Curr Atheroscler Rep (2016) 18: 13 DOI 10.1007/s11883-016-0565-6

CORONARY HEART DISEASE (S. VIRANI AND S. NADERI, SECTION EDITORS)

An Update on the Utility of Coronary Artery Calcium Scoring for Coronary Heart Disease and Cardiovascular Disease Risk Prediction Sina Kianoush 1 & Mahmoud Al Rifai 1 & Miguel Cainzos-Achirica 1,2 & Priya Umapathi 1 & Garth Graham 4,5 & Roger S. Blumenthal 1 & Khurram Nasir 1,6,7,8 & Michael J. Blaha 1,2,3

Published online: 15 February 2016 # Springer Science+Business Media New York 2016

Abstract Estimating cardiovascular disease (CVD) risk is necessary for determining the potential net benefit of primary prevention pharmacotherapy. Risk estimation relying exclusively on traditional CVD risk factors may misclassify risk, resulting in both undertreatment and overtreatment. Coronary artery calcium (CAC) scoring personalizes risk prediction through direct visualization of calcified coronary atherosclerotic plaques and provides improved accuracy for coronary heart disease (CHD) or CVD risk estimation. In this review, we discuss the most recent studies on CAC, which unlike historical studies, focus sharply on clinical application. We describe the MESA CHD risk calculator, a recently developed CAC-based 10-year CHD risk estimator, which can help guide preventive therapy

This article is part of the Topical Collection on Coronary Heart Disease * Michael J. Blaha [email protected]

1

Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD 21287, USA

2

Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD 21287, USA

3

Blalock 524 D1, 600 N. Wolfe St., Baltimore, MD 21287, USA

4

Aetna Foundation, Hartford, CT, USA

5

University of Connecticut School of Medicine, Farmington, CT, USA

6

Center for Healthcare Advancement and Outcomes & Miami Cardiac and Vascular Institute, Baptist Health South Florida, Miami, FL, USA

7

Department of Epidemiology, Robert Stempel College of Public Health, Miami, FL, USA

8

Department of Medicine, Herbert Wertheim College of Medicine, Miami, FL, USA

allocation by better identifying both high- and low-risk individuals. In closing, we discuss calcium density, regional distribution of CAC, and extra-coronary calcification, which represent the future of CAC and CVD risk assessment research and may lead to further improvements in risk prediction. Keywords Coronary artery calcium . Coronary heart disease . Cardiovascular disease . Risk assessment . Primary prevention . Statins

Abbreviations ACC/AHA American College of Cardiology /American Heart Association ASCVD Atherosclerotic cardiovascular disease CAC Coronary artery calcium CAC = 0 Coronary artery calcium score of zero CHD Coronary heart disease CTA Computed tomographic angiography CVD Cardiovascular disease DHS Dallas Heart Study ECC Extra-coronary calcification HRS Heinz-Nixdorf Recall Study MESA Multiethnic Study of Atherosclerosis PCE Pooled Cohort Equations cPCE Recalibrated Pooled Cohort Equations ROC Receiver-operator characteristic

Introduction Cardiovascular disease (CVD) is the leading cause of death worldwide [1]. To effectively reduce the burden of atherosclerotic CVD (ASCVD) events, recent guideline recommendations are directed toward risk prediction prior to the decision

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to treat with pharmacotherapy to best match treatment to those most likely to benefit [2]. For this aim, current widely used risk scores estimate 10-year coronary heart disease (CHD) or ASCVD risk [3] using traditional risk factors such as age, gender, blood pressure, diabetes, and serum cholesterol levels. Such focus on traditional risk factors rather than on the direct assessment of disease in the target vessels [4], an approach that medical technology has made possible since the early 1990s [5], has limited for long the accuracy of these scores, often contributing to misclassification of risk and subsequent undertreatment or overtreatment [6, 7•]. In this context, the latest US risk estimator (the 2013 American College of Cardiology/American Heart Association [ACC/AHA] Risk Estimator) placed particular emphasis on age and gender [3, 7•], which have become key drivers of risk predictions. As a consequence, subpopulations with characteristics placing them at higher risk of CHD and ASCVD may be overlooked, resulting in insufficient risk management. This may include young or middle-aged individuals with metabolic syndrome traits or a family history of premature CHD (characteristics not incorporated in most risk estimators) [8•], women with pre-eclampsia [9], non-elderly men with vascular erectile dysfunction [10], and non-elderly non-White, non-African-American racial/ethnic subgroups at an increased risk of CHD, such as those of South Asian origin [11]. On the other hand, this also results in the overestimation of risk in a large proportion of elderly individuals, particularly among men—resulting in potentially harmful overtreatment. These limitations of current risk algorithms call attention to the need for a more personalized risk assessment, which might allow for a better identification of high-risk individuals who will benefit from pharmacological treatments, while also withholding unnecessary lifelong preventive pharmacotherapies from truly low-risk asymptomatic individuals [7•]. Coronary artery calcium (CAC) testing via non-contrast cardiac-gated computed tomography enables direct visualization of calcified atherosclerosis [7•, 12]. Importantly, while traditional risk scores utilize risk factor assessment at a single point in time (for example by measuring blood pressure during a single office visit), CAC represents the cumulative downstream effects of both measured and unmeasured CVD risk factors over an individual person’s lifetime [7•]. Consequently, CAC has been shown to be a superior prognosticator of future events compared to different combinations of single-time measurements of traditional risk factors [7•, 8•, 13••, 14••, 15, 16••, 17•, 18••]. The aim of this review is to discuss the most recent studies on the epidemiology and the clinical utility of CAC for risk prediction. While the general epidemiology of CAC has been known for some time, in this review, we pay special attention to studies investigating the predictive value of CAC beyond 10 years, as well as to those assessing CAC as a predictor of cerebrovascular events. Regarding its clinical application,

