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1. Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses.

Author

Gaziano L, Sun L, Arnold M, Bell S, Cho K, Kaptoge SK, Song RJ, Burgess S, Posner DC, Mosconi K, Robinson-Cohen C, Mason AM, Bolton TR, Tao R, Allara E, Schubert P, Chen L, Staley JR, Staplin N, Altay S, Amiano P, Arndt V, Ärnlöv J, Barr ELM, Björkelund C, Boer JMA, Brenner H, Casiglia E, Chiodini P, Cooper JA, Coresh J, Cushman M, Dankner R, Davidson KW, de Jongh RT, Donfrancesco C, Engström G, Freisling H, de la Cámara AG, Gudnason V, Hankey GJ, Hansson PO, Heath AK, Hoorn EJ, Imano H, Jassal SK, Kaaks R, Katzke V, Kauhanen J, Kiechl S, Koenig W, Kronmal RA, Kyrø C, Lawlor DA, Ljungberg B, MacDonald C, Masala G, Meisinger C, Melander O, Moreno Iribas C, Ninomiya T, Nitsch D, Nordestgaard BG, Onland-Moret C, Palmieri L, Petrova D, Garcia JRQ, Rosengren A, Sacerdote C, Sakurai M, Santiuste C, Schulze MB, Sieri S, Sundström J, Tikhonoff V, Tjønneland A, Tong T, Tumino R, Tzoulaki I, van der Schouw YT, Monique Verschuren WM, Völzke H, Wallace RB, Wannamethee SG, Weiderpass E, Willeit P, Woodward M, Yamagishi K, Zamora-Ros R, Akwo EA, Pyarajan S, Gagnon DR, Tsao PS, Muralidhar S, Edwards TL, Damrauer SM, Joseph J, Pennells L, Wilson PWF, Harrison S, Gaziano TA, Inouye M, Baigent C, Casas JP, Langenberg C, Wareham N, Riboli E, Gaziano JM, Danesh J, Hung AM, Butterworth AS, Wood AM, and Di Angelantonio E

Subjects
Humans, Mendelian Randomization Analysis methods, Prospective Studies, Risk Factors, Kidney, Cardiovascular Diseases diagnosis, Cardiovascular Diseases epidemiology, Cardiovascular Diseases genetics, Coronary Disease diagnosis, Coronary Disease epidemiology, Coronary Disease genetics, Diabetes Mellitus epidemiology, Stroke diagnosis, Stroke epidemiology, Stroke genetics
Abstract

Background: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke., Methods: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank., Results: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min -1 ·1.73 m -2 , compared with those with eGFR between 60 and 105 mL·min -1 ·1.73 m -2 . Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min -1 ·1.73 m -2 , with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min -1 ·1.73 m -2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min -1 ·1.73 m -2 . Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD., Conclusions: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.

Published
2022
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2. Identification of a plausible serum uric acid cut-off value as prognostic marker of stroke: the Uric Acid Right for Heart Health (URRAH) study.

Author

Tikhonoff V, Casiglia E, Spinella P, Barbagallo CM, Bombelli M, Cicero AFG, Cirillo M, Cirillo P, Desideri G, D'elia L, Ferri C, Galletti F, Gesualdo L, Giannattasio C, Iaccarino G, Mallamaci F, Maloberti A, Masi S, Mazza A, Muiesan ML, Nazzaro P, Palatini P, Parati G, Pontremoli R, Quarti-Trevano F, Rattazzi M, Rivasi G, Salvetti M, Tocci G, Ungar A, Verdecchia P, Viazzi F, Virdis A, Volpe M, Grassi G, and Borghi C

Subjects
Humans, Uric Acid, Prognosis, Risk Factors, Stroke diagnosis, Hypertension diagnosis
Abstract

The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad hoc study aimed at searching for prognostic cut-off values of serum uric acid (SUA) in predicting combined (fatal and non-fatal) cerebrovascular (CBV) events in the whole database. The URic acid Right for heArt Health study is a nationwide, multicenter, observational cohort study involving data on subjects aged 18-95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 120.7 ± 61.8 months. A total of 14,588 subjects were included in the analysis. A prognostic cut-off value of SUA able to discriminate combined CBV events (>4.79 mg/dL or >284.91 µmol/L) was identified by means of receiver operating characteristic curve in the whole database. Multivariate Cox regression analysis adjusted for confounders (age, sex, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, body mass index, low-density lipoprotein cholesterol, and use of diuretics) identified an independent association between SUA and combined CBV events in the whole database (HR 1.249, 95% confidence interval, 1.041-1.497, p = 0.016). The results of the present study confirm that SUA is an independent risk marker for CBV events after adjusting for potential confounding variables, including arterial hypertension, and demonstrate that >4.79 mg/dL is a valid prognostic cut-off value., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Published
2022
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3. High dietary fiber intake prevents stroke at a population level.

