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Coronary CT Angiography Guided Medical Therapy in Subclinical Atherosclerosis Journal of Clinical Medicine Review Coronary CT Angiography Guided Medical Therapy in Subclinical Atherosclerosis Alyssa L. S. Chow 1,2, Saad D. Alhassani 2, Andrew M. Crean 2 and Gary R. Small 2,* 1 Royal College of Surgeons in Ireland, Dublin 2, Ireland; [email protected] 2 Department of Medicine University of Ottawa, Division of Cardiology, Ottawa, ON K1Y 4W7, Canada; [email protected] (S.D.A.); [email protected] (A.M.C.) * Correspondence: [email protected]; Tel.: +1-613-696-7279 Abstract: The goals of primary prevention in coronary atherosclerosis are to avoid sudden cardiac death, myocardial infarction or the need for revascularization procedures. Successful prevention will rely on accurate identification, effective therapy and monitoring of those at risk. Identification and potential monitoring can be achieved using cardiac computed tomography (CT). Cardiac CT can determine coronary artery calcification (CAC), a useful surrogate of coronary atherosclerosis burden. Cardiac CT can also assess coronary CT angiography (CCTA). CCTA can identify arterial lumen narrowing and highlight mural atherosclerosis hitherto hidden from other anatomical approaches. Herein we consider the role of CCTA and CAC-scoring in subclinical atherosclerosis. We explore the use of these modalities in screening and discuss data that has used CCTA for guiding primary prevention. We examine therapeutic trials using CCTA to determine the effects of plaque-modifying therapies. Finally, we address the role of CCTA and CAC to guide therapy as defined in current primary prevention documents. CCTA has emerged as an essential tool in the detection and man- agement of clinical coronary artery disease. To date, its role in subclinical atherosclerosis is less well defined, yet with modern CT scanners and continued pharmacotherapy development, CCTA is likely Citation: Chow, A.L.S.; Alhassani, to achieve a more prominent place in the primary prevention of coronary atherosclerosis. S.D.; Crean, A.M.; Small, G.R. Coronary CT Angiography Guided Keywords: primary prevention; atherosclerosis; coronary CT angiography Medical Therapy in Subclinical Atherosclerosis. J. Clin. Med. 2021, 10, 625. https://doi.org/10.3390/ jcm10040625 1. Introduction Academic Editor: Michael Henein The first Chinese medical text (2600BC) foresightedly taught, “Inferior doctors treat Received: 31 December 2020 the full-blown disease, mediocre doctors treat the disease before evident, superior doctors Accepted: 1 February 2021 prevent the disease” [1]. Although as medical practitioners, we might not enjoy the im- Published: 7 February 2021 plications of the statement, there is wisdom in the saying that still holds true today. In healthcare we most commonly focus on symptomatic patients, often neglecting a popula- Publisher’s Note: MDPI stays neutral tion who may benefit from preventative treatment. This approach, however, is changing. with regard to jurisdictional claims in Increasingly, across medical specialties, we are witnessing advances in technology and published maps and institutional affil- imaging that present unprecedented opportunities to intervene before overt symptomatic iations. disease occurs [2]. This is especially so in cardiovascular disease, which remains a leading cause of death worldwide, claiming 17.9 million lives per year [3] of which approximately 50% of cases are attributed to coronary heart disease [4]. To address this need, coronary CT angiography Copyright: © 2021 by the authors. (CCTA) has gradually emerged over 20 years as an important diagnostic tool and begun to Licensee MDPI, Basel, Switzerland. impact disease prevention [5–8]. It readily identifies both obstructive and non-obstructive This article is an open access article coronary artery atherosclerotic plaque which is the forerunner of coronary artery disease distributed under the terms and (CAD) [9–11]. Not only does CCTA identify the presence of atherosclerotic plaque, it conditions of the Creative Commons accurately risk-stratifies patients at risk of suffering coronary atherosclerotic events [12,13]. Attribution (CC BY) license (https:// Thus, as we work to have CCTA employed in primary prevention, we strive to become the creativecommons.org/licenses/by/ ‘superior’ doctors outlined by ancient Chinese wisdom. 