2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.

Note from the National Guideline Clearinghouse (NGC): National Heart, Lung and Blood Institute (NHLBI) Evidence Statements are included for each recommendation. See Appendices 4 and 5 in the original guideline document.

Each recommendation has been mapped from the NHLBI grading format to the American College of Cardiology/American Heart Association Class of Recommendation/Level of Evidence (ACC/AHA COR/LOE) construct and is expressed in both formats. Because of the inherent differences in grading systems and the clinical questions driving the recommendations, alignment between the NHLBI and ACC/AHA formats is in some cases imperfect. Definitions for the NHLBI strength of recommendation (A-E, N) and quality of evidence (High, Moderate, Low) and the ACC/AHA levels of the evidence (LOE: A-C) and classes of recommendations (COR: I-III) are provided at the end of the "Major Recommendations" field.

Summary of Recommendations for Risk Assessment

Assessment of 10-Year Risk of a First Hard Atherosclerotic Cardiovascular Disease (ASCVD) Event

1. The race- and sex-specific Pooled Cohort Equations* to predict 10-year risk of a first hard ASCVD event should be used in non-Hispanic African Americans and non-Hispanic whites, 40–79 years of age. NHLBI Grade: B (Moderate); ACC/AHA COR: I; ACC/AHA LOE: B (Dawber, Kannel, & Lyell, 1963; Fried et al., 1991; Kannel et al., 1979; "The Atherosclerosis Risk in Communities (ARIC) Study," 1989)
2. Use of the sex-specific Pooled Cohort Equations for non-Hispanic whites may be considered for estimation of risk in patients from populations other than African Americans and non-Hispanic whites. NHLBI Grade: E (Expert Opinion); ACC/AHA COR: IIb; ACC/AHA LOE: C

Critical Question (CQ) 1: Use of Newer Risk Markers after Quantitative Risk Assessment

1. If, after quantitative risk assessment, a risk-based treatment decision is uncertain, assessment of ≥1 of the following–family history, high-sensitivity C-reactive protein (hs-CRP), coronary artery calcium (CAC) score, or ankle-brachial index (ABI)–may be considered to inform treatment decision making. NHLBI Grade: E (Expert Opinion); ACC/AHA COR: IIb†; ACC/AHA LOE: B (Buckley et al., 2009; Empana et al., 2011; Ankle Brachial Index Collaboration et al., 2008; Helfand et al., 2009; Emerging Risk Factors Collaboration et al., 2010; Kashani et al., 2013; U.S. Preventive Services Task Force (USPSTF), 2013; Peters et al., 2012; Schnell-Inderst et al., 2010)
2. Routine measurement of carotid intima-media thickness (CIMT) is not recommended in clinical practice for risk assessment for a first ASCVD event. NHLBI Grade: N (No recommendation for or against); ACC/AHA COR: III: No Benefit†; ACC/AHA LOE: B (Helfand et al., 2009; Peters et al., 2012; Den Ruijter et al., 2012)
3. The contribution of apolipoprotein B (ApoB), chronic kidney disease (CKD), albuminuria, and cardiorespiratory fitness to risk assessment for a first ASCVD event is uncertain at present. NHLBI Grade: N (No recommendation for or against)

CQ2: Long-Term Risk Assessment

1. It is reasonable to assess traditional ASCVD risk factors‡ every 4 to 6 years in adults 20 to 79 years of age who are free from ASCVD and to estimate 10-year ASCVD risk every 4 to 6 years in adults 40 to 79 years of age who are free from ASCVD. NHLBI Grade: B (Moderate); ACC/AHA COR: IIa; ACC/AHA LOE: B (Karp et al., 2004; Pencina et al., 2009)
2. Assessment of 30-year or lifetime ASCVD risk on the basis of traditional risk factors‡ may be considered in adults 20 to 59 years of age who are free from ASCVD and are not at high short-term risk. NHLBI Grade: C (Weak); ACC/AHA COR: IIb; ACC/AHA LOE: C (Pencina et al., 2009; Lloyd-Jones et al., 2006; Lloyd-Jones et al., 2004)

A downloadable spreadsheet enabling estimation of 10-year and lifetime risk of ASCVD and a Web-based calculator is available from the American Heart Association Web site 

and the American College of Cardiology Web site 

.

*Derived from the ARIC (Atherosclerosis Risk in Communities) study (1989), Cardiovascular Health Study (Fried et al., 1991), CARDIA (Coronary Artery Risk Development in Young Adults) study (Friedman et al., 1988), and Framingham original and offspring cohorts (Dawber, Kannel, & Lyell, 1963; Kannel et al., 1979).

