Physicians' Academy for Cardiovascular Education

Subclinical atherosclerosis found in over half of individuals considered low-risk by risk scores

Literature - Fernández-Friera L et al., Circulation. April 16, 2015

Prevalence, Vascular Distribution and Multi-territorial Extent of Subclinical Atherosclerosis in a Middle-Aged Cohort: The PESA (Progression of Early Subclinical Atherosclerosis) Study

Fernández-Friera L, Peñalvo JL, Fernández-Ortiz A et al.,
Circulation. April 16, 2015. doi: 10.1161/CIRCULATIONAHA.114.014310


The natural history of atherosclerosis involves a subclinical phase. Currently, risk stratification scores rely on identifiable risk factors and levels of biochemical markers, but in low-risk groups conventional risk assessment has well-recognised limitations [1,2].
Noninvasive imaging techniques, including vascular ultrasound, computed tomography (CT) and magnetic resonance imaging, allow evaluation of atherosclerosis in asymptomatic populations. Indeed, the presence of subclinical carotid atherosclerosis and coronary artery calcification (CAC) has been linked to clinical outcomes in the MESA study [3-5] and the US High Risk Plaque Study [6].
Many imaging studies evaluated individual vascular territories, although a multi-territory analysis might give a more comprehensive overview of the burden of this systemic condition. The prospective PESA (Progression of Early Subclinical Atherosclerosis) study evaluated atherosclerosis in the carotid, aortic, coronary and ilio-femoral territories, by means of accessible noninvasive imaging techniques in asymptomatic middle-aged individuals, without prior CV disease [7]. This article presents the prevalence, vascular distribution and extent of subclinical atherosclerosis (presence of plaque or CACS>1) in relatively young adults (n=4002, average age 45.8 years), and the relation of these features to CV risk algorithms.

Main results

  • The prevalence of subclinical atherosclerosis was 63%. Plaques were detected by ultrasound in 60% of individuals, of whom 31% had plaques in the carotids, 25% in the aorta and 44% in the ilio-femoral arteries. 18% of participants had CAC (CACS 1-99: 14%, 100-399: 3% and >400: 0.7%).
  • Men (71%) more often showed subclinical atherosclerosis that women (48%). Prevalence of atherosclerosis increased with age for both genders and in all vascular territories.
  • Presence of ilio-femoral disease was more strongly correlated with aortic disease (HR: 4.85, 95%CI: 4.09-5.75, P<0.001) and CAC (HR: 3.16, 95%CI: 2.60-3.94, P<0.001) than with carotid disease (HR: 2.13, 95%CI: 1.84-2.64, P<0.001).
  • 21% of patients showed focal disease, 28% intermediate and 13% generalised disease. Generalised disease was more common in men than in women, and increased with age, and with presence of obesity and traditional risk factors.
  • The extent of subclinical atherosclerosis in men of 40-44 years was similar to the extent in women who were 5-10 years older.
  • In the PESA cohort, mean Framingham Heart Study (FHS) 10-year risk score was 6%, with 85% of participants at low-risk, 14% at moderate risk and 1% at high risk. According to the European SCORE model, 85% were at low-risk and 15% at moderate-high risk.
    Among participants at low 10-year FHS risk, 58% had subclinical atherosclerosis, of whom 36% had intermediate or generalised disease. 95% of FHS high-risk individuals had atherosclerosis (86% intermediate or generalised). Similar proportions were seen for SCORE.
    When using the 10-year ASCVD risk algorithm, subclinical atherosclerosis was seen in 57% of people in the <5% group, as compared with 80% in 5-7.5% and 92% in the >7.5% group.


This study in the PESA cohort shows that subclinical atherosclerosis is highly prevalent in middle-aged asymptomatic individuals, and that the ilio-femoral territory is the most frequently affected site at early stages of atherosclerosis. Most individuals considered to be at high risk by traditional risk scores indeed have subclinical atherosclerosis, but atherosclerosis is also seen in almost 60% of participants who are classified at low risk according to the risk scores. Ongoing PESA follow-up will allow investigation of the association between subclinical disease and subsequent CV events.
Find this article online at Circulation


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