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Although basic research has suggested that oxidized low-density lipoprotein (ox-LDL) is involved in the pathogenesis of atherosclerosis, population observational studies have yielded conflicting results about the association between circulating ox-LDL and atherosclerotic cardiovascular disease (ASCVD). Therefore, we performed a systematic review and meta-analysis of currently available prospective observational studies to verify the association between circulating ox-LDL and ASCVD.
We systematically searched PubMed and the Cochrane Library from their inception to April 27, 2017, for nested case-control studies, case-cohort studies, and prospective cohort studies on the relationship between ox-LDL and ASCVD. Studies which did not assess the hazard ratio, relative risk, or odds ratio of ox-LDL or which did not adjust for other risk factors were excluded. The summarized effect size was combined using fixed-effect models because of low statistical heterogeneity. Subgroup analyses were also performed based on study quality, study design, definition of ASCVD events, effect size types, types of ox-LDL assay, ox-LDL contrast level, and whether LDL-C was adjusted in a multivariate model.
A total of 12 included studies consisted of three nested case-control studies, one case-cohort study, five hospital-based cohort studies, and three community-based cohort studies. The summary effect size of high-level circulating ox-LDL was 1.79 (95% confidence interval: 1.56-2.05) for ASCVD. Similar associations between circulating ox-LDL and ASCVD were demonstrated in all subgroups.
Our findings indicate that increased levels of circulating ox-LDL are associated with clinical ASCVD events. Further well-designed community-based cohort studies or intervention studies are needed to confirm our findings.