†Based on new evidence reviewed during ACC/AHA update of evidence.

‡Age, sex, total cholesterol, high-density lipoprotein cholesterol, systolic BP, use of antihypertensive therapy, diabetes, and current smoking.

Definitions:

NHLBI Grading of the Strength of Recommendations

Note: Each recommendation has been mapped from the National Heart, Lung and Blood Institute (NHLBI) grading format below to the American College of Cardiology/American Heart Association (ACC/AHA) Classification of Recommendation/Level of Evidence (COR/LOE) construct (see the "Rating Scheme for the Strength of the Evidence" field) and is expressed in both formats.

NHLBI Grading of the Strength of Recommendations

Grade	Strength of Recommendation*
A	Strong recommendation There is high certainty based on evidence that the net benefit† is substantial.
B	Moderate recommendation There is moderate certainty based on evidence that the net benefit is moderate to substantial, or there is high certainty that the net benefit is moderate.
C	Weak recommendation There is at least moderate certainty based on evidence that there is a small net benefit.
D	Recommendation against There is at least moderate certainty based on evidence that there is no net benefit or that risks/harms outweigh benefits.
E	Expert opinion ("There is insufficient evidence or evidence is unclear or conflicting, but this is what the Work Group recommends.") Net benefit is unclear. Balance of benefits and harms cannot be determined because of no evidence, insufficient evidence, unclear evidence, or conflicting evidence, but the Work Group thought it was important to provide clinical guidance and make a recommendation. Further research is recommended in this area.
N	No recommendation for or against ("There is insufficient evidence or evidence is unclear or conflicting.") Net benefit is unclear. Balance of benefits and harms cannot be determined because of no evidence, insufficient evidence, unclear evidence, or conflicting evidence, and the Work Group thought no recommendation should be made. Further research is recommended in this area.

*In most cases, the strength of the recommendation should be closely aligned with the quality of the evidence; however, under some circumstances, there may be valid reasons for making recommendations that are not closely aligned with the quality of the evidence (e.g., strong recommendation when the evidence quality is moderate, such as smoking cessation to reduce cardiovascular disease [CVD] risk or ordering an electrocardiogram [ECG] as part of the initial diagnostic work-up for a patient presenting with possible myocardial infarction [MI]). Those situations should be limited and the rationale explained clearly by the Work Group.

†Net benefit is defined as benefits minus risks/harms of the service/intervention.

NHLBI Quality Rating of the Strength of Evidence

Type of Evidence	Quality Rating*
Well-designed, well-executed† randomized controlled trials (RCTs) that adequately represent populations to which the results are applied and directly assess effects on health outcomes. Meta-analyses of such studies. Highly certain about the estimate of effect. Further research is unlikely to change confidence in the estimate of effect.	High
RCTs with minor limitations‡ affecting confidence in, or applicability of, the results. Well-designed, well-executed nonrandomized controlled studies§ and well-designed, well-executed observational studies¶. Meta-analyses of such studies. Moderately certain about the estimate of effect. Further research may have an impact on confidence in the estimate of effect and may change the estimate.	Moderate
RCTs with major limitations. Nonrandomized controlled studies and observational studies with major limitations affecting confidence in, or applicability of, the results. Uncontrolled clinical observations without an appropriate comparison group (e.g., case series, case reports). Physiological studies in humans. Meta-analyses of such studies. Low certainty about the estimate of effect. Further research is likely to have an impact on confidence in the estimate of effect and is likely to change the estimate.	Low

*In some cases, other evidence, such as large all-or-none case series (e.g., jumping from airplanes or tall structures), can represent high- or moderate-quality evidence. In such cases, the rationale for the evidence rating exception should be explained by the Work Group and clearly justified.

†"Well-designed, well-executed" refers to studies that directly address the question; use adequate randomization, blinding, and allocation concealment; are adequately powered; use intention-to-treat analyses; and have high follow-up rates.

‡Limitations include concerns with the design and execution of a study that result in decreased confidence in the true estimate of the effect. Examples of such limitations include but are not limited to: inadequate randomization, lack of blinding of study participants or outcome assessors, inadequate power, outcomes of interest that are not prespecified for the primary outcomes, low follow-up rates, and findings based on subgroup analyses. Whether the limitations are considered minor or major is based on the number and severity of flaws in design or execution. Rules for determining whether the limitations are considered minor or major and how they will affect rating of the individual studies will be developed collaboratively with the methodology team.

§Nonrandomized controlled studies refer to intervention studies where assignment to intervention and comparison groups is not random (e.g., quasi-experimental study design).

¶Observational studies include prospective and retrospective cohort, case-control, and cross-sectional studies.

