CVD Risk Assessment and Prevention in 2019 and Beyond: How, When, - - PDF document

CVD Risk Assessment and Prevention in 2019 and Beyond: How, When, and Why?

Donald M. Lloyd‐Jones, MD ScM FACC FAHA Eileen M. Foell Professor Chair, Dept. of Preventive Medicine Senior Associate Dean Director, NUCATS Institute Northwestern Feinberg School of Medicine

Disclosures

• Dr. Lloyd‐Jones has no RWI/COI

Grant funding: NIH, CMS, AHA

• Members of the 2018 Cholesterol Guidelines and 2019

Primary Prevention Guidelines Panels had no RWI/COI

Case

52‐year‐old South Asian male presents for routine follow‐up

• PMH: CKD (eGFR 50 mL/min/1.73 m2), HTN
• SH: denies tobacco, alcohol
• Meds: lisinopril 10 mg PO daily
• BP 142/86 mm Hg; Waist 42”
• Lipids (mg/dL): TC 225 HDL‐C 35 LDL‐C 150 TG 200
• 10‐yr ASCVD risk 9.7%

Case

Question #1: According to the 2018 ACC/AHA cholesterol and 2019 primary prevention guidelines, which risk category is most applicable for this patient?

• A. Low risk primary prevention
• B. Borderline risk primary prevention
• C. Intermediate risk primary prevention
• D. High risk primary prevention

Case

Question #2: According to the 2018 ACC/AHA cholesterol and 2019 primary prevention guidelines, which initial treatment strategy should be considered for this patient?

• A. Lifestyle modifications only
• B. Lifestyle modifications + moderate‐intensity statin
• C. Lifestyle modifications + high‐intensity statin
• D. Lifestyle modifications + high‐intensity statin + ezetimibe

Topics

• Rationale and evidence base for quantitative risk assessment
• Current guideline recommendations
• Strengths/limitations of existing risk scores
• Refining risk estimates for individual patients

 Clinician‐patient discussion  Risk‐enhancing factors  Measurement of CAC

• Implementing risk assessment and shared decision making –

practical approaches

Lloyd‐Jones et al. Circulation 2019; JACC 2019

Cholesterol Treatment Trialists Blood Pressure Lowering Treatment Trialists

• Allows identification of patients at sufficient risk

to merit treatment with higher likelihood of net individual and societal benefit

• Allows direct comparison of potential benefits

and harms from drug therapy

CTT, Lancet 2012 BPLTTC, Lancet 2014 Lloyd‐Jones et al., Circ and JACC 2018

Rationale for Absolute Risk Estimation

Karmali et al., Cochrane Reviews 2017 Lloyd‐Jones et al., Circ and JACC 2018

Evidence Base for Risk Estimation

• Providing CVD risk score data had

statistically significant but modest effects on:

• Initiation/intensification of BP and cholesterol medications
• Levels of CVD risk factors
• Estimated 10‐year CVD risk at follow‐up
• Harm very unlikely
• Use of validated, quantitative risk assessment scores appears to be

appropriate, safe, and moderately efficacious in helping to control risk factors … with the potential for additional value to improve decision‐making

2017 ACC/AHA Hypertension Guidelines

2018 AHA/ACC/Multi‐Specialty Cholesterol Guidelines

Primary Prevention Recommendations for Adults 40 to 75 Years of Age With LDL levels 70 to 189 mg/dL Referenced studies that support recommendations are summarized in Online Data Supplement 16. COR LOE Risk Assessment‐Related Recommendations I B‐NR For the primary prevention of clinical ASCVD* in adults 40 to 75 years of age without diabetes mellitus and with an LDL‐C level of 70 to 189 mg/dL (1.7 to 4.8 mmol/L), the 10‐year ASCVD risk

• f a first “hard” ASCVD event (fatal and nonfatal MI or stroke) should be estimated by using the

race‐ and sex‐specific PCE, and adults should be categorized as being at low risk (<5%), borderline risk (5% to <7.5%), intermediate‐risk (7.5% to <20%), and high‐risk (20%). I B‐NR Clinicians and patients should engage in a risk discussion that considers risk factors, adherence to healthy lifestyle, the potential for ASCVD risk‐reduction benefits, and the potential for adverse effects and drug–drug interactions, as well as patient preferences, for an individualized treatment decision. IIa B‐R In intermediate‐risk adults, risk‐enhancing factors favor initiation or intensification of statin therapy. IIa B‐NR In intermediate‐risk or selected borderline‐risk adults, if the decision about statin use remains uncertain, it is reasonable to use a CAC score in the decision to withhold, postpone or initiate statin therapy.

