Beta-Secretase-1 Antisense RNA Is Associated with Vascular Ageing and Atherosclerotic Cardiovascular Disease.

Background:  The noncoding antisense transcript for β-secretase-1 () is a long noncoding RNA with a pivotal role in the regulation of amyloid-β (Aβ). We aimed to explore the clinical value of expression in atherosclerotic cardiovascular disease (ASCVD).

Methods:  Expression of and its target, β-secretase 1 () mRNA, was measured in peripheral blood mononuclear cells derived from 434 individuals (259 without established ASCVD [non-CVD], 90 with stable coronary artery disease [CAD], and 85 with acute coronary syndrome). Intima-media thickness and atheromatous plaques evaluated by ultrasonography, as well as arterial wave reflections and pulse wave velocity, were measured as markers of subclinical ASCVD. Patients were followed for a median of 52 months for major adverse cardiovascular events (MACE).

Results:  In the cross-sectional arm, expression correlated with expression ( = 0.396,  < 0.001) and marginally with Aβ1-40 levels in plasma ( = 0.141,  = 0.008). Higher was associated with higher estimated CVD risk assessed by HeartScore for non-CVD subjects and by European Society of Cardiology clinical criteria for the total population ( < 0.05 for both). was associated with higher prevalence of CAD (odds ratio [OR] = 1.85, 95% confidence interval [CI]: 1.37-2.5), multivessel CAD (OR = 1.36, 95% CI: 1.06-1.75), and with higher number of diseased vascular beds (OR = 1.31, 95% CI: 1.07-1.61, for multiple diseased vascular beds) after multivariable adjustment for traditional cardiovascular risk factors. In the prospective arm, was an independent predictor of MACE in high cardiovascular risk patients (adjusted hazard ratio = 1.86 per ascending tertile, 95% CI: 1.011-3.43,  = 0.046).

Conclusion:   is associated with the incidence and severity of ASCVD.