CME INDIA Presentation by Dr. Ashish K. Saxena, MD (Medicine), FRCP Edn., FIAE (Echo), PGDD (Diabetes), FIACM, Fellow Indian Society of Hypertension, Fellow Diabetes India. Consultant Internal Medicine, Diabetes and Non-Invasive Cardiology Diabetes and Heart centre, Delta Heart Centre, Ludhiana.

(Based on a presentation at ISCCON-2023)

Why it is Important?

• Coronary Artery Disease (CAD) stands as a primary contributor to morbidity and mortality associated with diseases, accounting for one out of every ten deaths.
• Among the symptoms frequently observed in CAD, chronic angina is notable, and it’s worth mentioning that a substantial percentage of individuals, as many as 50%, will initially present with a myocardial infarction.
• Efforts in prevention should prioritize the identification of asymptomatic individuals at risk, enabling timely detection and intervention for CAD.

CAC: Emerging role

• CAC – coronary artery calcium serves as a precise indicator of atherosclerosis.
• Non – contrast computed tomography (CT) is used to quantify coronary calcium.
• This method is considered promising for enhancing risk stratification and reclassification in asymptomatic individuals.

What is CAC?

• Coronary Artery Calcium (CAC) refers to the build-up of calcium deposits within the coronary arteries during the progression of atherosclerotic plaques.
• The association between coronary calcium and atherosclerosis was first recognized in the 1970s, when the detection of calcium using fluoroscopy was linked to cardiovascular issues.

A surrogate for the burden of atherosclerosis

• CT imaging has unveiled the connection between coronary calcium and atherosclerotic plaque volume, evident in both pathological specimens and living subjects through intravascular ultrasonography.
• The calcium score, functioning as a surrogate for the burden of atherosclerosis, mirrors an individual’s lifelong exposure to risk factors.

How a Calcium Scoring Performed?

• Calcium scoring entails a CT scan of the heart using a 3mm slice thickness
• The procedure is brief, taking about 10 minutes and involves a low radiation dose, roughly around 1 mSv.
• It’s conducted without use of contrast agents, so it doesn’t assess luminal stenosis.
• In contrast, coronary CT angiography is typically carried out for symptomatic patients suspected of having obstructive CAD.

Coronary artery calcium in the left anterior descending (LAD) and first diagonal (D1) arteries. Courtesy: AJGP,2020 .August. Volume 49, Issue 8, August 2020(Ref-1)

CAC-Interpretation

• Calcium scores are quantified as an absolute numerical measurement and a percentile, adjusted according to gender, age, and ethnic background. The Cardiac Society of Australia and New Zealand (CSANZ) classifies calcium scores into four categories:
• CAC=0
• CAC=1-100
• CAC=101-400
• CAC>400

Benefits of Calcium Scoring

Limitations of CAC

1. High risk and low risk asymptomatic patients 
2. Symptomatic patients
3. Non calcified plaque
4. Cost effectiveness

What should undergo and not undergo Calcium Scoring?

Courtesy: Liew G, Chow C, van Pelt N, et al. Cardiac Society of Australia and New Zealand position statement: Coronary artery calcium scoring. Heart Lung Circ 2017;26(12):1239–51

CAC: As a guide in management

• As a rule, aspirin is not the first choice for preventive measures, as the potential advantages it offers for heart health do not offset the increased risk of bleeding. Nevertheless, calcium scoring has been shown to identify a specific subset of patients who could potentially gain from preventive aspirin therapy.
• Research has also delved into how calcium scoring can guide the decision of when to prescribe cholesterol-lowering medications such as statins. The Number Needed to Treat (NNT) with statins to prevent one cardiovascular issue was 549 for individuals with no coronary calcium (CAC=0) as opposed to 24 for those with substantial calcium (CAC>100). This implies that while statins may be warranted for individuals with CAC>100, they might be unnecessary for those with CAC=0.

