Coronary Artery Calcium and Its Role in Lipid-Lowering: The Latest From Two Landmark Papers in JACC

There has been considerable discussion recently regarding the selective use of coronary artery calcium (CAC) measurements to improve risk prediction and when clinicians should incorporate it in clinical practice. Over the past few decades, there have been a multitude of noninvasive imaging methods proposed to assess the amount of atherosclerotic cardiovascular disease (ASCVD) to improve cardiac risk prediction. Such imaging modalities include stress echocardiography, electrocardiography (resting and stress), computed tomographic angiography (CTA), myocardial perfusion imaging, and CT CAC scoring.1

According to the 2013 American Heart Association (AHA)/American College of Cardiology (ACC) cholesterol guidelines, treating to a strict target low-density lipoprotein cholesterol (LDL-C) is no longer recommended. The guidelines recommend the initial use of a moderate-to-high-intensity statin in high-risk patient groups, which include patients with 1) clinical ASCVD, 2) LDL-C ≥190 mg/dL, 3) diabetes between ages 40-75 years with LDL-C 70 to 189 mg/dL and without clinical ASCVD, or 4) without diabetes or clinical ASCVD with LDL-C 70 to 189 mg/dL and estimated 10-year ASCVD risk ≥7.5%. Furthermore, the role of CAC received a Class IIb recommendation in patients for whom it is uncertain to treat with statin therapy after traditional risk assessment and clinician-patient risk discussion.

Nevertheless, recent investigations have shown that with CAC testing in persons with an ASCVD risk estimate of 5-20%, we can more appropriately assess the true risk of patients in order to determine treatment choices and guide them as such. Typically, recommendations are for the use of CAC in intermediate-risk patients in order to properly risk stratify them into the appropriate risk groups (low vs. high) to guide shared decision making about treatment.

With age being the dominant factor for calculating ASCVD risk, most patients will have an estimated risk of ≥7.5% as they age. In addition, nearly every African man ≥55 years and most Caucasian men ≥60 years of age reach this risk estimate threshold, even if they have normal lipid values. Risk scores often are misleading in women and young to middle aged adults with metabolic syndrome traits and a family history of premature CVD because this information is not captured in the ASCVD risk estimator.2 This makes shared decision making about treatments challenging and opens the door for a test like a CAC score to provide greater clarity.

In the Multi-Ethnic Study of Atherosclerosis (MESA), patients with elevated CAC levels and no risk factors had considerably increased event rates (3.5 times higher) when compared to patients with CAC scores of 0 and multiple risk factors.3,4 CAC was also shown to be a much better and more potent risk discriminator when compared to other methods, such as high-sensitivity C-reactive protein.5,6

MESA data also showed that when CAC was 0, absolute event rates remained relatively low, whereas individuals with levels of CAC ≥100 had event rates similar to that seen in secondary prevention populations.7 Of note, the use of serial CAC scans is not recommended to assess CAC progression.

Interestingly, Polonsky et al. demonstrated in the MESA cohort that utilization of CAC significantly improves risk classification in the intermediate risk group. By using CAC, an additional 23% of individuals who experienced events were appropriately placed in the high-risk group whereas an additional 13% of individuals who did not experience events were correctly reclassified into the low-risk group.8 It is important to mention that intermediate risk is defined as an ASCVD risk of 10-20% by the 2004 National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III guidelines. However, the new 2013 AHA/ACC guidelines no longer use the intermediate risk category.

So, what recent information is currently available regarding CAC, and where do health care providers go from here?

A study by Nasir et al. found that approximately 50% of patients were eligible for either moderate- or high-intensity statin therapy.9 In the study, 41% of participants who were recommended for statins had CAC of zero and had just 5.2 ASCVD events over 1,000 person-years.9 Additionally, 44% of individuals who were eligible for statin therapy had a CAC of 0 and an ASCVD event rate of 4.2 per 1,000 person-years.9 Moreover, most of the ASCVD events in persons with no CAC were strokes, which are often non-atherosclerotic in nature and more likely related to atrial fibrillation and hypertension rather than dyslipidemia.

