BACKGROUND: Alcohol use and hepatitis C virus (HCV) often coexist and are associated with cardiovascular disease. One of the underlying drivers is dyslipidemia. We assessed lipid and lipoprotein levels and the relationship between alcohol use and atherogenic lipid profiles, specifically small dense low-density lipoprotein cholesterol (sdLDL-C), in Latinos with and without HCV. METHODS: From June 1, 2002, to January 1, 2016, 150 Latino adults underwent demographic, clinical, metabolic, lipid/lipoprotein, and genetic evaluations. Linear regression (adjusted for age, sex, and recent alcohol use) assessed factors associated with sdLDL-C. RESULTS: Participant characteristics were as follows: median age 44 years, 64% male, 39% HCV+, and alcohol use in the last 12 months was 19% heavy and 47% moderate. Ancestries were as follows: 52% European, 40% Native American (NA), and 4.3% African. 29% had non-CC PNPLA3, 89% non-CC TM6SF2, and 73% non-CC IL-28b genotypes. High-density lipoprotein (HDL) cholesterol, HDL-3, apolipoprotein A-1, and lipoprotein-associated phospholipase A2 levels differed by alcohol use groups (p <
0.05). On multivariable analysis, female sex (est. -6.08, p <
0.002), HCV+ status (est. -8.49, p <
0.002), and heavy alcohol use (vs. none) (est. -4.32, p = 0.03) were associated with lower, while NA ancestry (est. 0.92
p = 0.01) and adipose tissue insulin resistance (est. 3.30, p <
0.002) were associated with higher sdLDL-C levels. The positive association between NA ancestry and sdLDL-C was dampened by the presence of a non-CC IL28b genotype (interaction est. -1.95, p = 0.01). CONCLUSIONS: In this Latino cohort, ancestry and metabolic dysfunction, independent of alcohol use and HCV, were associated with atherogenic risk. In addition to HCV treatment in this population, cardiometabolic health should be optimized.