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3. Serum from COVID-19 patients promotes endothelial cell dysfunction through protease-activated receptor 2

Author

Vieceli Dalla Sega, Francesco, Fortini, Francesca, Licastro, Danilo, Monego, Simeone Dal, Degasperi, Margherita, Ascierto, Alessia, Marracino, Luisa, Severi, Paolo, D’Accolti, Maria, Soffritti, Irene, Brambilla, Marta, Camera, Marina, Tremoli, Elena, Contoli, Marco, Spadaro, Savino, Campo, Gianluca, Ferrari, Roberto, Caselli, Elisabetta, and Rizzo, Paola

Published
2024
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8. Cell Surface Platelet Tissue Factor Expression: Regulation by P2Y12 and Link to Residual Platelet Reactivity

Author

Brambilla, Marta, Becchetti, Alessia, Rovati, Gian Enrico, Cosentino, Nicola, Conti, Maria, Canzano, Paola, Giesen, Peter L.A., Loffreda, Alessia, Bonomi, Alice, Cattaneo, Marco, De Candia, Erica, Podda, Gian Marco, Trabattoni, Daniela, Werba, Pablo Josè, Campodonico, Jeness, Pinna, Christian, Marenzi, Giancarlo, Tremoli, Elena, and Camera, Marina

Published
2023
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9. Causal analysis of plasma IL-8 on carotid intima media thickness, a measure of subclinical atherosclerosis

Author

Velásquez, Ilais Moreno, Malarstig, Anders, Baldassarre, Damiano, Borne, Yan, de Faire, Ulf, Engström, Gunnar, Eriksson, Per, Giral, Philippe, Humphries, Steve E., Kurl, Sudhir, Leander, Karin, Lind, Lars, Lindén, Anders, Orsini, Nicola, Pirro, Matteo, Silveira, Angela, Smit, Andries J., Tremoli, Elena, Veglia, Fabrizio, Strawbridge, Rona J., and Gigante, Bruna

Published
2023
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10. Immature Surfactant Protein B Increases in the Serum of Patients with Calcific Severe Aortic Stenosis

Author

Eligini, Sonia, primary, Savini, Carlo, additional, Ghilardi, Stefania, additional, Mallia, Alice, additional, Vieceli Dalla Sega, Francesco, additional, Fortini, Francesca, additional, Mikus, Elisa, additional, Munno, Marco, additional, Modafferi, Gloria, additional, Agostoni, Piergiuseppe, additional, Tremoli, Elena, additional, and Banfi, Cristina, additional

Published
2024
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11. GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes.

Author

Franceschini, Nora, Giambartolomei, Claudia, de Vries, Paul S, Finan, Chris, Bis, Joshua C, Huntley, Rachael P, Lovering, Ruth C, Tajuddin, Salman M, Winkler, Thomas W, Graff, Misa, Kavousi, Maryam, Dale, Caroline, Smith, Albert V, Hofer, Edith, van Leeuwen, Elisabeth M, Nolte, Ilja M, Lu, Lingyi, Scholz, Markus, Sargurupremraj, Muralidharan, Pitkänen, Niina, Franzén, Oscar, Joshi, Peter K, Noordam, Raymond, Marioni, Riccardo E, Hwang, Shih-Jen, Musani, Solomon K, Schminke, Ulf, Palmas, Walter, Isaacs, Aaron, Correa, Adolfo, Zonderman, Alan B, Hofman, Albert, Teumer, Alexander, Cox, Amanda J, Uitterlinden, André G, Wong, Andrew, Smit, Andries J, Newman, Anne B, Britton, Annie, Ruusalepp, Arno, Sennblad, Bengt, Hedblad, Bo, Pasaniuc, Bogdan, Penninx, Brenda W, Langefeld, Carl D, Wassel, Christina L, Tzourio, Christophe, Fava, Cristiano, Baldassarre, Damiano, O'Leary, Daniel H, Teupser, Daniel, Kuh, Diana, Tremoli, Elena, Mannarino, Elmo, Grossi, Enzo, Boerwinkle, Eric, Schadt, Eric E, Ingelsson, Erik, Veglia, Fabrizio, Rivadeneira, Fernando, Beutner, Frank, Chauhan, Ganesh, Heiss, Gerardo, Snieder, Harold, Campbell, Harry, Völzke, Henry, Markus, Hugh S, Deary, Ian J, Jukema, J Wouter, de Graaf, Jacqueline, Price, Jacqueline, Pott, Janne, Hopewell, Jemma C, Liang, Jingjing, Thiery, Joachim, Engmann, Jorgen, Gertow, Karl, Rice, Kenneth, Taylor, Kent D, Dhana, Klodian, Kiemeney, Lambertus ALM, Lind, Lars, Raffield, Laura M, Launer, Lenore J, Holdt, Lesca M, Dörr, Marcus, Dichgans, Martin, Traylor, Matthew, Sitzer, Matthias, Kumari, Meena, Kivimaki, Mika, Nalls, Mike A, Melander, Olle, Raitakari, Olli, Franco, Oscar H, Rueda-Ochoa, Oscar L, Roussos, Panos, Whincup, Peter H, Amouyel, Philippe, and Giral, Philippe

Subjects
MEGASTROKE Consortium, Humans, Coronary Disease, Genetic Predisposition to Disease, Amino Acid Oxidoreductases, Protein-Lysine 6-Oxidase, Risk Factors, Lod Score, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Genome-Wide Association Study, Plaque, Atherosclerotic, Carotid Intima-Media Thickness, ADAMTS9 Protein, Plaque, Atherosclerotic, Polymorphism, Single Nucleotide
Abstract

Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.

Published
2018

14. The State-of-the-Art of Mycobacterium chimaera Infections and the Causal Link with Health Settings: A Systematic Review.

