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Guideline Summary
Guideline Title
Using nontraditional risk factors in coronary heart disease risk assessment: U.S. Preventive Services Task Force recommendation statement.
Bibliographic Source(s)
U.S. Preventive Services Task Force. Using nontraditional risk factors in coronary heart disease risk assessment: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2009 Oct 6;151(7):474-82. [40 references] PubMed External Web Site Policy
Guideline Status

This is the current release of the guideline.

Scope

Disease/Condition(s)

Coronary heart disease (CHD)

Guideline Category
Prevention
Risk Assessment
Screening
Clinical Specialty
Cardiology
Family Practice
Internal Medicine
Nursing
Preventive Medicine
Intended Users
Advanced Practice Nurses
Allied Health Personnel
Health Care Providers
Nurses
Physician Assistants
Physicians
Guideline Objective(s)

To summarize the current U.S. Preventive Services Task Force (USPSTF) recommendations and supporting scientific evidence on using nontraditional risk factors in coronary heart disease (CHD) risk assessment

Target Population

Asymptomatic men and women with no history of coronary heart disease (CHD), diabetes, or any CHD risk equivalent

Interventions and Practices Considered

Screening for coronary heart disease (CHD) using the following nontraditional risk factors:

  • High-sensitivity C-reactive protein (hs-CRP)
  • Ankle–brachial index (ABI)
  • Leukocyte count
  • Fasting blood glucose level
  • Periodontal disease
  • Carotid intima–media thickness (carotid IMT)
  • Coronary artery calcification (CAC) score on electron-beam computed tomography (EBCT)
  • Homocysteine level
  • Lipoprotein(a) level
Major Outcomes Considered

Key Question 1: Compared with Framingham risk factors alone, does risk stratification of asymptomatic adults using novel risk markers lead to reduced incidence of cardiovascular events (myocardial infarction, angina, sudden death, cerebrovascular accident), coronary heart disease (CHD) events, or overall mortality?

Key Question 2: What novel risk markers accurately predict cardiovascular events independent of Framingham risk factors? What is the added predictive value of novel risk markers?

Key Question 2a: What is the prevalence of these risk markers among intermediate-risk and low-risk individuals?

Key Question 2b: At what frequency does application of these novel risk markers significantly change the 10-year risk of cardiovascular events based on traditional risk factors alone (e.g., from intermediate risk [10-20%] to high risk [>20%] or to low risk [<10%])?

Key Question 3: What are the harms of risk assessment?

Key Question 4a: In groups identified as high-risk (>20% 10-year risk) by novel risk markers, does aggressive risk factor modification (treatment to lower blood pressure and lipid targets or more intense counseling) lead to improved intermediate outcomes (e.g., reduction in lipid levels; reduction in blood pressure; increased physical activity; healthy dietary changes, etc.)?

Key Question 4b: Does improvement in intermediate outcomes lead to reduced incidence of cardiovascular events (myocardial infarction, angina, sudden death, cerebrovascular accident), cardiovascular disease-specific mortality, overall mortality?

Key Question 5: What are the harms of aggressive risk factor modification?

Key Question 6: What are the costs associated with risk factor assessment and aggressive risk factor modification?

Methodology

Methods Used to Collect/Select the Evidence
Hand-searches of Published Literature (Primary Sources)
Hand-searches of Published Literature (Secondary Sources)
Searches of Electronic Databases
Description of Methods Used to Collect/Select the Evidence

Note from the National Guideline Clearinghouse (NGC): A systematic review of the literature was prepared by the Oregon Evidence-based Practice Center (EPC) for use by the U.S. Preventive Services Task Force (USPSTF) (see the "Availability of Companion Documents" field).

Literature Search and Strategy

For each risk factor listed in Table 2 of the Evidence Synthesis (see the "Availability of Companion Documents" field), EPC staff conducted multiple searches of MEDLINE (1966 to March 2006). Searches were focused on identifying epidemiologic studies relevant to the independent predictive ability of the risk factor when used in intermediate-risk individuals (Appendix I in the Evidence Synthesis [see the "Availability of Companion Documents" field]). Additional articles were obtained from recent systematic reviews, reference lists of pertinent studies, reviews, editorials, websites, and by consulting experts.

Eligibility Criteria

EPC staff reviewed abstracts and full-text articles identified by the searches for relevance (Appendix II in the Evidence Synthesis [see the "Availability of Companion Documents" field]). Eligible articles had English-language abstracts and provided primary data relevant to the key questions. Studies conducted exclusively in adults with previously diagnosed coronary disease or coronary disease equivalent (e.g., diabetes) were excluded. Studies were included if they reported, at minimum, outcomes of coronary deaths and non-fatal myocardial infarctions (MIs). Only prospective cohort studies (including those based on a cohort included in a randomized trial) and nested case-control studies were considered for assessing the predictive value of the novel risk factors.

EPC staff listed the cohorts represented among included studies and grouped publications by cohort. When more than one paper was published using data from a single cohort, findings were analyzed for the cohort study rather than the nested case control study, or from the analysis with the highest validity and applicability to the study questions based on the EPC's quality ratings. For each cohort, EPC staff reviewed included and excluded publications to determine whether a particular risk factor had been measured. Then they determined whether published studies reported results in a manner that would allow them to determine the odds ratio for the novel risk factor among patients who did not have known cardiovascular disease (CVD) or diabetes and were intermediate-risk. When it was clear that a risk factor had been measured, but the independent contribution of the risk factor for predicting CHD events in the target population could not be determined, authors were contacted for more information that would enable EPC staff to include the cohort in the review.

