Personalized Risk Assessment to Prevent Premature ASCVD Event

Atherosclerotic cardiovascular disease (ASCVD) represents a constellation of conditions including coronary artery disease, cerebrovascular disease, and peripheral artery disease. It is a leading cause of morbidity and mortality worldwide, including in Indonesia. Traditional risk factors for ASCVD include hypertension, dyslipidemia, diabetes, smoking, and family history. However, despite controlling these risk factors, a significant number of individuals still develop ASCVD, emerging in the younger population, so-called premature ASCVD. This has led to an exploration into the role of genetics in the development and progression of the disease.

From a genomic perspective, there are 2 strategies:

1. Polygenic Risk Scores (PRS) With the advent of genome-wide association studies (GWAS), numerous genetic markers have been identified that correlate with ASCVD risk. By aggregating the effects of multiple genetic variants into a single score, PRS provides a quantitative measure of genetic susceptibility to ASCVD. Many PRS models are derived from studies predominantly in European populations. Their predictive accuracy may vary across different ethnic groups. The initial study will validate the existing PRS model in the local population, along with the development of our own PRS based on data from the Indonesian population.
   
2. Monogenic Disorders Some individuals inherit single gene mutations that dramatically increase their risk for ASCVD. For example, familial hypercholesterolemia is a genetic disorder characterized by extremely high cholesterol levels and early-onset ASCVD. Early genetic detection can prompt aggressive preventive measures.

Vision

Decoding the genomic intricacies of premature ASCVD, aiming for preventing ASCVD events, early diagnosis, precise risk stratification, personalized therapeutic approaches, and a significant reduction in the disease's early-onset impact on health.

Disease Target

Premature ASCVD, subtype premature Coronary Artery Disease (CAD)

Outcome

• Personalized Risk Assessment and Early Intervention By integrating genetic data with traditional risk factors [PRS + clinical risk], clinicians can provide a more comprehensive risk assessment, allowing for tailored preven*ve and therapeutic strategies for ASCVD. Identifying high-risk individuals at an early age can lead to earlier lifestyle modifications, pharmaceutical interventions, and close monitoring.
• Pharmacogenomics Statin is one of the long-life drugs for ASCVD patients along with anti-platelets. Understanding an individual's genetic makeup will provide insights into how they might respond to statin medications, allowing for a more personalized and effective plan on which statin shall be used.