What are the features of calculators used to estimated cardiovascular disease risk?

Introduction
Cardiovascular disease (CVD) is a broad term encompassing any type of condition that affects the heart or blood vessels.¹ A type of CVD known as atherosclerotic cardiovascular disease (ASCVD) is a disease of the heart and blood vessels caused by accumulation of lipids, inflammatory cells, and smooth muscle cells that form plaques, which disrupt adequate blood flow to organs and limbs.² Table 1 below summarizes the conditions and manifestations of ASCVD.

According to the American Heart Association (AHA), close to 50% of adult Americans and almost 60% of non-Hispanic Black adults had some form of CVD between 2017 and 2020.³ In 2021, the leading cause of CVD deaths was coronary heart disease (CHD) and direct and indirect annual costs due to overall CVD surpassed US\$400 billion in 2019. Efforts toward ASCVD prevention continue to evolve as this condition remains a significant contributor to morbidity, mortality, and healthcare costs.

Primary prevention of ASCVD involves prevention of disease development itself. According to the 2019 American College of Cardiology/American Heart Association (ACC/AHA) guideline on primary prevention of CVD, to prevent atherosclerosis, all individuals (at-risk or not) should follow a healthy lifestyle defined as a balanced diet (with minimal intake of trans fats, processed meats, refined carbohydrates and sweetened beverages), physical activity (150 minutes per week of moderate intensity), and avoidance/cessation of tobacco use.⁴ Additional measures are recommended for patients with risk factors. The implementation of preventive measures of ASCVD events is dependent on the level of individual risk. Using results of long-term observational cohort studies, patient databases, and clinical studies, experts have collaboratively identified these risk factors and developed various methods to calculate an individual’s risk for ASCVD events over a given time period.

Assessment of ASCVD risk in adults is recommended by AHA/ACC as follows⁴:

1. Routinely for those 40 to 75 years old, assess 10-year ASCVD risk using a risk calculator
2. Every 4 to 6 years for those 20 to 39 years old, assess for risk factors and/or estimate 30-year ASCVD risk using a risk calculator

The purpose of this FAQ is to provide an overview of the features of the 2 risk calculators currently available for use in the US population to estimate 10-year and 30-year ASCVD risk – the AHA Predicting Risk of CVD Events (PREVENT) calculator and the ASCVD Risk Estimator Plus. The newer risk calculator, AHA PREVENT, is not mentioned in the 2019 ACC/AHA guideline as it became available after publication of the guideline.

ASCVD Risk calculators
To estimate risk, components incorporated into the risk calculator include the specific outcome for which the risk is being assessed, the proven independent factors that increase risk, the extent to which that risk is increased, and the timeframe over which the risk occurs.⁵ These components are determined by the population dataset that is used to create the risk calculator and known risk factors as defined by available guidelines.

The AHA PREVENT calculator, developed in 2023, is based on data from over 6.6 million patients collected from 1992 to 2017.^5,6 About 80% of patients in the dataset were non-Hispanic Whites, 9% were black, 5% Hispanic, 2.5% were Asian, and approximately 4% were unspecified as other or missing.⁶ In contrast, the 2018 ASCVD Risk Estimator Plus is an update of the 2013 ACC/AHA pooled cohort equations (PCE) using longitudinal cohort data and the 2018 AHA/ACC guidelines.^5,7 Data for the ASCVD Risk Estimator Plus comes from multiple cohort studies from over 50,000 non-Hispanic White and Black patients collected from 1948 to 2014. Table 2 provides an overview of the 2 calculators.

In addition to the differences in population data, other key differences in the AHA PREVENT calculator include the prediction of heart failure and total CVD risk. the exclusion of race and the inclusion of weight, renal function, and current statin therapy.^5-9 The exclusion of race in the PREVENT calculator is replaced by the inclusion of patient location. According to the 2019 ACC/AHA guideline, social factors that can interfere with implementation of lifestyle changes include literacy, food access, income, safety, access to facilities for physical activity, lack of support, stress, and depression, which may be correlated to the patient’s location.⁴ These social determinants of health are recommended for incorporation into risk assessments to account for important disparities in resource-limited populations.

Limitations to both tools include the lack of inclusion of family history, metabolic syndrome, specific lipid measurements and biomarkers, and inflammatory disorders. Exclusion of these factors is likely due to lack of sufficient data collection of these factors in the population cohorts. However, these factors, known as risk-enhancing factors, should be considered (if present) when assessing risk and implementing preventive strategies.⁷

Choosing a risk calculator
To date, one recent report comparing AHA PREVENT’s risk prediction to the 2013 ACC/AHA pooled cohort equations (PCE) found a small improvement in prediction with AHA PREVENT but, according to the authors, not a meaningful difference to impact a change in current practice.¹⁰ Studies comparing these 2 specific calculators, however, are not yet available.