Applying Classification of Recommendations and Level of Evidence

		Size of Treatment Effect
		CLASS I Benefit >>> Risk Procedure/Treatment SHOULD be performed/ administered	CLASS IIa Benefit >> Risk Additional studies with focused objectives needed IT IS REASONABLE to perform procedure/administer treatment	CLASS IIb Benefit ≥ Risk Additional studies with broad objectives needed; additional registry data would be helpful Procedure/Treatment MAY BE CONSIDERED	CLASS III No Benefit or Class III Harm
						Procedure/Test	Treatment
					COR III: No Benefit	Not helpful	No proven benefit
					COR III: Harm	Excess cost without benefit or harmful	Harmful to patients
Estimate of Certainty (Precision) of Treatment Effect	LEVEL A Multiple populations evaluated* Data derived from multiple randomized clinical trials or meta-analyses	Recommendation that procedure or treatment is useful/effective Sufficient evidence from multiple randomized trials or meta-analyses	Recommendation in favor of treatment or procedure being useful/effective Some conflicting evidence from multiple randomized trials or meta-analyses	Recommendation's usefulness/efficacy less well established Greater conflicting evidence from multiple randomized trials or meta-analyses	Recommendation that procedure or treatment is not useful/effective and may be harmful Sufficient evidence from multiple randomized trials or meta-analyses
	LEVEL B Limited populations evaluated* Data derived from a single randomized trial or nonrandomized studies	Recommendation that procedure or treatment is useful/effective Evidence from single randomized trial or nonrandomized studies	Recommendation in favor of treatment or procedure being useful/effective Some conflicting evidence from single randomized trial or nonrandomized studies	Recommendation's usefulness/efficacy less well established Greater conflicting evidence from single randomized trial or nonrandomized studies	Recommendation that procedure or treatment is not useful/effective and may be harmful Evidence from single randomized trial or nonrandomized studies
	LEVEL C Very limited populations evaluated* Only consensus opinion of experts, case studies, or standard of care	Recommendation that procedure or treatment is useful/effective Only expert opinion, case studies, or standard of care	Recommendation in favor of treatment or procedure being useful/effective Only diverging expert opinion, case studies, or standard of care	Recommendation's usefulness/efficacy less well established Only diverging expert opinion, case studies, or standard of care	Recommendation that procedure or treatment is not useful/effective and may be harmful Only expert opinion, case studies, or standard of care

A recommendation with Level of Evidence B or C does not imply that the recommendation is weak. Many important clinical questions addressed in the guidelines do not lend themselves to clinical trials. Although randomized trials are unavailable, there may be a very clear clinical consensus that a particular test or therapy is useful or effective.

*Data available from clinical trials or registries about the usefulness/efficacy in different subpopulations, such as sex, age, history of diabetes, history of prior myocardial infarction, history of heart failure, and prior aspirin use.

†For comparative-effectiveness recommendations (Class I and IIa; Level of Evidence A and B only), studies that support the use of comparator verbs should involve direct comparisons of the treatments or strategies being evaluated.

An algorithm titled "Implementation of Risk Assessment Work Group Recommendations" is provided in the original guideline document.

Note from the National Guideline Clearinghouse (NGC): National Heart, Lung and Blood Institute (NHLBI) Evidence Statements are included for each recommendation. See Appendices 4 and 5 in the original guideline document.

Each recommendation has been mapped from the NHLBI grading format to the American College of Cardiology/American Heart Association Class of Recommendation/Level of Evidence (ACC/AHA COR/LOE) construct and is expressed in both formats. Because of the inherent differences in grading systems and the clinical questions driving the recommendations, alignment between the NHLBI and ACC/AHA formats is in some cases imperfect. Definitions for the NHLBI strength of recommendation (A-E, N) and quality of evidence (High, Moderate, Low) and the ACC/AHA levels of the evidence (LOE: A-C) and classes of recommendations (COR: I-III) are provided at the end of the "Major Recommendations" field.

Summary of Recommendations for Risk Assessment

Assessment of 10-Year Risk of a First Hard Atherosclerotic Cardiovascular Disease (ASCVD) Event

1. The race- and sex-specific Pooled Cohort Equations* to predict 10-year risk of a first hard ASCVD event should be used in non-Hispanic African Americans and non-Hispanic whites, 40–79 years of age. NHLBI Grade: B (Moderate); ACC/AHA COR: I; ACC/AHA LOE: B (Dawber, Kannel, & Lyell, 1963; Fried et al., 1991; Kannel et al., 1979; "The Atherosclerosis Risk in Communities (ARIC) Study," 1989)
2. Use of the sex-specific Pooled Cohort Equations for non-Hispanic whites may be considered for estimation of risk in patients from populations other than African Americans and non-Hispanic whites. NHLBI Grade: E (Expert Opinion); ACC/AHA COR: IIb; ACC/AHA LOE: C

