Major Global Coronary Artery Calcium Guidelines: Key Points

Golub IS, Termeie OG, Kristo S, et al.
Major Global Coronary Artery Calcium Guidelines. JACC Cardiovasc Imaging 2022;Sep 15:[Epub ahead of print].

The following are key points to remember from this state-of-the-art paper on major global coronary artery calcium (CAC) guidelines:

  1. Clinical practice guideline(s) for prevention and treatment of coronary heart disease (CHD) include structuring systematic and universally applicable recommendations that aid practitioner and patient decision making. This review summarizes the framework behind multinational guidelines for use of CAC scores in atherosclerotic cardiovascular disease (ASCVD) risk assessment that helps to facilitate physician-patient decisions regarding treatment options.
  2. Despite similar goals, global best use of CAC varied considerably. By comparing similarities and differences in recommendations, the review identifies most notable common features for the application of CAC. In developing the guidelines for CAC use, the US and England recommendations are limited to randomized controlled trials and meta-analysis/systematic reviews. The European and Canadian guidelines are rigorous but do not restrict categories of studies, and Chinese guidelines were determined from a platform of clinical and epidemiological studies of the Chinese population. The authors also included statements made by the National Lipid Association (NLA), Society of Cardiovascular Computed Tomography (SCCT), and US Preventive Services Task Force (USPSTF).
  3. Reducing CHD mortality and morbidity necessitates a highly sensitive risk assessment tool, followed by risk stratification, which facilitates treatment strategies. Understanding the parallels among international CAC guidelines may help clinicians to correctly adjudicate personalized decisions for statins and possibly aspirin, antihypertensive therapy, and CAC rescanning time intervals.
  4. Despite similarities, the individual global guidelines vary considerably and vary in complexity. Regarding risk stratification, most clinical practice guidelines agree that CAC scoring is vital to up- or down-classify intermediate-risk individuals.
  5. The American College of Cardiology/American Heart Association guideline to estimate 10-year risk of ASCVD uses standard risk factors and consideration of risk-enhancing factors to guide clinician-patient risk discussion for intermediate-risk adults (7.5%-20% 10-year ASCVD risk) and adults at borderline risk (5%-7.5% 10-year ASCVD risk). These include family history of premature ASCVD, persistently elevated low-density lipoprotein cholesterol (LDL-C) >160 mg/dL or triglycerides >175 mg/dL, chronic kidney disease, metabolic syndrome, conditions specific to women (e.g., pre-eclampsia, premature menopause), inflammatory diseases (rheumatoid arthritis, psoriasis, and HIV), high-risk race or ethnicity (e.g., South Asian origin), and in selected persons, if measured, elevated high-sensitivity C-reactive protein (hsCRP: ≥2 mg/dL), lipoprotein(a) [Lp(a)] >50 mg/mL or >125 nmol/L, apolipoprotein B (apo B) ≥130 mg/dL, and ankle brachial index <0.9. If risk-based choices for preventive interventions remain ambiguous, consider CAC as an adjudicator to upgrade risk (e.g., young patients and women) or to de-risk if CAC = 0 with no statin and repeat CAC in 5-10 years with the exception that stains be given in diabetes, family history of premature CHD, or cigarette smokers. CAC = 1-99 favors statin, especially after age 55 years. If CAC = 100+ and ≥75th percentile for age/sex, initiate statin therapy at any age.
  6. The Canadian Cardiovascular Society (CCS) guideline is much more lenient for statins and uses CAC infrequently. CCS uses the Framingham Risk Score (FRS: <10% low-risk, 10-19.9% intermediate-risk, and high-risk FRS ≥20%. All get health behavior modifications. For those with FRS <5%, statins are used if LDL-C >190 mg/dL or apo B >145 mg/dL, and for those FRS 5%-9.9% with LDL-C >130 mg/dL, or apo B >105 mg/dL, particularly with other risk modifiers including family history of CHD, Lp(a) ≥50 mg/dL, or CAC >0. For FRS 10-19.9%%, same lipid parameters as 5%-19.9%. But statins are also indicated in men aged ≥50 and women ≥60 years with one or more additional risk besides age including low HDL-C, impaired fasting glucose, smoker, hypertension, hsCRP >2 g/dL CAC >0, family history, or Lp(a) >50 mg/dL. Once statin is initiated if LDL-C remains >75 mg/dL or apo B >80 mg/dL, suggest adding ezetimibe. For high-risk patients, initiate statins and add ezetimibe if not at goal. If statins are withheld, CAC should be repeated every 5 years in men and women aged 40-75 years.
