Thoracic aortic calcium, cardiovascular disease events, and all-cause mortality in asymptomatic individuals with zero coronary calcium: The Multi-Ethnic Study of Atherosclerosis (MESA).
TAC is associated with incident CVD and all-cause mortality. Nevertheless, the independent 10-year prognostic value of TAC in individuals with CAC = 0 beyond traditional risk factors is not well established.
3415 MESA participants with baseline CAC = 0 were followed for CHD, CVD events and all-cause mortality. TAC was measured in the ascending and descending aorta in all participants and quantified using Agatston's score. Multivariable Cox proportional hazards regression models were used to study the associations between TAC and incident CHD, CVD events and all-cause mortality. Likelihood ratio tests were used to compare prediction models including traditional risk factors plus TAC versus risk factors alone.
406 participants (11.9%) had TAC>0 at baseline. Over a median follow-up of 11.3 years, unadjusted event rates per 1000 person-years were higher in TAC>0 than in TAC = 0 participants: CHD 2.18 vs. 2.03; CVD 6.85 vs. 3.42; all-cause mortality 12.84 vs. 4.96. However, in multivariable Cox regression analyses adjusting for CVD risk factors, neither TAC>0, TAC>100 nor log(TAC+1) were independently associated with any of the study outcomes, nor improved their prediction compared to traditional risk factors alone (p value of likelihood ratio tests >0.05).
In a multi-ethnic, modern US population of asymptomatic individuals with CAC = 0 at baseline, the prevalence of TAC>0 was low, and TAC did not improve 10-year estimation of prognosis beyond traditional risk factors. In the presence of CAC = 0, measurement of TAC is unlikely to provide sufficient additional prognostic information to further improve risk assessment.
Kim J
，Budoff MJ
，Nasir K
，Wong ND
，Yeboah J
，Al-Mallah MH
，Shea S
，Dardari ZA
，Blumenthal RS
，Blaha MJ
，Cainzos-Achirica M
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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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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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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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