Author

Bolcato, Vittorio, Bassetti, Matteo, Basile, Giuseppe, Bianco Prevot, Luca, Speziale, Giuseppe, Tremoli, Elena, Maffessanti, Francesco, and Tronconi, Livio Pietro

Subjects
CROSS infection prevention, MYCOBACTERIAL diseases, MENINGES, CROSS infection, RESEARCH funding, AEROSOLS, HEALTH policy, ECOSYSTEMS, HYGIENE, SYSTEMATIC reviews, MEDLINE, STERILIZATION (Disinfection), CENTRAL venous catheters, HEALTH facilities, ONLINE information services, COLLECTION & preservation of biological specimens, CARDIAC surgery, INFECTIOUS disease transmission
Abstract

(1) Background. A definition of healthcare-associated infections is essential also for the attribution of the restorative burden to healthcare facilities in case of harm and for clinical risk management strategies. Regarding M. chimaera infections, there remains several issues on the ecosystem and pathogenesis. We aim to review the scientific evidence on M. chimaera beyond cardiac surgery, and thus discuss its relationship with healthcare facilities. (2) Methods. A systematic review was conducted on PubMed and Web of Science on 7 May 2024 according to PRISMA 2020 guidelines for reporting systematic reviews, including databases searches with the keyword "Mycobacterium chimaera". Article screening was conducted by tree authors independently. The criterion for inclusion was cases that were not, or were improperly, consistent with the in-situ deposition of aerosolised M. chimaera. (3) Results. The search yielded 290 eligible articles. After screening, 34 articles (377 patients) were included. In five articles, patients had undergone cardiac surgery and showed musculoskeletal involvement or disseminated infection without cardiac manifestations. In 11 articles, respiratory specimen reanalyses showed M. chimaera. Moreover, 10 articles reported lung involvement, 1 reported meninges involvement, 1 reported skin involvement, 1 reported kidney involvement after transplantation, 1 reported tendon involvement, and 1 reported the involvement of a central venous catheter; 3 articles reported disseminated cases with one concomitant spinal osteomyelitis. (4) Conclusions. The scarce data on environmental prevalence, the recent studies on M. chimaera ecology, and the medicalised sample selection bias, as well as the infrequent use of robust ascertainment of sub-species, need to be weighed up. The in-house aerosolization, inhalation, and haematogenous spread deserve experimental study, as M. chimaera cardiac localisation could depend to transient bacteraemia. Each case deserves specific ascertainment before tracing back to the facility, even if M. chimaera represents a core area for healthcare facilities within a framework of infection prevention and control policies. [ABSTRACT FROM AUTHOR]

Published
2024
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15. Stereotactic radioablation for the treatment of ventricular tachycardia: preliminary data and insights from the STRA-MI-VT phase Ib/II study

Author

Carbucicchio, Corrado, Andreini, Daniele, Piperno, Gaia, Catto, Valentina, Conte, Edoardo, Cattani, Federica, Bonomi, Alice, Rondi, Elena, Piccolo, Consiglia, Vigorito, Sabrina, Ferrari, Annamaria, Pepa, Matteo, Giuliani, Mattia, Mushtaq, Saima, Scarà, Antonio, Calò, Leonardo, Gorini, Alessandra, Veglia, Fabrizio, Pontone, Gianluca, Pepi, Mauro, Tremoli, Elena, Orecchia, Roberto, Pompilio, Giulio, Tondo, Claudio, and Jereczek-Fossa, Barbara Alicja

Published
2021
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16. An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans

Author

Scott, Robert A, Scott, Laura J, Mägi, Reedik, Marullo, Letizia, Gaulton, Kyle J, Kaakinen, Marika, Pervjakova, Natalia, Pers, Tune H, Johnson, Andrew D, Eicher, John D, Jackson, Anne U, Ferreira, Teresa, Lee, Yeji, Ma, Clement, Steinthorsdottir, Valgerdur, Thorleifsson, Gudmar, Qi, Lu, Van Zuydam, Natalie R, Mahajan, Anubha, Chen, Han, Almgren, Peter, Voight, Ben F, Grallert, Harald, Müller-Nurasyid, Martina, Ried, Janina S, Rayner, William N, Robertson, Neil, Karssen, Lennart C, van Leeuwen, Elisabeth M, Willems, Sara M, Fuchsberger, Christian, Kwan, Phoenix, Teslovich, Tanya M, Chanda, Pritam, Li, Man, Lu, Yingchang, Dina, Christian, Thuillier, Dorothee, Yengo, Loic, Jiang, Longda, Sparso, Thomas, Kestler, Hans A, Chheda, Himanshu, Eisele, Lewin, Gustafsson, Stefan, Frånberg, Mattias, Strawbridge, Rona J, Benediktsson, Rafn, Hreidarsson, Astradur B, Kong, Augustine, Sigurðsson, Gunnar, Kerrison, Nicola D, Luan, Jian'an, Liang, Liming, Meitinger, Thomas, Roden, Michael, Thorand, Barbara, Esko, Tõnu, Mihailov, Evelin, Fox, Caroline, Liu, Ching-Ti, Rybin, Denis, Isomaa, Bo, Lyssenko, Valeriya, Tuomi, Tiinamaija, Couper, David J, Pankow, James S, Grarup, Niels, Have, Christian T, Jørgensen, Marit E, Jørgensen, Torben, Linneberg, Allan, Cornelis, Marilyn C, van Dam, Rob M, Hunter, David J, Kraft, Peter, Sun, Qi, Edkins, Sarah, Owen, Katharine R, Perry, John RB, Wood, Andrew R, Zeggini, Eleftheria, Tajes-Fernandes, Juan, Abecasis, Goncalo R, Bonnycastle, Lori L, Chines, Peter S, Stringham, Heather M, Koistinen, Heikki A, Kinnunen, Leena, Sennblad, Bengt, Mühleisen, Thomas W, Nöthen, Markus M, Pechlivanis, Sonali, Baldassarre, Damiano, Gertow, Karl, Humphries, Steve E, Tremoli, Elena, Klopp, Norman, Meyer, Julia, and Steinbach, Gerald

Subjects
Human Genome, Diabetes, Obesity, Genetics, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Diabetes Mellitus, Type 2, Gene Expression Regulation, Genetic Variation, Genome-Wide Association Study, Humans, White People, DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Medical and Health Sciences, Endocrinology & Metabolism
Abstract

To characterize type 2 diabetes (T2D)-associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D case and 132,532 control subjects of European ancestry after imputation using the 1000 Genomes multiethnic reference panel. Promising association signals were followed up in additional data sets (of 14,545 or 7,397 T2D case and 38,994 or 71,604 control subjects). We identified 13 novel T2D-associated loci (P < 5 × 10-8), including variants near the GLP2R, GIP, and HLA-DQA1 genes. Our analysis brought the total number of independent T2D associations to 128 distinct signals at 113 loci. Despite substantially increased sample size and more complete coverage of low-frequency variation, all novel associations were driven by common single nucleotide variants. Credible sets of potentially causal variants were generally larger than those based on imputation with earlier reference panels, consistent with resolution of causal signals to common risk haplotypes. Stratification of T2D-associated loci based on T2D-related quantitative trait associations revealed tissue-specific enrichment of regulatory annotations in pancreatic islet enhancers for loci influencing insulin secretion and in adipocytes, monocytes, and hepatocytes for insulin action-associated loci. These findings highlight the predominant role played by common variants of modest effect and the diversity of biological mechanisms influencing T2D pathophysiology.