  7. Australia and New Zealand guidelines (CSANZ) have tighter thresholds for statin: CAC = 0 withhold statins, CAC = 1-100 favors lifestyle improvement, CAC 101-400 indicates statin if score is >75th percentile, and >400 requires statin therapy. Although patients with low CAC (1-100) have a 2-fold relative risk compared to CAC = 0, CSANZ asserts that evidence for pharmacotherapy is weak.
  8. Key agreements among country guidelines for common indication for CAC is to begin at age >40 years, and for intermediate-risk and asymptomatic patients with threshold CAC >100, initiate/consider statin; and for CAC = 0, downgrade risk and withhold statin with repeat in 5-10 years. The global guideline concluded a CAC of 101-400 is high-risk and could benefit from statins. This was based on the MESA study (Multi-Ethnic Study of Atherosclerosis} in which 10-year event rates varied from 1.3%-5.6% for CAC = 0, and from 13.1%-26.6% for CAC >300. With other CV risk factors held constant, the MESA study estimated a 14% relative risk increment for every doubling of CAC.
  9. The low-risk cohort, defined as <5%, has too few CAC >0 to benefit from CAC, but can help decide statins in those with risk enhancers, which vary, but are used by nearly all countries. CSANZ recommends CAC for lower-risk patients (10-year CV risk 6%-10%) with a family history of premature CVD and diabetic patients 40-60 years of age. The European Society of Cardiology/European Atherosclerosis Society guidelines recommend CAC to decide statin therapy in low- to moderate-risk patients in whom CAC >100 should be considered for statins.
  10. In addition to variation between country guidelines, there are differences within and between specialty guidelines. US and CCS use CAC as an arbitrator for statin use on intermediate-risk. The UK uses CAC as a tool for adjudicating statin allocation and for deciding significance of suggested electrocardiographic changes for ischemia in asymptomatic patients. Australia uses CAC as a risk assessing tool, risk re-classification, and therapy determinant, specifically in low-risk patients with strong family history or other concerning features and high-risk patients reluctant to accept treatment. The European group emphasizes deciding statin use in diabetics by type 1 versus 2 and age without other risk factors. The Chinese Society of Cardiology guidelines use CAC as an arbitrator for aspirin allocation. The Japanese Atherosclerosis Society guidelines use CAC as a prognostic tool in intermediate- to high-risk individuals but requires local studies, considering that the prevalence of CHD is relatively low. The NLA and SCCT encourage the CAC to facilitate the decision for statins and need for intensifying dosing. NLA has CAC rationale with risk and CAC for use of aspirin and antihypertensive therapy. The SCCT recommends CAC for all but those with 10-year ASCVD risk >20%. Those with a CAC = 0 should not be treated with statins and those with a CAC >100 have high-intensity statin + aspirin 81 mg. The USPSTF concluded there is insufficient evidence for CAC in addition to traditional CV risk assessment in asymptomatic adults for ASCVD prevention.
  11. None of the countries has a simple protocol. Some favor greater use of the CAC score and a relatively high threshold for statin use (CAC >100) compared to the US, which recommends statins with CAC = 1-99 favors statins at any age, especially after age 55 years. Additionally, for a CAC = 100+ or ≥75th percentile for age/sex initiate statin therapy at any age.
  12. The CCS seems to be most logical in that it qualifies the most persons for inexpensive statins without use of CAC, and that while relatively inexpensive, does not detect ASCVD in many young persons who are at high life-time risk. I find one of the most valuable uses of CAC is to help the patient make the statin decision, particularly those who are relatively young or who have been statin intolerant and need to be informed of the potential need for trying a different or low-dose, high-intensity statin in combination with a nonstatin.

Clinical Topics: Cardiovascular Care Team, Diabetes and Cardiometabolic Disease, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Advanced Lipid Testing, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Interventions and Imaging, Computed Tomography, Nuclear Imaging, Hypertension, Smoking

Keywords: Antihypertensive Agents, Atherosclerosis, Apolipoproteins B, Aspirin, Cholesterol, LDL, Computed Tomography Angiography, Coronary Disease, C-Reactive Protein, Diabetes Mellitus, Diagnostic Imaging, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypertension, Inflammation, Lipids, Lipoprotein(a), Metabolic Syndrome, Plaque, Atherosclerotic, Primary Prevention, Risk Assessment, Risk Factors, Smoking, Tomography, X-Ray Computed

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