Elevated soluble LOX-1 predicts risk of first-time myocardial infarction

Abstract

Background

There is an unmet clinical need for novel therapies addressing the residual risk in patients receiving guideline preventive therapy for coronary heart disease. Experimental studies have identified a pro-atherogenic role of the oxidized LDL receptor LOX-1. We investigated the association between circulating soluble LOX-1 (sLOX-1) and the risk for development of myocardial infarction.

Methods

The study subjects (n = 4658) were part of the Malmö Diet and Cancer study. The baseline investigation was carried out 1991-1994 and the incidence of cardiovascular events monitored through national registers during a of 19.5 ± 4.9 years follow-up. sLOX-1 and other biomarkers were analyzed by proximity extension assay and ELISA in baseline plasma.

Results

Subjects in the highest tertile of sLOX-1 had an increased risk of myocardial infarction (hazard ratio (95% CI) 1.76 (1.40-2.21) as compared with those in the lowest tertile. The presence of cardiovascular risk factors was related to elevated sLOX-1, but the association between sLOX-1 and risk of myocardial infarction remained significant when adjusting for risk factors.

Conclusions

In this prospective population study we found an association between elevated sLOX-1, the presence of carotid disease and the risk for first-time myocardial infarction. Taken together with previous experimental findings of a pro-atherogenic role of LOX-1, this observation supports LOX-1 inhibition as a possible target for prevention of myocardial infarction.

KEY MESSAGES

Activation of the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) represents a possible target for treatment of the residual inflammatory risk in cardiovascular patients on guideline therapy.

Having high levels of soluble LOX-1, a marker of cellular LOX-1 activation, is associated with an increased risk for development of myocardial infarction and heart failure.

sLOX-1 levels correlated with major cardiovascular risk factors and biomarkers reflecting LDL oxidation.

Keywords:

• LOX-1
• myocardial infarction
• risk prediction
• population cohort
• disease mechanisms

Disclosure statement

Jan Nilsson has received consultant fees from AstraZeneca. He is also board member of Abcentra (CA) and is co-inventor on patents relating to immunomodulation against LDL antigens assigned to Abcentra.

Data availability

The data underlying this article will be shared on reasonable request to the corresponding author.

Additional information

Funding

This study was supported by grants from the Swedish Medical Research Council, the Swedish Heart-Lung foundation, Skåne University Hospital funds and by an unrestricted research grant from AstraZeneca. Hjärt-Lungfonden; Vetenskapsrådet;