Published
2017

17. Determinants of Carotid Wall Echolucency in a Cohort of European High Cardiovascular Risk Subjects: A Cross-Sectional Analysis of IMPROVE Baseline Data

Author

Frigerio, Beatrice, primary, Coggi, Daniela, additional, Bonomi, Alice, additional, Amato, Mauro, additional, Capra, Nicolò, additional, Colombo, Gualtiero I., additional, Sansaro, Daniela, additional, Ravani, Alessio, additional, Savonen, Kai, additional, Giral, Philippe, additional, Gallo, Antonio, additional, Pirro, Matteo, additional, Gigante, Bruna, additional, Eriksson, Per, additional, Strawbridge, Rona J., additional, Mulder, Douwe J., additional, Tremoli, Elena, additional, Veglia, Fabrizio, additional, and Baldassarre, Damiano, additional

Published
2024
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18. Cardiac arrhythmia catheter ablation procedures guided by x-ray imaging: N-acetylcysteine protection against radiation-induced cellular damage (CARAPACE study): study design

Author

Catto, Valentina, Stronati, Giulia, Porro, Benedetta, Fiorelli, Susanna, Ricci, Veronica, Vavassori, Chiara, Russo, Eleonora, Guerra, Federico, Gasperetti, Alessio, Ribatti, Valentina, Sicuso, Rita, Dello Russo, Antonio, Veglia, Fabrizio, Tondo, Claudio, Cavalca, Viviana, Colombo, Gualtiero I., Tremoli, Elena, and Casella, Michela

Published
2021
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20. Platelet and Endothelial Activation as Potential Mechanisms Behind the Thrombotic Complications of COVID-19 Patients

Author

Canzano, Paola, Brambilla, Marta, Porro, Benedetta, Cosentino, Nicola, Tortorici, Elena, Vicini, Stefano, Poggio, Paolo, Cascella, Andrea, Pengo, Martino F., Veglia, Fabrizio, Fiorelli, Susanna, Bonomi, Alice, Cavalca, Viviana, Trabattoni, Daniela, Andreini, Daniele, Omodeo Salè, Emanuela, Parati, Gianfranco, Tremoli, Elena, and Camera, Marina

Published
2021
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22. Exploring Mitochondrial Interactions with Pulsed Electromagnetic Fields: An Insightful Inquiry into Strategies for Addressing Neuroinflammation and Oxidative Stress in Diabetic Neuropathy.

Author

Chianese, Diego, Bonora, Massimo, Sambataro, Maria, Sambato, Luisa, Paola, Luca Dalla, Tremoli, Elena, Cappucci, Ilenia Pia, Scatto, Marco, Pinton, Paolo, Picari, Massimo, Ferroni, Letizia, and Zavan, Barbara

Subjects
DIABETIC neuropathies, ELECTROMAGNETIC fields, ELECTROMAGNETIC interactions, DIABETIC foot, CELL cycle regulation, MAGNETIC field effects, OXIDATIVE stress
Abstract

Pulsed electromagnetic fields (PEMFs) are recognized for their potential in regenerative medicine, offering a non-invasive avenue for tissue rejuvenation. While prior research has mainly focused on their effects on bone and dermo-epidermal tissues, the impact of PEMFs on nervous tissue, particularly in the context of neuropathy associated with the diabetic foot, remains relatively unexplored. Addressing this gap, our preliminary in vitro study investigates the effects of complex magnetic fields (CMFs) on glial-like cells derived from mesenchymal cell differentiation, serving as a model for neuropathy of the diabetic foot. Through assessments of cellular proliferation, hemocompatibility, mutagenicity, and mitochondrial membrane potential, we have established the safety profile of the system. Furthermore, the analysis of microRNAs (miRNAs) suggests that CMFs may exert beneficial effects on cell cycle regulation, as evidenced by the upregulation of the miRNAs within the 121, 127, and 142 families, which are known to be associated with mitochondrial function and cell cycle control. This exploration holds promise for potential applications in mitigating neuropathic complications in diabetic foot conditions. [ABSTRACT FROM AUTHOR]

Published
2024
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23. The Role of Microbes in Surgical Decision Making for Infective Endocarditis: Mitral Valve Repair or Replacement?

Author

Mikus, Elisa, Fiorentino, Mariafrancesca, Sangiorgi, Diego, Pascale, Renato, Costantino, Antonino, Nocera, Chiara, Calvi, Simone, Tenti, Elena, Tremoli, Elena, Tripodi, Alberto, and Savini, Carlo

Subjects
MITRAL valve, MITRAL valve surgery, INFECTIVE endocarditis, STREPTOCOCCAL diseases, EARLY death
Abstract

Background: The benefits of mitral repair versus replacement for endocarditis are inconclusive. This study compares outcomes of patients with infective endocarditis undergoing mitral valve repair versus replacement and investigates the impact of microbial etiology. Methods: All 251 patients undergoing mitral valve surgery for active endocarditis between 2010 and 2023 were enrolled, 180 (71.7%) replacement and 71 (28.3%) repair. To adjust for imbalances, inverse probability of treatment weighting was applied and 187 patients were obtained. Results: The analysis between groups, following the application of inverse probability of treatment weighting, showed no statistically significant differences across all considered outcomes. Early and late death was observed respectively in 6 (8.5%) and 11 (15.5%) patients in the repair group versus 24 (13.3%) and 45 (25.0%) in the replacement group without statistical significance (p = 0.221 and p = 0.446). Relapse occurred in six patients (8.5%) in the repair group after a median time of 4.0 months and in six (3.3%) in the replacement after 6.9 months (p = 0.071). Conclusions: Surgical strategy in mitral endocarditis has no effect on major postoperative complications, mortality, or medium/long-term survival. Staphylococcus aureus and Coagulase-negative Staphylococci represent a risk for early mortality and relapse. However, mitral valve repair for endocarditis can be pursued when it ensures the complete eradication of all infected tissue, particularly in cases caused by Streptococcus infection, in young patients, and after a minimum of 18 days of antibiotic therapy. [ABSTRACT FROM AUTHOR]