Curr Atheroscler Rep (2016) 18: 13

studies in 2015 are unique in their use of applied epidemiologic techniques to hone in on the appropriate use of CAC in clinical practice within the context of the most recent guidelines. We discuss those studies in detail, including the recently published BMESA Risk Score.^ Lastly, we review the emerging concepts with regard to the role of coronary calcium density, regional distribution of coronary calcium, and extra-coronary calcification (ECC) in CHD and ASCVD risk prediction (Table 1). CAC in the 2013 ACC/AHA Prevention Guidelines The 2013 ACC/AHA ASCVD Prevention Guidelines included recommendations on risk assessment and treatment of blood cholesterol. A new 10-year ASCVD risk estimator was developed, and there was an increased emphasis on absolute risk for initiating lipid-lowering therapy with statins, followed by a clinician-patient risk discussion considering the benefits and harms of treatment [19]. Integrated in the guidelines was the use of CAC for further risk assessment if Bthe decision to start statin therapy is unclear after quantitative risk assessment^ [3]. According to the Writing Group of the risk assessment document, a CAC score ≥300 Agatston units or ≥75th percentile for age, sex, and ethnicity would favor statin use (Class IIb recommendation) [3]. Recent studies have suggested a wider use of CAC in clinical practice for a more personalized risk assessment, arguing for a more broad interpretation of CAC testing under the new guidelines. Indeed, studies in 2015 have shown that incorporating patient-specific atherosclerosis imaging data within the broader scope of traditional ASCVD risk may better delineate risk groups. Latest Research on the Role of CAC for Accurate Identification of Risk Groups CAC is a powerful tool for discrimination of CHD risk beyond that provided by traditional risk factors [20••]. Prior studies demonstrated that individuals who had high CAC without known traditional cardiovascular risk factors were at higher risk of CHD events compared with those who had no CAC (CAC = 0) and a high burden of traditional risk factors [15]. For example, CAC has been shown to predict CHD risk independent of age [21, 22] and even below the typical age of treatment under the current preventive guidelines [23]. Importantly, an increasing CAC burden imparts a continuously graded decrease in survival with no apparent upper threshold [24]. CAC for BUpgrading^ Risk The new Pooled Cohort Equations (PCE) form the basis of the 10-year ACC/AHA 2013 ASCVD risk estimator. Nevertheless, the equations were derived from older cohorts, which results in a notable overestimation of

Curr Atheroscler Rep (2016) 18: 13 Table 1

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Summary of most important new studies regarding coronary artery calcification

Clinical application

Longer-term prediction with CAC

Beyond the Agatston score

First author (year)

Type of study and study population

Important note

Yeboah (2015)

Prospective (MESA)

Presence of CACa can detect unheralded risk and upgrade the risk of CVD in individuals who are low risk using a recalibrated ACC/AHA Risk Estimator.

Nasir (2015)

Prospective (MESA)

Absence of CAC can downgrade and reclassify CVD risk into a no treatment group using the conventional ACC/AHA Risk Estimator

McClelland (2015)

Prospective (MESA)

First publication of a 10-year risk score incorporating CAC. The MESA Risk Score enables calculation of risk before and after knowledge of a CAC score.

Shaw (2015)

Retrospective cohort

Valenti (2015)

Retrospective cohort

The predictive value of CAC extends out to 15 years, without significant interaction with duration of follow-up, confirming long-term value of CAC for mortality risk prediction. Confirms that the time that all-cause mortality rate remained

An Update on the Utility of Coronary Artery Calcium Scoring for Coronary Heart Disease and Cardiovascular Disease Risk Prediction.

Estimating cardiovascular disease (CVD) risk is necessary for determining the potential net benefit of primary prevention pharmacotherapy. Risk estima...
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