CAC and could prove to be a preferred marker for these events.
Jacobs PC
,Prokop M
,van der Graaf Y
,Gondrie MJ
,Janssen KJ
,de Koning HJ
,Isgum I
,van Klaveren RJ
,Oudkerk M
,van Ginneken B
,Mali WP
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Greater Volume but not Higher Density of Abdominal Aortic Calcium Is Associated With Increased Cardiovascular Disease Risk: MESA (Multi-Ethnic Study of Atherosclerosis).
Abdominal aortic calcium (AAC) and coronary artery calcium (CAC) independently and similarly predict cardiovascular disease (CVD) events. The standard AAC and CAC score, the Agatston method, upweights for greater calcium density, thereby modeling higher calcium density as a CVD hazard.
Computed tomography scans were used to measure AAC and CAC volume and density in a multiethnic cohort of community-dwelling individuals, and Cox proportional hazard was used to determine their independent association with incident coronary heart disease (CHD, defined as myocardial infarction, resuscitated cardiac arrest, or CHD death), cardiovascular disease (CVD, defined as CHD plus stroke and stroke death), and all-cause mortality. In 997 participants with Agatston AAC and CAC scores >0, the mean age was 66±9 years, and 58% were men. During an average follow-up of 9 years, there were 77 CHD, 118 CVD, and 169 all-cause mortality events. In mutually adjusted models, additionally adjusted for CVD risk factors, an increase in ln(AAC volume) per standard deviation was significantly associated with increased all-cause mortality (hazard ratio=1.20; 95% confidence interval, 1.08-1.33; P<0.01) and an increased ln(CAC volume) per standard deviation was significantly associated with CHD (hazard ratio=1.17; 95% confidence interval, 1.04-1.59; P=0.02) and CVD (hazard ratio=1.20; 95% confidence interval, 1.05-1.36; P<0.01). In contrast, both AAC and CAC density were not significantly associated with CVD events.
The Agatston method of upweighting calcium scores for greater density may be inappropriate for CVD risk prediction in both the abdominal aorta and coronary arteries.
Forbang NI
,Michos ED
,McClelland RL
,Remigio-Baker RA
,Allison MA
,Sandfort V
,Ix JH
,Thomas I
,Rifkin DE
,Criqui MH
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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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