Search

Your search keyword '"Liliana Grigore"' showing total 123 results
Start Over Author "Liliana Grigore"
123 results on '"Liliana Grigore"'

1. High dietary inflammatory index associates with inflammatory proteins in plasma

Author

Elisa Mattavelli, Elisa Piperni, Francesco Asnicar, Laura Redaelli, Liliana Grigore, Fabio Pellegatta, Amir Nabinejad, Sabrina Tamburini, Nicola Segata, Alberico Luigi Catapano, and Andrea Baragetti

Subjects
Diet, Inflammation, Proteomics, Cardio-metabolic prevention, Nutritional diseases. Deficiency diseases, RC620-627
Abstract

Abstract Background and aim Unhealthy dietary habits and highly caloric foods induce metabolic alterations and promote the development of the inflammatory consequences of obesity, insulin resistance, diabetes and cardiovascular diseases. Describing an inflammatory effect of diet is difficult to pursue, owing lacks of standardized quali-quantitative dietary assessments. The Dietary Inflammatory Index (DII) has been proposed as an estimator of the pro- or anti-inflammatory effect of nutrients and higher DII values, which indicate an increased intake of nutrients with pro-inflammatory effects, relate to an increased risk of metabolic and cardiovascular diseases and we here assessed whether they reflect biologically relevant plasmatic variations of inflammatory proteins. Methods In this cross-sectional study, seven days dietary records from 663 subjects in primary prevention for cardiovascular diseases were analyzed to derive the intake of nutrients, foods and to calculate DII. To associate DII with the Normalized Protein eXpression (NPX), an index of abundance, of a targeted panel of 368 inflammatory biomarkers (Olink™) measured in the plasma, we divided the population by the median value of DII (1.60 (0.83–2.30)). Results 332 subjects with estimated DII over the median value reported a higher intake of saturated fats but lower intakes of poly-unsaturated fats, including omega-3 and omega-6 fats, versus subjects with estimated dietary DII below the median value (N = 331). The NPX of 61 proteins was increased in the plasma of subjects with DII > median vs. subjects with DII median (Area Under the Curve = 0.601 (0.519–0.668), p = 0.035). Conclusion This large-scale proteomic study supports that higher DII reflects changes in the plasmatic abundance of inflammatory proteins. Larger studies are warranted to validate.

Published
2024
Full Text
View/download PDF

2. Association of Intima‐Media Thickness Measured at the Common Carotid Artery With Incident Carotid Plaque: Individual Participant Data Meta‐Analysis of 20 Prospective Studies

Author

Lena Tschiderer, Lisa Seekircher, Raffaele Izzo, Costantino Mancusi, Maria V. Manzi, Damiano Baldassarre, Mauro Amato, Elena Tremoli, Fabrizio Veglia, Tomi‐Pekka Tuomainen, Jussi Kauhanen, Ari Voutilainen, Bernhard Iglseder, Lars Lind, Tatjana Rundek, Moise Desvarieux, Akihiko Kato, Eric de Groot, Gülay Aşçi, Ercan Ok, Stefan Agewall, Joline W. J. Beulens, Christopher D. Byrne, Philip C. Calder, Hertzel C. Gerstein, Paolo Gresele, Gerhard Klingenschmid, Michiaki Nagai, Michael H. Olsen, Grace Parraga, Maya S. Safarova, Naveed Sattar, Michael Skilton, Coen D. A. Stehouwer, Heiko Uthoff, Michiel A. van Agtmael, Amber A. van der Heijden, Dorota A. Zozulińska‐Ziółkiewicz, Hyun‐Woong Park, Moo‐Sik Lee, Jang‐Ho Bae, Oscar Beloqui, Manuel F. Landecho, Matthieu Plichart, Pierre Ducimetiere, Jean Philippe Empana, Lena Bokemark, Göran Bergström, Caroline Schmidt, Samuela Castelnuovo, Laura Calabresi, Giuseppe D. Norata, Liliana Grigore, Alberico Catapano, Dong Zhao, Miao Wang, Jing Liu, M. Arfan Ikram, Maryam Kavousi, Michiel L. Bots, Michael J. Sweeting, Matthias W. Lorenz, and Peter Willeit

Subjects
carotid intima‐media thickness, carotid plaque, individual participant data meta‐analysis, prospective studies, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background The association between common carotid artery intima‐media thickness (CCA‐IMT) and incident carotid plaque has not been characterized fully. We therefore aimed to precisely quantify the relationship between CCA‐IMT and carotid plaque development. Methods and Results We undertook an individual participant data meta‐analysis of 20 prospective studies from the Proof‐ATHERO (Prospective Studies of Atherosclerosis) consortium that recorded baseline CCA‐IMT and incident carotid plaque involving 21 494 individuals without a history of cardiovascular disease and without preexisting carotid plaque at baseline. Mean baseline age was 56 years (SD, 9 years), 55% were women, and mean baseline CCA‐IMT was 0.71 mm (SD, 0.17 mm). Over a median follow‐up of 5.9 years (5th–95th percentile, 1.9–19.0 years), 8278 individuals developed first‐ever carotid plaque. We combined study‐specific odds ratios (ORs) for incident carotid plaque using random‐effects meta‐analysis. Baseline CCA‐IMT was approximately log‐linearly associated with the odds of developing carotid plaque. The age‐, sex‐, and trial arm–adjusted OR for carotid plaque per SD higher baseline CCA‐IMT was 1.40 (95% CI, 1.31–1.50; I2=63.9%). The corresponding OR that was further adjusted for ethnicity, smoking, diabetes, body mass index, systolic blood pressure, low‐ and high‐density lipoprotein cholesterol, and lipid‐lowering and antihypertensive medication was 1.34 (95% CI, 1.24–1.45; I2=59.4%; 14 studies; 16 297 participants; 6381 incident plaques). We observed no significant effect modification across clinically relevant subgroups. Sensitivity analysis restricted to studies defining plaque as focal thickening yielded a comparable OR (1.38 [95% CI, 1.29–1.47]; I2=57.1%; 14 studies; 17 352 participants; 6991 incident plaques). Conclusions Our large‐scale individual participant data meta‐analysis demonstrated that CCA‐IMT is associated with the long‐term risk of developing first‐ever carotid plaque, independent of traditional cardiovascular risk factors.

Published
2023
Full Text
View/download PDF

3. The Role of Registers in Increasing Knowledge and Improving Management of Children and Adolescents Affected by Familial Hypercholesterolemia: the LIPIGEN Pediatric Group

Author

Marta Gazzotti, Manuela Casula, Stefano Bertolini, Maria Elena Capra, Elena Olmastroni, Alberico Luigi Catapano, Cristina Pederiva, the LIPIGEN Paediatric Group, Massimiliano Allevi, Marcello Arca, Renata Auricchio, Maurizio Averna, Davide Baldera, Giuseppe Banderali, Andrea Bartuli, Giacomo Biasucci, Claudio Borghi, Patrizia Bruzzi, Raffaele Buganza, Paola Sabrina Buonuomo, Paolo Calabrò, Sebastiano Calandra, Francesca Carubbi, Arturo Cesaro, Francesco Cipollone, Nadia Citroni, Giuseppe Covetti, Annalaura Cremonini, Sergio D’Addato, Maria Del Ben, Maria Donata Di Taranto, Giuliana Fortunato, Roberto Franceschi, Federica Galimberti, Simonetta Genovesi, Antonina Giammanco, Liliana Grigore, Ornella Guardamagna, Arcangelo Iannuzzi, Gabriella Iannuzzo, Lorenzo Iughetti, Lidia Lascala, Fabiana Locatelli, Sara Madaghiele, Giuseppe Mandraffino, Massimo Raffaele Mannarino, Bucci Marco, Lorenzo Maroni, Ilenia Minicocci, Giuliana Mombelli, Sandro Muntoni, Fabio Nascimbeni, Gianfranco Parati, Angelina Passaro, Chiara Pavanello, Fabio Pellegatta, Francesco Massimo Perla, Matteo Pirro, Livia Pisciotta, Arturo Pujia, Francesco Purrello, Elisabetta Rinaldi, Riccardo Sarzani, Roberto Scicali, Patrizia Suppressa, Patrizia Tarugi, Sabrina Verachtert, Giovanni Battista Vigna, Josè Pablo Werba, Alberto Zambon, Sabina Zambon, and Maria Grazia Zenti

Subjects
familial hypercholesterolemia, pediatric cohort, genetic diagnosis, pathology register, clinical diagnosis, cardiovascular genetics, Genetics, QH426-470
Abstract

