Triglyceride-glucose index threshold for cardiovascular mortality in hypertensive individuals - URRAH project

Lanfranco D'Elia¹, Ferruccio Galletti¹, Masulli Maria¹, Agostino Virdis², Edoardo Casiglia³, Valerie Tikhonoff⁴, Fabio Angeli^{5

6}, Carlo Maria Barbagallo⁷, Michele Bombelli⁸, Federica Cappelli², Rosario Cianci⁹, Michele Ciccarelli¹⁰, Arrigo F G Cicero^{11

12}, Massimo Cirillo¹³, Pietro Cirillo¹⁴, Giovambattista Desideri¹⁵, Claudio Ferri¹⁶, Loreto Gesualdo¹⁴, Cristina Giannattasio^{17

18}, Guido Grassi¹⁹, Guido Iaccarino¹, Luciano Lippa²⁰, Francesca Mallamaci²¹, Alessandro Maloberti^{17

18}, Stefano Masi², Alberto Mazza²², Alessandro Mengozzi^{2

23

24}, Maria Lorenza Muiesan²⁵, Pietro Nazzaro²⁶, Paolo Palatini³, Gianfranco Parati^{27

28}, Roberto Pontremoli^{29

30}, Fosca Quarti-Trevano¹⁹, Marcello Rattazzi³¹, Gianpaolo Reboldi³², Giulia Rivasi³³, Elisa Russo^{29

30}, Massimo Salvetti²⁵, Giuliano Tocci³⁴, Andrea Ungar³³, Paolo Verdecchia³⁵, Francesca Viazzi^{29

30}, Massimo Volpe^{36

37}, Claudio Borghi^{11

12}; Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension (SIIA)

Affiliations

¹ Department of Clinical Medicine and Surgery, "Federico II" University of Naples, 80131 Naples, Italy.
² Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy.
³ Studium Patavinum, Department of Medicine, University of Padua, 35100 Padua, Italy.
⁴ Department of Medicine, University of Padua, 35100 Padua, Italy.
⁵ Department of Medicine and Technological Innovation (DiMIT), University of Insubria, Varese, Italy.
⁶ Department of Medicine and Cardiopulmonary Rehabilitation, Maugeri Care and Research Institutes, IRCCS Tradate (VA), Italy.
⁷ Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90100 Palermo, Italy.
⁸ Internal Medicine, Pio XI Hospital of Desio, ASST Brianza, Department of Medicine and Surgery, University of Milano, Bicocca, Italy.
⁹ Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy.
¹⁰ Department of Medicine and Surgery, University of Salerno, Salerno, Italy.
¹¹ Hypertension and Cardiovascular Disease Research Center, Medical and Surgical Sciences Department, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy.
¹² Cardiovascular medicine unit, Heart-Chest-Vascular Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40126 Bologna, Italy.
¹³ Dipartimento Scuola Medica Salernitana, Università di Salerno, Baronissi SA, Italy.
¹⁴ Dipartimento di Medicina di Precisione e Rigenerativa e Area Jonica (DiMePRe-J), "Aldo Moro" University of Bari, 70122 Bari, Italy.
¹⁵ Department of Clinical, Internal Medicine, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy.
¹⁶ Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.
¹⁷ Cardiology IV, "A.De Gasperi's" Department, Niguarda Ca' Granda Hospital, 20162 Milan, Italy.
¹⁸ School of Medicine and Surgery, Milano-Bicocca University, 20126 Milan, Italy.
¹⁹ Clinica Medica, Department of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy.
²⁰ Italian Society of General Medicine (SIMG), 67051 Avezzano, Italy.
²¹ Department of Nephrology, Dialysis and Transplantation GOM "Bianchi-Melacrino-Morelli" & CNR-IFC, Institute of Clinical Physiology, Research Unit of Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension (European Society of Hypertension, ESH, Excellence Centre) of Reggio Calabria, Italy.
²² Department of Internal Medicine, Santa Maria Della Misericordia General Hospital, AULSS 5 Polesana, 45100 Rovigo, Italy.
²³ Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, University Hospital Zurich, University of Zurich, 8952 Schlieren, Switzerland.
²⁴ Dipartimento Scuola Medica Salernitana, Università di Salerno, 84084 Baronissi-SA, Italy.
²⁵ Department of Clinical and Experimental Sciences and "Centro studi diagnosi e cura dell'ipertensione arteriosa e del rischio cardiovascolare ", University of Brescia, 25121 Brescia, Italy.
²⁶ Department of Precision and Regenerative Medicine and Jonic Area (DiMePRe-J), Neurosciences and Sense Organs, University of Bari Medical School, 70122 Bari, Italy.
²⁷ S.Luca Hospital, IRCCS, Istituto Auxologico Italiano, 20149 Milan, Italy.
²⁸ Department of Medicine and Surgery, University of Milano-Bicocca, 20126 Milan, Italy.
²⁹ Dipartimento di Medicina Interna e Specialità Mediche, Università degli Studi di Genova, Italy.
³⁰ IRCCS Ospedale Policlinico San Martino, Genova, Italy.
³¹ Department of Medicine-DIMED, University of Padova, Medicina Interna 1°, Ca' Foncello University Hospital, 31100 Treviso, Italy.
³² Department of Medicine and Surgery, University of Perugia, 06100 Perugia, Italy.
³³ Department of Geriatric and Intensive Care Medicine, Careggi Hospital, University of Florence, 50121 Florence, Italy.
³⁴ Department of Clinical and Molecular Medicine, University of Rome Sapienza, Sant'Andrea Hospital, 00189 Rome, Italy.
³⁵ Hospital S. Maria della Misericordia, 06100 Perugia, Italy.
³⁶ Dipartimento di Medicina Clinica e Molecolare, Università di Roma Sapienza, Roma, Italy.
³⁷ IRCCS San Raffaele Roma, Italy.

