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151. Sex steroids and markers of micro- and macrovascular damage among women and men from the general population

Author: M. A. Ikram, J L Roeters van Lennep, Caroline C W Klaver, Daniel Bos, Fariba Ahmadizar, E Aribas, Unal Mutlu, Maryam Kavousi, Joop S.E. Laven, Mohammad Kamran Ikram, Epidemiology, Radiology & Nuclear Medicine, Obstetrics & Gynecology, Ophthalmology, and Internal Medicine
Subjects: Male, medicine.medical_specialty, Epidemiology, medicine.drug_class, Population, 030204 cardiovascular system & hematology, Carotid Intima-Media Thickness, Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12], 03 medical and health sciences, Rotterdam Study, chemistry.chemical_compound, 0302 clinical medicine, Sex hormone-binding globulin, Dehydroepiandrosterone sulfate, Internal medicine, Sex Hormone-Binding Globulin, medicine, Humans, Testosterone, Androstenedione, education, Gonadal Steroid Hormones, education.field_of_study, biology, business.industry, Dehydroepiandrosterone Sulfate, Odds ratio, Androgen, medicine.disease, Menopause, Endocrinology, Cross-Sectional Studies, chemistry, biology.protein, Androgens, Female, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery, Biomarkers
Abstract: Aims The contribution of sex hormones to micro- and macrovascular damage might differ among women and men. In particular, little is known about the association between sex hormones and small vessel disease. Therefore, we examined the association of total oestradiol, total testosterone, free-androgen index (FAI), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), and androstenedione levels with micro- and macrovascular diseases. Methods and results This cross-sectional study included 2950 women and 2495 men from the population-based Rotterdam Study. As proxy of microvascular damage, we measured diameters of retinal arterioles and venules. Markers of macrovascular damage included carotid intima-media thickness and carotid plaque, coronary artery calcification (CAC), and peripheral artery disease. Linear and logistic regression models were used and adjusted for age, cardiovascular risk factors, and years since menopause. Associations with microvasculature: In women, total testosterone [mean difference per 1-unit increase in natural-log transformed total testosterone (95% confidence interval, CI): 2.59 (0.08–5.09)] and androstenedione [4.88 (1.82–7.95)] and in men DHEAS [2.80 (0.23–5.37)] and androstenedione [5.83 (2.19–9.46)] were associated with larger venular caliber. Associations with markers of large vessel disease: In women, higher total testosterone [−0.29 (−0.56 to −0.03)], FAI [−0.33 (−0.56 to −0.10)], and androstenedione levels [−0.33 (−0.64 to −0.02)] were associated with lower CAC burden and FAI [odds ratio (95% CI): 0.82 (0.71–0.94)] was associated with lower prevalence of plaque. Conclusion A more androgenic profile was associated with more microvascular damage in both women and men. Among women, however, higher androgen levels were also associated with less macrovascular damage. Our findings suggest that androgens might have distinct effects on the vasculature, depending on the vascular bed and stages of the atherosclerosis process.
Published: 2022

152. Associations of Sex Steroids and Sex Hormone-Binding Globulin with Non-Alcoholic Fatty Liver Disease: A Population-Based Study and Meta-Analysis

Author: Xiaofang Zhang, Yuchan Mou, Elif Aribas, Masoud Amiri, Jana Nano, Wichor M. Bramer, Maryam Kavousi, Robert J. de Knegt, Eralda Asllanaj, Mohsen Ghanbari, Epidemiology, Erasmus MC other, and Gastroenterology & Hepatology
Subjects: Male, Estradiol, Nafld, Gonadal Steroid Hormones, Meta-analysis, Non-alcoholic Fatty Liver Disease, Sex Characteristics, gonadal steroid hormones, non-alcoholic fatty liver disease, NAFLD, sex characteristics, meta-analysis, digestive system diseases, All institutes and research themes of the Radboud University Medical Center, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Sex Hormone-Binding Globulin, Genetics, Humans, Female, Testosterone, Genetics (clinical)
Abstract: Background: Prior studies have reported inconsistent results or less well-explored associations between sex hormones and non-alcoholic fatty liver disease (NAFLD). Here, we aimed to investigate the associations of NAFLD with sex steroids and sex hormone-binding globulin (SHBG) in the population-based study and conduct a comprehensive systematic review and meta-analysis of all published observational studies. Methods: Analyses included 755 men and 1109 women with available data on sex steroids, SHBG, and ultrasound-based NAFLD from the Rotterdam Study. Multivariable regression models were used to examine the associations. Additionally, we searched five databases from inception to 1 April 2022 and performed a systematic review and meta-analysis. Random-effects (DerSimonian-Laird) method was used for meta-analysis, odds ratios (ORs) were calculated for the effect estimate, subgroup and leave-one-out sensitivity analyses were conducted, and meta-regression was performed to explore the pooled statistics with high heterogeneity. Results: In the Rotterdam Study, lower levels of SHBG were associated with NAFLD in both sexes, while lower testosterone was associated with NAFLD only among women. Similarly, the meta-analysis of 16 studies indicated no sex-specific association between SHBG and NAFLD (men: OR = 0.37, 95%CI 0.21–0.53; women: OR = 0.40, 95%CI 0.21–0.60), yet there was a sex-specific association between testosterone and NAFLD (men: OR = 0.59, 95%CI 0.42–0.76; women: OR = 1.06, 95%CI 0.68–1.44). Moreover, men with NAFLD had lower estradiol levels than those without NAFLD. Conclusions: Lower SHBG levels were associated with NAFLD in both sexes, but testosterone levels were associated in a sex-specific manner. In addition, our results showed estradiol with the potential as a protective factor for NAFLD in healthy men.
Published: 2022

153. Association between arterial stiffness/remodeling and new-onset type 2 diabetes mellitus in general population

Author: Fariba Ahmadizar, Kan Wang, Maurits Roos, Maxime Bos, Francesco Mattace- Raso, Maryam Kavousi, Epidemiology, and Internal Medicine
Subjects: Endocrinology, SDG 3 - Good Health and Well-being, Endocrinology, Diabetes and Metabolism, Internal Medicine, General Medicine
Abstract: Objective We studied if largeartery stiffnessis involved in type 2 diabetes pathogenesis. We also investigated the effect of genetic risk for type 2 diabetes in these associations and the causality. Research design and Methods In the prospective population-based Rotterdam Study (n=3,055; mean age, 67.2years), markers of aortic and carotid stiffnesses and measures of arterial remodeling were assessed. Coxproportional hazard regression analysisestimated the associations between arterial stiffness measures with incident type 2 diabetes. We used 403single nucleotide polymorphismsto calculate the genetic risk score (GRS) for type 2 diabetes. We adopted Mendelian randomization (MR) analysis to evaluate the causal associations. Results Over a median follow-up of 14.0years, higher carotid-femoralpulse wave velocity(hazard ratio,1.18; 95%CI: 1.04–1.35), carotid distensibility coefficient (1.17; 1.04–1.32), and carotid intima-media thickness (1.15; 1.01–1.32) were independently associated with incident diabetes. The associations were stronger among individuals with a higher GRS for type 2 diabetes. MR analysis did not support the causality of the observed associations. Conclusions Elevated arterial stiffness is independently associated with incident type 2 diabetes. For most arterial stiffness markers, the associations with incident type 2 diabetes were more robust in individuals with a higher GRS for diabetes.
Published: 2023
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154. Atherosclerotic calcification in major vessel beds in chronic obstructive pulmonary disease: The Rotterdam Study

Author: Guy Brusselle, Bruno H. Stricker, Maryam Kavousi, Daniel Bos, Aad van der Lugt, Meike W. Vernooij, Lies Lahousse, Sara R.A. Wijnant, Epidemiology, Radiology & Nuclear Medicine, Medical Informatics, and Pulmonary Medicine
Subjects: Carotid Artery Diseases, Male, 0301 basic medicine, Arteriosclerosis, Epidemiology, Coronary Artery Disease, 030204 cardiovascular system & hematology, Pulmonary Disease, Chronic Obstructive, Rotterdam Study, 0302 clinical medicine, Risk Factors, Prevalence, Medicine and Health Sciences, Prospective Studies, Chronic, Lung, Computed tomography, Netherlands, Aged, 80 and over, COPD, education.field_of_study, ASSOCIATION, Middle Aged, Intracranial Arteriosclerosis, CAROTID ATHEROSCLEROSIS, Cardiology, Female, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Population, AIR-FLOW LIMITATION, DIAGNOSIS, Risk Assessment, 03 medical and health sciences, FEV1/FVC ratio, CORONARY-ARTERY CALCIUM, Internal medicine, MANAGEMENT, medicine, Humans, Airflow obstruction, Vascular Calcification, education, Aged, business.industry, Odds ratio, medicine.disease, PREVENTION, COMORBIDITIES, respiratory tract diseases, Cross-Sectional Studies, 030104 developmental biology, RISK-FACTORS, Aortic arch calcification, business, Calcification
Abstract: Background and aims: COPD is associated with an increased risk of cardiovascular morbidity and mortality, potentially by mechanisms of atherosclerosis. Insight into location-specific vulnerability to atherosclerosis in COPD, including intracranial arteries, is lacking. We aimed to investigate the relation between COPD and atherosclerosis in multiple vessel beds within a large population-based cohort study. Methods: From 2003 to 2006, a random sample of 2187 elderly participants (mean age, 69.6 +/- 6.8 years; 50.9% female; 11.7% COPD) from the population-based Rotterdam Study underwent computed tomography to quantify atherosclerotic coronary artery calcification (CAC), aortic arch calcification (AAC), extracranial carotid artery calcification (ECAC), and intracranial carotid artery calcification (ICAC). We investigated the association of COPD [ratio of forced expiratory volume in the first second to forced vital capacity (FEV1/FVC) < 70%] with the presence of calcification and with calcification volumes in each vessel bed using logistic and linear regression, with adjustments for cardiovascular risk factors including smoking. Results: The prevalence of CAC, AAC and ECAC was significantly higher in subjects with COPD compared to those without. After adjusting for age and smoking, COPD remained associated with the presence of ECAC (odds ratio 1.46 [95% confidence interval, 1.02-2.07, p = 0.037]). COPD was significantly associated with larger calcification volumes in all four vessel beds in people in whom calcification was present. Conclusions: The results of this study suggest that COPD plays a role in extracranial carotid artery atherosclerosis initiation and systemic atherosclerosis aggravation.
Published: 2019
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155. Liver stiffness not fatty liver disease is associated with atrial fibrillation: The Rotterdam study

Author: Laurens A. van Kleef, Zuolin Lu, M. Arfan Ikram, Natasja M.S. de Groot, Maryam Kavousi, Robert J. de Knegt, Gastroenterology & Hepatology, Epidemiology, and Cardiology
Subjects: Liver Cirrhosis, Male, SDG 3 - Good Health and Well-being, Hepatology, Non-alcoholic Fatty Liver Disease, Atrial Fibrillation, Elasticity Imaging Techniques, Humans, Female, Prospective Studies
Abstract: Background & Aims: Fatty liver disease has become the most prevalent chronic liver disease globally and is linked to cardiovascular disease, including arrhythmias. However, there have been inconsistent reports on the association between fatty liver disease and atrial fibrillation, while the role of liver stiffness in this association remains unclear. Methods: Within the Rotterdam Study, a large prospective ongoing cohort, participants attending the abdominal ultrasound program between 2009-2014 were included. Exclusion criteria were no atrial fibrillation data or >20% missing data across analysis variables. Steatosis was assessed by ultrasound, liver stiffness by transient elastography and atrial fibrillation by 12-lead electrocardiograms. Incident atrial fibrillation was based on medical records and complete until 2014. Logistic and Cox-regression were used to quantify associations between fatty liver disease and atrial fibrillation. Results: We included 5,825 participants (aged 69.5±9.1, 42.9% male), 35.7% had steatosis, liver stiffness measurement was available in 73.3%, and 7.0% had prevalent atrial fibrillation. Steatosis was not associated with prevalent atrial fibrillation in fully adjusted models (odds ratio [OR] 0.80; 95% CI 0.62-1.03), findings were consistent for non-alcoholic or metabolic dysfunction-associated fatty liver disease. Liver stiffness was significantly associated with prevalent atrial fibrillation (OR 1.09 per kPa, 95% CI 1.03-1.16); however, this was only persistent among those without steatosis (OR 1.18 per kPa, 95% CI 1.08-1.29). Lastly, no associations were found between steatosis (hazard ratio 0.88; 95% CI 0.59-1.33; follow-up 2.1 [1.1–3.2] years) and incident atrial fibrillation. Conclusions: Fatty liver disease was not associated with prevalent or incident atrial fibrillation, while liver stiffness was significantly associated with atrial fibrillation, especially among those without steatosis. This association might be driven by venous congestion instead of fibrogenesis, but this awaits further validation. We recommend assessing cardiovascular health in participants with high liver stiffness, especially in the absence of overt liver disease. Clinical trial number: NTR6831. Lay summary: There have been inconsistent reports about the potential links between fatty liver disease and atrial fibrillation (an irregular and often very fast heart rhythm). Herein, we show that liver stiffness (which is a marker of liver fibrosis), but not fatty liver disease, was associated with a higher prevalence of atrial fibrillation. We hypothesis that atrial fibrillation, rather than fibrosis, may be the cause of increased liver stiffness in participants without overt liver disease.
Published: 2021

156. Are we targeting the right population? Application of eligibility criteria of 10 dementia prevention trials to the general population

Author: Silvan Licher, Frank J Wolters, Jelena Pavlović, Maryam Kavousi, Maarten JG Leening, M Kamran Ikram, and M Arfan Ikram
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published: 2021
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157. Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

