Abstract P248: Oxidized Phospholipids and Risk of Peripheral Arterial Disease in Men
Background: Peripheral arterial disease (PAD) is highly prevalent, found in 25% of adults ≥70 years, but its risk factors are less well studied than coronary and carotid atherosclerosis. Proinflammatory oxidized phospholipids (OxPL) are a novel cardiovascular risk factor produced by oxidative stress and are preferentially bound and transported by lipoprotein (a) [Lp(a)] in plasma. Previous studies have shown an association between OxPL on apolipoprotein B-100 (OxPL/apoB) and carotid and femoral atherosclerosis. However, no previous studies have specifically examined the prospective association between OxPL/apoB and risk of PAD in a population-based cohort. Methods: We conducted a nested case-control study among men free of cardiovascular disease within the Health Professionals Follow-up Study (1994–2008) including 143 men with PAD and 429 controls matched on age, month of blood draw, and smoking. OxPL/apoB and Lp(a) were measured in stored baseline plasma. We identified cases of clinically significant PAD based on at least one of the following: (1) amputation, bypass, or other revascularization procedure for occlusive arterial disease, (2) angiogram/ultrasound confirming at least 50% stenosis of at least one artery with congruent symptoms in the ipsilateral limb, (3) ankle-brachial index < 0.9, or (4) physician's diagnosis. We used conditional logistic regression to estimate odds ratios (OR) for PAD according to level of OxPL/apoB. Results: The OR for PAD was 1.24 (95% CI 1.05–1.46) for each 1-standard deviation (SD) increase in OxPL/apoB after adjusting for matching factors. Additional adjustment for family history of MI, triglycerides, HDL-C, LDL-C, C-reactive protein, hemoglobin A1c, pack-years of smoking, physical activity, hypertension, diabetes, hypercholesterolemia, body-mass index, and aspirin use did not change this estimate: 1.24 (95% CI 1.00–1.54). OxPL/apoB was not correlated with any conventional risk factors: Spearman correlation coefficients ranged from 0.0 to 0.13. We observed no interaction with age or LDL-C. Similarly, the OR for PAD was 1.25 (95% CI 0.95–1.63) for each 1- SD increase in ln[Lp(a)] after adjusting for all of the above covariates. Conclusion: OxPL/apoB is positively associated with risk of PAD in men with no appreciable attenuation after adjustment for conventional risk factors.