*! Very-High-Risk Atherosclerotic Cardiovascular Disease Status Among Patients with CAC >1000: Implications for Intensive Lipid-Lowering Therapy

Background/Synopsis Individuals with coronary artery calcium (CAC) >1000 experience secondary prevention-level risk and thus may optionally be placed on combination lipid-lowering therapy regimens. However, the risk markers in individuals with CAC >1000 that equate to very-high-risk status and corresponding low-density lipoprotein cholesterol (LDL-C) target goals have not yet been studied. Objective/Purpose Among persons with CAC >1000, we sought to identify risk markers that were associated with atherosclerotic cardiovascular disease (ASCVD) mortality rates approaching that of very-high-risk status in secondary prevention. Methods We studied 2,869 primary prevention patients with CAC >1000 from the CAC Consortium. Multivariable Cox proportional hazards regression assessed the association of risk markers with ASCVD mortality during a median follow-up of 11.8 years. Crude ASCVD mortality rates were compared to those previously reported for patients meeting very-high ASCVD risk, defined by a history of >2 major ASCVD events or a history of 1 major event along with >2 high-risk conditions (1.4 per 100 person-years). Results The mean age of participants was 66.3 years, 14% were female, 13% were non-white, and 48% were on statin medication at the time of CAC scanning. The median CAC score was 1,572, 65% had left main CAC and 5% had severe left main CAC (>300). Beyond age (HR=2.54, 95% CI: 1.82-3.55, per 10-years older), diabetes (HR=2.06, 95% CI: 1.21-3.51), and severe left main CAC (HR=2.70, 95% CI: 1.46-4.87), there were no other risk markers independently associated with ASCVD mortality. The ASCVD mortality per 100 person-years for all patients was 0.8 (95% CI: 0.7-0.9), though much higher event rates were observed for persons with diabetes (1.4, 95% CI: 0.8-1.9), severe left main CAC (1.3, 95% CI: 0.6-2.0), and both diabetes and severe left main CAC (7.1, 95% CI: 3.4-10.8) (Central Illustration). Conclusions Among primary prevention patients with CAC >1000, the presence of diabetes and severe left main CAC are independent prognostic markers of excess risk. There is a spectrum of commensurate secondary prevention level risk for patients with CAC >1000 that corresponds to individualized LDL-C treatment target goals as low as 55 mg/dL, especially for those with diabetes and/or severe left main CAC burden. External Funding No Individuals with coronary artery calcium (CAC) >1000 experience secondary prevention-level risk and thus may optionally be placed on combination lipid-lowering therapy regimens. However, the risk markers in individuals with CAC >1000 that equate to very-high-risk status and corresponding low-density lipoprotein cholesterol (LDL-C) target goals have not yet been studied. Among persons with CAC >1000, we sought to identify risk markers that were associated with atherosclerotic cardiovascular disease (ASCVD) mortality rates approaching that of very-high-risk status in secondary prevention. We studied 2,869 primary prevention patients with CAC >1000 from the CAC Consortium. Multivariable Cox proportional hazards regression assessed the association of risk markers with ASCVD mortality during a median follow-up of 11.8 years. Crude ASCVD mortality rates were compared to those previously reported for patients meeting very-high ASCVD risk, defined by a history of >2 major ASCVD events or a history of 1 major event along with >2 high-risk conditions (1.4 per 100 person-years). The mean age of participants was 66.3 years, 14% were female, 13% were non-white, and 48% were on statin medication at the time of CAC scanning. The median CAC score was 1,572, 65% had left main CAC and 5% had severe left main CAC (>300). Beyond age (HR=2.54, 95% CI: 1.82-3.55, per 10-years older), diabetes (HR=2.06, 95% CI: 1.21-3.51), and severe left main CAC (HR=2.70, 95% CI: 1.46-4.87), there were no other risk markers independently associated with ASCVD mortality. The ASCVD mortality per 100 person-years for all patients was 0.8 (95% CI: 0.7-0.9), though much higher event rates were observed for persons with diabetes (1.4, 95% CI: 0.8-1.9), severe left main CAC (1.3, 95% CI: 0.6-2.0), and both diabetes and severe left main CAC (7.1, 95% CI: 3.4-10.8) (Central Illustration). Among primary prevention patients with CAC >1000, the presence of diabetes and severe left main CAC are independent prognostic markers of excess risk. There is a spectrum of commensurate secondary prevention level risk for patients with CAC >1000 that corresponds to individualized LDL-C treatment target goals as low as 55 mg/dL, especially for those with diabetes and/or severe left main CAC burden.