Author: Maryam Sharafkhah, Emanuel Zitt, Majid Ezzati, Luxia Zhang, Young-Ho Khang, Ellina Rakhimova, Kairit Mikkel, Tiina Vlasoff, Eruke E. Egbagbe, Sidsel Graff-Iversen, Ilona Nenko, Magdalena Klimek, Mathilde Savy, Sanjib Kumar Sharma, Alfonso Siani, Luís Lopes, Vanina Bongard, Gregor Jurak, Jacqueline F. Price, Christina-Paulina Lambrinou, Maria Lc Iurilli, Rainford J. Wilks, Bontha V. Babu, Fereidoun Azizi, Harunobu Nakamura, Marialaura Bonaccio, Angela Döring, Zhenyu Zhang, Naser Ahmadi, Jolanta Słowikowska-Hilczer, Ana Paula Carlos Cândido, Clive Osmond, Thirunavukkarasu Sathish, Robert J. Adams, Themistoklis Tzotzas, Reina Engle-Stone, Atul Trivedi, Shoichiro Tsugane, Niels Møller, Jorge Bezerra, Dénes Molnár, Muhammad Fadhli Mohd Yusoff, Badreya Al-Lahou, J. Jaime Miranda, Bahram Mohajer, Sigmund A. Anderssen, Lital Keinan Boker, Eero Kajantie, Martin Gulliford, Maties Torrent, Sumit Bharadwaj, Toshiharu Ninomiya, Zbigniew Gaciong, Nayu Ikeda, Li Juan Wu, Adrian Richter, Licia Iacoviello, Marc J. Gunter, Wenbin Wei, Norsyamlina Che Abdul Rahim, Eman Aly, Ambady Ramachandran, Nils Lehmann, Soile E. Puhakka, Giovanni Veronesi, Hongsheng Bi, Eiji Oda, Jia Li Duan, Per Tynelius, José María Huerta, Janne Schurmann Tolstrup, Rodrigo M. Carrillo-Larco, Rosangela Fernandes Lucena Batista, Victoria E Soto-Rojas, Hanno Ulmer, Shukri F. Mohamed, Anthony Kafatos, Suyeon Park, Mohsen Ibrahim, Hamed Pouraram, Bin Zhou, May Soe Aung, Lars Bo Andersen, Erfan Ghasemi, René Charles Sylva, Himanshu K. Chaturvedi, Luc Dauchet, Ahmad Ali Zainuddin, Angela Chetrit, Dan Zhu, Valérie Deschamps, Ko Ko Zaw, Peter Vollenweider, Tomas Vega, Yves Martin-Prével, Mahfuzar Rahman, Dorja Vočanec, Roman Topor-Madry, Vinay Nangia, Herculina S. Kruger, Asher Fawwad, Emily Sonestedt, Elena Pahomova, Aleksander Giwercman, Elżbieta Dziankowska-Zaborszczyk, Cecilia Björkelund, Tatjana Hejgaard, Maria Puiu, Maria Benedetta Donati, Andrew Wong, Carlos P. Boissonnet, Santosh K. Bhargava, Patrick Kolsteren, Dermot O'Reilly, Bahareh Kheiri, Wolfgang Kratzer, Susanne R. de Rooij, H. Bas Bueno-de-Mesquita, Günther Fink, José R. Banegas, Michele Monroy-Valle, Drude Molbo, Mahmudur Rahman, Hynek Pikhart, Rafael N. Pichardo, Massimo Salvetti, Hui Cai, Sarah Filippi, Georg Posch, Hung-Kwan So, Yonghua Hu, Katsuyasu Kouda, Joana Carvalho, Gailute Bernotiene, Hannu Uusitalo, Thein Thein Htay, Felix Kaducu, Maigeng Zhou, Lars Ängquist, Thi Tuyet-Hanh Tran, Charles Lunogelo, Michel Joffres, Sabina Zambon, Ronald D. Gregor, Vayia Rarra, Seyed Mohammad Hashemi-Shahri, Loreto Santa Marina, Galina Obreja, Rudolf Kaaks, Aya Mostafa, Maria do Carmo Franco, Beata Gurzkowska, Chien-Jen Chen, Marie Moitry, Nizal Sarrafzadegan, Xiangjun Wang, Diego Giulliano Destro Christofaro, Imperia Brajkovich, Fangfang Chen, Francesco Panza, Ling Yang, Holly E. Syddall, Cecily Kelleher, Michael Tornaritis, Ningli Wang, Lutgarde Thijs, Marjolein Visser, Angelika Schaffrath Rosario, María José Tormo, Jostein Steene-Johannessen, Norbert Amougou, Emmanuella Magriplis, Mar Alvarez-Pedrerol, Jingli Gao, Stig E. Bojesen, Giuseppe Grosso, Seongjun Ha, Lauren Lissner, Mikhail Benet, Anastasia Markaki, Sanjay Rampal, Antônio Augusto Moura da Silva, Maria Lorenza Muiesan, Angelique Chan, Yvonne T. van der Schouw, Annamari Lundqvist, Philippe Amouyel, Kristyna Zejglicova, Charalambos Hadjigeorgiou, João Breda, Jørgen Meisfjord, Fatima Zahra Laamiri, Carl Lachat, Kai-Uwe Saum, Vilma Irazola, Leng Huat Foo, Óscar Lopes, Dickman Gareta, Flavio Nervi, Imre Janszky, Ruzena Kubinova, Terho Lehtimäki, Mario V. Capanzana, Moyses Szklo, Ramfis Nieto-Martínez, Viswanathan Mohan, Shuohua Chen, Arvind Pandey, Luigi Palmieri, Roya Kelishadi, Srinivasan Kannan, Jie Mi, Robert Beaglehole, Liliana Dacica, Jyrki K. Virtanen, Mohan Deepa, Peter Ueda, Isti Ilmiati Fujiati, Hermann Pohlabeln, Morten Sodemann, Jytte Halkjær, Zbigniew Kułaga, Sophie Visvikis-Siest, Farshad Farzadfar, Mohsen Azimi-Nezhad, Henry Völzke, Karolina Milkowska, Zahra Mohammadi, Belgin Ünal, Magda Gasull, George S. Stergiou, Marshall K. Tulloch-Reid, Seppo Koskinen, James E. Bennett, Marcela González-Gross, Virginija Dulskiene, Idris Guessous, Assembekov Batyrbek, Kamarul Imran Musa, Jeannette Lee, Josep Redon, Bihungum Bista, Luisa M Macieira, Johan Sundström, Andres Metspalu, Lariane M Ono, Flora A. Ukoli, Salar Rahimikazerooni, Andrea Gualtieri, Trevor S. Ferguson, Félicité Tchibindat, Eliza Cinteza, Ha Tp Do, Tajana Zeljkovic Vrkic, Tuyen D Le, Alison J. Hayes, Abdul Basit, Chandini Nekkantti, Teresa Norat, Eunice Ugel, Gulmira Aitmurzaeva, Mariachiara Di Cesare, Abdul Hamid Zargar, Vincenzo Solfrizzi, Garry L. Jennings, Aline Meirhaeghe, Kaare Christensen, Päivi Mäki, Xu Lin, Ali Esmaeili, Joanna Baran, Aneta Grajda, Renata Cifkova, Alexandre C. Pereira, Martin Bobak, Iuliia A Rusakova, Keiu Nelis, Damian K Francis, Guansheng Ma, Axel C. Carlsson, Alejandro Diaz, Alireza Ansari-Moghaddam, N Capkova, Zumin Shi, Maria Turley, Imelda A. Agdeppa, Helena I. S. Nogueira, Marcia Scazufca, Katharina Maruszczak, Natascia Rinaldo, Paulo A. Lotufo, Nuno Lunet, Thor Aspelund, Caroline H.D. Fall, Antonio Cabrera de León, Ahmad Faudzi Yusoff, Holger Theobald, Beatriz D'Agord Schaan, Pedro Marques-Vidal, William A. Neal, Mihai Gafencu, Tandi E. Matsha, Ana B. Crujeiras, Ahmad Reza Dorosty, Alain Morejon, Weili Yan, Dominique Hange, Bekbolat Zholdin, Frédéric Gottrand, Jorge Mota, Jana Námešná, Stevo Popovic, Louise Eriksen, Line Lund Kårhus, Cihangir Erem, Juergen Breckenkamp, Mathilde Kersting, Yi Song, Martin McKee, Aleksandra Gomula, Rafaela Rosário, Enzo Manzato, S. Goya Wannamethee, Sounnia Mediene Benchekor, Azim Nejatizadeh, Krishna Kumar Aryal, Juan P. González-Rivas, Vedrana Sember, Stephen T. McGarvey, Jukka T. Salonen, Patrick Pasquet, Patricia Varona-Pérez, Amelia C. Crampin, Ramin Heshmat, Violeta Iotova, Juvenal Soares Dias-da-Costa, Oye Gureje, Aletta E. Schutte, João Luiz Bastos, Anelise Reis Gaya, Konrad Jamrozik, Dalia Luksiene, Amina Barkat, Maria Paula Santos, José Camolas, Azli Baharudin, Diego Vanuzzo, Doris Stöckl, Rosalynn Siantar, Jouko Saramies, Albertino Damasceno, Davood Khalili, Simona Bo, Martina Müller-Nurasyid, Dominique Cottel, Markku Peltonen, Fikru Tullu, Ana Isabel Rito, Angélica Ochoa-Avilés, Annette J. Dobson, Christopher T. Cowell, Charumathi Sabanayagam, Rildo de Souza Wanderley Júnior, Oanh T. H. Trinh, Farahnaz Joukar, Mostafa K. Mohamed, Mostafa Qorbani, Jeongseon Kim, Helmut Schröder, Machi Suka, Natasja M. van Schoor, Jussi Kauhanen, Teresa Haugsgjerd, Goodarz Danaei, M. Fernanda Lima-Costa, Yong Tao, Elisabetta L. Romeo, Grazyna Jasienska, Victor Guillermo Sequera, Kazem Mohammad, Yanina Zócalo, Fernanda Cunha Soares, Jianfeng Wu, Mohammad Esmaeel Motlagh, María Elena Díaz-Sánchez, Monika Zuziak, Eldridge Ferrer, Anette Varbo, Leila Beltrami Moreira, Jeremy M. Jacobs, Kenneth James, Elena Sacchini, Pascal Bovet, Mahboubeh Parsaeian, Tania Lopez, Ya Xing Wang, Wojciech Drygas, Jody C Miller, Svetlana A. Shalnova, Maria Elisa Zapata, Chung T Nguyen, Nimmathota Arlappa, Edwige Landais, Thorkild I. A. Sørensen, Jeannette Klimont, Amirabbas Momenan, Erik J. Timmermans, Mari-Liis Tammesoo, Jost B. Jonas, Stefania Toselli, Maria Teresa Anselmo Olinto, Bahman Cheraghian, Kouamelan Doua, Esteban Carmuega, Marjeta Mišigoj-Duraković, Bo Werner, M. Arfan Ikram, Breige A. McNulty, Christa Meisinger, Clara Homs, Namuna Shrestha, Alina Kerimkulova, Youcef Laid, Claes Ohlsson, Alicia Matijasevich, Alison J Price, Ala'a Alkerwi, Kristine H. Allin, Lorenza Pilotto, Mohannad Al Nsour, Ingunn Holden Bergh, Marianna Noale, Heba Fouad, Vilnis Dzerve, Novie O. Younger-Coleman, Peter Willeit, Andrea R. V. R. Horimoto, Freda Pitakaka, Habiba Ben Romdhane, Savvas C. Savva, Rajeev Gupta, Jennifer Servais, Cristina Padez, Sarah P. Garnett, Maria del Cristo Rodriguez-Perez, Michala Lustigová, Tien Yin Wong, Rosa Haghshenas, Jonathan Giovannelli, Christina Howitt, Marleen E. Hendriks, Fadia AlBuhairan, Huashuai Chen, Gretchen A Stevens, Luís B. Sardinha, David Goltzman, Jenny M. Kindblom, Karina Mary de Paiva, Yousef Khader, Eric Monterrubio-Flores, Rajendra Pradeepa, Yi-Ting Lin, Martin Neovius, Juan Francisco Miquel, Ellis Owusu-Dabo, Anil Poudyal, Marzieh Katibeh, Tanja Stocks, Veronica Mocanu, Ulla Roggenbuck, Robespierre Ribeiro, Gabriele Eiben, Mary Simon, Christine Cameron, Hamid Hakimi, Kamel Ajlouni, Jakub Stokwiszewski, Iulia Jurca Simina, Pietro Amedeo Modesti, Frederick C. W. Wu, Peter Kristensen, Charles Mondo, Felix Gutzwiller, Mariana Sbaraini, Martijn Huisman, Betina H. Thuesen, Queenie Chan, Antonisamy Belavendra, Artur Mazur, Ulf Ekelund, Laura A. Rodríguez-Villamizar, Marcos André Moura-dos-Santos, Jean Ferrières, Farhad Zamani, Shina Avi, Yves Kameli, Luis Paulo Gomes Mascarenhas, Aluísio J D Barros, Thomas Meinertz Dantoft, Hossein Poustchi, Farid Najafi, Giovanni de Gaetano, Azaliia M Tuliakova, Vera Lanska, Tint Swe Latt, Matthias Bopp, Abbas Rezaianzadeh, Rod Jackson, Johan Van der Heyden, Reecha Sofat, Koen Van Herck, Allan G. Hill, Con Burns, Emanuela Pettenuzzo, Ming-Dong Wang, Stela McLachlan, Ulrike Gehring, Ranko Stevanovic, Nagalla Balakrishna, Lekhraj Rampal, Marjolijn C. E. Bragt, Saeid Eslami, Napoleón Pérez-Farinós, G. K. Mini, Viktoria Anna Kovacs, Rosemarie Martin, Nahla Hwalla, Wei Zheng, Hoang Van Minh, Edward D Janus, Laetitia Huiart, Farhad Pourfarzi, Sudha Ramachandra Rao, Fred Paccaud, Marcia Makdisse, Aye Aye Sein, Enrique Gutiérrez-González, Yang Yang, Anneke Blokstra, Henrike Galenkamp, Jaume Marrugat, Nazan Yardim, Wan Nazaimoon Wan Mohamud, Jesús Ibarluzea, Julio Zuñiga Cisneros, Laura Lauria, Argyro Karakosta, Dragana P Jovic, Jun Hata, Elio Riboli, Piotr Bandosz, Xun Tang, Parvina Mukhtorova, Jean Dallongeville, Jean-Bernard Ruidavets, Anne Tjønneland, Guillermo Frontera, Rahul Malhotra, Thomas Ferrao, Aleksandra Piwońska, Dusan Grafnetter, Mette Rasmussen, Daniel Weghuber, Sherali Rakhmatulloev, Martine Vrijheid, Johann Willeit, Motahareh Kheradmand, Małgorzata Mossakowska, Lechaba Tshepo, Dongfeng Gu, Hyeon Chang Kim, Vilmundur Gudnason, Maria Forsner, Peter Bjerregaard, Leon A. Simons, Rachael McLean, Japhet Killewo, Ramón Suárez-Medina, Y Nikitin, Eng Joo Tan, Jean Claude Mbanya, Aroor Bhagyalaxmi, Renata Kuciene, Kairat Davletov, Jose Eugenio Lozano, Afshin Ostovar, Niloofar Peykari, Guy De Backer, Soheir H Ahmed, Nicholas J. Wareham, Sai Yin Ho, Constanta Huidumac Petrescu, Maria Hassapidou, Iris Pigeot, Myriam Galfo, Susana Cararo Confortin, Blanca Sandra Ruiz-Betancourt, W. M. Monique Verschuren, Catterina Ferreccio, Fabio Galvano, Leila Houti, Daniel Bia, Annika Rosengren, Marcin Rutkowski, Biruta Velika, Joana Araújo, Fernando Rigo, Angela Spinelli, Scott B. McLean, Shirin Djalalinia, Marie Kunešová, Boban Mugoša, Sania Nishtar, Mangesh S. Pednekar, Shahla AlDhukair, Helle-Mai Loit, Antonis Zampelas, Altan Onat, Maciej Banach, Shohreh Naderimagham, Hajer Aounallah-Skhiri, Maja Bæksgaard Jørgensen, Yin Guo, Ewelina Czenczek-Lewandowska, Parasmani Dasgupta, Elvis Oa Wambiya, Inge Huybrechts, Raimund Erbel, Jari Jokelainen, Ana P. Ortiz, Stefan Kiechl, Emmanuel Cohen, Caleb Ochimana, Shynar Abdrakhmanova, Laura Censi, Iqbal Bata, Geetha R Menon, Snehalatha Chamukuttan, Pedro Plans-Rubio, Domenico Palli, Ana Azevedo, Slawomir Koziel, Benoît Salanave, Parinaz Mehdipour, Shu Ti Chiou, Lela Sturua, Lubica Ticha, Felipe Vogt Cureau, Jin Soo Moon, Ming-Hui Zhao, Urho M. Kujala, Nathalie Michels, Ertugrul Celikcan, Jaakko Tuomilehto, Judith Benedics, Tobias F. Rinke de Wit, Agnès Le Port, Reza Homayounfar, Andrea Rodriguez-Martinez, Tai Hing Lam, Yn-Tz Sung, Jürgen König, Kodavanti Mallikharjuna Rao, Hazzaa M. Al-Hazzaa, Karen Morgan, Bogdan Wojtyniak, Cynthia M. Pérez, Ilse Khouw, Manoli Garcia-de-la-Hera, Dong Wook Shin, Genc Burazeri, Ausra Petrauskiene, Charles Sossa Jérome, Kenisha Russell Jonsson, José Boggia, Daniela Galeone, Alice Bonilla-Vargas, Han Cg Kemper, Rahman Shiri, Stefaan Demarest, Else Karin Grøholt, San-Lin You, Adelheid Weber, Juha Auvinen, Aida Pilav, Sibel Gogen, Suzanne N Morin, Wan Mohamad Wan Bebakar, Viviane Cunha Cardoso, Kavumpurathu Raman Thankappan, Hana Zamrazilová, Frank Claessens, Karien Stronks, Helen Gonçalves, Tahir Aris, Luis Revilla, Sérgio Viana Peixoto, Zhamilya Battakova, Jing Liu, Eliza Markidou Ioannidou, Leticia Hernandez Cadena, Priscilla Duboz, Sandjaja, Tiina Laatikainen, Rafel Ramos, Sareh Eghtesad, Judith Simons, Orn Olafsson, E. Shyong Tai, Louise A. Baur, Nihal Thomas, Aung Soe Htet, Bente Sparboe-Nilsen, Paul Elliott, Soon-Woo Park, Angel R. Gonzalez, Ying-Wei Wang, Rob M. van Dam, Ryutaro Ohtsuka, Ludmila Sevcikova, Suhaila Abdul Ghaffar, Lynell V Maniego, Fariborz Mansour-Ghanaei, Maria Dorobantu, Giovanni Viegi, Xiaoguang Yang, Honor Bixby, Prakash C. Gupta, Ofra Kalter-Leibovici, Eugene Sobngwi, Ričardas Radišauskas, Jurate Medzioniene, Roy A Wong-McClure, Kim F. Michaelsen, Antonia Trichopoulou, Tania Tello, Francesco Branca, Johanna Gunnlaugsdottir, Els Clays, Wei-Yen Lim, Suzanne C. Ho, Toomas Veidebaum, Rebecca Goldsmith, Margot González-León, Matthias Nauck, Alibek Mereke, Marta Buoncristiano, Jakob Tarp, Rosalba Rojas-Martínez, Maya Tanrygulyyeva, Reza Malekzadeh, Abdonas Tamosiunas, Dimitrios Poulimeneas, Pedro Ordunez, Isabelle Herter-Aeberli, Khanh Le Nguyen Bao, Anne Juolevi, Vassilis Zafiropulos, Emanuela Gualdi-Russo, Jordi Sunyer, Manu Raj, Chaoqiang Jiang, Sofia Malyutina, Efthymios Kapantais, Maria Lazo-Porras, Maung Maung Than Htike, Michael Hobbs, Ranjit Mohan Anjana, Merike Liivak, Johan G. Eriksson, Margarita Samoutian, Andreia N. Pizarro, Mohammed Rasoul Tarawneh, Jean Woo, Kaspar Staub, Maria Teresa Menzano, Mojtaba Farjam, Adroaldo Cesar Araujo Gaya, Mohammad El-khateeb, Zulfiqar A Bhutta, Mukharram M. Bikbov, Hsien-Ho Lin, Oscar Noboa, Thomas Waldhör, Garry Brian, Simona Costanzo, Frank Tanser, Nor Azwany Yaacob, Michelle Cilia, Ivo Rakovac, Bill Stavreski, Ioannis Pagkalos, Ivan Pećin, Carlo M. Barbagallo, Abla M. Sibai, Yuna He, Matsuda Fumihiko, Bharathi Viswanathan, Ali Reza Safarpour, Wei Cheng Lo, Abdullatif Husseini, Jiang He, Liv Elin Torheim, Nipa Rojroongwasinkul, Aicha Soumare, Astrid Petersmann, Tomasz Grodzicki, Davide Noto, Panayiotis K. Yiallouros, Kelias P. Msyamboza, William R. Tebar, Yingfeng Zheng, Eha Nurk, Bhawesh Koirala, Ana Jelakovic, Suhad Bahijri, Freja B Kampmann, Qi Sheng You, Marika Ferrari, María-Elena González-Villalpando, Aline Wagner, Olfa Saidi, Anwar Batieha, Eduardo Capuano, Coimbatore Subramaniam Shanthirani, Dong Wook Kim, Albina A Fakhretdinova, Tom Wilsgaard, Maria Avdicova, Moesijanti Soekatri, Chiara Donfrancesco, Salim Mohanna, Paola Russo, Uruwan Yamborisut, Rafael dos Santos Henrique, Martin Nankap, Allan Linneberg, Khairil Si-Ramlee, Kirsten Mehlig, Christina Mavrogianni, Raluca Pop, Lèlita Santos, Graziella Bruno, Valentina Peterkova, Iná S. Santos, Georg Lappas, Alberto Palloni, Malay K. Mridha, Andrzej Pajak, Marta García-Solano, Stefaan De Henauw, Daniel Ferrante, Rute Santos, Anders Grøntved, Lucjan Szponar, Mihaela Vladulescu, Chien-An Sun, Jan A. Staessen, Paula Duarte de Oliveira, Norazizah Ibrahim Wong, Maria Nordendahl, Elaine M. Dennison, Jeonghee Lee, Diego Salmerón, Ida Maria Schmidt, Gao Pei, Noushin Mohammadifard, Igor Spiroski, Fernando Rodríguez-Artalejo, Xu Ma, Elin Pettersen Sørgjerd, Valéria Regecová, Cláudia S. Minderico, Johanna A. Otero, Jamila Abubakar Garba, Vesselka Duleva, Rui Ornelas, Ilpo Huhtaniemi, Cesar G. Victora, Lijuan Liu, Rody G. Sy, Mahmood Moosazadeh, Ali Ahmadi, Antonio Pedro Graça, Natalia Nowak-Szczepanska, Miao Li Chee, Michael Sjöström, Charles Agyemang, Shiqi Zhen, Xiu-Hua Guo, Pawel Kurjata, Jardena J. Puder, Mehrdad Azmin, Neil Murphy, Kaosar Afsana, Alireza Sadjadi, Johanna M. Geleijnse, Prashant Mathur, Elysée Claude Bika Lele, Raphael Mendes Ritti-Dias, Yannis Manios, Majid Shirani, Rosemary B. Duda, Liis Nelis, Jurate Klumbiene, Zhengming Chen, Wichai Aekplakorn, Alun Evans, Andrzej Wiecek, Lars Lind, Denise Eldemire-Shearer, Bernardo L. Horta, Macia Enguerran, Seyed Rasoul Zakavi, Daniel Fernández-Bergés, Kumiko Ohara, Ursula Kiechl-Kohlendorfer, Hermann Brenner, Przemyslaw Slusarczyk, Espen Bjertness, Jutta Stieber, Augusto Di Castelnuovo, Joel G. R. Roy, Aryeh D. Stein, Ruth Frikke-Schmidt, Vera Musil, Amaneh Shayanrad, Marcel Goldberg, Ramon O. Jimenez, Mohammad Reza Fattahi, Jolanda Hyska, Amir Houshang Mehrparvar, Elin Kolle, Mohamed Bamoshmoosh, Michelle Holdsworth, Felipe F. Casanueva, Børge G. Nordestgaard, Niels Wedderkopp, Eva Corpeleijn, Elias F. Gudmundsson, Antonio Mistretta, Daniel Lemogoum, Larissa Pruner Marques, Slavica Sović, Olli T. Raitakari, Marco Aurélio Peres, Alexandra Cucu, Gregorio Varela-Moreiras, Janine Clarke, Andrea Gazzinelli, Mieczysław Litwin, Sara Schramm, Xenophon Theodoridis, Harshpal Singh Sachdev, Mohammad Reza Mirjalili, Dimitrios Papandreou, Peter T. Katzmarzyk, Benjamin Acosta-Cazares, Ben Schöttker, Prabhdeep Kaur, Norlaila Mustafa, Shariq Rashid Masoodi, Sadaf G. Sepanlou, Adolfo Rubinstein, Francis Delpeuch, Julianne Williams, Abbas Dehghan, Leanne M. Riley, Heloisa Bettiol, Gabriele Nagel, Ellisiv B. Mathiesen, Ekaterina Stoyanova, Alisha N. Wade, Zhamyila Usupova, Arnaud Chiolero, Oonagh Markey, Jacqueline Ramke, Elena Bogova, Niveen M E Abu-Rmeileh, Nguyen D Nguyen, Tomasz Zdrojewski, Marjo-Riitta Järvelin, Jose Sanchez-Abanto, Rômulo Araújo Fernandes, Lourdes Ribas-Barba, Nalan Uysal, Mohamad Hasnan Ahmad, Krista Fischer, Maria Wany Louzada Strufaldi, Ramiro Guerrero, Farnam Mohebi, Tran Quoc Bao, Flávio Danni Fuchs, Salim Berkinbayev, Enisa Kujundzic, Sari Voutilainen, Farzad Hadaegh, Robert Lundqvist, Saeid Safiri, Iraj Mohebbi, George Luiz Lins Machado-Coelho, Annette Peters, Gonzalo Valdivia, Magdalena Korzycka, Rajiv T Erasmus, Masanori Iwasaki, Charmaine A. Duante, Sheikh Mohammed Shariful Islam, Quang Ngoc La, Ricky Eddie, Petra Rust, Daniela Rodrigues, Dirk De Bacquer, Karen Sparrenberger, Agneta Sjöberg, Thet Thet Mu, Katarzyna Dereń, Cora L. Craig, Jorge Motta, Janina Petkeviciene, Boyd Swinburn, Paibul Suriyawongpaisal, Visnja Djordjic, Ramón Alberto Rascón-Pacheco, Pradeep Joshi, Daan Kromhout, Marius B. Bjertness, Stefano Marventano, Juel Jarani, Alireza Khosravi, Eva Martos, David De Ridder, Lizzy M. Brewster, Nico Dragano, Liam Smeeth, Kenji Shibuya, Emma Ruiz Moreno, Hashem Jaddou, Grzegorz Sobek, Dimitrios Trichopoulos, Marvin Cervantes-Loaiza, Abu Am Hanif, Elaine M. Murtagh, Carlos A. Aguilar-Salinas, Graziella D'Arrigo, Kyungwon Oh, Heiner Boeing, Regina Heidinger-Felso, André Luiz Sena Guimarães, Balkish M. Naidu, Avula Laxmaiah, Ana M. B. Menezes, Marie Eliasen, Francesco Pistelli, Yuan He, Dusko Bjelica, José A. Casajús, Guang Ning, Lutgart Braeckman, Dirk Vanderschueren, Jochanan Stessman, Ivana Radic, Yi Zeng, Hans Concin, Damaskini Valvi, Sari Hantunen, Catherine Kyobutungi, Diego Augusto Santos Silva, Wenhua Zhao, Sok King Ong, Anne W. Taylor, Iraj Nabipour, Justyna Godos, Cyrus Cooper, Mattias Johansson, Samuel C. Dumith, Magdalena Muc, Sabine Schipf, Idowu O Senbanjo, Jim Mann, Rajaa Al-Raddadi, Yih Chung Tham, Kay-Tee Khaw, Joseph Cacciottolo, Ana Henriques, Sahar Saeedi Moghaddam, Reza Mohammadpourhodki, Bernhard O. Boehm, Songhomitra Panda-Jonas, Iveta Pudule, Elisabete Ramos, Lacramioara Aurelia Brinduse, Paul H. Lee, Terence W O'Neill, Javad Aghazadeh-Attari, Margus Punab, Bojan Jelaković, Camilla T. Damsgaard, Takafumi Ishida, Ekaterina Chikova-Iscener, Mirjam M. Heinen, Tazeen H. Jafar, Semánová Csilla, Constance Schultsz, Santiago F. Gomez, Raija Korpelainen, Edward W. Gregg, Laura Gutierrez, Pierre Traissac, Victor M. Herrera, Aristides M. Machado-Rodrigues, Fatemeh Malekzadeh, Shouling Wu, Jennifer L. Baker, Clicerio González-Villalpando, Eleonora d'Orsi, Irene G. M. van Valkengoed, Anna Fijałkowska, Wen-Harn Pan, Gregor Starc, Meghnath Dhimal, Murat Topbaş, George Moschonis, Robert Eggertsen, Abdullah Alkandari, Quang Ngoc Nguyen, Janette Walton, Elnaz Faramarzi, Saeed Dastgiri, Lien Braeckevelt, Nasheeta Peer, Radka Taxová Braunerová, Mohamed M. Ali, Steiner Krokstad, Harald Geiger, Morteza Shamshirgaran, Lela Shengelia, María Ángeles Dal Re Saavedra, Silvana Donoso, Khem Bahadur Karki, Timothy J. Key, Maria G. Grammatikopoulou, Susana Vale, Felix K. Assah, Juan A Rivera, Peter H. Whincup, Oana-Florentina Gheorghe-Fronea, Cassiano Ricardo Rech, Paul Ferdinand M. Reganit, Rachakulla Hari Kumar, Jaakko Mursu, Luis A. Moreno, Glen Gironella, Jelena Kos, Tilema Cama, Haakon E. Meyer, Jun Ma, Raphael E. Arku, Ziad Abdeen, Dianna J. Magliano, Jitendra Jonnagaddala, Konstantinos Gkiouras, Paola Nardone, Alberto Barceló, Tomi-Pekka Tuomainen, Francesco Gianfagna, Stefania Maggi, Mohammad Hossein Somi, Behrooz Hamzeh, Miquel Porta, Vesna Jureša, Alexander D. Deev, David Faeh, Antonio Bernabe-Ortiz, Sirkka Keinänen-Kiukaanniemi, Ian Hambleton, Stefan Savin, Andre Pascal Kengne, R. Krishna Kumar, Kurt Widhalm, Marco M Ferrario, Parisa Amiri, Anjani Kumar Jha, Thamara Hubler Figueiró, Jana Kratenova, Claudia M. Hormiga, Maria Tsigga, Zivka Dika, Indrapal I. Meshram, Ei Ei K. Nang, Ian Rouse, Rusidah Selamat, Paul Korrovits, Grethe S. Tell, Julie Taylor, Anabela Mota-Pinto, Paolo Vineis, Kotsedi D Monyeki, Khuong Quynh Long, Frank J Rühli, Shelly R. McFarlane, Sara Santos Sanz, Edyta Łuszczki, Maria G. Stathopoulou, Tara Coppinger, Karin De Ridder, Lucie Viet, Anna Bugge, Mehdi Yaseri, Safiah Md Yusof, Sandra C. Fuchs, Muhammad Islam, Irfan Nuhoglu, Rui Providência, Bernard Maire, Leandra Abarca-Gómez, Sinead Brophy, Maria Ruiz-Castell, Daniela Pierannunzio, Cristina Taddei, Gowri Mahasampath, Gustavo Velasquez-Melendez, Hanna Tolonen, Sudhir Kowlessur, Bagher Larijani, Laura Torres-Collado, Susi Kriemler, Ali Akbar Shayesteh, Cynthia Robitaille, Jorge Escobedo-de la Peña, Yufang Bi, Chinh Nguyen Huu, Line Tang Møllehave, Vincent Jr DeGennaro, Noor Ani Ahmad, Anar Dushpanova, Agustinus Soemantri, Susana Sans, Ionela Pascanu, Gwenaëlle Le Coroller, Inger Ariansen, Kodanda R Kanala, Gert B. M. Mensink, Abhijit Sen, Sergej M. Ostojic, Hanan F. Abdul Rahim, Hélène Delisle, Francisco J. Félix-Redondo, Yadlapalli S. Kusuma, Michael Knoflach, Moein Yoosefi, Tanja G. M. Vrijkotte, Wolfgang Ahrens, Osvaldo Santos, Bethlehem D. Solomon, Erik Lykke Mortensen, Nikhil D. 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Chan School of Public Health, Middlesex University [London], Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Montpellier Interdisciplinary center on Sustainable Agri-food systems (Social and nutritional sciences) (UMR MoISA), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Centre International de Hautes Etudes Agronomiques Méditerranéennes - Institut Agronomique Méditerranéen de Montpellier (CIHEAM-IAMM), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Wellcome TrustEuropean Commission, Clinical Developmental Psychology, APH - Mental Health, Sociology, The Social Context of Aging (SoCA), Nutrition and Health, Iurilli, Maria LC [0000-0003-0409-1635], Zhou, Bin [0000-0002-1741-8628], Ezzati, Majid [0000-0002-2109-8081], Apollo - University of Cambridge Repository, Epidemiology and Data Science, APH - Aging & Later Life, APH - Societal Participation & Health, Public and occupational health, APH - Health Behaviors & Chronic Diseases, VU University medical center, APH 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Ltd, Orebro University, University of London, Universitas Indonesia, Institute of Food and Nutrition Development of Ministry of Agriculture and Rural Affairs, Children’s Hospital of Fudan University, University of Cyprus, Niigata University, International Medical University, Iran University of Medical Sciences, Center for Diabetes and Endocrine Care, Peking University First Hospital, Jiangsu Provincial Center for Disease Control and Prevention, Sun Yat-sen University, West Kazakhstan Medical University, Inner Mongolia Medical University, University of Ghana, Maria Lc Iurilli , Bin Zhou , James E Bennett , Rodrigo M Carrillo-Larco , Marisa K Sophiea , Andrea Rodriguez-Martinez , Honor Bixby , Bethlehem D Solomon , Cristina Taddei , Goodarz Danaei , Mariachiara Di Cesare , Gretchen A Stevens , Leanne M Riley , Stefan Savin , Melanie J Cowan , Pascal Bovet , Albertino Damasceno , Adela Chirita-Emandi , Alison J Hayes , Nayu Ikeda , Rod T Jackson , Young-Ho Khang , Avula Laxmaiah , Jing 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Jelena Kos , Seppo Koskinen , Katsuyasu Kouda , Viktoria A Kovacs , Sudhir Kowlessur , Slawomir Koziel , Jana Kratenova , Wolfgang Kratzer , Susi Kriemler , Peter Lund Kristensen , Steinar Krokstad , Daan Kromhout , Herculina S Kruger , Ruzena Kubinova , Renata Kuciene , Urho M Kujala , Enisa Kujundzic , Zbigniew Kulaga , R Krishna Kumar , Marie Kunešová , Pawel Kurjata , Yadlapalli S Kusuma , Kari Kuulasmaa , Catherine Kyobutungi , Quang Ngoc La , Fatima Zahra Laamiri , Tiina Laatikainen , Carl Lachat , Youcef Laid , Tai Hing Lam , Christina-Paulina Lambrinou , Edwige Landais , Vera Lanska , Georg Lappas , Bagher Larijani , Tint Swe Latt , Laura Lauria , Maria Lazo-Porras , Gwenaëlle Le Coroller , Khanh Le Nguyen Bao , Agnès Le Port , Tuyen D Le , Jeannette Lee , Jeonghee Lee , Paul H Lee , Nils Lehmann , Terho Lehtimäki , Daniel Lemogoum , Naomi S Levitt , Yanping Li , Merike Liivak , Christa L Lilly , Wei-Yen Lim , M Fernanda Lima-Costa , Hsien-Ho Lin , Xu Lin , Yi-Ting Lin , Lars 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Stronks, Karien, Strufaldi, Maria Wany, Sturua, Lela, Suárez-Medina, Ramón, Suka, Machi, Sun, Chien-An, Sundström, Johan, Sung, Yn-Tz, Sunyer, Jordi, Suriyawongpaisal, Paibul, Swinburn, Boyd A, Sy, Rody G, Syddall, Holly E, Sylva, René Charle, Szklo, Moyse, Szponar, Lucjan, Tai, E Shyong, Tammesoo, Mari-Lii, Tamosiunas, Abdona, Tan, Eng Joo, Tang, Xun, Tanrygulyyeva, Maya, Tanser, Frank, Tao, Yong, Tarawneh, Mohammed Rasoul, Tarp, Jakob, Tarqui-Mamani, Carolina B, Braunerová, Radka Taxová, Taylor, Anne, Taylor, Julie, Tchibindat, Félicité, Tebar, William R, Tell, Grethe S, Tello, Tania, Tham, Yih Chung, Thankappan, KR, Theobald, Holger, Theodoridis, Xenophon, Thijs, Lutgarde, Thomas, Nihal, Thuesen, Betina H, Tichá, Lubica, Timmermans, Erik J, Tjonneland, Anne, Tolonen, Hanna K, Tolstrup, Janne S, Topbas, Murat, Topór-Madry, Roman, Torheim, Liv Elin, Tormo, María José, Tornaritis, Michael J, Torrent, Matie, Torres-Collado, Laura, Toselli, Stefania, Touloumi, Giota, Traissac, Pierre, Tran, Thi Tuyet-Hanh, Trichopoulos, Dimitrio, Trichopoulou, Antonia, Trinh, Oanh TH, Trivedi, Atul, Tshepo, Lechaba, Tsigga, Maria, Tsugane, Shoichiro, Tuliakova, Azaliia M, Tulloch-Reid, Marshall K, Tullu, Fikru, Tuomainen, Tomi-Pekka, Tuomilehto, Jaakko, Turley, Maria L, Twig, Gilad, Tynelius, Per, Tzotzas, Themistokli, Tzourio, Christophe, Ueda, Peter, Ugel, Eunice, Ukoli, Flora AM, Ulmer, Hanno, Unal, Belgin, Usupova, Zhamyila, Uusitalo, Hannu MT, Uysal, Nalan, Vaitkeviciute, Justina, Valdivia, Gonzalo, Vale, Susana, Valvi, Damaskini, van Dam, Rob M, Van der Heyden, Johan, van der Schouw, Yvonne T, Van Herck, Koen, Van Minh, Hoang, Van Schoor, Natasja M, van Valkengoed, Irene GM, Vanderschueren, Dirk, Vanuzzo, Diego, Varbo, Anette, Varela-Moreiras, Gregorio, Varona-Pérez, Patricia, Vasan, Senthil K, Vega, Toma, Veidebaum, Tooma, Velasquez-Melendez, Gustavo, Velika, Biruta, Veronesi, Giovanni, Verschuren, WM Monique, Victora, Cesar G, Viegi, Giovanni, Viet, Lucie, Villalpando, Salvador, Vineis, Paolo, Vioque, Jesu, Virtanen, Jyrki K, Visser, Marjolein, Visvikis-Siest, Sophie, Viswanathan, Bharathi, Vladulescu, Mihaela, Vlasoff, Tiina, Vocanec, Dorja, Vollenweider, Peter, Völzke, Henry, Voutilainen, Ari, Voutilainen, Sari, Vrijheid, Martine, Vrijkotte, Tanja GM, Wade, Alisha N, Wagner, Aline, Waldhör, Thoma, Walton, Janette, Wambiya, Elvis OA, Bebakar, Wan Mohamad Wan, Mohamud, Wan Nazaimoon Wan, de Souza Wanderley Júnior, Rildo, Wang, Ming-Dong, Wang, Ningli, Wang, Qian, Wang, Xiangjun, Wang, Ya Xing, Wang, Ying-Wei, Wannamethee, S Goya, Wareham, Nichola, Weber, Adelheid, Wedderkopp, Niel, Weerasekera, Deepa, Weghuber, Daniel, Wei, Wenbin, Weres, Aneta, Werner, Bo, Whincup, Peter H, Widhalm, Kurt, Widyahening, Indah S, Wiecek, Andrzej, Wilks, Rainford J, Willeit, Johann, Willeit, Peter, Williams, Julianne, Wilsgaard, Tom, Wojtyniak, Bogdan, Wong-McClure, Roy A, Wong, Andrew, Wong, Jyh Eiin, Wong, Tien Yin, Woo, Jean, Woodward, Mark, Wu, Frederick C, Wu, Jianfeng, Wu, Li Juan, Wu, Shouling, Xu, Haiquan, Xu, Liang, Yaacob, Nor Azwany, Yamborisut, Uruwan, Yan, Weili, Yang, Ling, Yang, Xiaoguang, Yang, Yang, Yardim, Nazan, Yaseri, Mehdi, Yasuharu, Tabara, Ye, Xingwang, Yiallouros, Panayiotis K, Yoosefi, Moein, Yoshihara, Akihiro, You, Qi Sheng, You, San-Lin, Younger-Coleman, Novie O, Md Yusof, Safiah, Yusoff, Ahmad Faudzi, Zaccagni, Luciana, Zafiropulos, Vassili, Zainuddin, Ahmad A, Zakavi, Seyed Rasoul, Zamani, Farhad, Zambon, Sabina, Zampelas, Antoni, Zamrazilová, Hana, Zapata, Maria Elisa, Zargar, Abdul Hamid, Ko Zaw, Ko, Zdrojewski, Tomasz, Zejglicova, Kristyna, Vrkic, Tajana Zeljkovic, Zeng, Yi, Zhang, Luxia, Zhang, Zhen-Yu, Zhao, Dong, Zhao, Ming-Hui, Zhao, Wenhua, Zhen, Shiqi, Zheng, Wei, Zheng, Yingfeng, Zholdin, Bekbolat, Zhou, Maigeng, Zhu, Dan, Zins, Marie, Zitt, Emanuel, Zocalo, Yanina, Cisneros, Julio Zuñiga, Zuziak, Monika, Ezzati, Majid, Filippi, Sarah, Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)
Subjects: Population -- Health aspects, Leanness, Baixo peso/Underweight, none, Double burden, alipainoisuus, tulotaso, global health, systematic analysis, Sedentary behaviors, RC1200, Prospective associations, 0302 clinical medicine, underweight, nälänhätä, Biology (General), skin and connective tissue diseases, Children, ComputingMilieux_MISCELLANEOUS, Body mass index, Human Nutrition & Health, education.field_of_study, Humane Voeding & Gezondheid, ylipaino, General Medicine, kansainvälinen vertailu, 3. Good health, World health, Medicine, A100 Pre-clinical Medicine, Population distribution, medicine.medical_specialty, QH301-705.5, Science, Socio-culturale, Nursing, Social sciences, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Thinness, SDG 3 - Good Health and Well-being, BMI, epidemiology, obesity, None, Humans, Obesidade/Obesity, SDG 2 - Zero Hunger, education, VLAG, US adults, Omvårdnad, body mass index, malnutrition, obesity, underweight, nutritional and metabolic diseases, medicine.disease, terveellisyys, Obesity, Faculdade de Ciências Sociais, Body Mass Index, Prevalence, Risk Factors, General Biochemistry, WIAS, lihavuus, RA, Demography, N.A, double burden, Settore MED/09 - Medicina Interna, alueelliset erot, Nutrition and Disease, Animal Nutrition, [SDV]Life Sciences [q-bio], Medizin, 030204 cardiovascular system & hematology, 0601 Biochemistry and Cell Biology, Change distribution of body mass index, RA0421, Voeding en Ziekte, Epidemiology, Medicine and Health Sciences, Global health, Índice de massa corporal/Body Mass Index, 030212 general & internal medicine, Underweight, painoindeksi, 2. Zero hunger, General Neuroscience, aliravitsemus, elintarvikkeet, health, Public Health, Global Health, Social Medicine and Epidemiology, Diervoeding, 3142 Public health care science, environmental and occupational health, purl.org/pe-repo/ocde/ford#3.01.03 [https], Chinese adults, pooled analysis, medicine.symptom, Diet quality, B120 Physiology, Research Article, trends, purl.org/pe-repo/ocde/ford#1.06.03 [https], prevalence, Population, Mothers, Genetics and Molecular Biology, 3121 Internal medicine, medicine, Life Science, ddc:610, 3125 Otorhinolaryngology, ophthalmology, kehonkoostumus, Nutrition, Australian adults, General Immunology and Microbiology, purl.org/pe-repo/ocde/ford#3.01.04 [https], Ciências sociais, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Malnutrition, Epidemiology and Global Health, sense organs, Estilos de Vida e Impacto na Saúde
Abstract: From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions., Wellcome Trust, Medical Research Council, peer-reviewed
Published: 2021
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158. Longitudinal Anthropometric Measures and Risk of New-Onset Atrial Fibrillation Among Community-Dwelling Men and Women

