Coronary Artery Calcification

Coronary artery calcification is deposition of calcium hydroxyapatite in the coronary wall, mainly within atherosclerotic plaque. It is a direct marker of atherosclerotic plaque burden and a strong independent predictor of cardiovascular events. It also makes percutaneous coronary intervention harder.

Prevalence rises steeply with age. It appears about 10 years later in women than in men. It is accelerated by diabetes, chronic kidney disease, dialysis, hyperparathyroidism and vitamin K antagonist therapy.

The Agatston score from non-contrast CT is graded as 0 (none), 1 to 99 (mild), 100 to 399 (moderate), 400 or more (severe), and over 1000 (extensive). A score of 0 identifies low short term risk, and risk climbs steadily with higher scores.

Medial calcification (Monckeberg) is a separate pattern that follows the vessel wall in kidney disease and diabetes and is common in peripheral arteries.

Pathophysiology.

Smooth muscle cells transform into osteoblast like cells under the influence of inflammation, oxidised lipids, hyperphosphataemia, raised calcium phosphate product and loss of calcification inhibitors such as matrix Gla protein (which depends on vitamin K) and fetuin-A.

Early calcification appears as microcalcification in inflamed plaque, which can be unstable. Dense, large calcified plaque is more stable, so statins raise the density of calcium while lowering events.

A heavily calcified lesion resists balloon expansion, damages stent polymer, and causes stent underexpansion, which predicts stent thrombosis and restenosis.

Calcification itself causes no symptoms. Patients present with angina, an acute coronary syndrome, or an incidental finding on chest CT. A calcified left main or proximal vessel may produce stable exertional symptoms. Features of causes include renal failure, hyperparathyroidism, and hypercalcaemia.

• Non-contrast ECG-gated CT with 3 mm slices: calcified area of 1 mm2 or more with density of 130 Hounsfield units or more. Report the Agatston score, number of vessels, and the age- and sex matched percentile. Calcium on a chest CT done for another reason should be reported at least qualitatively.
• Fluoroscopy and angiography: moderate calcification appears as densities only during cardiac motion, and severe calcification as densities visible without motion on both sides of the wall.
• Intravascular ultrasound or optical coherence tomography before intervention: calcium arc over 180 degrees, thickness over 0.5 mm and length over 5 mm predict stent underexpansion.
• Metabolic tests: calcium, phosphate, parathyroid hormone, 25-hydroxyvitamin D, creatinine and eGFR, HbA1c, lipids and lipoprotein(a).
• CT coronary angiography is less accurate in heavily calcified vessels because of blooming.

Differential diagnosis.

• Calcified nodule and calcified thrombus.
• Medial calcification of kidney or diabetic disease.
• Pericardial and valve annular calcification.
• Vasculitis, hypervitaminosis D and calciphylaxis.

Prevention by score (no established coronary disease).

• Score of 0: usually defer statin and aspirin unless diabetes, current smoking, strong family history or very high LDL cholesterol. Repeat in 5 to 10 years.
• Score of 1 to 99: favour a statin, particularly over age 55 and with other risk factors.
• Score of 100 or more, or over the 75th percentile: start a statin.
• Score of 400 or more: high intensity statin and target LDL cholesterol under 1.8 mmol/L (under 1.4 mmol/L when disease is established). Low dose aspirin 75 to 100 mg daily may be used when bleeding risk is low, though evidence is weak.
• Atorvastatin 40 to 80 mg orally once daily (maximum 80 mg) or rosuvastatin 20 to 40 mg once daily (maximum 40 mg; start 5 mg and limit to 10 mg when eGFR is under 30 mL/min/1.73 m2). Check lipids at 4 to 12 weeks, then yearly. ALT at baseline and with symptoms. Add ezetimibe 10 mg daily, then a PCSK9 monoclonal antibody (evolocumab 140 mg every 2 weeks or alirocumab 75 to 150 mg every 2 weeks) when targets are unmet.
• Control blood pressure (under 130/80 mmHg), glucose, weight and smoking.

Treat accelerating factors.

• Chronic kidney disease: phosphate control with dietary restriction and sevelamer carbonate 800 to 1600 mg orally three times daily with meals (maximum 13 g daily; reduce if serum phosphate is low); avoid calcium based binders in large doses; correct vitamin D deficiency; cinacalcet 30 mg daily titrated every 2 to 4 weeks to 180 mg for secondary hyperparathyroidism (monitor calcium weekly at first).
• Replace warfarin with a direct oral anticoagulant when the indication allows.
• Avoid unnecessary calcium and vitamin D supplements.

Percutaneous treatment of heavily calcified lesions.

• Prepare the lesion before stenting. Use a non-compliant or super-high-pressure balloon, or scoring or cutting balloon.
• Rotational atherectomy: burr-to-vessel ratio 0.5 to 0.6, speed 140,000 to 150,000 revolutions each minute, runs under 20 seconds with no more than a 5,000 revolution drop, flush with heparinised saline and nitroglycerin. Contraindicated in thrombus containing lesions, vein grafts, severe dissection and, with caution, unprotected left main. A temporary pacing wire is often placed for right or dominant circumflex lesions. Complications are slow flow, perforation and burr entrapment.
• Orbital atherectomy or intravascular lithotripsy (10 pulses each cycle, usually 80 pulses in total, at balloon pressure of 4 atmospheres) are alternatives, and excimer laser is used for uncrossable lesions.
• Intravascular imaging after stenting to confirm full expansion, with high pressure post-dilatation.
• Surgical revascularisation for multivessel or left main disease with extreme calcification.
• Antiplatelet therapy is by indication, with aspirin 75 to 100 mg daily plus a P2Y12 inhibitor for 6 to 12 months after stenting.

Monitoring. Lipids at 4 to 12 weeks then yearly, blood pressure and HbA1c at each visit, calcium, phosphate and parathyroid hormone every 3 to 6 months in kidney disease. Repeat calcium scoring is not needed solely to monitor treatment.

Referral and escalation. Refer for angiography when symptoms are typical or a score of 400 or more comes with a positive functional test. Refer to nephrology for abnormal mineral metabolism.

Special groups.

• Pregnancy: statins are stopped; manage risk after delivery.
• Dialysis: calcification is progressive and often extreme, so plan intervention with experienced operators.
• Older adults: statin intensity by frailty; weigh bleeding when considering aspirin.