Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE): a prospective cohort study

Mahshid Dehghan, Andrew Mente, Xiaohe Zhang, Sumathi Swaminathan, Wei Li, Viswanathan Mohan, Romaina Iqbal, Rajesh Kumar, Edelweiss Wentzel-Viljoen, Annika Rosengren, Leela Itty Amma, Alvaro Avezum, Jephat Chifamba, Rafael Diaz, Rasha Khatib, Scott Lear, Patricio Lopez-Jaramillo, Xiaoyun Liu, Rajeev Gupta, Noushin Mohammadifard, Nan Gao, Aytekin Oguz, Anis Safura Ramli, Pamela Seron, Yi Sun, Andrzej Szuba, Lungiswa Tsolekile, Andreas Wielgosz, Rita Yusuf, Afzal Hussein Yusufali, Koon K Teo, Sumathy Rangarajan, Gilles Dagenais, Shrikant I Bangdiwala, Shofiqul Islam, Sonia S Anand, Salim Yusuf, R Diaz, A Orlandini, B Linetsky, S Toscanelli, G Casaccia, JM Maini Cuneo, O Rahman, R Yusuf, AK Azad, KA Rabbani, HM Cherry, A Mannan, I Hassan, AT Talukdar, RB Tooheen, MU Khan, M Sintaha, T Choudhury, R Haque, S Parvin, A Avezum, GB Oliveira, CS Marcilio, AC Mattos, K Teo, S Yusuf, J Dejesus, D Agapay, T Tongana, R Solano, I Kay, S Trottier, J Rimac, W Elsheikh, L Heldman, E Ramezani, G Dagenais, P Poirier, G Turbide, D Auger, A LeBlanc De Bluts, MC Proulx, M Cayer, N Bonneville, S Lear, D Gasevic, E Corber, V de Jong, I Vukmirovich, A Wielgosz, G Fodor, A Pipe, A Shane, F Lanas, P Seron, S Martinez, A Valdebenito, M Oliveros, Li Wei, Liu Lisheng, Chen Chunming, Wang Xingyu, Zhao Wenhua, Zhang Hongye, Jia Xuan, Hu Bo, Sun Yi, Bo Jian, Zhao Xiuwen, Chang Xiaohong, Chen Tao, Chen Hui, Chang Xiaohong, Deng Qing, Cheng Xiaoru, Deng Qing, He Xinye, Hu Bo, Jia Xuan, Li Jian, Li Juan, Liu Xu, Ren Bing, Sun Yi, Wang Wei, Wang Yang, Yang Jun, Zhai Yi, Zhang Hongye, Zhao Xiuwen, Zhu Manlu, Lu Fanghong, Wu Jianfang, Li Yindong, Hou Yan, Zhang Liangqing, Guo Baoxia, Liao Xiaoyang, Zhang Shiying, Bian Rongwen, Tian Xiuzhen, Li Dong, Chen Di, Wu Jianguo, Xiao Yize, Liu Tianlu, Zhang Peng, Dong Changlin, Li Ning, Ma Xiaolan, Yang Yuqing, Lei Rensheng, Fu Minfan, He Jing, Liu Yu, Xing Xiaojie, Zhou Qiang, P Lopez-Jaramillo, PA Camacho Lopez, R Garcia, LJA Jurado, D Gómez-Arbeláez, JF Arguello, R Dueñas, S Silva, LP Pradilla, F Ramirez, DI Molina, C Cure-Cure, M Perez, E Hernandez, E Arcos, S Fernandez, C Narvaez, J Paez, A Sotomayor, H Garcia, G Sanchez, T David, A Rico, P Mony, M Vaz, A V Bharathi, S Swaminathan, K Shankar AV Kurpad, KG Jayachitra, N Kumar, HAL Hospital, V Mohan, M Deepa, K Parthiban, M Anitha, S Hemavathy, T Rahulashankiruthiyayan, D Anitha, K Sridevi, R Gupta, RB Panwar, I Mohan, P Rastogi, S Rastogi, R Bhargava, R Kumar, J S Thakur, B Patro, PVM Lakshmi, R Mahajan, P Chaudary, V Raman Kutty, K Vijayakumar, K Ajayan, G Rajasree, AR Renjini, A Deepu, B Sandhya, S Asha, HS Soumya, R Kelishadi, A Bahonar, N Mohammadifard, H Heidari, K Yusoff, TST Ismail, KK Ng, A Devi, NM Nasir, MM Yasin, M Miskan, EA Rahman, MKM Arsad, F Ariffin, SA Razak, FA Majid, NA Bakar, MY Yacob, N Zainon, R Salleh, MKA Ramli, NA Halim, SR Norlizan, NM Ghazali, MN Arshad, R Razali, S Ali, HR Othman, CWJCW Hafar, A Pit, N Danuri, F Basir, SNA Zahari, H Abdullah, MA Arippin, NA Zakaria, I Noorhassim, MJ Hasni, MT Azmi, MI Zaleha, KY Hazdi, AR Rizam, W Sazman, A Azman, R Khatib, U Khammash, A Khatib, R Giacaman, R Iqbal, A Afridi, R Khawaja, A Raza, K Kazmi, W Zatonski, A Szuba, K Zatonska, R Ilow, M Ferus, B Regulska-Ilow, D Rózanska, M Wolyniec, Alkamel, M Ali, M A Kruger, H H Voster, A E Schutte, E Wentzel-Viljoen, FC Eloff, H de Ridder, H Moss, J Potgieter, AA Roux, M Watson, G de Wet, A Olckers, JC Jerling, M Pieters, T Hoekstra, T Puoane, E Igumbor, L Tsolekile, D Sanders, P Naidoo, N Steyn, N Peer, B Mayosi, B