Number of Source Documents

Searches yielded 4,088 citations (Appendix IV in the Evidence Synthesis [see the "Availability of Companion Documents" field]), from which Oregon Evidence-based Practice Center (EPC) staff identified relevant analyses of emerging risk factors from 64 cohorts (Table 3 in the Evidence Synthesis [see the "Availability of Companion Documents" field]).

Methods Used to Assess the Quality and Strength of the Evidence
Expert Consensus
Rating Scheme for the Strength of the Evidence

Not applicable

Methods Used to Analyze the Evidence
Meta-Analysis
Review of Published Meta-Analyses
Systematic Review with Evidence Tables
Description of the Methods Used to Analyze the Evidence

Note from the National Guideline Clearinghouse (NGC): A systematic review of the literature was prepared by the Oregon Evidence-based Practice Center (EPC) for use by the U.S. Preventive Services Task Force (USPSTF) (see the "Availability of Companion Documents" field).

Approach to Assessing the Strength of Evidence

The overall strength of evidence is a function of the validity and applicability of individual studies as well as several dimensions of a body of studies.

The Validity of Individual Studies

The validity assessment evaluates the extent to which one can be confident that a study’s estimate of effect is correct. Investigators rated the validity of evidence of each study using criteria specific to cohort and nested case-control studies (Appendix III in the Evidence Synthesis [see the "Availability of Companion Documents" field]). These criteria were applied previously to large bodies of observational studies of hormone replacement therapy and of vitamins and the long-term risk of cardiovascular events.

Applicability of Individual Studies

Investigators assessed the applicability of each study’s sample, risk assessment, and outcome measures to the targets for this review. In rating the applicability of each study, investigators assessed the following study characteristics:

  1. Study Sample. Ideally, the study sample was drawn from the general population or a demographic subset of asymptomatic adults who would be classified as "intermediate risk" in the Adult Treatment Panel (ATP)-III risk stratification scheme. Samples that included patients with known coronary heart disease (CHD) or diabetes were acceptable if multivariate analyses adjusted for these characteristics or the results for the target population could be extracted from the study. A poor rating for Framingham Risk Factor assessment (next item) would reduce the likelihood that the study sample was representative of intermediate-risk individuals. Inclusion of additional risk factors (e.g., family history, triglyceride level) did not reduce the applicability rating.
  2. Framingham Risk Factor measurement. Many studies used risk stratification schemes that were not identical to the components of the Framingham score; for example, some studies used the patient's report of whether they had a history of hypercholesterolemia as a proxy for an actual total cholesterol level, while others had components (e.g., triglyceride level, family history) that were not included in the Framingham risk scoring model. Investigators compared the actual measures used for each component of the risk assessment method and coefficients from the study's prediction model to the gold standard of the measurements and model coefficients used in developing the Framingham risk score.
  3. Emerging Risk Factor measurement and categories. Clinical, radiologic and laboratory test methods varied among studies. Some of this variation reflected improvement over time in assay or radiologic methods (for example, higher-sensitivity assays or higher-resolution radiographs). EPC staff recorded the methods used to measure the emerging risk factor and to define abnormal results. For many of these tests, a gold standard definition of abnormality has not been defined, and studies used a variety of quantiles (tertiles, quintiles, deciles) to make statistical comparisons.
  4. Outcomes (Events). Studies used a variety of measures of the incidence of coronary or cardiovascular events. For the purpose of this review, the ideal measure included fatal and nonfatal myocardial infarction (MI) and death due to coronary disease ("hard CHD" events.) When possible, EPC staff analyzed results for these events, but they also analyzed studies in which these events could not be separated out from broader measures that included other coronary events, such as unstable angina and percutaneous coronary intervention; and measures that included hard CHD events plus stroke ("major cardiovascular events," CVD).

Strength of Evidence for a Body of Studies

Judgments about the validity or strength of evidence for a body of studies require consideration of study design, limitations of quality within a given design, consistency and applicability of the evidence. By a "body" of studies, EPC staff means all evidence that addressed a specific question. For example, a body of evidence might include 10 cohort studies and 5 nested case-control studies addressing the predictive ability of high-sensitivity C-reactive protein (hs-CRP) in intermediate-risk subjects. In rating the strength of a body of studies, investigators considered:

  • The aggregate validity and applicability of the body of studies.
  • The number and range of studies. A higher number of independent cohorts and a wider range of study circumstances compared with other risk factors would improve the rating.
  • The consistency of results, that is, the similarity of effect across studies and, if applicable, across study designs. Evidence of consistency related to a dose response relationship, or the use of various cut-offs for an elevated test result, would also strengthen confidence in the validity of the body of literature.
  • The precision of the results.
  • The risk of reporting bias.
  • The likelihood that there is a flaw common to most or all of the studies in a body of evidence. This criterion protects against the circumstance in which consistency of results reflects a consistent bias or flaw in study design. For example, failure of most or all studies to address a known potential confounder, or failure of some studies to adjust for a confounder that was important in other studies, would weaken confidence in the validity of the body of evidence.

Approach to Assessing the Magnitude of Benefit

As noted above, the predictive ability of a risk factor, its prevalence, and the number of people who are reclassified as high risk affect the outcome of interest, that is, the reduction in the incidence of "hard CHD" events that would occur when the risk factor is applied.

Predictive Ability

EPC staff reviewed population-based, epidemiologic studies that assess the ability of the risk factor to predict major CHD events independently of Framingham risk factors in intermediate-risk subjects (Key Question 2). For each risk factor that had consistent, fair-to-good-quality evidence, a meta-analysis of epidemiologic studies was conducted to determine the combined estimate of association between various risk factors and CHD events after controlling for Framingham risk factors. Estimates of risk ratio (relative risk [RR], hazard ratio [HR] or odds ratio [OR]) were obtained from a model with adjustment of Framingham risk factors from each study.