Pathology registers can be a useful tool to overcome obstacles in the identification and management of familial hypercholesterolemia since childhood. In 2018, the LIPIGEN pediatric group was constituted within the Italian LIPIGEN study to focus on FH subjects under 18 years. This work aimed at discussing its recent progress and early outcomes. Demographic, biochemical, and genetic baseline characteristics were collected, with an in-depth analysis of the genetic defects. The analysis was carried out on 1,602 children and adolescents (mean age at baseline 9.9 ± 4.0 years), and almost the whole cohort underwent the genetic test (93.3%). Overall, the untreated mean value of LDL-C was 220.0 ± 97.2 mg/dl, with an increasing gradient from subjects with a negative (N = 317; mean untreated LDL-C = 159.9 ± 47.7 mg/dl), inconclusive (N = 125; mean untreated LDL-C = 166.4 ± 56.5 mg/dl), or positive (N = 1,053; mean untreated LDL-C = 246.5 ± 102.1 mg/dl) genetic diagnosis of FH. In the latter group, the LDL-C values presented a great variability based on the number and the biological impact of involved causative variants. The LIPIGEN pediatric group represents one of the largest cohorts of children with FH, allowing the deepening of the characterization of their baseline and genetic features, providing the basis for further longitudinal investigations for complete details.

Published
2022
Full Text
View/download PDF

4. Myeloid apolipoprotein E controls dendritic cell antigen presentation and T cell activation

Author

Fabrizia Bonacina, David Coe, Guosu Wang, Maria P. Longhi, Andrea Baragetti, Annalisa Moregola, Katia Garlaschelli, Patrizia Uboldi, Fabio Pellegatta, Liliana Grigore, Lorenzo Da Dalt, Andrea Annoni, Silvia Gregori, Qingzhong Xiao, Donatella Caruso, Nico Mitro, Alberico L. Catapano, Federica M. Marelli-Berg, and Giuseppe D. Norata

Subjects
Science
Abstract

Cholesterol homeostasis can modulate immunity via multiple pathways. Here the authors show that apolipoprotein E, an important regulator of cholesterol, produced by myeloid cells can regulate T cell activation by controlling the antigen presentation activity of dendritic cells in both humans and mice.

Published
2018
Full Text
View/download PDF

5. The Association of Proprotein Convertase Subtilisin/Kexin Type 9 to Plasma Low-Density Lipoproteins: An Evaluation of Different Methods

Author

Laura Canclini, Amir Mohammad Malvandi, Patrizia Uboldi, Najoua Jabnati, Liliana Grigore, Alberto Zambon, Andrea Baragetti, and Alberico Luigi Catapano

Subjects
PCSK9, lipids, LDL, cardiovascular diseases, atherosclerosis, lipoproteins, Microbiology, QR1-502
Abstract

Proprotein convertase subtilisin/kexin type-9 (PCSK9) is key regulator of low-density lipoprotein (LDL) metabolism. A significant proportion of PCSK9 is believed to be associated with LDL in plasma as it circulates, although this finding is still a matter of debate. The purpose of this study was to establish an experimental method to investigate the presence of such an interaction in the bloodstream. We compared a number of well-established methods for lipoprotein (LP) isolation to clarify whether PCSK9 associates differently to circulating lipoproteins, such as KBr gradient ultracentrifugation, physical precipitation of ApoB-LPs, fast protein liquid chromatography (FPLC) and iodixanol gradient ultracentrifugation. Our data show heterogeneity in PCSK9 association to lipoproteins according to the method used. Two methods, iodixanol ultracentrifugation and column chromatography, which did not involve precipitation or high salt concentration, consistently showed an interaction of PCSK9 with a subfraction of LDL that appeared to be more buoyant and have a lower size than average LDL. The percent of PCSK9 association ranged from 2 to 30% and did not appear to correlate to plasma or LDL cholesterol levels. The association of PCSK9 to LDL appeared to be sensitive to high salt concentrations. FPLC and iodixanol gradient ultracentrifugation appeared to be the most suitable methods for the study of this association.

Published
2021
Full Text
View/download PDF

6. Identification of AnnexinA1 as an Endogenous Regulator of RhoA, and Its Role in the Pathophysiology and Experimental Therapy of Type-2 Diabetes

Author

Gareth S. D. Purvis, Massimo Collino, Rodrigo A. Loiola, Andrea Baragetti, Fausto Chiazza, Martina Brovelli, Madeeha H. Sheikh, Debora Collotta, Alessia Cento, Raffaella Mastrocola, Manuela Aragno, Juan C. Cutrin, Chris Reutelingsperger, Liliana Grigore, Alberico L. Catapano, Magdi M. Yaqoob, Giuseppe Danilo Norata, Egle Solito, and Christoph Thiemermann

Subjects
type-2 diabetes, metabolism, Annexin A1, nephropathy, hepatosteatosis, Rho A, Immunologic diseases. Allergy, RC581-607
Abstract

Annexin A1 (ANXA1) is an endogenously produced anti-inflammatory protein, which plays an important role in the pathophysiology of diseases associated with chronic inflammation. We demonstrate that patients with type-2 diabetes have increased plasma levels of ANXA1 when compared to normoglycemic subjects. Plasma ANXA1 positively correlated with fatty liver index and elevated plasma cholesterol in patients with type-2 diabetes, suggesting a link between aberrant lipid handling, and ANXA1. Using a murine model of high fat diet (HFD)-induced insulin resistance, we then investigated (a) the role of endogenous ANXA1 in the pathophysiology of HFD-induced insulin resistance using ANXA1−/− mice, and (b) the potential use of hrANXA1 as a new therapeutic approach for experimental diabetes and its microvascular complications. We demonstrate that: (1) ANXA1−/− mice fed a HFD have a more severe diabetic phenotype (e.g., more severe dyslipidemia, insulin resistance, hepatosteatosis, and proteinuria) compared to WT mice fed a HFD; (2) treatment of WT-mice fed a HFD with hrANXA1 attenuated the development of insulin resistance, hepatosteatosis and proteinuria. We demonstrate here for the first time that ANXA1−/− mice have constitutively activated RhoA. Interestingly, diabetic mice, which have reduced tissue expression of ANXA1, also have activated RhoA. Treatment of HFD-mice with hrANXA1 restored tissue levels of ANXA1 and inhibited RhoA activity, which, in turn, resulted in restoration of the activities of Akt, GSK-3β and endothelial nitric oxide synthase (eNOS) secondary to re-sensitization of IRS-1 signaling. We further demonstrate in human hepatocytes that ANXA1 protects against excessive mitochondrial proton leak by activating FPR2 under hyperglycaemic conditions. In summary, our data suggest that (a) ANXA1 is a key regulator of RhoA activity, which restores IRS-1 signal transduction and (b) recombinant human ANXA1 may represent a novel candidate for the treatment of T2D and/or its complications.

Published
2019
Full Text
View/download PDF

7. Correction: Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk - Results from the PROG-IMT collaboration.

Author

Matthias W Lorenz, Lu Gao, Kathrin Ziegelbauer, Giuseppe Danilo Norata, Jean Philippe Empana, Irene Schmidtmann, Hung-Ju Lin, Stela McLachlan, Lena Bokemark, Kimmo Ronkainen, Mauro Amato, Ulf Schminke, Sathanur R Srinivasan, Lars Lind, Shuhei Okazaki, Coen D A Stehouwer, Peter Willeit, Joseph F Polak, Helmuth Steinmetz, Dirk Sander, Holger Poppert, Moise Desvarieux, M Arfan Ikram, Stein Harald Johnsen, Daniel Staub, Cesare R Sirtori, Bernhard Iglseder, Oscar Beloqui, Gunnar Engström, Alfonso Friera, Francesco Rozza, Wuxiang Xie, Grace Parraga, Liliana Grigore, Matthieu Plichart, Stefan Blankenberg, Ta-Chen Su, Caroline Schmidt, Tomi-Pekka Tuomainen, Fabrizio Veglia, Henry Völzke, Giel Nijpels, Johann Willeit, Ralph L Sacco, Oscar H Franco, Heiko Uthoff, Bo Hedblad, Carmen Suarez, Raffaele Izzo, Dong Zhao, Thapat Wannarong, Alberico Catapano, Pierre Ducimetiere, Christine Espinola-Klein, Kuo-Liong Chien, Jackie F Price, Göran Bergström, Jussi Kauhanen, Elena Tremoli, Marcus Dörr, Gerald Berenson, Kazuo Kitagawa, Jacqueline M Dekker, Stefan Kiechl, Matthias Sitzer, Horst Bickel, Tatjana Rundek, Albert Hofman, Ellisiv B Mathiesen, Samuela Castelnuovo, Manuel F Landecho, Maria Rosvall, Rafael Gabriel, Nicola de Luca, Jing Liu, Damiano Baldassarre, Maryam Kavousi, Eric de Groot, Michiel L Bots, David N Yanez, Simon G Thompson, and PROG-IMT study group

Subjects
Medicine, Science
Abstract

[This corrects the article DOI: 10.1371/journal.pone.0191172.].