AHA PREVENT
The AHA PREVENT calculator is a newer tool that determines the risk of overall CVD, ASCVD, and HF in patients who do not currently have these conditions.^6,8 Both weight and renal function are needed to calculate risk, which are significant factors for patients who are overweight and/or have renal dysfunction. According to a 2023 AHA presidential advisory, to address full CVD risk, cardiovascular-kidney-metabolic (CKM) factors should be included in risk assessment, which also includes the level of diabetes control and nephropathy.^11,12 The use of patient location, as discussed above, in place of patient race, can address multiple social and environmental factors that can affect risk.

ASCVD Risk Estimator Plus
The ASCVD Risk Estimator Plus calculates the risk of ASCVD in patients without current ASCVD.⁹ In contrast to the PREVENT AHA calculator, components of this tool, specifically the Pooled Cohort Equations (PCE), have been validated by various researchers.^7,9 Its risk estimation will likely be most accurate for patients who are non-Hispanic White or Black. In patients of south Asian, Puerto Rican, and Indigenous origin, the 10-year risk may be underestimated potentially due to their higher risk of CVD and low representation in the population dataset.⁹ An overestimation of risk may be present for patients who are of east Asian and Mexican descent. Distinct features of this calculator are the provision of suggested interventions based on estimated risk at the initial visit, forecasting change in risk based on suggested interventions, and tracking change in actual risk once the outcome of an intervention is available.^7,9 These features can be helpful for clinicians to engage in shared decision making with patients and provide a stepwise plan that prioritizes the most impactful intervention.

Conclusion
Assessing ASCVD risk in otherwise healthy individuals without underlying disease identifies the need for interventions to prevent morbidity and mortality due to ASCVD and its sequelae. The complexity of factors that contribute to ASCVD and its prevention, however, are difficult to incorporate into a single tool. The current tools available to assess ASCVD risk have unique features and should be used based on patient and clinician characteristics and preferences.

References

1. Indicator definitions – cardiovascular disease. Centers for Disease Control and Prevention. Updated July 4, 2023. Accessed May 28, 2024. https://www.cdc.gov/cdi/definitions/cardiovascular-disease.html
2. Atherosclerotic cardiovascular disease. American Heart Association. Accessed May 28, 2024. https://www.heart.org/en/professional/quality-improvement/ascvd
3. Martin SS, Aday AW, Almarzooq ZI, American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee, et al. 2024 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association. Circulation. 2024 Feb 20;149(8):e347-e913. doi: 10.1161/CIR.0000000000001209. Epub 2024 Jan 24.
4. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;140(11):e596-e646. doi: 10.1161/CIR.0000000000000678.
5. Wilson, PWF. Cardiovascular disease risk assessment for primary prevention: risk calculators. In: Post, T. ed. UpToDate. UpToDate; 2024. Accessed May 28, 2024.
6. Khan SS, Matsushita K, Sang Y, et al, Chronic Kidney Disease Prognosis Consortium and the American Heart Association Cardiovascular-Kidney-Metabolic Science Advisory Group. Development and Validation of the American Heart Association’s PREVENT Equations. Circulation. 2024;149(6):430-449. doi: 10.1161/CIRCULATIONAHA.123.067626.
7. Lloyd-Jones DM, Braun LT, Ndumele CE, et al. Use of Risk Assessment Tools to Guide Decision-Making in the Primary Prevention of Atherosclerotic Cardiovascular Disease: A Special Report From the American Heart Association and American College of Cardiology. Circulation. 2019;139(25):e1162-e1177. doi: 10.1161/CIR.0000000000000638
8. PREVENT™ Online calculator. American Heart Association. Accessed June 4, 2024. https://professional.heart.org/en/guidelines-and-statements/prevent-calculator
9. ASCVD Risk Estimator Plus calculator. American College of Cardiology. Accessed June 4, 2024. https://tools.acc.org/ascvd-risk-estimator-plus/#!/calculate/estimate/
10. Osude N, Granger C. PREVENT equations predicted risk for incident CVD in adults aged 30 to 79 y. Ann Intern Med. 2024 Jun 4. doi: 10.7326/ANNALS-24-00208-JC.
11. Ndumele CE, Rangaswami J, Chow SL, et al; American Heart Association. Cardiovascular-Kidney-Metabolic Health: A Presidential Advisory From the American Heart Association. Circulation. 2023;148(20):1606-1635. doi: 10.1161/CIR.0000000000001184.
12. Khan SS, Coresh J, Pencina MJ, et al; American Heart Association. Novel Prediction Equations for Absolute Risk Assessment of Total Cardiovascular Disease Incorporating Cardiovascular-Kidney-Metabolic Health: A Scientific Statement From the American Heart Association. Circulation. 2023 ;148(24):1982-2004. doi: 10.1161/CIR.0000000000001191

Prepared by:
Rita Soni, PharmD, BCPS
Clinical Assistant Professor, Drug Information Specialist
University of Illinois at Chicago College of Pharmacy

June 2024

The information presented is current as of June 4, 2024. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making.