Association of progressive thoracic aortic calcification with future cardiovascular events and all-cause mortality: ability to improve risk prediction? Results of the Heinz Nixdorf Recall (HNR) study.

Thoracic aortic calcification (TAC) is measured by computed tomography (CT). We investigated the association of TAC-progression with incident cardiovascular (CV) events and all-cause mortality in a population-based cohort and to determine its predictive value for these endpoints. In 3080 participants (45-74 years, 53.6% women), risk factors and TAC via CT were measured at baseline and at a second examination after 5.1 ± 0.3 years. Hard coronary, hard CV events as well as CV events including revascularization and all-cause mortality were recorded during a follow-up time of 7.8 ± 2.2 years after the second CT scan. Cox regression analysis determined the association of TAC-progression with observed endpoints. The predictive value of TAC-progression was assessed using Harrell's C index. We observed 81 hard coronary, 154 hard CV, 231 CV events including revascularization, and 266 deaths. In the crude analysis, event rates increased continuously with the level of TAC-change over 5 years for all endpoints. After adjustment, the significant association of TAC-progression with hard CV events [hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.05-1.57] and all-cause mortality (HR 1.34, 95% CI 1.14-1.58) persisted, per one standard deviation increase in TAC-progression (log(TAC + 1)). Regarding aortic segments separately, HRs were consistently higher for descending thoracic aorta. When adding TAC (baseline and progression) to the model containing classical risk factors and coronary artery calcification (CAC), Harrell's C indices did not increase for any of the observed endpoints. TAC-progression is associated with incident hard CV events and all-cause mortality but fails to improve event prediction over CAC.

Kälsch H ，Mahabadi AA ，Moebus S ，Reinsch N ，Budde T ，Hoffmann B ，Stang A ，Jöckel KH ，Erbel R ，Lehmann N ... -  《-》

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 ... -  《-》

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 ... -  《-》

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 ... -  《-》

Sex Differences in Coronary Artery and Thoracic Aorta Calcification and Their Association With Cardiovascular Mortality in Heavy Smokers.

The aim of this study was to investigate sex differences in the prevalence, extent, and association of coronary artery calcium (CAC) and thoracic aorta calcium (TAC) scores with cardiovascular mortality in a population eligible for lung screening. CAC and TAC scores derived from chest computed tomography (CT) might be useful biomarkers for individualized cardiovascular disease prevention and could be especially relevant in high-risk populations such as heavy smokers. Therefore, it is important to know the prevalence of arterial calcifications in male and female heavy smokers, and if there are differences in the predictive value calcifications carry. We performed a nested case-control study with 5,718 participants of the CT arm of the NLST (National Lung Screening Trial). Prevalence and extent of CAC and TAC were resampled to the full cohort to provide unbiased estimates of the typical calcium burden of male and female heavy smokers. Weighted Cox proportional hazards regression was used to assess differences in the association of CAC and TAC scores with all-cause and cardiovascular mortality. CAC was substantially more common and more severe in men (prevalence: 81% vs. 60%; median volume: 104 mm³ vs. 12 mm³). Women had CAC comparable to that of men who were 10 years younger. TAC was equally common in men and women, with a tendency to be more pronounced in women (prevalence: 92% vs. 93%; median volume: 388 mm³ vs. 404 mm³). Both types of calcification were associated with increased cardiovascular and all-cause mortality. TAC scores improved the prediction of coronary heart disease mortality over CAC in men, but not in women. In both sexes, TAC, but not CAC, was associated with cardiovascular mortality other than coronary heart disease. CAC develops later in women, whereas TAC develops equally in both sexes. CAC is strongly associated with coronary heart disease, whereas TAC is especially associated with extracardiac vascular mortality in either sex.

Lessmann N ，de Jong PA ，Celeng C ，Takx RAP ，Viergever MA ，van Ginneken B ，Išgum I ... -  《-》