Author + information
- Received March 15, 2016
- Revision received May 17, 2016
- Accepted May 26, 2016
- Published online August 30, 2016.
- Martin Bødtker Mortensen, MD, PhDa,
- Valentin Fuster, MD, PhDb,
- Pieter Muntendam, MDc,
- Roxana Mehran, MDb,
- Usman Baber, MD, MSb,
- Samantha Sartori, PhDb and
- Erling Falk, MD, DMSca,∗ ()
- aDepartment of Cardiology, Aarhus University Hospital, Aarhus, Denmark
- bCardiovascular Institute, Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai, New York, New York
- cscPharmaceuticals, Lexington, Massachusetts
- ↵∗Reprint requests and correspondence:
Dr. Erling Falk, Department of Cardiology, Aarhus University Hospital, Palle Juul-Jensens Boulevard, DK-8200 Aarhus, Denmark.
Background The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines recommend primary prevention with statins for individuals with ≥7.5% 10-year risk for atherosclerotic cardiovascular disease (ASCVD). Everyone living long enough will become eligible for risk-based statin therapy due to age alone.
Objectives This study sought to personalize ACC/AHA risk-based statin eligibility using noninvasive assessment of subclinical atherosclerosis.
Methods In 5,805 BioImage participants without known ASCVD at baseline, those with ≥7.5% 10-year ASCVD risk were down-classified from statin eligible to ineligible if imaging revealed no coronary artery calcium (CAC) or carotid plaque burden (cPB). Intermediate-risk individuals were up-classified from optional to clear statin eligibility if CAC was ≥100 (or equivalent cPB).
Results At a median follow-up of 2.7 years, 91 patients had coronary heart disease and 138 had experienced a cardiovascular disease event. Mean age of the participants was 69 years, and 86% qualified for ACC/AHA risk-based statin therapy, with high sensitivity (96%) but low specificity (15%). CAC or cPB scores of 0 were common (32% and 23%, respectively) and were associated with low event rates. With CAC-guided reclassification, specificity for coronary heart disease events improved 22% (p < 0.0001) without any significant loss in sensitivity, yielding a binary net reclassification index (NRI) of 0.20 (p < 0.0001). With cPB-guided reclassification, specificity improved 16% (p < 0.0001) with a minor loss in sensitivity (7%), yielding an NRI of 0.09 (p = 0.001). For cardiovascular disease events, the NRI was 0.14 (CAC-guided) and 0.06 (cPB-guided). The positive NRIs were driven primarily by down-classifying the large subpopulation with CAC = 0 or cPB = 0.
Conclusions Withholding statins in individuals without CAC or carotid plaque could spare a significant proportion of elderly people from taking a pill that would benefit only a few. This individualized disease-guided approach is simple and easy to implement in routine clinical practice.
In 2013, the American College of Cardiology (ACC) and the American Heart Association (AHA) released new guidelines on risk assessment (1) and cholesterol treatment (2). For use in primary prevention of atherosclerotic cardiovascular disease (ASCVD), a new risk model on the basis of the Pooled Cohort Equations (PCE) was introduced (1), together with an online ASCVD risk calculator (3). The indication for statin therapy in individuals without ASCVD or diabetes was expanded by lowering the threshold for treatment to ≥7.5% 10-year ASCVD risk estimated by the PCE-based risk calculator (Class I recommendation) (2). That threshold to initiate statin therapy was supported by risk-benefit and cost-effectiveness analyses (1,2,4).
With the growing elderly population, the dominant effect of age on eligibility for statin therapy might need reconsideration (5–7). All healthy people with optimal cardiovascular risk factors will automatically, due to age-related risk alone, pass the 7.5% 10-year ASCVD risk threshold and qualify for ACC/AHA-recommended statin therapy between age 63 and 71 years (depending on sex and ethnicity). This universal eligibility for statin therapy with aging will inevitably lead to overtreatment of many older individuals who do not have the disease (atherosclerosis) that the treatment is intended to prevent or stabilize. Another related concern: PCEs tend to overestimate 10-year ASCVD risk in contemporary lower-risk populations, which also may lead to overtreatment (2,8–10).