4.0/). J. Clin. Med. 2021, 10, 625. https://doi.org/10.3390/jcm10040625 https://www.mdpi.com/journal/jcm J. Clin. Med. 2021, 10, x FOR PEER REVIEW 2 of 14 J. Clin. Med. 2021, 10, 625 2 of 14 In this review we consider the definition of subclinical atherosclerosis, the pathogen- esis of atherosclerosis, its prevalence and current recommendations for atherosclerosis In this review we consider the definition of subclinical atherosclerosis, the pathogen- esisscreening. of atherosclerosis, We look at its t prevalencehe application and currentof cardiac recommendations CT in primary for prevention atherosclerosis by assessing screening.how it: (a) We refines look atrisk the prediction, application ( ofb) cardiacis employed CT in primaryto investigate prevention treatment by assessing, and (c) directs howtherapy it: (a) in refines primary risk prediction,prevention (b) guidelines. is employed to investigate treatment, and (c) directs therapy in primary prevention guidelines. 2. Subclinical versus Clinical Atherosclerosis 2. Subclinical versus Clinical Atherosclerosis Atherosclerosis is defined as an area in the intima layer of an artery that is lipid rich, Atherosclerosis is defined as an area in the intima layer of an artery that is lipid rich, contains cellular debris, lipid-laden cells, and inflammatory cells and is often calcified contains cellular debris, lipid-laden cells, and inflammatory cells and is often calcified (Figure(Figure1)[ 1)14 [14].]. Clinical Clinical obstructive obstructive atherosclerosis atherosclerosisdevelops develops when thiswhen area this encroaches area encroaches upon upon 50%50% or or more more of theof the vessel vessel lumen lumen and causesand causes ischemic ischemic symptoms. symptoms. Alternatively, Alternatively,clinical clinical non-obstructivenon-obstructive atherosclerosis atherosclerosismay may also also exist exist in the in the absence absence of a of 50% a 50% luminal luminal narrowing narrowing but butfollowing following an an acute acute plaque plaque event thatthat has has presented presented as anas acutean acute coronary coronary syndrome. syndrome. In Incontrast, contrast, subclinicalsubclinical atherosclerosis atherosclerosis isis characterisedcharacterised by by the the presence presence of asymptomaticof asymptomatic non- non-obstructiveobstructive or orobstructive obstructive atherosclerosis. atherosclerosis. FigureFigure 1. 1.Schematic Schematic representation representation of atherogenesis. of atherogenesis. Atherosclerosis Atherosclerosis develops develops from the secondfrom the and second thirdand decadethird decade of life onwards of life onwards in Western in populations Western populations and is characterized and is bycharacterized the gradual accumulation by the gradual accu- ofmulation lipid-rich of material lipid-rich within material the intimal within layer the of intimal arteries layer (Figure of adapted arteries from (Figure [14]). adapted from [14]). 3.3. Prevalence Prevalence of of Subclinical Subclinical Atherosclerosis Atherosclerosis Subclinical atherosclerosis occurs usually in the second and third decades of life in Subclinical atherosclerosis occurs usually in the second and third decades of life in individuals from developed countries [15]. Its development is thought to reflect genetic, nutritionalindividuals and from cultural developed factors [countries16,17]. The [15 disease]. Its development traditionally progresses is thought slowly to reflect for genetic, decadesnutritional before and the cultural onset of factors symptoms. [16,17 Determining]. The disease prevalence traditionally of a subclinical progresses condition slowly for dec- canades be before challenging; the onset autopsy of symptoms. data from AmericanDetermining soldiers prevalence who died of in a combatsubclinical has beencondition can instructivebe challenging; to assess autopsy the presence data of from atherosclerosis American and soldiers to track who the changesdied in incombat the pattern has been in- ofstructive disease over to assess time [ 18the]. presence of atherosclerosis and to track the changes in the pattern of diseasePrevalence over in time the young [18]. has declined over the past 60–70 years. Atherosclerosis was foundPrevalence in 77% of Korean in the war young American has declined casualties, over 45% the of those past from60–70 the years. Vietnam Atherosclerosis war, and was 12% in those who died in combat between 2001 and 2011 [18–20]. The decline speaks to the found in 77% of Korean war American casualties, 45% of those from the Vietnam war, and success of health behaviour and primary prevention programs [18]. 12% in those who died in combat between 2001 and 2011 [18–20]. The decline speaks to the success of health behaviour and primary prevention programs [18]. The prevalence of subclinical atherosclerosis in middle and older age was studied in the Multi-Ethnic Study of Atherosclerosis (MESA) study [21]. MESA recruited 6814 par- J. Clin. Med. 2021, 10, 625 3 of 14 The prevalence of subclinical atherosclerosis in middle and older age was studied in the Multi-Ethnic Study of Atherosclerosis (MESA) study [21]. MESA recruited 6814 participants aged 45–84 years without known cardiovascular disease and underwent coronary calcium
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