What is the relationship between HMG-CoA reductase inhibitors (statins) and coronary artery calcium?

From the Guidelines

Statin therapy does not directly reduce coronary calcium scores and may actually increase calcium scores in some patients despite improving cardiovascular outcomes. This apparent paradox occurs because statins stabilize plaques by promoting calcification of soft, vulnerable plaques into more stable calcified lesions, as supported by the 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults 1. Therefore, an increase in coronary calcium score while on statin therapy should not be interpreted as treatment failure or disease progression.

Key Points to Consider

• The decision to start statin therapy should be based on overall cardiovascular risk assessment rather than coronary calcium scores alone, though a high calcium score (>300 Agatston units) generally indicates elevated cardiovascular risk and may support statin initiation, as noted in the 2010 ACCF/AHA guideline 1.
• Common statins used for cardiovascular risk reduction include atorvastatin (10-80mg daily), rosuvastatin (5-40mg daily), and simvastatin (10-40mg daily), with the choice of statin and dose depending on the individual patient's risk factors and lipid profile, as discussed in the 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults 1.
• Patients should understand that the goal of statin therapy is to reduce cardiovascular events through multiple mechanisms including lowering LDL cholesterol, reducing inflammation, and stabilizing plaques, rather than specifically reducing calcium scores.
• Regular lipid panel monitoring is recommended after starting statins, typically at 4-12 weeks initially and then annually, to assess the effectiveness of therapy and adjust the treatment plan as needed, based on the patient's response to therapy and overall cardiovascular risk profile.

Mechanism of Action

• Statins work by inhibiting the enzyme HMG-CoA reductase, which plays a key role in the production of cholesterol in the liver, as discussed in the 2013 ACC/AHA guideline 1.
• By reducing the production of cholesterol, statins lower the levels of low-density lipoprotein (LDL) cholesterol, also known as "bad" cholesterol, in the blood, which can help to slow the progression of atherosclerosis and reduce the risk of cardiovascular events.
• Statins also have anti-inflammatory properties, which can help to stabilize plaques and reduce the risk of acute coronary events, as supported by the evidence from the Cholesterol Treatment Trialists (CTT) collaboration 1.

From the Research

Statin and Coronary Calcium Relationship

• The relationship between statin use and coronary calcium is complex, with studies indicating that coronary artery calcium (CAC) scoring can be used to clarify atherosclerotic cardiovascular disease (ASCVD) risk in patients with severe hypercholesterolemia 2.
• CAC scores are associated with a higher risk for ASCVD events, and a higher CAC category is associated with increased statin use after CAC scoring 2.
• The use of moderate-intensity statins plus ezetimibe has been compared to high-intensity statins in patients with atherosclerotic cardiovascular disease, with similar rates of major adverse cardiovascular events observed in both groups 3.

Predictive Value of Coronary Artery Calcium

• CAC scores have been shown to be predictive of long-term cardiovascular events in patients with stable coronary artery disease, with a CAC score ≥100 or a cardio-ankle vascular index (CAVI) ≥9.0 predicting the long-term occurrence of major adverse cardiovascular events (MACEs) 4.
• The prognostic significance of both absolute and percentile coronary calcium scores has been examined among older adults, with higher coronary calcium scores and percentiles associated with increased cardiovascular and all-cause mortality risk 5.
• CAC scores indicating secondary prevention level risk have been determined, with a CAC score of 781 corresponding to an annualized ASCVD mortality rate equivalent to that observed in the FOURIER trial 6.

Clinical Implications

• CAC scoring may be used to guide treatment for the prevention of future cardiovascular events, particularly in patients with severe hypercholesterolemia or stable coronary artery disease 2, 4.
• The use of CAC scores to risk-stratify patients and guide statin therapy may be particularly useful in older adults, where coronary calcium burden is strongly predictive of cardiovascular and all-cause mortality 5.