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Observational Study
. 2014 Nov 7;35(42):2960-71.
doi: 10.1093/eurheartj/ehu288. Epub 2014 Jul 25.

Progression of coronary artery calcification seems to be inevitable, but predictable - results of the Heinz Nixdorf Recall (HNR) study

Raimund Erbel  1 , Nils Lehmann  2 , Sofia Churzidse  3 , Michael Rauwolf  3 , Amir A Mahabadi  3 , Stefan Möhlenkamp  4 , Susanne Moebus  2 , Marcus Bauer  3 , Hagen Kälsch  3 , Thomas Budde  5 , Michael Montag  5 , Axel Schmermund  6 , Andreas Stang  7 , Dagmar Führer-Sakel  8 , Christian Weimar  9 , Ulla Roggenbuck  2 , Nico Dragano  10 , Karl-Heinz Jöckel  2 ; Heinz Nixdorf Recall Study Investigators
Collaborators, Affiliations
Observational Study

Progression of coronary artery calcification seems to be inevitable, but predictable - results of the Heinz Nixdorf Recall (HNR) study

Raimund Erbel et al. Eur Heart J. .

Abstract

Aim: Coronary artery calcification (CAC), as a sign of atherosclerosis, can be detected and progression quantified using computed tomography (CT). We develop a tool for predicting CAC progression.

Methods and results: In 3481 participants (45-74 years, 53.1% women) CAC percentiles at baseline (CACb) and after five years (CAC₅y) were evaluated, demonstrating progression along gender-specific percentiles, which showed exponentially shaped age-dependence. Using quantile regression on the log-scale (log(CACb+1)) we developed a tool to individually predict CAC₅y, and compared to observed CAC₅y. The difference between observed and predicted CAC₅y (log-scale, mean±SD) was 0.08±1.11 and 0.06±1.29 in men and women. Agreement reached a kappa-value of 0.746 (95% confidence interval: 0.732-0.760) and concordance correlation (log-scale) of 0.886 (0.879-0.893). Explained variance of observed by predicted log(CAC₅y+1) was 80.1% and 72.0% in men and women, and 81.0 and 73.6% including baseline risk factors. Evaluating the tool in 1940 individuals with CACb>0 and CACb<400 at baseline, of whom 242 (12.5%) developed CAC₅y>400, yielded a sensitivity of 59.5%, specificity 96.1%, (+) and (-) predictive values of 68.3% and 94.3%. A pre-defined acceptance range around predicted CAC₅y contained 68.1% of observed CAC₅y; only 20% were expected by chance. Age, blood pressure, lipid-lowering medication, diabetes, and smoking contributed to progression above the acceptance range in men and, excepting age, in women.

Conclusion: CAC nearly inevitably progresses with limited influence of cardiovascular risk factors. This allowed the development of a mathematical tool for prediction of individual CAC progression, enabling anticipation of the age when CAC thresholds of high risk are reached.

Keywords: CT; Coronary artery calcification; Epidemiology; Heinz Nixdorf Recall study; Imaging; Progression of atherosclerosis.

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Figures

Figure 1
Figure 1
Derivation scheme and use of coronary artery calcification quantile calculator.
Figure 2
Figure 2
(A) Observed and fitted 50th, 75th, and 90th percentile of the coronary artery calcification distribution for men by age categories. In dark colors for the baseline values, when the participants (1633 men) were aged between 45 and 74 years, and in light colors for the 5-year follow-up data, when the cohort was aged 50–79 years. Note the exponential shape of the increase of coronary artery calcification. Dots represent observed percentile values for each 5-year age categories, lines show linear quantile regression on a log scale after retransformation. (B) Observed and fitted 50th, 75th, and 90th percentile of the coronary artery calcification distribution for men by age categories. In dark colors for the baseline values, when the participants (1848 women) were aged between 45 and 74 years, and in light colors for the 5-year follow-up data, when the cohort was aged 50–79 years. Note the exponential shape of the increase of coronary artery calcification. Dots represent observed percentile values for each 5-year age categories, lines show linear quantile regression on a log scale after retransformation. The y-axis range in Figure 1A and B differ by a factor of 2.5 in men compared with women.
Figure 3
Figure 3
(A) Predicted age, at which a man reaches a coronary artery calcification value, as function of coronary artery calcification percentile. The red band around the curve for CAC = 400 represents respective prediction limits. A man with an observed coronary artery calcification on the 80th percentile reaches CAC = 400 at 63.3 (61.3–69.6) years. (B) Predicted age, at which a woman reaches a coronary artery calcification value, as function of coronary artery calcification percentile. The red band around the curve for CAC = 400 represents respective prediction limits. A woman with an observed coronary artery calcification on the 80th percentile reaches CAC = 400 at 73.4 (71.5–82.9) years, 10 years later than her male counterpart.
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