The purpose of the present study was to evaluate a more personalized approach to primary prevention with statins by adding a simple disease-guided reclassification step after formal ACC/AHA-recommended risk assessment. Thus, the decision to treat with statins is simply guided by the absence (do not treat) or presence (treat) of subclinical atherosclerosis detected by noninvasive imaging of the coronary and carotid arteries (Central Illustration). We tested this practical, disease-guided reclassification approach to statin allocation for primary prevention of ASCVD in the contemporary, multiethnic BioImage cohort.
The design and objectives of the BioImage Study (NCT00738725) have been published previously (11). BioImage was a prospective observational cohort of men 55 to 80 years of age and women 60 to 80 years of age without known ASCVD at baseline examination between January 2008 and June 2009. The BioImage cohort is sex-balanced and included racial/ethnic minorities corresponding to the overall U.S. population. The primary objective was to identify predictive biomarkers for near-term ASCVD events in the noninvasive imaging group (n = 6,102) (12). The study was approved by the Western Institutional Review Board, Olympia, Washington. Informed consent and Health Insurance Portability and Accountability Act authorization were obtained from all study participants.
Baseline examination included assessment of cardiovascular risk factors and screening for subclinical (asymptomatic) atherosclerosis as previously described (12) and specified in the Online Appendix. All study participants underwent noncontrast computed tomography scanning to determine the Agatston coronary artery calcium (CAC) score and carotid ultrasound imaging to detect and quantify carotid plaque. By using a novel sweep method, described previously (13) and in the Online Appendix, all cross-sectional plaque areas were summed as carotid plaque burden (cPB).
The PCEs are applicable to ASCVD-free individuals 40 to 79 years of age (1). The ACC/AHA guidelines (2) define 4 statin-benefit groups; the following 3 are relevant for primary prevention of ASCVD (Class 1 recommendation):
1. Individuals without ASCVD or diabetes, 40 to 75 years of age, with a low-density lipoprotein cholesterol (LDL-C) of 70 to 189 mg/dl, and with an estimated 10-year ASCVD risk of ≥7.5%.
2. Individuals with diabetes, 40 to 75 years of age, and LDL-C 70 to 189 mg/dl.
3. Individuals with primary elevations of LDL-C ≥190 mg/dl
Additionally, statin therapy is reasonable when the 10-year ASCVD risk is 5% to <7.5% (Class IIa recommendation) and might be considered at even lower risk and beyond the age range of 40 to 75 years (Class IIb recommendation) (2).
Accepting these recommended cut-points for primary prevention with statins as a useful starting point, we tested the following disease-guided reclassification approach:
• To improve specificity (less overtreatment), individuals with ≥7.5% 10-year ASCVD risk estimated by PCE are down-classified from statin eligible to ineligible if CAC or cPB is absent.
• To improve sensitivity (less undertreatment), individuals with “intermediate” ASCVD risk (5% to <7.5% estimated by PCE) are up-classified from optional to statin eligible if the CAC is ≥100 or cPB is ≥300 mm2 (equivalent to CAC ≥100).
The 2013 ACC/AHA guidelines changed the predicted outcome from coronary heart disease (CHD) to ASCVD (CHD + stroke) using the PCE-based risk calculator, and the threshold for statin therapy was lowered (2). Consequently, the evidence base for the clinical utility of atherosclerosis imaging in risk assessment under the previous ACC/AHA guidelines (14) was no longer applicable and needed to be updated (1,2). To inform this revision, we present results separately for the following outcomes: 1) CHD (spontaneous myocardial infarction [MI], unstable angina [UA], and coronary revascularization); and 2) cardiovascular disease (CVD) (CHD + ischemic stroke, and cardiovascular death). An independent clinical events committee used source medical records to adjudicate CHD and CVD events as described in the Online Appendix.
Baseline characteristics of BioImage participants were analyzed according to 10-year ASCVD risk estimated using the PCEs underlying the ACC/AHA online risk calculator (1–3). To compare the clinical performance of CAC and cPB, we created 3 comparable groups (zero, middle, and top) for each modality, with a similar proportion of BioImage participants in the 2 top groups. The top CAC group comprised those with CAC ≥100, and the top cPB group comprised those with cPB ≥300 mm2 (chosen to match the percentile for CAC = 100, giving 2 top groups of similar size but selected differently). The zero groups were absence of CAC (CAC = 0) and cPB (cPB = 0), respectively. We then calculated the number needed to screen (NNS) to identify 1 person belonging to the zero or top group of subclinical atherosclerosis by dividing 100 by the percentage of people with the given amount of disease.
