Low LDL-cholesterol drives the risk of bleeding in patients treated with aspirin: A 15-year study in a real-world large population
We aimed to investigate the link between LDL cholesterol (LDL-C) levels and hemorrhage risk over an extended period, both in subjects taking aspirin and in individuals not receiving any antiplatelet agent. We calculated the predicted adjusted relative hazard of bleeding by LDL-C concentration for th...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-05-01
|
| Series: | Pharmacological Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661825001136 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849712850848710656 |
|---|---|
| author | Valentina Trimarco Raffaele Izzo Daniela Pacella Fahimeh Varzideh Maria Virginia Manzi Paola Gallo Giuseppe Giugliano Roberto Piccinocchi Giovanni Esposito Gaetano Piccinocchi Luca Bardi Carmine Morisco Francesco Rozza Maria Lembo Bruno Trimarco Gaetano Santulli |
| author_facet | Valentina Trimarco Raffaele Izzo Daniela Pacella Fahimeh Varzideh Maria Virginia Manzi Paola Gallo Giuseppe Giugliano Roberto Piccinocchi Giovanni Esposito Gaetano Piccinocchi Luca Bardi Carmine Morisco Francesco Rozza Maria Lembo Bruno Trimarco Gaetano Santulli |
| author_sort | Valentina Trimarco |
| collection | DOAJ |
| description | We aimed to investigate the link between LDL cholesterol (LDL-C) levels and hemorrhage risk over an extended period, both in subjects taking aspirin and in individuals not receiving any antiplatelet agent. We calculated the predicted adjusted relative hazard of bleeding by LDL-C concentration for the whole cohort and the aspirin-treated subgroup. The study included 39,784 individuals with a mean follow-up of 14.9 years, totaling over 500,000 patient-years. Across the cohort, 3380 bleeding events were reported, with a higher incidence in patients with LDL-C < 70 mg/dL compared to those with LDL-C ≥ 70 mg/dL (9.9 % vs 8.4 %). In aspirin-treated patients, multivariable analysis revealed that hemorrhagic events were significantly associated with aging, male sex, body mass index, hypertension, and LDL-C < 70 mg/dL. These patients had a significantly lower event-free survival probability if their LDL-C was < 70 mg/dL compared to ≥ 70 mg/dL. Low LDL-C values were a significant risk factor (HR >1) while higher LDL-C values were protective (HR <1). A stepwise increase of 10 mg/dL in LDL-C from < 30 to ≥ 200 mg/dL was associated with a decreasing trend for bleeding events in both the entire cohort and the aspirin-treated subgroup. This is the first report specifically addressing the relationship between LDL-C levels and bleeding risk in a population receiving low-intensity antithrombotic therapy. Our data demonstrate that in patients taking aspirin, LDL-C levels below 70 mg/dL significantly increase the risk of bleeding, with major implications for long-term cardiovascular risk management. |
| format | Article |
| id | doaj-art-1605d37578ad4533b61998cc81e774d0 |
| institution | DOAJ |
| issn | 1096-1186 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj-art-1605d37578ad4533b61998cc81e774d02025-08-20T03:14:08ZengElsevierPharmacological Research1096-11862025-05-0121510768810.1016/j.phrs.2025.107688Low LDL-cholesterol drives the risk of bleeding in patients treated with aspirin: A 15-year study in a real-world large populationValentina Trimarco0Raffaele Izzo1Daniela Pacella2Fahimeh Varzideh3Maria Virginia Manzi4Paola Gallo5Giuseppe Giugliano6Roberto Piccinocchi7Giovanni Esposito8Gaetano Piccinocchi9Luca Bardi10Carmine Morisco11Francesco Rozza12Maria Lembo13Bruno Trimarco14Gaetano Santulli15Department of Neuroscience, Reproductive Sciences and Dentistry, “Federico II” University, Naples, ItalyDepartment of Advanced Biomedical Sciences, “Federico II” University, Naples, ItalyDepartment