Refer to the Evidence Synthesis (see the "Availability of Companion Documents" field) for additional information on this process.

Prevalence

Even if a risk factor has been shown to provide independent information, its usefulness in screening cannot be reliably assessed unless there are reliable estimates of its prevalence in the target population. For risk factors that had statistically significant and independent predictive ability, the prevalence of the risk factor in the intermediate-risk population was assessed, with particular attention to the availability and reliability of estimates of prevalence among demographic subgroups. When available, nationally representative data were used to estimate prevalence. EPC staff considered lack of data about prevalence in the target population (intermediate-risk adults) to be a serious limitation. For tests that lacked such information, EPC staff did not proceed to subsequent steps in examining the magnitude of benefit.

Other Considerations

If meta-analysis of the population-based studies indicated that use of the test is able to improve overall prediction beyond that of traditional risk factors, several other characteristics that affect its actual impact in practice were examined, including:

  1. The ability to standardize the assay and to control the variability of the measurement
  2. The presence of population norms to guide interpretation of results
  3. The costs, burden, and harms of using the test

Among risk factors that had similar predictive ability and prevalence, differences in cost, convenience, technical characteristics such as intra-assay or inter-observer reliability, and harms could affect the acceptability and cost-effectiveness of testing intermediate-risk individuals. EPC staff examined evidence about these characteristics to choose candidate risk factors for further analysis.

Number of Reclassified Individuals

For risk factors that had at least fair-quality data about prevalence in intermediate-risk individuals from the general population, information was extracted about the number of intermediate-risk individuals reclassified as high-risk or low-risk by using the novel risk factor when it was available in published studies.

Net Benefit

At present, no randomized controlled trials have assessed whether risk stratification of intermediate risk patients using a novel risk factor, and more aggressive risk factor modification of patients identified as high-risk on the basis of a novel risk factor, improves outcomes (Key Questions 1 and 4b.) There are also no data from adequately powered controlled trials that would permit a direct measurement of the benefits or harms of treatment decisions arising from use of a novel risk factor in intermediate-risk patients (Key Questions 4a and 5).

A body of evidence, however, indirectly supports the view that the benefits of aggressive risk factor management with lipid-lowering therapy depends on overall risk, even when low density lipoprotein levels are not elevated. If the benefits of aggressive risk factor management are more related to overall risk than to the specific contributing risk factors, correctly classifying more high-risk patients would be expected to be beneficial. Therefore, after consultation with USPSTF members, EPC staff chose to estimate the net benefit to reclassified individuals by assuming that they have a net benefit similar to those of high-risk and very-high-risk subjects in major lipid-lowering trials.

This approach provides an estimate of the upper bound of potential benefit rather than the expected or likely benefit. Moreover, the validity of this assumption is likely to differ for different risk factors or categories of risk factors. For example, the validity of this assumption might be different for inflammatory markers, such as hs-CRP or periodontal disease, than for markers of atherosclerosis such as artery calcification or ankle--brachial index; or lipid-related markers such as triglyceride or lipoprotein(a) levels.

The literature review and meta-analyses described above resulted in information about the strength of evidence, prevalence, and adjusted odds for predicting the 10-year risk of CHD events for each risk factor. EPC staff tabulated this information, adding in information about reliability and cost, to select risk factors for further analysis of the number of individuals who would be reclassified by using the risk factor to further stratify intermediate-risk subjects. To be selected for additional analysis, the risk factor had to have at least fair strength of evidence; there also had to be reliable information about the prevalence of the risk factor among intermediate-risk individuals in the adult population (or in a defined demographic subgroup of the general population); and the estimate of the adjusted odds ratio for the 10-year risk of hard CHD events had to be statistically significant and relatively high compared with others.

Refer to the Evidence Synthesis (see the "Availability of Companion Documents" field) for information on modeling potential benefits of risk factor testing.

Statistical Analysis

Analysis of logit equation approach was performed by using the Microsoft Excel Solver utility (Microsoft, Inc, Redmond, WA) and the alternative approach using Cox regression was conducted by using SAS 9.1 (SAS institute Inc., Cary, NC). When calculating population means for Framingham risk factors, CRP, predicted 10-year risk and population proportions for each risk group (low, intermediate or high), EPC staff used the combined 1999 to 2002 4-year final examination weights from National Health and Nutrition Examination Survey (NHANES) data. Calculations of standard errors and 95% confidence intervals (CI) incorporated stratification and sampling unit data from the NHANES datasets to account for the complex sampling design used in the study. Population estimates were age-adjusted by the direct method using population age-distribution estimates for the year 2000. All data analyses were performed using the JK-1 jackknife replication procedure in WESVAR® 4.2 statistical software (Westvar, Rockville, MD). To check the reliability of their analyses, EPC staff also analyzed the population distributions for Framingham risk factors and demographic variables (Table 1 and Table 2 in the Evidence Synthesis [see the "Availability of Companion Documents" field]), and population distributions of CHD risk before and after adjusting for CRP (Table 3 in the Evidence Synthesis [see the "Availability of Companion Documents" field]) using the Taylor series linearization method in SUDAAN Version 8 software (RTI, Research Triangle Park, NC) and found nearly identical results.

Methods Used to Formulate the Recommendations
Balance Sheets
Expert Consensus
Description of Methods Used to Formulate the Recommendations

The U.S. Preventive Services Task Force (USPSTF) systematically reviews the evidence concerning both the benefits and harms of widespread implementation of a preventive service. It then assesses the certainty of the evidence and the magnitude of the benefits and harms. On the basis of this assessment, the USPSTF assigns a letter grade to each preventive service signifying its recommendation about provision of the service (see Table below). An important, but often challenging, step is determining the balance between benefits and harms to estimate "net benefit" (that is, benefits minus harms).

