Genetic Risk Score Enables a Vaccine for Early Primary Prevention of CAD

Area of Science:

• Cardiovascular Medicine
• Genetics
• Preventive Cardiology

Background:

• Early primary prevention of coronary artery disease (CAD) is hindered by the lack of reliable biomarkers in young, asymptomatic individuals.
• Traditional CAD risk factors like hypertension typically manifest later in life, limiting early intervention effectiveness.
• Genetic predisposition accounts for 50% of CAD risk and can be assessed at any age using a polygenic risk score (PRS).

Purpose of the Study:

• To advocate for a novel primary prevention strategy for coronary artery disease (CAD).
• To explore the potential of early, long-term interventions to mitigate genetically influenced CAD risk.
• To propose a method for significantly delaying the onset of myocardial infarction (MI).

Main Methods:

• Reviewing the role of genetic risk (polygenic risk score - PRS) in early CAD.
• Analyzing the impact of low-density lipoprotein (LDL) exposure duration (age x LDL) on myocardial infarction (MI) risk.
• Proposing a hypothetical intervention involving annual administration of a long-acting lipid-lowering drug starting at age 30.

Main Results:

• Genetic risk, assessed by PRS, is a significant, age-independent factor in CAD.
• CAD risk is cumulative, determined by the product of age and low-density lipoprotein (LDL) levels (mg-years).
• A hypothetical annual lipid-lowering drug regimen initiated at age 30 could potentially delay the threshold for myocardial infarction (MI) to age 100.

Conclusions:

• A proactive, lifelong approach to managing genetically predisposed CAD risk is warranted.
• Early intervention with lipid-lowering therapies, informed by PRS, offers a promising strategy for primary prevention.
• Delaying the cumulative LDL exposure threshold could dramatically reduce the incidence of premature myocardial infarction (MI).