Published
2024
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24. Sex-specific predictors of PCSK9 levels in a European population: The IMPROVE study

Author

Ferri, Nicola, Ruscica, Massimiliano, Coggi, Daniela, Bonomi, Alice, Amato, Mauro, Frigerio, Beatrice, Sansaro, Daniela, Ravani, Alessio, Veglia, Fabrizio, Capra, Nicolò, Lupo, Maria G., Macchi, Chiara, Castelnuovo, Samuela, Savonen, Kai, Silveira, Angela, Kurl, Sudhir, Giral, Philippe, Pirro, Matteo, Strawbridge, Rona J., Gigante, Bruna, Smit, Andries J., Tremoli, Elena, Colombo, Gualtiero I., and Baldassarre, Damiano

Published
2020
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28. Post-Operative Delirium and Cognitive Dysfunction in Aged Patients Undergoing Cardiac Surgery: A Randomized Comparison between Two Blood Oxygenators

Author

Mantovani, Lorenzo, primary, Mikus, Elisa, additional, Tenti, Elena, additional, Sangiorgi, Diego, additional, Zannoni, Samantha, additional, Cavallucci, Andrea, additional, Ferroni, Letizia, additional, Cimaglia, Paolo, additional, Tolio, Valentina, additional, Tremoli, Elena, additional, and Savini, Carlo, additional

Published
2023
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31. The overlap of genetic susceptibility to schizophrenia and cardiometabolic disease can be used to identify metabolically different groups of individuals

Author

Strawbridge, Rona J., Johnston, Keira J. A., Bailey, Mark E. S., Baldassarre, Damiano, Cullen, Breda, Eriksson, Per, deFaire, Ulf, Ferguson, Amy, Gigante, Bruna, Giral, Philippe, Graham, Nicholas, Hamsten, Anders, Humphries, Steve E., Kurl, Sudhir, Lyall, Donald M., Lyall, Laura M., Pell, Jill P., Pirro, Matteo, Savonen, Kai, Smit, Andries J., Tremoli, Elena, Tomainen, Tomi-Pekka, Veglia, Fabrizio, Ward, Joey, Sennblad, Bengt, and Smith, Daniel J.

Published
2021
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32. HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials

Author

Swerdlow, Daniel I, Preiss, David, Kuchenbaecker, Karoline B, Holmes, Michael V, Engmann, Jorgen EL, Shah, Tina, Sofat, Reecha, Stender, Stefan, Johnson, Paul CD, Scott, Robert A, Leusink, Maarten, Verweij, Niek, Sharp, Stephen J, Guo, Yiran, Giambartolomei, Claudia, Chung, Christina, Peasey, Anne, Amuzu, Antoinette, Li, KaWah, Palmen, Jutta, Howard, Philip, Cooper, Jackie A, Drenos, Fotios, Li, Yun R, Lowe, Gordon, Gallacher, John, Stewart, Marlene CW, Tzoulaki, Ioanna, Buxbaum, Sarah G, van der A, Daphne L, Forouhi, Nita G, Onland-Moret, N Charlotte, van der Schouw, Yvonne T, Schnabel, Renate B, Hubacek, Jaroslav A, Kubinova, Ruzena, Baceviciene, Migle, Tamosiunas, Abdonas, Pajak, Andrzej, Topor-Madry, Romanvan, Stepaniak, Urszula, Malyutina, Sofia, Baldassarre, Damiano, Sennblad, Bengt, Tremoli, Elena, de Faire, Ulf, Veglia, Fabrizio, Ford, Ian, Jukema, J Wouter, Westendorp, Rudi GJ, de Borst, Gert Jan, de Jong, Pim A, Algra, Ale, Spiering, Wilko, der Zee, Anke H Maitland-van, Klungel, Olaf H, de Boer, Anthonius, Doevendans, Pieter A, Eaton, Charles B, Robinson, Jennifer G, Duggan, David, DIAGRAM Consortium, MAGIC Consortium, Kjekshus, John, Downs, John R, Gotto, Antonio M, Keech, Anthony C, Marchioli, Roberto, Tognoni, Gianni, Sever, Peter S, Poulter, Neil R, Waters, David D, Pedersen, Terje R, Amarenco, Pierre, Nakamura, Haruo, McMurray, John JV, Lewsey, James D, Chasman, Daniel I, Ridker, Paul M, Maggioni, Aldo P, Tavazzi, Luigi, Ray, Kausik K, Seshasai, Sreenivasa Rao Kondapally, Manson, JoAnn E, Price, Jackie F, Whincup, Peter H, Morris, Richard W, Lawlor, Debbie A, Smith, George Davey, Ben-Shlomo, Yoav, Schreiner, Pamela J, Fornage, Myriam, Siscovick, David S, Cushman, Mary, Kumari, Meena, Wareham, Nick J, Verschuren, WM Monique, Redline, Susan, Patel, Sanjay R, Whittaker, John C, and Hamsten, Anders

