Amit C Achhra1,2, Caroline Sabin3, Lene Ryom4, Camilla Hatleberg4, Monforte Antonella dʼAminio5, Stephane de Wit6, Andrew Phillips3, Christian Pradier7, Rainer Weber8, Peter Reiss9,10, Wafaa El-Sadr11, Fabrice Bonnet12, Amanda Mocroft3, Jens Lundgren4, Matthew G Law1. 1. The Kirby Institute, UNSW Australia, Sydney, Australia. 2. Internal Medicine, New York Presbyterian/Weill Cornell Medical Center, New York, NY. 3. Institute for Global Health, UCL, London, United Kingdom. 4. CHIP, Department of Infectious Diseases, Section 2100, 2Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 5. Dipartimento di Scienze della Salute, Clinica di Malattie Infettive e Tropicali, Azienda Ospedaliera-Polo Universitario San Paolo, Milan, Italy. 6. Division of Infectious Diseases, Saint Pierre University Hospital, Université Libre de Bruxelles, Brussels, Belgium. 7. Department of Public Health, Nice University Hospital, Nice, France. 8. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Switzerland. 9. Division of Infectious Diseases, Department of Global Health, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. 10. HIV Monitoring Foundation, Amsterdam, the Netherlands. 11. ICAP-Columbia University and Harlem Hospital, New York, NY. 12. ISPED, INSERM U1219, CHU de Bordeaux, Université de Bordeaux, Bordeaux, France.
Abstract
BACKGROUND: The relationship between body mass index (BMI) [weight (kg)/height (m)] and serious non-AIDS events is not well understood. METHODS: We followed D:A:D study participants on antiretroviral therapy from their first BMI measurement to the first occurrence of the endpoint or end of follow-up (N = 41,149 followed for 295,147 person-years). The endpoints were cardiovascular disease (CVD); diabetes; non-AIDS-defining cancers (NADCs) and BMI-NADCs (cancers known to be associated with BMI in general population); and all-cause mortality. Using Poisson regression models, we analyzed BMI as time-updated, lagged by 1 year, and categorized at: 18.5, 23, 25, 27.5, and 30 kg/m. RESULTS: Participants were largely male (73%) with the mean age of 40 years (SD 9.7) and baseline median BMI of 23.3 (interquartile range: 21.2-25.7). Overall, BMI showed a statistically significant J-shaped relationship with the risk of all outcomes except diabetes. The relative risk (RR) for the BMI of <18.5 and >30 (95% confidence interval) compared with 23-25, respectively, was as follows: CVD: 1.46 (1.15-1.84) and 1.31 (1.03-1.67); NADCs: 1.78 (1.39-2.28) and 1.17 (0.88-1.54); and "BMI-NADCs": 1.29 (0.66-2.55) and 1.92 (1.10-3.36). For all-cause mortality, there was an interaction by sex (P < 0.001): RR in males: 2.47 (2.12-2.89) and 1.21 (0.97-1.50); and in females: 1.60 (1.30-1.98) and 1.02 (0.74-1.42). RR remained around 1 for intermediate categories of BMI. The risk of diabetes linearly increased with increasing BMI (P < 0.001). CONCLUSIONS: Risk of CVD, a range of cancers, and all-cause mortality increased at low BMI (<18.5) and then tended to increase only at BMI > 30 with a relatively low risk at BMI of 23-25 and 25-30. High BMI was also associated with risk of diabetes.
BACKGROUND: The relationship between body mass index (BMI) [weight (kg)/height (m)] and serious non-AIDS events is not well understood. METHODS: We followed D:A:D study participants on antiretroviral therapy from their first BMI measurement to the first occurrence of the endpoint or end of follow-up (N = 41,149 followed for 295,147 person-years). The endpoints were cardiovascular disease (CVD); diabetes; non-AIDS-defining cancers (NADCs) and BMI-NADCs (cancers known to be associated with BMI in general population); and all-cause mortality. Using Poisson regression models, we analyzed BMI as time-updated, lagged by 1 year, and categorized at: 18.5, 23, 25, 27.5, and 30 kg/m. RESULTS:Participants were largely male (73%) with the mean age of 40 years (SD 9.7) and baseline median BMI of 23.3 (interquartile range: 21.2-25.7). Overall, BMI showed a statistically significant J-shaped relationship with the risk of all outcomes except diabetes. The relative risk (RR) for the BMI of <18.5 and >30 (95% confidence interval) compared with 23-25, respectively, was as follows: CVD: 1.46 (1.15-1.84) and 1.31 (1.03-1.67); NADCs: 1.78 (1.39-2.28) and 1.17 (0.88-1.54); and "BMI-NADCs": 1.29 (0.66-2.55) and 1.92 (1.10-3.36). For all-cause mortality, there was an interaction by sex (P < 0.001): RR in males: 2.47 (2.12-2.89) and 1.21 (0.97-1.50); and in females: 1.60 (1.30-1.98) and 1.02 (0.74-1.42). RR remained around 1 for intermediate categories of BMI. The risk of diabetes linearly increased with increasing BMI (P < 0.001). CONCLUSIONS: Risk of CVD, a range of cancers, and all-cause mortality increased at low BMI (<18.5) and then tended to increase only at BMI > 30 with a relatively low risk at BMI of 23-25 and 25-30. High BMI was also associated with risk of diabetes.
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