Peripheral Neuropathy and All-Cause and Cardiovascular Mortality in U.S. Adults
Background: Growing evidence indicates that peripheral neuropathy (PN) is common even in the absence of diabetes. How- ever, the clinical sequelae of PN have not been quantified in the general population.
Objective: To assess the associations of PN with all-cause and cardiovascular mortality in the general adult population of the United States.
Design: Prospective cohort study.
Setting: NHANES (National Health and Nutrition Examination
Survey), 1999 to 2004.
Participants: 7116 adults aged 40 years or older who had stan- dardized monofilament testing for PN.
Measurements: Cox regression to evaluate the associations of PN with all-cause and cardiovascular mortality after adjustment for demographic and cardiovascular risk factors, overall and stratified by diabetes status.
Results: The overall prevalence of PN (±SE) was 13.5% ± 0.5% (27.0% ± 1.4% in adults with diabetes and 11.6% ± 0.5% in adults without diabetes). During a median follow-up of 13 years, 2128 participants died, including 488 of cardiovascular causes. Incidence rates (per 1000 person-years) of all-cause mortality were 57.6 (95% CI, 48.4 to 68.7) in adults with dia-
Peripheral neuropathy (PN) results in decreased lower–extremity sensation that can lead to substantial complications in affected adults (1, 2). Although most commonly associated with diabetes (3, 4), PN affects adults with impaired glucose tolerance and normoglycemia as well (5, 6).
Adults with diabetes and PN have higher risks for foot ulcers, major amputation, and falls than those with- out PN (7–10). Relative risk for death is more than 2-fold higher in adults with diabetes who have PN and a foot ulcer than in adults without PN or a foot ulcer (11). In addition, PN has been described as an independent risk factor for death among adults with diabetes (12, 13). However, prior studies have typically focused on clinical populations, and the mortality implications of PN have not been examined in the general population.
The clinical sequelae of PN in the absence of dia- betes are poorly defined. The condition is indepen- dently associated with functional impairments, work disability, and lower-limb amputations in clinical popu- lations of persons with and without diabetes (14). To our knowledge, no studies have examined the associa- tion between nondiabetic PN and mortality. Diabetes and PN, 34.3 (CI, 30.3 to 38.8) in adults with PN but no diabetes, 27.1 (CI, 23.4 to 31.5) in adults with diabetes but no PN, and 13.0 (CI, 12.1 to 14.0) in adults with no diabetes and no PN. In adjusted models, PN was significantly associated with all-cause mortality (hazard ratio [HR], 1.49 [CI, 1.15 to 1.94]) and cardiovascular mortality (HR, 1.66 [CI, 1.07 to 2.57]) in participants with diabetes. In those without diabetes, PN was significantly associated with all-cause mortality (HR, 1.31 [CI, 1.15 to 1.50]), but the association between PN and cardio- vascular mortality was not statistically significant after adjust- ment (HR, 1.27 [CI, 0.98 to 1.66]).
Limitation: Prevalent cardiovascular disease was self-reported, and PN was defined by monofilament testing only.
Conclusion: Peripheral neuropathy was common and was independently associated with mortality in the U.S. population, even in the absence of diabetes. These findings suggest that de- creased sensation in the foot may be an under-recognized risk factor for death in the general population.