Author

Casiglia E, Tikhonoff V, Caffi S, Boschetti G, Grasselli C, Saugo M, Giordano N, Rapisarda V, Spinella P, and Palatini P

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Cohort Studies, Dietary Fiber administration & dosage, Dietary Fiber analysis, Female, Humans, Incidence, Italy epidemiology, Longitudinal Studies, Male, Middle Aged, Prevalence, Risk Factors, Solubility, Stroke epidemiology, Surveys and Questionnaires, Survival Analysis, Young Adult, Dietary Fiber therapeutic use, Stroke prevention & control
Abstract

Background & Aims: This research was aimed at clarifying whether high dietary fiber intake has an impact on incidence and risk of stroke at a population level., Methods: In 1647 unselected subjects, dietary fiber intake (DFI) was detected in a 12-year population-based study, using other dietary variables, anagraphics, biometrics, blood pressure, heart rate, blood lipids, glucose, insulin, uricaemia, fibrinogenaemia, erytrosedimentation rate, diabetes, insulin resistance, smoking, pulmonary disease and left ventricular hypertrophy as covariables., Results: In adjusted Cox models, high DFI reduced the risk of stroke. In analysis based on quintiles of fiber intake adjusted for confounders, HR for incidence of stroke was lower when the daily intake of soluble fiber was >25 g or that of insoluble fiber was >47 g. In multivariate analyses, using these values as cut-off of DFI, the risk of stroke was lower in those intaking more that the cut-off of soluble (HR 0.31, 0.17-0.55) or insoluble (HR 0.35, 0.19-0.63) fiber. Incidence of stroke was also lower (-50%, p < 0.003 and -46%, p < 0.01, respectively)., Conclusions: Higher dietary DFI is inversely and independently associated to incidence and risk of stroke in general population., (Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Published
2013
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5. Blood pressure as a prognostic factor after acute stroke.

Author

Tikhonoff V, Zhang H, Richart T, and Staessen JA

Subjects
Antihypertensive Agents therapeutic use, Brain physiopathology, Clinical Trials as Topic, Humans, Hypertension drug therapy, Prognosis, Stroke etiology, Blood Pressure physiology, Brain blood supply, Hypertension complications, Stroke physiopathology
Abstract

Stroke is the second most common cause of death worldwide and is the complication of hypertension that is most directly linked to blood pressure. Hypertension affects nearly 30% of the world's population; therefore, reducing blood pressure is key for the prevention of stroke. Unlike the established role of hypertension as a risk factor for stroke, the prognostic importance of blood pressure in determining outcome after acute stroke is unclear. The acute hypertensive response occurs in more than 50% of all patients with acute stroke and is associated with poor prognosis. The relation between the outcome of acute stroke and blood pressure is U-shaped, with the best outcome at systolic blood-pressure levels ranging from about 140 to 180 mm Hg. The evidence that decreasing blood pressure in hypertensive patients with acute ischaemic or haemorrhagic stroke improves prognosis needs further confirmation. Whether raising blood pressure to improve perfusion of ischaemic brain areas is beneficial remains even more uncertain. Present guidelines for the management of blood pressure in patients with acute stroke are not evidence-based, but results from ongoing trials might provide more informed recommendations for the future.

Published
2009
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6. Arterial hypertension and mortality in the elderly.

Author

Casiglia E, Mazza A, Tikhonoff V, Scarpa R, Guglielmi F, and Pessina AC

Subjects
Adult, Aged, Aged, 80 and over, Aging, Analysis of Variance, Coronary Disease etiology, Female, Heart Failure etiology, Humans, Hypertension mortality, Hypertension physiopathology, Italy epidemiology, Male, Middle Aged, Prospective Studies, Pulmonary Embolism etiology, Pulmonary Embolism mortality, Risk Factors, Sex Factors, Stroke etiology, Coronary Disease mortality, Heart Failure mortality, Hypertension complications, Stroke mortality
Abstract