Author: Zuolin Lu, Sven Geurts, Banafsheh Arshi, Martijn J. Tilly, Elif Aribas, Jeanine Roeters van Lennep, Natasja de Groot, Dimitris Rizopoulos, M. Arfan Ikram, Maryam Kavousi, Epidemiology, Internal Medicine, and Cardiology
Subjects: Male, SDG 3 - Good Health and Well-being, Risk Factors, Waist-Hip Ratio, Atrial Fibrillation, Humans, Female, General Medicine, Independent Living, Prospective Studies, Middle Aged, Waist Circumference, Body Mass Index
Abstract: Objective: To assess the sex-specific evolution of various anthropometric measures and the association of their longitudinal trajectories with new-onset atrial fibrillation (AF). Methods: Among 5266 men and 7218 women free of AF at baseline from the prospective population-based Rotterdam Study, each anthropometric measure was measured 1 to 5 times from 1989 to 2014. Anthropometric measures were standardized to obtain hazard ratios per 1 SD increase to enable comparison. Joint models were used to assess the longitudinal association between anthropometric measures and incident AF. Use of the joint models is a preferred method for simultaneous analyses of repeated measurements and survival data for conferring less biased estimates. Results: Mean (SD) age was 63.9 (8.9) years for men and 64.9 (9.8) years for women. Median follow-up time was 10.5 years. Longitudinal evolution of weight, height, waist circumference, hip circumference, and body mass index was associated with an increased risk of new-onset AF in both men and women. In joint models, larger height in men (hazard ratio [95% credible interval] per 1 SD, 1.27 [1.17 to 1.38]) and weight in women (1.24 [1.16 to 1.34]) showed the largest associations with AF. In joint models, waist to hip ratio was significantly associated with incident AF only in women (1.10 [1.03 to 1.18]). Conclusion: Considering the entire longitudinal trajectories in joint models, anthropometric measures were positively associated with an increased risk for new-onset AF among men and women in the general population. Increase in measure of central obesity showed a stronger association with increased risk of AF onset among women compared with men.
Published: 2021

159. Obesity Partially Mediates the Diabetogenic Effect of Lowering LDL Cholesterol

Author: Peitao Wu, Giulianini Franco, Daniel I. Chasman, Jerome I. Rotter, Georgy Hindy, Tom G. Richardson, M. Arfan Ikram, Ping An, Rafael R C Cuadrat, Jørgen K. Kanters, Sridharan Raghavan, Paul M. Ridker, Rita R. Kalyani, Jonas L. Isaksen, Morten S. Olesen, Xiuqing Guo, André G. Uitterlinden, Marju Orho-Melander, Lluís Masana, Lisa R. Yanek, Iyas Daghlas, Mohsen Ghanbari, Mary F. Feitosa, Jennifer A. Brody, Jose C Florez, Ulrika Ericson, James S. Floyd, Bianca Porneala, Jianwen Cai, Dhananjay Vaidya, Jee-Young Moon, James B. Meigs, George Davey Smith, Ching-Ti Liu, Susanne Jäger, Maryam Kavousi, Josée Dupuis, Christina Ellervik, Qibin Qi, Fariba Ahmadizar, Matthias B. Schulze, Mark O. Goodarzi, Dipender Gill, Josep M Mercader, Bruce M. Psaty, Laura M. Raffield, Leslie A. Lange, Colleen M. Sitlani, Robert C. Kaplan, Jie Yao, Jordi Merino, Michael A. Province, Epidemiology, and Internal Medicine
Subjects: Research design, medicine.medical_specialty, Cardiovascular and Metabolic Risk, Diabetes risk, Endocrinology, Diabetes and Metabolism, Adipose tissue, Type 2 diabetes, SDG 3 - Good Health and Well-being, Risk Factors, Diabetes mellitus, Internal medicine, Mendelian randomization, Internal Medicine, medicine, Humans, Obesity, Advanced and Specialized Nursing, business.industry, Odds ratio, Cholesterol, LDL, Mendelian Randomization Analysis, medicine.disease, Endocrinology, Diabetes Mellitus, Type 2, business, Genome-Wide Association Study
Abstract: OBJECTIVE LDL cholesterol (LDLc)-lowering drugs modestly increase body weight and type 2 diabetes risk, but the extent to which the diabetogenic effect of lowering LDLc is mediated through increased BMI is unknown. RESEARCH DESIGN AND METHODS We conducted summary-level univariable and multivariable Mendelian randomization (MR) analyses in 921,908 participants to investigate the effect of lowering LDLc on type 2 diabetes risk and the proportion of this effect mediated through BMI. We used data from 92,532 participants from 14 observational studies to replicate findings in individual-level MR analyses. RESULTS A 1-SD decrease in genetically predicted LDLc was associated with increased type 2 diabetes odds (odds ratio [OR] 1.12 [95% CI 1.01, 1.24]) and BMI (β = 0.07 SD units [95% CI 0.02, 0.12]) in univariable MR analyses. The multivariable MR analysis showed evidence of an indirect effect of lowering LDLc on type 2 diabetes through BMI (OR 1.04 [95% CI 1.01, 1.08]) with a proportion mediated of 38% of the total effect (P = 0.03). Total and indirect effect estimates were similar across a number of sensitivity analyses. Individual-level MR analyses confirmed the indirect effect of lowering LDLc on type 2 diabetes through BMI with an estimated proportion mediated of 8% (P = 0.04). CONCLUSIONS These findings suggest that the diabetogenic effect attributed to lowering LDLc is partially mediated through increased BMI. Our results could help advance understanding of adipose tissue and lipids in type 2 diabetes pathophysiology and inform strategies to reduce diabetes risk among individuals taking LDLc-lowering medications.
Published: 2021
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160. Longitudinal changes of thoracic aortic diameters in the general population aged 55 years or older