Critical Question (CQ) 1: Use of Newer Risk Markers after Quantitative Risk Assessment

1. If, after quantitative risk assessment, a risk-based treatment decision is uncertain, assessment of ≥1 of the following–family history, high-sensitivity C-reactive protein (hs-CRP), coronary artery calcium (CAC) score, or ankle-brachial index (ABI)–may be considered to inform treatment decision making. NHLBI Grade: E (Expert Opinion); ACC/AHA COR: IIb†; ACC/AHA LOE: B (Buckley et al., 2009; Empana et al., 2011; Ankle Brachial Index Collaboration et al., 2008; Helfand et al., 2009; Emerging Risk Factors Collaboration et al., 2010; Kashani et al., 2013; U.S. Preventive Services Task Force (USPSTF), 2013; Peters et al., 2012; Schnell-Inderst et al., 2010)
2. Routine measurement of carotid intima-media thickness (CIMT) is not recommended in clinical practice for risk assessment for a first ASCVD event. NHLBI Grade: N (No recommendation for or against); ACC/AHA COR: III: No Benefit†; ACC/AHA LOE: B (Helfand et al., 2009; Peters et al., 2012; Den Ruijter et al., 2012)
3. The contribution of apolipoprotein B (ApoB), chronic kidney disease (CKD), albuminuria, and cardiorespiratory fitness to risk assessment for a first ASCVD event is uncertain at present. NHLBI Grade: N (No recommendation for or against)

CQ2: Long-Term Risk Assessment

1. It is reasonable to assess traditional ASCVD risk factors‡ every 4 to 6 years in adults 20 to 79 years of age who are free from ASCVD and to estimate 10-year ASCVD risk every 4 to 6 years in adults 40 to 79 years of age who are free from ASCVD. NHLBI Grade: B (Moderate); ACC/AHA COR: IIa; ACC/AHA LOE: B (Karp et al., 2004; Pencina et al., 2009)
2. Assessment of 30-year or lifetime ASCVD risk on the basis of traditional risk factors‡ may be considered in adults 20 to 59 years of age who are free from ASCVD and are not at high short-term risk. NHLBI Grade: C (Weak); ACC/AHA COR: IIb; ACC/AHA LOE: C (Pencina et al., 2009; Lloyd-Jones et al., 2006; Lloyd-Jones et al., 2004)

A downloadable spreadsheet enabling estimation of 10-year and lifetime risk of ASCVD and a Web-based calculator is available from the American Heart Association Web site 

and the American College of Cardiology Web site 

.

*Derived from the ARIC (Atherosclerosis Risk in Communities) study (1989), Cardiovascular Health Study (Fried et al., 1991), CARDIA (Coronary Artery Risk Development in Young Adults) study (Friedman et al., 1988), and Framingham original and offspring cohorts (Dawber, Kannel, & Lyell, 1963; Kannel et al., 1979).

†Based on new evidence reviewed during ACC/AHA update of evidence.

‡Age, sex, total cholesterol, high-density lipoprotein cholesterol, systolic BP, use of antihypertensive therapy, diabetes, and current smoking.

Definitions:

NHLBI Grading of the Strength of Recommendations

Note: Each recommendation has been mapped from the National Heart, Lung and Blood Institute (NHLBI) grading format below to the American College of Cardiology/American Heart Association (ACC/AHA) Classification of Recommendation/Level of Evidence (COR/LOE) construct (see the "Rating Scheme for the Strength of the Evidence" field) and is expressed in both formats.

NHLBI Grading of the Strength of Recommendations

Grade	Strength of Recommendation*
A	Strong recommendation There is high certainty based on evidence that the net benefit† is substantial.
B	Moderate recommendation There is moderate certainty based on evidence that the net benefit is moderate to substantial, or there is high certainty that the net benefit is moderate.
C	Weak recommendation There is at least moderate certainty based on evidence that there is a small net benefit.
D	Recommendation against There is at least moderate certainty based on evidence that there is no net benefit or that risks/harms outweigh benefits.
E	Expert opinion ("There is insufficient evidence or evidence is unclear or conflicting, but this is what the Work Group recommends.") Net benefit is unclear. Balance of benefits and harms cannot be determined because of no evidence, insufficient evidence, unclear evidence, or conflicting evidence, but the Work Group thought it was important to provide clinical guidance and make a recommendation. Further research is recommended in this area.
N	No recommendation for or against ("There is insufficient evidence or evidence is unclear or conflicting.") Net benefit is unclear. Balance of benefits and harms cannot be determined because of no evidence, insufficient evidence, unclear evidence, or conflicting evidence, and the Work Group thought no recommendation should be made. Further research is recommended in this area.