Published
2018
Full Text
View/download PDF

8. Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk - Results from the PROG-IMT collaboration.

Author

Matthias W Lorenz, Lu Gao, Kathrin Ziegelbauer, Giuseppe Danilo Norata, Jean Philippe Empana, Irene Schmidtmann, Hung-Ju Lin, Stela McLachlan, Lena Bokemark, Kimmo Ronkainen, Mauro Amato, Ulf Schminke, Sathanur R Srinivasan, Lars Lind, Shuhei Okazaki, Coen D A Stehouwer, Peter Willeit, Joseph F Polak, Helmuth Steinmetz, Dirk Sander, Holger Poppert, Moise Desvarieux, M Arfan Ikram, Stein Harald Johnsen, Daniel Staub, Cesare R Sirtori, Bernhard Iglseder, Oscar Beloqui, Gunnar Engström, Alfonso Friera, Francesco Rozza, Wuxiang Xie, Grace Parraga, Liliana Grigore, Matthieu Plichart, Stefan Blankenberg, Ta-Chen Su, Caroline Schmidt, Tomi-Pekka Tuomainen, Fabrizio Veglia, Henry Völzke, Giel Nijpels, Johann Willeit, Ralph L Sacco, Oscar H Franco, Heiko Uthoff, Bo Hedblad, Carmen Suarez, Raffaele Izzo, Dong Zhao, Thapat Wannarong, Alberico Catapano, Pierre Ducimetiere, Christine Espinola-Klein, Kuo-Liong Chien, Jackie F Price, Göran Bergström, Jussi Kauhanen, Elena Tremoli, Marcus Dörr, Gerald Berenson, Kazuo Kitagawa, Jacqueline M Dekker, Stefan Kiechl, Matthias Sitzer, Horst Bickel, Tatjana Rundek, Albert Hofman, Ellisiv B Mathiesen, Samuela Castelnuovo, Manuel F Landecho, Maria Rosvall, Rafael Gabriel, Nicola de Luca, Jing Liu, Damiano Baldassarre, Maryam Kavousi, Eric de Groot, Michiel L Bots, David N Yanez, Simon G Thompson, and PROG-IMT study group

Subjects
Medicine, Science
Abstract

AIMS:Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk. METHODS AND RESULTS:From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies. In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95-1.02) in group A, 0.98 (0.93-1.04) in group B, and 0.95 (0.89-1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07-1.23) in group A, 1.13 (1.05-1.22) in group B, and 1.12 (1.05-1.20) in group C. CONCLUSIONS:We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals.

Published
2018
Full Text
View/download PDF

9. Epicardial Adipose Tissue (EAT) Thickness Is Associated with Cardiovascular and Liver Damage in Nonalcoholic Fatty Liver Disease.

Author

Anna Ludovica Fracanzani, Giuseppina Pisano, Dario Consonni, Silvia Tiraboschi, Andrea Baragetti, Cristina Bertelli, Giuseppe Danilo Norata, Paola Dongiovanni, Luca Valenti, Liliana Grigore, Tatiana Tonella, Alberico Catapano, and Silvia Fargion

Subjects
Medicine, Science
Abstract

Epicardial adipose tissue (EAT) has been proposed as a cardiometabolic and hepatic fibrosis risk factor in patients with non alcoholic fatty liver disease (NAFLD). Aim of this study was to evaluate the role of EAT in NAFLD by analyzing 1) the association between EAT, the other metabolic parameters and the severity of steatosis 2) the relationship between cardiovascular (cIMT, cplaques, E/A), liver (presence of NASH and significant fibrosis) damage and metabolic risk factors including EAT 3) the relationship between EAT and genetic factors strongly influencing liver steatosis.In a cross-sectional study, we considered 512 consecutive patients with NAFLD (confirmed by biopsy in 100). EAT, severity of steatosis, carotid intima-media thickness (cIMT) and plaques were evaluated by ultrasonography and results analysed by multiple linear and logistic regression models. Variables independently associated with EAT (mm) were female gender (p = 0.003), age (p = 0.001), BMI (p = 0.01), diastolic blood pressure (p = 0.009), steatosis grade 2 (p = 0.01) and 3 (p = 0.04), fatty liver index (p = 0.001) and statin use (p = 0.03). Variables independently associated with carotid IMT were age (p = 0.0001), hypertension (p = 0.009), diabetes (p = 0.04), smoking habits (p = 0.04) and fatty liver index (p = 0.02), with carotid plaques age (p = 0.0001), BMI (p = 0.03), EAT (p = 0.02),) and hypertension (p = 0.02), and with E/A age (p = 0.0001), diabetes (p = 0.005), hypertension (p = 0.04) and fatty liver index (p = 0.004). In the 100 patients with available liver histology non alcoholic steatohepatitis (NASH) was independently associated with EAT (p = 0.04) and diabetes (p = 0.054) while significant fibrosis with EAT (p = 0.02), diabetes (p = 0.01) and waist circumference (p = 0.05). No association between EAT and PNPLA3 and TM6SF2 polymorphisms was found.In patients with NAFLD, EAT is associated with the severity of liver and vascular damage besides with the known metabolic risk factors.

Published
2016
Full Text
View/download PDF

10. Combination therapy in cholesterol reduction: focus on ezetimibe and statins

Author

Liliana Grigore, Giuseppe Danilo Norata, and Alberico L Catapano

Subjects
Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Liliana Grigore1, Giuseppe Danilo Norata1,2, Alberico L Catapano1,21Department of Pharmacological Sciences, University of Milan, Milan, Italy; 2Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello B, ItalyAbstract: Although widely used in lipid lowering therapy, HMG CoA reductase inhibitors (even when administered at high doses) are frequently insufficient to achieve guideline-recommended LDL-C goals for many patients with hypercholesterolemia in everyday clinical practice. Many patients do not achieve LDL-C goal on the initial dose of statin and the majority of these patients does not reach their goal after 6 months. As a consequence, a wide therapeutic gap exists between target LDL-C levels and those typically achieved in clinical practice. A recent and more effective therapeutic hypocholesterolemic strategy is to treat the two main sources of cholesterol simultaneously (production of cholesterol, mainly in the liver, and absorption of cholesterol in the intestine) with a complementary mechanism of action, by co-administering ezetimibe, a novel agent inhibiting cholesterol absorption, with a statin, which inhibits cholesterol production in the liver. Ezetimibe can be effectively and safely co-administered with any dose of any statin and, compared with the single inhibition of cholesterol production, afforded by statins alone, provides consistently greater reductions in LDL-C through dual inhibition of both cholesterol production and absorption. We summarize the pivotal role of both the liver and intestine in the overall balance of cholesterol in the body and describe the clinical impact and relevance of using ezetimibe either alone or co-administered with statins in controlling elevated levels of plasma LDL cholesterol.Keywords: hypercholesterolemia, cholesterol absorption, cholesterol biosynthesis, ezetimibe, HMG CoA reductase inhibitors, LDL-C

Published
2008

11. IDOL N342S Variant, Atherosclerosis Progression and Cardiovascular Disorders in the Italian General Population.

Author

Ashish Dhyani, Gianpaolo Tibolla, Andrea Baragetti, Katia Garlaschelli, Fabio Pellegatta, Liliana Grigore, Giuseppe Danilo Norata, and Alberico Luigi Catapano

Subjects
Medicine, Science
Abstract

Inducible degrader of the low density lipoprotein receptor (IDOL), is an E3 ubiquitin ligase that negatively modulates low density lipoprotein receptor (LDL-R) expression. Genome-wide association studies (GWAS) indicated that genetic variants in IDOL gene contributes to variation in LDL-C plasma levels and the detailed analysis of a specific locus resulted in the identification of the functional common single nucleotide polymorphism (SNP) rs9370867 (c.G1025A, p.N342S) associates with increased LDL-R degradation and increased LDL-C levels. These findings, however, were not confirmed in two other independent cohorts and no data about the impact of this variant on atherosclerosis progression and cardiovascular risk are available. Aim of this study was to investigate the association between a functional variant in IDOL and atherosclerosis progression in an Italian general population. 1384 subjects enrolled in the PLIC study (Progression of Lesions in the Intima of Carotid) were genotyped by Q-PCR allelic discrimination and the association with anthropometric parameters, plasma lipids and the carotid intima media thickness (cIMT) and the impact on cardiovascular disease (CVD) incidence were investigated. The N342S variant was not associated with changes of the plasma lipid profile among GG, AG or AA carriers, including total cholesterol (249±21, 249±19 and 248±21 mg/dl respectively), LDL-C (158±25, 161±22 and 160±23 mg/dL), cIMT (0.74±0.14, 0.75±0.17 and 0.77±0.15 mm) and CVD incidence. In agreement, the expression of LDLR and the uptake of LDL was similar in macrophages derived from GG and AA carriers. Taken together our findings indicate that the N342S variant does not impact plasma lipid profile and is not associated with atherosclerosis progression and CVD in the general population, suggesting that other variants in the IDOL gene might be functionally linked with cholesterol metabolism.

