Supplementary Information Effects of cold and hot temperature on dehydration: A mechanism of cardiovascular burden Authors: Youn-Hee Lim, PhD1,2*, Min-Seon Park, MD3*, Yoonhee Kim, PhD4, Ho Kim, PhD4,5,, Yun-Chul Hong, MD, PhD1,6§ *These authors contributed equally to this work. 1 Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul, Korea 2 Environmental Health Center, Seoul National University College of Medicine, Seoul, Korea 3 Department of Family Medicine, Seoul National University Hospital, Seoul, Korea 4 Department of Biostatistics and Epidemiology, School of Public Health, Seoul National University, Seoul, Korea 5 Institute of Health and Environment, Seoul National University, Seoul, Korea 6 Institute of Medical Research, Seoul National University Bundang Hospital, Seongnam, Republic of Korea § Corresponding author: Y-C Hong, Institute of Environmental Medicine, Seoul National University Medical Research Center, 103 Daehakro, Jongro-gu, Seoul 110-799, Republic of Korea. Telephone: +82-2-740-8394; Fax: +82-2-747-4830; E-mail: ychong1@snu.ac.kr 1 Tables of Contents Supplementary Tables Supplementary Table S1. Monthly average of four markers (Mean (P-valuea)) ........................................... 3 Supplementary Table S2. Effects of daily mean temperature on dehydration indices per 1°C decrease/ incr ease at below or above the flexion temperature. ........................................................................................... 7 Supplementary Table S3. Amount of variance (%) explained by apparent temperature (AT): Using individ ual patients’ dehydration makers................................................................................................................... 8 Supplementary Table S4. Amount of variance (%) explained by apparent temperature (AT): Using daily a verage of dehydration markers...................................................................................................................... 9 Supplementary Figures Supplementary Figure S1. Monthly patterns of four markers and apparent temperature (AT)..................... 4 Supplementary Figure S2. Estimated effects per 1°C decrease/increase of mean temperature below /above temperature flexion points (stratified by hypertension group). .................................................................... 5 Supplementary Figure S3. Plots of changes in dehydration markers according to daily mean temperature c hange. ............................................................................................................................................................ 6 2 Supplementary Table S1. Monthly average of four markers (Mean (P-valuea)) Plasma Tonicity BUN/Creatinine Urine specific gravityb (mOsm/l) January 16.11 1022.12 42.55 February 16.30 (0.1079) 1022.18 (0.6765) 42.45 (0.3116) March 16.33 (0.0514) 1022.15 (0.8351) 42.19 (0.0002) April 16.28 (0.1404) 1021.45 (<0.0001) 42.13 (<0.0001) May 16.01 (0.3877) 1020.92 (<0.0001) 42.06 (<0.0001) June 15.94 (0.1342) 1019.94 (<0.0001) 42.09 (<0.0001) July 16.23 (0.2725) 1019.75 (<0.0001) 41.69 (<0.0001) August 15.63 (<0.0001) 1020.17 (<0.0001) 41.69 (<0.0001) September 15.61 (<0.0001) 1020.18 (<0.0001) 41.82 (<0.0001) October 15.60 (<0.0001) 1020.80 (<0.0001) 42.07 (<0.0001) November 16.02 (0.4486) 1020.93 (<0.0001) 42.45 (0.3171) December 16.27 (0.1610) 1021.51 (<0.0001) 42.24 (0.0009) a P-value for Student’s t-test for month difference (Reference: January) b Urine specific gravity was multiplied by 1,000. 3 Haematocrit (%) 297.05 296.11 (<0.0001) 296.52 (<0.0001) 297.01 (0.7500) 296.26 (<0.0001) 296.19 (<0.0001) 296.20 (<0.0001) 296.09 (<0.0001) 296.01 (<0.0001) 296.96 (0.4323) 296.81 (0.0402) 296.96 (0.4411) Supplementary Figure S1. Monthly patterns of four markers and apparent temperature (AT) BUN/CR: BUN/Creatinine ratio; Usg: Urine specific gravity; Tonicity: Plasma tonicity; HCT: Haematocrit; AT: apparent temperature 4 Supplementary Figure S2. Estimated effects per 1°C decrease/increase of mean temperature below /above temperature flexion points (stratified by hypertension group). Flexion temperature points and lag days were 25.0°C (lag 0–5), 22.8°C (lag 0), and 26.8°C (lag 0–5) for (a) urine specific gravity, (b) plasma tonicity, and (c) haematocrit, respectively. 5 Supplementary Figure S3. Plots of changes in dehydration markers according to daily mean temperature change. (A), (B), (C), and (D) are Bun/Creatinine ratio, urine specific gravity, plasma tonicity, and haematocrit, respectively. All models were adjusted for sex, age, body mass index, alcohol consumption, household income, smoking status, haemoglobin (for haematocrit only), daily mean relative humidity, season, and year. . 6 Supplementary Table S2. Effects of daily mean temperature on dehydration indices per 1°C decrease/ increase at below or above the flexion temperature. Dehydration Index Temperature (°C, Lag days) Bun/Creatinine ratio Below flexion Above flexion Betaa (SE) P-value Betaa (SE) P-value 22.4 (lag 0-1) 0.036 (0.005) <0.0001 0.083 (0.021) 0.0001 Urine specific gravityb 24.0 (lag 0-5) 0.073 (0.007) <0.0001 0.292 (0.041) <0.0001 Plasma tonicity 22.2 (lag 0) 0.045 (0.005) <0.0001 0.169 (0.022) <0.0001 Haematocrit 24.8 (lag 0-5) 0.009 (0.001) <0.0001 0.038 (0.009) <0.0001 a All models were adjusted for sex, age, body mass index, alcohol consumption, household income, smoking status, haemoglobin (for haematocrit only), daily mean relative humidity, season, and year. b Urine specific gravity was multiplied by 1,000. 7 Supplementary Table S3. Amount of variance (%) explained by apparent temperature (AT): Using individual patients’ dehydration makers BUN/CR ratio Model All dataa Cold tails (< flexion point)a Warm tails (> flexion point) a a Hydration markers Urine specific Plasma gravity tonicity Haematocrit 0.3 2.2 0.3 0.3 0.3 1.9 0.3 0.2 0.6 0.4 0.3 0.1 Generalized linear modeling (GLM) with natural cubic splines of AT in 5 degrees of freedom 8 Supplementary Table S4. Amount of variance (%) explained by apparent temperature (AT): Using daily average of dehydration markers BUN/CR ratio Model All dataa Cold tails (< flexion point)a Warm tails (> flexion point) a a Hydration markers Urine specific Plasma gravity tonicity Haematocrit 1.4 5.8 0.5 1.5 1.4 5.8 0.5 1.5 2.7 3.0 0.7 1.4 Generalized linear modeling (GLM) with natural cubic splines of AT in 5 degrees of freedom. 9