Obesity and Obesity-Related Factors and Risk of Herpes Zoster and Postherpetic Neuralgia

Brief Summary

Detailed Description

Research Questions: Hypotheses 1. The investigators hypothesize that greater body adiposity is associated with increased risk of developing herpes zoster (HZ). Specifically, the investigators hypothesize that higher body mass index (BMI), larger waist circumference, and higher waist to hip ratio, waist to height ratio, predicted fat mass, predicted percent fat and ABSI are associated with increased risk of developing HZ. The investigators will also examine whether these associations differ by age, sex and other factors. 2. The investigators hypothesize that plasma biomarkers of obesity and of inflammation are independently and longitudinally associated with risk of HZ. Specifically, The investigators hypothesize that lower plasma total and high-molecular-weight (HMW) adiponectin, and higher plasma leptin, IL-6 and CRP are independently associated with higher risk of HZ. 3. The investigators hypothesize that greater body adiposity is associated with increased risk of developing postherpetic neuralgia (PHN). Specifically, The investigators hypothesize that higher body mass index, larger waist circumference, and higher waist to hip ratio, waist to height ratio, predicted fat mass, predicted percent fat and ABSI are associated with increased risk of developing post-herpetic neuralgia (PHN) among those who develop HZ. 4. The investigators hypothesize that obesity-related metabolic dysregulation contributes to HZ risk. Specifically, The investigators hypothesize that circulating levels of metabolites and metabolic pathways that are altered by adiposity and may influence cell-mediated immune function, such as glutamine, arginine, the branched chain amino acids isoleucine, leucine and valine, the tryptophan metabolite kynurenine, and certain fatty acids, such as lysophosphatidylcholines, are associated with risk of developing HZ. 5. The investigators hypothesize that obesity-related metabolic dysregulation contributes to risk of developing PHN among women with HZ. Specifically, the investigators hypothesize that alterations of plasma levels of certain metabolites and metabolic pathways previously implicated in chronic neuroimmune inflammation and increased neurosensitivity, including abnormal fatty acid and amino acid metabolism (e.g. arachidonic acid derived eicosanoids, glutamate-aspartate, tryptophan-kynurenine, and arginine-ornithine metabolic pathways), are associated with the development of PHN among women with HZ. III. Objectives A. Objective 1a: To examine whether anthropomorphic measures of obesity from early through middle and later adult life are independently and longitudinally associated with risk of HZ. The investigators will use information on BMI, waist circumference, hip circumference, predicted fat mass and percent fat, ABSI and HZ that has been longitudinally collected across the lifespan among \>200,000 women and men. WThe investigators e hypothesize that higher body mass index (BMI), larger waist circumference, higher waist to hip ratio, higher waist to height ratio, higher predicted fat mass, predicted percent fat and ABSI are associated with increased risk of developing HZ. The investigators will also examine whether these associations differ by age, sex and other factors. B. Objective 1b: To examine whether plasma biomarkers of obesity, the immunomodulatory adipokines leptin and adiponectin, and markers of inflammation, interleukin-6 (IL-6) and C-reactive protein (CRP), are independently and longitudinally associated with risk of HZ. Using existing plasma biomarker information from \>19,000 participants, including over 2,500 that developed HZ after the time of the blood collection (incident HZ), the investigators will examine associations of these plasma biomarkers and risk of developing HZ, and examine whether the proposed association between obesity and HZ risk is mediated through immunomodulatory adipokines or inflammation. The investigators hypothesize that lower total and high-molecular-weight (HMW) adiponectin, and higher plasma leptin, IL-6 and CRP are independently associated with higher risk of HZ. C. Objective 1c: To investigate whether anthropomorphic measures of obesity are associated with higher risk of developing postherpetic neuralgia (PHN) among women with HZ. In a substudy of over 10,000 NHS I and NHS II participants who reported a history of "shingles," the investigators collected detailed information on HZ course, treatment and related complications on a Zoster Supplemental Questionnaire (ZSQ). Information on PHN was validated by medical record review. The investigators hypothesize that higher body mass index, larger waist circumference, and higher waist to hip ratio, waist to height ratio, predicted fat mass, predicted percent fat and ABSI are associated with increased risk of developing PHN. D. Objective 2a: To assess how obesity-related metabolic dysregulation contributes to HZ risk. The investigators will conduct an agnostic analysis to identify individual metabolites and metabolic pathways associated with obesity among \>13,000 women and men for whom the investigators have comprehensive information on plasma metabolomics profiles. The investigators hypothesize that circulating levels of metabolites and metabolic pathways that are altered by body adiposity and may influence cell-mediated immune function, such as glutamine, arginine, the branched chain amino acids isoleucine, leucine and valine, the tryptophan metabolite kynurenine, and certain fatty acids, such as lysophosphatidylcholines, are associated with risk of developing HZ. The investigators will create a metabolite-based obesity score and assess the degree to which the association between obesity and HZ risk is mediated by the metabolite-based obesity score. Secondarily, the investigators will conduct an agnostic investigation to identify individual metabolites and metabolic pathways associated with risk of developing HZ. E. Objective 2b: To assess how obesity-related metabolic dysregulation contributes to risk of developing postherpetic neuralgia (PHN) among women with HZ. Among participants who had HZ and completed the Zoster Supplementary Questionnaire (ZSQ) that collected additional details about HZ course, complications and treatment, and for whom information on metabolomics information is available (n=1,005 to date), the investigators will assess the degree to which the potential association between obesity and PHN risk is mediated by the metabolite-based obesity score (developed in Aim 2a above). Secondarily, the investigators will conduct an agnostic investigation to identify individual metabolites and metabolic pathways associated with risk of developing PHN. The investigators hypothesize that alterations of plasma levels of certain metabolites and metabolic pathways previously implicated in chronic neuroimmune inflammation and increased neurosensitivity, including abnormal fatty acid and amino acid metabolism (e.g. arachidonic acid derived eicosanoids, glutamate-aspartate, tryptophan-kynurenine, and arginine-ornithine metabolic pathways), are involved in the development of PHN among women with HZ.

Primary Outcomes

Secondary Outcomes

• Post-herpetic neuralgia assessed by questionnaire(2000-2024)