Published
2015
Full Text
View/download PDF

12. 374 T/A RAGE polymorphism is associated with chronic kidney disease progression in subjects affected by nephrocardiovascular disease.

Author

Ivano Baragetti, Giuseppe Danilo Norata, Cristina Sarcina, Andrea Baragetti, Francesco Rastelli, Laura Buzzi, Liliana Grigore, Katia Garlaschelli, Claudio Pozzi, and Alberico Luigi Catapano

Subjects
Medicine, Science
Abstract

Chronic kidney disease (CKD) patients present elevated advanced glycation end products (AGEs) blood levels. AGEs promote inflammation through binding to their receptor (RAGE), located on the membrane of mesangial cells, endothelial cells and macrophages. Several genetic polymorphisms influence RAGE transcription, expression and activity, including the substitution of a thymine with an adenine (T/A) in the position -374 of the gene promoter of RAGE. Our study investigates the role of -374 T/A RAGE polymorphism in CKD progression in subjects affected by nephrocardiovascular disease.174 patients (119 males (68.4%) mean age 67.2±0.88 years; 55 females (31.6%): mean age 65.4±1.50 years) affected by mild to moderate nephrocardiovascular CKD were studied. Each subject was prospectively followed for 84 months, every 6-9 months. The primary endpoint of the study was a rise of serum creatinine concentrations above 50% of basal values or end stage renal disease.Carriers of the A/A and T/A genotype presented higher plasma levels of interleukin 6 (A/A 29.5±15.83; T/A 30.0±7.89, vs T/T 12.3±5.04 p = 0.01 for both) and Macrophages chemoattractant protein 1 (A/A 347.1±39.87; T/A 411.8±48.41, vs T/T 293.5±36.20, p = 0.04 for both) than T/T subjects. Carriers of the A allele presented a faster CKD progression than wild type patients (Log-Rank test: Chi square = 6.84, p = 0,03). Cox regression showed that -374 T/A RAGE polymorphism (p = 0.037), albuminuria (p = 0.01) and LDL cholesterol (p = 0.038) were directly associated with CKD progression. HDL cholesterol (p = 0.022) and BMI (p = 0.04) were inversely related to it. No relationship was found between circulating RAGE and renal function decline.-374 T/A RAGE polymorphism could be associated with CKD progression and inflammation. Further studies should confirm this finding and address whether inhibiting RAGE downstream signalling would be beneficial for CKD progression.

Published
2013
Full Text
View/download PDF

13. Association between OLR1 K167N SNP and intima media thickness of the common carotid artery in the general population.

Author

Irene Marta Predazzi, Giuseppe Danilo Norata, Lucia Vecchione, Katia Garlaschelli, Francesca Amati, Liliana Grigore, Lucia Cutuli, Angela Pirillo, Simona Tramontana, Francesco Romeo, Giuseppe Novelli, and Alberico Luigi Catapano

Subjects
Medicine, Science
Abstract

Background and purposeThe lectin-like oxidised LDL receptor-1 (OLR1) gene encodes a scavenger receptor implicated in the pathogenesis of atherosclerosis. Although functional roles have been suggested for two variants, epidemiological studies on OLR1 have been inconsistent.MethodsWe tested the association between the non-synonymous substitution K167N (rs11053646) and intima media thickness of the common carotid artery (CCA-IMT) in 2,141 samples from the Progression of Lesions in the Intima of the Carotid (PLIC) study (a prospective population-based study).ResultsSignificantly increased IMT was observed in male carriers of the minor C (N) allele compared to GC and GG (KN and KK) genotype. Functional analysis on macrophages suggested a decreased association to Ox-LDL in NN carriers compared to KN and KK carriers which is also associated with a reduced OLR1 mRNA expression. Macrophages from NN carriers present also a specific inflammatory gene expression pattern compared to cells from KN and KK carriers.ConclusionsThese data suggest that the 167N variant of LOX-1 receptor affects the atherogenic process in the carotid artery prior to evidence of disease through an inflammatory process.

Published
2012
Full Text
View/download PDF

14. Lipoprotein(a) Genotype Influences the Clinical Diagnosis of Familial Hypercholesterolemia

Author

Olmastroni, Elena, Gazzotti, Marta, Averna, Maurizio, Arca, Marcello, Tarugi, Patrizia, Calandra, Sebastiano, Bertolini, Stefano, Catapano, Alberico L, Casula, Manuela, Laura D'Erasmo, Angelo Baldassare Cefalu, Andrea Bartuli, Paola Sabrina Buonuomo, Andrea Benso, Guglielmo Beccuti, Giacomo Biasucci, Maria Elena Capra, Gianni Biolo, Pierandrea Vinci, Luca Bonanni, Claudio Borghi, Sergio D'Addato, Antonio Carlo Bossi, Giancarla Meregalli, Adriana Branchi, Paolo Calabrò, Francesca Carubbi, Fabio Nascimbeni, Francesco Cipollone, Marco Bucci, Nadia Citroni, Maria Del Ben, Francesco Baratta, Massimo Federici, Martina Montagna, Claudio Ferri, Serena Notargiacomo, Anna Maria Fiorenza, Emanuela Colombo, Giuliana Fortunato, Maria Donata Di Taranto, Andrea Giaccari, Simona Moffa, Francesco Giorgino, Sergio Di Molfetta, Ornella Guardamagna, Luisa De Sanctis, Arcangelo Iannuzzi, Raimondo Cavallaro, Gabriella Iannuzzo, Marco Gentile, Lorenzo Iughetti, Patrizia Bruzzi, Salvatore Lia, Alessandro Lupi, Giuseppe Mandraffino, Arianna Toscano, Rossella Marcucci, Martina Berteotti, Lorenzo Maroni, Fabiana Locatelli, Tiziana Montalcini, Giuliana Mombelli, Sandro Muntoni, Davide Baldera, Gianfranco Parati, Angelina Passaro, Valerio Pecchioli, Cristina Pederiva, Giuseppe Banderali, Antonio Pipolo, Debora D'Elia, Matteo Pirro, Vanessa Bianconi, Livia Pisciotta, Elena Formisano, Francesco Purrello, Roberto Scicali, Elena Repetti, Elena Cantino, Elisabetta Rinaldi, Elena Sani, Riccardo Sarzani, Francesco Spannella, Francesco Sbrana, Beatrice Dal Pino, Patrizia Suppressa, Veronica Cocco, Chiara Trenti, Emanuele Alberto Negri, Josè Pablo Werba, Alessandra Romandini, Sabina Zambon, Alberto Zambon, Maria Grazia Zenti, Giulia Fainelli, Fabio Pellegatta, Liliana Grigore, Katia Bonomo, Eleonora Capatti, Ada Cutolo, Fabio Fimiani, Simonetta Genovesi, Sandro Inchiostro, Chiara Pavanello, Roberta Pujia, Alon Schaffer, Olmastroni, Elena, Gazzotti, Marta, Averna, Maurizio, Arca, Marcello, Tarugi, Patrizia, Calandra, Sebastiano, Bertolini, Stefano, Catapano, Alberico L, Casula, Manuela, and Laura D'Erasmo, Angelo Baldassare Cefalu, Andrea Bartuli, Paola Sabrina Buonuomo, Andrea Benso, Guglielmo Beccuti, Giacomo Biasucci, Maria Elena Capra, Gianni Biolo, Pierandrea Vinci, Luca Bonanni, Claudio Borghi, Sergio D'Addato, Antonio Carlo Bossi, Giancarla Meregalli, Adriana Branchi, Paolo Calabrò, Francesca Carubbi, Fabio Nascimbeni, Francesco Cipollone, Marco Bucci, Nadia Citroni, Maria Del Ben, Francesco Baratta, Massimo Federici, Martina Montagna, Claudio Ferri, Serena Notargiacomo, Anna Maria Fiorenza, Emanuela Colombo, Giuliana Fortunato, Maria Donata Di Taranto, Andrea Giaccari, Simona Moffa, Francesco Giorgino, Sergio Di Molfetta, Ornella Guardamagna, Luisa De Sanctis, Arcangelo Iannuzzi, Raimondo Cavallaro, Gabriella Iannuzzo, Marco Gentile, Lorenzo Iughetti, Patrizia Bruzzi, Salvatore Lia, Alessandro Lupi, Giuseppe Mandraffino, Arianna Toscano, Rossella Marcucci, Martina Berteotti, Lorenzo Maroni, Fabiana Locatelli, Tiziana Montalcini, Giuliana Mombelli, Sandro Muntoni, Davide Baldera, Gianfranco Parati, Angelina Passaro, Valerio Pecchioli, Cristina Pederiva, Giuseppe Banderali, Antonio Pipolo, Debora D'Elia, Matteo Pirro, Vanessa Bianconi, Livia Pisciotta, Elena Formisano, Francesco Purrello, Roberto Scicali, Elena Repetti, Elena Cantino, Elisabetta Rinaldi, Elena Sani, Riccardo Sarzani, Francesco Spannella, Francesco Sbrana, Beatrice Dal Pino, Patrizia Suppressa, Veronica Cocco, Chiara Trenti, Emanuele Alberto Negri, Josè Pablo Werba, Alessandra Romandini, Sabina Zambon, Alberto Zambon, Maria Grazia Zenti, Giulia Fainelli, Fabio Pellegatta, Liliana Grigore, Katia Bonomo, Eleonora Capatti, Ada Cutolo, Fabio Fimiani, Simonetta Genovesi, Sandro Inchiostro, Chiara Pavanello, Roberta Pujia, Alon Schaffer

