Value of Progression of Coronary Artery Calcification for Risk Prediction of Coronary and Cardiovascular Events: Result of the HNR Study (Heinz Nixdorf Recall)

Abstract

Background: Computed tomography (CT) allows estimation of coronary artery calcium (CAC) progression. We evaluated several progression algorithms in our unselected, population-based cohort for risk prediction of coronary and cardiovascular events.

Methods: In 3281 participants (45-74 years of age), free from cardiovascular disease until the second visit, risk factors, and CTs at baseline (b) and after a mean of 5.1 years (5y) were measured. Hard coronary and cardiovascular events, and total cardiovascular events including revascularization, as well, were recorded during a follow-up time of 7.8±2.2 years after the second CT. The added predictive value of 10 CAC progression algorithms on top of risk factors including baseline CAC was evaluated by using survival analysis, C-statistics, net reclassification improvement, and integrated discrimination index. A subgroup analysis of risk in CAC categories was performed.

Results: We observed 85 (2.6%) hard coronary, 161 (4.9%) hard cardiovascular, and 241 (7.3%) total cardiovascular events. Absolute CAC progression was higher with versus without subsequent coronary events (median, 115 [Q1-Q3, 23-360] versus 8 [0-83], P<0.0001; similar for hard/total cardiovascular events). Some progression algorithms added to the predictive value of baseline CT and risk assessment in terms of C-statistic or integrated discrimination index, especially for total cardiovascular events. However, CAC progression did not improve models including CAC_5y and 5-year risk factors. An excellent prognosis was found for 921 participants with double-zero CAC_b=CAC_5y=0 (10-year coronary and hard/total cardiovascular risk: 1.4%, 2.0%, and 2.8%), which was for participants with incident CAC 1.8%, 3.8%, and 6.6%, respectively. When CAC_b progressed from 1 to 399 to CAC_5y≥400, coronary and total cardiovascular risk were nearly 2-fold in comparison with subjects who remained below CAC_5y=400. Participants with CAC_b≥400 had high rates of hard coronary and hard/total cardiovascular events (10-year risk: 12.0%, 13.5%, and 30.9%, respectively).

Conclusions: CAC progression is associated with coronary and cardiovascular event rates, but adds only weakly to risk prediction. What counts is the most recent CAC value and risk factor assessment. Therefore, a repeat scan >5 years after the first scan may be of additional value, except when a double-zero CT scan is present or when the subjects are already at high risk.

Keywords: atherosclerosis; coronary disease; disease progression; risk assessment; tomography; vascular calcification.

Figure 1.

Flowchart of Heinz Nixdorf Recall study population. CT indicates computed tomography.

Figure 2.

Added predictive value analyses for hard coronary, hard cardiovascular, and total cardiovascular events. A, Added predictive value analysis for hard coronary events (for different CAC progression algorithms, with respect to baseline risk assessment and baseline CAC). Upper left, hazard ratios; upper right, change in C-statistics; lower left, NRI; lower right, IDI. Base model: log(CAC+1) at baseline and, evaluated at baseline examination, age, sex, LDL, HDL, diabetes mellitus, present smoking, systolic blood pressure, intake of cholesterol-lowering or antihypertensive medications. Base model C-statistics: for the cohort with baseline CAC>0 (Raggi and Percent) C=0.728, all other C=0.750. For definition of progression algorithms, see Table 1. Hazard ratios for continuous measures are given per SD, see Table 1. B, Added predictive value analysis as in Figure 2A, but for hard cardiovascular events. Base model C-statistics: for the cohort with baseline CAC>0 (Raggi and Percent) C=0.705, all other C=0.747. For definition of progression algorithms, see Table 1. Hazard ratios for continuous measures are given per SD, see Table 1. C, Added predictive value analysis as in Figure 2A, but for total cardiovascular events. Base model C-statistics: for the cohort with baseline CAC>0 (Raggi and Percent) C=0.723, all other C=0.764. For definition of progression algorithms, see Table 1. Hazard ratios for continuous measures are given per SD, see Table 1. CAC indicates coronary artery calcium; CI, confidence interval; exp, expected; HDL, high-density lipoprotein; IDI, integrated discrimination index; LDL, low-density lipoprotein; NRI, net reclassification improvement; obs, observed.