of Public Health, “Federico II” University, Naples, ItalyDepartment of Molecular Pharmacology, Fleischer Institute for Diabetes and Metabolism (FIDAM), Institute for Neuroimmunology and Inflammation (INI), Albert Einstein College of Medicine, New York City, NY, USADepartment of Advanced Biomedical Sciences, “Federico II” University, Naples, ItalyDepartment of Advanced Biomedical Sciences, “Federico II” University, Naples, ItalyDepartment of Advanced Biomedical Sciences, “Federico II” University, Naples, ItalyLuigi Vanvitelli” Hospital, Naples, ItalyDepartment of Advanced Biomedical Sciences, “Federico II” University, Naples, ItalyCOMEGEN Primary Care Physicians Cooperative, Italian Society of General Medicine (SIMG), Naples, ItalyDepartment of Advanced Biomedical Sciences, “Federico II” University, Naples, ItalyDepartment of Advanced Biomedical Sciences, “Federico II” University, Naples, Italy; International Translational Research and Medical Education (ITME) Consortium, Academic Research Unit, Naples, Italy; Italian Society for Cardiovascular Prevention (SIPREC), Rome, ItalyDepartment of Advanced Biomedical Sciences, “Federico II” University, Naples, ItalyDepartment of Advanced Biomedical Sciences, “Federico II” University, Naples, ItalyDepartment of Advanced Biomedical Sciences, “Federico II” University, Naples, Italy; International Translational Research and Medical Education (ITME) Consortium, Academic Research Unit, Naples, Italy; Italian Society for Cardiovascular Prevention (SIPREC), Rome, ItalyDepartment of Advanced Biomedical Sciences, “Federico II” University, Naples, Italy; Department of Molecular Pharmacology, Fleischer Institute for Diabetes and Metabolism (FIDAM), Institute for Neuroimmunology and Inflammation (INI), Albert Einstein College of Medicine, New York City, NY, USA; International Translational Research and Medical Education (ITME) Consortium, Academic Research Unit, Naples, Italy; Department of Medicine, Division of Cardiology, Wilf Family Cardiovascular Research Institute, Einstein-Mount Sinai Diabetes Research Center (ES-DRC), Einstein Institute for Aging Research, Albert Einstein College of Medicine, New York City, NY, USA; Correspondence to: Albert Einstein College of Medicine, 1300 Morris Park Avenue, New York City, NY 10461, USA.We aimed to investigate the link between LDL cholesterol (LDL-C) levels and hemorrhage risk over an extended period, both in subjects taking aspirin and in individuals not receiving any antiplatelet agent. We calculated the predicted adjusted relative hazard of bleeding by LDL-C concentration for the whole cohort and the aspirin-treated subgroup. The study included 39,784 individuals with a mean follow-up of 14.9 years, totaling over 500,000 patient-years. Across the cohort, 3380 bleeding events were reported, with a higher incidence in patients with LDL-C < 70 mg/dL compared to those with LDL-C ≥ 70 mg/dL (9.9 % vs 8.4 %). In aspirin-treated patients, multivariable analysis revealed that hemorrhagic events were significantly associated with aging, male sex, body mass index, hypertension, and LDL-C < 70 mg/dL. These patients had a significantly lower event-free survival probability if their LDL-C was < 70 mg/dL compared to ≥ 70 mg/dL. Low LDL-C values were a significant risk factor (HR >1) while higher LDL-C values were protective (HR <1). A stepwise increase of 10 mg/dL in LDL-C from < 30 to ≥ 200 mg/dL was associated with a decreasing trend for bleeding events in both the entire cohort and the aspirin-treated subgroup. This is the first report specifically addressing the relationship between LDL-C levels and bleeding risk in a population receiving low-intensity antithrombotic therapy. Our data demonstrate that in patients taking aspirin, LDL-C levels below 70 mg/dL significantly increase the risk of bleeding, with major implications for long-term cardiovascular risk management.http://www.sciencedirect.com/science/article/pii/S1043661825001136AspirinBleedingCholesterolDyslipidemiaHemorrhageLDL |