Table 1. U.S. Preventive Services Task Force Recommendation Grid*

Certainty of Net Benefit Magnitude of Net Benefit
Substantial Moderate Small Zero/Negative
High A B C D
Moderate B B C D
Low Insufficient

*A, B, C, D, and I (Insufficient) represent the letter grades of recommendation or statement of insufficient evidence assigned by the U.S. Preventive Services Task Force after assessing certainty and magnitude of net benefit of the service (see the "Rating Scheme for the Strength of the Recommendations" field).

The overarching question that the Task Force seeks to answer for every preventive service is whether evidence suggests that provision of the service would improve health outcomes if implemented in a general primary care population. For screening topics, this standard could be met by a large randomized, controlled trial (RCT) in a representative asymptomatic population with follow-up of all members of both the group "invited for screening" and the group "not invited for screening."

Direct RCT evidence about screening is often unavailable, so the Task Force considers indirect evidence. To guide its selection of indirect evidence, the Task Force constructs a "chain of evidence" within an analytic framework. For each key question, the body of pertinent literature is critically appraised, focusing on the following 6 questions:

  1. Do the studies have the appropriate research design to answer the key question(s)?
  2. To what extent are the existing studies of high quality? (i.e., what is the internal validity?)
  3. To what extent are the results of the studies generalizable to the general U.S. primary care population and situation? (i.e., what is the external validity?)
  4. How many studies have been conducted that address the key question(s)? How large are the studies? (i.e., what is the precision of the evidence?)
  5. How consistent are the results of the studies?
  6. Are there additional factors that assist the Task Force in drawing conclusions (e.g., presence or absence of dose–response effects, fit within a biologic model)?

The next step in the Task Force process is to use the evidence from the key questions to assess whether there would be net benefit if the service were implemented. In 2001, the USPSTF published an article that documented its systematic processes of evidence evaluation and recommendation development. At that time, the Task Force's overall assessment of evidence was described as good, fair, or poor. The Task Force realized that this rating seemed to apply only to how well studies were conducted and did not fully capture all of the issues that go into an overall assessment of the evidence about net benefit. To avoid confusion, the USPSTF has changed its terminology. Whereas individual study quality will continue to be characterized as good, fair, or poor, the term certainty will now be used to describe the Task Force's assessment of the overall body of evidence about net benefit of a preventive service and the likelihood that the assessment is correct. Certainty will be determined by considering all 6 questions listed above; the judgment about certainty will be described as high, moderate, or low.

In making its assessment of certainty about net benefit, the evaluation of the evidence from each key question plays a primary role. It is important to note that the Task Force makes recommendations for real-world medical practice in the United States and must determine to what extent the evidence for each key question—even evidence from screening RCTs or treatment RCTs—can be applied to the general primary care population. Frequently, studies are conducted in highly selected populations under special conditions. The Task Force must consider differences between the general primary care population and the populations studied in RCTs and make judgments about the likelihood of observing the same effect in actual practice.

It is also important to note that one of the key questions in the analytic framework refers to the potential harms of the preventive service. The Task Force considers the evidence about the benefits and harms of preventive services separately and equally. Data about harms are often obtained from observational studies because harms observed in RCTs may not be representative of those found in usual practice and because some harms are not completely measured and reported in RCTs.

Putting the body of evidence for all key questions together as a chain, the Task Force assesses the certainty of net benefit of a preventive service by asking the 6 major questions listed above. The Task Force would rate a body of convincing evidence about the benefits of a service that, for example, derives from several RCTs of screening in which the estimate of benefits can be generalized to the general primary care population as "high" certainty (see the "Rating Scheme for the Strength of Recommendations" field). The Task Force would rate a body of evidence that was not clearly applicable to general practice or has other defects in quality, research design, or consistency of studies as "moderate" certainty. Certainty is "low" when, for example, there are gaps in the evidence linking parts of the analytic framework, when evidence to determine the harms of treatment is unavailable, or when evidence about the benefits of treatment is insufficient. Table 4 in the methodology document listed below (see "Availability of Companion Documents" field) summarizes the current terminology used by the Task Force to describe the critical assessment of evidence at all 3 levels: individual studies, key questions, and overall certainty of net benefit of the preventive service.

Sawaya GF et al. Update on the methods of the U.S. Preventive Services Task Force: estimating certainty and magnitude of net benefit. Ann Intern Med. 2007;147:871-875 [5 references].

I Statements

For I statements, the USPSTF has a new plan to commission its Evidence-based Practice Centers to collect information in 4 domains pertinent to clinical decisions about prevention and to report this information routinely. This plan is described in the paper: Petitti DB et al. Update on the methods of the U.S. Preventive Services Task Force: insufficient evidence. Ann Intern Med. 2009;150:199-205 (see "Availability of Companion Documents" field).

The first domain is potential preventable burden of suffering from the condition. When evidence is insufficient, provision of an intervention designed to prevent a serious condition (such as dementia) might be viewed more favorably than provision of a service designed to prevent a condition that does not cause as much suffering (such as rash). The USPSTF recognized that "burden of suffering" is subjective and involves judgment. In clinical settings, it should be informed by patient values and concerns.

The second domain is potential harm of the intervention. When evidence is insufficient, an intervention with a large potential for harm (such as major surgery) might be viewed less favorably than an intervention with a small potential for harm (such as advice to watch less television). The USPSTF again acknowledges the subjective nature and the difficulty of assessing potential harms: For example, how bad is a "mild" stroke?