Subjects
cardiovascular risk, lipoprotein(a), familial hypercholesterolemia
Abstract

Background Evidence suggests that LPA risk genotypes are a possible contributor to the clinical diagnosis of familial hypercholesterolemia (FH). This study aimed at determining the prevalence of LPA risk variants in adult individuals with FH enrolled in the Italian LIPIGEN (Lipid Transport Disorders Italian Genetic Network) study, with (FH/M+) or without (FH/M-) a causative genetic variant. Methods and Results An lp(a) [lipoprotein(a)] genetic score was calculated by summing the number risk-increasing alleles inherited at rs3798220 and rs10455872 variants. Overall, in the 4.6% of 1695 patients with clinically diagnosed FH, the phenotype was not explained by a monogenic or polygenic cause but by genotype associated with high lp(a) levels. Among 765 subjects with FH/M- and 930 subjects with FH/M+, 133 (17.4%) and 95 (10.2%) were characterized by 1 copy of either rs10455872 or rs3798220 or 2 copies of either rs10455872 or rs3798220 (lp(a) score ≥1). Subjects with FH/M- also had lower mean levels of pretreatment low-density lipoprotein cholesterol than individuals with FH/M+ (t test for difference in means between FH/M- and FH/M+ groups

Published
2023

15. Automatic identification of variables in epidemiological datasets using logic regression.

Author

Matthias W. Lorenz, Negin Ashtiani Abdi, Frank Scheckenbach, Anja Pflug, Alpaslan Bülbül, Alberico L. Catapano, Stefan Agewall, Marat Ezhov, Michiel L. Bots, Stefan Kiechl, Andreas Orth, Giuseppe D. Norata, Jean Philippe Empana, Hung-Ju Lin, Stela McLachlan, Lena Bokemark, Kimmo Ronkainen, Mauro Amato, Ulf Schminke, Sathanur R. Srinivasan, Lars Lind, Akihiko Kato, Chrystosomos Dimitriadis, Tadeusz Przewlocki, Shuhei Okazaki, Coen D. A. Stehouwer, Tatjana Lazarevic, Peter Willeit, David N. Yanez, Helmuth Steinmetz, Dirk Sander, Holger Poppert, Moise Desvarieux, Mohammad Arfan Ikram, Sebastjan Bevc, Daniel Staub, Cesare R. Sirtori, Bernhard Iglseder, Gunnar Engström, Giovanni Tripepi, Oscar Beloqui, Moo-Sik Lee, Alfonsa Friera, Wuxiang Xie, Liliana Grigore, Matthieu Plichart, Ta-Chen Su, Christine Robertson, Caroline Schmidt, Tomi-Pekka Tuomainen, Fabrizio Veglia, Henry Völzke, Giel Nijpels, Aleksandar Jovanovic, Johann Willeit, Ralph L. Sacco, Oscar H. Franco, Radovan Hojs, Heiko Uthoff, Bo Hedblad, Hyun Woong Park, Carmen Z. Suarez, Dong Zhao, Pierre Ducimetiere, Kuo-Liong Chien, Jackie F. Price, Göran Bergström, Jussi Kauhanen, Elena Tremoli, Marcus Dörr, Gerald Berenson, Aikaterini Papagianni, Anna Kablak-Ziembicka, Kazuo Kitagawa, Jaqueline M. Dekker, Radojica Stolic, Joseph F. Polak, Matthias Sitzer, Horst Bickel, Tatjana Rundek, Albert Hofman, Robert Ekart, Beat Frauchiger, Samuela Castelnuovo, Maria Rosvall, Carmine Zoccali, Manuel F. Landecho, Jang-Ho Bae, Rafael Gabriel, Jing Liu, Damiano Baldassarre, and Maryam Kavousi

Published
2017
Full Text
View/download PDF

16. Evaluation of lipoprotein(a) in the prevention and management of atherosclerotic cardiovascular disease: A survey among the Lipid Clinics Network