Author: Carlijn G E Thijssen, Ferit O Mutluer, Janine E van der Toorn, Lidia R Bons, Arjen L Gökalp, Johanna JM Takkenberg, Mostafa M Mokhles, Roland R J van Kimmenade, Meike W Vernooij, Aad van der Lugt, Ricardo P J Budde, Jolien W Roos-Hesselink, Maryam Kavousi, Daniel Bos, Cardiology, Epidemiology, Radiology & Nuclear Medicine, Cardiothoracic Surgery, and Department of Business-Society Management
Subjects: Cardiology and Cardiovascular Medicine
Abstract: ObjectiveLongitudinal data on age-related changes in the diameters of the thoracic aorta are scarce. To better understand normal variation and to identify factors influencing this process, we aimed to report male-female-specific and age-specific aortic growth rate in the ageing general population and identify factors associated with growth rate.MethodsFrom the prospective population-based Rotterdam Study, 943 participants (52.0% females, median age at baseline 65 years (62–68)) underwent serial non-enhanced cardiac CT. We measured the diameters of the ascending (AA) and descending aorta (DA) at two time points and expressed absolute and relative differences. Linear mixed effects analysis was performed to identify determinants associated with change in aortic diameters.ResultsMean AA diameter at baseline was 37.3±3.6 mm in male population and 34.7±3.2 mm in female population, mean DA diameter was 29.6±2.3 in male population and 26.9±2.2 mm in female population. The median absolute change in diameters during follow-up (mean scan interval 14.1±0.3 years) was 1 mm (0–2) for both the AA and DA. Absolute change per decade in AA diameter was significantly larger in males than in females (0.72 mm/decade (0.00–1.43) vs 0.70 mm/decade (0.00–1.41), p=0.006), as well as absolute change in AD diameter (0.71 mm/decade (0.00–1.42) vs 0.69 mm/decade (0.00–1.36), p=0.008). There was no significant difference between male and female population in relative change of their aortic diameters during follow-up. Age, male sex, higher body mass index (BMI) and higher diastolic blood pressure (DBP) showed a statistically significant independent association with increase in AA and DA diameters over time.ConclusionsSome degree of increase in thoracic aortic diameters is typical in both men and women of an aging population. Factors associated with this change in thoracic aortic diameters were sex, age, BMI and DBP.
Published: 2021

161. Genetic analyses of the QT interval and its components in over 250K individuals identifies new loci and pathways affecting ventricular depolarization and repolarization

Author: Peter W. Macfarlane, Niels Grarup, Ruth J. F. Loos, Marcus Dörr, Peter P. Pramstaller, Torben Hansen, James F. Wilson, Lu-Chen Weng, Eduardo Tarazona-Santos, Honghuang Lin, Yong Qian, Jeffrey R. O'Connell, Maria Pina Concas, Claudia Schurmann, Michele Orini, Joshua C. Bis, Archie Campbell, Susan R. Heckbert, Jie Yao, Eulalia Catamo, Claus Graff, James G. Wilson, Pashupati P. Mishra, Massimo Mangino, Martina Müller-Nurasyid, Borbala Mifsud, Linda Repetto, Stephan B. Felix, Julia Ramirez, Rebecca D. Jackson, Eric Boerwinkle, Monika Stoll, Elsayed Z. Soliman, Maryam Kavousi, David J. Porteous, Nina Mononen, Dan E. Arking, Laura Andreasen, Lorenz Risch, Antonio Luiz Pinho Ribeiro, Pier D. Lambiase, Mika Kähönen, Xia Shen, Kenneth Rice, Eric A. Whitsel, Nona Sotoodehnia, Victor Nauffal, Konstantin Strauch, Jørgen K. Kanters, Henry Völzke, Daniel S. Evans, Jonas L. Isaksen, Alessandro De Grandi, Hao Mei, Alexander P. Reiner, Christy L. Avery, Thiago P. Leal, Alanna C. Morrison, Christian Fuchsberger, M. Arfan Ikram, Moritz Sinner, Yongmei Liu, Bruno H. Stricker, Francesco Cucca, Allan Linneberg, Patricia B. Munroe, Christina Ellervik, Olli T. Raitakari, Melanie Waldenberger, Reem Salman, Xiuqing Guo, Sandosh Padmanabhan, ThuyVy Duong, Dawood Darbar, Stefan Weiss, Arden Moscati, Alvaro Alonso, Cornelia M. van Duijn, Gianfranco Sinagra, Luisa Foco, Matthias Nauck, Kathleen A. Ryan, Kjell Nikus, Gustav Ahlberg, Helen R. Warren, Kent D. Taylor, Niek Verweij, Rebecca Freudling, Cristian Pattaro, Michael Preuss, Charles Kooperberg, Anne Richmond, David Conen, Oliver Hines, Juhani Junttila, Leo-Pekka Lyytikäinen, Nina Hutri-Kähönen, Kirill V. Tarasov, Ulrich Schotten, M. Benjamin Shoemaker, Marten E. van den Berg, Jerome I. Rotter, Michael J. Cutler, Adolfo Correa, Bruce M. Psaty, Caroline Hayward, Yalda Jamshidi, Pau Navarro, J W Benjamins, Patrick T. Ellinor, Massimo Mezzavilla, William J Young, Stefan Kääb, Lars Lind, Antonio De Luca, Heikki V. Huikuri, Marjo-Riitta Järvelin, Guillaume Paré, Stefan van Duijvenboden, Uwe Völker, Maria Fernanda Lima-Costa, Philippe Froguel, Jan A. Kors, Annette Peters, David Schlessinger, Christopher Newton-Cheh, J. Wouter Jukema, Andrew Tinker, Dennis O. Mook-Kanamori, Antoine R Baldassari, Stefanie Aeschbacher, Mariaelisa Graff, Najim Lahrouchi, Henry J. Lin, Giorgia Girotto, Giulia Pelliccione, Jeffrey Haessler, Aaron Isaacs, Rebecca N. Mitchell, Carolina Roselli, Massimiliano Cocca, Sina A. Gharib, Rozenn N. Lemaitre, Raymond Noordam, Morten S. Olesen, Steven A. Lubitz, Jun Ding, May E. Montasser, Jennifer A. Brody, Stella Trompet, Traci M. Bartz, Dania Raza, Thomas Meitinger, Andrew P. Morris, James P. Cook, Sébastien Thériault, Martin Gögele, André G. Uitterlinden, Pim van der Harst, Alan Pittman, Farah Ahmed, Simin Liu, Casia Nursyifa, Paul L. Huang, Kristen K. Patton, and Terho Lehtimäki
Subjects: medicine.medical_specialty, business.industry, Locus (genetics), Atrial fibrillation, medicine.disease, QT interval, Genetic architecture, Sudden cardiac death, QRS complex, Internal medicine, cardiovascular system, medicine, Cardiology, Repolarization, cardiovascular diseases, business, Ventricular depolarization
Abstract: The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization (QRS duration) and repolarization (JT interval). Abnormalities of the QT interval are associated with potentially fatal ventricular arrhythmia. We conducted genome-wide multi-ancestry analyses in >250,000 individuals and identified 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identified associations with Mendelian disease genes. Enrichments were observed in established pathways for QT and JT, with new genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast, connective tissue components and processes for cell growth and extracellular matrix interactions were significantly enriched for QRS. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlighted potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.
Published: 2021

162. Arterial calcification at different sites and prediction of atherosclerotic cardiovascular disease among women and men

Author: M. Arfan Ikram, Maarten J.G. Leening, Daniel Bos, M. Kamran Ikram, Maryam Kavousi, Janine E. van der Toorn, Banafsheh Arshi, Meike W. Vernooij, Epidemiology, Radiology & Nuclear Medicine, Cardiology, and Neurology
Subjects: medicine.medical_specialty, education.field_of_study, business.industry, Population, medicine.disease, Rotterdam Study, Arterial calcification, SDG 3 - Good Health and Well-being, Internal medicine, Epidemiology, Cohort, medicine, Cardiology, Aortic arch calcification, Cardiology and Cardiovascular Medicine, Risk assessment, business, education, Calcification
Abstract: Background and aimsThe sex-specific contributions of arterial calcification to atherosclerotic cardiovascular disease (ASCVD) risk prediction and stratification in the light of recent modifications by cardiovascular prevention guidelines remain unclear. We assessed the sex-specific value of calcification in different arteries, beyond the Pooled Cohort Equations (PCE) risk factors, for 10-year ASCVD risk prediction.MethodsFrom 2003 to 2006, participants from the population-based Rotterdam Study (n = 2167) underwent CT to quantify coronary artery calcification (CAC), aortic arch calcification (AAC), extracranial (ECAC) and intracranial carotid artery calcification (ICAC). Follow-up for ASCVD was complete on January 1, 2015. We refitted the PCE (base model), and categorized participants into low (ResultsCAC predicted ASCVD in women [hazard-ratio (95%-CI) per 1-SD: 1.40 (1.14–1.73)] and men [1.62 (1.27–1.93)]. After addition of CAC to the base model, the c-statistic improved from 0.71 to 0.72 in women; from 0.65 to 0.68 in men. Addition of CAC led to NRIe of 14.3% in women, 4.8% in men and NRIne of 1.5% in women, 15.1% in men. Only in women, ICAC predicted ASCVD [hazard-ratio (95%-CI) per 1-SD: 1.62 (1.26–2.08)], and improved the model (c-statistic from 0.71 to 0.73, NRIe: 9.8% and NRIne: 5.9%).ConclusionsAssessment of CAC improves ASCVD risk prediction and stratification. In women, the added value of ICAC for ASCVD risk prediction is comparable to that of CAC.
Published: 2021

163. Heart rate variability and incident type 2 diabetes mellitus

Author: Kan Wang, Maryam Kavousi, Arfan Ikram, Fariba Ahmadizar, Jan A. Kors, and Banafsheh Arshi
Subjects: medicine.medical_specialty, business.industry, Internal medicine, Cardiology, Type 2 Diabetes Mellitus, Heart rate variability, Medicine, Cardiology and Cardiovascular Medicine, business
Abstract: Background Hyperglycemia and autonomic dysfunction are bidirectionally related. The implications from former cross-sectional studies regarding the association of autonomic dysfunction and diabetes are limited due to the potential reverse causation. We aimed to investigate the association of longitudinal evolution of heart rate variability (HRV) with incident type 2 diabetes mellitus (T2D) among the general population. Methods Using data from the prospective population-based cohort study, 7630 participants with available repeated assessments of HRV, who were free of T2D and atrial fibrillation, were included. Measurements of HRV were analyzed from standard 10-s electrocardiograms records, including heart rate and two time-domain HRV markers: the heart-rate corrected standard deviation of the normal-to-normal RR intervals (SDNNc) and heart-rate corrected root mean square of successive RR-interval differences (RMSSDc). Joint models with the Bayes approach were performed to assess the associations between longitudinal evolutions of heart rate and different HRV metrics with incident T2D during follow-up. Models were adjusted for age, sex, body mass index, smoking status, systolic blood pressure, total and high-density lipoprotein cholesterol, use of blood pressure-lowering or lipid-lowering medication, and prevalent cardiovascular disease. Spearmen correlation was used to examine the associations between HRV metrics and glycemic traits (fasting blood glucose, insulin, and homeostatic model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-β)) at baseline. Results During a median follow-up time of 8.6 years, 871 individuals developed T2D. Based on joint models, one standard deviation (SD) increment of heart rate (hazard ratio [HR], 1.21; 95% CI, 1.09–1.34), log(SDNNc) (HR, 1.10; 95% CI, 0.94–1.27), and log(RMSSDc) (HR, 1.15; 95% CI, 1.02–1.31) was associated with the risk of developing T2D in fully-adjusted models. Subgroup analyses suggested stronger associations among men. The HRs of incident T2D per SD increment were 1.25 (1.09, 1.43) for men and 1.16 (0.99, 1.35) for women for heart rate, 1.23 (1.01, 1.51) for men and 0.97 (0.78, 1.20) for women for log(SDNNc), and 1.24 (1.05, 1.48) for men and 1.09 (0.89, 1.31) for women for log(RMSSDc). Results did not change after excluding participants who were prediabetes at baseline or after exclusion of underweight participants. Spearmen correlation indicated that heart rate was significantly associated with baseline glycemic traits, while RMSSDc was only related to fasting blood glucose. Conclusion Our study suggests that both higher heart rate and heart rate variability are associated with an increased risk of T2D development, especially among men. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Erasmus MC and Erasmus University Rotterdam; Netherlands Organization for Scientific Research; Netherlands Organization for Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly; Netherlands Genomics Initiative; Netherlands Ministry of Education, Culture and Science; Netherlands Ministry of Health, Welfare and Sports; European Commission; and Municipality of Rotterdam. We would like to thank the China Scholarship Council for the scholarship to K.W. Forest plot
Published: 2021
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164. Lipoprotein(a) is associated with incidence but not progression of aortic valve calcium

Author: Erik S.G. Stroes, S.M. Boekholdt, Yannick Kaiser, J.E. Van Der Toorn, Daniel Bos, Eric J.G. Sijbrands, Meike W. Vernooij, Y B de Rijke, Maryam Kavousi, and Kang H. Zheng
Subjects: medicine.medical_specialty, biology, business.industry, Incidence (epidemiology), Internal medicine, biology.protein, Cardiology, medicine, Lipoprotein(a), Aortic calcification, Cardiology and Cardiovascular Medicine, business
Abstract: Background Lipoprotein(a) [Lp(a)] has been implicated in the etiology of aortic valve stenosis. Although Lp(a) is strongly associated with the presence of aortic valve calcium (AVC), there are no data evaluating the relationship of Lp(a) with AVC incidence and AVC progression. Purpose To assess whether high Lp(a) levels are associated with AVC incidence and progression. Methods In 922 individuals from the population-based Rotterdam Study (mean age 66.0±4.2 years, 47.7% men) for whom Lp(a) measurements were available, non-enhanced cardiac CT imaging was performed at baseline and after a median follow-up of 14.0 [13.9–14.2] years. AVC incidence was defined as an AVC score >0 on the second scan, in absence of AVC on the first scan. We performed logistic regression analyses to evaluate the relationship of Lp(a) with AVC incidence and linear regression analyses to assess the relationship between Lp(a) and AVC progression. All analyses were corrected for age, sex, body mass index, smoking, non-high-density lipoprotein cholesterol, use of lipid-lowering medication, and hypertension. Additionally, we analyzed the progression conditional on the baseline AVC-score. Results Of the 702 (76.1%) individuals without AVC at baseline, 415 (59.1%) showed incident AVC at follow-up. The 220 (23.9%) individuals with AVC on baseline had a median AVC score of 52 [15–131], with a median yearly progression of 13 [5–38]. Lp(a) concentration was independently associated with AVC incidence (OR 1.32 for each 105 nmol/L Lp(a) increase; 95% CI: 1.03–1.68), but not with AVC progression (β −4.3 AU/year for each 105 nmol/L Lp(a) increase; 95% CI: −12.3–3.7). Conclusions Lp(a) is associated with AVC incidence but not AVC progression, suggesting that Lp(a)-lowering interventions may be futile after AVC has been established. Future studies should focus on whether Lp(a) lowering interventions can prevent the development of AVC in high-risk individuals. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): The Rotterdam Study is supported by Erasmus MC and Erasmus University Rotterdam and the Netherlands Organization for Scientific Research
Published: 2021
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165. Distribution and risk profile of atrial fibrillation patterns among women and men from the general population

Author: N. M. S. de Groot, M.J Tilly, M. A. Ikram, S Geurts, M.P.M. de Maat, Z Lu, Mohammad Kamran Ikram, and Maryam Kavousi
Subjects: education.field_of_study, business.industry, Population, medicine, Distribution (pharmacology), Atrial fibrillation, Cardiology and Cardiovascular Medicine, medicine.disease, education, business, Risk profile, Demography
Abstract: Background In a clinical setting, atrial fibrillation (AF) subgroups are defined, including paroxysmal, persistent, and permanent AF. These subgroups differ in terms of clinical characteristics, management strategy, and long-term outcomes. Application of clinical classifications in population-based settings is challenging as they are based on the duration of symptoms, recurrence, and treatment. Purpose We aim to develop an objective and standardized classification for AF patterns in the general population and examine the associated cardiovascular risk profiles and outcomes for the identified AF patterns. Methods Participants with only one reported AF episode were categorized as single-documented AF, if at least two separate AF episodes were reported as multiple-documented AF and as longstanding persistent AF if at least two consecutive ECG's at the research center showed AF, not followed by an ECG showing sinus rhythm. We fitted mixed effect models with age as time scale to characterize sex-specific cardiovascular risk factor trajectories preceding each AF pattern. We further used Cox proportional hazard modelling to describe the risk of coronary heart disease (CHD), heart failure (HF), stroke, and all-cause mortality following AF. Results We included 14,620 men and women aged ≥45 years. 1137 participants were categorized as single-documented AF, 208 as multiple-documented AF, and 57 as longstanding persistent AF. We identified significant differences in the preceding trajectories of weight, body mass index, systolic blood pressure, diastolic blood pressure, waist circumference, hip circumference, and waist-hip ratio with various AF patterns. In general, both men and women with persistent-elevated levels of these risk factors were prone to longstanding persistent AF. AF was associated with a large risk for subsequent CHD, HF, stroke, and mortality in the general population. Among the different AF patterns, single-documented AF conferred the largest risk of CHD [hazard ratio, 95% confidence interval: 1.92 (1.19–3.03)] and mortality [1.70 (1.41–2.07)] as compared to multiple-documented AF, and as compared to longstanding persistent AF [1.45 (0.72–2.90) and 3.66 (2.25–5.95), respectively]. Conclusion We developed a classification for AF patterns within a general population. We identified differences in risk factor trajectories preceding each AF pattern, which implies differences in pathophysiological mechanisms underlying AF. Participants with single-documented AF showed worse prognosis than those with multiple AF episodes. This might be due to the subgroup definition, since participants should live for a longer period of time to be categorized in the multiple-documented AF and longstanding persistent AF groups. This can also imply that participants suffering from multiple AF episodes are more frequently monitored, and treated for other risk factors. However, this could also suggest that singular AF episodes are not as innocent as commonly thought. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): - Erasmus MC Mrace grant. - Netherlands Organization for the Health Research and Development (ZonMw) Figure 1Figure 2. Progosis of various AF patterns
Published: 2021
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166. Immunothrombosis and new-onset atrial fibrillation in the general population

Author: M.J Tilly, M.P.M. de Maat, Samantha J. Donkel, M. A. Ikram, N. M. S. de Groot, Maryam Kavousi, and S Geurts
Subjects: education.field_of_study, medicine.medical_specialty, business.industry, Internal medicine, Population, Cardiology, medicine, Cardiology and Cardiovascular Medicine, education, business, New onset atrial fibrillation
Abstract: Background Atrial fibrillation (AF) is the most common, age-related cardiac arrhythmia. However, the etiology underlying atrial fibrillation is still largely unknown. At the intersection of the innate immune system and hemostasis, immunothrombosis may be a possible cause of atrial remodeling, and therefore be an underlying cause of AF. Purpose We aim to evaluate the association between markers of immunothrombosis and new-onset AF in the general population Methods From 1990 to 2014, we followed 6,174 participants aged 55 and over, free from AF at inclusion. Immunothrombosis factors fibrinogen, von Willebrand factor, ADAMTS13, and neutrophil extracellular traps (NETs) levels were measured at baseline. Participants were followed until either onset of AF, death, loss-to-follow-up, or reaching the end-date of 01–01–2014. Cox proportional hazard modelling was used to calculated hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for cardiovascular risk factors. Results We followed 6,174 participants (mean age 69.1 years, 57% women) for a median follow-up time of 12.8 years. 364 men (13.7%, incidence rate 13.0/100 person-years) and 365 women (10.4%, incidence rate 8.9/1000 person-years) developed AF. We found no significant associations between markers of immunothrombosis and new-onset AF after adjusting for cardiovascular risk factors [HR 1.00 (95% CI 0.93–1.08) for fibrinogen, 1.04 (0.97–1.12) for von Willebrand factor, 1.00 (1.00–1.01) for ADAMTS13, and 1.01 (0.94–1.09) for NETs]. Additionally, we found no significant differences in associations between men and women. Conclusion We found no association between markers of immunothrombosis and new-onset AF in the general population. Our findings imply that inflammation and immunothrombosis may be associated with AF by other cardiovascular risk factors or predisposing conditions of AF. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Netherlands Organization for the Health Research and Development (ZonMw) Erasmus MC Mrace grant
Published: 2021
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167. Trajectories of metabolic risk factors and risk of new-onset atrial fibrillation among men and women