2018 AHA/ACC/Multi‐specialty Cholesterol Guidelines

Approach to Risk Assessment in 1o Prevention

Estimate Absolute 10‐year ASCVD Risk Low Risk 0 ‐ <5% High Risk ≥20% Intermediate Risk 7.5% ‐ <20%

If uncertainty or patient indecision remains, consider CAC score and revise decision based on results

Lifestyle and drug therapy Lifestyle modification Borderline Risk 5% ‐ <7.5% Clinician‐patient discussion considering risk‐enhancing factors and net benefit of therapy

Calculate Personalize Reclassify

C= Calculate: Use Pooled Cohort Equations for ASCVD Risk Estimation

• Recommended for use based on:

 Broad utilization and desired endpoint of hard ASCVD  Most widely validated score in contemporary US populations

• SR identified 23 manuscripts evaluating PCE in diverse populations

 PCE are well calibrated near decision thresholds (e.g., 7.5% 10‐year risk) in broad US clinical population  As with all risk scores, PCE can under‐ and over‐estimate true risk in some subgroups  Reclassification by CAC well understood

• New recommendations ‐ Deploy PCE with:

 Expanded clinician‐patient discussion with consideration of risk‐enhancing factors  Judicious use of CAC measurement in intermediate risk and selected borderline risk patients to reclassify risk

Performance of Pooled Cohort Equations in Diverse Population Samples: Predictable

‐ Over‐ Estimate Risk Under‐ Under‐ Estimate Risk Low SES, HIV, Inflammatory dz High SES, engaged patients Broad US Clinical Population Reasonable Calibration

Clinician-Patient Discussion

Estimated 10-y ASCVD Risk

C = Calculate: Tools for Risk Estimation

• Pooled Cohort Equations – App or Online (or EHR

programmable)

• ACC ASCVD Risk Estimator Plus (online/app)

 http://tools.acc.org/ASCVD‐Risk‐Estimator‐Plus/#!/calculate/estimate/

• AHA ASCVD Risk Calculator (online/app)

 http://static.heart.org/riskcalc/app/index.html#!/baseline‐risk

Guideline Clinical App

To download app search for “ACC Guideline Clinical App” in your app store

P = Personalize: Refine Risk for Individual Patients

Estimate Absolute 10‐year ASCVD Risk Low Risk 0 ‐ <5% High Risk ≥20% Intermediate Risk 7.5% ‐ <20% Lifestyle and drug therapy Lifestyle modification Borderline Risk 5% ‐ <7.5% Clinician‐patient discussion considering risk‐enhancing factors and net benefit of therapy

P = Personalize: Refine Risk for Individual Patients

• Family hx of premature ASCVD
• 1o hypercholesterolemia (LDL‐C

160‐189 mg/dL)

• Metabolic syndrome
• Chronic kidney disease
• Chronic inflammatory conditions

(RA, psoriasis, HIV)

• Hx premature menopause or

pregnancy‐associated risk conditions

• High‐risk race/ethnic groups
• Lipid/biomarkers

 1o hypertriglyceridemia  If measured: Elevated hs‐CRP ≥2 mg/L Elevated Lp(a) ≥50 mg/dL Elevated apoB ≥130 mg/dL ABI <0.9 Risk‐Enhancing Factors

Estimate Absolute 10‐year ASCVD Risk Low Risk 0 ‐ <5% High Risk ≥20% Intermediate Risk 7.5% ‐ <20%

If uncertainty or patient indecision remains, consider CAC score and revise decision based on results

Lifestyle and drug therapy Lifestyle modification Borderline Risk 5% ‐ <7.5% Clinician‐patient discussion considering risk‐enhancing factors and net benefit of therapy

R = Reclassify Risk in Selected Patients

10‐year risk 5% ‐ <7.5% or 7.5% ‐ <20% Below Threshold for Statin Benefit Consider avoiding or postponing drug therapy.* Above Threshold for Statin Benefit Recommend statin therapy. Consider CAC measurement If performed: Engage patient in discussion regarding net benefit of statin therapy CAC = 0 Decision for No Drug Therapy Decision for Drug Therapy CAC 1 – 99 and <75th %ile for age/sex race CAC ≥ 100 or ≥75th %ile for age/sex/race Subclinical atherosclerosis present; risk estimate

• similar. Repeat clinician‐patient discussion with new
• information. Consider statin therapy now or postpone

statin and consider repeat CAC in 5 years Decision Patient Undecided or Clinical Uncertainty Regarding Net Benefit of Statin Therapy See ACC/AHA 2018 Guideline for Cholesterol Management Consider risk‐enhancing factors *Clinicians and patients may not wish to postpone therapy in patients with a CAC score of 0 and diabetes mellitus, heavy current cigarette smoking, or strong family history of premature ASCVD.