Author

Catapano, Alberico L, Tokgözoğlu, Lale, Banach, Maciej, Gazzotti, Marta, Olmastroni, Elena, Casula, Manuela, Ray, Kausik K, the Lipid Clinics Network, Alaa ABDELRAZIK (University Hospital of North Midland, United Kingdom), Alberto MELLO E SILVA (Sociedade Portuguesa de Aterosclerose, Portugal), Alexander VONBANK (VIVIT Institute, Austria), Alexandros, D TSELEPIS (Dept of Chemistry, Atherothrombosis Research Center, University of Ioannina, Greece), Alper SONMEZ (Department of Endocrinology and Metabolism, Ankara Guven Hospital, Turkey), Angelina PASSARO (Department of Translational Medicine, University of Ferrara &amp, Center for the Study and Treatment of Metabolic Diseases, Atherosclerosis, and Clinical Nutrition, University Hospital of Ferrara Arcispedale Sant’Anna, Italy), Anja VOGT (Medizinische Klinik und Poliklinik IV, Klinikum der Universit¨at München, Germany), Ann MERTENS (Clinical and Experimental Endocrinology, Leuven, Ku, Leuven, Belgium), Ann VERHAEGEN (Antwerp University Hospital, Belgium), Arman, S POSTADZHIYAN (Medical University of Sofia, Saint Anna University Hospital, Departement of Cardiology, Bulgaria), BAHADIR KIRILMAZ (Canakkale Onsekiz Mart University, Medical Faculty Cardiology Dept, Baris GUNGOR (University of Health Sciences Dr. Siyami Ersek Hospital, Turkey), Berit S HEDEGAARD (Aalborg University, Denmark), Bertrand CARIOU (Nantes Universit´e, Chu, Nantes, Cnrs, Inserm, l’institut du thorax, Nantes, France), Britta OTTE (Universit¨atsklinikum Münster, Lipidambulanz, Germany), Bu˘gra ¨OZKAN (Mersin University, Turkey), of cardiology, Christ BERGE (Dept., Unversity Hopsital, Haukeland., Norway), F EBENBICHLER (Department for Internal Medicine I, Christoph, Medical University Innsbruck, Austria), Christoph J BINDER (Medical University of Vienna, Austria), Christoph OLIVIER (Department of Cardiology and Angiology, University Heart Center Freiburg-Bad Krozingen, Faculty of Medicine, University of Freiburg, Conrad AZZOPARDI (Mater Dei Hospital, Malta), Cristina SOLER (Lipid Unit, Hospital de Sta Caterina, Spain), Dan GAITA (Universitatea de Medicina si Farmacie Victor Babes din Timisoara &amp, Clinica de Cardiologie, Institutul de Boli Cardiovasculare Timisoara, Romania), Daniel WEGHUBER (Department of Pediatrics, Paracelsus Medical University, Dilek URAL (Koç University School of Medicine Department of Cardiology, Turkey), Diogo CRUZ (Hospital de Cascais - Dr. Jos´e de Almeida, Portugal), Dragos VINEREANU (University of Medicine and Pharmacy, University and Emergency Hospital, Bucharest, Romania), Elena D PENCU (Grand Hˆopital de Charleroi GHDC, Belgium), Emil HAGSTR¨OM (Dept of medical sciences, Uppsala, University, Sweden), Erik B SCHMIDT (Aalborg University, Denmark), Erik, S STROES (Dept of vascular medicine, Amsterdamumc, The, Netherlands), Evangelos LIBEROPOULOS (1st Department of Propedeutic Medicine, School of Medicine, National and Kapodistrian University of Athens, General Hospital of Athens Laiko, Fabian DEMEURE (CHU UCL Namur - Site Godinne, Belgium), Fabio FIMIANI (Azienda Ospedaliera di Rilievo Nazionale AORN Dei Colli, Monaldi', 'V., Unit of Inherited and Rare Cardiovascular Diseases, Italy, ), Fabio PELLEGATTA (Center for the Study of Atherosclerosis. Bassini Hospital. Cinisello Balsamo, Italy), Fahri BAYRAM (Erciyes University, Turkey), Finn L HENRIKSEN (Department of Cardiology Odense University Hospital, Denmark), Florian H¨OLLERL (1st Medical Department, Landstrasse, Clinic, Vienna Health Association, Francesco CIPOLLONE (Clinica Medica Institute of, Department of Medicine and Aging Sciences, d’Annunzio' University, 'G., Francisco ARAÚJO (Hospital Lusíadas, Portugal), Franck BOCCARA (Sorbonne Universit´e, Groupe de Recherche Clinique number 22, C2MV—Complications Cardiovasculaires et M´etaboliques chez les Patients Vivant avec le Virus de l’Immunod´eficience Humaine, Institut National de la Sant´e et de la Recherche M´edicale Unit´e Mixte de Recherche, S 938, Centre de Recherche Saint-Antoine, Institut Hospital Universitaire de Cardiom ´etabolisme et Nutrition Cardiologie, Hˆopital Saint Antoine Assistance Publique–Hˆopitaux de Paris, Paris, France), François PAILLARD (Cardiologie et Centre Clinico-Biologique des Lipides et Ath´eroscl´erose, Chu, Rennes, France), Imre University Teaching Hospital, Gabor SIMONYI (DBC St., Metabolic, Center, Lipid, Center, Hungary), Gabriella IANNUZZO (Department of Clinical Medicine and Surgery. University of Naples Federico II, Italy), Giuseppe MANDRAFFINO (Department of Clinical and Experimental Medicine, - Lipid Center, University of Messina, Graham BAYLY (Dept Clinical Biochemistry, University Hospitals Bristol, United, Kingdom), Gustavs LATKOVSKIS (Institute of Cardiology and Regenerative Medicine, University of Latvia &amp, Latvian Center of Cardiology, Pauls Stradins Clinical University Hospital &amp, University of Latvia, Latvia), Gy¨orgy PARAGH (Division of Metabolic Disorders, Department of Internal Medicine, University of Debrecen, Debrecen, Hungary), Hana ROSOLOVA (Charles University Prague Medical Hospital in Pilsen, Czech Republic), Handrean SORAN (Central Manchester University Hospital NHS Foundation Trust, United Kingdom), Helle KANSTRUP (Department of cardiology, Aarhus University hospital, Denmark), Hermann TOPLAK (Department of Medicine, Division of Endocrinology and Diabetology, Medical University Graz, Hülya ÇIÇEKÇIO ˘GLU (ankara bilkent city hospital, Turkey), Inanc ARTAC (Department of Cardiology, Kafkas University Hospital, Ioanna GOUNI-BERTHOLD (Center for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Faculty of Medicine and University Hospital Cologne, Irfan, V DUZEN (Gaziantep University, Cardiology, Department, Isabel M PALMA (CHUPORTO - Centro Hospitalar Universit ´ario do Porto, Portugal), Istvan REIBER (Szent Gyorgy University Teaching Hospital of Fejer County, Hungary), Iveta DZIVITE-KRISANE (Children’s University Hospital, Latvia), Jeanine, E ROETERS VAN LENNEP (Department of Internal medicine, Erasmus MC University Medical Center, Jean-Luc, J BALLIGAND (Institut de Recherche Exp´erimentale et Clinique, Universite catholique de Louvain, Bruxelles), Joao C PORTO (CHUC, Portugal), Jo˜ao, S DUARTE (Hospital Egas Moniz, Lisboa, Portugal), Johan DE SUTTER (AZ Maria Middelares Hospital Gent, Belgium), Jos´e L´OPEZ-MIRANDA (Lipid and Arteriosclerosis Unit. Department of Internal Medicine. Hospital Universitario Reina Sofia. IMIBIC. University of Cordoba. CiberOBN, Spain), Jose M MOSTAZA (Hospital La Paz-Carlos III, Spain), Jurgita PLISIENE (Lithuanian University of Health sciences, Lithuania), Kadir, U MERT (Eskis ¸ehir Osmangazi University, Department of Cardiology, Kirsten, B HOLVEN (Department of Nutrition, University of Oslo and National Advisory unit on FH, Oslo University Hospital, Kjetil RETTERSTØL (The Lipid Clinic, Oslo University Hospital and Department of Nutrition, University of Oslo, Kristian, K THOMSEN (University Hospital of South Denmark, Esbjerg, Denmark), Lale TOKGOZOGLU (Hacettepe University, Turkey), Laszlo BAJNOK (1st Department of Medicine, Medical, School, University of Pecs, Lia E BANG (Copenhagen University Hospital, Denmark), Liliana GRIGORE (IRCCS Multimedica, Italy), Lluís MASANA (Hospital Universitari Sant Joan. Universitat Rovira i Virgili. CIBERDEM. Reus, Spain), Loukianos S RALLIDIS (University General Hospital Attikon, Greece), Maciej BANACH (Department of Preventive Cardiology and Lipidology, Medical University of Lodz, Poland), Małgorzata WALU´S-MIARKA (Jagiellonian University Medical College, Of Metabolic Diseases and Diabetology, Dept., Manuel CASTRO CABEZAS (Franciscus Gasthuis &amp, Vlietland Rotterdam, The Netherlands), Marcello ARCA (Sapienza University of Rome, Italy), Margus VIIGIMAA (North Estonia Medical Centre, Tallinn University of Technology, Estonia), Martin, P BOGSRUD (Unit for Cardiac and Cardiovascular Genetics, Matej MLINARIˇC (Department of Endocrinology, Diabetes and Metabolism, University Children’s Hospital, University Medical Centre Ljubljana, Slovenia), Matteo PIRRO (Section of Internal Medicine, Angiology and Arteriosclerosis Diseases, Maurizio AVERNA (Department PROMISE-University of Palermo &amp, Istituto di Biofisica, Consiglio Nazionale delle Ricerche, Palermo, Italy), Meral KAYIKCIOGLU (Ege University Medical School Department of Cardiology, Turkey), Merete HEITMANN (Bispebjerg-Frederiksberg University Hospital, Denmark), Mette MOURIDSEN (Department of Cardiology, Herlev and Gentofte Hospital, University of Copenhagen, Michal VRABLIK (3rd Department of Internal Medicine, General University Hospital and 1st Medical Faculty, Charles, University, Prague, Czech, Republic), Michel FARNIER (PEC2, University of Bourgogne Franche-Comt´e, Laboratory Medicine, Michel R LANGLOIS (Dept., Jan Hospital, AZ St., Belgium), Milad KHEDR (Department of Clinical Biochemistry and Metabolic Medicine, Royal Liverpool University Hospital, Muge ILDIZLI DEMIRBAS (Kartal Kosuyolu Research and Training Hospital, Turkey), Myra TILNEY (Lipid Clinic, Mater Dei Hospital &amp, Dept of Medicine, University of Malta Medical School, Malta), Nadia CITRONI (Internal Medicine, APSS Trento Hospital, Of Internal Medicine, Niels P RIKSEN (Dept., Radboud university medical center, Nikolay M RUNEV (UMHAT Alexandrovska, Bulgaria), Nora KUPSTYTEKRISTAPONE (Hospital of Lithuanian University of Health Sciences Kaunas Clinics, Lithuania), Olena MITCHENKO (NSC, Clinical and Regenerative Medicine of the NAMS of Ukraine, Ukraine), Oliver WEING¨ARTNER (Universit¨atsklinikum Jena, Department of Internal Medicine, I, Oner OZDOGAN (University of Health Sciences, Izmir Faculty of Medicine, Tepecik Training and Research Hospital, Ovidio MU˜NIZGRIJALVO (Hospital Virgen del Rocío, Spain), Ozcan BASARAN (Mugla Sitki Kocman University, Pankaj GUPTA (University Hospitals of Leicester, United Kingdom), Paolo PARINI (Cardio Metabolic Unit, Karolinska, Institutet, and Theme Inflammation and Ageing, Karolinska University Hospital Huddinge, Patrizia SUPPRESSA (Department of Internal Medicine and rare disease Centre, Bari, Italy), Paul DOWNIE (Salisbury NHS Foundation trust, United Kingdom), Pavel JESINA (Metabolic Center General University Hospital, Czech Republic), of Internal Medicine, Pavel KRAML (Dept., Third Faculty of Medicine, Charles University and Kr´alovsk´e Vinohrady University Hospital Prague, Pawel BURCHARDT (Department of Cardiology, Cardiovascular, Unit, Hospital, J. Stru´s., Pozna´n, &amp, Department of Hypertension, Angiology and Internal Medicine, Poznan University of Medical Sciences, Pozna´n, Poland), Pedro VALDIVIELSO (Hospital VIRGEN DE LA VICTORIA, Spain), Pedro VON HAFE (Instituto Cuf, Portugal), Dept, Peter FASCHING (5th Med., Clinic, Ottakring, Philippe MOULIN (Hospices civils de Lyon/INSERM/Universit ´e Lyon1, Hˆopital Louis Pradel, F´ed´eration, D’Endocrinologie, Quit´eria RATO (Sociedade Portuguesa de Aterosclerose, Portugal), Reinhold INNERHOFER (Medical University Vienna, Austria), Renata C´IFKOV´A (Center for Cardiovascular Prevention, Charles University in Prague, First Faculty of Medicine and Thomayer University Hospital, Rene VALERO (Aix Marseille Univ, Aphm, Inserm, Inrae, C2vn, University Hospital La Conception, Department of Nutrition, Metabolic Diseases and Endocrinology, Scicali, Roberto, Robin URB´ANEK (Internal medicine, Obezita-Ormiga, s. r. o., Roma KAVALIAUSKIENE (Klaip˙ eda Seamen’s Hospital, Lituania), Roman CIBULKA (Department of paramedic science, medical diagnostics studies and public health, Faculty of Health Care Studies, University of West Bohemia, Sabina ZAMBON (Department of Medicine, - DIMED, University of Padova, Sergio D’ADDATO (University of Bologna. IRCCS S. Orsola Bologna, Italy), Stanislav ZEMEK (Lipidova ambulance, Czech Republic), Stefano ROMEO (Gothenburg University, Sweden), Stephanie K¨ONEMANN (Department of Internal Medicine, B, University Medicine Greifswald, DZHK (German Centre for Cardiovascular Research), Susanne GREBER-PLATZER (Clinical Division of Pediatric Pulmonology, Allergology and Endocrinology, Department of Pediatrics and Adolescent Medicine, Medical University Vienna, Thomas STULNIG (Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University Vienna &amp, Third Medical Department and Karl Landsteiner Institute for Metabolic Diseases and Nephrology, Clinic, Hietzing, Vienna, Austria), Thomas MUHR (Dept of Cardiology, Link¨oping University Hospital, Tina, Z KHAN (Consultant Cardiologist, Royal Brompton and Harefield Hospitals Part of Guy’s and St Thomas’ NHS Foundation Trust, Tomas FREIBERGER (Centre of Cardiovascular Surgery and Transplantation, Brno &amp, Medical, Faculty, Masaryk, University, Brno, Tom´aˇs ˇS´ALEK (Metabolic Clinic, Tomas Bata Hospital, Zlín, Tomas VASYLIUS (Republican Panevezys hospital, Of Cardiology, Dep., Lithuania), Ulrich LAUFS (Klinik und Poliklinik für Kardiologie, Universit ¨atsklinikum Leipzig, Ulrike SCHATZ (University Hospital Carl Gustav Carus Dresden at the Technical University Dresden, Department of Internal Medicine III, Urh GROSELJ (UMC, - University Children’s Hospital Ljubljana, University of Ljubljana, Victoria MARCO-BENEDI (Hospital Universitario Miguel Servet, Iisa, Cibercv, Vincent MAHER (Advanced Lipid Management and Research ALMAR centre, Tallaght University Hospital, Ireland), Vladimír BLAHA (University Hospital Hradec Kr´alov´e and Charles University, Faculty of Medicine in Hradec Kr´alov´e, 3rd Department of Internal Medicine, - Metabolism and Gerontology, Vladimir SOSKA (Department of Clinical Biochemistry, St. Anne’s University Hospital Brno, 2nd Clinic of Internal Medicine, Masaryk University Brno, Volker JJ SCHETTLER (Centre of Nephrology G¨ottingen, Germany), Wolfgang REINHARDT (SUS Malmoe, Sweden), Xavier PINT´O (Hospital Universitari de Bellvitge-Idibell-UB-CiberObn, Spain), Yoto YOTOV (Second Cardiology Clinic, Marina, University Hospital Sv., Medical University of Varna, Zaneta PETRULIONIENE (Vilnius University Medical Faculty, Vilnius University Hospital Santaros klinikos, Lithuania), ˇZeljko REINER (Department for Metabolic Diseases, University Hospital Center Zagreb, and Croatia, ).

