Prospective Electronic Polygenic Risk Study - Second Phase

Composite MACE in intermediate to high clinical risk population

Incident MACE. Binary outcome measured at 5-years post-enrollment by EHR analysis. An interim analysis will be performed at 3-years. MACE is defined as arterial revascularization or hospitalization for unstable angina, myocardial infarction, stroke, or death from cardiovascular causes. The rate of incident MACE will be compared across CAD vs glaucoma arms overall in individuals achieving a baseline PCE≥7.5%.

Composite MACE in high PRS

Incident MACE. Binary outcome measured at 3- and 5-years post-enrollment by EHR analysis. The rate of incident MACE will be compared across high CAD PRS individuals receiving vs blinded to their genetic risk in individuals achieving a baseline PCE≥5%.

MACE Components

Incident MACE components (arterial revascularization or hospitalization for unstable angina, myocardial infarction, stroke, or death from cardiovascular causes). Binary outcomes measured at 3- and 5-years post-enrollment by EHR analysis. The rate of each incident MACE component will be compared across CAD vs glaucoma arms overall in individuals achieving a baseline PCE≥7.5%.

Treated Glaucoma

Incident glaucoma diagnosis with initiation of treatment. Binary outcome measured at 3- and 5-years post-enrollment by EHR analysis. Incident treated glaucoma is defined as any individual with a claim for ophthalmic surgery (laser trabeculoplasty, laser peripheral iridotomy, cycloablation) or a prescription ophthalmic solution with one or a combination of the following active ingredients: prostaglandin analogs (tafluprost, bimatoprost, latanoprostene, travaprost, latanoprost), beta blockers (timolol, levobunolol, metipranolol, betaxolol, carteolol), alpha agonists (brimonidine, apraclonidine), cholinergic agonists (pilocarpine, carbachol), carbonic anhydrase inhibitors (methazolamide, dorzolamide, brinzolamide), and/or rho kinase inhibitor (netarsudil). The rate and age of incident glaucoma diagnosis with treatment will be compared across CAD and glaucoma arms overall, as well as across high glaucoma PRS individuals receiving vs blinded to their genetic risk.

LDL-C lowering

Adequate LDL-C lowering. Binary outcome measured at 2-, 3-, and 5-years post enrollment by EHR entry. Adequate LDL-C lowering is defined as 30% or more reduction from baseline study measured LDL-C. The rate of adequate LDL-C lowering will be compared across CAD vs glaucoma arms overall, across high CAD PRS individuals receiving vs blinded to their genetic risk, and in association with high vs low CAD PRS in individuals receiving vs blinded to their genetic risk. Within these groups, the rate of adequate LDL-C lowering will be determined in the total population, as well as subgroups stratified by baseline PCE status. PCE strata are: \<5%, 5%≤PCE\<7.5%, and ≥7.5%.

Lifestyle changes

Adoption of Healthy Lifestyle. Binary outcomes derived from baseline and 6-months post-enrollment by survey-based self-report. Adoption of a healthy lifestyle is defined among individuals who self-report non-smoking, active lifestyle, or healthy diet at 6-months after initially reporting the absence of any of these healthy behaviors at baseline. These factors will be analyzed as separate binary outcomes and as a composite healthy lifestyle factor defined by an increase in the number of healthy lifestyle factors self-reported at 6-months vs baseline