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SBP variability may be a target for mitigating end-organ damage associated with vascular disease. We evaluated the relationship between increased SBP variability and risk of incident diabetic foot ulceration.Using a nested case–control design, we followed patients diagnosed with diabetes and treated within the US Department of Veterans Affairs Healthcare system for development of a diabetic foot ulcer (event) between 2006 and 2010. Each case was randomly matched to up to five controls based on age, sex, race/ethnicity, and calendar time. SBP variability was computed using at least three blood pressure measurements from the year preceding the event. The association between SBP variability and foot ulceration was examined using conditional logistic regression. Potential protective effects of calcium channel blockers, which blunt SBP variability, were also explored.The study sample included 51 111 cases and 129 247 controls. Compared with those in quartile 1 (lowest variability), patients in quartiles 2–4 had higher adjusted odds ratios for diabetic foot ulcer development: 1.11 (95% CI 1.07–1.16), 1.20 (95% CI 1.15–1.25), 1.29 (95% CI 1.24–1.34) (P for trend <0.001). Calcium channel blockers were associated with reduced risks of ulceration for those without peripheral vascular disease (OR = 0.87, 95% CI 0.84–0.90, P < 0.001) or neuropathy (OR = 0.85, 95% CI 0.82–0.89, P < 0.001) in adjusted subgroup analyses.This study describes a graded relationship between SBP variability and risk of diabetic foot ulceration, providing a potential new and modifiable target to reduce this common complication.