The third domain is cost--not just monetary cost, but opportunity cost, in particular the amount of time a provider spends to provide the service, the amount of time the patient spends to partake of it, and the benefits that might derive from alternative uses of the time or money for patients, clinicians, or systems. Consideration of clinician time is especially important for preventive services with only insufficient evidence because providing them could "crowd out" provision of preventive services with proven value, services for conditions that require immediate action, or services more desired by the patient. For example, a decision to routinely inspect the skin could take up the time available to discuss smoking cessation, or to address an acute problem or a minor injury that the patient considers important.

The fourth domain is current practice. This domain was chosen because it is important to clinicians for at least 2 reasons. Clinicians justifiably fear that not doing something that is done on a widespread basis in the community may lead to litigation. More important, addressing patient expectations is a crucial part of the clinician-patient relationship in terms of building trust and developing a collaborative therapeutic relationship. The consequences of not providing a service that is neither widely available nor widely used are less serious than not providing a service accepted by the medical profession and thus expected by patients. Furthermore, ingrained care practices are difficult to change, and efforts should preferentially be directed to changing those practices for which the evidence to support change is compelling.

Although the reviewers did not explicitly recognize it when these domains were chosen, the domains all involve consideration of the potential consequences--for patients, clinicians, and systems--of providing or not providing a service. Others writing about medical decision making in the face of uncertainty have suggested that the consequences of action or inaction should play a prominent role in decisions.

Rating Scheme for the Strength of the Recommendations

What the United States Preventive Services Task Force (USPSTF) Grades Mean and Suggestions for Practice

Grade Grade Definitions Suggestions for Practice
A The USPSTF recommends the service. There is high certainty that the net benefit is substantial. Offer or provide this service.
B The USPSTF recommends the service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial. Offer or provide this service.
C The USPSTF recommends against routinely providing the service. There may be considerations that support providing the service in an individual patient. There is moderate or high certainty that the net benefit is small. Offer or provide this service only if other considerations support offering or providing the service in an individual patient.
D The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. Discourage the use of this service.
I
Statement
The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined. Read "Clinical Considerations" section of USPSTF Recommendation Statement (see "Major Recommendations" field). If this service is offered, patients should understand the uncertainty about the balance of benefits and harms.

USPSTF Levels of Certainty Regarding Net Benefit

Definition: The U.S. Preventive Services Task Force defines certainty as "likelihood that the USPSTF assessment of the net benefit of a preventive service is correct." The net benefit is defined as benefit minus harm of the preventive service as implemented in a general, primary care population. The USPSTF assigns a certainty level based on the nature of the overall evidence available to assess the net benefit of a preventive service.

Level of Certainty Description
High The available evidence usually includes consistent results from well-designed, well-conducted studies in representative primary care populations. These studies assess the effects of the preventive service on health outcomes. This conclusion is therefore unlikely to be strongly affected by the results of future studies.
Moderate The available evidence is sufficient to determine the effects of the preventive service on health outcomes, but confidence in the estimate is constrained by factors such as:
  • The number, size, or quality of individual studies
  • Inconsistency of findings across individual studies
  • Limited generalizability of findings to routine primary care practice
  • Lack of coherence in the chain of evidence
As more information becomes available, the magnitude or direction of the observed effect could change, and this change may be large enough to alter the conclusion.
Low The available evidence is insufficient to assess effects on health outcomes. Evidence is insufficient because of:
  • The limited number or size of studies
  • Important flaws in study design or methods
  • Inconsistency of findings across individual studies
  • Gaps in the chain of evidence
  • Findings not generalizable to routine primary care practice
  • A lack of information on important health outcomes
More information may allow an estimation of effects on health outcomes.
Cost Analysis

Costs

Because of limitations in the evidence of effectiveness, little information is available on the cost-effectiveness of using nontraditional risk factors in coronary heart disease (CHD) screening. When the evidence for effectiveness is clearer, evaluating cost-effectiveness will be a research priority.

Method of Guideline Validation
Comparison with Guidelines from Other Groups
External Peer Review
Internal Peer Review
Description of Method of Guideline Validation

Peer Review. Before the U.S. Preventive Services Task Force makes its final determinations about recommendations on a given preventive service, the Evidence-Based Practice Center and the Agency for Healthcare Research and Quality send a draft evidence review to 4 to 6 external experts and to federal agencies and professional and disease-based health organizations with interests in the topic. They ask the experts to examine the review critically for accuracy and completeness and to respond to a series of specific questions about the document. After assembling these external review comments and documenting the proposed response to key comments, the topic team presents this information to the Task Force in memo form. In this way, the Task Force can consider these external comments before it votes on its recommendations about the service. Draft recommendation statements are then circulated for comment from reviewers representing professional societies, voluntary organizations and Federal agencies. These comments are discussed before the final recommendations are confirmed.

Comparison with Guidelines from Other Groups. Recommendations for screening from the following groups were discussed: American Heart Association (AHA), Centers for Disease Control and Prevention (CDC), and the National Heart, Lung, and Blood Institute (NHLBI), National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III.

Recommendations

Major Recommendations

The U.S. Preventive Services Task Force (USPSTF) grades its recommendations (A, B, C, D, or I) and identifies the Levels of Certainty regarding Net Benefit (High, Moderate, and Low). The definitions of these grades can be found at the end of the "Major Recommendations" field.

Summary of Recommendation and Evidence

The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of using the nontraditional risk factors discussed in this statement to screen asymptomatic men and women with no history of coronary heart disease (CHD) to prevent CHD events. This is an I statement.

The nontraditional risk factors included in this recommendation are high-sensitivity C-reactive protein (hs-CRP), ankle–brachial index (ABI), leukocyte count, fasting blood glucose level, periodontal disease, carotid intima–media thickness (carotid IMT), coronary artery calcification (CAC) score on electron-beam computed tomography (EBCT), homocysteine level, and lipoprotein(a) level.