The association (hazard ratio [HR]) of CAC and cPB groups with development of CHD and CVD was assessed using Cox regression models analyzing time to event. Analyses were multivariable and adjusted for baseline characteristics. We used Kaplan-Meier estimates of cumulative incidence to compare (log-rank test) the occurrence of CHD and CVD events over time according to zero, middle, and top groups of CAC and cPB.
The clinical usefulness of assessing subclinical atherosclerosis in addition to the ACC/AHA guidelines depends on the ability to correctly reclassify individuals across decision thresholds. We therefore calculated the sensitivity, specificity, and binary net reclassification index (NRI) after applying the disease-guided reclassification described in the previous text. In the first analysis, only participants with a 10-year ASCVD risk of ≥7.5% to 15% could be down-classified from statin eligible to ineligible by absence of CAC or cPB. In the second analysis, all participants with a 10-year ASCVD risk of ≥7.5% could be down-classified to statin ineligible. The binary NRI (to treat or not to treat) is the sum of Δsensitivity and Δspecificity and can be in the range of −2 to 2.
In the BioImage study, 6,102 participants underwent noninvasive imaging to assess subclinical atherosclerosis. Due to missing data, 297 participants were excluded, yielding a final study population of 5,805 adults.
Per baseline characteristics (Table 1), the study population’s mean age was 69 years, and 56% of participants were women. The great majority (86%) of the BioImage cohort was statin eligible because of an estimated 10-year ASCVD risk ≥7.5%; risk was ≥15% in 55% of participants (Central Illustration).
According to the relationship between cardiovascular risk factors and subclinical atherosclerosis at baseline (Table 2), 10-year ASCVD risk correlated directly with the amount of subclinical atherosclerosis (Spearman correlation coefficient: 0.36 for CAC and 0.31 for cPB; p < 0.0001 for both). Absence of atherosclerosis was most common in lower-risk persons, whereas the opposite was true for the presence of severe atherosclerosis (Figure 1). Furthermore, with the methods used to assess subclinical disease in this study, absence of atherosclerosis was more common in the coronary arteries (32%) than in the carotid arteries (23%). Among individuals with ≥7.5% 10-year ASCVD risk, 28% had no CAC and 20% had no carotid plaque. The prevalence of significant atherosclerosis, defined as CAC ≥100 or cPB ≥300, was similar in the coronary and carotid arteries (39%).
The risk-dependent NNS to identify 1 person with absence or significant atherosclerosis is shown in Table 3. Regarding the potential for down-classification, the NNS to find 1 person with CAC = 0 was 2.6 and 4.5 among people with 10-year ASCVD risk of 7.5% to 15% and ≥15%, respectively. As for the potential for up-classification, the NNS to find 1 person with CAC ≥100 among people with 10-year ASCVD risk of <5% and 5% to 7.5% was 10 and 5.3, respectively. The same pattern was seen using cPB = 0 and ≥300 as cut-points for down- and up-classification, respectively (Table 3).
Over a median follow-up of 2.7 years, 91 patients had a first CHD event (MI, n = 34; UA, n = 18; coronary revascularization without MI or UA, n = 39) and 138 patients had a first CVD event (in total: MI, n = 34; UA, n = 18; coronary revascularization, n = 39; ischemic stroke, n = 30; cardiovascular death, n = 27).
There was a strong relationship between subclinical atherosclerosis and clinical events (Table 4). Event rates were low in participants without subclinical atherosclerosis, even those with diabetes. Only 1 and 2 clinical events were seen among patients with diabetes with CAC = 0 and cPB = 0, respectively. Kaplan-Meier cumulative-event curves for CHD and CVD are shown in Figure 2.