There has also been significant discussion regarding the use of CAC in practice, as there have been concerns regarding radiation exposure. However, the European Society of Cardiac Radiology and the North American Society for Cardiovascular Imaging advise that CAC testing should not be avoided as the benefits of CAC testing to impact therapy outweigh the minimal risk of excessive radiation exposure.10

In the same issue of JACC as the Nasir et al. paper, McClelland et al. found that the inclusion of CAC in the MESA risk score (which can be accessed online) proposed considerable improvements in prediction of risk, with the Dallas Heart Study and Heinz Nixdorf Recall Study validating excellent discrimination and calibration.11 The authors go on to further say that the addition of CAC to traditional risk factors can more correctly estimate 10-year ASCVD risk.11

Unfortunately, there are no randomized controlled trials as of yet to corroborate that the use of CAC improves ASCVD outcomes. However, many studies have shown the robust effect of CAC on improving ASCVD risk stratification. This information from the MESA investigators clearly shows that about half of persons with an ASCVD risk estimate of 5-15% have no CAC, and many more have just minimal CAC. Clinicians should share this information with their patients who are unsure about whether to go on long-term statin therapy, especially when their lipid values are thought to be good or if they have had a side effect with statin therapy in the past.


  1. Blumenthal RS, Hasan RK. "Actually, it is more of a guideline than a rule." J Am Coll Cardiol 2011;57:1601-3.
  2. Nasir K, Blaha MJ. Short and lifetime cardiovascular risk estimates: same wine, different bottles. Do we have the COURAGE to abandon risk scores? J Nuclear Cardiol 2014;21:46-9.
  3. Nasir K, Rubin J, Blaha MJ, et al. Interplay of coronary artery calcification and traditional risk factors for the prediction of all-cause mortality in asymptomatic individuals. Circ Cardiovasc Imaging 2012;5:467-73.
  4. Silverman MG, Blaha MJ, Krumholz HM, et al. Impact of coronary artery calcium on coronary heart disease events in individuals at the extremes of traditional risk factor burden: the Multi-Ethnic Study of Atherosclerosis (MESA). Eur Heart J 2014;35:2232-41.
  5. Blaha MJ, Budoff MJ, DeFilippis AP, et al. Associations between C-reactive protein, coronary artery calcium, and cardiovascular events: implications for the JUPITER population from MESA, a population-based cohort study. Lancet 2011;378:684-92.
  6. Amin NP, Martin SS, Blaha MJ, Nasir K, Blumenthal RS, Michos ED. Headed in the right direction but at risk for miscalculation: a critical appraisal of the 2013 ACC/AHA risk assessment guidelines. J Am Coll Cardiol 2014;63(25 Pt A):2789-94.
  7. Martin SS, Blaha MJ, Blankstein R, et al. Dyslipidemia, coronary artery calcium, and incident atherosclerotic cardiovascular disease: implications for statin therapy from the multi-ethnic study of atherosclerosis. Circulation 2014;129:77-86.
  8. Polonsky TS, McClelland RL, Jorgensen NW, et al. Coronary artery calcium score and risk classification for coronary heart disease prediction. JAMA 2010;303:1610-6.
  9. Nasir K, Bittencourt MS, Blaha MJ, et al. Implications of coronary artery calcium testing among statin candidates according to American College of Cardiology/American Heart Association Cholesterol Management Guidelines: MESA (Multi-Ethnic Study of Atherosclerosis). J Am Coll Cardiol 2015;66:1657-68.
  10. Oudkerk M, Stillman AE, Halliburton SS, et al. Coronary artery calcium screening: current status and recommendations from the European Society of Cardiac Radiology and North American Society for Cardiovascular Imaging. Eur Radiol 2008;18:2785-807.
  11. McClelland RL, Jorgensen NW, Budoff M, et al. 10-Year coronary heart disease risk prediction using coronary artery calcium and traditional risk factors: derivation in the MESA (Multi-Ethnic Study of Atherosclerosis) with validation in the HNR (Heinz Nixdorf Recall) Study and the DHS (Dallas Heart Study). J Am Coll Cardiol 2015;66:1643-53.

Clinical Topics: Arrhythmias and Clinical EP, Diabetes and Cardiometabolic Disease, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Atrial Fibrillation/Supraventricular Arrhythmias, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Interventions and Imaging, Angiography, Computed Tomography, Echocardiography/Ultrasound, Nuclear Imaging, Hypertension

Keywords: American Heart Association, Angiography, Atherosclerosis, Atrial Fibrillation, C-Reactive Protein, Calcium, Calibration, Cholesterol, LDL, Cohort Studies, Coronary Vessels, Decision Making, Diabetes Mellitus, Dyslipidemias, Echocardiography, Stress, Electrocardiography, Health Personnel, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypertension, Lipoproteins, LDL, Metabolic Syndrome X, Myocardial Perfusion Imaging, Randomized Controlled Trials as Topic, Research Personnel, Risk, Risk Assessment, Risk Factors, Secondary Prevention, Stroke, Tomography, X-Ray Computed

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