Clinical Considerations

Patient Population Under Consideration

The USPSTF intends this recommendation for asymptomatic men and women with no history of CHD, diabetes, or any CHD risk equivalent.

Suggestions for Practice Regarding the I Statement

Clinicians should use the Framingham model to assess CHD risk and to guide risk-based therapy until further evidence is obtained.

Because adding nontraditional risk factors to CHD assessment requires additional patient and clinical staff time and effort, routinely screening with nontraditional risk factors could result in lost opportunities for provision of other important health services of proven benefit.

Assessment of Risk

This recommendation is to be used for those who fall into a 10% to 20% (intermediate) 10-year risk category after being screened for CHD risk by using traditional CHD risk factors. Using a risk assessment tool is a key step in managing CHD risk in patients. One validated method of assessing CHD risk is the Framingham model. Persons with low (<10%) Framingham risk scores do not benefit from aggressive risk factor modification, whereas those with high (>20%) Framingham risk scores do benefit. Examples of persons who fall into the intermediate-risk category include a 60-year-old male smoker with untreated hypertension or a 60-year-old female with untreated hypertension and hyperlipidemia. The current recommendation used the National Heart, Lung, and Blood Institute (NHLBI), National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) Framingham risk calculator (available at http://hp2010.nhlbihin.net/atpiii/calculator.asp?usertype=prof External Web Site Policy) and does not include diabetic populations.

Treatment

About 31% of asymptomatic U.S. men and 7% of asymptomatic U.S. women age 40 to 79 years without diabetes will fall into the intermediate-risk category. No evidence or consensus is available regarding how to treat and counsel these persons.

Useful Resources

Other USPSTF recommendations (1–5) provide guidance for preventing CHD events.

Definitions:

What the United States Preventive Services Task Force (USPSTF) Grades Mean and Suggestions for Practice

Grade Grade Definitions Suggestions for Practice
A The USPSTF recommends the service. There is high certainty that the net benefit is substantial. Offer or provide this service.
B The USPSTF recommends the service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial. Offer or provide this service.
C The USPSTF recommends against routinely providing the service. There may be considerations that support providing the service in an individual patient. There is moderate or high certainty that the net benefit is small. Offer or provide this service only if other considerations support offering or providing the service in an individual patient.
D The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. Discourage the use of this service.
I
Statement
The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined. Read "Clinical Considerations" section of USPSTF Recommendation Statement (see "Major Recommendations" field). If this service is offered, patients should understand the uncertainty about the balance of benefits and harms.

USPSTF Levels of Certainty Regarding Net Benefit

Definition: The U.S. Preventive Services Task Force defines certainty as "likelihood that the USPSTF assessment of the net benefit of a preventive service is correct." The net benefit is defined as benefit minus harm of the preventive service as implemented in a general, primary care population. The USPSTF assigns a certainty level based on the nature of the overall evidence available to assess the net benefit of a preventive service.

Level of Certainty Description
High The available evidence usually includes consistent results from well-designed, well-conducted studies in representative primary care populations. These studies assess the effects of the preventive service on health outcomes. This conclusion is therefore unlikely to be strongly affected by the results of future studies.
Moderate The available evidence is sufficient to determine the effects of the preventive service on health outcomes, but confidence in the estimate is constrained by factors such as:
  • The number, size, or quality of individual studies
  • Inconsistency of findings across individual studies
  • Limited generalizability of findings to routine primary care practice
  • Lack of coherence in the chain of evidence
As more information becomes available, the magnitude or direction of the observed effect could change, and this change may be large enough to alter the conclusion.
Low The available evidence is insufficient to assess effects on health outcomes. Evidence is insufficient because of:
  • The limited number or size of studies
  • Important flaws in study design or methods
  • Inconsistency of findings across individual studies
  • Gaps in the chain of evidence
  • Findings not generalizable to routine primary care practice
  • A lack of information on important health outcomes
More information may allow an estimation of effects on health outcomes.
Clinical Algorithm(s)

None provided

Evidence Supporting the Recommendations

Type of Evidence Supporting the Recommendations

The type of supporting evidence is not specifically stated for each recommendation.

Benefits/Harms of Implementing the Guideline Recommendations

Potential Benefits

Benefits of Screening and Additional Risk Assessment

The evidence is insufficient to determine the magnitude of any reduction in coronary heart disease (CHD) events and CHD-related deaths obtained by using nontraditional risk factors in CHD screening. This constitutes a critical gap in the evidence for benefit from screening.

Potential Harms

Harms of Screening and Additional Risk Assessment

Little evidence is available to determine the harms of using nontraditional risk factors in coronary heart disease (CHD) screening. Harms include lifelong use of medications without proof of benefit but with expense and potential side effects. Statins are the class of medication most commonly used; these medications have been demonstrated to be safe but are associated with the rare but serious side effect of rhabdomyolysis. Psychological and other harms may result from being put into a higher risk category for CHD events.

Qualifying Statements

Qualifying Statements

  • The U.S. Preventive Services Task Force (USPSTF) makes recommendations about preventive care services for patients without recognized signs or symptoms of the target condition.
  • Recommendations are based on a systematic review of the evidence of the benefits and harms and an assessment of the net benefit of the service.
  • The USPSTF recognizes that clinical or policy decisions involve more considerations than this body of evidence alone. Clinicians and policy-makers should understand the evidence but individualize decision making to the specific patient or situation.

