Final Research Plan
Enhanced Risk Assessment for Cardiovascular Disease: Coronary Artery Calcium Scoring
September 26, 2024
Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
Abbreviations: CAC = coronary artery calcium; CVD = cardiovascular disease; KQ = key question.
- What is the effectiveness or comparative effectiveness of enhanced cardiovascular disease risk assessment with coronary artery calcium scoring on cardiovascular health outcomes?
1a. What is the effectiveness or comparative effectiveness of enhanced cardiovascular disease risk assessment with coronary artery calcium scoring on physiologic outcomes, behavioral outcomes, or patient and provider decision-making outcomes?
- Does the use of coronary artery calcium scoring to predict cardiovascular disease risk improve measures of calibration, discrimination, and risk reclassification compared with the use of multivariate cardiovascular disease risk assessment without these risk markers?
- What are the harms of cardiovascular disease risk assessment with coronary artery calcium scoring?
- Does treatment guided by coronary artery calcium scoring lead to improved health outcomes?
- What are the harms of treatment guided by coronary artery calcium scoring?
Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.
- What is the rate of incidental findings on computed tomography for coronary artery calcium measurement? What are the benefits and harms of detecting these incidental findings?
- What is the incidence and distribution of positive coronary artery calcium as an incidental finding in thoracic imaging?
- What are other risk markers used in enhanced cardiovascular disease risk assessment and what is their role in clinical decision making?
- What are the limitations of existing cardiovascular disease risk assessment models or use of coronary artery calcium scoring in different populations?
- What is the comparative performance and agreement between PREVENT (Predicting Risk of cardiovascular disease EVENTs) and PCE (Pooled Cohort Equations)? How do 10-year risk scores compare between the two models? What are the strengths and limitations of each of the models?
Health equity will be considered throughout the review using several approaches. For key questions, we will describe the population characteristics of the included studies to assess the degree to which the evidence is representative of diverse populations. Further, we will characterize whether race, ethnicity, or social determinants of health were explicitly included as predictors or stratifying factors in prediction models. For risk prediction studies, we will abstract model performance outcomes by race and ethnicity and compare results. We will also analyze benefits and harms of treatment interventions by specific populations to the extent that this is reported in the included studies for selected populations of interest. These groups include racial and ethnic groups, socioeconomic and insurance status, or other social risk factors. We will also include a contextual question to explore limitations of existing cardiovascular disease risk assessment models or use of coronary artery calcium scoring in different populations.
The Research Approach identifies the study characteristics and criteria that the Evidence-based Practice Center will use to search for publications and to determine whether identified studies should be included or excluded from the Evidence Report. Criteria are overarching as well as specific to each of the key questions.
| Category | Included | Excluded |
|---|---|---|
| Condition Definition | Atherosclerotic cardiovascular disease, including coronary heart disease, cerebrovascular disease, and peripheral artery disease | Heart failure |
| Risk Factors | CAC score | |
| Populations | Adults without known cardiovascular disease
Populations being screened for lung cancer Analyses will include examination of effects by population characteristics such as sex, race or ethnicity, and comorbid conditions KQs 4, 5: Populations with elevated CAC score |
Populations selected exclusively based on having advanced chronic kidney disease* or chronic inflammatory disease (e.g., rheumatoid arthritis) |
| Intervention | KQs 1–3: Enhanced risk assessment:
KQs 4, 5: Interventions aimed at preventing CVD events:
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| Comparisons | KQs 1–3: Base model risk assessment:
KQs 4, 5: Usual care, no treatment, or placebo |
Models predicting mortality only or heart failure only |
| Outcomes | KQs 1, 4: Cardiovascular disease events (e.g., myocardial infarction, stroke), cardiovascular disease–specific and all-cause mortality KQ1a: Physiologic outcomes (e.g., lipid levels, blood pressure), behavioral outcomes (e.g., smoking cessation, physical activity levels, improvement in diet), and decision-making outcomes (e.g., prescribing and adherence to preventive cardiovascular disease treatments) KQ 2: Net reclassification index, discrimination (e.g., area under the curve, c-statistic, integrated discrimination improvement), calibration (e.g., agreement between observed and predicted risks), and decision curve analysis KQs 3, 5: Serious adverse events from risk factor assessment or risk factor modification resulting in unexpected or unwanted medical attention (e.g., major bleeding, development of diabetes), exposure to radiation, and adverse psychological outcomes from risk factor assessment |
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| Country | Studies conducted in countries categorized as “Very High” on the 2021 Human Development Index (as defined by the United Nations Development Programme) | |
| Study designs | KQs 1, 4: RCTs, CCTs, and NRSIs with contemporaneous control
KQ 2: Prognostic prediction model studies KQs 3, 5: RCTs, CCTs, NRSIs with contemporaneous control, single-arm cohort studies for estimation of radiation exposure or incidental findings, and case-control studies for rare events |
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| Language | English language only | |
| Study Quality | “Fair” or “Good” quality only |
Abbreviations: CAC = coronary artery calcium; CCT = clinical controlled trial; eGFR = estimated glomerular filtration rate; GLP-1 = glucagon-like peptide 1; KQ = key question; NRSI = nonrandomized study of interventions; PCE = Pooled Cohort Equations; PCSK-9 = proprotein convertase subtilisin/kexin type 9; PREVENT = Predicting Risk of cardiovascular disease EVENTS; RCT = randomized, controlled trial; SGLT-2 = sodium-glucose transport protein 2.
A draft of this Research Plan was posted for public comment on the U.S. Preventive Services Task Force website from April 25 to May 22, 2024. In response to public comments, we have excluded the ankle brachial index (ABI) as a risk enhancing marker for cardiovascular disease. Instead, the clinical utility of ABI will be evaluated as a screening test in a separate future topic, “Screening for Peripheral Artery Disease.” We have also expanded our inclusion criteria to include nonrandomized studies of interventions to evaluate the effectiveness of risk assessment with CAC score and of treatment guided by CAC score, as well as to include physiologic, behavioral, and decision-making outcomes to evaluate the potential benefit of risk assessment with CAC score. We will examine the incremental value of CAC score over Framingham Risk Score if we have limited evidence on PCE and PREVENT. The timeline of this topic will accommodate the results of ongoing CAC trials.