ARTICLE: Peripheral Neuropathy and All-Cause and Cardiovascular Mortality in U.S. Adults: A Prospective Cohort Study

AUTHORS: Caitlin W Hicks, Dan Wang, Kunihiro Matsushita, B Gwen Windham, Elizabeth Selvin

JOURNAL: Ann Intern Med. 2021 Feb;174(2):167-174. doi: 10.7326/M20-1340. Epub 2020 Dec 8.


Background: Growing evidence indicates that peripheral neuropathy (PN) is common even in the absence of diabetes. However, 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 standardized 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 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 cardiovascular mortality was not statistically significant after adjustment (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 decreased sensation in the foot may be an underrecognized risk factor for death in the general population.

Primary funding source: National Institute of Diabetes and Digestive and Kidney Diseases and National Heart, Lung, and Blood Institute of the National Institutes of Health.

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