Value of CAC Progression for Risk Prediction of Cardiac Events

Study Questions:

Does progression of coronary artery calcification (CAC) in an unselected, population-based cohort improve risk prediction of coronary and cardiovascular (CV) events?


This portion of the original HNR (Heinz Nixdorf Recall) Study of CAC included 3,281 participants (45–74 years, 54% women) free from CV disease until the second visit at 5 years, risk factors, and CAC score at baseline (b) and after a mean of 5.1 years. Risk factors were treated at the discretion of the primary care physician. CAC scores were not made available to the participants or their physicians at baseline, but were reported after the second computed tomography (CT) scan. Hard coronary and CV events as well as total CV events including revascularization 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 using survival analysis, C-statistics, net reclassification improvement, and integrated discrimination index (IDI). A subgroup analysis of risk in CAC categories was performed.


The overall observation period was 12.9 ± 2.2 years. CAC = 0 was found at baseline in 1,214 (37%) and after 5 years in 1,179 (36%) participants. Risk factor profiles were significantly different between those with and without hard coronary and CV events, and changes of the risk factor profiles in the 5-year interval did not discriminate between those with and without events. There were 85 (2.6%) hard coronary, 161 (4.9%) hard CV, and 241 (7.3%) total CV events. Absolute CAC progression was higher with vs. without subsequent coronary events [median 115 (Q1-Q3 23-360) vs. 8 (0-83), p < 0.0001; similar for hard/total CV events]. Some progression algorithms added to predictive value of baseline CT and risk assessment in terms of C-statistic or IDI, especially for total CV events. However, CAC progression did not improve models including CAC5y and 5-year risk factors. An excellent prognosis was found for 921 participants with double zero CACb = CAC5y = 0 [10-year coronary and hard/total CV risk: 1.4%, 2.0%, and 2.8%], which was for participants with incident CAC 1.8%, 3.8%, and 6.6%, respectively. When CACb progressed from 1-399 to CAC5y ≥400, coronary and total CV risk were nearly twofold compared to subjects who remained below CAC5y = 400. Participants with CACb ≥400 had high rates of hard coronary and hard/total CV events [10-year risk; 12.0%, 13.5%, and 30.9% respectively].


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


Based on a cohort with a baseline CAC not known to the clinician, which is not a clinical scenario, the authors recommend when a CAC is >0 and <400, repeat CT scan after 5 years will provide a 10-year risk readjustment due to increased risk when CAC = 400 is reached. That high CAC threshold appears in conflict with the MESA (Multi-Ethnic Study of Atherosclerosis) Risk Score Calculator for predicting 10-year coronary events (coronary heart disease [CHD]; not total hard CV events) for deciding use of statins (>7.5% 10-year total CV risk based on the American College of Cardiology/American Heart Association guideline), which was derived using the baseline MESA data and validated using the HNR Study and the Dallas Heart Study (McClelland RL, et al., J Am Coll Cardiol 2015;66:1643-53). Example: In 60-year-old men with a 5% 10-year CHD risk based on MESA data, a CAC of 100 increases the risk to 7.5% and a CAC of 300 to 10%. And in men with the same risk factors, at age 60, a CAC of 50 increases 10-year CHD event rate to 6.3%, and a second study 5 years later with a progression to 100 increases 10-year CHD event to >8%, supporting the value of a second CT.

Clinical Topics: Dyslipidemia, Noninvasive Imaging, Prevention, Nonstatins, Novel Agents, Statins, Computed Tomography, Nuclear Imaging

Keywords: Atherosclerosis, Coronary Artery Disease, Diagnostic Imaging, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Plaque, Atherosclerotic, Primary Prevention, Risk Assessment, Risk Factors, Tomography, Tomography, X-Ray Computed

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