Subjects
Epidemiology, Biomedical and Clinical Sciences, Health Sciences, Clinical Trials and Supportive Activities, Clinical Research, Genetics, Nutrition, Diabetes, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Metabolic and endocrine, Aged, Body Mass Index, Body Weight, Cholesterol, HDL, Cholesterol, LDL, Diabetes Mellitus, Type 2, Female, Genetic Testing, Humans, Hydroxymethylglutaryl CoA Reductases, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Male, Middle Aged, Polymorphism, Single Nucleotide, Randomized Controlled Trials as Topic, Risk Factors, DIAGRAM Consortium, MAGIC Consortium, InterAct Consortium, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundStatins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target.MethodsWe used single nucleotide polymorphisms in the HMGCR gene, rs17238484 (for the main analysis) and rs12916 (for a subsidiary analysis) as proxies for HMGCR inhibition by statins. We examined associations of these variants with plasma lipid, glucose, and insulin concentrations; bodyweight; waist circumference; and prevalent and incident type 2 diabetes. Study-specific effect estimates per copy of each LDL-lowering allele were pooled by meta-analysis. These findings were compared with a meta-analysis of new-onset type 2 diabetes and bodyweight change data from randomised trials of statin drugs. The effects of statins in each randomised trial were assessed using meta-analysis.FindingsData were available for up to 223 463 individuals from 43 genetic studies. Each additional rs17238484-G allele was associated with a mean 0·06 mmol/L (95% CI 0·05-0·07) lower LDL cholesterol and higher body weight (0·30 kg, 0·18-0·43), waist circumference (0·32 cm, 0·16-0·47), plasma insulin concentration (1·62%, 0·53-2·72), and plasma glucose concentration (0·23%, 0·02-0·44). The rs12916 SNP had similar effects on LDL cholesterol, bodyweight, and waist circumference. The rs17238484-G allele seemed to be associated with higher risk of type 2 diabetes (odds ratio [OR] per allele 1·02, 95% CI 1·00-1·05); the rs12916-T allele association was consistent (1·06, 1·03-1·09). In 129 170 individuals in randomised trials, statins lowered LDL cholesterol by 0·92 mmol/L (95% CI 0·18-1·67) at 1-year of follow-up, increased bodyweight by 0·24 kg (95% CI 0·10-0·38 in all trials; 0·33 kg, 95% CI 0·24-0·42 in placebo or standard care controlled trials and -0·15 kg, 95% CI -0·39 to 0·08 in intensive-dose vs moderate-dose trials) at a mean of 4·2 years (range 1·9-6·7) of follow-up, and increased the odds of new-onset type 2 diabetes (OR 1·12, 95% CI 1·06-1·18 in all trials; 1·11, 95% CI 1·03-1·20 in placebo or standard care controlled trials and 1·12, 95% CI 1·04-1·22 in intensive-dose vs moderate dose trials).InterpretationThe increased risk of type 2 diabetes noted with statins is at least partially explained by HMGCR inhibition.FundingThe funding sources are cited at the end of the paper.