PMID: 40687937
PMCID: PMC12271081
DOI: 10.1016/j.ajpc.2025.101053

Triglyceride-glucose index threshold for cardiovascular mortality in hypertensive individuals - URRAH project

Lanfranco D'Elia et al. Am J Prev Cardiol. 2025.

. 2025 Jun 29:23:101053.

doi: 10.1016/j.ajpc.2025.101053. eCollection 2025 Sep.

Authors

Affiliations

¹ Department of Clinical Medicine and Surgery, "Federico II" University of Naples, 80131 Naples, Italy.
² Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy.
³ Studium Patavinum, Department of Medicine, University of Padua, 35100 Padua, Italy.
⁴ Department of Medicine, University of Padua, 35100 Padua, Italy.
⁵ Department of Medicine and Technological Innovation (DiMIT), University of Insubria, Varese, Italy.
⁶ Department of Medicine and Cardiopulmonary Rehabilitation, Maugeri Care and Research Institutes, IRCCS Tradate (VA), Italy.
⁷ Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90100 Palermo, Italy.
⁸ Internal Medicine, Pio XI Hospital of Desio, ASST Brianza, Department of Medicine and Surgery, University of Milano, Bicocca, Italy.
⁹ Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy.
¹⁰ Department of Medicine and Surgery, University of Salerno, Salerno, Italy.
¹¹ Hypertension and Cardiovascular Disease Research Center, Medical and Surgical Sciences Department, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy.
¹² Cardiovascular medicine unit, Heart-Chest-Vascular Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40126 Bologna, Italy.
¹³ Dipartimento Scuola Medica Salernitana, Università di Salerno, Baronissi SA, Italy.
¹⁴ Dipartimento di Medicina di Precisione e Rigenerativa e Area Jonica (DiMePRe-J), "Aldo Moro" University of Bari, 70122 Bari, Italy.
¹⁵ Department of Clinical, Internal Medicine, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy.
¹⁶ Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.
¹⁷ Cardiology IV, "A.De Gasperi's" Department, Niguarda Ca' Granda Hospital, 20162 Milan, Italy.
¹⁸ School of Medicine and Surgery, Milano-Bicocca University, 20126 Milan, Italy.
¹⁹ Clinica Medica, Department of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy.
²⁰ Italian Society of General Medicine (SIMG), 67051 Avezzano, Italy.
²¹ Department of Nephrology, Dialysis and Transplantation GOM "Bianchi-Melacrino-Morelli" & CNR-IFC, Institute of Clinical Physiology, Research Unit of Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension (European Society of Hypertension, ESH, Excellence Centre) of Reggio Calabria, Italy.
²² Department of Internal Medicine, Santa Maria Della Misericordia General Hospital, AULSS 5 Polesana, 45100 Rovigo, Italy.
²³ Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, University Hospital Zurich, University of Zurich, 8952 Schlieren, Switzerland.
²⁴ Dipartimento Scuola Medica Salernitana, Università di Salerno, 84084 Baronissi-SA, Italy.
²⁵ Department of Clinical and Experimental Sciences and "Centro studi diagnosi e cura dell'ipertensione arteriosa e del rischio cardiovascolare ", University of Brescia, 25121 Brescia, Italy.
²⁶ Department of Precision and Regenerative Medicine and Jonic Area (DiMePRe-J), Neurosciences and Sense Organs, University of Bari Medical School, 70122 Bari, Italy.
²⁷ S.Luca Hospital, IRCCS, Istituto Auxologico Italiano, 20149 Milan, Italy.
²⁸ Department of Medicine and Surgery, University of Milano-Bicocca, 20126 Milan, Italy.
²⁹ Dipartimento di Medicina Interna e Specialità Mediche, Università degli Studi di Genova, Italy.
³⁰ IRCCS Ospedale Policlinico San Martino, Genova, Italy.
³¹ Department of Medicine-DIMED, University of Padova, Medicina Interna 1°, Ca' Foncello University Hospital, 31100 Treviso, Italy.
³² Department of Medicine and Surgery, University of Perugia, 06100 Perugia, Italy.
³³ Department of Geriatric and Intensive Care Medicine, Careggi Hospital, University of Florence, 50121 Florence, Italy.
³⁴ Department of Clinical and Molecular Medicine, University of Rome Sapienza, Sant'Andrea Hospital, 00189 Rome, Italy.
³⁵ Hospital S. Maria della Misericordia, 06100 Perugia, Italy.
³⁶ Dipartimento di Medicina Clinica e Molecolare, Università di Roma Sapienza, Roma, Italy.
³⁷ IRCCS San Raffaele Roma, Italy.

