The Prevent Coronary Artery Disease Trial
Despite increasing evidence that exposure to cardiovascular risk factors (CVRF) at an early age increases the prevalence of subclinical atherosclerosis and is associated with a greater risk of cardiovascular events later in life, there is a lack of randomized trial evidence to support primary prevention strategies in adults aged 30-50 years. The researchers have designed a randomized controlled trial to evaluate whether strict control of CVRF in young adults without known cardiovascular disease, will reduce the progression of total atherosclerosis burden, a surrogate endpoint for symptomatic cardiovascular disease, compared with usual care. The researchers propose a randomized controlled trial enrolling 1,600 healthy young adults who meet the inclusion criteria and who do not meet any exclusion criteria. Eligible study participants will be randomized, in a 1:1 ratio, to either the intervention group (active treatment strategy) or to the control group (guideline-directed medical therapy). Randomization will be stratified by the presence or absence of atherosclerotic plaque in vascular ultrasound.
• Male or female subjects between 30 to 50 years of age.
• No prior history of coronary artery disease, cerebrovascular disease or peripheral artery disease.
• Serum LDL-C \> 1.8 mmol/l (70 mg/dl).
• Presence of subclinical atherosclerosis as assessed by 3DVUS or by the presence of coronary artery calcium (defined as coronary artery calcium score ≥25), independent of risk calculators; and/or high lifetime risk (≥30%) using the ASCVD calculator; and/or intermediate 10-year risk (≥7.5%) using the ASCVD calculator in the presence of 2 risk enhancers.
⁃ The presence of atherosclerotic plaque by 3DVUS will be defined according to the PESA study definitions14: plaque is defined as a focal protrusion into the arterial lumen of thickness \>0.5 mm or \>50% if the intima media thickness or intima media thickness \>1.5 mm. CT scan for coronary artery calcium assessment will not be part of the protocol but will be used where available.
⁃ Risk enhancers are defined as15:
• Family history of premature atherosclerotic CVD
• Persistently elevated LDL-C ≥ 160 mg/dl
• Chronic kidney disease
• Metabolic syndrome
• Conditions specific to women (e.g. preeclampsia, premature menopause)
• Inflammatory diseases (especially rheumatoid arthritis, psoriasis, HIV)
• Ethnicity (e.g., South Asian ancestry)
• Persistently elevated triglycerides (≥175 mg/dl)
• Hs-CRP ≥2 mg/L
• Lp(a) levels \>50 mg/dl
• apoB ≥130 mg/dl
• Ankle-brachial index \<0.9