CV Academy 2021: detecting subclinical atherosclerosis

The Amgen-sponsored CV Academy 2021 invited Professor Christian Hamilton-Craig from Noosa Hearts Cardiology and Prof of Medicine at UQ and Griffith, to speak about his vast experience in detecting subclinical atherosclerosis.

 Subclinical atherosclerosis

Atherosclerosis starts early in life and has a long subclinical phase allowing a large window of opportunity to detect patients, predominately with imaging but also with risk prediction tools in a broader context,” said Prof Hamilton-Craig. He explained that Vietnam war autopsy studies showed early atherosclerosis in up to 50% of young, thought-to-be healthy 20-year-olds and this data was mirrored in the Cardiovascular Health Study.1 Subclinical atherosclerosis was first measured by ultrasound and then later computed tomography (CT), he said.

Prof Hamilton-Craig showed a video of the development of an atherosclerosis plaque and the path to plaque rupture to emphasise what clinicians are trying to prevent. “When that is going to happen – and in what patient – is hard to tell,” he noted. What we can do is look at the carotid, a large vascular subcutaneous structure that is easily imaged, Prof Hamilton-Craig explained. Carotid intimal-media thickness (CIMT) takes into account the intra and inter-observer variability and can be measured both with ultrasound and with MRI.2 CIMT may be due to subclinical atherosclerosis, but can also be the result of nonatherosclerotic processes such as smooth muscle cell hyperplasia and fibrocellular hypertrophy. Prof Hamilton-Craig stated that a more precise way is to look at carotid with MRI. High resolution MRAngiography, Black Blood and post-contrast imaging can delineate plaque with lipid-rich necrotic core and calcification (although CT is more sensitive for calcium).3

For overlap with coronary artery disease, Prof Hamilton-Craig discussed a study out of Spain, the Progression of Early Subclinical Atherosclerosis (PESA) trial with 4184 asymptomatic subjects aged 40-54.4 They looked at the extent of atherosclerosis in various vascular territories; carotid, aorta, iliac-femoral, and coronary arteries. “The message from this large observational cohort is subclinical atherosclerosis is highly prevalent in asymptomatic middle-aged subjects.”

Coronary artery calcium score (CAC)

Prof Hamilton-Craig explained that imaging of subclinical coronary atherosclerosis was first looked at with coronary artery calcium (CAC) and is the most widely-used technique for demonstrating subclinical coronary atherosclerosis. CAC is an ECG-gated non-contrast CT scan of the chest.

To highlight the use of CAC score, Prof Hamilton-Craig discussed a patient who was initially assessed as a low-intermediate risk patient and not recommended for therapy but with imaging of coronary arteries and a high calcium score was reclassified as high risk. “Using risk predictors, even validated ones, is very helpful in assessing populations but when it comes down to the individual patient, knowing where that patient sits in the risk bell curve, you have greater precision when you image the coronary arteries or carotids to know if there is atherosclerosis in that particular patient,” he explained.

Prof Hamilton-Craig showed the MESA calculator, and how the estimated 10-year risk of a CHD event can increase when including the calcium score.5 He explained that as CAC increases, so does mortality.6  To summarise, he noted that if you want to see if someone has subclinical coronary atherosclerosis it is important to do an imaging test like CAC to detect it.

Coronary CT Angiography

Prof Hamilton-Craig said that Coronary CT Angiography is a different test requiring a lot more patient input. It is an extremely accurate, non-invasive test for both atherosclerosis and non-calcified atherosclerosis in appropriate patients. Of note, Prof Hamilton-Craig stated that coronary CT is far more sensitive to plaque than invasive angiography. “CT high risk features do correlate with downstream acute coronary syndrome,” he said. There are four main features of coronary CT, positive remodelling, low density HU, napkin ring sign and spotty calcium explained Prof Hamilton-Craig.7 Finally he discussed peri-coronary adipose tissue (PCAT) as a non-invasive and surrogate marker of coronary inflammation with the potential to image changes associated with coronary artery disease (CAD) in both stable and ‘vulnerable’ populations.8

In conclusion, Prof Hamilton-Craig explained that each vascular bed can have dedicated imaging to find out if an individual has subclinical atherosclerosis. In the coronary arteries the CAC score still remains the strongest independent predictor of risk, he said.


  1. Gatto L, Prati F. European Heart Journal Supplements, Volume 22, June 2020: E87–E90.
  2. Simova, ESC Cardiology Practice Vol. 13, N21 – 05 May 2015.
  3. Kerwin WS, et al. MRI of Carotid Atherosclerosis. American Journal of Roentgenology. 2013;200:W304-313.
  4. Fernández-Friera et al. PESA Study. Circulation2015;131:2104–2113.
  6. Budoff et al, JACC 2007. 2007;49:1860–1870
  7. Motoyama et al, JACC 2009;54(1):49-57.
  8. Yuvaraj, J, et al. Cells. 2021;10:1196.

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