Statin use and lower extremity amputation risk in nonelderly diabetic patients.

OBJECTIVE: To examine the association between use of statin and nonstatin cholesterol-lowering medications and risk of nontraumatic major lower extremity amputations (LEAs) and treatment failure (LEA or death). METHODS: A retrospective cohort of patients with Type I and Type 2 diabetes mellitus (diabetes) was followed for 5 years between 2004 and 2008. The follow-up exposure duration was divided into 90-day periods. Use of cholesterol-lowering agents, diabetic medications, hemoglobin A1c, body mass index, and systolic and diastolic blood pressures were observed in each period. Demographic factors were observed at baseline. Major risk factors of LEA including peripheral neuropathy, peripheral artery disease, and foot ulcers were observed at baseline and were updated for each period. LEA and deaths were assessed in each period and their hazard ratios (HRs) were estimated. The study took place in the U.S. Department of Veterans Affairs Healthcare system, and the subjects consisted of cholesterol drug-naïve patients with Type I or II diabetes who were treated in the U.S. Department of Veterans Affairs Healthcare system in 2003 and were <65 years old at the end of follow-up. RESULTS: Of 83,953 patients in the study cohort, 217 (0.3%) patients experienced a major LEA and 11,716 (14.0%) patients experienced an LEA or death (treatment failure) after a mean follow-up of 4.6 years. Compared with patients who did not use cholesterol-lowering agents, statin users were 35% to 43% less likely to experience an LEA (HR, 0.65; 95% confidence interval [CI], 0.42-0.99) and a treatment failure (HR, 0.57; 95% CI, 0.54-0.60). Users of other cholesterol-lowering medications were not significantly different in LEA risk (HR, 0.95; 95% CI, 0.35-2.60) but had a 41% lower risk of treatment failure (HR, 0.59; 95% CI, 0.51-0.68). CONCLUSIONS: This is the first study to report a significant association between statin use and diminished amputation risk among patients with diabetes. In this nonrandomized cohort, beneficial effects of statin therapy were similar to that seen in large-scale clinical trial experience. For LEA risk, those given nonstatins did not have a statistically significant benefit and its effect on LEA risk was much smaller compared with statins. Unanswered questions to be explored in future studies include a comparison of statins of moderate vs high potency in those with high risk of coronary heart disease and an exploration of whether the effects seen in this study are simply effects of cholesterol-lowering or possibly pleiotropic effects.

Obesity paradox in amputation risk among nonelderly diabetic men.

The association between BMI and amputation risk is not currently well known. We used data for a cohort of diabetic patients treated in the US Department of Veterans Affairs Healthcare System in 2003. Men aged <65 years at the end of follow-up were examined for their amputation risk and amputation-free survival during the next 5 years (2004-2008). Compared to overweight individuals (BMI 25-29.9 kg/m(2)), the risks of amputation and treatment failure (amputation or death) were higher for patients with BMI <25 kg/m(2) and were lower for those with BMI ≥30 kg/m(2). Individuals with BMI ≥40 kg/m(2) were only half as likely to experience any (hazard ratios (HR) = 0.49; 95% confidence interval (CI), 0.30-0.80) and major amputations (HR = 0.53; 95% CI, 0.39-0.73) during follow-up as overweight individuals. While the amputation risk continued to decrease for higher BMI, amputation-free survival showed a slight upturn at BMI >40 kg/m(2). The association between obesity and amputation risk in our data shows a pattern consistent with "obesity paradox" observed in many health conditions. More research is needed to better understand pathophysiological mechanisms that may explain the paradoxical association between obesity and lower-extremity amputation (LEA) risk.