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Author: David L. Narotsky, MD, Johns Hopkins
University School of Medicine, Class of 2013
Introduction: Low serum 25(OH) D levels are
associated with higher prevalence of peripheral arterial disease
(PAD). It has been proposed that this inverse relationship is
non-linear in that the association diminishes with rising 25(OH) D
levels. To test this hypothesis, we examined the relationship
between 25 (OH) D and PAD as measured by Ankle-Brachial index (ABI)
in healthy adult US population.
Methods: We analyzed data from the continuous
National Health and Nutrition Examination Survey for years
2001-2004. ABI was treated as a continuous variable and the minimum
of the two reported ABI values was chosen for each individual. To
examine the non-linear relationship between 25(OH) D and ABI, we
introduced a spline, with a single knot at the median serum levels
(21ng/mL) of 25(OH) D. The same analysis was performed later with a
single spline of 27 ng/ml (75th percentile). The effect of 25(OH) D
was calculated for every 10 ng/mL increase below and above each
spline. Regression models were adjusted for age, sex, race, body
mass index, blood pressure, serum glucose, c-reactive protein,
smoking, total cholesterol, and renal function.
Results: Of the 4979 individuals, 48% were
females and 58% were Caucasians. The mean (SD) age, 25 (OH) D,
c-reactive protein, and ABI was 60.4 (13.22) years, 22.1(8.68)
ng/mL, 0.46(0.81) mg/dL and 1.07(0.15), respectively. In both
unadjusted and adjusted linear regression models without a spline,
we found that 25(OH) D was associated with a significant increase
in ABI (0.018, 95% CI: 0.013 to 0.023 and 0.018, 95% CI: 0.012 to
0.024, respectively) for each 10 ng/mL increase in serum 25(OH) D.
In the unadjusted linear regression model with spline, any change
in ABI with rising serum 25(OH) D was much larger before 21 ng/mL
(0.04, 95% CI: 0.03 to 0.05) than after 21 ng/mL (0.01, 95% CI:
0.003 to 0.013), for each 10 ng/mL increase in serum 25(OH) D. In
adjusted analysis, the association between ABI and 25(OH) D
remained statistically significant before 21 ng/mL (0.04, 95% CI:
0.02 to 0.05 ) but not after 21 ng/mL (0.008, 95% CI: - 0.0008 to
0.017) for each 10 ng/mL increase in 25(OH) D. Once serum 25 (OH) D
levels increases above 27 ng/mL (75th percentile), we found no
statistically significant increase in ABI in regression analysis
adjusted for traditional cardiovascular risk factors.
Conclusions: ABI increases as serum 25(OH) D
levels increases, however, the change is nonlinear and it appears
to plateau after 21 ng/mL of 25(OH) D and disappear after 27 ng/ml
in healthy adults. It is likely that the benefit of 25(OH) D
supplementation for the prevention of PAD may only be seen in
individuals with 25(OH) D levels below 21 ng/mL.
September 2013 Issue of IMpact