Nontraditional Risk Factors in Cardiovascular Disease Risk Assessment: Updated Evidence Report and Systematic Review
Jennifer S Lin1, Corinne V Evans1, Eric Johnson1
1Kaiser Permanente Research Affiliates Evidence-based Practice Center, Center for Health Research, Kaiser Permanente, Portland, Oregon.
Insights
Nontraditional risk factors like ABI, hsCRP, and CAC scores can improve cardiovascular disease risk assessment, but more clinical trials are needed to confirm their impact on patient outcomes.
Area of Science:
- Cardiology
- Preventive Medicine
- Medical Diagnostics
Background:
- Traditional cardiovascular disease (CVD) risk assessment models may be enhanced by incorporating nontraditional risk factors.
- The US Preventive Services Task Force (USPSTF) requires systematic reviews on the benefits and harms of potential interventions.
Purpose of the Study:
- To systematically review the evidence on the benefits and harms of using the ankle-brachial index (ABI), high-sensitivity C-reactive protein (hsCRP) level, and coronary artery calcium (CAC) score in cardiovascular risk assessment.
- To evaluate the impact of these nontraditional risk factors on risk assessment performance measures.
Main Methods:
- A systematic review of MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials was conducted for studies published up to February 2018.
- Included studies focused on asymptomatic adults without known CVD.
- Data abstraction and critical appraisal were performed independently by two reviewers.
Main Results:
- Forty-three studies with 267,244 participants were included. No adequately powered trials assessed the clinical effect of risk assessment with these factors on patient health outcomes.
- The addition of ABI, hsCRP, or CAC score improved discrimination and reclassification, with varying consistency and magnitude.
- CAC score demonstrated the largest improvements in discrimination and reclassification, but potential for inappropriate risk reclassification was noted. Harms were limited to low radiation exposure from CAC scoring.
Conclusions:
- There is insufficient evidence from adequately powered clinical trials to evaluate the incremental effect of ABI, hsCRP, or CAC score on risk assessment and preventive therapy initiation.
- The clinical significance of improvements in risk prediction measures like calibration, discrimination, and reclassification remains uncertain.
Importance:
Incorporating nontraditional risk factors may improve the performance of traditional multivariable risk assessment for cardiovascular disease (CVD).
Objective:
To systematically review evidence for the US Preventive Services Task Force on the benefits and harms of 3 nontraditional risk factors in cardiovascular risk assessment: the ankle-brachial index (ABI), high-sensitivity C-reactive protein (hsCRP) level, and coronary artery calcium (CAC) score.
Data Sources:
MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials for studies published through May 22, 2017. Surveillance continued through February 7, 2018.
Study Selection:
Studies of asymptomatic adults with no known cardiovascular disease.
Data Extraction And Synthesis:
Independent critical appraisal and data abstraction by 2 reviewers.
Main Outcomes And Measures:
Cardiovascular events, mortality, risk assessment performance measures (calibration, discrimination, or risk reclassification), and serious adverse events.
Results:
Forty-three studies (N = 267 244) were included. No adequately powered trials have evaluated the clinical effect of risk assessment with nontraditional risk factors on patient health outcomes. The addition of the ABI (10 studies), hsCRP level (25 studies), or CAC score (19 studies) can improve both discrimination and reclassification; the magnitude and consistency of improvement varies by nontraditional risk factor. For the ABI, improvements in performance were the greatest for women, in whom traditional risk assessment has poor discrimination (C statistic change of 0.112 and net reclassification index [NRI] of 0.096). Results were inconsistent for hsCRP level, with the largest analysis (n = 166 596) showing a minimal effect on risk prediction (C statistic change of 0.0039, NRI of 0.0152). The largest improvements in discrimination (C statistic change ranging from 0.018 to 0.144) and reclassification (NRI ranging from 0.084 to 0.35) were seen for CAC score, although CAC score may inappropriately reclassify individuals not having cardiovascular events into higher-risk categories, as determined by negative nonevent NRI. Evidence for the harms of nontraditional risk factor assessment was limited to computed tomography imaging for CAC scoring (8 studies) and showed that radiation exposure is low but may result in additional testing.
Conclusions And Relevance:
There are insufficient adequately powered clinical trials evaluating the incremental effect of the ABI, hsCRP level, or CAC score in risk assessment and initiation of preventive therapy. Furthermore, the clinical meaning of improvements in measures of calibration, discrimination, and reclassification risk prediction studies is uncertain.
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