Published
2015

33. SMIM1 absence is associated with reduced energy expenditure and excess weight

Author

Banasik, Karina, Bay, Jakob, Boldsen, Jens Kjærgaard, Brodersen, Thorsten, Brunak, Søren, Burgdorf, Kristoffer, Chalmer, Mona Ameri, Didriksen, Maria, Dinh, Khoa Manh, Dowsett, Joseph, Erikstrup, Christian, Feenstra, Bjarke, Geller, Frank, Gudbjartsson, Daniel, Hansen, Thomas Folkmann, Hindhede, Lotte, Hjalgrim, Henrik, Jacobsen, Rikke Louise, Jemec, Gregor, Jensen, Bitten Aagaard, Kaspersen, Katrine, Kjerulff, Bertram Dalskov, Kogelman, Lisette, Hørup Larsen, Margit Anita, Louloudis, Ioannis, Lundgaard, Agnete, Susan, Mikkelsen, Christina, Nissen, Ioanna, Nyegaard, Mette, Ostrowski, Sisse Rye, Pedersen, Ole Birger, Henriksen, Alexander Pil, Rohde, Palle Duun, Rostgaard, Klaus, Schwinn, Michael, Stefansson, Kari, Stefánsson, Hreinn, Sørensen, Erik, þorsteinsdóttir, Unnur, Thørner, Lise Wegner, Bruun, Mie Topholm, Ullum, Henrik, Werge, Thomas, Westergaard, David, Chen, Ji, Spracklen, Cassandra N., Marenne, Gaëlle, Varshney, Arushi, Corbin, Laura J., Luan, Jian’an, Willems, Sara M., Wu, Ying, Zhang, Xiaoshuai, Horikoshi, Momoko, Boutin, Thibaud S., Mägi, Reedik, Waage, Johannes, Li-Gao, Ruifang, Katie Chan, Kei Hang, Yao, Jie, Anasanti, Mila D., Chu, Audrey Y., Claringbould, Annique, Heikkinen, Jani, Hong, Jaeyoung, Hottenga, Jouke-Jan, Huo, Shaofeng, Kaakinen, Marika A., Louie, Tin, März, Winfried, Moreno-Macias, Hortensia, Ndungu, Anne, Nelson, Sarah C., Nolte, Ilja M., North, Kari E., Raulerson, Chelsea K., Ray, Debashree, Rohde, Rebecca, Rybin, Denis, Schurmann, Claudia, Sim, Xueling, Southam, Loz, Stewart, Isobel D., Wang, Carol A., Wang, Yujie, Wu, Peitao, Zhang, Weihua, Ahluwalia, Tarunveer S., Appel, Emil V.R., Bielak, Lawrence F., Brody, Jennifer A., Burtt, Noël P., Cabrera, Claudia P., Cade, Brian E., Chai, Jin Fang, Chai, Xiaoran, Chang, Li-Ching, Chen, Chien-Hsiun, Chen, Brian H., Chitrala, Kumaraswamy Naidu, Chiu, Yen-Feng, de Haan, Hugoline G., Delgado, Graciela E., Demirkan, Ayse, Duan, Qing, Engmann, Jorgen, Fatumo, Segun A., Gayán, Javier, Giulianini, Franco, Gong, Jung Ho, Gustafsson, Stefan, Hai, Yang, Hartwig, Fernando P., He, Jing, Heianza, Yoriko, Huang, Tao, Huerta-Chagoya, Alicia, Hwang, Mi Yeong, Jensen, Richard A., Kawaguchi, Takahisa, Kentistou, Katherine A., Kim, Young Jin, Kleber, Marcus E., Kooner, Ishminder K., Lai, Shuiqing, Lange, Leslie A., Langefeld, Carl D., Lauzon, Marie, Li, Man, Ligthart, Symen, Liu, Jun, Loh, Marie, Long, Jirong, Lyssenko, Valeriya, Mangino, Massimo, Marzi, Carola, Montasser, May E., Nag, Abhishek, Nakatochi, Masahiro, Noce, Damia, Noordam, Raymond, Pistis, Giorgio, Preuss, Michael, Raffield, Laura, Rasmussen-Torvik, Laura J., Rich, Stephen S., Robertson, Neil R., Rueedi, Rico, Ryan, Kathleen, Sanna, Serena, Saxena, Richa, Schraut, Katharina E., Sennblad, Bengt, Setoh, Kazuya, Smith, Albert V., Southam, Lorraine, Sparsø, Thomas, Strawbridge, Rona J., Takeuchi, Fumihiko, Tan, Jingyi, Trompet, Stella, van den Akker, Erik, van der Most, Peter J., Verweij, Niek, Vogel, Mandy, Wang, Heming, Wang, Chaolong, Wang, Nan, Warren, Helen R., Wen, Wanqing, Wilsgaard, Tom, Wong, Andrew, Wood, Andrew R., Xie, Tian, Zafarmand, Mohammad Hadi, Zhao, Jing-Hua, Zhao, Wei, Amin, Najaf, Arzumanyan, Zorayr, Astrup, Arne, Bakker, Stephan J.L., Baldassarre, Damiano, Beekman, Marian, Bergman, Richard N., Bertoni, Alain, Blüher, Matthias, Bonnycastle, Lori L., Bornstein, Stefan R., Bowden, Donald W., Cai, Qiuyin, Campbell, Archie, Campbell, Harry, Chang, Yi Cheng, de Geus, Eco J.C., Dehghan, Abbas, Du, Shufa, Eiriksdottir, Gudny, Farmaki, Aliki Eleni, Frånberg, Mattias, Fuchsberger, Christian, Gao, Yutang, Gjesing, Anette P., Goel, Anuj, Han, Sohee, Hartman, Catharina A., Herder, Christian, Hicks, Andrew A., Hsieh, Chang-Hsun, Hsueh, Willa A., Ichihara, Sahoko, Igase, Michiya, Ikram, M. Arfan, Johnson, W. Craig, Jørgensen, Marit E., Joshi, Peter K., Kalyani, Rita R., Kandeel, Fouad R., Katsuya, Tomohiro, Khor, Chiea Chuen, Kiess, Wieland, Kolcic, Ivana, Kuulasmaa, Teemu, Kuusisto, Johanna, Läll, Kristi, Lam, Kelvin, Lawlor, Deborah A., Lee, Nanette R., Lemaitre, Rozenn N., Li, Honglan, Lin, Shih-Yi, Lindström, Jaana, Linneberg, Allan, Liu, Jianjun, Lorenzo, Carlos, Matsubara, Tatsuaki, Matsuda, Fumihiko, Mingrone, Geltrude, Mooijaart, Simon, Moon, Sanghoon, Nabika, Toru, Nadkarni, Girish N., Nadler, Jerry L., Nelis, Mari, Neville, Matt J., Norris, Jill M., Ohyagi, Yasumasa, Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Qi, Qibin, Raven, Dennis, Reilly, Dermot F., Reiner, Alex, Rivideneira, Fernando, Roll, Kathryn, Rudan, Igor, Sabanayagam, Charumathi, Sandow, Kevin, Sattar, Naveed, Schürmann, Annette, Shi, Jinxiu, Stringham, Heather M., Taylor, Kent D., Teslovich, Tanya M., Thuesen, Betina, Timmers, Paul R.H.J., Tremoli, Elena, Tsai, Michael Y., Uitterlinden, Andre, van Dam, Rob M., van Heemst, Diana, van Hylckama Vlieg, Astrid, Van Vliet-Ostaptchouk, Jana V., Vangipurapu, Jagadish, Vestergaard, Henrik, Wang, Tao, Willems van Dijk, Ko, Zemunik, Tatijana, Abecasis, Goncalo R., Adair, Linda S., Aguilar-Salinas, Carlos Alberto, Alarcón-Riquelme, Marta E., An, Ping, Aviles-Santa, Larissa, Becker, Diane M., Beilin, Lawrence J., Bergmann, Sven, Bisgaard, Hans, Black, Corri, Boehnke, Michael, Boerwinkle, Eric, Böhm, Bernhard O., Bønnelykke, Klaus, Boomsma, D.I., Bottinger, Erwin P., Buchanan, Thomas A., Canouil, Mickaël, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Ida Chen, Yii-Der, Cheng, Ching-Yu, Collins, Francis S., Correa, Adolfo, Cucca, Francesco, Janaka de Silva, H., Dedoussis, George, Elmståhl, Sölve, Evans, Michele K., Ferrannini, Ele, Ferrucci, Luigi, Florez, Jose C., Franks, Paul W., Frayling, Timothy M., Froguel, Philippe, Gigante, Bruna, Goodarzi, Mark O., Gordon-Larsen, Penny, Grallert, Harald, Grarup, Niels, Grimsgaard, Sameline, Groop, Leif, Gudnason, Vilmundur, Guo, Xiuqing, Hamsten, Anders, Hansen, Torben, Hayward, Caroline, Heckbert, Susan R., Horta, Bernardo L., Huang, Wei, Ingelsson, Erik, James, Pankow S., Jarvelin, Marjo-Ritta, Jonas, Jost B., Jukema, J. Wouter, Kaleebu, Pontiano, Kaplan, Robert, Kardia, Sharon L.R., Kato, Norihiro, Keinanen-Kiukaanniemi, Sirkka M., Kim, Bong-Jo, Kivimaki, Mika, Koistinen, Heikki A., Kooner, Jaspal S., Körner, Antje, Kovacs, Peter, Kuh, Diana, Kumari, Meena, Kutalik, Zoltan, Laakso, Markku, Lakka, Timo A., Launer, Lenore J., Leander, Karin, Li, Huaixing, Lin, Xu, Lind, Lars, Lindgren, Cecilia, Liu, Simin, Loos, Ruth J.F., Magnusson, Patrik K.E., Mahajan, Anubha, Metspalu, Andres, Mook-Kanamori, Dennis O., Mori, Trevor A., Munroe, Patricia B., Njølstad, Inger, O'Connell, Jeffrey R., Oldehinkel, Albertine J., Ong, Ken K., Padmanabhan, Sandosh, Palmer, Colin N.A., Palmer, Nicholette D., Pedersen, Oluf, Pennell, Craig E., Porteous, David J., Pramstaller, Peter P., Province, Michael A., Psaty, Bruce M., Qi, Lu, Raffel, Leslie J., Rauramaa, Rainer, Redline, Susan, Ridker, Paul M., Rosendaal, Frits R., Saaristo, Timo E., Sandhu, Manjinder, Saramies, Jouko, Schneiderman, Neil, Schwarz, Peter, Scott, Laura J., Selvin, Elizabeth, Sever, Peter, Shu, Xiao-Ou, Slagboom, P. Eline, Small, Kerrin S., Smith, Blair H., Snieder, Harold, Sofer, Tamar, Sørensen, Thorkild I.A., Spector, Tim D., Stanton, Alice, Steves, Claire J., Stumvoll, Michael, Sun, Liang, Tabara, Yasuharu, Tai, E. Shyong, Timpson, Nicholas J., Tönjes, Anke, Tuomilehto, Jaakko, Tusie, Teresa, Uusitupa, Matti, van der Harst, Pim, van Duijn, Cornelia, Vitart, Veronique, Vollenweider, Peter, Vrijkotte, Tanja G.M., Wagenknecht, Lynne E., Walker, Mark, Wang, Ya X., Wareham, Nick J., Watanabe, Richard M., Watkins, Hugh, Wei, Wen B., Wickremasinghe, Ananda R., Willemsen, Gonneke, Wilson, James F., Wong, Tien-Yin, Wu, Jer-Yuarn, Xiang, Anny H., Yanek, Lisa R., Yengo, Loïc, Yokota, Mitsuhiro, Zeggini, Eleftheria, Zheng, Wei, Zonderman, Alan B., Rotter, Jerome I., Gloyn, Anna L., McCarthy, Mark I., Dupuis, Josée, Meigs, James B., Scott, Robert A., Prokopenko, Inga, Leong, Aaron, Liu, Ching-Ti, Parker, Stephen C.J., Mohlke, Karen L., Langenberg, Claudia, Wheeler, Eleanor, Morris, Andrew P., Barroso, Inês, Stefanucci, Luca, Moslemi, Camous, Tomé, Ana R., Virtue, Samuel, Bidault, Guillaume, Gleadall, Nicholas S., Watson, Laura P.E., Kwa, Jing E., Burden, Frances, Farrow, Samantha, Võsa, Urmo, Burling, Keith, Walker, Lindsay, Ord, John, Barker, Peter, Warner, James, Frary, Amy, Renhstrom, Karola, Ashford, Sofie E., Piper, Jo, Biggs, Gail, Erber, Wendy N., Hoffman, Gary J., Schoenmakers, Nadia, Rieneck, Klaus, Dziegiel, Morten H., Azzu, Vian, Vacca, Michele, Aparicio, Hugo Javier, Hui, Qin, Cho, Kelly, Sun, Yan V., Wilson, Peter W., Bayraktar, Omer A., Vidal-Puig, Antonio, Ostrowski, Sisse R., Astle, William J., Olsson, Martin L., Storry, Jill R., Pedersen, Ole B., Ouwehand, Willem H., Chatterjee, Krishna, Vuckovic, Dragana, and Frontini, Mattia

