Baseline characteristics stratified by sex are presented in . The distribution of FRS-determined risk categories for subjects aged 30 to 65 years is presented in . One percent (n = 19) of women and 15.4% (n = 179) of men were at MHR and would thus be eligible for CAC screening according to present recommendations. Defining the MHR group by FRS-estimated 10-year risk of 10% to 20%, <0.1% of women (n = 1) and only 1.1% of all men (n = 13) would be reclassified to the high-risk group based on the presence of CAC ≥400 (). Expanding the pool of imaging candidates to include subjects with FRS 10-year risk of 6% to 20%7
had minimal effect on the proportion of women eligible for imaging (3.4%) and had no effect on the proportion promoted to the high-risk category (<0.1%). In men, using this expanded group greatly increased the proportion eligible for imaging (27.0%), but had negligible effect on those reclassified to high risk (1.8%). The above results were not significantly altered by including the ≥2 traditional CHD risk factor criteria as part of the NCEP definition for MHR. Furthermore, sensitivity analyses adjusting the effect of statin treatment on total cholesterol and excluding statin users did not significantly alter the results (data not shown).
Baseline characteristics stratified by sex
Distribution of Framingham risk categories.
Impact of varying calcium thresholds and age range
displays the impact of varying the CAC imaging strategy by (a
) restricting the cohort eligible for imaging to subjects aged 45 to 65 years and (b
) using different CAC thresholds for risk category promotion.1,7
Restricting to an older age range only increased the proportion of women eligible for imaging to 2.1%, but had no impact on the proportion promoted to the high-risk group. Using an alternate CAC threshold of ≥100 or ≥75th percentile for age/sex did not appreciably change the small proportion of women that would change risk categories (<1%). On the other hand, in men, there was a small increase in the proportion of men promoted to the high-risk group when screening was restricted to the older age range (from 1.1% to 2.5%); however, this was accompanied by a large increase in the proportion of men eligible for imaging, from 15.4% to 29.8%. A greater proportion of men changed risk categories using a CAC threshold of ≥100 or ≥75th percentile for age/sex compared to ≥400, particularly among the older age group.
demonstrates the efficiency of a CAC screening strategy targeting the MHR group. With a CAC threshold of ≥400 for reclassification of risk, >100 women (aged 30–65 years) would need to be scanned to detect one subject whose risk category would change and >99% of women with underestimated risk would remain undetected. In men, 14.3 subjects would need to be scanned to identify one informative subject and almost three quarters of all LR and MHR men with underestimated risk would fail to be detected. Whereas altering the age range of the cohort had little effect on the efficiency of CAC screening, using a CAC threshold of ≥100 greatly improved the efficiency of CAC scanning for both sexes. However, only a small proportion of those in the LR or MHR groups with CAC above this score would be detected in women and still just over half of such men. The efficiency of scanning was maximized using the threshold of ≥75th percentile for age/sex, but resulted in further reductions in the proportion of LR and MHR subjects with underestimated risk that were detected.
Efficiency of imaging strategies targeted to MHR subjects
The impact of using a bidirectional reclassification strategy for CAC scanning is demonstrated in . When applied to the entire population aged 30 to 65 years, 27.5% of men and 12.5% of women would be reclassified, with the majority of these being downward reclassifications (23.2% and 9.6% of each sex, respectively). The NNS to identify one subject for reclassification was 3.6 in men and 8.0 in women overall, and 1.2 and 1.6 when restricting to just the MHR and high-risk subgroups.
Figure 2 Distribution of Framingham risk categories after screening for CAC using a bidirectional reclassification strategy. Part A, Women; Part B, men. Upwards reclassification occurred for low-risk subjects with CAC ≥100 or MHR subjects with CAC ≥400. (more ...)
In women aged 30 to 65 years, 72.3% of those with CAC scores of 100 to 399 and 23.6% of those with CAC ≥400 were in the LR group, representing 2.6% and 0.3% of the overall female population, respectively. In men, 29.9% and 26.9% of those with CAC scores 100 to 399 and ≥400, respectively, were found in the LR group, representing 2.4% and 0.8% of the male population. Thus, to develop an alternate strategy of CAC scanning in select LR subjects, the prevalence of CAC within 5-year age bins of LR subjects was evaluated (). Less than 0.1% of men aged <40 years and women aged <45 had CAC ≥100, meaning scanning such individuals would have little yield. On the other hand, more than one half of all CAC values ≥100 were found in men aged ≥50 years or women ≥60 years, resulting in an NNS of 5.7 and 4.1 in these older age groups, respectively.
Coronary artery calcium prevalence by age categories in LR subjects. Part A, Women; Part B, Men. *Number needed to scan to identify one subject with CAC ≥100 in each respective age category.
The efficiency of various other eligibility criteria to target CAC screening to select LR subjects is presented in . The only eligibility criteria that reduced the NNS to <10 were FRS 10-year risk 6% to 9% among men and 3% to 9% among women, and only age and FRS adequately discriminated subjects with CAC ≥100 (c statistics 0.8), whereas all other risk factors did not (c statistics ≤0.6)
Efficiency of various eligibility criteria for CAC screening in LR subjects
With the use of the most efficient eligibility criteria of age and FRS, a simple CAC screening strategy for LR subjects was developed (). Based upon this strategy, 15.0% of all men and 12.7% of all women aged 30 to 65 years would be eligible for CAC screening. The cross-validated estimates of the NNS to identify one subject with CAC ≥100 were 6.8 for men (95% CI 4.6–13.3) and 5.2 for women (95% CI 3.4–11.4), and 51.1% of men and 84.2% of women with underestimated risk from the whole cohort would have been detected using this strategy (). Applying this same LR screening strategy to detect subjects with CAC ≥75th percentile for age/sex improved the efficiency but slightly reduced the overall yield of CAC screening.
Coronary artery calcium screening strategy for select LR subjects.
Efficiency of an imaging strategy targeted to select LR subjects