Coronary Artery Calcium
2018; Lippincott Williams & Wilkins; Volume: 137; Issue: 7 Linguagem: Inglês
10.1161/circulationaha.117.031951
ISSN1524-4539
Autores Tópico(s)Coronary Interventions and Diagnostics
ResumoHomeCirculationVol. 137, No. 7Coronary Artery Calcium Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBCoronary Artery CalciumIf Measuring Once Is Good, Is Twice Better? Amit Khera, MD, MSc and Philip Greenland, MD Amit KheraAmit Khera Department of Internal Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas (A.K.) and Philip GreenlandPhilip Greenland Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (P.G.) Originally published13 Feb 2018https://doi.org/10.1161/CIRCULATIONAHA.117.031951Circulation. 2018;137:680–683Article, see p 665You're always you, and that don't change,and you're always changing, and there's nothing you can do about it.—Neil Gaiman, The Graveyard BookAtherosclerosis is a dynamic process that is constantly changing and morphing. Unchecked, this constant change can lead to advancement and disruption, culminating in ischemic heart disease and myocardial infarction. However, this dynamic nature also offers opportunities to intervene with preventive therapies to halt or reverse course before these adverse outcomes occur. These properties also offer the allure of quantifying change in atherosclerosis to better pinpoint and personalize atherosclerotic cardiovascular disease (ASCVD) risk estimates.Several novel screening tests have been evaluated to improve ASCVD risk assessment; of these tests, coronary artery calcium (CAC) scanning has emerged as the top contender. High CAC scores are associated with a markedly increased risk of coronary heart disease (CHD) (4- to 10-fold higher) independent of other risk factors, and CAC has been shown to improve clinical reclassification of CHD and ASCVD risk.1–3 In addition, those with no CAC have a relatively good prognosis and may consider deferring preventive therapies such as statins.4 There has been growing interest in exploring whether repeat CAC scanning, thereby evaluating change in the CAC score, could enhance cardiovascular risk prediction. An early study from 2004 suggested that change in CAC may be a meaningful and additive contribution to predicting an individual's risk.5 However, only in the last several years have population-based studies become available with paired scans and adequate numbers of ASCVD events.6,7Using MESA (Multi-Ethnic Study of Atherosclerosis), Budoff et al6 examined the relationship of CAC progression to CHD outcomes in a cohort of 6778 subjects with an interscan interval of 2.5 years. They demonstrated that CAC change of a fairly large magnitude (>100 U/y) was associated with hard CHD independent of CHD risk factors and baseline CAC score (hazard ratio, 1.3; 95% confidence interval, 1.1–1.5). However, no data were provided regarding the incremental value of CAC progression to baseline CAC regarding metrics such as improvement in the C statistic of the model or net reclassification improvement. Also, CAC change was only the fifth strongest risk marker for CHD, following after baseline CAC, male sex, systolic blood pressure, and total cholesterol. In a study by Radford et al8 from the Cooper Center Longitudinal Study, a referred clinic population, CAC progression was similarly independently associated with ASCVD events. However, the contribution of CAC change to the prediction of these events was again modest when compared with the information contained in the baseline CAC score.In the current issue of Circulation, Lehmann et al7 revisit this topic in the population-based Heinz Nixdorf Recall study. They evaluated 3281 subjects with paired scans performed over a larger interscan interval, 5.1 years, and with 7.8 years of follow-up after the second scan, resulting in 85 hard coronary, 161 hard cardiovascular, and 241 total cardiovascular events inclusive of revascularization. The unique contributions of this article beyond the longer interscan and follow-up periods include the assessment of 10 different proposed algorithms to quantify CAC progression and the inclusion of rigorous statistical metrics to interrogate the incremental value of CAC progression to outcome prediction. Although various measures of CAC progression were independently associated with outcomes, none of the 10 CAC progression algorithms demonstrated an improvement in the C statistic or net reclassification of risk for hard CHD or hard ASCVD compared with models including risk factors and baseline CAC score.Taken together, these studies and other recent publications in this area are beginning to form a framework for how to conceptualize the potential utility and application of repeat CAC scanning in clinical practice. Although no formal guidelines are available, we believe that in general, the majority of the predictive information is obtained from the initial CAC scan, with little benefit from a second scan. However, several nuances and caveats to this statement are best described through subsetting of patients by CAC score category.High Baseline CAC Score (≥400)Patients with a high baseline CAC score are at considerable CHD and ASCVD risk (≈10% to 15% 10-year risk).2,7 The current American College of Cardiology/American Heart Association 2013 Cholesterol Guidelines state that when the decision to initiate a statin remains unclear, a CAC score ≥300 may be used to inform decision making (ie, can be used to up-classify risk).9 As such, most patients with high CAC scores warrant statin therapy. In this group, the value of repeat scanning is negligible. High-intensity statin therapy is already reasonable because most will have a 10-year ASCVD risk >7.5%, and withdrawing or withholding therapy based on subsequent scan results would be misguided. Thus, repeat scanning in this group should be avoided.Intermediate CAC Score (>1–399)From both a Bayesian and clinical decision-making perspective, most tests are best applied to intermediate-risk patients. Here, patients