The Relationship between Circulating APOA-1 and Atherosclerosis Initiation and Progression in Psoriasis.

APOA-1 is central to the high-density lipoprotein function of reverse cholesterol transport measured by cholesterol efflux capacity. Psoriasis is a systemic inflammatory disease associated with poor cholesterol efflux capacity and accelerated noncalcified coronary burden (NCB) as measured by coronary computed tomographic angiography. In this study, we characterized the relationship between APOA-1, cholesterol efflux capacity, and progression of NCB over 4 years. Consecutively recruited participants with psoriasis underwent coronary computed tomographic angiography for NCB quantification (Medis QAngio, Leiden, The Netherlands) at baseline (n = 310) and at four years (n = 124). Blood was assessed for cardiometabolic biomarkers. The lowest quartile of APOA-1 was associated with cardiometabolic blood markers (insulin, homeostatic model assessment for insulin resistance, and cholesterol efflux capacity) and higher NCB (P < 0.001). The low APOA-1 quartile had higher NCB at 4 years (ß = -0.36, P = 0.02) in fully adjusted models. Finally, a 10-unit decrease of APOA-1 was associated with a 16% increase in NCB progression over 4 years (OR = 0.83, 95% confidence interval = 0.70-0.99, P = 0.04). In addition to being associated with cardiometabolic disease, low APOA-1 was associated with more NCB over time. These findings show that low APOA-1 is correlated with initiation and progression of coronary artery disease and may have clinical utility in identifying high-risk populations for development of cardiovascular disease.

Cholesterol efflux capacity is associated with lipoprotein size and vascular health in mild to moderate psoriasis.

Background and objective: Psoriasis is a systemic inflammatory condition with poor cholesterol transport measured by cholesterol efflux capacity (CEC) that is associated with a heightened risk of cardiovascular disease (CVD). In psoriasis patients, we sought to characterize the lipoprotein profile by size using a novel nuclear magnetic resonance algorithm in patients with low CEC compared to normal CEC. Methods: Lipoprotein profile was assessed using the novel nuclear magnetic resonance LipoProfile-4 deconvolution algorithm. Aortic vascular inflammation (VI) and non-calcified burden (NCB) were characterized via positron emission tomography-computed tomography and coronary computed tomography angiography. To understand the relationship between lipoprotein size and markers of subclinical atherosclerosis, linear regression models controlling for confounders were constructed. Results: Psoriasis patients with low CEC had higher more severe psoriasis (p = 0.04), VI (p = 0.04) and NCB (p = 0.001), concomitant with smaller high-density lipoprotein (HDL) (p < 0.001) and low-density lipoprotein (LDL) particles (p < 0.001). In adjusted models HDL size (ß = -0.19; p = 0.02) and LDL size (ß = -0.31; p < 0.001) associated with VI and NCB. Lastly, HDL size strongly associated with LDL size in fully adjusted models (ß = -0.27; p < 0.001). Conclusion: These findings demonstrate that in psoriasis, low CEC associates with a lipoprotein profile comprised of smaller HDL and LDL particles which correlates with vascular health and may be driving early onset atherogenesis. Further, these results demonstrate a relationship between HDL and LDL size and provide novel insights into the complexities of HDL and LDL as biomarkers of vascular health.