R = Reclassify Risk in Selected Patients

Nasir et al., MESA Study, JACC 2015

Example: MESA Study

7.5% 10‐year risk Threshold for considering statin

Reclassification of Risk by CAC

Nasir et al., MESA Study, JACC 2015

Example: MESA Study

Reclassification of Risk by CAC

Identifies pts with event rates below net statin benefit range

Nasir et al., MESA Study, JACC 2015

Example: MESA Study

Reclassification of Risk by CAC Approach to Risk Assessment in 1o Prevention: CPR

Estimate Absolute 10‐year ASCVD Risk Low Risk 0 ‐ <5% High Risk ≥20% Intermediate Risk 7.5% ‐ <20%

If uncertainty or patient indecision remains, consider CAC score and revise decision based on results

Lifestyle and drug therapy Lifestyle modification Borderline Risk 5% ‐ <7.5% Clinician‐patient discussion considering risk‐enhancing factors and net benefit of therapy

Calculate Personalize Reclassify

Perform CPR …Then Treat Accordingly

• Risk‐based and risk‐enhanced algorithm for selecting

patients considered for treatment with statins in primary prevention likely to lead to better decisions and greater patient satisfaction/adherence

• This CPR now or that CPR later

Step Resources and Tools Estimating 10‐year and lifetime risks for ASCVD  Many EHRs can calculate 10‐y ASCVD risk automatically  ACC ASCVD Risk Estimator Plus  AHA ASCVD Risk Calculator Clinician‐patient discussion  ACC ASCVD Risk Estimator Plus  Mayo Clinic Shared Decision Making Cardiovascular Primary Prevention Choice tool (https://shareddecisions.mayoclinic.org/decision‐aid‐information/decision‐ aids‐for‐chronic‐disease/cardiovascular‐prevention/ )  Martin SS et al., JACC 2015  Table 7 in 2018 Cholesterol Guideline Interpretation of CAC score (age/sex/race %ile)  MESA CAC Tools (https://www.mesa‐nhlbi.org/Calcium/input.aspx) Monitoring indicators of response to therapy routinely (LDL‐C, BP levels)  ACC LDL‐C Manager (https://www.acc.org/LDLCmanager)

Supporting Resources and Tools

Case

52‐year‐old South Asian male presents for routine follow‐up

• PMH: CKD (eGFR 50 mL/min/1.73 m2), HTN
• SH: denies tobacco, alcohol
• Meds: lisinopril 10 mg PO daily
• BP 142/86 mm Hg; Waist 42”
• Lipids (mg/dL): TC 225 HDL‐C 35 LDL‐C 150 TG 200
• 10‐yr ASCVD risk 9.7%

Case

52‐year‐old South Asian male presents for routine follow‐up

• PMH: CKD (eGFR 50 mL/min/1.73 m2), HTN, (no DM)
• SH: denies tobacco, alcohol
• Meds: lisinopril 10 mg PO daily
• BP 142/86 mm Hg; Waist 42”
• Lipids (mg/dL): TC 225 HDL‐C 35 LDL‐C 150 TG 200
• 10‐yr ASCVD risk 9.7%

Case

52‐year‐old South Asian male presents for routine follow‐up

• PMH: CKD (eGFR 50 mL/min/1.73 m2), HTN, (no DM)
• SH: denies tobacco, alcohol
• Meds: lisinopril 10 mg PO daily
• BP 142/86 mm Hg; Waist 42”
• Lipids (mg/dL): TC 225 HDL‐C 35 LDL‐C 150 TG 200
• 10‐yr ASCVD risk 9.7%

Case

Risk category

• Intermediate risk primary prevention

Risk enhancing factors

• South Asian
• CKD
• Metabolic syndrome (waist, HTN, low HDL‐C, elevated TG)

Initial treatment strategy:

• Lifestyle modifications + moderate‐intensity statin

Case – Next Steps

After the clinician‐patient discussion, the patient is hesitant to initiate statin therapy based on the information discussed. According to the 2018 ACC/AHA cholesterol guideline, what else may be done to assess this patient’s risk and aid in decision making?

2018 ACC/AHA cholesterol guideline

Summary

• 10‐year and lifetime risk estimates can assist with decision making regarding

intensity of prevention efforts

• These data start the discussion, they do not prescribe a drug
• When applying risk scores to individual patients, in the context of a clinician‐

patient discussion, consider personalized risk‐enhancing factors

• If clinical uncertainty or patient indecision remain, consider CAC

measurement in intermediate risk and selected borderline risk patients

• CAC=0 can meaningfully down‐classify risk; statin avoidance reasonable
• CAC 1‐99 and <75th %ile for age/sex/race does not meaningfully reclassify

risk; use clinical judgment

• CAC ≥100 or ≥75th %ile for age/sex/race can meaningfully up‐classify risk;

confirms likely statin benefit

Take Home Points

• Treatment strategy should match ASCVD risk
• With primary prevention + 10‐yr ASCVD risk 5 ‐ <20%,

consider ASCVD risk enhancers

• Use clinician‐patient shared decision making to

determine treatment strategy

• With uncertain treatment decision for 10‐yr ASCVD risk

≥7.5 ‐ <20%, may use a CAC score in the risk assessment and treatment decision

Lloyd‐Jones et al. Circulation 2019; JACC 2019