Published
2024
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35. Cell Surface Platelet Tissue Factor Expression: Regulation by P2Y 12 and Link to Residual Platelet Reactivity

Author

Brambilla, Marta, primary, Becchetti, Alessia, additional, Rovati, Gianenrico, additional, Cosentino, Nicola, additional, Conti, Maria, additional, Canzano, Paola, additional, Giesen, Peter L.A., additional, Loffreda, Alessia, additional, Bonomi, Alice, additional, Cattaneo, Marco, additional, De Candia, Erica, additional, Podda, Gian Marco, additional, Trabattoni, Daniela, additional, Werba, Josè, additional, Campodonico, Jeness, additional, Pinna, Christian, additional, Marenzi, Giancarlo, additional, Tremoli, Elena, additional, and Camera, Marina, additional

Published
2023
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39. Association of lifelong occupation and educational level with subclinical atherosclerosis in different European regions. Results from the IMPROVE study

Author

Tedesco, Calogero C., Veglia, Fabrizio, de Faire, Ulf, Kurl, Sudhir, Smit, Andries J., Rauramaa, Rainer, Giral, Philippe, Amato, Mauro, Bonomi, Alice, Ravani, Alessio, Frigerio, Beatrice, Castelnuovo, Samuela, Sansaro, Daniela, Mannarino, Elmo, Humphries, Steve E., Hamsten, Anders, Tremoli, Elena, and Baldassarre, Damiano

Published
2018
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40. D-dimer is associated with arterial and venous coronary artery bypass graft occlusion

Author

Zanobini, Marco, Roberto, Maurizio, Porqueddu, Massimo, Naliato, Moreno, Kassem, Samer, Mushtaq, Saima, Bertella, Erika, Pepi, Mauro, Annoni, Andrea, Formenti, Alberto, Brambilla, Marta, Ghilardi, Stefania, Brioschi, Maura, Barbieri, Silvia, Parolari, Alessandro, Cavallotti, Laura, Andreini, Daniele, Myasoedova, Veronika, Banfi, Cristina, Camera, Marina, Poggio, Paolo, Barili, Fabio, Pontone, GianLuca, Mussoni, Luciana, Centenaro, Chiara, Alamanni, Francesco, and Tremoli, Elena

Published
2018
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42. Identification of a novel proinsulin-associated SNP and demonstration that proinsulin is unlikely to be a causal factor in subclinical vascular remodelling using Mendelian randomisation

Author

Strawbridge, Rona J., Silveira, Angela, Hoed, Marcel den, Gustafsson, Stefan, Luan, Jian'an, Rybin, Denis, Dupuis, Josée, Li-Gao, Ruifang, Kavousi, Maryam, Dehghan, Abbas, Haljas, Kadri, Lahti, Jari, Gådin, Jesper R., Bäcklund, Alexandra, de Faire, Ulf, Gertow, Karl, Giral, Phillipe, Goel, Anuj, Humphries, Steve E., Kurl, Sudhir, Langenberg, Claudia, Lannfelt, Lars L., Lind, Lars, Lindgren, Cecilia C.M., Mannarino, Elmo, Mook-Kanamori, Dennis O., Morris, Andrew P., de Mutsert, Renée, Rauramaa, Rainer, Saliba-Gustafsson, Peter, Sennblad, Bengt, Smit, Andries J., Syvänen, Ann-Christine, Tremoli, Elena, Veglia, Fabrizio, Zethelius, Björn, Björck, Hanna M., Eriksson, Johan G., Hofman, Albert, Franco, Oscar H., Watkins, Hugh, Jukema, J. Wouter, Florez, Jose C., Wareham, Nicholas J., Meigs, James B., Ingelsson, Erik, Baldassarre, Damiano, and Hamsten, Anders