Subjects
Clinicians, Clinical evaluation, Cardiology and Cardiovascular Medicine, Cardiovascular risk, Lipoprotein(a)
Published
2023

17. Targeted Plasma Proteomics to Predict the Development of Carotid Plaques

Author

Andrea Baragetti, Elisa Mattavelli, Liliana Grigore, Fabio Pellegatta, Paolo Magni, and Alberico Luigi Catapano

Subjects
Carotid Artery Diseases, Proteomics, Advanced and Specialized Nursing, Carotid Arteries, Risk Factors, Humans, Longitudinal Studies, Neurology (clinical), Atherosclerosis, Cardiology and Cardiovascular Medicine, Carotid Intima-Media Thickness, Plaque, Atherosclerotic
Abstract

Background: Cardiovascular risk stratification in primary prevention is a clinical challenge. We recently identified a large set of circulating proteins improving the risk prediction for cardiovascular events. We now evaluate which of these proteins predicts the development of subclinical carotid atherosclerosis (SCA) in primary cardiovascular prevention. Methods: Three hundred sixty-eight proteins were quantified, by proximity extension assay, from the plasma collected at basal visit from 586 subjects without previous cardiovascular events and without preclinical atherosclerosis. These subjects were reevaluated 11 years after median follow-up (10–12) in a longitudinal observational analysis, to assess the development of SCA, defined as the formation of focal lesion in any carotid tract and detected by carotid ultrasound at basal visit and after follow-up. Common carotid (intima-media thickness [IMT]) was also measured by ultrasound during the same follow-up to identify subjects with faster common carotid intima-media thickness (IMT) progression (increase IMT)>1.3 mm in the common carotid tract). Results: The variation of 68 proteins predicted SCA development and, among them, higher levels of PIgR2 (polymeric immunoglobulin receptor), chemokine (C-C motif) ligand 18, CA1 (carbonic anhydrase 1), Fc gamma receptor IIa and reduced MMP10 (matrix metallopeptidase 10), GT (gastrotropin), IL7R (interleukin 7 receptor) were the most predictive for SCA development. These 7 proteins improved the sensitivity and the specificity for SCA development versus risk factors (age, sex, overweight, hypertension, low HDL-cholesterol, high triglyceride); area under the curve: 0.747 ([0.707–0.784] versus 0.620 [0.577–0.663]; P P Conclusions: A new set of circulating proteins have been identified that may be considered as markers of preclinical atherosclerosis development. The difference of the protein identified to predict SCA versus IMT progression may reflect different etiological factors.