Background: The aim of this study was to evaluate at a population level whether hypertension is a risk factor for cardiovascular mortality and to verify whether or not this is true for both genders at any age., Methods: This population-based, long-lasting, prospective study includes a 14-year mortality (institutional epidemiology in primary care). Unselected, unbiased subjects (5185) aged 22 to 95 years were recruited from the Italian general population, and divided into normotensive (<140 mm Hg systolic blood pressure [BP] and <90 mm Hg diastolic BP and untreated) and hypertensive groups. The main aim was to identify the significant predictors of mortality due to stroke, coronary artery disease, heart failure, and pulmonary embolism, and to quantify the age-adjusted relative risk of hypertension in men and women, at different age classes (<70, 70 to 79, >or =80 years) for each mortality cause. The analysis was repeated among 1091 normotensive and 1091 hypertensive age-matched subjects to clean statistics from the effects of age., Results: There were 846 cardiovascular deaths, 178 due to stroke, 273 to coronary disease, 351 to heart failure, and 44 to pulmonary embolism. Hypertension predicted stroke mortality, but not that due to other causes. This prediction was only significant in women, not in men. No prediction was possible after the age of 80 years. Age-matching increased the significance level of stroke mortality prediction in women aged <80 years; in these women, systolic BP predicted stroke mortality directly and diastolic inversely. CONCLUSIONS; In this population, hypertension predicted only stroke mortality in women aged <80 years. High systolic and low diastolic BP were predictive of stroke mortality, confirming a prognostic role for high pulse pressure.

Published
2002
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7. Relative and Absolute Risk to Guide the Management of Pulse Pressure, an Age-Related Cardiovascular Risk Factor.

Author

Melgarejo, Jesus D, Thijs, Lutgarde, Wei, Dong-Mei, Bursztyn, Michael, Yang, Wen-Yi, Li, Yan, Asayama, Kei, Hansen, Tine W, Kikuya, Masahiro, Ohkubo, Takayoshi, Dolan, Eamon, Stolarz-Skrzypek, Katarzyna, Cheng, Yi-Bang, Tikhonoff, Valérie, Malyutina, Sofia, Casiglia, Edoardo, Lind, Lars, Sandoya, Edgardo, Filipovský, Jan, and Narkiewicz, Krzysztof

Subjects
OLDER people, CARDIOVASCULAR diseases risk factors, QUALITY of life, CARDIOVASCULAR disease related mortality, YOUNG adults, STROKE, PRESBYCUSIS
Abstract

Background Pulse pressure (PP) reflects the age-related stiffening of the central arteries, but no study addressed the management of the PP-related risk over the human lifespan. Methods In 4,663 young (18–49 years) and 7,185 older adults (≥50 years), brachial PP was recorded over 24 hours. Total mortality and all major cardiovascular events (MACEs) combined were coprimary endpoints. Cardiovascular death, coronary events, and stroke were secondary endpoints. Results In young adults (median follow-up, 14.1 years; mean PP, 45.1 mm Hg), greater PP was not associated with absolute risk; the endpoint rates were ≤2.01 per 1,000 person-years. The adjusted hazard ratios expressed per 10-mm Hg PP increments were less than unity (P ≤ 0.027) for MACE (0.67; 95% confidence interval [CI], 0.47–0.96) and cardiovascular death (0.33; 95% CI, 0.11–0.75). In older adults (median follow-up, 13.1 years; mean PP, 52.7 mm Hg), the endpoint rates, expressing absolute risk, ranged from 22.5 to 45.4 per 1,000 person-years and the adjusted hazard ratios, reflecting relative risk, from 1.09 to 1.54 (P < 0.0001). The PP-related relative risks of death, MACE, and stroke decreased >3-fold from age 55 to 75 years, whereas absolute risk rose by a factor 3. Conclusions From 50 years onwards, the PP-related relative risk decreases, whereas absolute risk increases. From a lifecourse perspective, young adulthood provides a window of opportunity to manage risk factors and prevent target organ damage as forerunner of premature death and MACE. In older adults, treatment should address absolute risk, thereby extending life in years and quality. [ABSTRACT FROM AUTHOR]

Published
2021
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8. Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses

Author

Liam Gaziano, Luanluan Sun, Matthew Arnold, Steven Bell, Kelly Cho, Stephen K. Kaptoge, Rebecca J. Song, Stephen Burgess, Daniel C. Posner, Katja Mosconi, Cassianne Robinson-Cohen, Amy M. Mason, Thomas R. Bolton, Ran Tao, Elias Allara, Petra Schubert, Lingyan Chen, James R. Staley, Natalie Staplin, Servet Altay, Pilar Amiano, Volker Arndt, Johan Ärnlöv, Elizabeth L.M. Barr, Cecilia Björkelund, Jolanda M.A. Boer, Hermann Brenner, Edoardo Casiglia, Paolo Chiodini, Jackie A. Cooper, Josef Coresh, Mary Cushman, Rachel Dankner, Karina W. Davidson, Renate T. de Jongh, Chiara Donfrancesco, Gunnar Engström, Heinz Freisling, Agustín Gómez de la Cámara, Vilmundur Gudnason, Graeme J. Hankey, Per-Olof Hansson, Alicia K. Heath, Ewout J. Hoorn, Hironori Imano, Simerjot K. Jassal, Rudolf Kaaks, Verena Katzke, Jussi Kauhanen, Stefan Kiechl, Wolfgang Koenig, Richard A. Kronmal, Cecilie Kyrø, Deborah A. Lawlor, Börje Ljungberg, Conor MacDonald, Giovanna Masala, Christa Meisinger, Olle Melander, Conchi Moreno Iribas, Toshiharu Ninomiya, Dorothea Nitsch, Børge G. Nordestgaard, Charlotte Onland-Moret, Luigi Palmieri, Dafina Petrova, Jose Ramón Quirós Garcia, Annika Rosengren, Carlotta Sacerdote, Masaru Sakurai, Carmen Santiuste, Matthias B. Schulze, Sabina Sieri, Johan Sundström, Valérie Tikhonoff, Anne Tjønneland, Tammy Tong, Rosario Tumino, Ioanna Tzoulaki, Yvonne T. van der Schouw, W.M. Monique Verschuren, Henry Völzke, Robert B. Wallace, S. Goya Wannamethee, Elisabete Weiderpass, Peter Willeit, Mark Woodward, Kazumasa Yamagishi, Raul Zamora-Ros, Elvis A. Akwo, Saiju Pyarajan, David R. Gagnon, Philip S. Tsao, Sumitra Muralidhar, Todd L. Edwards, Scott M. Damrauer, Jacob Joseph, Lisa Pennells, Peter W.F. Wilson, Seamus Harrison, Thomas A. Gaziano, Michael Inouye, Colin Baigent, Juan P. Casas, Claudia Langenberg, Nick Wareham, Elio Riboli, J.Michael Gaziano, John Danesh, Adriana M. Hung, Adam S. Butterworth, Angela M. Wood, Emanuele Di Angelantonio, Anna Koettgen, Jonathan Shaw, Robert Atkins, Paul Zimmet, Peter Whincup, Johann Willeit, Christoph Leitner, Anne Tybjaerg-Hansen, Peter Schnohr, Shoaib Afzal, David Lora Pablos, Cristina Martin Arriscado, Carmen Romero Ferreiro, Hannah Stocker, Ben Schöttker, Bernd Holleczek, Angela Chetrit, Lennart Welin, Kurt Svärdsudd, Lauren Lissner, Dominique Hange, Kirsten Mehlig, Dorothea Nagel, Paul E. Norman, Osvaldo Almeida, Leon Flicker, Jun Hata, Takanori Honda, Yoshihiko Furuta, Hiroyasu Iso, Akihiko Kitamura, Isao Muraki, Jukka T. Salonen, Tomi-Pekka Tuomainen, E. M. van Zutphen, N. M. van Schoor, Cinzia Lo Noce, Richard Kronmal, Georg Lappas, Peter M. Nilsson, Bo Hedblad, Jonathan Shaffer, Joseph Schwartz, Daichi Shimbo, Shinichi Sato, Mina Hayama-Terada, Simerjot Jassal, Thor Aspelund, Bolli Thorsson, Gunnar Sigurdsson, Layal Chaker, Kamran M. Ikram, Maryam Kavousi, Hugh Tunstall-Pedoe, Günay Can, Hüsniye Yüksel, Uğur Özkan, Hideaki Nakagawa, Yuko Morikawa, Masao Ishizaki, Edith Feskens, Johanna M Geleijnse, Daan Kromhout, Internal Medicine, Neurology, Epidemiology, Bell, Steven [0000-0001-6774-3149], Posner, Daniel C [0000-0002-3056-6924], Mason, Amy M [0000-0002-8019-0777], Allara, Elias [0000-0002-1634-8330], Staplin, Natalie [0000-0003-4482-4418], Arndt, Volker [0000-0001-9320-8684], Ärnlöv, Johan [0000-0002-6933-4637], Barr, Elizabeth LM [0000-0003-4284-1716], Boer, Jolanda MA [0000-0002-9714-4304], Brenner, Hermann [0000-0002-6129-1572], Casiglia, Edoardo [0000-0002-0003-3289], Chiodini, Paolo [0000-0003-0139-2264], Coresh, Josef [0000-0002-4598-0669], Cushman, Mary [0000-0002-7871-6143], Davidson, Karina W [0000-0002-9162-477X], de Jongh, Renate T [0000-0001-8414-3938], Engström, Gunnar [0000-0002-8618-9152], de la Cámara, Agustín Gómez [0000-0001-6827-6319], Gudnason, Vilmundur [0000-0001-5696-0084], Hankey, Graeme J [0000-0002-6044-7328], Hansson, Per-Olof [0000-0001-6323-0506], Heath, Alicia K [0000-0001-6517-1300], Hoorn, Ewout