Rayner, V Lambert, N Levitt, T Kolbe-Alexander, L Ntyintyane, G Hughes, R Swart, J Fourie, M Muzigaba, S Xapa, N Gobile, K Ndayi, B Jwili, K Ndibaza, B Egbujie, A Rosengren, K Bengtsson Boström, A Gustavsson, M Andreasson, M Snällman, L Wirdemann, A Oguz, N Imeryuz, Y Altuntas, S Gulec, A Temizhan, K Karsidag, KBT Calik, AAK Akalin, OT Caklili, MV Keskinler, AN Erbakan, AM Yusufali, W Almahmeed, H Swidan, EA Darwish, ARA Hashemi, N Al-Khaja, JM Muscat-Baron, SH Ahmed, TM Mamdouh, WM Darwish, MHS Abdelmotagali, SA Omer Awed, GA Movahedi, F Hussain, H Al Shaibani, RIM Gharabou, DF Youssef, AZS Nawati, ZAR Abu Salah, RFE Abdalla, SM Al Shuwaihi, MA Al Omairi, OD Cadigal, R.S. Alejandrino, J Chifamba, L Gwaunza, G Terera, C Mahachi, P Murambiwa, T Machiweni, R Mapanga

The relationship between macronutrients and cardiovascular disease and mortality is controversial. Most available data are from European and North American populations where nutrition excess is more likely, so their applicability to other populations is unclear. The Prospective Urban Rural Epidemiology (PURE) study is a large, epidemiological cohort study of individuals aged 35-70 years (enrolled between Jan 1, 2003, and March 31, 2013) in 18 countries with a median follow-up of 7·4 years (IQR 5·3-9·3). Dietary intake of 135 335 individuals was recorded using validated food frequency questionnaires. The primary outcomes were total mortality and major cardiovascular events (fatal cardiovascular disease, non-fatal myocardial infarction, stroke, and heart failure). Secondary outcomes were all myocardial infarctions, stroke, cardiovascular disease mortality, and non-cardiovascular disease mortality. Participants were categorised into quintiles of nutrient intake (carbohydrate, fats, and protein) based on percentage of energy provided by nutrients. We assessed the associations between consumption of carbohydrate, total fat, and each type of fat with cardiovascular disease and total mortality. We calculated hazard ratios (HRs) using a multivariable Cox frailty model with random intercepts to account for centre clustering. During follow-up, we documented 5796 deaths and 4784 major cardiovascular disease events. Higher carbohydrate intake was associated with an increased risk of total mortality (highest [quintile 5] vs lowest quintile [quintile 1] category, HR 1·28 [95% CI 1·12-1·46], ptrend=0·0001) but not with the risk of cardiovascular disease or cardiovascular disease mortality. Intake of total fat and each type of fat was associated with lower risk of total mortality (quintile 5 vs quintile 1, total fat: HR 0·77 [95% CI 0·67-0·87], ptrend<0·0001; saturated fat, HR 0·86 [0·76-0·99], ptrend=0·0088; monounsaturated fat: HR 0·81 [0·71-0·92], ptrend<0·0001; and polyunsaturated fat: HR 0·80 [0·71-0·89], ptrend<0·0001). Higher saturated fat intake was associated with lower risk of stroke (quintile 5 vs quintile 1, HR 0·79 [95% CI 0·64-0·98], ptrend=0·0498). Total fat and saturated and unsaturated fats were not significantly associated with risk of myocardial infarction or cardiovascular disease mortality. High carbohydrate intake was associated with higher risk of total mortality, whereas total fat and individual types of fat were related to lower total mortality. Total fat and types of fat were not associated with cardiovascular disease, myocardial infarction, or cardiovascular disease mortality, whereas saturated fat had an inverse association with stroke. Global dietary guidelines should be reconsidered in light of these findings. Full funding sources listed at the end of the paper (see Acknowledgments).