Author: M.J Tilly, N. M. S. de Groot, Z Lu, E Aribas, J.E. Roeters van Lennep, Maryam Kavousi, J. van Rosmalen, and M. A. Ikram
Subjects: medicine.medical_specialty, business.industry, Internal medicine, Metabolic risk, Cardiology, Medicine, Cardiology and Cardiovascular Medicine, business, New onset atrial fibrillation
Abstract: Background Atrial fibrillation (AF) is the most common cardiac arrhythmia with major public health impact. Obesity and hypertension are among the most important risk factors to AF development. The link between AF and its pathogenetic factors are complex and comprehensive assessment of the impact of various long-term trajectories of anthropometric measures and blood pressure on incident AF among men and women is sparse. Purpose To investigate sex-specific trajectories of various anthropometric measures and blood pressure at population level, and further assess the impact of these trajectories on incident AF. Methods We included 5263 participants (mean age 72.1 years) with available repeated assessments measured 2 to 4 times for weight, body mass index (BMI), hip circumference (HC), waist circumference (WC), waist-to-hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP) and mean arterial pressure (MAP). Latent class linear mixed model with age as the time scale were fitted to identify the potential various classes in each risk factor. Cox proportional hazards regression models were used to assess the association between risk factors' trajectories and risk of new-onset AF, with the most favorable trajectory as a reference. Models were adjusted for traditional cardiovascular risk factors. Results 2159 (41.0%) of all participants were men. Median follow-up time was 9.76 years during which the incidence rate of AF was 16.2 per 1000 person-years for men, and 11.3 per 1000 person-years for women. In full-adjusted model, various trajectories of BMI, HC, and MAP were significantly associated with incident AF among men, and trajectories of weight, BMI, WC, HC, SBP, PP and MAP were significantly associated with incident AF among women. For BMI, persistent-increasing BMI trajectory carried the highest risk for AF with hazard ratio (HR) and 95% confidence interval (95% CI) of 1.39 (1.05–1.85) in men and 1.60 (1.19–2.15) in women. Also, persistently increasing trajectories of weight [1.69 (1.20–2.37)], WC [1.39 (1.04–1.86)] and HC [1.56 (1.05–2.34)] among women conferred the largest risks. For SBP, the persistently hypertensive trajectory carried the largest risk for AF among women [2.06 (1.25–3.39)], while intensively increasing SBP trajectory conferred the largest risk among men [1.34 (0.89–2.02)], albeit non-significant. Similar associations were observed for MAP among men and women; associated risks were 1.77 (1.25–2.51) for the persistent-hypertensive trajectory in women and 1.64 (1.16–2.33) for the intensive-increasing trajectory in men. Conclusions Various trajectories of metabolic risk factors were associated with new-onset AF among men and women. Sex-specific associations between SBP and MAP with AF could imply the differential long-term impact of vascular function on AF development among men and women. This highlights the importance of sex-specific preventive strategies for AF in general population. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Gender and Prevention grant, ZonMwCSC scholarship for PhD research
Published: 2021
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168. Sex-specific normal values and determinants of infrarenal abdominal aortic diameter among non-aneurysmal elderly population

Author: Banafsheh Arshi, Fang Zhu, Robert J. de Knegt, M. Arfan Ikram, Maryam Kavousi, Epidemiology, and Gastroenterology & Hepatology
Subjects: Male, medicine.medical_specialty, Waist, Epidemiology, Body Surface Area, Science, Population, Normal values, Article, Rotterdam Study, SDG 3 - Good Health and Well-being, Reference Values, Internal medicine, Elderly population, medicine, Humans, Aorta, Abdominal, Obesity, Prospective Studies, education, Aged, Netherlands, Ultrasonography, Body surface area, Aged, 80 and over, education.field_of_study, Sex Characteristics, Multidisciplinary, Anthropometry, business.industry, Aneurysm, Lipids, Blood pressure, Risk factors, Nonlinear Dynamics, Cardiology, Medicine, Female, business, Body mass index
Abstract: To establish age- and sex-specific distribution of the infrarenal abdominal aortic diameters (IAD) among non-aneurysmal elderly population and to investigate the associations between traditional cardiovascular risk factors and IAD in men and women. We included 4032 participants (mean age 67.2 years; 60.4% women) from the population-based Rotterdam Study, free of cardiovascular disease, who underwent IAD ultrasound assessment between 2009–2014. Linear regression analysis was used to identify determinants of IAD. The medians (inter-quartile range) of absolute IAD and body surface area (BSA)-adjusted IAD were 17.0 (15.0–18.0) mm and 9.3 (8.5–10.2) mm for women and 19.0 (18.0–21.0) mm and 9.4 (8.6–10.3) mm for men, respectively. There was a non-linear relationship between age and IAD. IAD increased steeply with advancing age and up to 70 years. After around 75 years of age, the diameter values reached a plateau. Waist circumference and diastolic blood pressure were associated with larger diameters in both sexes. Body mass index [Effect estimate (95% CI): 0.04 (0.00 to 0.08)], systolic blood pressure [− 0.01(− 0.02 to 0.00)], current smoking [0.35 (0.06 to 0.65)], total cholesterol levels [− 0.21 (− 0.31 to − 0.11)], and lipid-lowering medication [− 0.43 (− 0.67 to − 0.19)] were significantly associated with IAD in women. Sex differences in IAD values diminished after taking BSA into account. The increase in diameters was attenuated after 70 years. Differences were observed in the associations of several cardiovascular risk factors with IAD among men and women.
Published: 2021
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169. The genomics of heart failure: design and rationale of the HERMES consortium

Author: Svati H. Shah, Olle Melander, Neneh Sallah, Quinn S. Wells, Jerome I. Rotter, Faye Zhao, Charlotte Andersson, Guðmundur Thorgeirsson, Ghazaleh Fatemifar, Alex S. F. Doney, Michael E. Dunn, David E. Lanfear, Ian Ford, Eric Boersma, Sonia Shah, Christopher Newton-Cheh, Douglas L. Mann, Niek Verweij, Carolina Roselli, Laura M. Yerges-Armstrong, Jian Yang, Christian Torp-Pedersen, Veikko Salomaa, Mary L. Biggs, Alaa Shalaby, Christoph Nowak, Stefan Gross, Patrick T. Ellinor, Mari Liis Tammesoo, Diane T. Smelser, Peter M. Visscher, Hans L. Hillege, Ruth C. Lovering, Honghuang Lin, Colin N. A. Palmer, Louis Philippe Lemieux Perreault, Jeffrey Brandimarto, Uwe Völker, Perttu Salo, Andrea Koekemoer, Rebecca Gutmann, Åsa K. Hedman, Nilesh J. Samani, Heming Xing, Faiez Zannad, Jaison Jacob, Harry Hemingway, Michael R. Brown, Franco Giulianini, Anubha Mahajan, Xing Chen, Alexander Niessner, Peter Almgren, Daniel I. Swerdlow, Gunnar Engström, Lars Lind, Tõnu Esko, Tomasz Czuba, Anna Helgadottir, Harvey D. White, David J. Stott, Johan Ärnlöv, Lars Køber, Chim C. Lang, Krishna G. Aragam, Kent D. Taylor, Anders Mälarstig, Frederick K. Kamanu, Kenneth B. Margulies, Michelle L. O'Donoghue, Andrew D. Morris, Sahar Ghasemi, J. Wouter Jukema, Jessica van Setten, Abbas Dehghan, Guillaume Paré, Luca A. Lotta, Giorgio E. M. Melloni, Albert Henry, Bruce M. Psaty, Paul M. Ridker, David J. Carey, Marie-Pierre Dubé, John S. Gottdiener, Xiaosong Wang, Per H. Svensson, Xu Chen, Patrik K. E. Magnusson, Claudia Langenberg, Alexander Teumer, Vilmantas Giedraitis, Simon de Denus, Michael W. Nagle, Marcus Dörr, Thomas P. Cappola, André G. Uitterlinden, Michael Morley, Eliana Portilla-Fernandez, J. Gustav Smith, Abirami Veluchamy, Peter Weeke, Ify R. Mordi, Unnur Thorsteinsdottir, Naveed Sattar, Folkert W. Asselbergs, Daniel I. Chasman, Daníel F. Guðbjartsson, Jonathan H. Chung, Marcus E. Kleber, Raul Weiss, Christopher P. Nelson, Spiros Denaxas, Bing Yu, Simon P. R. Romaine, Nicholas A Marston, Anjali T. Owens, Cecilia M. Lindgren, John J.V. McMurray, Joshua D. Backman, Michael V. Holmes, Stella Trompet, Hilma Holm, Kerri L. Wiggins, Jian'an Luan, Stephan B. Felix, Yifan Yang, Jemma B. Wilk, Maryam Kavousi, Markus Perola, Christian T. Ruff, Jean-Claude Tardif, G Sveinbjörnsson, Samuel C. Dudley, Nicholas J. Wareham, Teemu J. Niiranen, Andrew P. Morris, Danny Tuckwell, Maris Teder-Laving, R. Thomas Lumbers, James P. Cook, Géraldine Asselin, William A. Chutkow, Winfried März, Steven A. Lubitz, John G.F. Cleland, Bill Kraus, Ramachandran S. Vasan, Christopher M. Haggerty, Olympe Chazara, Chris Finan, Heather L. Bloom, Hans-Peter Brunner-La Rocca, Francoise Fougerousse, Kenneth Rice, Craig L. Hyde, Graciela E. Delgado, Mark Chaffin, Marc S. Sabatine, Alanna C. Morrison, Kay-Tee Khaw, Kari Stefansson, Felix Vaura, Barry London, Isabella Kardys, Aroon D. Hingorani, Hongsheng Gui, Steen Stender, René Fouodjio, Mohsen Ghanbari, Pim van der Harst, Nicholas L. Smith, Karoline Kuchenbaecker, Adriaan A. Voors, Benoit Tyl, University College of London [London] (UCL), University College London Hospitals (UCLH), Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Lund University [Lund], Pfizer, Karolinska Institutet [Stockholm], Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], University of Groningen [Groningen], University of Oxford [Oxford], Dalarna University, Massachusetts General Hospital [Boston], Montreal Heart Institute - Institut de Cardiologie de Montréal, Regeneron Genetics Center, 777 Old Saw Mill River Road, Tarrytown, University of Washington [Seattle], Emory University [Atlanta, GA], Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Pennsylvania [Philadelphia], The University of Texas Health Science Center at Houston (UTHealth), Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Department of Molecular and Functional Genomics, Geisinger, Danville, PA, Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), AstraZeneca, Novartis Institutes for BioMedical Research (NIBR), University of Glasgow, University of Liverpool, Université de Montréal (UdeM), Imperial College London, University of Heidelberg, Medical Faculty, University of Dundee, Universität Greifswald - University of Greifswald, University of Minnesota Medical School, University of Minnesota System, German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Institut de Recherches Internationales Servier [Suresnes] (IRIS), Uppsala University, University of Maryland School of Medicine, University of Maryland System, University of Iceland [Reykjavik], deCODE genetics [Reykjavik], Henry Ford Hospital, Carver College of Medicine, University of Iowa, Geisinger Autism & Developmental Medicine Institute [Danville, PA, USA] (ADMI), ICIN - Netherlands Heart Institute, Leiden University Medical Center (LUMC), Netherlands Heart Institute, Partenaires INRAE, University of Cambridge [UK] (CAM), Rigshospitalet [Copenhagen], Copenhagen University Hospital, University of Leicester, Duke University [Durham], University of Iowa [Iowa City], Genentech, Inc., Genentech, Inc. [San Francisco], Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Skane University Hospital [Malmo], University of Edinburgh, Medizinische Universität Wien = Medical University of Vienna, University of Turku, National Institute for Health and Welfare [Helsinki], McMaster University [Hamilton, Ontario], Kaiser Permanente Washington Health Research Institute [Seattle] (KPWHRI), Harbor UCLA Medical Center [Torrance, Ca.], University Medical Center [Utrecht], University of Pittsburgh Medical Center [Pittsburgh, PA, États-Unis] (UPMC), University of Tartu, Aalborg University [Denmark] (AAU), Leiden University, University of Queensland [Brisbane], Ohio State University [Columbus] (OSU), Auckland City Hospital, GlaxoSmithKline, Glaxo Smith Kline, University of Texas Health Science Center, Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Duke University Medical Center, Regeneron Pharmaceuticals [Tarrytown], Vanderbilt University [Nashville], European Project, Langenberg, Claudia [0000-0002-5017-7344], Luan, Jian'an [0000-0003-3137-6337], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Cardiovascular Centre (CVC), Life Course Epidemiology (LCE), Groningen Kidney Center (GKC), Cardiology, University of Oxford, University of Pennsylvania, Universiteit Leiden, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), RS: Carim - H02 Cardiomyopathy, Epidemiology, and Internal Medicine
Subjects: Male, Study Designs, Cardiomyopathy, Disease, 030204 cardiovascular system & hematology, 0302 clinical medicine, AFRICAN ANCESTRY, Epidemiology, 80 and over, WIDE ASSOCIATION, EPIDEMIOLOGY, Cardiac and Cardiovascular Systems, AGING RESEARCH, RISK, Aged, 80 and over, 0303 health sciences, Kardiologi, Genomics, Middle Aged, Prognosis, 3. Good health, Female, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Heart failure, CLASSIFICATION, Heart Failure/genetics, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Genetic model, medicine, Genetics, Diseases of the circulatory (Cardiovascular) system, Humans, Allele frequency, Genotyping, METAANALYSIS, 030304 developmental biology, Aged, Association studies, Study Design, business.industry, Odds ratio, ADULTS, COHORTS, medicine.disease, RC666-701, REPLICATION, business, Biomarkers, Genome-Wide Association Study
Abstract: Aims The HERMES (HEart failure Molecular Epidemiology for Therapeutic targets) consortium aims to identify the genomic and molecular basis of heart failure.Methods and results The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of >1.10 for common variants (allele frequency > 0.05) and >1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 x 10(-8) under an additive genetic model.Conclusions HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.
Published: 2021
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170. Epicardial fat volume and the risk of cardiometabolic diseases among women and men from the general population

Author: Meike W. Vernooij, Oscar H. Franco, Adela Brahimaj, Mohammad Kamran Ikram, Mohammad Arfan Ikram, Daniel Bos, Maryam Kavousi, Theo van Walsum, Abbas Dehghan, Fariba Ahmadizar, General Practice, Epidemiology, Radiology & Nuclear Medicine, and Neurology
Subjects: Male, medicine.medical_specialty, education.field_of_study, Epidemiology, business.industry, Population, Type 2 diabetes, Intra-Abdominal Fat, medicine.disease, Obesity, Epicardial fat, Adipose Tissue, Cardiovascular Diseases, Risk Factors, Internal medicine, medicine, Cardiology, Humans, Female, Cardiology and Cardiovascular Medicine, business, education, Pericardium, Volume (compression)
Published: 2021
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171. Reporting of sex-specific outcomes in trials of interventions for cardiovascular disease: Has there been progress?

Author: Maryam Kavousi, J.W. Roos Hesselink, Eric Boersma, Jorie Versmissen, J.E. Roeters van Lennep, Michelle M. Schreuder, Loes E. Visser, Cardiology, Epidemiology, and Internal Medicine
Subjects: Male, medicine.medical_specialty, Intervention trials, Cardiovascular research, Psychological intervention, Disease, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Medicine, Humans, Cardiovascular drug, 030212 general & internal medicine, Intensive care medicine, Randomized Controlled Trials as Topic, Publishing, Sex Characteristics, 030219 obstetrics & reproductive medicine, business.industry, Obstetrics and Gynecology, Cardiovascular Agents, Sex specific, Clinical trial, Treatment Outcome, Cardiovascular Diseases, Female, business
Abstract: In the past decade, the leading international cardiology societies have released statements that emphasize the importance of sex-specific reporting of the findings of clinical trials in cardiovascular research. To find out whether this has led to improvement, we compared sex-specific reporting of efficacy and safety outcomes for trials of cardiovascular drug interventions presented at the major clinical trials sessions of the European Society of Cardiology (ESC), American Heart Association (AHA) and the American College of Cardiology (ACC) before and after publication of these statements. We found that sex-specific efficacy and safety outcomes of the most influential cardiovascular intervention trials are still not systematically presented.
Published: 2021

172. Multiethnic Genome-Wide Association Study of Subclinical Atherosclerosis in Individuals With Type 2 Diabetes

Author: Stefan Weiss, Gauti Kjartan Gislason, Matthew J. Budoff, Valborg Gudmundsdottir, Xiuqing Guo, Lawrence F. Bielak, Joshua C. Bis, Jie Yao, Latchezar Dimitrov, Leslie A. Lange, Patricia A. Peyser, Lingyi Lu, Vilmundur Gudnason, Jerome I. Rotter, Barry I. Freedman, Lihua Wang, M. Arfan Ikram, Mohsen Ghanbari, Yingchang Lu, Jiaxi Zhu, Elias F Gudmundsson, Gerardo Heiss, Yi-Ping Fu, Maryam Kavousi, Shih-Jen Hwang, Sharon L.R. Kardia, Laura M. Raffield, André G. Uitterlinden, Carl D. Langefeld, Donald W. Bowden, Ping An, Daniel Bos, Kent D. Taylor, Ulf Schminke, Albert V. Smith, Bruce M. Psaty, James G. Wilson, Shyh-Huei Chen, Maggie C.Y. Ng, Christopher J. O'Donnell, Mary F. Feitosa, Nora Franceschini, Epidemiology, Radiology & Nuclear Medicine, and Internal Medicine
Subjects: 0301 basic medicine, Aging, Carotid arteries, Genome-wide association study, Type 2 diabetes, 030204 cardiovascular system & hematology, Cardiovascular, Coronary artery disease, 0302 clinical medicine, 2.1 Biological and endogenous factors, Aetiology, Diabetes, General Medicine, Heart Disease, cardiovascular system, Cardiology, medicine.symptom, Type 2, coronary artery disease, medicine.medical_specialty, carotid intima-media thickness, Black People, Asymptomatic, White People, Article, Diabetes Complications, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, Diabetes Mellitus, Genetics, medicine, Humans, Genetic Predisposition to Disease, cardiovascular diseases, Heart Disease - Coronary Heart Disease, genome-wide association study, business.industry, Prevention, Human Genome, nutritional and metabolic diseases, Atherosclerosis, medicine.disease, Good Health and Well Being, 030104 developmental biology, Diabetes Mellitus, Type 2, Genetic Loci, Subclinical atherosclerosis, Coronary artery calcification, business, Genome-Wide Association Study
Abstract: Background: Coronary artery calcification (CAC) and carotid artery intima-media thickness (cIMT) are measures of subclinical atherosclerosis in asymptomatic individuals and strong risk factors for cardiovascular disease. Type 2 diabetes (T2D) is an independent cardiovascular disease risk factor that accelerates atherosclerosis. Methods: We performed meta-analyses of genome-wide association studies in up to 2500 T2D individuals of European ancestry (EA) and 1590 T2D individuals of African ancestry with or without exclusion of prevalent cardiovascular disease, for CAC measured by cardiac computed tomography, and 3608 individuals of EA and 838 individuals of African ancestry with T2D for cIMT measured by ultrasonography within the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium. Results: We replicated 2 loci (rs9369640 and rs9349379 near PHACTR1 and rs10757278 near CDKN2B ) for CAC and one locus for cIMT (rs7412 and rs445925 near APOE-APOC1 ) that were previously reported in the general EA populations. We identified one novel CAC locus (rs8000449 near CSNK1A1L/LINC00547/POSTN at 13q13.3) at P =2.0×10 -8 in EA. No additional loci were identified with the meta-analyses of EA and African ancestry. The expression quantitative trait loci analysis with nearby expressed genes derived from arterial wall and metabolic tissues from the Genotype-Tissue Expression project pinpoints POSTN , encoding a matricellular protein involved in bone formation and bone matrix organization, as the potential candidate gene at this locus. In addition, we found significant associations ( P -4 ) for 3 previously reported coronary artery disease loci for these subclinical atherosclerotic phenotypes (rs2891168 near CDKN2B-AS1 and rs11170820 near FLJ12825 for CAC, and rs7412 near APOE for cIMT). Conclusions: Our results provide potential biological mechanisms that could link CAC and cIMT to increased cardiovascular disease risk in individuals with T2D.
Published: 2021

173. Association of Insulin Resistance and Type 2 Diabetes With Gut Microbial Diversity: A Microbiome-Wide Analysis From Population Studies