J [0000-0002-8738-3571], Imano, Hironori [0000-0002-6661-4254], Katzke, Verena [0000-0002-6509-6555], Kiechl, Stefan [0000-0002-9836-2514], Koenig, Wolfgang [0000-0002-2064-9603], Kronmal, Richard A [0000-0002-9897-7076], Kyrø, Cecilie [0000-0002-9083-8960], Ljungberg, Börje [0000-0002-4121-3753], MacDonald, Conor [0000-0002-4989-803X], Masala, Giovanna [0000-0002-5758-9069], Ninomiya, Toshiharu [0000-0003-1345-9032], Nordestgaard, Børge G [0000-0002-1954-7220], Onland-Moret, Charlotte [0000-0002-2360-913X], Palmieri, Luigi [0000-0002-4298-2642], Rosengren, Annika [0000-0002-5409-6605], Schulze, Matthias B [0000-0002-0830-5277], Sieri, Sabina [0000-0001-5201-172X], Sundström, Johan [0000-0003-2247-8454], Tikhonoff, Valérie [0000-0001-7846-0101], Tong, Tammy [0000-0002-0284-8959], Tzoulaki, Ioanna [0000-0002-4275-9328], van der Schouw, Yvonne T [0000-0002-4605-435X], Wannamethee, S Goya [0000-0001-9484-9977], Weiderpass, Elisabete [0000-0003-2237-0128], Willeit, Peter [0000-0002-1866-7159], Woodward, Mark [0000-0001-9800-5296], Yamagishi, Kazumasa [0000-0003-3301-5519], Zamora-Ros, Raul [0000-0002-6236-6804], Gagnon, David R [0000-0002-6367-3179], Tsao, Philip S [0000-0001-7274-9318], Edwards, Todd L [0000-0003-4318-6119], Damrauer, Scott M [0000-0001-8009-1632], Joseph, Jacob [0000-0002-7279-4896], Pennells, Lisa [0000-0002-8594-3061], Gaziano, Thomas A [0000-0002-5985-345X], Langenberg, Claudia [0000-0002-5017-7344], Wareham, Nick [0000-0003-1422-2993], Hung, Adriana M [0000-0002-3203-1608], Butterworth, Adam S [0000-0002-6915-9015], Di Angelantonio, Emanuele [0000-0001-8776-6719], Apollo - University of Cambridge Repository, Gaziano, Liam, Sun, Luanluan, Arnold, Matthew, Bell, Steven, Cho, Kelly, Kaptoge, Stephen K, Song, Rebecca J, Burgess, Stephen, Posner, Daniel C, Mosconi, Katja, Robinson-Cohen, Cassianne, Mason, Amy M, Bolton, Thomas R, Tao, Ran, Allara, Elia, Schubert, Petra, Chen, Lingyan, Staley, James R, Staplin, Natalie, Altay, Servet, Amiano, Pilar, Arndt, Volker, Ärnlöv, Johan, Barr, Elizabeth L M, Björkelund, Cecilia, Boer, Jolanda M A, Brenner, Hermann, Casiglia, Edoardo, Chiodini, Paolo, Cooper, Jackie A, Coresh, Josef, Cushman, Mary, Dankner, Rachel, Davidson, Karina W, de Jongh, Renate T, Donfrancesco, Chiara, Engström, Gunnar, Freisling, Heinz, de la Cámara, Agustín Gómez, Gudnason, Vilmundur, Hankey, Graeme J, Hansson, Per-Olof, Heath, Alicia K, Hoorn, Ewout J, Imano, Hironori, Jassal, Simerjot K, Kaaks, Rudolf, Katzke, Verena, Kauhanen, Jussi, Kiechl, Stefan, Koenig, Wolfgang, Kronmal, Richard A, Kyrø, Cecilie, Lawlor, Deborah A, Ljungberg, Börje, Macdonald, Conor, Masala, Giovanna, Meisinger, Christa, Melander, Olle, Moreno Iribas, Conchi, Ninomiya, Toshiharu, Nitsch, Dorothea, Nordestgaard, Børge G, Onland-Moret, Charlotte, Palmieri, Luigi, Petrova, Dafina, Garcia, Jose Ramón Quiró, Rosengren, Annika, Sacerdote, Carlotta, Sakurai, Masaru, Santiuste, Carmen, Schulze, Matthias B, Sieri, Sabina, Sundström, Johan, Tikhonoff, Valérie, Tjønneland, Anne, Tong, Tammy, Tumino, Rosario, Tzoulaki, Ioanna, van der Schouw, Yvonne T, Monique Verschuren, W M, Völzke, Henry, Wallace, Robert B, Wannamethee, S Goya, Weiderpass, Elisabete, Willeit, Peter, Woodward, Mark, Yamagishi, Kazumasa, Zamora-Ros, Raul, Akwo, Elvis A, Pyarajan, Saiju, Gagnon, David R, Tsao, Philip S, Muralidhar, Sumitra, Edwards, Todd L, Damrauer, Scott M, Joseph, Jacob, Pennells, Lisa, Wilson, Peter W F, Harrison, Seamu, Gaziano, Thomas A, Inouye, Michael, Baigent, Colin, Casas, Juan P, Langenberg, Claudia, Wareham, Nick, Riboli, Elio, Gaziano, J Michael, Danesh, John, Hung, Adriana M, Butterworth, Adam S, Wood, Angela M, Di Angelantonio, Emanuele, Internal medicine, AMS - Ageing & Vitality, AMS - Musculoskeletal Health, Amsterdam Gastroenterology Endocrinology Metabolism, Epidemiology and Data Science, APH - Aging & Later Life, and APH - Personalized Medicine