*In most cases, the strength of the recommendation should be closely aligned with the quality of the evidence; however, under some circumstances, there may be valid reasons for making recommendations that are not closely aligned with the quality of the evidence (e.g., strong recommendation when the evidence quality is moderate, such as smoking cessation to reduce cardiovascular disease [CVD] risk or ordering an electrocardiogram [ECG] as part of the initial diagnostic work-up for a patient presenting with possible myocardial infarction [MI]). Those situations should be limited and the rationale explained clearly by the Work Group.

†Net benefit is defined as benefits minus risks/harms of the service/intervention.

NHLBI Quality Rating of the Strength of Evidence

Type of Evidence	Quality Rating*
Well-designed, well-executed† randomized controlled trials (RCTs) that adequately represent populations to which the results are applied and directly assess effects on health outcomes. Meta-analyses of such studies. Highly certain about the estimate of effect. Further research is unlikely to change confidence in the estimate of effect.	High
RCTs with minor limitations‡ affecting confidence in, or applicability of, the results. Well-designed, well-executed nonrandomized controlled studies§ and well-designed, well-executed observational studies¶. Meta-analyses of such studies. Moderately certain about the estimate of effect. Further research may have an impact on confidence in the estimate of effect and may change the estimate.	Moderate
RCTs with major limitations. Nonrandomized controlled studies and observational studies with major limitations affecting confidence in, or applicability of, the results. Uncontrolled clinical observations without an appropriate comparison group (e.g., case series, case reports). Physiological studies in humans. Meta-analyses of such studies. Low certainty about the estimate of effect. Further research is likely to have an impact on confidence in the estimate of effect and is likely to change the estimate.	Low

*In some cases, other evidence, such as large all-or-none case series (e.g., jumping from airplanes or tall structures), can represent high- or moderate-quality evidence. In such cases, the rationale for the evidence rating exception should be explained by the Work Group and clearly justified.

†"Well-designed, well-executed" refers to studies that directly address the question; use adequate randomization, blinding, and allocation concealment; are adequately powered; use intention-to-treat analyses; and have high follow-up rates.

‡Limitations include concerns with the design and execution of a study that result in decreased confidence in the true estimate of the effect. Examples of such limitations include but are not limited to: inadequate randomization, lack of blinding of study participants or outcome assessors, inadequate power, outcomes of interest that are not prespecified for the primary outcomes, low follow-up rates, and findings based on subgroup analyses. Whether the limitations are considered minor or major is based on the number and severity of flaws in design or execution. Rules for determining whether the limitations are considered minor or major and how they will affect rating of the individual studies will be developed collaboratively with the methodology team.

§Nonrandomized controlled studies refer to intervention studies where assignment to intervention and comparison groups is not random (e.g., quasi-experimental study design).

¶Observational studies include prospective and retrospective cohort, case-control, and cross-sectional studies.

Applying Classification of Recommendations and Level of Evidence

		Size of Treatment Effect
		CLASS I Benefit >>> Risk Procedure/Treatment SHOULD be performed/ administered	CLASS IIa Benefit >> Risk Additional studies with focused objectives needed IT IS REASONABLE to perform procedure/administer treatment	CLASS IIb Benefit ≥ Risk Additional studies with broad objectives needed; additional registry data would be helpful Procedure/Treatment MAY BE CONSIDERED	CLASS III No Benefit or Class III Harm
						Procedure/Test	Treatment
					COR III: No Benefit	Not helpful	No proven benefit
					COR III: Harm	Excess cost without benefit or harmful	Harmful to patients
Estimate of Certainty (Precision) of Treatment Effect	LEVEL A Multiple populations evaluated* Data derived from multiple randomized clinical trials or meta-analyses	Recommendation that procedure or treatment is useful/effective Sufficient evidence from multiple randomized trials or meta-analyses	Recommendation in favor of treatment or procedure being useful/effective Some conflicting evidence from multiple randomized trials or meta-analyses	Recommendation's usefulness/efficacy less well established Greater conflicting evidence from multiple randomized trials or meta-analyses	Recommendation that procedure or treatment is not useful/effective and may be harmful Sufficient evidence from multiple randomized trials or meta-analyses
	LEVEL B Limited populations evaluated* Data derived from a single randomized trial or nonrandomized studies	Recommendation that procedure or treatment is useful/effective Evidence from single randomized trial or nonrandomized studies	Recommendation in favor of treatment or procedure being useful/effective Some conflicting evidence from single randomized trial or nonrandomized studies	Recommendation's usefulness/efficacy less well established Greater conflicting evidence from single randomized trial or nonrandomized studies	Recommendation that procedure or treatment is not useful/effective and may be harmful Evidence from single randomized trial or nonrandomized studies
	LEVEL C Very limited populations evaluated* Only consensus opinion of experts, case studies, or standard of care	Recommendation that procedure or treatment is useful/effective Only expert opinion, case studies, or standard of care	Recommendation in favor of treatment or procedure being useful/effective Only diverging expert opinion, case studies, or standard of care	Recommendation's usefulness/efficacy less well established Only diverging expert opinion, case studies, or standard of care	Recommendation that procedure or treatment is not useful/effective and may be harmful Only expert opinion, case studies, or standard of care