Published
2017
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44. Rationale and design of the CV-PREVITAL study: an Italian multiple cohort randomised controlled trial investigating innovative digital strategies in primary cardiovascular prevention

Author

Baldassarre, Damiano, primary, Iacoviello, Licia, additional, Baetta, Roberta, additional, Roncaglioni, Maria Carla, additional, Condorelli, Gianluigi, additional, Remuzzi, Giuseppe, additional, Gensini, Gianfranco, additional, Frati, Luigi, additional, Ricciardi, Walter, additional, Conaldi, Pier Giulio, additional, Uccelli, Antonio, additional, Blandini, Fabio, additional, Bosari, Silvano, additional, Scambia, Giovanni, additional, Fini, Massimo, additional, Di Malta, Antonio, additional, Amato, Mauro, additional, Veglia, Fabrizio, additional, Bonomi, Alice, additional, Klersy, Catherine, additional, Colazzo, Francesca, additional, Pengo, Martino, additional, Gorini, Francesca, additional, Auteri, Luciana, additional, Ferrante, Giuseppe, additional, Baviera, Marta, additional, Ambrosio, Giuseppe, additional, Catapano, Alberico, additional, Gialluisi, Alessandro, additional, Malavazos, Alexis Elias, additional, Castelvecchio, Serenella, additional, Corsi-Romanelli, Massimiliano Marco, additional, Cardani, Rosanna, additional, Rovere, Maria Teresa La, additional, Agnese, Valentina, additional, Pane, Bianca, additional, Prati, Daniele, additional, Spinardi, Laura, additional, Liuzzo, Giovanna, additional, Arbustini, Eloisa, additional, Volterrani, Maurizio, additional, Visconti, Marco, additional, Werba, José Pablo, additional, Genovese, Stefano, additional, Bilo, Grzegorz, additional, Invitti, Cecilia, additional, Di Blasio, Anna, additional, Lombardi, Carolina, additional, Faini, Andrea, additional, Rosa, Debora, additional, Ojeda-Fernández, Luisa, additional, Foresta, Andreana, additional, De Curtis, Amalia, additional, Di Castelnuovo, Augusto, additional, Scalvini, Simonetta, additional, Pierobon, Antonia, additional, Gorini, Alessandra, additional, Valenti, Luca, additional, Luzi, Livio, additional, Racca, Annarosa, additional, Bandi, Manuela, additional, Tremoli, Elena, additional, Menicanti, Lorenzo, additional, Parati, Gianfranco, additional, and Pompilio, Giulio, additional

Published
2023
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46. Carotid plaque-thickness and common carotid IMT show additive value in cardiovascular risk prediction and reclassification

Author

Amato, Mauro, Veglia, Fabrizio, de Faire, Ulf, Giral, Philippe, Rauramaa, Rainer, Smit, Andries J., Kurl, Sudhir, Ravani, Alessio, Frigerio, Beatrice, Sansaro, Daniela, Bonomi, Alice, Tedesco, Calogero C., Castelnuovo, Samuela, Mannarino, Elmo, Humphries, Steve E., Hamsten, Anders, Tremoli, Elena, and Baldassarre, Damiano

Published
2017
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50. A machine learning based approach to identify carotid subclinical atherosclerosis endotypes.

Author

Chen, Qiao Sen, Bergman, Otto, Ziegler, Louise, Baldassarre, Damiano, Veglia, Fabrizio, Tremoli, Elena, Strawbridge, Rona J, Gallo, Antonio, Pirro, Matteo, Smit, Andries J, Kurl, Sudhir, Savonen, Kai, Lind, Lars, Eriksson, Per, and Gigante, Bruna

Subjects
MACHINE learning, ATHEROSCLEROSIS, SYSTOLIC blood pressure, ATHEROSCLEROTIC plaque, CARDIOVASCULAR diseases risk factors
Abstract

Aims To define endotypes of carotid subclinical atherosclerosis. Methods and results We integrated demographic, clinical, and molecular data (n = 124) with ultrasonographic carotid measurements from study participants in the IMPROVE cohort (n = 3340). We applied a neural network algorithm and hierarchical clustering to identify carotid atherosclerosis endotypes. A measure of carotid subclinical atherosclerosis, the c-IMTmean-max, was used to extract atherosclerosis-related features and SHapley Additive exPlanations (SHAP) to reveal endotypes. The association of endotypes with carotid ultrasonographic measurements at baseline, after 30 months, and with the 3-year atherosclerotic cardiovascular disease (ASCVD) risk was estimated by linear (β , SE) and Cox [hazard ratio (HR), 95% confidence interval (CI)] regression models. Crude estimates were adjusted by common cardiovascular risk factors, and baseline ultrasonographic measures. Improvement in ASCVD risk prediction was evaluated by C -statistic and by net reclassification improvement with reference to SCORE2, c-IMTmean-max, and presence of carotid plaques. An ensemble stacking model was used to predict endotypes in an independent validation cohort, the PIVUS (n = 1061). We identified four endotypes able to differentiate carotid atherosclerosis risk profiles from mild (endotype 1) to severe (endotype 4). SHAP identified endotype-shared variables (age, biological sex, and systolic blood pressure) and endotype-specific biomarkers. In the IMPROVE, as compared to endotype 1, endotype 4 associated with the thickest c-IMT at baseline (β , SE) 0.36 (0.014), the highest number of plaques 1.65 (0.075), the fastest c-IMT progression 0.06 (0.013), and the highest ASCVD risk (HR, 95% CI) (1.95, 1.18–3.23). Baseline and progression measures of carotid subclinical atherosclerosis and ASCVD risk were associated with the predicted endotypes in the PIVUS. Endotypes consistently improved measures of ASCVD risk discrimination and reclassification in both study populations. Conclusions We report four replicable subclinical carotid atherosclerosis—endotypes associated with progression of atherosclerosis and ASCVD risk in two independent populations. Our approach based on endotypes can be applied for precision medicine in ASCVD prevention. [ABSTRACT FROM AUTHOR]

Published
2023
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