Investigation of the Negative Association between Hypertension and Age- Associated Peripheral Neuropathy Dong Yung Cho, MD, James W. Mold, MD, Michelle Roberts, M.S. Dept of Family and Preventive Medicine University of Oklahoma Health Sciences Center

Backgrounds In a prior study involving the OKLAHOMA Studies cohort, a negative association was found between HTN & peripheral neuropathy. Mold JW, Vesely S. The prevalence and consequences of peripheral sensory neuropathy in older patients. JABFP 2004; 17(5): Several studies of patients with diabetic neuropathy suggest that HTN might be an aggravating factor.

Purposes of this study Investigate associations between a variety of HTN-related variables and age-associated peripheral neuropathy (AAPN) Investigate these same associations in older patients with diabetes

Research Questions 1.Is AAPN associated with history of hypertension? 2.Is AAPN associated with current systolic, diastolic, pulse pressure, and/or orthostatic change in BP? 3.Is AAPN associated with current BP medications (type or number) or NSAIDs (known to increase BP)? 4.Is diabetic neuropathy associated with any of the factors listed in #1, 2, and 3?

Methods Patients : OKLAHOMA studies cohort > 65 y.o. recruited from 23 primary care practices and evaluated annually for 5 years (those enrolled in year 1 only; N=584) 2 research nurses : reviewed self-administered questionnaires and performed peripheral neurologic examinations In year 3, current medications were reviewed

Methods Nurses trained by a neurologist Inter-rater reliability nearly 100% Definition of PN: Bilateral absence of DTR, vibratory sense, position sense, and/or touch sense in ankles or feet Definition of AAPN: PN and no history of disease known to cause PN

Independent variables Age, gender, BMI, history of military service Self-reported history of hypertension Systolic BP, diastolic BP, pulse pressure, orthostatic drop in systolic BP (at baseline) Total number of and use of specific groups of antihypertensive medications (in year 3)

Statistical Analyses Univariate associations between hypertension-related variables & peripheral neuropathy in two subsets of patients 1.Those with no history of diabetes, autoimmune diseases, B 12 deficiency, chronic hepatitis, chronic renal failure, Crohn’s disease, sarcoidosis, or hereditary neuropathy 2.Those with diabetes mellitus Logistic regression modeling

Univariate – AAPN Variables p-values Age < BMI 0.08 Hx HTN 0.07 Diast. BP (standing) 0.12 Beta Blockers NSAIDs Number of reported PCP visits was associated with HTN but not with PN

Regression Models – AAPN Year 1 (N=584) Variables Odds Ratio (C.I. 95% ) Age 1.10/yr ( ) BMI 1.06 /unit ( ) Hx HTN 0.60 ( )

Regression Models – AAPN Year 3 (N=287) Variables Odds Ratio (C.I. 95% ) Beta Blocker 3.56 ( ) NSAID 2.65 ( )

Associations Between Medications and Deficits Deficit Medication P-Value Ankle DTR B-Blocker NSAID 0.18 Position B-Blocker 0.05 NSAID 0.04 Vibration B-Blocker 0.13 NSAID Touch B-Blocker 0.77 NSAID 0.02

Univariate – Diabetics Variables p-values Hx Military Service 0.10 BMI Hx HTN 0.14 Systolic BP (lying) 0.17 Pulse Pressure (lying) 0.19 CCBs 0.01 Diuretics 0.07 Number BP Meds 0.09

Regression Models – Diabetics Year 1 (N=110) Variables Odds Ratio (C.I. 95% ) Military Service 2.77 ( ) BMI 1.14 /unit ( ) Hx HTN 0.31 ( ) Pulse Pressure 1.03/mmHg ( ) Interactions: Military service and greater BMI reduced the size of the association between pulse pressure and peripheral neuropathy

Regression Models – Diabetics Year 3 (N=45) Variables Odds Ratio (C.I. 95% ) Military Service 31.3 (1.8 – 550.1) BMI 1.4 (1.1 – 1.7) Systolic BP 1.1 (1.0 – 1.1) CCB 26.6 (1.3 – 547.4)

Summary Age-Associated Peripheral Neuropathy : 1.Negative association between history of HTN & PN 2.No association with current BP, pulse pressure, or orthostatic BP 3.No association with number of BP meds (severity of HTN) 4.Can’t explain based upon HTN medications 5.Positive association with & NSAIDs) ß-blocker association may be due to suppression of DTR primarily (not actually neuropathy)

Summary Diabetics: 1.No association between history of HTN & PN 2.Positive association between current pulse pressure & PN 3.Positive association between PN & CCBs even after controlling for PP and other variables

Comparison to Other Studies Prior studies showing a positive association between HTN and PN: 1.Included only overtly symptomatic patients or patients referred to a neurologist and/or 2.Did not control for BMI, military service, and medications

Cross-sectional study Relatively healthy, non-demented population High drop-out rate between years one and three when medication usage was documented Limitations

Limitations History of HTN not verified by medical record review (one-third of those with no hx of HTN had a baseline systolic BP > 140) Diagnosis of PN based upon examination only AAPN defined as absence of self-reported medical conditions known to cause neuropathy (no verification or work-up)

Questions