A recommendation with Level of Evidence B or C does not imply that the recommendation is weak. Many important clinical questions addressed in the guidelines do not lend themselves to clinical trials. Although randomized trials are unavailable, there may be a very clear clinical consensus that a particular test or therapy is useful or effective.

*Data available from clinical trials or registries about the usefulness/efficacy in different subpopulations, such as sex, age, history of diabetes, history of prior myocardial infarction, history of heart failure, and prior aspirin use.

†For comparative-effectiveness recommendations (Class I and IIa; Level of Evidence A and B only), studies that support the use of comparator verbs should involve direct comparisons of the treatments or strategies being evaluated.

An algorithm titled "Implementation of Risk Assessment Work Group Recommendations" is provided in the original guideline document.

Note from the National Guideline Clearinghouse (NGC): National Heart, Lung and Blood Institute (NHLBI) Evidence Statements are included for each recommendation. See Appendices 4 and 5 in the original guideline document.

Each recommendation has been mapped from the NHLBI grading format to the American College of Cardiology/American Heart Association Class of Recommendation/Level of Evidence (ACC/AHA COR/LOE) construct and is expressed in both formats. Because of the inherent differences in grading systems and the clinical questions driving the recommendations, alignment between the NHLBI and ACC/AHA formats is in some cases imperfect. Definitions for the NHLBI strength of recommendation (A-E, N) and quality of evidence (High, Moderate, Low) and the ACC/AHA levels of the evidence (LOE: A-C) and classes of recommendations (COR: I-III) are provided at the end of the "Major Recommendations" field.

Summary of Recommendations for Risk Assessment

Assessment of 10-Year Risk of a First Hard Atherosclerotic Cardiovascular Disease (ASCVD) Event

1. The race- and sex-specific Pooled Cohort Equations* to predict 10-year risk of a first hard ASCVD event should be used in non-Hispanic African Americans and non-Hispanic whites, 40–79 years of age. NHLBI Grade: B (Moderate); ACC/AHA COR: I; ACC/AHA LOE: B (Dawber, Kannel, & Lyell, 1963; Fried et al., 1991; Kannel et al., 1979; "The Atherosclerosis Risk in Communities (ARIC) Study," 1989)
2. Use of the sex-specific Pooled Cohort Equations for non-Hispanic whites may be considered for estimation of risk in patients from populations other than African Americans and non-Hispanic whites. NHLBI Grade: E (Expert Opinion); ACC/AHA COR: IIb; ACC/AHA LOE: C

Critical Question (CQ) 1: Use of Newer Risk Markers after Quantitative Risk Assessment

1. If, after quantitative risk assessment, a risk-based treatment decision is uncertain, assessment of ≥1 of the following–family history, high-sensitivity C-reactive protein (hs-CRP), coronary artery calcium (CAC) score, or ankle-brachial index (ABI)–may be considered to inform treatment decision making. NHLBI Grade: E (Expert Opinion); ACC/AHA COR: IIb†; ACC/AHA LOE: B (Buckley et al., 2009; Empana et al., 2011; Ankle Brachial Index Collaboration et al., 2008; Helfand et al., 2009; Emerging Risk Factors Collaboration et al., 2010; Kashani et al., 2013; U.S. Preventive Services Task Force (USPSTF), 2013; Peters et al., 2012; Schnell-Inderst et al., 2010)
2. Routine measurement of carotid intima-media thickness (CIMT) is not recommended in clinical practice for risk assessment for a first ASCVD event. NHLBI Grade: N (No recommendation for or against); ACC/AHA COR: III: No Benefit†; ACC/AHA LOE: B (Helfand et al., 2009; Peters et al., 2012; Den Ruijter et al., 2012)
3. The contribution of apolipoprotein B (ApoB), chronic kidney disease (CKD), albuminuria, and cardiorespiratory fitness to risk assessment for a first ASCVD event is uncertain at present. NHLBI Grade: N (No recommendation for or against)