Courtesy: Divakaran S, Cheezum MK, Hulten EA, et al. Use of cardiac CT and calcium scoring for detecting coronary plaque: Implications on prognosis and patient management. Br J Radiol 2015;88(1046):20140594. doi: 10.1259/bjr.20140594.(Adapted by Alexander Chua Ron Blankstein Brian Ko – doi: 10.31128/AJGP-03-20-5277  

When to repeat CAC?

• Coronary artery calcium tends to exhibit stability or growth over time, rather than diminishing. When there is a potential alteration in patient management contingent upon a follow-up calcium score, it may be performed to re-evaluate cardiovascular risk.
• For individuals initially prescribed statins after having a calcium score of 0, reconsidering a repeat calcium scoring after five years could be prudent.
• On the other hand, patients with a calcium score exceeding 100 should forego repeat scoring, as they are already recommended for preventive treatment.
• The utility of repeat scoring might diminish after undergoing statin therapy, as statins can induce a slight increase in coronary calcium due to their plaque-stabilizing effect.

Final Point

• The coronary calcium score serves as an assessment of calcified plaque within the arteries, offering predictive insights into the risk of heart disease and mortality. It is commonly administered to individuals with a moderate risk profile who are asymptomatic. This score plays a valuable role in enhancing the precision of risk assessment tools and aids in making informed decisions regarding preventive medications.

CME INDIA Learning EDGE

(2023 Update: J Am Coll Cardiol Img. 2023 Jan, 16 (1) 98–117.)

• Clinical practice guidelines for coronary heart disease (CHD) prevention and treatment serve as comprehensive and universally applicable frameworks that assist both healthcare practitioners and patients in making informed decisions.
• Despite sharing similar objectives, the optimal use of CAC scores varies significantly on a global scale.
• The development of these guidelines’ hinges on different criteria. For instance, guidelines from the United States and England rely primarily on randomized controlled trials, meta-analyses, and systematic reviews. In contrast, the European and Canadian guidelines are stringent but do not impose restrictions on the types of studies considered.
• The American College of Cardiology/American Heart Association guidelines for estimating the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) employ standard risk factors along with consideration of risk-enhancing factors to guide discussions between clinicians and patients regarding risk assessment.
• These guidelines address intermediate-risk adults (with a 10-year ASCVD risk between 7.5% and 20%) and adults at borderline risk (with a 10-year ASCVD risk between 5% and 7.5%).
• Risk-enhancing factors encompass various elements, such as family history of premature ASCVD, persistently elevated low-density lipoprotein cholesterol (LDL-C) exceeding 160 mg/dL or triglycerides surpassing 175 mg/dL, chronic kidney disease, metabolic syndrome, conditions more relevant to women (e.g., pre-eclampsia, premature menopause), inflammatory diseases like rheumatoid arthritis, psoriasis, and HIV, high-risk racial or ethnic backgrounds (e.g., South Asian origin), and in specific cases, elevated high-sensitivity C-reactive protein (hsCRP) at or above 2 mg/dL, elevated lipoprotein(a) [Lp(a)] exceeding 50 mg/mL or 125 nmol/L, apolipoprotein B (apo B) at or above 130 mg/dL, and an ankle brachial index below 0.9.
