5/13/2019 Astro-CHARM, the First 10-year ASCVD Risk Estimator Incorporating Coronary Calcium - American College of Cardiology

Astro-CHARM, the First 10-year ASCVD Risk

Estimator Incorporating Coronary Calcium
Aug 07, 2018 | Anum Minhas, MD; Roger S. Blumenthal, MD, FACC; Seth Shay Martin, MD,
MHS, FACC

Expert Analysis

Approaches to cardiovascular disease risk assessment range in focus from the

broad endpoint of global composite cardiovascular disease, including myocardial
infarction (MI), stroke, coronary or peripheral revascularization, incident heart
failure and atrial fibrillation, to more narrow approaches focused only on coronary
events or cardiovascular mortality or to approaches in the middle looking at hard
atherosclerotic cardiovascular disease (ASCVD) events such as MI or stroke. The
2013 Risk Assessment Guidelines recommended the latter approach. Numerous
risk scores have been developed in US cohorts in the past, including the
Framingham Coronary Heart Disease (CHD) score and Reynolds Risk Scores for
men and women.1-3

The 2013 ACC/AHA Guidelines on the Assessment of Cardiovascular Risk advised

using the Pooled Cohort Equations (PCE) to predict 10-year risk of a first hard
ASCVD event.4 The PCE variables include age, total cholesterol, high density
lipoprotein (HDL) cholesterol, systolic blood pressure, diabetes and current
smoking status to provide a sex and race-specific estimate of the 10-year ASCVD
risk for African American and white men and women. The risk output is validated
and provides reasonable risk estimation using a significant number of African
Americans and whites.4 However, the PCE may overestimate risk in other
races/ethnicities and in populations with less social deprivation,5 which requires
attention when making medical decisions.

Many studies have demonstrated that use of a coronary artery calcium (CAC)
score often helps improve risk assessment.6-8 In this setting, the Multi-Ethnic
Study of Atherosclerosis (MESA) investigators developed a risk score integrating
CAC.9 However, this risk score only predicts coronary heart disease risk and does
not include stroke; in addition, it was derived from a cohort of 45-85 year olds.
Due to a need for improved risk assessment for a younger population in high risk

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5/13/2019 Astro-CHARM, the First 10-year ASCVD Risk Estimator Incorporating Coronary Calcium - American College of Cardiology

occupations, such as astronauts, the National Space Biomedical Research Institute

(NSBRI) recently sponsored a study developing the Astronaut Cardiovascular
Health and Risk Modification (Astro-CHARM) calculator.10

Astro-CHARM was developed as the first integrated ASCVD risk calculator,

incorporating traditional risk factors, as used in the PCE, and CAC, along with high-
sensitivity C-reactive protein (hsCRP) and family history of MI. Data were derived
from individual participant level data from three large, population-based cohorts:
MESA, the Dallas Heart Study (DHS), and the Prospective Army Coronary Calcium
Project (PACC). An external validation cohort was derived from the Framingham
Heart Study (FHS) Offspring and Third Generation cohorts.

Baseline risk factors were defined by each derivation cohort. For instance, family
history of MI was defined as any first degree relative with MI at any age for MESA
and DHS, but as a history of sudden death, MI or coronary revascularization in
any first or second degree relative for PACC and as family history of coronary
disease in FHS, but in both studies only for events before age 55 for men and age
65 for women. For all studies, CAC was determined using standard Agatston unit
methodology. The primary endpoint of the study included a composite of non-
fatal MI, non-fatal stroke or death from CHD or stroke. These components were
available for MESA, DHS and FHS, but only non-fatal MI and CVD death were
available for PACC.

Baseline characteristics included an average age of 51 years, with roughly equal

numbers of men and women (55% and 45%, respectively). Approximately 30% of
individuals were black, 45% were white, and 17% were Hispanic. Statin use at
baseline was uncommon with only 9% reporting use in the overall cohort.
Participants were relatively healthy with only 8% having diabetes, 16% with
current smoking and 22% on antihypertensive medications. Additionally, the mean
baseline CAC was 0, and event rate was low at 4.27 per 1000 person-years, with
304 hard ASCVD events occurring. Median follow-up was 10.9 years.

The c-statistics for the baseline risk factor model and full Astro-CHARM model
were 0.78 and 0.82 (p < 0.0001), respectively. Consistent with its incorporation of
CAC, the Astro-CHARM model was superior for prediction of MI (c-statistic risk
factor model was 0.74 and Astro-CHARM 0.83) as compared to stroke (c-statistic
risk factor model was 0.78 and Astro-CHARM 0.78). Overall, the Astro-CHARM
model was well-calibrated internally and showed good discrimination in the
external validation cohort (FHS).

Astro-CHARM was developed as the first integrated ASCVD risk calculator,

incorporating most notably CAC into risk calculation. Current ACC/AHA guidelines
recommend aspirin and statin use based upon 10-year ASCVD risk.4 Guidelines
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note that a CAC >300 or >75th percentile for age, sex and ethnicity can be used to
increase precision in decisions regarding pharmacologic therapy. However, given
that CAC scores occur on a continuum, Astro-CHARM provides a unique
opportunity for fuller integration of CAC into risk assessment in those patients.