The ACC/AHA risk-based approach to statin allocation had high sensitivity (96%) but low specificity (15%) (Table 5). First, we assessed the consequences of down-classifying those with a 10-year ASCVD risk of 7.5% to <15% from statin eligible to ineligible if CAC was 0, and up-classifying those with an “intermediate” ASCVD risk of 5% to <7.5% if CAC was ≥100 from optional to clear statin eligible (Table 5, Online Tables 1 and 2). The specificity increased substantially from 15% to 25% for both CHD and CVD without any significant loss in sensitivity, leading to a binary NRI of 0.11 for CHD and 0.08 for CVD. Then we expanded the candidate population for down-classification to all with a 10-year ASCVD risk ≥7.5% (not capped at 15%) and CAC = 0. The gain in specificity doubled, resulting in a binary NRI of 0.20 for CHD and 0.14 for CVD (Table 5, Central Illustration). These changes were driven mainly by down-classifying the subpopulation with CAC = 0 (Online Tables 1 to 4).
Assessment of the binary disease-guided reclassification approach using cPB cut-points of 0 and 300 (equivalent to CAC = 100) is shown in Table 5 and Online Tables 5 to 8. Limiting down-classification (withholding statins) to those with 7.5% to <15% 10-year ASCVD risk decreased sensitivity to nearly the same extent as specificity increased, giving rise to no net effect on NRI. However, if everyone with a 10-year ASCVD risk ≥7.5% was down-classified to statin ineligible if cPB was 0, the specificity increased more than the sensitivity decreased (NRI = 0.09 for CHD and 0.06 for CVD) (Table 5, Central Illustration).
Excluding coronary revascularization from the endpoints did not change the results. The HR for CAC ≥100 and CHD events tended to be slightly lower (Online Table 9), but CAC- and cPB-guided NRIs remained similar for both CHD and CVD events, driven by a substantial increase in specificity with no or minimal loss in sensitivity (Online Table 10).
In study participants who were not on lipid-lowering drugs at baseline examination (n = 3,814), 60 CHD and 95 CVD events were observed during follow-up (Online Table 11). The relationship between subclinical atherosclerosis and clinical events (HRs, Online Table 12) and disease-guided reclassification (NRI up to 0.20 for CHD and 0.14 for CVD, Online Table 13) remained similar to the overall results.
Among individuals already on lipid-lowering drugs at baseline examination, those with CAC = 0 or cPB = 0 had low event rates per 1,000 person-years (0 or 0 for CHD and 3.2 or 3.1 for CVD, respectively), and those with CAC ≥100 or cPB ≥300 mm2 had relatively high event rates (10.6 or 9.7 for CHD and 13.1 or 11.9 for CVD, respectively).
In the contemporary BioImage cohort, 86% had a 10-year ASCVD risk ≥7.5% and qualified for primary prevention with statins. This ACC/AHA risk-based approach to statin allocation showed high sensitivity (96%) but low specificity (15%). Event rates were low in those without detectable atherosclerosis. Using a simple disease-guided reclassification approach based on well-defined cut-points for CAC (and corresponding cPB cut-points) led to a substantial gain in specificity (less overtreatment) with no or only minor loss in sensitivity. In this elderly cohort, CAC performed better than cPB. The binary NRI was up to 0.20 for CHD events, driven primarily by withholding statins in those with CAC = 0. Limiting primary prevention with statins to individuals with CAC >0 could spare 1 in 4 elderly patients from taking medication that will benefit only a few.
Statin therapy for all elderly people?
Because ASCVD risk is strongly age-dependent, Wald and Law (15) suggested in 2003 that everyone ≥55 years of age should be offered treatment with safe risk-reducing drugs. By introducing a treatment threshold as low as 7.5% 10-year ASCVD risk, the ACC/AHA guidelines indirectly supported such a “universal” treatment principle because everyone with optimal risk factors will now qualify for statin therapy if they live long enough (African-American [AA] men age 66 years, non-AA men age 63 years, AA women age 70 years, and non-AA women age 71 years) (3,5). However, the ACC/AHA guidelines remind clinicians that primary prevention with statins should not only depend on predicted risk, but also include a discussion with the individual patient regarding potential treatment benefits, adverse effects, drug–drug interactions, and patient preferences (2).