• When the choice of preventive interventions based on risk assessment remains uncertain, the guidelines recommend considering Coronary Artery Calcium (CAC) scoring to help make a more informed decision. CAC scoring can either elevate the perceived risk (for instance, in young patients and women) or reduce it (e.g., CAC = 0) when deciding whether to prescribe statins.
• For those with CAC scores ranging from 1 to 99, particularly after the age of 55, statin therapy is favored. If the CAC score is 100 or higher and falls above the 75th percentile for one’s age and sex, statin therapy should be initiated regardless of age.
• The Canadian Cardiovascular Society (CCS) guidelines take a more conservative approach to statin use and utilize Coronary Artery Calcium (CAC) scoring sparingly. The CCS relies on the Framingham Risk Score (FRS) to categorize individuals into risk groups, which are as follows: FRS <10% for low risk, 10-19.9% for intermediate risk, and FRS ≥20% for high risk. All individuals receive recommendations for health behavior modifications.
• For those with an FRS <5%, statin use is recommended if their low-density lipoprotein cholesterol (LDL-C) exceeds 190 mg/dL or apolipoprotein B (apo B) is above 145 mg/dL. For individuals with an FRS between 5% and 9.9% and LDL-C over 130 mg/dL, or apo B exceeding 105 mg/dL, particularly if they have other risk factors like a family history of coronary heart disease (CHD), elevated lipoprotein(a) [Lp(a)] levels of 50 mg/dL or higher, or a CAC score greater than 0, statins are considered.
• For those with an FRS of 10-19.9%, the same lipid parameters apply as in the 5%-19.9% category. Additionally, statins are indicated in men aged 50 and older and women aged 60 and older if they have one or more additional risk factors aside from age, which may include low high-density lipoprotein cholesterol (HDL-C), impaired fasting glucose, smoking, hypertension, high-sensitivity C-reactive protein (hsCRP) over 2 g/dL, a CAC score above 0, a family history of CHD, or Lp(a) levels of 50 mg/dL or higher. If, after initiating statin therapy, LDL-C remains above 75 mg/dL or apo B exceeds 80 mg/dL, the addition of ezetimibe is suggested. High-risk patients should start statins and add ezetimibe if necessary. If statins are not prescribed, CAC should be reassessed every 5 years for individuals aged 40-75.
• In contrast, the guidelines of Australia and New Zealand (CSANZ) employ stricter thresholds for statin use based on CAC scores. For individuals with CAC = 0, statins are not recommended. A CAC score of 1-100 suggests focusing on lifestyle improvements. When CAC is in the range of 101-400, statins are indicated if the score exceeds the 75th percentile, and a CAC score exceeding 400 necessitates statin therapy. Although patients with low CAC (1-100) have a relative risk that is twice as high compared to those with CAC = 0, CSANZ maintains that the evidence for pharmacotherapy in this group is weak.