Subjects
kidney disease, General Practice, Emerging Risk Factors Collaboration/EPIC-CVD/Million Veteran Program, Coronary Disease, coronary disease, Kidney, Malalties coronàries, 1117 Public Health and Health Services, Coronary diseases, SDG 3 - Good Health and Well-being, cardiovascular disease, Risk Factors, Physiology (medical), Diabetes Mellitus, Humans, Cardiac and Cardiovascular Systems, Prospective Studies, 1102 Cardiorespiratory Medicine and Haematology, Kardiologi, Kidney diseases, Malalties cardiovasculars, Cardiovascular Diseases, Kidney Diseases, Stroke, 1103 Clinical Sciences, Mendelian Randomization Analysis, kidney diseases, stroke, Allmänmedicin, Cardiovascular diseases, Cardiovascular System & Hematology, Malalties del ronyó, Cardiology and Cardiovascular Medicine, cardiovascular diseases
Abstract

Background: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. Methods: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition–Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. Results: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values 105 mL·min –1 ·1.73 m –2 , compared with those with eGFR between 60 and 105 mL·min –1 ·1.73 m –2 . Mendelian randomization analyses for CHD showed an association among participants with eGFR –1 ·1.73 m –2 , with a 14% (95% CI, 3%–27%) higher CHD risk per 5 mL·min –1 ·1.73 m –2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min –1 ·1.73 m –2 . Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. Conclusions: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.

Published
2022

9. Identification of a plausible serum uric acid cut-off value as prognostic marker of stroke: the Uric Acid Right for Heart Health (URRAH) study