Additionally, hsCRP and family history were also independently predictive of

ASCVD and were therefore included in the full Astro-CHARM model. Family history
was defined in different ways among the three cohorts in the derivation group
(MESA, DHS and PACC) and in the external validation cohort (FHS). This is
simplified to family history of heart attack in the online calculator
(http://astrocharm.org/calculator-working/ ) and the limitations of this
simplification are uncertain.

One of the other proposed advantages of Astro-CHARM over the existing MESA
CHD risk calculator is its inclusion of stroke within ASCVD in risk assessment.9
While Astro-CHARM includes stroke as an endpoint, its prediction was stronger for
MI than for stroke; this suggests that perhaps Astro-CHARM is more useful as a
risk prediction model for coronary heart disease compared to stroke. Another
intended advantage of Astro-CHARM is its risk prediction for a younger
population. While the Astro-CHARM model predicts risk for a mean age lower than
PCE (Astro-CHARM age range is 40-65 years and PCE age range is 40-79 years), the
risk prediction still begins starting at age 40 years for both, so persons under age
40 are excluded from both models.

In summary, Astro-CHARM provides a new risk prediction model, intended for a

young, relatively healthy population, with unique incorporation of CAC, hsCRP and
family history of MI. The Astro-CHARM model appears to increase precision in risk
assessment and thereby has the potential to improve shared decision-making
regarding initiation of preventive medications. As the global population continues
to have growing risk factors for the development of atherosclerosis, accurate risk
estimation will become increasingly more important. Models such as Astro-CHARM
will likely provide an advantage in targeting individuals for earlier and more
appropriate medication initiation.

References

1. Wilson PW, D'Agostino RB, Levy D, Belanger AM, SIlbershatz H, Kannel WB.
Prediction of coronary heart disease using risk factor categories. Circulation
1998;97:1837-47.
2. Ridker PM, Buring JE, Rifai N, Cook NR. Development and validation of
improved algorithms for the assessment of global cardiovascular risk in
women: the Reynolds Risk Score. JAMA 2007;297:611-9.

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5/13/2019 Astro-CHARM, the First 10-year ASCVD Risk Estimator Incorporating Coronary Calcium - American College of Cardiology

3. Ridker PM, Paynter NP, Rifai N, Gaziano JM, Cook NR. C-reactive protein and
parental history improve global cardiovascular risk prediction: the Reynolds
Risk Score for men. Circulation 2008;118:2243-51.
4. Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 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. J Am
Coll Cardiol 2014;63:2935-59.
5. Colantonio LD, Richman JS, Carson AP, et al. Performance of the
atherosclerotic cardiovascular disease pooled cohort risk equations by social
deprivation status. J Am Heart Assoc 2017;6.
6. Hoffmann U, Massaro JM, D'Agostino RB Sr, Kathiresan S, Fox CS, O'Donnell CJ.
Cardiovascular event prediction and risk reclassification by coronary, aortic,
and valvular calcification in the Framingham Heart Study. J Am Heart Assoc
2016;5.
7. Paixao AR, Ayers CR, El Sabbagh A, et al. Coronary artery calcium improves risk
classification in younger populations. JACC Cardiovasc Imaging 2015;8:1285-93.
8. Yeboah J, Young R, McClelland RL, et al. Utility of nontraditional risk markers in
atherosclerotic cardiovascular disease risk assessment. J Am Coll Cardiol
2016;67:139-47.
9. McClelland RL, Jorgensen NW, Budoff M, et al. 10-year coronary heart disease
risk prediction using coronary artery calcium and traditional risk factors:
derivation in the MESA (Multi-Ethnic Study of Atherosclerosis) with validation in
the HNR (Heinz Nixdorf Recall) study and the DHS (Dallas Heart Study). J Am
Coll Cardiol 2015;66:1643-53.
10. Khera A, Budoff MJ, O'Donnell CJ, et al. The Astronaut Cardiovascular Health
and Risk Modification (Astro-CHARM) coronary calcium atherosclerotic
cardiovascular disease risk calculator. Circulation. Epub ahead of print.

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Clinical Topics: Arrhythmias and Clinical EP, Diabetes and Cardiometabolic

Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Atrial
Fibrillation/Supraventricular Arrhythmias, Lipid Metabolism, Nonstatins, Novel
Agents, Statins, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Dyslipidemias, Risk Factors, Antihypertensive Agents, Hydroxymethylglutaryl-CoA

Reductase Inhibitors, C-Reactive Protein, Cholesterol, HDL, Calcium, Atrial Fibrillation, Aspirin,
Blood Pressure, Coronary Vessels, Research Personnel, Cardiovascular Diseases, Myocardial
Infarction, Stroke, Risk Assessment, Atherosclerosis, Coronary Disease, Heart Failure, Diabetes
Mellitus, Decision Making, Biomedical Research

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