Implementation of the Guideline

Description of Implementation Strategy

The experiences of the first and second U.S. Preventive Services Task Force (USPSTF), as well as that of other evidence-based guideline efforts, have highlighted the importance of identifying effective ways to implement clinical recommendations. Practice guidelines are relatively weak tools for changing clinical practice when used in isolation. To effect change, guidelines must be coupled with strategies to improve their acceptance and feasibility. Such strategies include enlisting the support of local opinion leaders, using reminder systems for clinicians and patients, adopting standing orders, and audit and feedback of information to clinicians about their compliance with recommended practice.

In the case of preventive services guidelines, implementation needs to go beyond traditional dissemination and promotion efforts to recognize the added patient and clinician barriers that affect preventive care. These include clinicians' ambivalence about whether preventive medicine is part of their job, the psychological and practical challenges that patients face in changing behaviors, lack of access to health care or of insurance coverage for preventive services for some patients, competing pressures within the context of shorter office visits, and the lack of organized systems in most practices to ensure the delivery of recommended preventive care.

Dissemination strategies have changed dramatically in this age of electronic information. While recognizing the continuing value of journals and other print formats for dissemination, the Agency for Healthcare Research and Quality will make all U.S. Preventive Services Task Force (USPSTF) products available through its Web site External Web Site Policy. The combination of electronic access and extensive material in the public domain should make it easier for a broad audience of users to access U.S. Preventive Services Task Force materials and adapt them for their local needs. Online access to U.S. Preventive Services Task Force products also opens up new possibilities for the appearance of the annual, pocket-size Guide to Clinical Preventive Services.

To be successful, approaches for implementing prevention have to be tailored to the local level and deal with the specific barriers at a given site, typically requiring the redesign of systems of care. Such a systems approach to prevention has had notable success in established staff-model health maintenance organizations, by addressing organization of care, emphasizing a philosophy of prevention, and altering the training and incentives for clinicians. Staff-model plans also benefit from integrated information systems that can track the use of needed services and generate automatic reminders aimed at patients and clinicians, some of the most consistently successful interventions. Information systems remain a major challenge for individual clinicians' offices, however, as well as for looser affiliations of practices in network-model managed care and independent practice associations, where data on patient visits, referrals, and test results are not always centralized.

Implementation Tools
Foreign Language Translations
Mobile Device Resources
Patient Resources
Pocket Guide/Reference Cards
Staff Training/Competency Material
For information about availability, see the Availability of Companion Documents and Patient Resources fields below.

Institute of Medicine (IOM) National Healthcare Quality Report Categories

IOM Care Need
Staying Healthy
IOM Domain
Effectiveness
Patient-centeredness

Identifying Information and Availability

Bibliographic Source(s)
U.S. Preventive Services Task Force. Using nontraditional risk factors in coronary heart disease risk assessment: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2009 Oct 6;151(7):474-82. [40 references] PubMed External Web Site Policy
Adaptation

Not applicable: The guideline was not adapted from another source.

Date Released
2009 Oct 6
Guideline Developer(s)
U.S. Preventive Services Task Force - Independent Expert Panel
Guideline Developer Comment

The U.S. Preventive Services Task Force (USPSTF) is a federally-appointed panel of independent experts. Conclusions of the U.S. Preventive Services Task Force do not necessarily reflect policy of the U.S. Department of Health and Human Services (DHHS) or its agencies.

Source(s) of Funding

United States Government

Guideline Committee

U.S. Preventive Services Task Force (USPSTF)

Composition of Group That Authored the Guideline

Task Force Members*: Ned Calonge, MD, MPH, Chair (Colorado Department of Public Health and Environment, Denver, Colorado); Diana B. Petitti, MD, MPH, Vice Chair (Arizona State University, Phoenix, Arizona); Thomas G. DeWitt, MD (Children's Hospital Medical Center, Cincinnati, Ohio); Kimberly D. Gregory, MD, MPH (Cedars-Sinai Medical Center, Los Angeles, California); Russell Harris, MD, MPH (University of North Carolina School of Medicine, Chapel Hill, North Carolina); George Isham, MD, MS (HealthPartners, Minneapolis, Minnesota); Michael L. LeFevre, MD, MSPH (University of Missouri School of Medicine, Columbia, Missouri); Carol Loveland-Cherry, PhD, RN (University of Michigan School of Nursing, Ann Arbor, Michigan); Lucy N. Marion, PhD, RN (School of Nursing, Medical College of Georgia, Augusta, Georgia); Virginia A. Moyer, MD, MPH (Baylor College of Medicine, Houston, Texas); Judith K. Ockene, PhD (University of Massachusetts Medical School, Worcester, Massachusetts); George F. Sawaya, MD (University of California, San Francisco, San Francisco, California); Albert L. Siu, MD, MSPH (Mount Sinai Medical Center, New York, New York); Steven M. Teutsch, MD, MPH (Merck & Company, West Point, Pennsylvania); and Barbara P. Yawn, MD, MSc (Olmsted Medical Center, Rochester, Minnesota)

* Members of the Task Force at the time this recommendation was finalized. For a list of current Task Force members, go to www.ahrq.gov/clinic/uspstfab.htm External Web Site Policy.

Recused from voting.

Financial Disclosures/Conflicts of Interest

The U.S. Preventive Services Task Force has an explicit policy concerning conflict of interest. All members disclose at each meeting if they have a significant financial, professional/business, or intellectual conflict for each topic being discussed. Task Force members with conflicts may be recused from discussing or voting on recommendations about the topic in question.

Guideline Status

This is the current release of the guideline.

Guideline Availability

Electronic copies: Available from the U.S. Preventive Services Task Force (USPSTF) Web site External Web Site Policy and from the Annals of Internal Medicine Web site External Web Site Policy.

