2.1. Study Population

To determine ASCVD-related metabolic and inflammatory risk and responses to lipid-lowering therapies in the US individuals comparing to their AS cohort, we analyzed data from the Carotid Plaque Composition by MRI (CPC) study,[7] a longitudinal study that monitored the change in carotid plaque morphology and composition during lipid therapy treatment. Study participants were recruited from both urban and rural regions at three locations: University of Washington in Seattle, WA, the Yakima Heart Center in Yakima, WA, and University of Southern California in Los Angeles, CA. The definition of rural and urban areas was based on 2010 RUCA codes.[8]

A total of 217 subjects with a mean age of 56 years and 60% of male were enrolled in CPC. Among these 217 study participants enrolled between 2005 and 2011, 184 were classified as AS, while 33 classified as US based on self-reported healthcare coverage. US individuals include those who reported having inadequate or a lack of healthcare insurance. AS individuals include those who reported having healthcare insurance with adequate and sufficient coverage. Specific study inclusion criteria included: 1) age <67 years for males and <70 years old for females; 2) family history of cardiovascular disease; 3) medically stable; 4) no contraindications to MRI; 5) angiographically confirmed coronary artery disease (defined as having ≥1 50% stenosis or ≥3 30% coronary lesions) or carotid disease (defined as having a ≥15% stenosis by ultrasound); 6) apolipoprotein (Apo) B ≥120 mg/dL; 7) not receiving lipid therapy >1 year prior to enrollment. All subjects received atorvastatin-based lipid therapy for 2 years and were randomized to 1 of 3 treatment groups: (1) single therapy - atorvastatin (10-80 mg per day) alone, placebos for extended release (ER) niacin and colesevelam or ezetimib; (2) double therapy – atorvastatin plus ER-niacin (2 g/day), and placebo for colesevelam or ezetimib; (3) triple therapy – atorvastatin, ER-niacin plus colesevelam (3.8 g/day) or ezetimibe (10 mg/day). The treatment target for LDL-C was ≤80 mg/dl for the single and double therapy groups and ≤60 mg/dl for the triple therapy group. The mean dose of atorvastatin received was 53 mg and 48 mg daily in the US and AS groups during the study. Additionally, subjects received dietary and lifestyle consultation using American Heart Association recommendations throughout the study period.

All study protocol and procedures received approvals of local Institutional Review Boards.