in progress

Draft Research Plan

Enhanced Risk Assessment for Cardiovascular Disease: Coronary Artery Calcium Scoring

April 25, 2024

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Figure 1 is the analytic framework that depicts the five Key Questions (KQs) addressed in the systematic review. The figure illustrates how enhanced risk factor assessment (specifically, coronary artery calcium [CAC] score and ankle brachial index [ABI]) may result in improved health outcomes, including cardiovascular morbidity and mortality (KQ1) and decision making and physiologic outcomes (KQ1a). Additionally, the figure illustrates how enhanced risk factor assessment may improve measures of calibration, discrimination, and risk reclassification (KQ2) and how treatment based on nontraditional risk factor assessment may improve health outcomes (KQ4). Further, the figure depicts whether enhanced risk factor assessment or treatment based on enhanced risk factor assessment are associated with any adverse events (KQ3 and KQ5).

Abbreviations: ABI = ankle brachial index; CAC = coronary artery calcium; CVD = cardiovascular disease; KQ = key question.

1.  What is the effectiveness or comparative effectiveness of enhanced cardiovascular disease risk assessment with coronary artery calcium scoring or the ankle brachial index on cardiovascular health outcomes?
1a. What is the effectiveness or comparative effectiveness of enhanced cardiovascular disease risk assessment with coronary artery calcium scoring or the ankle brachial index on physiologic outcomes or patient and provider decision-making outcomes?
2.  Does the use of coronary artery calcium scoring or the ankle brachial index 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?
3.  What are the harms of using coronary artery calcium scoring or the ankle brachial index for enhanced cardiovascular disease risk assessment?
4.  Does treatment guided by coronary artery calcium scoring or the ankle brachial index lead to improved health outcomes?
5.  What are the harms of treatment guided by coronary artery calcium scoring or the ankle brachial index?

Contextual Questions will not be systematically reviewed and are not shown in the Analytic Framework.

  1. 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?
  2. What is the incidence and distribution of positive coronary artery calcium as an incidental finding in thoracic imaging?
  3. What are other risk markers used in enhanced cardiovascular disease risk assessment and what is their role in clinical decision making?
  4. What are the limitations of existing cardiovascular disease risk assessment or use of coronary artery calcium scoring or ankle brachial index in different populations?
  5. 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 the limitations of existing cardiovascular disease risk assessment or use of coronary artery calcium scoring or ankle brachial index in different populations.

The proposed 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 Review. 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
  • ABI
  
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, ethnicity, and comorbidities		 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:
  • Base model risk assessment (e.g., PREVENT, PCE, FRS) + CAC score
  • Base model risk assessment (e.g., PREVENT, PCE, FRS) + ABI
  • CAC score alone
  • ABI alone
  • CAC score or ABI in addition to other risk factors (KQs 1, 3 only)

KQs 4, 5: Interventions aimed at preventing CVD events:

  • Aspirin
  • Statins
  • Antihypertensive medications
  • Lifestyle modification
  • SGLT-2 inhibitors
  • GLP-1 agonists
  • PCSK9 inhibitors
  
Comparisons KQs 1-3: Base model risk assessment:
  • Base model CVD risk assessment (e.g., PREVENT, PCE, FRS)
  • Usual care or no screening (KQs 1, 3 only)

KQs 4, 5: Usual care, no treatment, or placebo

 Models predicting mortality only or heart failure only
Outcomes KQs 1, 4: CVD events (e.g., myocardial infarction, stroke) and mortality

KQ1a: In trials also reporting CVD events, the below outcomes will be captured:
  • Physiologic outcomes (e.g., lipid levels, blood pressure)
  • Decision-making outcomes (e.g., prescribing and adherence to preventive CVD 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) and exposure to radiation)

  
Country Studies conducted in countries categorized as “Very High” on the 2021 Human Development Index (as defined by the United Nations Development Program)  
Study designs KQs 1, 4, 5: RCTs, CCTs

KQ 2: Prognostic prediction model studies

KQs 3, 5: RCTs, CCTs, large cohort studies with contemporaneous control, single-arm cohort studies for estimation of radiation exposure or incidental findings, and case-control studies for rare events

  
Language English language only  
Study Quality “Fair” or “Good” quality only  

* eGFR <30 mL/min.

Abbreviations: ABI = ankle brachial index; CAC = coronary artery calcium; CCT = clinical controlled trial; CVD = cardiovascular disease; eGFR = estimated glomerular filtration rate; FRS = Framingham Risk Score; GLP-1 = glucagon-like peptide 1; KQ = key question; 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.