Print copies: Available from the Agency for Healthcare Research and Quality (AHRQ) Publications Clearinghouse. For more information, go to http://www.ahrq.gov/research/publications/index.html External Web Site Policy or call 1-800-358-9295 (U.S. only).

Availability of Companion Documents

The following are available:

Evidence Reviews:

  • Helfand M, Buckley D, Fleming C, Fu R, Freeman M, Humphrey L, Rogers K, Walker M. Screening for intermediate risk factors for coronary heart disease: systematic evidence synthesis. Evidence Synthesis No. 73. AHRQ Publication No. 10-05141-EF-1. Rockville, Maryland: Agency for Healthcare Research and Quality, 2009 Oct. Electronic copies: Available from the U.S. Preventive Services Task Force (USPSTF) Web site External Web Site Policy.
  • Buckley DI, Fu R, Freeman M, Rogers K, Helfand M. C-reactive protein as a risk factor for coronary heart disease: a systematic review and meta-analyses for the U.S. Preventive Services Task Force. Ann Intern Med. 2009;151:483-495. Electronic copies: Available from the Annals of Internal Medicine Web site External Web Site Policy.
  • Helfand M, Buckley DI, Freeman M, Fu R, Rogers K, Flemin C, Humphrey LL. Emerging risk factors for coronary heart disease: a summary of systematic reviews conducted for the U.S. Preventive Services Task Force. Ann Intern Med. 2009;151:496-507. Electronic copies: Available from the Annals of Internal Medicine Web site External Web Site Policy.

The following are also available:

Background Articles:

  • Barton M et al. How to read the new recommendation statement: methods update from the U.S. Preventive Services Task Force. Ann Intern Med. 2007;147:123-127.
  • Guirguis-Blake J et al. Current processes of the U.S. Preventive Services Task Force: refining evidence-based recommendation development. Ann Intern Med. 2007;147:117-122. [2 references]
  • Sawaya GF et al. Update on the methods of the U.S. Preventive Services Task Force: estimating certainty and magnitude of net benefit. Ann Intern Med. 2007;147:871-875. [5 references].
  • Petitti DB et al. Update on the methods of the U.S. Preventive Services Task Force: insufficient evidence. Ann Intern Med. 2009;150:199-205.

Electronic copies: Available from U.S. Preventive Services Task Force (USPSTF) Web site External Web Site Policy.

The following is also available:

  • The guide to clinical preventive services, 2009. Recommendations of the U.S. Preventive Services Task Force. Rockville (MD): Agency for Healthcare Research and Quality (AHRQ), 2009. 249 p. Electronic copies available from the AHRQ Web site External Web Site Policy.

Print copies: Available from the Agency for Healthcare Research and Quality Publications Clearinghouse. For more information, go to http://www.ahrq.gov/research/publications/index.html External Web Site Policy or call 1-800-358-9295 (U.S. only).

The Electronic Preventive Services Selector (ePSS) External Web Site Policy, available as a PDA application and a web-based tool, is a quick hands-on tool designed to help primary care clinicians identify the screening, counseling, and preventive medication services that are appropriate for their patients. It is based on current recommendations of the USPSTF and can be searched by specific patient characteristics such as age, sex, and selected behavioral risk factors.

Patient Resources

The following are available:

  • Using nontraditional risk factors to estimate risk for coronary heart disease: U.S. Preventive Services Task Force recommendation. Summaries for patients. 2009. Available from the Annals of Internal Medicine Web site External Web Site Policy.
  • Men: Stay Healthy at Any Age – Checklist for Your Next Checkup. Rockville (MD): Agency for Healthcare Research and Quality. AHRQ Pub. No. 07-IP006-A. February 2007. Electronic copies: Available in English External Web Site Policy and Spanish External Web Site Policy from the USPSTF Web site. See the related QualityTool summary on the Health Care Innovations Exchange Web site External Web Site Policy.
  • Women: Stay Healthy at Any Age – Checklist for Your Next Checkup. Rockville (MD): Agency for Healthcare Research and Quality. AHRQ Pub. No. 07-IP005-A. February 2007. Electronic copies: Available in English External Web Site Policy and Spanish External Web Site Policy from the USPSTF Web site. See the related QualityTool summary on the Health Care Innovations Exchange Web site External Web Site Policy.

Print copies: Available from the Agency for Healthcare Research and Quality (AHRQ) Publications Clearinghouse. For more information, go to http://www.ahrq.gov/research/publications/index.html External Web Site Policy or call 1-800-358-9295 (U.S. only).

Myhealthfinder is a new tool that provides personalized recommendations for clinical preventive services specific to the user's age, gender, and pregnancy status. It features evidence-based recommendations from the USPSTF and is available at www.healthfinder.gov External Web Site Policy.

Please note: This patient information is intended to provide health professionals with information to share with their patients to help them better understand their health and their diagnosed disorders. By providing access to this patient information, it is not the intention of NGC to provide specific medical advice for particular patients. Rather we urge patients and their representatives to review this material and then to consult with a licensed health professional for evaluation of treatment options suitable for them as well as for diagnosis and answers to their personal medical questions. This patient information has been derived and prepared from a guideline for health care professionals included on NGC by the authors or publishers of that original guideline. The patient information is not reviewed by NGC to establish whether or not it accurately reflects the original guideline's content.

NGC Status

This summary was completed by ECRI Institute on November 24, 2009. The information was verified by the developer on January 6, 2010.

Copyright Statement

Requests regarding copyright should be sent to: Randie A. Siegel, Electronic Dissemination Advisor, Division of Print and Electronic Publishing, Agency for Healthcare Research and Quality, 540 Gaither Road, Rockville, MD 20850. Facsimile: 301-427-1873. E-mail: Randie.siegel@ahrq.hhs.gov.

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