Author

Guido Grassi, Francesca Viazzi, Andrea Ungar, Lanfranco D'Elia, Massimo Salvetti, Paolo Spinella, Massimo Volpe, Agostino Virdis, Gianfranco Parati, Roberto Pontremoli, Stefano Masi, Giulia Rivasi, Loreto Gesualdo, Giuliano Tocci, Claudio Ferri, Ferruccio Galletti, Francesca Mallamaci, Alessandro Maloberti, Maria Lorenza Muiesan, Pietro Nazzaro, Valérie Tikhonoff, Michele Bombelli, Massimo Cirillo, Cristina Giannattasio, Paolo Palatini, Carlo M. Barbagallo, Paolo Verdecchia, Marcello Rattazzi, Alberto Mazza, Claudio Borghi, Edoardo Casiglia, Guido Iaccarino, Fosca Quarti-Trevano, Pietro Cirillo, Giovambattista Desideri, Arrigo F G Cicero, Tikhonoff, Valérie, Casiglia, Edoardo, Spinella, Paolo, Barbagallo, Carlo M., Bombelli, Michele, Cicero, Arrigo F. G., Cirillo, Massimo, Cirillo, Pietro, Desideri, Giovambattista, D’Elia, Lanfranco, Ferri, Claudio, Galletti, Ferruccio, Gesualdo, Loreto, Giannattasio, Cristina, Iaccarino, Guido, Mallamaci, Francesca, Maloberti, Alessandro, Masi, Stefano, Mazza, Alberto, Muiesan, Maria Lorenza, Nazzaro, Pietro, Palatini, Paolo, Parati, Gianfranco, Pontremoli, Roberto, Quarti-Trevano, Fosca, Rattazzi, Marcello, Rivasi, Giulia, Salvetti, Massimo, Tocci, Giuliano, Ungar, Andrea, Verdecchia, Paolo, Viazzi, Francesca, Virdis, Agostino, Volpe, Massimo, Grassi, Guido, Borghi, Claudio, Tikhonoff, V, Casiglia, E, Spinella, P, Barbagallo, C, Bombelli, M, Cicero, A, Cirillo, M, Cirillo, P, Desideri, G, D'Elia, L, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Iaccarino, G, Mallamaci, F, Maloberti, A, Masi, S, Mazza, A, Muiesan, M, Nazzaro, P, Palatini, P, Parati, G, Pontremoli, R, Quarti-Trevano, F, Rattazzi, M, Rivasi, G, Salvetti, M, Tocci, G, Ungar, A, Verdecchia, P, Viazzi, F, Virdis, A, Volpe, M, Grassi, G, Borghi, C, and Tikhonoff V, Casiglia E, Spinella P, Barbagallo CM, Bombelli M, Cicero AFG, Cirillo M, Cirillo P, Desideri G, D'elia L, Ferri C, Galletti F, Gesualdo L, Giannattasio C, Iaccarino G, Mallamaci F, Maloberti A, Masi S, Mazza A, Muiesan ML, Nazzaro P, Palatini P, Parati G, Pontremoli R, Quarti-Trevano F, Rattazzi M, Rivasi G, Salvetti M, Tocci G, Ungar A, Verdecchia P, Viazzi F, Virdis A, Volpe M, Grassi G, Borghi C

Subjects
medicine.medical_specialty, Settore MED/09 - Medicina Interna, uric acid, cardiovascular risk, serum uric acid, stroke, hypertension, cardiovascular prevention, cardiovascular disease, chemistry.chemical_compound, Risk Factors, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, Stroke, uric acid, hypertension, business.industry, Confounding, Prognosis, medicine.disease, Confidence interval, Uric Acid, chemistry, Hypertension, Uric acid, business, Body mass index, Cohort study, Kidney disease
Abstract

The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad hoc study aimed at searching for prognostic cut-off values of serum uric acid (SUA) in predicting combined (fatal and non-fatal) cerebrovascular (CBV) events in the whole database. The URic acid Right for heArt Health study is a nationwide, multicenter, observational cohort study involving data on subjects aged 18-95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 120.7 ± 61.8 months. A total of 14,588 subjects were included in the analysis. A prognostic cut-off value of SUA able to discriminate combined CBV events (>4.79 mg/dL or >284.91 µmol/L) was identified by means of receiver operating characteristic curve in the whole database. Multivariate Cox regression analysis adjusted for confounders (age, sex, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, body mass index, low-density lipoprotein cholesterol, and use of diuretics) identified an independent association between SUA and combined CBV events in the whole database (HR 1.249, 95% confidence interval, 1.041-1.497, p = 0.016). The results of the present study confirm that SUA is an independent risk marker for CBV events after adjusting for potential confounding variables, including arterial hypertension, and demonstrate that >4.79 mg/dL is a valid prognostic cut-off value.

Published
2021

10. The association of uric acid with mortality modifies at old age: data from the uric acid right for heart health (URRAH) study

