Identifying Risk-De-Escalating Markers in PREVENT-Defined Intermediate-Risk Older Adults: Insights From ASPREE.
Zhen Zhou1, Chenglong Yu1,2, Paul Lacaze1
1School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia (Z.Z., C.Y., P.L., R.W., A.M.T., R.L.W., J.T.N., C.T., J.R.).
Circulation. Population Health and Outcomes
|July 2, 2026
Summary
Polygenic risk for coronary artery disease best identifies older adults at intermediate atherosclerotic cardiovascular disease (ASCVD) risk who may not need intensive treatment. This marker helps personalize prevention strategies by accurately down-grading risk for many individuals.
Area of Science:
- Cardiovascular disease risk assessment
- Geriatric medicine
- Preventive cardiology
Background:
- Existing atherosclerotic cardiovascular disease (ASCVD) risk calculators, like the Pooled Cohort Equations, tend to overestimate risk in older adults.
- The PREVENT equation shows improved performance, but further refinement of risk estimates is needed for personalized prevention in this demographic.
- Identifying novel biomarkers is crucial for accurately stratifying risk and guiding treatment de-escalation in intermediate-risk older individuals.
Purpose of the Study:
- To evaluate the clinical utility of six potential biomarkers for reclassifying ASCVD risk in older adults.
- To specifically assess the ability of these markers to identify individuals who may be candidates for risk de-escalation.
- To compare the performance of these markers against the established PREVENT equation for risk prediction.
Main Methods:
- A post hoc analysis of the ASPREE randomized trial (NCT01038583) involving adults aged 70 years and older.
- Six markers were assessed: lowest quartile (Q1) of NT-proBNP, hs-TnI, hs-CRP, polygenic risk scores for Lp(a) and CAD, and absence of family history of ASCVD.
- Statistical methods included diagnostic likelihood ratios, change in Harrell C statistic (ΔC), and net reclassification index (NRI) compared to a PREVENT-based model.
Main Results:
- The study included 7764 participants (median age 74 years) with a median follow-up of 10.3 years; 725 (9.3%) experienced ASCVD events.
- Q1 polygenic risk for coronary artery disease (CAD) demonstrated the strongest risk-down-grading capability, reducing risk by 37% (DLR: 0.627) and improving discrimination (ΔC: +1.44%, P=0.004).
- Q1 hs-TnI showed the second-best performance, with a diagnostic likelihood ratio of 0.727, a ΔC of +0.71%, and an NRI of 0.075.
Conclusions:
- Polygenic risk for coronary artery disease is a powerful tool for refining ASCVD risk estimates in older adults.
- Incorporating polygenic risk for CAD into the PREVENT equation can enhance personalized risk assessment for intermediate-risk individuals.
- These findings support the use of polygenic risk scores to aid clinical decision-making and potentially de-escalate preventive therapies.
Related Concept Videos
01:23Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches
Biopharmaceutical studies constitute a vital field aiming to enhance drug delivery methods and refine therapeutic approaches, drawing upon diverse interdisciplinary knowledge. In research methodologies, the choice between controlled and non-controlled studies significantly influences the study's reliability and accuracy.
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast, controlled...
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast, controlled...
01:12Relative Risk
Relative risk (RR) is a statistical measure commonly used in epidemiology to compare the likelihood of a particular event occurring between two groups. This metric is important for evaluating the relationship between exposure to a specific risk factor and the probability of a particular outcome. It plays a crucial role in medical research, public health studies, and risk assessment. Relative risk quantifies how much more (or less) likely an event is to occur in an exposed group compared to an...
01:29Alzheimer Disease l: Introduction
Alzheimer disease is a chronic, progressive, and irreversible neurodegenerative disorder and the most common cause of dementia in older adults. It leads to gradual neuronal loss, causing cognitive decline, behavioral changes, and loss of functional independence.Risk Factors and EtiologyThe disease is multifactorial. Age is the strongest risk factor, with prevalence doubling every 5 years after age 65. Genetic factors include mutations in genes such as APP, PSEN1, and PSEN2, which are associated...
01:26Atherosclerosis III: Management
Management of atherosclerosis involves an integrated strategy encompassing pharmacological treatment, surgical interventions, lifestyle changes, and nutrition therapy to address the multifactorial nature of the disease.Pharmacological TherapyA cornerstone of atherosclerosis management is the use of pharmacological agents. Statins, such as atorvastatin, are pivotal in inhibiting HMG-CoA reductase, an enzyme that catalyzes an initial step in cholesterol synthesis in the liver. This reduction in...
01:26Coronary Artery Disease IV: Preventive Measures
Effective preventive measures for coronary artery disease (CAD) focus on controlling modifiable risk factors, including cholesterol abnormalities and lifestyle changes.Cholesterol ManagementFirst, the Mediterranean diet and the American Heart Association advocate for maintaining low-density lipoprotein (LDL) cholesterol levels below 100 mg/dL, with a more stringent recommendation of below 70 mg/dL for individuals at high risk. LDL cholesterol, often termed "bad cholesterol," can lead to the...
01:25Aortic Regurgitation III: Medical Management
Aortic regurgitation (AR) is when the aortic valve does not close or seal properly, leading to backward blood circulation from the aorta into the left ventricle during diastole. Common causes of AR include rheumatic heart disease, congenital valve defects, and aortic root dilation. Managing AR requires a multifaceted approach to alleviate symptoms, preserve left ventricular function, and address the underlying cause of the regurgitation. Patients with symptomatic AR or significant left...