| spellingShingle | Valentina Trimarco Raffaele Izzo Daniela Pacella Fahimeh Varzideh Maria Virginia Manzi Paola Gallo Giuseppe Giugliano Roberto Piccinocchi Giovanni Esposito Gaetano Piccinocchi Luca Bardi Carmine Morisco Francesco Rozza Maria Lembo Bruno Trimarco Gaetano Santulli Low LDL-cholesterol drives the risk of bleeding in patients treated with aspirin: A 15-year study in a real-world large population Pharmacological Research Aspirin Bleeding Cholesterol Dyslipidemia Hemorrhage LDL |
| title | Low LDL-cholesterol drives the risk of bleeding in patients treated with aspirin: A 15-year study in a real-world large population |
| title_full | Low LDL-cholesterol drives the risk of bleeding in patients treated with aspirin: A 15-year study in a real-world large population |
| title_fullStr | Low LDL-cholesterol drives the risk of bleeding in patients treated with aspirin: A 15-year study in a real-world large population |
| title_full_unstemmed | Low LDL-cholesterol drives the risk of bleeding in patients treated with aspirin: A 15-year study in a real-world large population |
| title_short | Low LDL-cholesterol drives the risk of bleeding in patients treated with aspirin: A 15-year study in a real-world large population |
| title_sort | low ldl cholesterol drives the risk of bleeding in patients treated with aspirin a 15 year study in a real world large population |
| topic | Aspirin Bleeding Cholesterol Dyslipidemia Hemorrhage LDL |
| url | http://www.sciencedirect.com/science/article/pii/S1043661825001136 |
| work_keys_str_mv | AT valentinatrimarco lowldlcholesteroldrivestheriskofbleedinginpatientstreatedwithaspirina15yearstudyinarealworldlargepopulation AT raffaeleizzo lowldlcholesteroldrivestheriskofbleedinginpatientstreatedwithaspirina15yearstudyinarealworldlargepopulation AT danielapacella lowldlcholesteroldrivestheriskofbleedinginpatientstreatedwithaspirina15yearstudyinarealworldlargepopulation AT fahimehvarzideh lowldlcholesteroldrivestheriskofbleedinginpatientstreatedwithaspirina15yearstudyinarealworldlargepopulation AT mariavirginiamanzi lowldlcholesteroldrivestheriskofbleedinginpatientstreatedwithaspirina15yearstudyinarealworldlargepopulation AT paolagallo lowldlcholesteroldrivestheriskofbleedinginpatientstreatedwithaspirina15yearstudyinarealworldlargepopulation AT giuseppegiugliano lowldlcholesteroldrivestheriskofbleedinginpatientstreatedwithaspirina15yearstudyinarealworldlargepopulation AT robertopiccinocchi lowldlcholesteroldrivestheriskofbleedinginpatientstreatedwithaspirina15yearstudyinarealworldlargepopulation AT giovanniesposito lowldlcholesteroldrivestheriskofbleedinginpatientstreatedwithaspirina15yearstudyinarealworldlargepopulation AT gaetanopiccinocchi lowldlcholesteroldrivestheriskofbleedinginpatientstreatedwithaspirina15yearstudyinarealworldlargepopulation AT lucabardi lowldlcholesteroldrivestheriskofbleedinginpatientstreatedwithaspirina15yearstudyinarealworldlargepopulation AT carminemorisco lowldlcholesteroldrivestheriskofbleedinginpatientstreatedwithaspirina15yearstudyinarealworldlargepopulation AT francescorozza lowldlcholesteroldrivestheriskofbleedinginpatientstreatedwithaspirina15yearstudyinarealworldlargepopulation AT marialembo lowldlcholesteroldrivestheriskofbleedinginpatientstreatedwithaspirina15yearstudyinarealworldlargepopulation AT brunotrimarco lowldlcholesteroldrivestheriskofbleedinginpatientstreatedwithaspirina15yearstudyinarealworldlargepopulation AT gaetanosantulli lowldlcholesteroldrivestheriskofbleedinginpatientstreatedwithaspirina15yearstudyinarealworldlargepopulation |