Author

Andrea Ungar, Giulia Rivasi, Mauro Di Bari, Agostino Virdis, Edoardo Casiglia, Stefano Masi, Alessandro Mengozzi, Carlo M. Barbagallo, Michele Bombelli, Bernardino Bruno, Arrigo F.G. Cicero, Massimo Cirillo, Pietro Cirillo, Giovambattista Desideri, Lanfranco D’elia, Claudio Ferri, Ferruccio Galletti, Loreto Gesualdo, Cristina Giannattasio, Guido Iaccarino, Michele Ciccarelli, Luciano Lippa, Francesca Mallamaci, Alessandro Maloberti, Alberto Mazza, Maria Lorenza Muiesan, Pietro Nazzaro, Paolo Palatini, Gianfranco Parati, Roberto Pontremoli, Fosca Quarti-Trevano, Marcello Rattazzi, Massimo Salvetti, Valérie Tikhonoff, Giuliano Tocci, Rosario Cianci, Paolo Verdecchia, Francesca Viazzi, Massimo Volpe, Guido Grassi, Claudio Borghi, Ungar, Andrea, Rivasi, Giulia, Di Bari, Mauro, Virdis, Agostino, Casiglia, Edoardo, Masi, Stefano, Mengozzi, Alessandro, Barbagallo, Carlo M, Bombelli, Michele, Bruno, Bernardino, Cicero, Arrigo F G, Cirillo, Massimo, Cirillo, Pietro, Desideri, Giovambattista, D'Elia, Lanfranco, Ferri, Claudio, Galletti, Ferruccio, Gesualdo, Loreto, Giannattasio, Cristina, Iaccarino, Guido, Ciccarelli, Michele, Lippa, Luciano, Mallamaci, Francesca, Maloberti, Alessandro, Mazza, Alberto, Muiesan, Maria Lorenza, Nazzaro, Pietro, Palatini, Paolo, Parati, Gianfranco, Pontremoli, Roberto, Quarti-Trevano, Fosca, Rattazzi, Marcello, Salvetti, Massimo, Tikhonoff, Valérie, Tocci, Giuliano, Cianci, Rosario, Verdecchia, Paolo, Viazzi, Francesca, Volpe, Massimo, Grassi, Guido, Borghi, Claudio, Ungar, A, Rivasi, G, Di Bari, M, Virdis, A, Casiglia, E, Masi, S, Mengozzi, A, Barbagallo, C, Bombelli, M, Bruno, B, Cicero, A, Cirillo, M, Cirillo, P, Desideri, G, D'Elia, L, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Iaccarino, G, Ciccarelli, M, Lippa, L, Mallamaci, F, Maloberti, A, Mazza, A, Muiesan, M, Nazzaro, P, Palatini, P, Parati, G, Pontremoli, R, Quarti-Trevano, F, Rattazzi, M, Salvetti, M, Tikhonoff, V, Tocci, G, Cianci, R, Verdecchia, P, Viazzi, F, Volpe, M, Grassi, G, Borghi, C, and Ungar A, Rivasi G, Di Bari M, Virdis A, Casiglia E, Masi S, Mengozzi A, Barbagallo CM, Bombelli M, Bruno B, Cicero AFG, Cirillo M, Cirillo P, Desideri G, D'elia L, Ferri C, Galletti F, Gesualdo L, Giannattasio C, Iaccarino G, Ciccarelli M, Lippa L, Mallamaci F, Maloberti A, Mazza A, Muiesan ML, Nazzaro P, Palatini P, Parati G, Pontremoli R, Quarti-Trevano F, Rattazzi M, Salvetti M, Tikhonoff V, Tocci G, Cianci R, Verdecchia P, Viazzi F, Volpe M, Grassi G, Borghi C

Subjects
Settore MED/09 - Medicina Interna, hypertension, Physiology, Aged, Humans, Prognosis, Proportional Hazards Models, Risk Factors, Uric Acid, uric acid, elderly, cardiovascular prevention, stroke, myocardial infarction, Acid Urc, mortality, old age, Cardiovascular risk, older adult, Cardiovascular prevention, Older adults, Mortality, Uric acid, Internal Medicine, Cardiology and Cardiovascular Medicine
Abstract

Objectives: In older individuals, the role of serum uric acid (SUA) as risk factor for mortality is debated. This study investigated the association of SUA with all-cause and cardiovascular (CV) mortality in older adults participating in the large multicentre observational uric acid right for heart health (URRAH) study. Methods: Eight thousand URRAH participants aged 65+ were included in the analysis. The predictive role of SUA was assessed using Cox regression models stratified according to the cut-off age of 75. SUA was tested as continuous and categorical variable (age-specific quartiles). The prognostic threshold of SUA for mortality was analysed using receiver operating characteristic curves. Results: Among participants aged 65-74, multivariate Cox regression analysis adjusted for CV risk factors and comorbidities identified an independent association of SUA with both all-cause mortality (hazard ratio [HR] 1.169, 95% confidence interval [CI] 1.107-1.235) and CV mortality (HR 1.146, 95% CI 1.064-1.235). The cut-off value of 4.8 mg/dl discriminated mortality status. In participants aged 75+, we observed a J-shaped relationship of SUA with all-cause and CV mortality, with risk increasing at extreme SUA levels. Conclusions: These results confirmed the predictive role of SUA for all-cause and CV mortality in older adults, while revealing considerable age-related differences. Mortality risk increased at higher SUA levels in participants aged 65-74, with a prognostic threshold of 4.8 mg/dl. The relationship between SUA and mortality was J-shaped in oldest participants. Large interventional studies are needed to clarify the benefits and possible risks of urate-lowering treatments in older adults.

Published
2021

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