Association Between Cumulative Exposure to Increased Low-Density Lipoprotein Cholesterol and the New Occurrence of Peripheral Artery Disease

Background and Purpose: Peripheral artery disease (PAD) is a manifestation of systemic atherosclerosis with increased risk of severe cardiovascular and cerebrovascular events. The relationship between one-time measuring of low-density lipoprotein cholesterol (LDL-C) and PAD is inconsistent. Increasing evidence shows that the predictive value of non-high-density lipoprotein cholesterol (non-HDLC) on atherosclerosis disease is superior to LDL-C. We aimed to investigate the relationship between cumulative exposure to increased LDL-C and the risk of newly developed PAD and compare the predictive value of LDL-C with non-HDLC. Materials and Methods: In the Asymptomatic Polyvascular Abnormalities Community study, we enrolled 2,923 participants with LDL-C and non-HDLC measured every 2 years from 2006 to 2012. Cumulative exposure to increased LDL-C and non-HDLC, defined as LDL-C burden and non-HDLC burden, respectively, was calculated as the weighted sum of the difference between the measured value and the cutoff value. A new occurrence of PAD was identified through ankle brachial index measured in 2010 and 2012. Multivariate models were adopted to analyze the association of LDL-C burden and non-HDLC burden with the newly developed PAD. The receiver operating curve was drawn, and the area under the curve was calculated to compare the predictive performance of LDL-C burden with a single measure of LDL-C in 2006 and non-HDL-C burden adjusted with a model including traditional risk factors. Results: Of the 2,923 participants, 5.4% (158/2,923) were diagnosed as newly developed PAD. In the univariate analysis, the highest quartile of LDL-C burden was significantly associated with new occurrence of PAD [odds ratio (OR) 1.75, 95% confidence interval (CI) 1.13-2.73]. After adjustment for confounding factors, the same result was obtained (OR 1.59, 95%CI 1.01-2.49). The non-HDLC burden failed to show any statistical significance on the newly developed PAD (OR 1.31, 95% CI 0.84-2.04). Though LDL-C burden had a tendency to show better predictive performance than non-HDLC, it did not reach statistical significance (AUC(LDL-C) = 0.554 vs. AUC(non-HDLC) = 0.544, P = 0.655). Conclusions: Cumulative exposure to increased LDL-C is an independent risk factor of newly developed PAD. The predictive value of non-HDLC burden was not revealed.