Low serum vitamin C correlates with an increased risk of peripheral arterial disease in current smokers: Results from NHANES 2003–2004

BACKGROUND: Cigarette smoking is one of the most critical risk factors for peripheral arterial disease (PAD) and inversely correlated Vitamin C. Here we determine whether serum vitamin C correlates with the risk of PAD, especially among current smokers. METHODS: A cross-sectional analysis of 2383 individuals ≥40 y was performed from the U.S. National Health and Nutrition Examination Survey (NHANES 2003–2004), including measurement of ankle-brachial index (ABI), smoking status and serum vitamin C. We examined the interactions between plasma vitamin C and exposure to smoking on the risk of PAD. RESULTS: 912 (38.2%) were current smokers while 207 participants were diagnosed with PAD based on ABI(ABI≤0.9). Current smokers in the lowest vitamin C quartile had the highest prevalence of PAD (14.1%) compared to other quartiles. However, this trend was not significant in nonsmokers. Current smokers in the lowest quartile had a 2.32-fold risk (95% CI, 1.03–5.32; P = 0.04) for PAD after weighted adjustment for potential confounders, including vitamin D and C-reactive protein. In contrast, non-smokers did not have a differing risk of PAD as a function of vitamin C (P for interaction = 0.019). CONCLUSIONS: As an anti-oxidant and anti-inflammatory, low serum vitamin C appears to associates with the risk of PAD in smokers. A relationship between PAD and vitamin C in non-current smokers is not apparent. Modulating vitamin C in current smokers may help mitigate the risk of PAD and should be a target of mechanistic study.