and physicians may be on the fence about treatment, and CAC scoring appears to be particularly informative for this group.10 The 10-year CHD/ASCVD risk ranges from 3% to 6%,7 although there is a large spectrum of CAC scores and accompanying risk levels in this group. Whether repeat CAC scoring provides incremental risk information in this subgroup was not explored by the study by Lehmann et al,7 but the totality of evidence suggests that any added information will be modest. Lehmann et al7 also suggested that those with a CAC score >400 on the subsequent scan are at higher risk than those remaining <400, yet the hard ASCVD risks with either subsequent score range ( 100–399In our view, those on the higher end of this spectrum (ie, >100) would achieve little benefit from repeat scanning because their risk level would generally be >5% 10-year ASCVD risk, a threshold where statins are already an appropriate option.9 It is worth noting that in patients with prevalent CAC, change in CAC is "inevitable" and "predictable", as demonstrated by the Heinz Nixdorf investigators11 in a prior manuscript. Applying their predictive equation to the current study, the authors demonstrated that 68% of subjects had expected CAC progression, with 19% having rapid progression and only 13% with slow progression. In our experience, patients often do not appreciate that some increase in CAC score over time is generally expected and sometimes erroneously interpret this change as a failure of preventive interventions. Without evidence for significant incremental information of repeat CAC scanning in this group, the potential for misinformation and radiation risks appear to outweigh potential benefits.CAC Score 1–100In patients with CAC scores of 1 to 100 who elect to defer statin therapy or other preventive interventions, a case could be made for reassessment of CAC in concert with repeat global ASCVD risk assessment after an appropriate interval (ie, 5 years). Such a strategy should only be pursued after an informed discussion with the patient and only if the results would change management. Patients with CAC in this range are often younger, meaning the modest incremental cancer risk of repeat CAC scanning is greater than in older individuals, which should be incorporated in this discussion. More definitive data in this subgroup of patients are needed.CAC of 0With much data now available, the prognostic value of a CAC score of 0 has come into focus, and many such patients receive a revised risk estimate below the statin treatment threshold.4 A particularly valuable observation from the study by Lehmann et al7 is the excellent prognosis in those with repeat CAC scores of 0 (ie, double zero group). In contrast, those patients who convert and develop CAC have a slightly worse prognosis (≈1.5-fold higher risk). Some studies have suggested that the warranty of a CAC score of 0 is ≈5 years in that the probability of a significant change in CAC is low when the scanning interval is less than this. It should be noted that although those who develop CAC have a higher risk, their absolute 10-year ASCVD risk is still quite low (<5%). However, these patients would have a higher lifetime risk of ASCVD,12 and they are likely on a different long-term risk trajectory than those who remain at 0. Taking this lifetime view in perspective, a repeat scan usually would not be indicated unless there were significant levels of traditional risk factors making the warranty of CAC of 0 questionable on a long-term basis.How to Interpret the Repeat ScoreA final consideration for those who elect to undergo repeat scanning is, what is the optimal way to quantify CAC change? Several algorithms have been proposed, including 10 explored by the Heinz Nixdorf Recall study investigators,7,13 with no clear consensus on the best method. In fact, these algorithms provide only modestly concordant results for categorizing progressors.14 The Cooper Clinic study demonstrated that the second CAC score alone was as good in predictive accuracy as the baseline CAC score and CAC change variable, and that CAC change was not associated with ASCVD events when accounting for the second CAC score.8 This observation was replicated in the current study by Lehmann et al.7 Therefore, in those where a second CAC scan is performed, the best strategy seems to be to incorporate the most recent CAC score into risk assessment, rather than focusing on the rate of change. The MESA investigators have developed a useful tool for this purpose, an integrated CAC and risk factor calculator to predict CHD risk, and other such calculators are in development to predict ASCVD.15Although atherosclerosis is a dynamic process, it is also a lifelong one. By the time a patient undergoes CAC scanning in middle or older age, he or she has been exposed to a risk factor and lifestyle milieu for decades on the backdrop of a genetic code programmed from birth, which is integrated into a quantity of atherosclerosis captured by the CAC scan. By and large, by that point, they are who they are, and reassessing their atherosclerosis burden after a mere 5 years cannot override the dominant risk information of this baseline scan. The current data suggest that repeat scanning will offer insightful and important information in relatively few people.DisclosuresNone.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.http://circ.ahajournals.orgAmit Khera, MD, MSc, Division of Cardiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390–8830. E-mail [email protected]References1. 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February 13, 2018Vol 137, Issue 7 Advertisement Article InformationMetrics © 2018 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.117.031951PMID: 29440196 Originally publishedFebruary 13, 2018 Keywordsrisk factorsprimary preventionEditorialscomputerized tomographyPDF download Advertisement SubjectsAtherosclerosisCardiovascular DiseaseCoronary Artery Disease
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