CQ2: Long-Term Risk Assessment

1. It is reasonable to assess traditional ASCVD risk factors‡ every 4 to 6 years in adults 20 to 79 years of age who are free from ASCVD and to estimate 10-year ASCVD risk every 4 to 6 years in adults 40 to 79 years of age who are free from ASCVD. NHLBI Grade: B (Moderate); ACC/AHA COR: IIa; ACC/AHA LOE: B (Karp et al., 2004; Pencina et al., 2009)
2. Assessment of 30-year or lifetime ASCVD risk on the basis of traditional risk factors‡ may be considered in adults 20 to 59 years of age who are free from ASCVD and are not at high short-term risk. NHLBI Grade: C (Weak); ACC/AHA COR: IIb; ACC/AHA LOE: C (Pencina et al., 2009; Lloyd-Jones et al., 2006; Lloyd-Jones et al., 2004)

A downloadable spreadsheet enabling estimation of 10-year and lifetime risk of ASCVD and a Web-based calculator is available from the American Heart Association Web site 

and the American College of Cardiology Web site 

.

*Derived from the ARIC (Atherosclerosis Risk in Communities) study (1989), Cardiovascular Health Study (Fried et al., 1991), CARDIA (Coronary Artery Risk Development in Young Adults) study (Friedman et al., 1988), and Framingham original and offspring cohorts (Dawber, Kannel, & Lyell, 1963; Kannel et al., 1979).

†Based on new evidence reviewed during ACC/AHA update of evidence.

‡Age, sex, total cholesterol, high-density lipoprotein cholesterol, systolic BP, use of antihypertensive therapy, diabetes, and current smoking.

Definitions:

NHLBI Grading of the Strength of Recommendations

Note: Each recommendation has been mapped from the National Heart, Lung and Blood Institute (NHLBI) grading format below to the American College of Cardiology/American Heart Association (ACC/AHA) Classification of Recommendation/Level of Evidence (COR/LOE) construct (see the "Rating Scheme for the Strength of the Evidence" field) and is expressed in both formats.

NHLBI Grading of the Strength of Recommendations

Grade	Strength of Recommendation*
A	Strong recommendation There is high certainty based on evidence that the net benefit† is substantial.
B	Moderate recommendation There is moderate certainty based on evidence that the net benefit is moderate to substantial, or there is high certainty that the net benefit is moderate.
C	Weak recommendation There is at least moderate certainty based on evidence that there is a small net benefit.
D	Recommendation against There is at least moderate certainty based on evidence that there is no net benefit or that risks/harms outweigh benefits.
E	Expert opinion ("There is insufficient evidence or evidence is unclear or conflicting, but this is what the Work Group recommends.") Net benefit is unclear. Balance of benefits and harms cannot be determined because of no evidence, insufficient evidence, unclear evidence, or conflicting evidence, but the Work Group thought it was important to provide clinical guidance and make a recommendation. Further research is recommended in this area.
N	No recommendation for or against ("There is insufficient evidence or evidence is unclear or conflicting.") Net benefit is unclear. Balance of benefits and harms cannot be determined because of no evidence, insufficient evidence, unclear evidence, or conflicting evidence, and the Work Group thought no recommendation should be made. Further research is recommended in this area.

*In most cases, the strength of the recommendation should be closely aligned with the quality of the evidence; however, under some circumstances, there may be valid reasons for making recommendations that are not closely aligned with the quality of the evidence (e.g., strong recommendation when the evidence quality is moderate, such as smoking cessation to reduce cardiovascular disease [CVD] risk or ordering an electrocardiogram [ECG] as part of the initial diagnostic work-up for a patient presenting with possible myocardial infarction [MI]). Those situations should be limited and the rationale explained clearly by the Work Group.

†Net benefit is defined as benefits minus risks/harms of the service/intervention.

NHLBI Quality Rating of the Strength of Evidence

Type of Evidence	Quality Rating*
Well-designed, well-executed† randomized controlled trials (RCTs) that adequately represent populations to which the results are applied and directly assess effects on health outcomes. Meta-analyses of such studies. Highly certain about the estimate of effect. Further research is unlikely to change confidence in the estimate of effect.	High
RCTs with minor limitations‡ affecting confidence in, or applicability of, the results. Well-designed, well-executed nonrandomized controlled studies§ and well-designed, well-executed observational studies¶. Meta-analyses of such studies. Moderately certain about the estimate of effect. Further research may have an impact on confidence in the estimate of effect and may change the estimate.	Moderate
RCTs with major limitations. Nonrandomized controlled studies and observational studies with major limitations affecting confidence in, or applicability of, the results. Uncontrolled clinical observations without an appropriate comparison group (e.g., case series, case reports). Physiological studies in humans. Meta-analyses of such studies. Low certainty about the estimate of effect. Further research is likely to have an impact on confidence in the estimate of effect and is likely to change the estimate.	Low

*In some cases, other evidence, such as large all-or-none case series (e.g., jumping from airplanes or tall structures), can represent high- or moderate-quality evidence. In such cases, the rationale for the evidence rating exception should be explained by the Work Group and clearly justified.