Author: M. Arfan Ikram, Trudy Voortman, Fariba Ahmadizar, Djawad Radjabzadeh, Lianmin Chen, Alexander Kurilshikov, Maryam Kavousi, André G. Uitterlinden, Jingyuan Fu, Zhangling Chen, Alexandra Zhernakova, Robert Kraaij, Epidemiology, Internal Medicine, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Translational Immunology Groningen (TRIGR), and Center for Liver, Digestive and Metabolic Diseases (CLDM)
Subjects: Adult, Blood Glucose, Male, medicine.medical_treatment, Population, Physiology, Type 2 diabetes, GLUCOSE, Rotterdam Study, Feces, Insulin resistance, SDG 3 - Good Health and Well-being, Diabetes mellitus, RNA, Ribosomal, 16S, medicine, Humans, Insulin, Microbiome, Prospective Studies, education, Netherlands, RISK, education.field_of_study, Bacteria, business.industry, Correction, General Medicine, Middle Aged, medicine.disease, Gastrointestinal Microbiome, METAGENOME, RNA, Bacterial, Online Only, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Homeostatic model assessment, Female, Other, Insulin Resistance, business
Abstract: IMPORTANCE Previous studies have indicated that gut microbiome may be associated with development of type 2 diabetes. However, these studies are limited by small sample size and insufficient for confounding. Furthermore, which specific taxa play a role in the development of type 2 diabetes remains unclear.OBJECTIVE To examine associations of gut microbiome composition with insulin resistance and type 2 diabetes in a large population-based setting controlling for various sociodemographic and lifestyle factors.DESIGN, SETTING, AND PARTICIPANTS This cross-sectional analysis included 2166 participants from 2 Dutch population-based prospective cohorts: the Rotterdam Study and the LifeLines-DEEP study.EXPOSURES The 16S ribosomal RNA method was used to measure microbiome composition in stool samples collected between January 1, 2012, and December 31, 2013. The alpha diversity (Shannon, richness, and Inverse Simpson indexes), beta diversity (Bray-Curtis dissimilarity matrix), and taxa (from domain to genus level) were identified to reflect gut microbiome composition.MAIN OUTCOMES AND MEASURES Associations among alpha diversity, beta diversity, and taxa with the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and with type 2 diabetes were examined. Glucose and insulin were measured to calculate the HOMA-IR. Type 2 diabetes cases were identified based on glucose levels and medical records from January 2012 to December 2013. Analyses were adjusted for technical covariates, lifestyle, sociodemographic, and medical factors. Data analysis was performed from January 1, 2018, to December 31, 2020.RESULTS There were 2166 participants in this study: 1418 from the Rotterdam Study (mean [SD] age, 62.4 [5.9] years; 815 [57.5%] male) and 748 from the LifeLines-DEEP study (mean [SD] age, 44.7 [13.4] years; 431 [57.6%] male); from this total, 193 type 2 diabetes cases were identified. Lower microbiome Shannon index and richness were associated with higher HOMA-IR (eg, Shannon index, -0.06; 95% CI, -0.10 to -0.02), and patients with type 2 diabetes had a lower richness than participants without diabetes (odds ratio [OR], 0.93; 95% CI, 0.88-0.99). The beta diversity (Bray-Curtis dissimilarity matrix) was associated with insulin resistance (R-2 = 0.004, P = .001 in the Rotterdam Study and R-2 = 0.005, P = .002 in the LifeLines-DEEP study). A total of 12 groups of bacteria were associated with HOMA-IR or type 2 diabetes. Specifically, a higher abundance of Christensenellaceae (beta = -0.08; 95% CI, -0.12 to -0.03: P < .001), Christensenellaceae R7 group (beta = -0.07; 95% CI, -0.12 to -0.03; P < .001), Marvinbryantia (beta = -0.07; 95% CI, -0.11 to -0.03; P < .001), Ruminococcaceae UCG005 (beta = -0.09; 95% CI, -0.13 to -0.05; P < .001), Ruminococcaceae UCG008 (beta = -0.07; 95% CI, -0.11 to -0.03; P < .001), Ruminococcaceae UCG010 (beta = -0.08; 95% CI, -0.12 to -0.04; P < .001), or Ruminococcaceae NK4A214 group (beta = -0.09; 95% CI, -0.13 to -0.05; P < .001) was associated with lower HOMA-IR. A higher abundance of Clostridiaceae 1 (OR, 0.51; 95% CI, 0.41-0.65; P < .001), Peptostreptococcaceae (OR, 0.56; 95% CI, 0.45-0.70; P < .001), C sensu stricto 1 (OR, 0.51; 95% CI, 0.40-0.65; P < .001), Intestinibacter (OR, 0.60; 95% CI, 0.48-0.76; P < .001), or Romboutsia (OR, 0.55; 95% CI, 0.44-0.70; P < .001) was associated with less type 2 diabetes. These bacteria are all known to produce butyrate.CONCLUSIONS AND RELEVANCE In this cross-sectional study, higher microbiome alpha diversity, along with more butyrate-producing gut bacteria, was associated with less type 2 diabetes and with lower insulin resistance among individuals without diabetes. These findings could help provide insight into the etiology, pathogenesis, and treatment of type 2 diabetes.
Published: 2021

174. Genetic susceptibility, obesity and lifetime risk of type 2 diabetes

Author: Alanna C. Morrison, James S. Pankow, M. Arfan Ikram, Abbas Dehghan, Maarten J.G. Leening, Symen Ligthart, Natalie R Hasbani, Eric J.G. Sijbrands, Paul S. de Vries, Maryam Kavousi, André G. Uitterlinden, Elizabeth Selvin, Eric Boerwinkle, Fariba Ahmadizar, Thijs T. W. van Herpt, Intensive Care, Epidemiology, Internal Medicine, and Cardiology
Subjects: Male, Risk, Multifactorial Inheritance, Endocrinology, Diabetes and Metabolism, Population, Type 2 diabetes, Article, White People, Rotterdam Study, Endocrinology, SDG 3 - Good Health and Well-being, Diabetes mellitus, Internal Medicine, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, Obesity, education, Aric study, Life Style, Aged, education.field_of_study, business.industry, Genetic Variation, Middle Aged, medicine.disease, Diabetes Mellitus, Type 2, Lifetime risk, Female, business, Demography
Abstract: Aims: Both lifestyle factors and genetic background contribute to the development of type 2 diabetes. Estimation of the lifetime risk of diabetes based on genetic information has not been presented, and the extent to which a normal body weight can offset a high lifetime genetic risk is unknown. Methods: We used data from 15,671 diabetes-free participants of European ancestry aged 45 years and older from the prospective population-based ARIC study and Rotterdam Study (RS). We quantified the remaining lifetime risk of diabetes stratified by genetic risk and quantified the effect of normal weight in terms of relative and lifetime risks in low, intermediate and high genetic risk. Results: At age 45 years, the lifetime risk of type 2 diabetes in ARIC in the low, intermediate and high genetic risk category was 33.2%, 41.3% and 47.2%, and in RS 22.8%, 30.6% and 35.5% respectively. The absolute lifetime risk for individuals with normal weight compared to individuals with obesity was 24% lower in ARIC and 8.6% lower in RS in the low genetic risk group, 36.3% lower in ARIC and 31.3% lower in RS in the intermediate genetic risk group, and 25.0% lower in ARIC and 29.4% lower in RS in the high genetic risk group. Conclusions: Genetic variants for type 2 diabetes have value in estimating the lifetime risk of type 2 diabetes. Normal weight mitigates partly the deleterious effect of high genetic risk.
Published: 2021

175. Updated treatment thresholds in the 2019 ESC/EAS dyslipidaemia guidelines substantially expand indications for statin use for primary prevention at population level: Results from the Rotterdam Study

Author: Jelena Pavlović, M. Arfan Ikram, Maarten J.G. Leening, Maryam Kavousi, Epidemiology, Neurology, Radiology & Nuclear Medicine, and Cardiology
Subjects: medicine.medical_specialty, Statin, Population level, business.industry, medicine.drug_class, Statin treatment, Lipids, Primary Prevention, Rotterdam Study, Cardiovascular Diseases, Risk Factors, Primary prevention, Epidemiology, Humans, Medicine, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiology and Cardiovascular Medicine, business, Intensive care medicine, Dyslipidemias
Published: 2020
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176. Chronic obstructive pulmonary disease and the development of atrial fibrillation

Author: Jan Heeringa, Oscar H. Franco, Vincent Vakaet, Maxim Grymonprez, Maryam Kavousi, M. Arfan Ikram, Bruno H. Stricker, Lies Lahousse, Guy Brusselle, Epidemiology, Internal Medicine, and Pulmonary Medicine
Subjects: medicine.medical_specialty, Exacerbation, Atrial enlargement, INTERLEUKIN-6, Epidemiology, Population, PATHOPHYSIOLOGY, Pathophysiological mechanisms, 030204 cardiovascular system & hematology, 03 medical and health sciences, Rotterdam Study, COPD exacerbation, 0302 clinical medicine, Internal medicine, medicine, Medicine and Health Sciences, 030212 general & internal medicine, Incident atrial fibrillation, education, RISK, education.field_of_study, COPD, Systemic inflammation, business.industry, MORTALITY, Hazard ratio, Atrial fibrillation, ASSOCIATION, medicine.disease, C-REACTIVE PROTEIN, respiratory tract diseases, PREVALENCE, REDUCED LUNG-FUNCTION, ATHEROSCLEROSIS, Cardiology, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Cohort study
Abstract: Background: Chronic obstructive pulmonary disease (COPD) has been associated with atrial fibrillation (AF). More insight into the epidemiology and underlying mechanisms is required to optimize management. Methods: The Rotterdam Study is a large, population-based cohort study with long-term follow-up. Time dependent Cox proportional hazard models were constructed to study the effect of COPD on incident AF, adjusted for age, sex and pack years of cigarette smoking, and additionally stratified according to exacerbation frequency, left atrial size and baseline systemic inflammatory levels. Results: 1369 of 10,943 subjects had COPD, of whom 804 developed AF. The AF incidence rate was 14 per 1000 person years in COPD and 8 per 1000 person years in subjects without COPD. The adjusted hazard ratio (HR) for COPD subjects to develop AF as compared to subjects without COPD was 1.28 (95% CI [1.04, 1.57]). COPD subjects with frequent exacerbations had a twofold increased AF risk (HR 1.99 [1.42, 2.79]) and COPD subjectswith a left atrial size >= 40 mm also had an elevated AF risk (HR 1.77 [1.07, 2.94]). COPD subjects with baseline systemic inflammatory levels above the median had significantly increased AF risks (hsCRP=1.83 mg/L: HR 1.51 [1.13, 2.03] and IL6 >= 1.91 ng/L: HR 2.49 [1.18, 5.28]), whereas COPD subjects below the median had in both analyses no significantly increased AF risk. Conclusions: COPD subjects had a 28% increased AF risk, which further increased with frequent exacerbations and an enlarged left atrium. The risk was driven by COPD subjects having elevated systemic inflammatory levels.
Published: 2019

177. Association of migraine with calcification in major vessel beds: The Rotterdam Study

Author: Ke-xin Wen, Antoinette MaassenVanDenBrink, Mohammad Arfan Ikram, Oscar H. Franco, Daniel Bos, Maryam Kavousi, Meike W. Vernooij, Erasmus MC other, Radiology & Nuclear Medicine, Epidemiology, and Internal Medicine
Subjects: Carotid Artery Diseases, Male, medicine.medical_specialty, Migraine Disorders, Aorta, Thoracic, Cohort Studies, Rotterdam Study, Risk Factors, Internal medicine, Epidemiology, Medicine, Humans, Prospective Studies, Vascular Calcification, Aged, Netherlands, business.industry, General Medicine, Cerebral Arteries, Middle Aged, medicine.disease, Coronary Vessels, Arterial calcification, Carotid Arteries, Migraine, Cardiology, Female, Neurology (clinical), business, Calcification, Cohort study
Abstract: Background To explore the role of large-artery atherosclerosis in migraine, we investigated the association between migraine and arterial calcification in different intracranial and extracranial vessels. Methods 1856 participants were included, mean age (standard deviation) 67.4 (5.8) years, from the population-based Rotterdam Study cohort. Migraine was assessed by validated questionnaire and vascular calcification was assessed by computed tomography (expressed in Agatston score for the coronary arteries and volume in mm3 for the aortic arch, intracranial, and extracranial carotid arteries). Per vessel, the association of migraine with calcification was investigated by linear regression, adjusted for age, sex, cardiovascular risk factors, and calcification in other vessels. Results Of the participants, 279 (15%) were identified as persons with lifetime migraine. In multivariable adjusted models, migraine was associated with smaller intracranial carotid artery calcification volume (difference in log-transformed calcification volume in persons with migraine compared to persons without migraine: −0.19[−0.29, −0.08]). While subjects with migraine also showed a lower calcification burden in the remaining arterial beds, those associations did not reach statistical significance. Conclusions Persons with migraine, compared to those without, had less arterial calcification in the intracranial carotid artery, but not in other arterial beds. Future studies are needed to confirm these findings.
Published: 2019
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178. Thyroid Function and Cardiovascular Disease: The Mediating Role of Coagulation Factors

Author: Francesco U.S. Mattace-Raso, Oscar H. Franco, Moniek P.M. de Maat, Ferdows Atiq, Layal Chaker, Robin P. Peeters, Maryam Kavousi, Frank W.G. Leebeek, Arjola Bano, Epidemiology, Hematology, and Internal Medicine
Subjects: Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Thyroid Gland, ADAMTS13 Protein, 030209 endocrinology & metabolism, Context (language use), 030204 cardiovascular system & hematology, Fibrinogen, Biochemistry, 03 medical and health sciences, Rotterdam Study, 0302 clinical medicine, Endocrinology, SDG 3 - Good Health and Well-being, hemic and lymphatic diseases, Internal medicine, von Willebrand Factor, medicine, Humans, Prospective Studies, Prospective cohort study, Blood Coagulation, Aged, Proportional Hazards Models, Aged, 80 and over, business.industry, Proportional hazards model, Biochemistry (medical), Middle Aged, ADAMTS13, Thyroxine, Coagulation, Cardiovascular Diseases, Female, Thyroid function, business, medicine.drug
Abstract: CONTEXT Mechanisms linking high and high-normal thyroid function to an increased cardiovascular risk remain unclear. Hypothetically, coagulation can play a role. OBJECTIVE To investigate: (i) the association of thyroid function with coagulation factors, (ii) whether coagulation factors mediate the association of thyroid function with cardiovascular disease (CVD). DESIGN AND SETTING Rotterdam Study, a population-based, prospective study. PARTICIPANTS AND MAIN OUTCOME MEASUREMENTS In 5918 participants (mean age, 69.1 years), we measured thyrotropin, free thyroxine (FT4) and coagulation factors (von Willebrand factor antigen [VWF:Ag], ADAMTS13 activity, fibrinogen). Participants were followed for the occurrence of cardiovascular events and deaths. Associations of thyroid function with coagulation factors (standardized Z scores) and CVD were assessed through linear regression and Cox-proportional hazard models, adjusted for potential confounders. We performed causal mediation analyses to evaluate if the effect of thyroid function on CVD is mediated by coagulation. RESULTS Higher FT4 levels were associated with higher VWF:Ag (β=0.34; 95% confidence interval [95%CI]=0.22,0.47), lower ADAMTS13 activity (β=-0.22; 95%CI=-0.35,-0.09), and higher fibrinogen (β=0.26; 95%CI=0.13,0.39). 857 incident cardiovascular events and 690 cardiovascular deaths occurred. FT4 levels were positively associated with cardiovascular events and deaths. The effect of FT4 on incident cardiovascular events was minimally mediated by fibrinogen (1.6%), but not by VWF:Ag and ADAMTS13. VWF:Ag and fibrinogen together mediated 10.0% of the effect of FT4 on cardiovascular deaths. CONCLUSIONS Higher FT4 levels were associated with higher VWF:Ag, lower ADAMTS13 activity and higher fibrinogen, indicating a procoagulant state. VWF:Ag and fibrinogen explained up to 10% of the link between FT4 with CVD.
Published: 2019

179. Novel metabolic indices and incident type 2 diabetes among women and men: the Rotterdam Study

Author: Adela Brahimaj, Eric J.G. Sijbrands, Taulant Muka, Oscar H. Franco, Maryam Kavousi, Abbas Dehghan, Fernando Rivadeneira, General Practice, Internal Medicine, and Epidemiology
Subjects: 0301 basic medicine, Male, Epidemiology, Endocrinology, Diabetes and Metabolism, Type 2 diabetes, Body Mass Index, Rotterdam Study, 0302 clinical medicine, Absorptiometry, Photon, Risk Factors, 610 Medicine & health, Adiposity, DXA, Anthropometry, Middle Aged, Obesity, Abdominal, Android fat, Female, Android fat distribution, TyG, 360 Social problems & social services, medicine.medical_specialty, Diabetes risk, 030209 endocrinology & metabolism, Intra-Abdominal Fat, Article, 03 medical and health sciences, BMI, SDG 3 - Good Health and Well-being, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Humans, Aged, Proportional Hazards Models, Proportional hazards model, business.industry, medicine.disease, VAI, 030104 developmental biology, Diabetes Mellitus, Type 2, Gynoid fat, LAP, Combined indices, business
Abstract: Aims/hypothesis Both visceral and truncal fat have been associated with metabolic disturbances. We aimed to investigate the associations of several novel metabolic indices, combining anthropometric and lipid measures, and dual-energy x-ray absorptiometry (DXA) measurements of body fat, with incident type 2 diabetes among women and men from the large population-based Rotterdam Study. Methods Cox proportional hazards models were used to investigate associations of visceral adiposity index (VAI), lipid accumulation product (LAP), the product of triacylglycerol and glucose (TyG), their formula components and DXA measures with incident type 2 diabetes. Associations were adjusted for traditional diabetes risk factors. Results Among 5576 women and 3988 men free of diabetes, 511 women and 388 men developed type 2 diabetes during a median follow-up of 6.5 years. In adjusted models, the three metabolic indices VAI (per 1 SD naturally log-transformed HR; 95% CI) (1.49; 1.36, 1.65 in women; 1.37; 1.22, 1.53 in men), LAP (1.35; 1.16, 1.56 in women; 1.19; 1.01, 1.42 in men) and TyG (1.73; 1.52, 1.98 in women; 1.43; 1.26, 1.62 in men), gynoid fat mass (0.63; 0.45, 0.89) and android to gynoid fat ratio (1.51; 1.16, 1.97) in women were associated with incident type 2 diabetes. BMI (1.45; 1.28, 1.65) was the strongest predictor of type 2 diabetes in men. Conclusions/interpretation Among women, novel combined metabolic indices were stronger risk markers for type 2 diabetes than the traditional anthropometric and laboratory measures and were comparable with DXA measures. Neither combined metabolic indices nor DXA measures were superior to traditional anthropometric and lipid measures in association with type 2 diabetes among men. Electronic supplementary material The online version of this article (10.1007/s00125-019-4921-2) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
Published: 2019
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180. Superhydrophobic and super-oleophilic natural sponge sorbent for crude oil/water separation

Author: Maryam Kavousi Heidari, Mona Fouladi, Houman Asghari Sooreh, and Omid Tavakoli
Subjects: Process Chemistry and Technology, Safety, Risk, Reliability and Quality, Waste Management and Disposal, Biotechnology
Published: 2022
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181. Hepatic steatosis is not associated with increased mortality in the elderly-time for a paradigm shift?

Author: Laurens van Kleef, Milan Sonneveld, Maryam Kavousi, Arfan Ikram, Robert De Man, and Robert De Knegt
Subjects: Hepatology
Published: 2022
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182. Cardiovascular health, genetic predisposition, and lifetime risk of type 2 diabetes

Author: Maryam Kavousi, Kan Wang, Mohsen Ghanbari, Fariba Ahmadizar, M. Arfan Ikram, Trudy Voortman, and Epidemiology
Subjects: Male, Epidemiology, Health Status, Population, Blood Pressure, Type 2 diabetes, Cardiovascular System, Rotterdam Study, SDG 3 - Good Health and Well-being, Risk Factors, Genetic predisposition, Medicine, Humans, Genetic Predisposition to Disease, Prospective Studies, education, Aged, education.field_of_study, business.industry, Incidence (epidemiology), Middle Aged, medicine.disease, Blood pressure, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Lifetime risk, Female, Cardiology and Cardiovascular Medicine, business, Body mass index, Demography
Abstract: Aims Data on the lifetime risk of type 2 diabetes (T2D) incidence across different cardiovascular health (CVH) categories are scarce. Moreover, it remains unclear whether a genetic predisposition modifies this association. Methods and results Using data from the prospective population-based Rotterdam Study, a CVH score (body mass index, blood pressure, total cholesterol, smoking status, diet, and physical activity) was calculated and further categorized at baseline. Genetic predisposition to T2D was assessed and divided into tertiles by creating a genetic risk score (GRS). We estimated the lifetime risk for T2D within different CVH and GRS categories. Among 5993 individuals free of T2D at baseline [mean (standard deviation) age, 69.1 (8.5) years; 58% female], 869 individuals developed T2D during follow-up. At age 55 years, the remaining lifetime risk of T2D was 22.6% (95% CI: 19.4–25.8) for ideal, 28.3% (25.8–30.8) for intermediate, and 32.6% (29.0–36.2) for poor CVH. After further stratification by GRS tertiles, the lifetime risk for T2D was still the lowest for ideal CVH in the lowest GRS tertiles [21.5% (13.7–29.3)], in the second GRS tertile [20.8% (15.9–25.8)], and in the highest tertile [23.5% (18.5–28.6)] when compared with poor and intermediate CVH. Conclusion Our results highlight the importance of favourable CVH in preventing T2D among middle-aged individuals regardless of their genetic predisposition.
Published: 2021

183. MiR-139-5p is a causal biomarker for type 2 diabetes; Results from genome-wide microRNA profiling and Mendelian randomization analysis in a population-based study

Author: Mohsen Ghanbari, Abbas Dehghan, Fariba Ahmadizar, Marina Evangelou, M. A. Ikram, Maryam Kavousi, Rima Mustafa, and Michelle M. J. Mens
Subjects: education.field_of_study, Population, Mendelian Randomization Analysis, Type 2 diabetes, Biology, Bioinformatics, medicine.disease, Rotterdam Study, Diabetes mellitus, microRNA, Mendelian randomization, medicine, Biomarker (medicine), education
Abstract: MicroRNAs (miRNAs) have emerged as key regulators of gene expression. Differential expression of miRNAs has been linked to diabetes, but underlying pathways remain poorly understood. We performed genome-wide miRNAs profiling and tested the causal associations between miRNAs and type 2 diabetes in the general population. Subsequently, we investigated target genes and metabolites of miRNAs to provide insight into the metabolic disturbances that emerge with type 2 diabetes. Between 2002 and 2005, plasma levels of 2083 circulatory miRNAs were profiled in 1900 participants (mean age 71.4 years) of the population-based Rotterdam Study cohort. The associations of 591 well-expressed miRNAs with prevalent and incident type 2 diabetes were examined until 2015. Two-sample Mendelian Randomization (MR) was conducted to investigate the causal associations and miRNA-target genes and metabolites were studied in relation to type 2 diabetes. At baseline, higher plasma levels of miR-139-5p and miR-193a-5p were associated (FDR9.0 years, 209 participants developed type 2 diabetes. Plasma levels of miR-99a-5p, miR-4664-3p, miR-29a-3p, miR-122-5p, and miR-125b-5p were significantly associated with incident type 2 diabetes (n=209). Two-sample MR confirmed a causal effect for miR-139-5p (MR-IWV-beta=0.10, p=3.51×10−4) on type 2 diabetes. We found several target genes and metabolites that could link miR-139-5p to pathways underlying type 2 diabetes. Our study indicates a causal relationship between miR-139-5p and type 2 diabetes and suggests this miRNA as a plasma biomarker of type 2 diabetes.
Published: 2021
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184. Association between circulatory microRNAs in plasma and atrial fibrillation among men and women from the general population

