Statins and coronary artery calcium: What's the score?

In this issue of Atherosclerosis, Osei et al. sought to understand the prognostic value coronary artery calcium (CAC) for predicting risk among individuals already on statin therapy [[1]Osei AD, Mirbolouk M, Berman D, Budoff MJ, Miedema MD, Rozanski A, Prognostic Value Coronary Artery Calcium Score, Area, and Density Among Individuals Statin Therapy vs. Non-users: Consortium. Atherosclerosis..Google Scholar]. Risk assessment is bedrock primary prevention atherosclerotic cardiovascular disease (ASCVD). However, observations over last two decades consistently suggest that quantitative with a variety clinical scores imprecise can lead systematic under- or overestimation events. Most recently, quantification CAC was found significantly reclassify downward in approximately half all borderline (5% <7.5%) intermediate (7.5% <20%) based 10-year Pooled Cohort Equations [[2]Nasir K. Bittencourt M.S. Blaha M.J. Blankstein R. Agatson A.S. Rivera J.J. al.Implications testing candidates according American College Cardiology/American heart association cholesterol management guidelines.MESA (Multi-Ethnic Study Atherosclerosis). 2015; 66: 1657-1668Google Indeed, 2018 Heart Association (ACC/AHA) Cholesterol Guidelines, 2019 ACC/AHA Guideline Primary Prevention Cardiovascular Disease, European Society Cardiology/European Atherosclerosis Guidelines Management Dyslipidaemias emphasize importance refine estimation [3Grundy S.M. Stone N.J. Bailey A.L. Beam C. Birtcher K.K. Blumenthal R.S. al.AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline blood cholesterol: A Report Task Force Clinical Practice Guidelines.Circulation. 18 Jun 2019; 139 (Epub Nov 10): e1082-e1143https://doi.org/10.1161/CIR.0000000000000625Crossref PubMed Scopus (755) Google Scholar, 4Arnett D.K. Albert M.A. Buroker A.B. Goldberger Z.D. Hahn E.J. al.ACC/AHA disease: executive summary: report task force practice guidelines.J. Am. Coll. Cardiol. : 2019Google 5Mach F. Baigent Catapano Koskinas K.C. Casula M. Badimon L. al.2019 ESC/EAS dyslipidaemias: lipid modification reduce risk.Eur. J. (PMID: 30586774; PMCID: PMC7403606): e1182-e1186Google scanning widely available, simple obtain, reproducible, cost-effective [[6]van Kempen B.J. Spronk S. Koller M.T. Elias-Smale S.E. Fleischmann K.E. Ikram al.Comparative effectiveness cost-effectiveness computed tomography screening asymptomatic individuals.J. 2011; 58: 1690-1701Crossref (55) Notably, guidelines should be considered when decision initiate uncertain patients without ASCVD, diabetes, severe hypercholesterolemia [[3]Grundy The endorsement national closely integrate as aid represents major advance from prior iterations. an unsettled relates utility who are therapy. It known statins increase Agatston score, primarily driven by increasing density, despite fact they decrease ASCVD events [[7]Henein Granåsen G. Wiklund U. Schmermund A. Guerci Erbel al.High dose long-term accelerate calcification.Int. 184: 581-586Abstract Full Text PDF (86) This apparent paradox led Committee state “CAC measurement has no treated Scholar].” examined significance users leveraging data Consortium, multicenter cohort underwent physician-ordered scans stratification Scholar,[8]Blaha Whelton S.P. Al Rifai Dardari Z.A. Shaw L.J. Al-Mallah M.H. al.Rationale design consortium: study.Journal Computed Tomography. 2017; 11: 54-61Abstract (41) Their analysis consisted 28,025 (6151 (22%)) were followed median 11.2 years included 395 (CVD) 182 (CHD) deaths. classified using standard categories: = 0, 1–99, 100–399, ≥400, natural-log transformed continuous variable. Additionally, area, volume, density also assessed. modest, significant negative interaction between score use observed both outcomes. While area volume predictive across baseline status, only (inversely) associated non-users. relationship complex must placed context. there several methods measure CAC, greatest validation large observational studies. Other scoring systems have been proposed, including mass though neither overtaken which remains gold [[9]Blaha Mortensen M.B. Kianoush Tota-Maharaj Cainzos-Achirica scoring: it time change methodology?.JACC Cardiovasc Imaging. 10: 923-937Crossref (99) As mentioned previously, total thought stabilize existing plaque [[10]Puri Nicholls S.J. Shao Kataoka Y. Uno Kapadia S.R. al.Impact serial calcification during atheroma progression regression.J. 65: 1273-1282Crossref (295) Scholar,[11]Blaha Martin S.S. How do work?: changing paradigms implications allocation.J. 2013; 62: 2392-2394Crossref (32) Accordingly, Criqui analyzed Multi-Ethnic (MESA) demonstrate (after adjusting volume) inversely incident outcomes, while density) positively outcomes Scholar,[12]Criqui Denenberg J.O. Ix J.H. McClelland R.L. Wassel C.L. Rifkin D.E. al.Calcium events.Jama. 2014; 311: 271-278Crossref (314) these models adjusted other factors. present study confirmed positive associations authors did not observe inverse users. maintained those Although acknowledge discrepancy non-users perplexing, important considerations. First, cohorts used studies vastly different. Compared MESA cohort, Consortium younger (66 vs 57 years), higher predominance men (58% 72%) white (44% 94%) participants [[12]Criqui Prior established substantial differences distribution race/ethnicity, interactions age gender race/ethnicity [[13]McClelland Chung H. Detrano Post W. Kronmal R.A. Distribution race, gender, age.Circulation. 2006; 113: 30-37Crossref (529) Second, composed clinically indicated scan after physician referral [[8]Blaha Scholar], may indication and/or selection bias, obtained priori at exam thus eliminating biases [[14]Bild Bluemke D.A. Burke G.L. Diez Roux A.V. Folsom A.R. al.Multi-ethnic Atherosclerosis: objectives design.Am. Epidemiol. 2002; 156: 871-881Crossref (2233) Third, provides information intensity duration therapy, likely influence making results challenging interpret. Finally, most concern exhibited characteristics. generally older, rates hypertension, hyperlipidemia, family history CHD, diabetes. Thus, multifactorial, related their burden factors biological effects morphology, relative contributions area/volume/density difficult discern one another. These confound Limitations aside, findings presented here intriguing. Does evidence allow clinicians confidently incorporate into stable chronic Scholar]? Let us consider 50-year-old male diabetes low-density lipoprotein (LDL)-cholesterol (LDL-C) 95mg/dL moderate sees his healthcare provider obtaining 400 units (AU). Is future truly optimized? addition lifestyle initiation baby aspirin [[15]Cainzos-Achirica M.D. McEvoy J.W. Greenland P. Z. al.Coronary personalized allocation 2019.Circulation. 2020; 141: 1541-1553Crossref (20) could argue LDL-C adequately controlled, given CAC>300 AU exhibit approaches secondary event [[16]Budoff Gransar Achenbach Bax D. al.When does equate prevention: insights confirm registry.J. 73: 1632Crossref process make intuitive sense, currently convincing setting specific thresholds extent improves Nonetheless, provide first step following reasoning its logical conclusion. Based presented, appears retains prediction observation lays groundwork investigate whether intensifying lowering high (i.e. AU) directed medical leads reductions congratulated expanding our thinking imagining where longer ‘one size fits all.’ declare competing financial interests personal relationships appeared work reported paper. vs. non-users: consortiumAtherosclerosisVol. 316PreviewStatins density. Therefore, we scanning. Full-Text