Previous versus new ACC/AHA guidelines
The previous ACC/AHA guidelines for cardiovascular risk assessment found it reasonable to measure CAC and carotid intima-media thickness (cIMT) for risk assessment in asymptomatic adults at intermediate risk (14). This Class IIa recommendation for imaging-guided risk assessment was, however, changed to Class IIb for CAC and Class III for cIMT in the 2013 ACC/AHA guidelines (2), primarily because the evidence for clinical utility vanished with the lower threshold for statin therapy (dwarfing the intermediate-risk group ) and the change of predicted outcome from CHD to ASCVD (CHD and stroke combined). The 2013 ACC/AHA Class III recommendation for cIMT was based on evidence provided by a single meta-analysis of the incremental predictive value of the mean common cIMT without separate plaque detection and assessment, thus disregarding the known predictive power of carotid plaque imaging (17).
In the present study, rather than reviving a larger intermediate group population of uncertain risk, we accepted the new Class I indication for risk-based statin therapy (≥7.5% 10-year ASCVD risk estimated by the ACC/AHA risk calculator) as a useful starting point, and then reclassified people across the 7.5% risk threshold guided by the absence or presence of subclinical atherosclerosis. Reclassification from statin eligible to ineligible and vice versa relied solely on disease-based cut-points (CAC of 0 and 100) that have documented incremental predictive value beyond traditional risk factor scoring (18–21). This approach performed well for both CHD and CVD outcomes, probably because most CVD events are CHD events.
Individualized statin therapy in the elderly is important for several reasons. Although universal treatment of all Americans ages 75 to 94 years might be cost effective (22), elderly patients are more vulnerable to statin-related adverse effects because of comorbidity, polypharmacy, and risk for functional limitation and possible cognitive impairment. Long-term effects of using low-dose computed tomography for CAC screening are less concerning in the elderly. Overall, such considerations are obvious topics for the patient-clinician discussion espoused by recent guidelines (2).
Downward reclassification in the absence of atherosclerosis
The Class IIb option in the 2013 ACC/AHA guidelines for using CAC for refined risk assessment when a risk-based treatment decision is uncertain applies only for up- and not down-classification of risk. In fact, these guidelines provide little guidance on how to personalize risk assessment to avoid overtreating healthy individuals who formally become statin eligible just because of normal aging.
Although most cardiovascular events occur in old age, many elderly patients do not have the underlying disease (atherosclerosis) responsible for the age-related risk for ASCVD. In the BioImage population (mean age 69 years), 86% qualified for risk-based statin therapy, but imaging revealed that up to one-third had no CAC, which was associated with a low cardiovascular event rate, even in patients with diabetes. Thus, there was a major gain in specificity (less overtreatment) by down-classifying those with ≥7.5% 10-year ASCVD risk estimated by PCE from statin eligible to ineligible if CAC was 0, not only in those with a borderline increased risk (PCE risk from 7.5% to 15%), but also in everyone with a PCE risk ≥7.5%. Thus, our study confirmed that CAC = 0 in asymptomatic people without known ASCVD is associated with a very low cardiovascular risk, called the power of zero (19). Our data extended this observation to a contemporary elderly population with a 10-year ASCVD risk well above the 7.5% (Class I) risk threshold for statin therapy.
Few studies have evaluated the potential effect of atherosclerosis imaging on statin allocation after formal risk assessment as recommended by the new ACC/AHA guidelines. In the less contemporary MESA (Multi-Ethnic Study of Atherosclerosis) cohort of individuals who were on average 10 years younger than those in our study, of those eligible for statin therapy per the 2013 ACC/AHA guidelines, 41% had CAC = 0 and a low ASCVD event rate (5.2 events per 1,000 person-years of follow-up) (23). Among a small excluded subgroup of MESA participants 75 years of age, almost all of whom were statin eligible, 18% had CAC = 0 and a low 10-year event rate. In an even younger cohort from the Framingham Heart Study, a CAC score of 0 identified a large low-risk group (33%) among the ACC/AHA statin-eligible participants (21). Our results from a contemporary elderly population agreed with these recent observations and provided clinically important performance measures for statin allocation, such as sensitivity, specificity, and NRI.