Author: Maryam Kavousi, Mmj Mens, S Geurts, M. A. Ikram, Mohsen Ghanbari, and M.M. Bos
Subjects: medicine.medical_specialty, education.field_of_study, Epidemiology, business.industry, Population, Atrial fibrillation, medicine.disease, Internal medicine, microRNA, Circulatory system, medicine, Cardiology, Cardiology and Cardiovascular Medicine, business, education
Abstract: Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. This project is further supported by the Gender and Prevention grant (555003017) from ZonMw. Background MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression. They have shown to play an important role in cardiovascular disease, but there is limited population-based data regarding the relationship between circulatory miRNAs in plasma and atrial fibrillation (AF). Moreover, it remains unclear if the associations between miRNAs with AF differ by sex. Purpose To determine the association of miRNAs with the risk of prevalent and incident AF among men and women from the general population. Methods Plasma levels of circulatory miRNAs were measured in 858 men and 1141 women from a large prospective population-based cohort study. Logistic regression and Cox Proportional Hazards models were used to assess the associations of 591 well-expressed miRNAs with the prevalence and incidence of AF. Models were adjusted for age and cardiovascular risk factors. We further examined the link between predicted target genes of identified miRNAs and AF. Results The mean age was 71.7 years (57.1% women), 58 men and 40 women had prevalent AF at baseline. Moreover, 96 men and 100 women developed AF during a median follow-up of 9.0 years. After adjusting for multiple testing, miR-4798-3p was significantly associated with prevalent AF among men; odds ratio: 0.39 (95% CI 0.24-0.66). No miRNAs were significantly associated with incident AF. MiR-4798-3p could potentially regulate the expression of AF-related genes, including genes involved in calcium and potassium handling in myocytes, protection of cells against oxidative stress, and cardiac fibrosis. Conclusions Plasma levels of miR-4798-3p were significantly associated with prevalent AF among men. Various target genes in relation to AF pathophysiology could potentially be regulated by miR-4798-3p that warrant further investigations in future experimental studies.
Published: 2021
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185. Cardiac biomarkers for cardiovascular risk prediction among women and men from the general population

Author: E Aribas, M. A. Ikram, Maryam Kavousi, Banafsheh Arshi, F Zhu, and Mohammad Kamran Ikram
Subjects: medicine.medical_specialty, education.field_of_study, Epidemiology, business.industry, Cardiac biomarkers, Internal medicine, Population, medicine, Cardiology and Cardiovascular Medicine, business, education
Abstract: Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): the Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Health Research and Development (ZonMw); Purpose To evaluate the sex-specific predictive value of two cardiac biomarkers; N-terminal pro B-type natriuretic peptide (NT-proBNP) and high sensitivity cardiac troponin T (hs-cTnT), alongside traditional cardiovascular risk factors, for 10-year cardiovascular risk prediction in general population. Methods A total of 5430 participants (mean age 68.1 years; 59.9% women) free of cardiovascular disease (CVD), with blood sample measurements between 1997 and 2001 were included. We developed a ‘base’ model using cardiovascular risk factors used in the Pooled Cohort Equation (includes age, sex, systolic blood pressure, treatment of hypertension, total and high-density lipoprotein cholesterol levels, smoking, and diabetes) and then extended the ‘base’ model with NT-proBNP or hs-cTnT. These models were developed for coronary heart disease (CHD), stroke, and heart failure (HF) and also for composite CVD outcomes. To evaluate biomarkers’ added predictive value, c-statistic, and net reclassification improvement index (NRI) for events and non-events were calculated. NRI was calculated using cutoffs of 5%, 7.5% and 20% to categorize participants as low, borderline, intermediate, or high risk. Results Adding NT-proBNP to the ‘base’ model significantly improved c-statistic for all outcomes (increases ranged between 0.012-0.047), with the largest improvement in HF [0.026 (95% CI, 0.013, 0.040) for women and 0.047 (95% CI, 0.026, 0.069) for men]. Adding hs-TnT to ‘base’ model increased the c-statistic for CHD in women by 0.040 (95% CI, 0.013, 0.067) and for HF in men by 0.032 (95% CI, 0.005, 0.059). Improvments in reclassification by both biomarkers were mostly limited to modest improvemetns in reclassification of non-events [largest non-event NRI for global CVD in women (NT-proBNP: 11.8%; hs-cTnT: 10.5%) and for HF in men (NT-proBNP: 9.6%; hs-cTnT: 8.4%)]. Conclusion NT-proBNP improved model performance for prediction of all cardiovascular outcomes, in particular for HF, beyond traditional risk factors for both women and men. Hs-cTnT showed modest added predictive value beyond traditional risk factors for CHD among women and for HF among men. Imropovements in reclassification by both biomarkers were modest and not clinically relevant. Improvements of 10-year risk predictions Events Adding NT-proBNP Adding troponin T Delta c-statistic* Event NRI, % Non-event NRI, % Delta c-statistic* Event NRI, % Non-event NRI, % WomenASCVD Global CVD 0.012 (0.004, 0.020) 0.018 (0.010, 0.026) -1.7 (-5.0, 1.5)-0.8 (-3.8, 2.2) 5.4 (3.5, 7.2)11.8 (9.6, 14.1) 0.028 (0.009, 0.048)0.025 (0.009, 0.040) -0.4 (-7.1, 6.2)2.9 (-2.4, 8.3) 6.9 (3.9, 9.9)10.5 (7.3, 13.8) MenASCVD Global CVD 0.016 (0.005, 0.027)0.023 (0.012, 0.033) 0.7 (-2.3, 3.7)-0.3 (-3.0, 2.4) 5.2 (3.2, 7.2)7.2 (4.9, 9.4) 0.007 (-0.002, 0.016)0.011 (0.000, 0.021) -1.1 (-5.0, 2.7)-1.6 (-6.0, 2.8) 4.0 (1.2, 6.9)6.4 (3.1, 9.7) ASCVD comprises coronary heart disease and stroke; Global CVD comprises coronary heart disease, stroke and heart failure.
Published: 2021
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186. Associations of markers of arterial stiffness and remodeling with new-onset type 2 diabetes mellitus

Author: Kan Wang, F.U.S. Mattace Raso, M. A. Ikram, Fariba Ahmadizar, and Maryam Kavousi
Subjects: Mean arterial pressure, medicine.medical_specialty, Epidemiology, Cholesterol, business.industry, Type 2 Diabetes Mellitus, medicine.disease, New onset, chemistry.chemical_compound, chemistry, Internal medicine, Heart rate, Arterial stiffness, Cardiology, Medicine, Aortic stiffness, Prediabetes, Cardiology and Cardiovascular Medicine, business
Abstract: Funding Acknowledgements Type of funding sources: None. Background. Arterial stiffness/remodeling results in impaired blood flow and, eventually, decreased glucose disposal in peripheral tissues and increased blood glucose. Besides, increased arterial stiffness/remodeling may lead to hypertension, as a potential reciprocal risk factor for type 2 diabetes mellitus (T2D). We, therefore, hypothesized that increased arterial stiffness/remodeling is associated with an increased risk of T2D. Purpose. To study the associations between arterial stiffness/remodeling and incident T2D. Methods. We used the prospective population-based Rotterdam Study. Common carotid arterial properties were ultrasonically determined in plaque-free areas. Aortic stiffness was estimated by carotid-femoral pulse wave velocity (cf_PWV), carotid stiffness was estimated by the carotid distensibility coefficient (carDC). Arterial remodeling was estimated by carotid artery lumen diameter (carDi), carotid intima-media thickness (cIMT), mean circumferential wall stress (CWSmean), and pulsatile circumferential wall stress (CWSpuls). Cox proportional hazard regression analysis was used to estimate the associations between arterial stiffness/remodeling and the risk of incident T2D, adjusted for age, sex, cohort, mean arterial pressure (MAP), antihypertensive medications, heart rate, non- high-density lipoprotein (HDL)-cholesterol, lipid-lowering medications, and smoking. We included interaction terms in the fully adjusted models to study whether any significant associations were modified by sex, age, blood glucose, or MAP. Spearman correlation analyses were applied to examine the correlations between measurements of arterial stiffness/remodeling and glycemic traits. Results. We included 3,055 individuals free of T2D at baseline (mean (SD) age, 67.2 (7.9) years). During a median follow-up of 14.0 years, 395 (12.9%) T2D occurred. After adjustments, higher cf_PWV (hazard ratio (HR),1.18; 95%CI:1.04-1.35), carDi (1.17; 1.04-1.32), cIMT (1.15; 1.01-1.32), and CWSpuls (1.28; 1.12-1.47) were associated with increased risk of incident T2D. After further adjustment for the baseline glucose, the associations attenuated but remained statistically significant. Sex, age, blood glucose, or MAP did not modify the associations between measurements of arterial stiffness/remodeling, and incident T2D. Among the population with prediabetes at baseline (n = 513) compared to the general population, larger cIMT was associated with a greater increase in the risk of T2D. Most measurements of arterial stiffness/remodeling significantly but weakly correlated with baseline glycemic traits, particularly with blood glucose. Conclusions. Our study suggests that greater arterial stiffness/remodeling is independently associated with an increased risk of T2D development. Blood glucose and hypertension do not seem to play significant roles in these associations. Further studies should disentangle the underlying mechanism that links arterial stiffness/remodeling and T2D.
Published: 2021
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187. Reply: Carotid Intraplaque Hemorrhage and Cardiovascular Events: Are Antithrombotic Therapies the Missing Piece of the Puzzle?

Author: Daniel, Bos, Meike W, Vernooij, Maryam, Kavousi, and Aad, van der Lugt
Subjects: Carotid Arteries, Fibrinolytic Agents, Cardiovascular Diseases, Humans, Hemorrhage
Published: 2021

188. Long-term association of pregnancy and maternal brain structure: the Rotterdam Study

Author: Jurate, Aleknaviciute, Tavia E, Evans, Elif, Aribas, Merel W, de Vries, Eric A P, Steegers, Mohammad Arfan, Ikram, Henning, Tiemeier, Maryam, Kavousi, Meike W, Vernooij, and Steven A, Kushner
Subjects: Cohort Studies, Pregnancy, Brain, Humans, Female, Gray Matter, Magnetic Resonance Imaging, White Matter, Aged
Abstract: The peripartum period is the highest risk interval for the onset or exacerbation of psychiatric illness in women's lives. Notably, pregnancy and childbirth have been associated with short-term structural and functional changes in the maternal human brain. Yet the long-term effects of pregnancy on maternal brain structure remain unknown. We investigated a large population-based cohort to examine the association between parity and brain structure. In total, 2,835 women (mean age 65.2 years; all free from dementia, stroke, and cortical brain infarcts) from the Rotterdam Study underwent magnetic resonance imaging (1.5 T) between 2005 and 2015. Associations of parity with global and lobar brain tissue volumes, white matter microstructure, and markers of vascular brain disease were examined using regression models. We found that parity was associated with a larger global gray matter volume (β = 0.14, 95% CI = 0.09-0.19), a finding that persisted following adjustment for sociodemographic factors. A non-significant dose-dependent relationship was observed between a higher number of childbirths and larger gray matter volume. The gray matter volume association with parity was globally proportional across lobes. No associations were found regarding white matter volume or integrity, nor with markers of cerebral small vessel disease. The current findings suggest that pregnancy and childbirth are associated with robust long-term changes in brain structure involving a larger global gray matter volume that persists for decades. Future studies are warranted to further investigate the mechanism and physiological relevance of these differences in brain morphology.
Published: 2021

189. A NOS1AP gene variant is associated with a paradoxical increase of the QT-interval shortening effect of digoxin

Author: Negin, Soroush, Albert-Jan, Aarnoudse, Maryam, Kavousi, Jan A, Kors, M Arfan, Ikram, Christopher, Newton-Cheh, Fariba, Ahmadizar, and Bruno H, Stricker
Subjects: Aged, 80 and over, Male, Digoxin, Cardiotonic Agents, Genotype, Genetic Variation, Middle Aged, Electrocardiography, Long QT Syndrome, Treatment Outcome, Linear Models, Humans, Female, Longitudinal Studies, Prospective Studies, Adaptor Proteins, Signal Transducing, Aged, Follow-Up Studies
Abstract: Digoxin is characterized by a small therapeutic window and a QT-interval shortening effect. Moreover, it has been shown that the genetic variants of the nitric oxide synthase-1 adaptor protein (NOS1AP) gene are associated with QT-interval prolongation. We investigated whether the rs10494366 variant of the NOS1AP gene decreases the QT-interval shortening effect of digoxin in patients using this drug. We included 10,057 individuals from the prospective population-based cohort of the Rotterdam Study during a median of 12.2 (interquartile range (IQR) 6.7-18.1) years of follow-up. At study entry, the mean age was 64 years and almost 59% of participants were women. A total of 23,179 ECGs were longitudinally recorded, of which 334 ECGs were from 249 individuals on digoxin therapy. The linear mixed model analysis was used to estimate the effect of the rs10494366 variant on the association between digoxin use and QT-interval duration, adjusted for age, sex, RR interval, diabetes, heart failure, and history of myocardial infarction. In non-users of digoxin, the GG genotype was associated with a significant 6.5 ms [95% confidence interval (CI) 5.5; 7.5] longer QT-interval duration than the TT variant. In current digoxin users, however, the GG variant was associated with a significantly -23.9 [95%CI -29.5; -18.5] ms shorter mean QT-interval duration than in those with the TT variant with -15.9 [95%CI -18.7; -13.1]. This reduction was strongest in the high digoxin dose category [≥0.250 mg/day] with the GG genotype group, with -40.8 [95%CI -52.5; -29.2] ms changes compared to non-users. Our study suggests that the minor homozygous GG genotype group of the NOS1AP gene rs10494366 variant is associated with a paradoxical increase of the QT-interval shortening effect of digoxin in a population of European ancestry.
Published: 2021

190. Association of circulating monocyte chemoattractant protein-1 levels with cardiovascular mortality: A meta-analysis of population-based studies

Author: Caroline Sun, Ron C. Hoogeveen, Olle Melander, Tiberiu A Pana, Phyo K. Myint, James A. de Lemos, Lana Fani, Astrid Zierer, Colby Ayers, Barbara Thorand, Christie M. Ballantyne, Emelia J. Benjamin, Martin Dichgans, Christian Herder, Annette Peters, Maryam Kavousi, Mohamed A. Elhadad, Wolfgang Koenig, S. Matthijs Boekholdt, Jan Nilsson, Gunnar Engström, Rainer Malik, Josée Dupuis, Marju Orho-Melander, Marios K. Georgakis, Biqi Wang, Harry Björkbacka, Epidemiology, ACS - Atherosclerosis & ischemic syndromes, Cardiology, and ACS - Heart failure & arrhythmias
Subjects: medicine.medical_specialty, blood [Myocardial Infarction], Population, mortality [Cardiovascular Diseases], Disease, 030204 cardiovascular system & hematology, epidemiology [Coronary Disease], blood [Coronary Disease], 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, blood [Cardiovascular Diseases], Internal medicine, blood [Chemokine CCL2], medicine, Humans, 030212 general & internal medicine, Myocardial infarction, ddc:610, education, Proportional Hazards Models, education.field_of_study, Unstable angina, business.industry, Proportional hazards model, Brief Report, Hazard ratio, medicine.disease, epidemiology [Myocardial Infarction], 3. Good health, Meta-analysis, Cardiology, Cardiology and Cardiovascular Medicine, business, Cohort study
Abstract: Importance: Human genetics and studies in experimental models support a key role of monocyte-chemoattractant protein-1 (MCP-1) in atherosclerosis. Yet, the associations of circulating MCP-1 levels with risk of coronary heart disease and cardiovascular death in the general population remain largely unexplored. Objective: To explore whether circulating levels of MCP-1 are associated with risk of incident coronary heart disease, myocardial infarction, and cardiovascular mortality in the general population. Data Sources and Selection: Population-based cohort studies, identified through a systematic review, that have examined associations of circulating MCP-1 levels with cardiovascular end points. Data Extraction and Synthesis: Using a prespecified harmonized analysis plan, study-specific summary data were obtained from Cox regression models after excluding individuals with overt cardiovascular disease at baseline. Derived hazard ratios (HRs) were synthesized using random-effects meta-analyses. Main Outcomes and Measures: Incident coronary heart disease (myocardial infarction, coronary revascularization, and unstable angina), nonfatal myocardial infarction, and cardiovascular death (from cardiac or cerebrovascular causes). Results: The meta-analysis included 7 cohort studies involving 21401 individuals (mean [SD] age, 53.7 [10.2] years; 10012 men [46.8%]). Mean (SD) follow-up was 15.3 (4.5) years (326392 person-years at risk). In models adjusting for age, sex, and race/ethnicity, higher MCP-1 levels at baseline were associated with increased risk of coronary heart disease (HR per 1-SD increment in MCP-1 levels: 1.06 [95% CI, 1.01-1.11]; P =.01), nonfatal myocardial infarction (HR, 1.07 [95% CI, 1.01-1.13]; P =.02), and cardiovascular death (HR, 1.12 [95% CI, 1.05-1.20]; P
Published: 2021
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191. Associations between macronutrient intake and coronary heart disease (CHD): The Rotterdam Study

Author: Maryam Kavousi, Zhangling Chen, Kim V.E. Braun, Carolin Girschik, Oscar H. Franco, Trudy Voortman, and Epidemiology
Subjects: Male, Carbohydrate, Nutrition and Disease, Saturated fat, Population, Coronary Disease, Critical Care and Intensive Care Medicine, Lower risk, Diet Surveys, Body Mass Index, Eating, Rotterdam Study, Environmental health, Voeding en Ziekte, Humans, Medicine, Mass index, Prospective Studies, education, 610 Medicine & health, Triglycerides, Aged, Proportional Hazards Models, education.field_of_study, Nutrition and Dietetics, business.industry, Incidence, Protein, Nutrients, Middle Aged, Diet, Coronary heart disease, Cholesterol, Adipose Tissue, Heart Disease Risk Factors, Plant protein, Fat, Body Composition, Regression Analysis, Female, Macronutrients, business, Body mass index, Substitution, 360 Social problems & social services, Follow-Up Studies, Cohort study
Abstract: Summary Background & aims Dietary intake of several specific macronutrients has been linked to risk of coronary heart disease (CHD). However, these associations may depend on overall macronutrient composition rather than effects of one single macronutrient. Therefore, we aimed to investigate the associations of macronutrient intake and CHD and its related risk factors, by taking into account different macronutrient substitutions. Methods This study was performed among 5873 participants from the Rotterdam Study, a population-based cohort study. Macronutrient intake was measured using a semi-quantitative food-frequency questionnaire. Cox proportional hazard regression analyses were used to examine associations between intakes of macronutrients and CHD incidence; and linear regression analyses were used to examine associations with the related risk factors, including triglycerides, total, high-density and low-density cholesterol levels, body mass index (BMI), fat mass index (FMI), and fat-free mass index (FFMI). Results We documented 669 CHD cases during 74,776 person-years of follow-up. In multivariable-adjusted models we observed no statistically significant associations between macronutrients and CHD incidence. Although non-significant, a higher plant protein intake tended to be associated with a lower risk of CHD when consumed at the expense of any of the other macronutrients. This association was strongest when 5% of energy (5 E%) of plant protein was consumed at the expense of animal protein (HR = 0.61; 95% CI 0.31, 1,21), mono- and disaccharides (HR = 0.62; 95% CI 0.29, 1.35) or saturated fat (HR = 0.61; 95% CI 0.31, 1.20). No consistent associations were observed for risk factors related to CHD. Conclusions Macronutrient composition was not significantly associated with CHD incidence or cardiometabolic risk factors in an adult population. Future studies should further investigate food sources and quality of macronutrients.
Published: 2021
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192. Antidiabetic Medications and Eye Diseases

Author: Joëlle E. Vergroesen, Eric F. Thee, Fariba Ahmadizar, Cornelia van Duijn, Bruno H. Stricker, Maryam Kavousi, Caroline C.W. Klaver, and Wishal D. Ramdas
Published: 2021
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193. Heart failure and promotion of physical activity before and after cardiac rehabilitation (HF-aPProACH)

Author: M.A.M. (Marlou) Limpens, M.T. (Muhammed) Gürgöze, M.J. (Mattie) Lenzen, S. (Stefan) Roest, R.G. (Trudy) Voortman, M. (Maryam) Kavousi, N. (Nienke) ter Hoeve, M (Madoka) Sunamura, I. (Iris) den Uijl, P.J. (Peter) van der Spek, J.J. (Jasper) Brugts, O.C. (Olivier) Manintveld, A.S. (Arne) IJpma, H. (Eric) Boersma, M.A.M. (Marlou) Limpens, M.T. (Muhammed) Gürgöze, M.J. (Mattie) Lenzen, S. (Stefan) Roest, R.G. (Trudy) Voortman, M. (Maryam) Kavousi, N. (Nienke) ter Hoeve, M (Madoka) Sunamura, I. (Iris) den Uijl, P.J. (Peter) van der Spek, J.J. (Jasper) Brugts, O.C. (Olivier) Manintveld, A.S. (Arne) IJpma, and H. (Eric) Boersma
Abstract: Aims: Lifestyle changes, such as increasing physical activity (PA), are a cornerstone of treatment of patients with chronic heart failure (HF). However, improving PA in HF patients is challenging, and low participation rates for cardiac rehabilitation (CR) as well as relapse to low PA levels after CR are major issues. We designed a randomized controlled trial to investigate if PA monitoring with motivational feedback before and after centre-based CR in HF patients with reduced ejection fraction (HFrEF) will lead to a clinically meaningful increase in physical fitness. Methods and results: A randomized controlled trial will be conducted in a sample of 180 HFrEF patients (New York Heart Association Class II/III) who are referred to 12-week standard CR. Patients will be randomized (2:1) to (1) standard of care (SoC) plus wearing a PA monitoring device (Fitbit Charge 3) with personalized step goals, feedback and motivation or (2) SoC only. The intervention lasts ±7 months: 4–5 weeks before CR, 12 weeks during CR and 12 weeks after CR. Measurements will take place at three time points. The primary endpoint is the change in the distance in 6-min walking test (6MWT) over the entire study period. Other endpoints include step count, grip strength, quality of life and all-cause mortality or hospitalization. Conclusions: HF-aPProACH will provide novel information on the effectiveness of remote PA stimulation and feedback before, during and after standard CR using a commercially available device to improve physical fitness in HFrEF patients.
Published: 2021
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194. Aging, Cardiovascular Risk, and SHBG Levels in Men and Women from the General Population