†"Well-designed, well-executed" refers to studies that directly address the question; use adequate randomization, blinding, and allocation concealment; are adequately powered; use intention-to-treat analyses; and have high follow-up rates.

‡Limitations include concerns with the design and execution of a study that result in decreased confidence in the true estimate of the effect. Examples of such limitations include but are not limited to: inadequate randomization, lack of blinding of study participants or outcome assessors, inadequate power, outcomes of interest that are not prespecified for the primary outcomes, low follow-up rates, and findings based on subgroup analyses. Whether the limitations are considered minor or major is based on the number and severity of flaws in design or execution. Rules for determining whether the limitations are considered minor or major and how they will affect rating of the individual studies will be developed collaboratively with the methodology team.

§Nonrandomized controlled studies refer to intervention studies where assignment to intervention and comparison groups is not random (e.g., quasi-experimental study design).

¶Observational studies include prospective and retrospective cohort, case-control, and cross-sectional studies.

Applying Classification of Recommendations and Level of Evidence

		Size of Treatment Effect
		CLASS I Benefit >>> Risk Procedure/Treatment SHOULD be performed/ administered	CLASS IIa Benefit >> Risk Additional studies with focused objectives needed IT IS REASONABLE to perform procedure/administer treatment	CLASS IIb Benefit ≥ Risk Additional studies with broad objectives needed; additional registry data would be helpful Procedure/Treatment MAY BE CONSIDERED	CLASS III No Benefit or Class III Harm
						Procedure/Test	Treatment
					COR III: No Benefit	Not helpful	No proven benefit
					COR III: Harm	Excess cost without benefit or harmful	Harmful to patients
Estimate of Certainty (Precision) of Treatment Effect	LEVEL A Multiple populations evaluated* Data derived from multiple randomized clinical trials or meta-analyses	Recommendation that procedure or treatment is useful/effective Sufficient evidence from multiple randomized trials or meta-analyses	Recommendation in favor of treatment or procedure being useful/effective Some conflicting evidence from multiple randomized trials or meta-analyses	Recommendation's usefulness/efficacy less well established Greater conflicting evidence from multiple randomized trials or meta-analyses	Recommendation that procedure or treatment is not useful/effective and may be harmful Sufficient evidence from multiple randomized trials or meta-analyses
	LEVEL B Limited populations evaluated* Data derived from a single randomized trial or nonrandomized studies	Recommendation that procedure or treatment is useful/effective Evidence from single randomized trial or nonrandomized studies	Recommendation in favor of treatment or procedure being useful/effective Some conflicting evidence from single randomized trial or nonrandomized studies	Recommendation's usefulness/efficacy less well established Greater conflicting evidence from single randomized trial or nonrandomized studies	Recommendation that procedure or treatment is not useful/effective and may be harmful Evidence from single randomized trial or nonrandomized studies
	LEVEL C Very limited populations evaluated* Only consensus opinion of experts, case studies, or standard of care	Recommendation that procedure or treatment is useful/effective Only expert opinion, case studies, or standard of care	Recommendation in favor of treatment or procedure being useful/effective Only diverging expert opinion, case studies, or standard of care	Recommendation's usefulness/efficacy less well established Only diverging expert opinion, case studies, or standard of care	Recommendation that procedure or treatment is not useful/effective and may be harmful Only expert opinion, case studies, or standard of care

A recommendation with Level of Evidence B or C does not imply that the recommendation is weak. Many important clinical questions addressed in the guidelines do not lend themselves to clinical trials. Although randomized trials are unavailable, there may be a very clear clinical consensus that a particular test or therapy is useful or effective.

*Data available from clinical trials or registries about the usefulness/efficacy in different subpopulations, such as sex, age, history of diabetes, history of prior myocardial infarction, history of heart failure, and prior aspirin use.

†For comparative-effectiveness recommendations (Class I and IIa; Level of Evidence A and B only), studies that support the use of comparator verbs should involve direct comparisons of the treatments or strategies being evaluated.

An algorithm titled "Implementation of Risk Assessment Work Group Recommendations" is provided in the original guideline document.