AUTHOR=Liu Xinmin , Wang Yu , Wu Jianwei , Wang Anxin , Zhang Xiaoli , Cao Zhentang , Zhao Xingquan 

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

JOURNAL=Frontiers in Neurology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.696695

DOI=10.3389/fneur.2021.696695

ISSN=1664-2295

ABSTRACT=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 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 (APAC) study, we enrolled 2923 participants with LDL-C and non-HDLC measured every two year from 2006 to 2012. Cumulative exposure to increased LDL-C and non-HDLC defined as LDL-C burden and non-HDLC burden were calculated as the weighted sum of the difference between measured value and cutoff value. New occurrence of PAD was identified through ABI (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 newly developed PAD. The receiver operating curve (ROC) was drawn, and the area under curve (AUC) was calculated to compare the predictive performance of LDL-C burden with single measure of LDL-C in 2006 and non-HDL-C burden adjusted with a model including traditional risk factors.
Results: Of the 2923 participants, 5.4% (158/2923) 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). Non-HDLC burden failed to show any statistical significance on 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 didn’t reach statistical significance. (AUCLDL-C=0.554 vs AUCnon-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 wasn’t revealed.
Key words：epidemiology, LDL-C, non-HDLC, PAD, risk factor