Upward reclassification in the presence of significant atherosclerosis
The ACC/AHA guidelines state that CAC ≥300 or ≥75th percentile for age, sex, and ethnicity may be considered for up-classification of risk in selected individuals (Class IIb recommendation) (2). Although this approach may be useful in some younger people (24), there is little room for meaningful up-classification of risk in older people, as most already qualify for risk-based statin therapy. In the BioImage cohort, only 14% had a 10-year ASCVD risk <7.5%. In this lower-risk subpopulation, we observed 4 CHD and 6 CVD events during follow-up, 2 of which would have been identified by the CAC-based screening approach, none by the cPB-based screening approach. Thus, the intermediate-risk strategy supported by the previous ACC/AHA guidelines (14) may still be relevant as assessed by the NNS, but relatively few elderly will benefit from such a strategy.
In the younger MESA cohort, the performance of the guideline-recommended cut-points for up-classification was recently tested using recalibrated PCEs (25), which is applicable only to MESA and therefore not generalizable to routine clinical practice like the present disease-guided proposal. In the MESA cohort, only a small subgroup (6.8%) was up-classified, becoming eligible for primary prevention with statins.
The clinical utility of detecting CAC and carotid plaque differs (26). If the goal is to predict CHD events, CAC is likely the optimal imaging test, whereas carotid plaque assessment may be superior for stroke prediction (27). However, PCE was devised to predict CHD and stroke combined (ASCVD), and this study is the first to compare the incremental predictive value of CAC and carotid plaque imaging beyond formal PCE-based risk assessment. Judged by the NRI, CAC performed better than cPB in terms of predicting both CHD events alone and the combined ASCVD outcome.
A major strength of the present analysis is that we did not evaluate the clinical performance of imaging cut-points derived from the BioImage study, but instead used CAC cut-points of proven value across multiple populations (18–21). We compared CAC and cPB with the same proportion of participants in the top category defined by imaging. Although the cPB cut-point of 300 mm2 corresponding to CAC = 100 may not be the optimal cut-point for the up-classification of risk based on cPB, the main drivers of the positive NRI in this cohort were CAC = 0 and cPB = 0.
As previously described in greater detail, we used a novel, highly sensitive ultrasound-based sweep method to detect atherosclerosis in the carotid arteries (13). It may not necessarily be advantageous in elderly people, most of whom have at least early atherosclerotic changes somewhere in the vasculature. Thus, in the BioImage cohort, more people had cPB >0 (77%) than CAC >0 (68%). However, in a younger cohort, early detection may be prioritized together with the use of a method not requiring radiation. The ongoing PESA (Progression of Early Subclinical Atherosclerosis) study, in which multiple vascular beds are screened for subclinical atherosclerosis, will clarify this issue (28). Regarding the cost of an atherosclerosis imaging test, most people are ready to pay the cost of a test to avoid taking a pill each day for the rest of their lives (29).
Another strength of the present study was that it built on the existing ACC/AHA guidelines, including the online risk calculator. Furthermore, the tested disease-guided reclassification approach is simple, is easy to implement clinically, is less dependent on a well-calibrated risk calculator, uses the strong evidence for low ASCVD risk universally across populations if CAC is 0, and focuses on the growing elderly, resource-consuming, at-risk population.
PCEs were designed to predict the natural history of ASCVD in the absence of intervention. A problem BioImage shared with other contemporary cohorts was the lower-than-expected event rates, which may be at least partly explained by the “healthy volunteer effect” and modern common use of preventive therapies in people free of ASCVD (8–10,30). We included coronary revascularization in the composite endpoints but recognize that knowledge of a high CAC score shared with the patient and/or physicians may in itself lead to revascularization. However, excluding revascularization from the composite endpoints did not change the study conclusions. The durability of our short-term results may be questioned, but growing evidence indicates that the “warranty period” for CAC = 0 may be as long as 15 years (20,31), likely indicating lifelong low risk in elderly people. CAC = 0 is well-defined and reproducible, whereas cBP = 0 is less well-defined and depends on the protocol used to scan the carotid arteries; our use of a sensitive ultrasound protocol may explain why cPB = 0 was less common than CAC = 0.
