Increasing SBP variability is associated with an increased risk of developing incident diabetic foot ulcers

Abstract

Objective: 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. Methods: 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. Results: 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. Conclusion: 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.

Retrospective cohort study of the relationship between systolic blood pressure variability and multiple sclerosis disability

“…They also had lower rates of hypertension in higher SBP variability tertiles with the lowest proportion observed in Tertile 3 (19% vs 41% in Tertile 1), a group with the highest SBP variability. This finding is consistent with previous studies by Sohn and his colleagues on diabetic complications 8 11 12. Our results also demonstrate that mean SBP was not significantly associated with PDDS groups, suggesting that there may be a different physiologic mechanism at play, not simply elevated blood pressures 13…”

“…Visit-to-visit systolic blood pressure (SBP) variability is an emerging risk factor for a wide array of health outcomes, including CVD, kidney failure, cognitive dysfunction, diabetic complications and all-cause mortality 6–10. Excessive SBP variability ( > 10 within-subject SD) has been associated with many of these outcomes independent of mean blood pressure and hypertension 8 11 12. Evidence suggests that visit-to-visit blood pressure variability may have stronger effects on cardiovascular outcomes than that of measures taken during a single visit or by 24 hours ambulatory monitoring devices 13–15.…”

Guidelines on multidisciplinary approaches for the prevention and management of diabetic foot disease (2020 edition)

“…Excessive systolic blood pressure can increase the incidence of DFUs. It has also been observed that calcium channel blockers can reduce the occurrence of DFUs, possibly by stabilizing systolic blood pressure [ 66 ]. Although we understand that patients with diabetic foot require good blood pressure control, the exact control target has not yet been determined.…”

Reply

“…Nagai et al commentary [1] adds to our nascent theory that increased SBP variability may be a novel risk factor for diabetic foot ulcers and major amputation [5,6]. It provides evidence for biologic plausibility.…”

“…Specifically, both typesets of studies suggest a trial of calcium channel blockers would be most effective in patients who have not yet developed peripheral arterial disease. Epidemiologically, we found that calcium channel blockers were associated with a reduced risk of foot ulcerations, but only for patients who were not diagnosed with peripheral vascular disease [5]. For patients with established peripheral vascular disease, SBP variability no longer predicted major amputation rates.…”