PRE-EMPT: Prospective RandomizEd Evaluation and Management of Premature aTherosclerosis

Heart disease is the leading cause of death for men, women, and people of most racial and ethnic groups in the United States. This clinical trial will test if screening and early treatment of mild heart disease works. PRE-EMPT will screen individuals at low 10-year risk of heart disease with heart disease risk factors to identify those who already have early cholesterol build up, also called "plaque", in their heart arteries. It consists of two phases: 1. A Screening Study - Participants will be assessed for plaque by one or both of these scans. * Coronary Artery Calcium (CAC) Scan: A CT scan that looks for calcium or plaque in heart arteries. * Coronary CT Angiography (CCTA) Scan: A CT scan that uses contrast dye to create detailed 3D pictures of heart arteries to look for plaque. 2. A Treatment Trial (approximately 1,500 participants) - Based on the results of the CCTA, participants may be randomized into a two-year trial to test medications aimed at reducing or stabilizing plaque. Participants will have a 1 in 4 chance of receiving only placebo, and a 3 in 4 chance of receiving at least one active medication. Participants will take two pills once a day-either both active medications, one active and one placebo, or both placebos. * Rosuvastatin 20 mg: a cholesterol-lowering medicine * Colchicine 0.5 mg: a medication that lowers inflammation Everyone in the trial will be given information and advice on heart-healthy diet and lifestyle. Participants will have up to two in-person visits for the screening study, then phone visits for the Treatment Trial at the beginning, 3 months, 12 months and 24 months when they will also have an in-person visit for a CCTA Scan. Participants will have blood drawn using an at-home collection device mailed to their home at the beginning, 3 months, and end of the study.

Inclusion Criteria: 1. Women aged 40-60 years; Men aged 30-50 years 2. Willing and able to provide informed consent and comply with study procedures 3. Smart phone user 4. Use of highly effective contraception by females with reproductive potential. 5. CAC score 1-99 in the screening study or entry through the known plaque pathway (with mild CAC or CAC\40kg/m2 or unable to have a CCTA scan for any reason 12. Allergy to iodinated intravenous contrast or other contraindication to CCTA 13. Current or previous use of lipid lowering therapy or colchicine 14. Known allergic reactions or sensitivity to the study intervention(s), including known intolerance or contraindication(s) to statin or colchicine, or long-term use of medications that are contraindicated with colchicine or rosuvastatin. 15. Systemic cancer undergoing active treatment 16. PREVENT ASCVD 10-year risk ≥5% 17. eGFR \