PMID: 40687937
PMCID: PMC12271081
DOI: 10.1016/j.ajpc.2025.101053

Abstract

Aims: The triglyceride-glucose (TyG) index is a surrogate marker of insulin resistance (IR). Data regarding this topic is constantly increasing, however, few and heterogeneous data are available on the relationship between this index and cardiovascular mortality risk in hypertensive populations. In this context, we aimed to explore the relationship between TyG and cardiovascular mortality in a large sample of hypertensive individuals from the URRAH cohort.

Methods: A total of 12,275 hypertensive participants without previous cardiovascular events were included in this analysis. The risk of cardiovascular mortality was evaluated by the Cox regression analysis and competing risk regression analysis.

Results: During a median follow-up of 10.5 years, 2151 deaths occurred, of which 986 were from cardiovascular disease. A linear association between TyG and cardiovascular mortality was found, in particular for a 1-standard deviation increase in TyG there was a significantly increased risk of 33 % (p < 0.0001). Furthermore, after stratification by the optimal cut-off point (4.54 Units), participants with TyG above the cut-off had a significantly increased risk of 67 % of cardiovascular mortality when compared with those with TyG below the cut-off (p < 0.0001). These results were also confirmed after adjustment for potential confounders.

Conclusions: The results of this study indicate that this TyG threshold is predictive of an increased risk of cardiovascular mortality in a large sample of hypertensive individuals. This cut-off can identify individuals at higher mortality risk in already high-risk patients, with a low-cost and simple non-invasive marker.

Keywords: Cardiovascular mortality; Hypertension; Insulin resistance; Triglyceride-glucose index.

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Conflict of interest statement

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: URRAH study group reports administrative support was provided by Fondazione of the Italian Society of Hypertension. Claudio Borghi reports a relationship with Menarini Corporate, Novartis Pharma, Alfasigma, Laboratoires Servier, Grunenthal, Takeda, Astellas, Teijin, Berlin Chemie, Sanofi that includes: consulting or advisory, funding grants, and speaking and lecture fees. The remaining authors have no disclosures to report.

Figures

Image, graphical abstract — **Graphical abstract**

Fig 1 — **Fig. 1**
Association between the triglyceride-glucose index (TyG) and risk of cardiovascular mortality using a restricted cubic spline regression model. Solid lines indicate hazard ratios (HRs), and shadow shapes indicate 95 % confidence intervals (CIs).

Fig 2 — **Fig. 2**
Time-dependent receiver-operating characteristic ROC curve for the relationship between triglyceride-glucose (TyG) index and cardiovascular mortality.

Fig 3 — **Fig. 3**
Kaplan-Meier curve for cardiovascular mortality for people with triglyceride-glucose (TyG) index lower and above 4.54 Units.

See this image and copyright information in PMC

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Triglyceride-glucose index threshold for cardiovascular mortality in hypertensive individuals - URRAH project

Affiliations

Triglyceride-glucose index threshold for cardiovascular mortality in hypertensive individuals - URRAH project

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

Full Text Sources