Final Research Plan
Cardiovascular Disease: Risk Assessment With Nontraditional Risk Factors
September 03, 2015
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.
The final Research Plan will be used to guide a systematic review of the evidence by researchers at an Evidence-based Practice Center. The resulting Evidence Report will form the basis of the USPSTF Recommendation Statement on this topic.
The draft Research Plan was available for comment from June 11 until July 8, 2015 at 5:00 p.m., ET.
Abbreviations: ABI = ankle–brachial index; CAC = coronary artery calcium; CVD = cardiovascular disease; HDL = high-density lipoprotein; hs-CRP = high-sensitivity C-reactive protein; KQ = key question; MI = myocardial infarction.
Figure 1 is the analytic framework that depicts the five Key Questions to be addressed in the systematic review. The figure illustrates how nontraditional risk factor assessment may result in improved health outcomes, including cardiovascular morbidity and mortality (KQ1). Additionally, the figure illustrates how nontraditional 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 nontraditional risk factor assessment or treatment based on nontraditional risk factor assessment are associated with any adverse events (KQ3 and KQ5).
- Compared with the Pooled Cohort Equations tool or Framingham risk factors alone, does risk assessment of asymptomatic adults using nontraditional risk factors—followed by treatment specific to risk level—lead to reduced incidence of cardiovascular events (e.g., myocardial infarction, cerebrovascular accident) and/or mortality?
- Does use of nontraditional risk factors in addition to traditional risk factors to predict cardiovascular disease risk improve measures of calibration, discrimination, and risk reclassification?
- What are the harms of nontraditional risk factor assessment?
- Does treatment guided by nontraditional risk factors in addition to traditional risk factors lead to reduced incidence of cardiovascular events (e.g., myocardial infarction, cerebrovascular accident) and/or mortality?
- What are the harms of treatment guided by nontraditional risk factors?
Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.
- Does nontraditional risk factor assessment lead to improved patient adherence to risk factor modification?
- What is the rate of incidental findings (including subsequent diagnostic workup) when screening for coronary artery calcium using electron beam computed tomography? Does detection of incidental findings improve patient outcomes? What are the harms of detecting incidental findings (including harms of subsequent diagnostic workup)?
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 (KQs).
| Include | |
|---|---|
| Condition definition | Atherosclerotic CVD, including coronary heart disease, cerebrovascular disease, and peripheral artery disease |
| Populations | Adults without known CVD, by sex, race/ethnicity, and diabetes status |
| Risk factors | High-sensitivity C-reactive protein, coronary artery calcium, and ankle–brachial index |
| Treatments | KQs 4, 5: Interventions aimed at preventing CVD events (i.e., aspirin, HMG-CoA reductase inhibitors, antihypertension medications, and lifestyle modifications such as diet and/or exercise) |
| Comparisons | KQs 1–3: Existing CVD risk assessment models (with a focus on CVD as opposed to coronary heart disease risk assessment)
KQs 4, 5: No treatment or usual care (as defined by the study) |
| Outcomes | KQs 1, 4: CVD events (e.g., myocardial infarction, cerebrovascular accident) and/or mortality
KQ 2: Measures of reclassification (e.g., net reclassification index, integrated discrimination improvement), discrimination (e.g., area under the curve, c-statistic), and calibration (e.g., agreement between observed and predicted risks) KQs 3, 5: Serious adverse events from risk factor assessment or aggressive risk factor modification resulting in unexpected or unwanted medical attention (e.g., major bleeding, development of diabetes); exposure to radiation |
| Countries | Studies conducted in countries categorized as “Very High” on the 2014 Human Development Index (as defined by the United Nations Development Programme) |
| Study designs | KQs 1, 4: Systematic reviews of trials, RCTs, and CCTs
KQ 2: Systematic reviews of trials, RCTs, CCTs; well-designed large prospective cohort studies; risk prediction studies KQs 3, 5: Systematic reviews, RCTs, CCTs, well-designed large prospective or retrospective cohort studies, well-designed case-control studies (only for rare events) |
| Publication language | English language only |
| Study quality | Fair or good quality only |
Abbreviations: CCT = controlled clinical trial; CVD = cardiovascular disease; RCT = randomized, controlled trial.
The draft Research Plan was posted on the USPSTF Web site from June 11 to July 8, 2015. Comments were received from 31 unique organizations or individuals. Overall, the nature of the comments was not unexpected; many of them addressed issues previously considered during the development of the Research Plan. Based on the comments received, the USPSTF made no substantive changes to the KQs or inclusion criteria. The USPSTF made minor edits to the wording of the KQs and added two contextual questions to the Research Plan.