Across various country guidelines, there are common agreements regarding the appropriate use of Coronary Artery Calcium (CAC) scoring. These include:

1. Commencing CAC assessments for individuals over the age of 40.
2. For intermediate-risk and asymptomatic patients with a CAC score exceeding 100, initiating or considering statin therapy.
3. For individuals with a CAC score of 0, reducing the assessed risk level and withholding statin therapy, with a recommendation to reassess in 5-10 years.

Furthermore, there is a global consensus that a CAC score falling in the range of 101-400 is indicative of high risk and could potentially benefit from statin therapy. This conclusion is drawn from studies like the Multi-Ethnic Study of Atherosclerosis (MESA), where the 10-year event rates ranged from 1.3% to 5.6% for individuals with CAC = 0, and from 13.1% to 26.6% for those with CAC >300. The MESA study, while holding other cardiovascular risk factors constant, estimated a 14% relative risk increase for every doubling of the CAC score.

The “low-risk” category, defined as a 10-year cardiovascular risk of less than 5%, often has too few cases with a CAC score greater than 0 to benefit from CAC scoring alone. However, it can still aid in decision-making for statin therapy in those who have additional risk enhancers, which may vary but are recognized and utilized by nearly all countries.

Specific guidelines from different regions also provide further recommendations:

• The Cardiac Society of Australia and New Zealand (CSANZ) recommends CAC scoring for lower-risk patients (with a 10-year cardiovascular risk between 6% and 10%) who have a family history of premature cardiovascular disease (CVD), as well as diabetic patients aged 40-60 years.
• The European Society of Cardiology/European Atherosclerosis Society guidelines recommend CAC scoring to determine statin therapy for low- to moderate-risk patients, with consideration given to those with a CAC score exceeding 100 for possible statin therapy.
• Calcium (CAC) scores and the prescription of statins across different countries and guidelines. Each approach has its own set of criteria and thresholds for determining who should receive statins based on CAC scores.
• Some countries favor a more extensive use of CAC scores and may set relatively high thresholds for statin initiation (e.g., CAC >100) when compared to guidelines in the United States. In the U.S., recommendations for statin therapy vary based on CAC scores, such as initiating statins for those with CAC scores between 1 and 99, with particular emphasis on individuals aged 55 and older. For those with CAC scores of 100 or more or those falling above the 75th percentile for their age and sex, statin therapy is suggested regardless of age.
• The approach taken by the Canadian Cardiovascular Society (CCS) is noteworthy for its inclusiveness, as it qualifies a larger number of individuals for statin therapy without solely relying on CAC scores. However, it’s also recognized that this approach may not detect atherosclerotic cardiovascular disease (ASCVD) in many young individuals who are at a high lifetime risk.
• One of the most valuable applications of CAC scoring is to assist patients in making informed decisions regarding statin therapy. This is particularly beneficial for those who are relatively young or who have experienced intolerance to statins. CAC scores can help these patients understand the potential need for alternative strategies, such as trying different or lower-dose, high-intensity statins in combination with non-statin interventions

CME INDIA Tail-Piece:

• SCORE2 exhibits only modest diagnostic efficacy in identifying subjects with high CACS. (Eur Heart J Cardiovasc Imaging 2022; 24:27-3)
• The measurement of Coronary Artery Calcium (CAC) scores using a standard chest CT scan conducted upon admission in patients with COVID-19 for the purpose of detecting pulmonary involvement serves as a prognostic indicator associated with higher mortality rates during the 12-month follow-up period. (European Heart Journal – Cardiovascular Imaging, Volume 24, Issue Supplement_1, June 2023)

References:

1. Chua, A,,Blankstein, R., Ko, B Coronary artery calcium in primary prevention.Australian Journal for General Practitioners.The Royal Australian College of General Practitioners (RACGP).2020; 464: 469( 49). https://www1.racgp.org.au/ajgp/2020/august/coronary-artery-calcium-in-primary-prevention
2. Liew G, Chow C, van Pelt N, et al. Cardiac Society of Australia and New Zealand position statement: Coronary artery calcium scoring. Heart Lung Circ 2017;26(12):1239–51. doi: 10.1016/j.hlc.2017.05.130
3. Greenland P, Alpert JS, Beller GA, et al. 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: Executive summary: A report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 2010;122(25):2748–64. doi: 10.1161/CIR.0b013e3182051bab.
4. Ties D, van der Ende YM, Pundziute G, et al..Current cardiovascular risk scores present limited accuracy in identifying people with increased coronary artery calcium score Eur Heart J Cardiovasc Imaging 2022; 24:27-35; https://doi.org/10.1093/ehjci/jeac137
5. C Braun, M Zehnpfennig, J Kasprzak, K Szymczyk, P Lipiec, Coronary artery calcium score predicts outcome in patients with COVID-19, European Heart Journal – Cardiovascular Imaging, Volume 24, Issue Supplement_1, June 2023, jead119.093, https://doi.org/10.1093/ehjci/jead119.093
6. Golub I, Termeie O, Kristo S, et al. Major Global Coronary Artery Calcium Guidelines. J Am Coll Cardiol Img. 2023 Jan, 16 (1) 98–117. https://doi.org/10.1016/j.jcmg.2022.06.018
7. Parth Parikh, MD, Nishant Shah, MD, Haitham Ahmed, MD, MPH, Paul Schoenhagen, MD and Maan Fares, MD.Coronary artery calcium scoring: Its practicality and clinical utility in primary care.Cleveland Clinic Journal of Medicine September 2018, 85 (9) 707-716; DOI: https://doi.org/10.3949/ccjm.85a.17097

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