Author: E. (Elif) Aribas, M. (Maryam) Kavousi, J.S.E. (Joop) Laven, M.A. (Arfan) Ikram, J.E. (Jeanine) Roeters van Lennep, E. (Elif) Aribas, M. (Maryam) Kavousi, J.S.E. (Joop) Laven, M.A. (Arfan) Ikram, and J.E. (Jeanine) Roeters van Lennep
Abstract: Aims: Prior studies have reported inconsistent results for the association between sex hormone-binding globulin (SHBG) and cardiovascular disease among men and women. Although it is suggested that SHBG levels change with aging, the exact trend of SHBG across age and cardiovascular risk and the underlying mechanisms of these changes remain to be elucidated. Methods: Using data of 3264 men and women from a large population-based cohort study, we first visualized the distribution of serum SHBG levels across age. Second, we computed a cardiovascular risk factor sum score and investigated the mean SHBG levels across categories of the risk factor sum score and stratified per age-category. Next, linear regression models were used to investigate the associations between serum SHBG levels and age and po
Published: 2021
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195. Arterial calcification at different sites and prediction of atherosclerotic cardiovascular disease among women and men

Author: J.E. (Janine) van der Toorn, D. (Daniel) Bos, B. (Banafsheh) Arshi, M.J.G. (Maarten) Leening, M.W. (Meike) Vernooij, M.A. (Arfan) Ikram, M.K. (Kamran) Ikram, M. (Maryam) Kavousi, J.E. (Janine) van der Toorn, D. (Daniel) Bos, B. (Banafsheh) Arshi, M.J.G. (Maarten) Leening, M.W. (Meike) Vernooij, M.A. (Arfan) Ikram, M.K. (Kamran) Ikram, and M. (Maryam) Kavousi
Abstract: Background and aims: The sex-specific contributions of arterial calcification to atherosclerotic cardiovascular disease (ASCVD) risk prediction and stratification in the light of recent modifications by cardiovascular prevention guidelines remain unclear. We assessed the sex-specific value of calcification in different arteries, beyond the Pooled Cohort Equations (PCE) risk factors, for 10-year ASCVD risk prediction. Methods: From 2003 to 2006, participants from the population-based Rotterdam Study (n = 2167) underwent CT to quantify coronary artery calcification (CAC), aortic arch calcification (AAC), extracranial (ECAC) and intracranial carotid artery calcification (ICAC). Follow-up for ASCVD was complete on January 1, 2015. We refitted the PCE (base model), and categorized participants into low (<5%), borderline (5%–7.5%), intermediate (7.5%–20%), and high (≥20%) ASCVD risk. We extended the models with calcifications and calculated c-statistics and net reclassification improvements for events (NRIe) and non-events (NRIne). Results: CAC predicted ASCVD in women [hazard-ratio (95%-CI) per 1-SD: 1.40 (1.14–1.73)] and men [1.62 (1.27–1.93)]. After addition of CAC to the base model, the c-statistic improved from 0.71 to 0.72 in women; from 0.65 to 0.68 in men. Addition of CAC led to NRIe of 14.3% in women, 4.8% in men and NRIne of 1.5% in women, 15.1% in men. Only in women, ICAC predicted ASCVD [hazard-ratio (95%-CI) per 1-SD: 1.62 (1.26–2.08)], and improved the model (c-statistic from 0.71 to 0.73, NRIe: 9.8% and NRIne: 5.9%). Conclusions: Assessment of CAC improves ASCVD risk prediction and stratification. In women, the added value of ICAC for ASCVD risk prediction is comparable to that of CAC.
Published: 2021
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196. Impaired fasting glucose, type 2 diabetes mellitus, and lifetime risk of cardiovascular disease among women and men

Author: F. (Fariba) Ahmadizar, K Wang, E. (Elif) Aribas, L (Lana) Fani, A. (Alis) Heshmatollah, M.K. (Kamran) Ikram, M. (Maryam) Kavousi, F. (Fariba) Ahmadizar, K Wang, E. (Elif) Aribas, L (Lana) Fani, A. (Alis) Heshmatollah, M.K. (Kamran) Ikram, and M. (Maryam) Kavousi
Abstract: Introduction Data on sex-specific lifetime risk of cardiovascular disease (CVD) across the glycemic spectrum, in particular in impaired fasting glucose (IFG) state, are scarce. Whether overweight/obesity modifies the CVD burden also remains unclear. Research design and methods Using a
Published: 2021
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197. Sex-specific normal values and determinants of infrarenal abdominal aortic diameter among non-aneurysmal elderly population

Author: F. (Fang) Zhu, B. (Banafsheh) Arshi, M.A. (Arfan) Ikram, R.J. (Rob) de Knegt, M. (Maryam) Kavousi, F. (Fang) Zhu, B. (Banafsheh) Arshi, M.A. (Arfan) Ikram, R.J. (Rob) de Knegt, and M. (Maryam) Kavousi
Abstract: To establish age- and sex-specific distribution of the infrarenal abdominal aortic diameters (IAD) among non-aneurysmal elderly population and to investigate the associations between traditional cardiovascular risk factors and IAD in men and women. We included 4032 participants (mean age 67.2 years; 60.4% women) from the population-based Rotterdam Study, free of cardiovascular disease, who underwent IAD ultrasound assessment between 2009–2014. Linear regression analysis was used to identify determinants of IAD. The medians (inter-quartile range) of absolute IAD and body surface area (BSA)-adjusted IAD were 17
Published: 2021
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198. Genetic susceptibility, obesity and lifetime risk of type 2 diabetes

Author: S. (Symen) Ligthart, Natalie R. Hasbani, F. (Fariba) Ahmadizar, T.T.W. (Thijs) van Herpt, M.J.G. (Maarten) Leening, A.G. (André) Uitterlinden, E.J.G. Sijbrands, Alanna C. Morrison, Eric Boerwinkle, James S. Pankow, Elizabeth Selvin, M. Arfan Ikram, M. (Maryam) Kavousi, PS de Vries, A. (Abbas) Dehghan, S. (Symen) Ligthart, Natalie R. Hasbani, F. (Fariba) Ahmadizar, T.T.W. (Thijs) van Herpt, M.J.G. (Maarten) Leening, A.G. (André) Uitterlinden, E.J.G. Sijbrands, Alanna C. Morrison, Eric Boerwinkle, James S. Pankow, Elizabeth Selvin, M. Arfan Ikram, M. (Maryam) Kavousi, PS de Vries, and A. (Abbas) Dehghan
Abstract: Aims: Both lifestyle factors and genetic background contribute to the development of type 2 diabetes. Estimation of the lifetime risk of diabetes based on genetic information has not been presented, and the extent to which a normal body weight can offset a high lifetime genetic risk is unknown. Methods: We used data from 15,671 diabetes-free participants of European ancestry aged 45 years and older from the prospective population-based ARIC study and Rotterdam Study (RS). We quantified the remaining lifetime risk of diabetes stratified by genetic risk and quantified the effect of normal weight in terms of relative and lifetime risks in low, intermediate and high genetic risk. Results: At age 45 years, the lifetime risk of type 2 diabetes in ARIC in the low, intermediate and high genetic risk category was 33.2%, 41.3% and 47.2%, and in RS 22.8%, 30.6% and 35.5% respectively. The absolute lifetime risk for individuals with normal weight compared to individuals with obesity was 24% lower in ARIC and 8.6% lower in RS in the low genetic risk group, 36.3% lower in ARIC and 31.3% lower in RS in the intermediate genetic risk group, and 25.0% lower in ARIC and 29.4% lower in RS in the high genetic risk group. Conclusions: Genetic variants for type 2 diabetes have value in estimating the lifetime risk of type 2 diabetes. Normal weight mitigates partly the deleterious effect of high genetic risk.
Published: 2021
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199. Circulatory markers of immunity and carotid atherosclerotic plaque

Author: Dianne H.K. van Dam-Nolen, Daniel Bos, Maryam Kavousi, Meike W. Vernooij, Lana Fani, Aad van der Lugt, Epidemiology, and Radiology & Nuclear Medicine
Subjects: 0301 basic medicine, medicine.medical_specialty, Lymphocyte, Population, Inflammation, Hemorrhage, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Immunity, Risk Factors, Internal medicine, medicine, Humans, Carotid Stenosis, education, education.field_of_study, business.industry, Monocyte, Odds ratio, Acquired immune system, Magnetic Resonance Imaging, Plaque, Atherosclerotic, 030104 developmental biology, medicine.anatomical_structure, Carotid Arteries, Cardiology, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Blood sampling
Abstract: Background and aims: We aimed to determine the association of circulatory markers of innate and adaptive immunity with carotid atherosclerotic plaque characteristics. Methods: In 1602 participants from the population-based Rotterdam Study with subclinicalcarotid atherosclerosis, blood sampling was performed to determine granulocyte, platelet, monocyte (innate immunity) and lymphocyte (adaptive immunity) counts, from which the granulocyte-to-lymphocyte ratio [GLR], platelet-to-lymphocyte ratio [PLR], monocyte-to-lymphocyte ratio [MLR] and systemic immune-inflammation index [SII] were calculated. All participants underwent carotid MRI for evaluation of plaque characteristics. Plaque size (stenosis >30%, maximum plaque thickness) and plaque composition (presence of intraplaque hemorrhage [IPH], lipid-rich necrotic core [LRNC], and calcification) were assessed. Using linear and logistic regression models, the association of innate and adaptive immunity markers with plaque size and plaque components, adjusting for relevant confounders, was assessed. Results: Higher levels of granulocytes were significantly associated with larger plaque thickness (mean difference [Ln (mm)] per Ln increase granulocyte count [95% CI]: 0.06 [0.02; 0.10]). Conversely, more lymphocytes related with smaller maximum plaque thickness (mean difference [Ln (mm)] per Ln increase lymphocyte count: 0.09 [-0.14;-0.04]) and a lower prevalence of IPH (odds ratio per Ln increase lymphocyte count: 0.60 [0.37; 0.97]). Moreover, all ratio measures were associated with larger plaque thickness, of which the MLR also associated with more frequent LRNC (odds ratio per Ln increase MLR: 1.26 [1.02; 1.56]). Conclusions: The innate immunity links to larger plaques, whilst the adaptive immunity seems to relate to smaller plaques and a lower frequency of IPH. These results suggest that an imbalance in innate and adaptive immunity may play a role in the vulnerability of carotid atherosclerotic plaques.
Published: 2020

200. Author response: Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

Author: Zahra Mohammadi, Abdul Basit, Helena I. S. Nogueira, Soile E. Puhakka, Hongsheng Bi, Ari Voutilainen, Davood Khalili, Bin Zhou, Dermot O'Reilly, Natascia Rinaldo, Paulo A. Lotufo, Bahareh Kheiri, Thein Thein Htay, Simona Giampaoli, Goodarz Danaei, M. Fernanda Lima-Costa, Simona Bo, Peter Schnohr, Jerzy Chudek, Francesco Panza, Ling Yang, Katia Vergetti Bloch, Vincenzo Capuano, Holly E. Syddall, Dong Zhao, Indah Suci Widyahening, Maria Lorenza Muiesan, Leng Huat Foo, Mohsen Azimi-Nezhad, Merete Osler, Laura Torres-Collado, Manu Raj, Adroaldo Cesar Araujo Gaya, Susi Kriemler, Ali Akbar Shayesteh, Aneta Grajda, Anette Varbo, Kazem Mohammad, Leila Beltrami Moreira, Shu Ti Chiou, Iuliia A Rusakova, Jyh Eiin Wong, Torben Jørgensen, Lela Sturua, Lubica Ticha, Hamid Hakimi, Hazzaa M. Al-Hazzaa, Yanina Zócalo, Freda Pitakaka, Savvas C. Savva, Rajeev Gupta, Jennifer Servais, Marie Kunešová, Johanna M. Geleijnse, Elysée Claude Bika Lele, Yannis Manios, Jorge Escobedo-de la Peña, Yufang Bi, Chinh Nguyen Huu, Sibel Gogen, Viviane Cunha Cardoso, Kristine H. Allin, Ana Azevedo, Line Tang Møllehave, Vincent Jr DeGennaro, Novie O. Younger-Coleman, Gretchen A Stevens, Dickman Gareta, Holger Theobald, Anja Schienkiewitz, Bekbolat Zholdin, Janice Luisa Lukrafka, Adela Chirita-Emandi, Ulla Roggenbuck, Kenisha Russell Jonsson, Robespierre Ribeiro, Gabriele Eiben, Eero Kajantie, Sounnia Mediene Benchekor, Fariborz Mansour-Ghanaei, Mary Simon, Prakash C. Gupta, Mohammad Esmaeel Motlagh, Emanuela Gualdi-Russo, María Elena Díaz-Sánchez, Pilar Guallar-Castillón, Bee Koon Poh, Cristina Padez, Azaliia M Tuliakova, Sarah P. Garnett, William R. Tebar, Yingfeng Zheng, Suhad Bahijri, Christina Mavrogianni, Mihaela Vladulescu, Jan A. Staessen, Paula Duarte de Oliveira, Rui Ornelas, Michael Sjöström, Charles Agyemang, Slawomir Koziel, Shohreh Naderimagham, Jari Jokelainen, Stephen T. McGarvey, Patrick Pasquet, Farnam Mohebi, Nader Saki, Aida Pilav, Azim Nejatizadeh, Marianna Noale, Habiba Ben Romdhane, Luís B. Sardinha, Laura Lauria, Jun Hata, Kodanda R Kanala, Gert B. M. Mensink, Nils Lehmann, Elio Riboli, Carolina Tarqui-Mamani, Rodrigo M. Carrillo-Larco, Rosangela Fernandes Lucena Batista, Victoria E Soto-Rojas, Luis Serra-Majem, Martina Müller-Nurasyid, Felipe Vogt Cureau, Lekhraj Rampal, Zhamilya Battakova, Ludmila Sevcikova, Suhaila Abdul Ghaffar, Fikru Tullu, Aung Soe Htet, Angel R. Gonzalez, Annette J. Dobson, Kavumpurathu Raman Thankappan, Hélène Delisle, Francisco J. Félix-Redondo, Ramón Suárez-Medina, Annika Rosengren, Sania Nishtar, Tanja G. M. Vrijkotte, Wolfgang Ahrens, Osvaldo Santos, Maria Cecília Formoso Assunção, Kazi M. Jamil, Stefano Marventano, Wenbin Wei, Norsyamlina Che Abdul Rahim, Shukri F. Mohamed, Bente Sparboe-Nilsen, Soon-Woo Park, Ana Isabel Rito, David Goltzman, W. M. 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Pérez, Vera Lanska, Tint Swe Latt, Dominique Hange, João Luiz Bastos, Eliza Markidou Ioannidou, Leticia Hernandez Cadena, Maya Tanrygulyyeva, Reza Malekzadeh, Dimitrios Poulimeneas, Pedro Ordunez, Thomas Waldhör, Ioannis Pagkalos, Carlo M. Barbagallo, Abla M. Sibai, Peter Vollenweider, Asher Fawwad, Emily Sonestedt, Elena Pahomova, Santosh K. Bhargava, Patrick Kolsteren, Aya Mostafa, Fangfang Chen, Flavio Nervi, Imre Janszky, Arvind Pandey, Renata Cifkova, Alexandre C. Pereira, Alejandro Diaz, Alireza Ansari-Moghaddam, Rachakulla Hari Kumar, Jaakko Mursu, Luis A. Moreno, Glen Gironella, Jelena Kos, Tilema Cama, Haakon E. Meyer, Jun Ma, Raphael E. Arku, Ziad Abdeen, Rusidah Selamat, Dianna J. Magliano, Jitendra Jonnagaddala, Konstantinos Gkiouras, Paul Korrovits, Paola Nardone, Paolo Vineis, Kotsedi D Monyeki, Khuong Quynh Long, Alberto Barceló, Camilla T. Damsgaard, Constance Schultsz, Frank J Rühli, Santiago F. Gomez, Tara Coppinger, Muhammad Islam, Pierre Traissac, Eleonora d'Orsi, Irfan Nuhoglu, Rui Providência, Bernard Maire, Leandra Abarca-Gómez, Sinead Brophy, Daniela Pierannunzio, Cristina Taddei, Wen-Harn Pan, Gregor Starc, Abdullah Alkandari, Saeed Dastgiri, Lien Braeckevelt, Gustavo Velasquez-Melendez, Sudhir Kowlessur, Bagher Larijani, Cynthia Robitaille, Mohamed M. Ali, Steiner Krokstad, Noor Ani Ahmad, Anar Dushpanova, Agustinus Soemantri, Susana Sans, Ionela Pascanu, Gwenaëlle Le Coroller, Inger Ariansen, Abhijit Sen, Sergej M. Ostojic, Silvana Donoso, Felix K. Assah, Juan A Rivera, Peter H. Whincup, Oana-Florentina Gheorghe-Fronea, Hanan F. Abdul Rahim, Yadlapalli S. Kusuma, Michael Knoflach, Moein Yoosefi, Cassiano Ricardo Rech, Paul Ferdinand M. Reganit, Tomi-Pekka Tuomainen, Francesco Gianfagna, Stefania Maggi, Mohammad Hossein Somi, Behrooz Hamzeh, Bethlehem D. Solomon, Herman Borghs, Zhanna Kalmatayeva, Heidi Klakk, Akram Pourshams, Naomi S. Levitt, Miquel Porta, Vesna Jureša, Alexander D. Deev, Son Thai Pham, Paula Margozzini, Silvia Bel-Serrat, Dora Romaguera, Monira Alarouj, Winsome R. Parnell, Marloes Cardol, David Faeh, Antonio Bernabe-Ortiz, Giota Touloumi, Maryam Kavousi, Sanja Musić Milanović, Jalila El Ati, Sauli Herrala, Liang Xu, Sirkka Keinänen-Kiukaanniemi, Ian Hambleton, Stefan Savin, Andre Pascal Kengne, R. Krishna Kumar, Kurt Widhalm, Marco M Ferrario, Parisa Amiri, Yi Song, Jianfeng Wu, Jeannette Klimont, Jean Ferrières, Farhad Zamani, Shina Avi, Luis Paulo Gomes Mascarenhas, Aluísio J D Barros, Reecha Sofat, Koen Van Herck, Hoang Van Minh, Enrique Gutiérrez-González, Martine Vrijheid, Susana Cararo Confortin, Antonis Zampelas, Bogdan Wojtyniak, Ausra Petrauskiene, Juha Auvinen, Maryam Sharafkhah, Emanuel Zitt, Majid Ezzati, Young-Ho Khang, Ellina Rakhimova, Magdalena Klimek, Luís Lopes, Erkin M. Mirrakhimov, Maria Lc Iurilli, Günay Can, Mark Woodward, Esther Lopez-Garcia, Mauro Virgílio Gomes de Barros, Ahmed A. Madar, Rainford J. Wilks, Shoaib Afzal, Melanie J. Cowan, Gareth Stratton, Eduardo Salazar Martinez, Sameer Narake, Norie Sawada, Li Juan Wu, Adrian Richter, Licia Iacoviello, Hanno Ulmer, Deepak Amarapurkar, Mohsen Ibrahim, Hamed Pouraram, Massimo Salvetti, Hung-Kwan So, Yonghua Hu, Lars Ängquist, Thi Tuyet-Hanh Tran, Charles Lunogelo, Sabina Zambon, Angelika Schaffrath Rosario, Lauren Lissner, Kamarul Imran Musa, Deepa Weerasekera, Bihungum Bista, Takafumi Ishida, Ekaterina Chikova-Iscener, Mirjam M. Heinen, Tazeen H. Jafar, Semánová Csilla, Raija Korpelainen, Edward W. Gregg, Laura Gutierrez, Victor M. Herrera, Aristides M. Machado-Rodrigues, Fatemeh Malekzadeh, Shouling Wu, Jennifer L. Baker, Clicerio González-Villalpando, Irene G. M. van Valkengoed, Anna Fijałkowska, Meghnath Dhimal, Murat Topbaş, George Moschonis, Robert Eggertsen, Quang Ngoc Nguyen, Janette Walton, Elnaz Faramarzi, Nasheeta Peer, Radka Taxová Braunerová, Harald Geiger, Morteza Shamshirgaran, Lela Shengelia, María Ángeles Dal Re Saavedra, Khem Bahadur Karki, Timothy J. Key, Maria G. Grammatikopoulou, Susana Vale, Bernhard O. Boehm, Songhomitra Panda-Jonas, Iveta Pudule, Elisabete Ramos, Lacramioara Aurelia Brinduse, Paul H. Lee, Terence W O'Neill, Javad Aghazadeh-Attari, Margus Punab, Bojan Jelaković, Eliza Cinteza, Ha Tp Do, and Alison J. Hayes
Subjects: education.field_of_study, business.industry, Population, Distribution (economics), medicine.disease, Obesity, Geography, medicine, Underweight, medicine.symptom, education, business, Body mass index, Demography
Published: 2020
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