Studies have investigated the effects of heat and temperature variability (TV) on mortality. However, few assessed whether TV modifies the heat-mortality association. Data on daily temperature and mortality in the warm season were collected from 717 locations across 36 countries. TV was calculated as the standard deviation of the average of the same and previous days' minimum and maximum temperatures. We used location-specific quasi-Poisson regression models with an interaction term between the cross-basis term for mean temperature and quartiles of TV to obtain heat-mortality associations under each quartile of TV, and then pooled estimates at the country, regional, and global levels. Results show the increased risk in heat-related mortality with increments in TV, accounting for 0.70% (95% confidence interval [CI]: -0.33 to 1.69), 1.34% (95% CI: -0.14 to 2.73), 1.99% (95% CI: 0.29-3.57), and 2.73% (95% CI: 0.76-4.50) of total deaths for Q1-Q4 (first quartile-fourth quartile) of TV. The modification effects of TV varied geographically. Central Europe had the highest attributable fractions (AFs), corresponding to 7.68% (95% CI: 5.25-9.89) of total deaths for Q4 of TV, while the lowest AFs were observed in North America, with the values for Q4 of 1.74% (95% CI: -0.09 to 3.39). TV had a significant modification effect on the heat-mortality association, causing a higher heat-related mortality burden with increments of TV. Implementing targeted strategies against heat exposure and fluctuant temperatures simultaneously would benefit public health.

Air Health Science Division Health Canada Ottawa ON K1A 0K9 Canada

Center for Climate Change Adaptation National Institute for Environmental Studies Tsukuba Ibaraki 305 8506 Japan

Center for Global Health Nanjing Medical University Nanjing 211166 China

Centre for Statistical Methodology London School of Hygiene and Tropical Medicine London WC1E 7HT UK

Centre on Climate Change and Planetary Health London School of Hygiene and Tropical Medicine London WC1E 7HT UK

CIBER de Epidemiología y Salud Pública Madrid 28029 Spain

Climate Air Quality Research Unit School of Public Health and Preventive Medicine Monash University Melbourne 3004 Australia

Department of Earth Sciences University of Turin Turin 10125 Italy

Department of Environmental Health Faculty of Public Health University of Medicine and Pharmacy at Ho Chi Minh City Ho Chi Minh City 17000 Vietnam

Department of Environmental Health Harvard T H Chan School of Public Health Harvard University Boston MA 02115 USA

Department of Environmental Health National Institute of Public Health Cuernavaca Morelos 62100 Mexico

Department of Environmental Health School of Public Health Fudan University Shanghai 200032 China

Department of Environmental Health University of São Paulo São Paulo 01246 904 Brazil

Department of Epidemiology and Preventive Medicine School of Public Health and Preventive Medicine Monash University Melbourne 3004 Australia

Department of Epidemiology Lazio Regional Health Service Rome 00147 Italy

Department of Geography University of Santiago de Compostela Santiago de Compostela 15705 Spain

Department of Global Health Policy Graduate School of Medicine The University of Tokyo Tokyo 113 8654 Japan

Department of Hygiene Epidemiology and Medical Statistics National and Kapodistrian University of Athens Athens 11527 Greece

Department of Occupational and Environmental Medicine School of Medicine Ewha Womans University Seoul 03760 South Korea

Department of Pathology Faculty of Medicine University of São Paulo São Paulo 05508 270 Brazil

Department of Physical Chemical and Natural Systems Universidad Pablo de Olavide Sevilla 41013 Spain

Department of Public Health and Clinical Medicine Umeå University Umeå 901 87 Sweden

Department of Public Health Environments and Society London School of Hygiene and Tropical Medicine London WC1E 7HT UK

Department of Quantitative Methods School of Medicine University of the Republic Montevideo 11200 Uruguay

Department of Statistics and Computational Research Universitat de València València 46003 Spain

Department of Statistics Computer Science and Applications G Parenti University of Florence Florence 50121 Italy

Environmental Health Department Instituto Nacional de Saúde Dr Ricardo Jorge Porto 4000 055 Portugal

EPIUnit Instituto de Saúde Pública Universidade do Porto Porto 4050 600 Portugal

Faculty of Environmental Sciences Czech University of Life Sciences Prague 165 00 Czech Republic

Faculty of Geography and Environmental Sciences Hakim Sabzevari University Sabzevar 9617976487 Iran

Faculty of Geography Babeş Bolyai University Cluj Napoca 400084 Romania

Gangarosa Department of Environmental Health Rollins School of Public Health Emory University Atlanta GA 30322 USA

Graduate School of Public Health Seoul National University Seoul 08826 Republic of Korea

Health Innovation Laboratory Institute of Tropical Medicine Alexander von Humboldt Universidad Peruana Cayetano Heredia Lima 15102 Peru

IBE Chair of Epidemiology Ludwig Maximilian University Munich Munich 81377 Germany

INSPER São Paulo 04546 042 Brazil

Institute for Environment Health and Societies Brunel University London London UB8 3PN UK

Institute of Atmospheric Physics Czech Academy of Sciences Prague 141 00 Czech Republic

Institute of Environmental Assessment and Water Research Spanish Council for Scientific Research Barcelona 08034 Spain

Institute of Epidemiology Helmholtz Zentrum München German Research Center for Environmental Health Neuherberg 85747 Germany

Institute of Family Medicine and Public Health University of Tartu Tartu 50090 Estonia

Institute of Social and Preventive Medicine University of Bern Bern 3012 Switzerland

Laboratório para a Investigação Integrativa e Translacional em Saúde Populacional Porto 4050 600 Portugal

National Agency for Public Health of the Ministry of Health Labour and Social Protection of the Republic of Moldova Chisinau MD 2009 Republic of Moldova

National Institute for Public Health and the Environment Centre for Sustainability and Environmental Health Bilthoven 3720 BA Netherlands

Oeschger Center for Climate Change Research University of Bern Bern 3012 Switzerland

Santé Publique France Department of Environmental Health French National Public Health Agency Saint Maurice 94 410 France

School of Epidemiology and Public Health Faculty of Medicine University of Ottawa Ottawa ON K1N 6N5 Canada

School of Population Health and Environmental Sciences King's College London London WC2R 2LS UK

School of Public Health and Social Work Queensland University of Technology Brisbane 4000 Australia

School of Public Health Institute of Environment and Human Health Anhui Medical University Hefei 230032 China

School of the Environment Yale University New Haven CT 06511 USA

School of Tropical Medicine and Global Health Nagasaki University Nagasaki 852 8521 Japan

Scripps Institution of Oceanography University of California San Diego La Jolla CA 92093 USA

Shanghai Children's Medical Centre Shanghai Jiao Tong University Shanghai 200025 China

Swiss Tropical and Public Health Institute Basel 4051 Switzerland

Technological University Dublin Dublin D07 EWV4 Ireland

Universidad de Buenos Aires Facultad de Ciencias Sociales Instituto de Investigaciones Gino Germani Buenos Aires C1053ABH Argentina

University of Basel Basel 4001 Switzerland

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