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Very High Coronary Artery Calcium and CVD Outcomes
Quick Takes
- CAC ≥1000 corresponds to an annualized 3-point MACE rate (nonfatal MI, nonfatal stroke, fatal CVD) of 3.4 per 100 person-years, similar to a high-risk stable treated secondary prevention population (3.3) and higher than lower risk subgroups.
- That very high CAC scores obtained for CVD risk estimate should be considered very high risk for clinical events and treated as CHD risk equivalents is common practice, but will need adequate evidence for payers.
- The high correlation between CAC scores in MESA and non-CVD events and diseases and total mortality confirms the importance of known and unknown CV risk factors for cancer, chronic kidney disease, end-stage renal disease, dementia, pneumonia, deep vein thrombosis/pulmonary embolism, and hip fracture.
Study Questions:
What is the implication of a very high coronary artery calcium score (CAC ≥1000) on cardiovascular disease (CVD), non-CVD, and mortality risks of primary prevention individuals in comparison to rates observed in secondary prevention populations?
Methods:
The study population consisted of 6,814 ethnically diverse individuals aged 45-84 years, free of known CVD from the MESA (Multi-Ethnic Study of Atherosclerosis) study. Mean follow-up time was 13.6 ± 4.4 years. Hazard ratios of CAC ≥1000 were compared to both CAC = 0 and CAC 400-999 for CVD events (myocardial infarction [MI], resuscitated cardiac arrest, stroke, adjudicated angina, CV death), non-CVD and events, and mortality outcomes using Cox proportional hazards regression adjusted for age, sex, and traditional risk factors. Using a sex-adjusted logarithmic model, the calculated event rates in MESA were derived as a function of CAC and compared to those in the placebo group of stable secondary prevention patients in the FOURIER (PCSK9 antibody) clinical trial.
Results:
Those with a CAC ≥1000 had a mean 10-year atherosclerotic CVD (ASCVD) risk score of 27.5%, CAC 400-999 24.5%, CAC 1-399 17%, and CAC = 0 8.5%. Compared to CAC 400-999, those with CAC ≥1000 (3.8%, n = 257) had similar average CAC density, but greater mean number of coronary vessels with CAC, greater total area of CAC, and more extensive extracoronary calcification (aorta, aortic valve, mitral valve). After full-adjustment, CAC ≥1000 demonstrated a 4.71-, 7.57-, 4.86-, and 1.94-fold increased risk for all CVD events, all coronary heart disease (CHD) events, hard CHD events, and all-cause mortality, respectively, compared to CAC = 0 and a 1.65-, 1.66-, 1.51-, and 1.34-fold increased risk compared to CAC 400-999. With increasing CAC, hazard ratios increased for all event types, with no apparent upper CAC threshold. CAC ≥1000 was associated with a 1.95- and 1.43-fold increased risk for a first non-CVD event compared to CAC = 0 and CAC 400-999, respectively. CAC = 1000 corresponded to an annualized 3-point major adverse cardiac event (MACE) rate (nonfatal MI, nonfatal stroke, CV death) of 3.4 per 100 person-years, similar to that of the total FOURIER trial population (3.3), and higher than lower risk FOURIER subgroups.
Conclusions:
Individuals with very high CAC (≥1000) are a unique population at substantially higher risk for CVD events, non-CVD outcomes, and mortality than those with lower CAC, and similar 3-point MACE rates as a stable treated secondary prevention population. Future guidelines should consider a less distinct stratification algorithm between primary versus secondary prevention patients in guiding aggressive preventive pharmacotherapy.
Perspective:
The utility and cost-benefit of computed tomography–derived CAC scores continues to impress. It is time for health insurers and/or employers to provide this very low-cost procedure so that it becomes commonplace in helping to influence the utilization, compliance with, and intensity of CVD prevention strategies.
Clinical Topics: Arrhythmias and Clinical EP, Noninvasive Imaging, Prevention, Implantable Devices, SCD/Ventricular Arrhythmias, Computed Tomography, Nuclear Imaging
Keywords: Angina Pectoris, Atherosclerosis, Cardiovascular Diseases, Coronary Disease, Cost-Benefit Analysis, Heart Arrest, Myocardial Infarction, Outcome Assessment, Health Care, PCSK9 protein, human, Plaque, Atherosclerotic, Primary Prevention, Risk Factors, Secondary Prevention, Stroke, Tomography, X-Ray Computed, Vascular Diseases
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