At the European Society of Cardiology Congress (ESC) held at the end of August 2024, one symposium focused on various approaches to risk stratification in the primary prevention of cardiovascular disease (CVD). Presenters discussed the role of cardiorespiratory fitness (CRF) and peak VO2, coronary artery calcium (CAC) scoring, genetic scores, and several biomarkers to guide clinicians in identifying patients with a high risk for developing CVD.
Benefits of Risk Stratification
“When it comes to cardiovascular prevention, there are components of risk related to lifestyle that require universal implementation of programs across all populations,” according to Eugenia Gianos, MD, chair of the American Heart Association’s (AHA) Clinical Lipidology, Lipoprotein, Metabolism and Thrombosis Science Committee, director of women’s heart health at Lenox Hill Hospital, and director of cardiovascular prevention for Northwell Health in New York, New York.1
“Beyond that, risk stratification can assist in getting early aggressive therapy to patients who can alter their clinical trajectory by optimizing their risk factors and defying their genetic destiny,” she told Cardiology Advisor.
CRF testing with VO2 max. Among the available tools that can be used to guide risk stratification in CVD prevention, Dr Gianos noted that CRF testing with VO2 max has been linked to longevity and numerous cardiovascular outcomes. Clausen et al, for example, examined the association between CRF and mortality in a study of 5,107 middle-aged men who were CVD-free at baseline.2
After 46 years of follow-up, the results showed that CRF above the upper limit of normal was associated with a mean life expectancy that was 4.9 years (95% CI, 3.1-6.7; P <.001) longer compared to CRF below the lower limit of normal. The findings also demonstrated a 45-day (95% CI, 30-61; P <.001) increase in longevity with each unit increase in VO2 max.2
VO2 max has been found to correlate with coronary artery disease, heart failure hospitalization, stroke, and myocardial infarction, and can be useful in risk stratification, diagnosis, and decisions regarding exercise regimens or earlier treatment for certain patients, Dr Gianos added.3-6
CAC scoring. “Based on its excellent 10-year predictive value for cardiovascular event risk, CAC scoring is a very powerful tool for risk prediction, and high scores can warrant more aggressive statin therapy and potentially aspirin for risk optimization,” Dr Gianos explained.7
According to the American College of Cardiology and AHA primary prevention guidelines regarding the use of CAC in atherosclerotic CVD (ASCVD) risk stratification, a CAC score of zero suggests the need to withhold statins, while CAC scores of 1 to 99 favor statin therapy for patients older than 55 years, and CAC scores over 100 warrant the initiation of statins.8
Regarding aspirin use, the associated bleeding risk outweighs the potential benefit for patient subgroups with a CAC score of zero, while those with CAC scores of 100 or greater have demonstrated a net benefit regardless of risk factors.8
Polygenic risk scores (PRS). “Although earlier in development, PRS can predict increased CVD risk at a much earlier stage to dictate treatment, possibly even before subclinical disease develops,” Dr Gianos said.9
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When it comes to CVD risk prediction, we also have newer risk calculators, such as the PREVENT calculator, that help capture risk related to social determinants of health and disease states such as atrial fibrillation and kidney disease.
In patients with the highest PRS scores, study findings have shown a significant increase in the risk for subclinical atherosclerosis and a greater benefit from statin therapy in preventing a first coronary heart disease event.10
In the ESC 2024 presentation on this topic, Maryam Kavousi, MD, PhD, cited the potential for PRS to improve the prediction of ASCVD risk in primary prevention. However, the incremental prediction accuracy of PRS remains relatively modest and requires further study. In addition, Dr Kavousi noted that PRS is an indicator of CVD risk and should not be considered a precise measure of CVD risk.
Biomarkers. “Lastly, a number of biomarkers appear to predict the risk for CVD in select populations and may become more commonly used as we determine how therapeutic algorithms can be applied,” Dr Gianos stated.
ESC 2024 presenter Reijo Laaksonen, MD, PhD, indicated that combining biomarkers may increase accuracy in CVD risk stratification and suggested the use of sensitive and specific CVD biomarkers in combination.
In a 2024 study, for example, Welsh et al reported that the combined use of growth differentiation factor-15 (GDF-15), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and cardiac troponin I (cTnI) was associated with improved CVD risk prediction in primary prevention compared to the use of single cardiac biomarkers.11
“When it comes to CVD risk prediction, we also have newer risk calculators, such as the PREVENT calculator, that help capture risk related to social determinants of health and disease states such as atrial fibrillation and kidney disease,” Dr Gianos said.
Looking Ahead
In the future, Dr Gianos anticipates a larger role for genomic studies in cardiovascular risk prediction.
She also predicts that primary prevention efforts in cardiology will include more aggressive strategies aiming to reduce low-density lipoprotein cholesterol (LDL-C) levels earlier in life. This expectation is “based on large registry data showing a direct association between area under the curve for LDL-C and outcomes, as well as numerous randomized controlled trials showing the safety of reducing LDL-C to low levels,” Dr Gianos said.12
Additionally, given the growing recognition of the significant influence of lipoprotein (a) (Lp[a]) on CVD risk prediction, and with many professional societies advocating for universal Lp(a) testing, addressing Lp(a)-related risk earlier in life will likely be indicated, she continued.13,14 “This comes at an opportune time when we not only can improve risk factors in patients with elevated Lp(a) but should soon have therapies available to directly target this risk.”
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