In individuals who qualified for ACC/AHA risk-based statin therapy, limiting treatment to those with CAC >0 or cPB >0 led to a substantial gain in specificity (less overtreatment) with no or only a minor loss in sensitivity. There was not much room for disease-based expansion of statin eligibility in this elderly cohort. A simple, individualized, disease-guided approach to statin allocation could potentially spare a significant proportion of asymptomatic elderly people from lifelong treatment of questionable benefit.
COMPETENCY IN PATIENT CARE AND PROCEDURAL SKILLS: In elderly people with no clinical history of atherosclerosis, the absence of coronary calcification and carotid plaque is associated with a low risk of cardiovascular events and might reasonably lead to a decision to forego statin therapy.
TRANSLATIONAL OUTLOOK: More work is needed to prospectively evaluate the outcomes of clinical decision strategies that individualize selection of preventive therapy based on a combination of population-based risk estimates and efficient incorporation of noninvasive imaging tests.
For an expanded Methods section and supplemental tables, please see the online version of this article.
The BioImage Study was designed by the High-Risk Plaque Initiative, a pre-competitive industry collaboration funded by BG Medicine, Abbott Vascular, AstraZeneca, Merck & Co., Philips, and Takeda. Dr. Mehran has received research grant support from Eli Lilly/Daiichi-Sankyo, Bristol-Myers Squibb, AstraZeneca, The Medicines Company, and OrbusNeich; has served as a consultant for Janssen Pharmaceuticals, Osprey Medical, Watermark Research Partners, and Medscape; and has served on the scientific advisory board of Abbott Laboratories. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Tasneem Naqvi, MD, served as Guest Editor for this paper.
- Abbreviations and Acronyms
- American College of Cardiology
- American Heart Association
- atherosclerotic cardiovascular disease
- coronary artery calcium
- coronary heart disease
- carotid plaque burden
- cardiovascular disease
- myocardial infarction
- Pooled Cohort Equations
- Received March 15, 2016.
- Revision received May 17, 2016.
- Accepted May 26, 2016.
- American College of Cardiology Foundation
- Goff D.C. Jr..,
- Lloyd-Jones D.M.,
- Bennett G.,
- et al.
- Stone N.J.,
- Robinson J.G.,
- Lichtenstein A.H.,
- et al.
- ↵American College of Cardiology, American Heart Association. ACC/AHA ASCVD risk calculator. Available at: http://tools.acc.org/ASCVD-Risk-Estimator/. Accessed June 18, 2016.
- Breslow J.L.
- Navar-Boggan A.M.,
- Peterson E.D.,
- D'Agostino R.B.,
- et al.
- Goff D.C. Jr..,
- D’Agostino R.B.,
- Pencina M.,
- et al.
- Pursnani A.,
- Massaro J.M.,
- Hoffmann U.
- Rana J.S.,
- Tabada G.H.,
- Solomon M.D.,
- et al.
- Baber U.,
- Mehran R.,
- Sartori S.,
- et al.
- Sillesen H.,
- Muntendam P.,
- Adourian A.,
- et al.
- Greenland P.,
- Alpert J.S.,
- Beller G.A.,
- et al.
- Wald N.J.,
- Law M.R.
- Stein J.H.,
- Tattersall M.C.
- Hecht H.S.
- Blaha M.J.,
- Silverman M.G.,
- Budoff M.J.
- Greenland P.
- Nasir K.,
- Bittencourt M.S.,
- Blaha M.J.,
- et al.
- Tota-Maharaj R.,
- Blaha M.J.,
- McEvoy J.W.,
- et al.
- Yeboah J.,
- Polonsky T.S.,
- Young R.,
- et al.
- Shah P.K.
- Blaha M.J.
- Fernández-Friera L.,
- Peñalvo J.L.,
- Fernández-Ortiz A.,
- et al.
- Hutchins R.,
- Viera A.J.,
- Sheridan S.L.,
- et al.
- Valenti V, Ó Hartaigh B, Heo R, et al. A 15-year warranty period for asymptomatic individuals without coronary artery calcium: a prospective follow-up of 9,715 individuals. J Am Coll Cardiol Img 2015;8:900–9.