Published
2022
Full Text
View/download PDF

18. The Role of Registers in Increasing Knowledge and Improving Management of Children and Adolescents Affected by Familial Hypercholesterolemia: the LIPIGEN Pediatric Group

Author

Gazzotti, Marta, Casula, Manuela, Bertolini, Stefano, Capra, Maria Elena, Olmastroni, Elena, Catapano, Alberico Luigi, Pederiva, Cristina, and the LIPIGEN Pediatric Group: Massimiliano Allevi, Internal Medicine and Geriatrics, Department of Clinical and Molecular Sciences, University 'Politecnica delle Marche' and IRCCS-INRCA, Ancona, Italy, Marcello, Arca, Dipartimento di Medicina Traslazionale, e di Precisione, O Policlinico Umberto I, Sapienza Università di Roma—A. U., Rome, Italy, Renata, Auricchio, Dipartimento di Scienze Mediche Traslazionali, AOU Policlinico Federico II, Naples, Italy, Averna, Maurizio, Dipartimento di Promozione della Salute, Materno-Infantile, di Medicina Interna, e Specialistica di Eccellenza, Università degli Studi di Palermo, Palermo, Italy, Davide, Baldera, Dipartimento di Scienze Biomediche, Università degli Studi di Cagliari and Centro per le Malattie Dismetaboliche, e l’Arteriosclerosi, Onlus Cagliari, Associazione ME. DI. CO., Cagliari, Italy, Giuseppe, Banderali, Clinica Pediatrica, U. O., Servizio Clinico Dislipidemie per lo Studio, e la Prevenzione dell’Aterosclerosi in età Pediatrica, ASSTSanti Paolo, e Carlo, Milan, Italy, Andrea, Bartuli, UOC Malattie Rare, e Genetica Medica, Ospedale Pediatrico Bambino Gesù, Irccs, Rome, Italy, Stefano, Bertolini, Department of Internal Medicine, University of Genova, Genova, Italy, Giacomo, Biasucci, Centro Dislipidemie in Età Evolutiva, Pediatria e Neonatologia, U. O., Ospedale Guglielmo da Saliceto, Piacenza, Italy, Claudio, Borghi, di Medicina Interna Cardiovascolare, U. O., Centro, Aterosclerosi, Ambulatorio, Dislipidemie, Orsola-Malpighi, IRCCS S. Orsola Ospedale Policlinico S., Bologna, Italy, Patrizia, Bruzzi, Pediatria, U. O. C., Azienda Ospedaliero Universitaria di Modena, Modena, Italy, Raffaele, Buganza, Paediatric, Endocrinology, Department of Public Health and Paediatric Sciences, Turin, University, Turin, Italy, Paola Sabrina Buonuomo, Paolo, Calabrò, U. O. C. Cardiologia Clinica a Direzione Universitaria e U. T. I. C., 'Sant’Anna e San Sebastiano', A. O. R. N., Italy and Dipartimento di Scienze Mediche Traslazionali, Università degli Studi della Campania, Sebastiano, Calandra, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Maria Elena Capra, Francesca, Carubbi, Medicina interna metabolica, U. O., Centro dislipidemie, e malattie metaboliche rare, Ospedale Civile Baggiovara, AOU di Modena, Manuela, Casula, Dipartimento di Scienze Farmacologiche, e Biomolecolari, Università degli Studi di Milano, and IRCCS MultiMedica, Sesto San Giovanni (Milan), Alberico Luigi Catapano, Arturo, Cesaro, Università degli Studi della Campania 'Luigi Vanvitelli', Francesco, Cipollone, Clinica, Medica, Centro di riferimento regionale per le Dislipidemie, Annunziata, Ospedale Policlinico S. S., Chieti, Italy, Nadia, Citroni, Centro Dislipidemie, e Aterosclerosi, UOC Medicina Interna, Ospedale di Trento, Trento, Italy, Giuseppe, Covetti, Medicina Interna 2, U. O., Centro per le malattie da arteriosclerosi, Aorn, Cardarelli, Annalaura, Cremonini, IRCCS Ospedale policlinico San Martino UOSD Dietetica, e Nutrizione Clinica and Dipartimento di Medicina Interna, Università di Genova, Sergio, D’Addato, Maria Del Ben, Dipartimento Scienze Cliniche, Internistiche, Anestesiologiche e Cardiovascolari, - Sapienza Università, Policlinico Umberto I, A. O., Maria Donata Di Taranto, Dipartimento di Medicina Molecolare, e Biotecnologie Mediche, Università degli studi di Napoli Federico II and CEINGE Biotecnologie Avanzate, s. c. a. r. l., Giuliana, Fortunato, Roberto, Franceschi, Uoc, Pediatria, Federica, Galimberti, Irccs, Multimedica, Marta, Gazzotti, Fondazione SISA (Società Italiana per lo Studio dell’Aterosclerosi), Simonetta, Genovesi, IRCCS Istituto Auxologico Italiano and Dipartimento di Medicina, e Chirurgia, Università di Milano- Bicocca, Antonina, Giammanco, Liliana, Grigore, Centro per lo Studio dell’Aterosclerosi, Italy and Centro per lo Studio dell’Aterosclerosi, Bassini, Ospedale E., Cinisello, Balsamo, Ornella, Guardamagna, Arcangelo, Iannuzzi, Gabriella, Iannuzzo, Dipartimento di Medicina Clinica, e Chirurgia, Centro Coordinamento regionale per le Iperlipidemie, Lidia Lascala, AOU Mater Domini, Fabiana, Locatelli, Ambulatorio ipertensione dislipidemie rischio cardiovascolare, ASST Valle Olona, Ospedale di Gallarate, Gallarate, Italy, Ospedale di Busto Arsizio, Busto, Arsizio, Lorenzo, Iughetti, Sara, Madaghiele, Frugoni' and Centro di Assistenza e Ricerca Malattie Rare, U. O. di Medicina Interna e Geriatria 'C., Universitaria Policlinico Consorziale, A. O., Università degli Studi di Bari 'Aldo Moro', Bari, Italy, Giuseppe, Mandraffino, Martino, Department of Clinical and Experimental Medicine—Lipid Center—University Hospital G., Messina, Italy, Massimo Raffaele Mannarino, Internal, Medicine, University of Perugia, Angiology and Arteriosclerosis Diseases. Department of Medicine and Surgery., Perugia, Italy, Bucci, Marco, Lorenzo, Maroni, Ilenia, Minicocci, Giuliana, Mombelli, Centro Dislipidemie ASST Grande Ospedale Metropolitano Niguarda, Sandro, Muntoni, Fabio, Nascimbeni, Elena, Olmastroni, Servizio di Epidemiologia, e Farmacologia Preventiva (SEFAP), Dipartimento di Science Farmacologiche, e Biomolecolari, Gianfranco, Parati, Università di Milano-Bicocca, Angelina, Passaro, Department of Translational Medicine, University of Ferrara, Italy and Research and Innovation Section, University Hospital of Ferrara Arcispedale Sant’Anna, Chiara, Pavanello, Milan, Italy and Centro Grossi Paoletti, Milano, Italy, Cristina, Pederiva, ASST-Santi Paolo, e Carlo, Fabio, Pellegatta, Francesco Massimo Perla, Dipartimento Materno Infantile, e Scienze Urologiche—Sapienza Università, Medicina, Generale, Ospedale di Trecenta, Trecenta, Rovigo, Matteo, Pirro, Livia, Pisciotta, Arturo, Pujia, Mater Domini, A. O. U., UOC di Nutrizione Clinica, Purrello, Francesco, Department of Clinical and Experimental Medicine, University of Catania, Ospedale, Garibaldi, Catania, Italy, Elisabetta, Rinaldi, Endocrinologia, U. O., Diabetologia, e Malattie del Metabolismo, Universitaria Integrata di Verona, Centro regionale specializzato per la diagnosi e terapia delle dislipidemie e aferesi terapeutica and A. O., Verona, Italy, Riccardo, Sarzani, Scicali, Roberto, Patrizia, Suppressa, Patrizia, Tarugi, Department of Life Sciences, Sabrina, Verachtert, Giovanni Battista Vigna, Josè Pablo Werba, Ambulatorio Prevenzione Aterosclerosi, U. O., IRCCS Centro Cardiologico Monzino, Alberto, Zambon, Dipartimento di Medicina, Università di Padova, Padua, Italy, Sabina, Zambon, Maria Grazia Zenti, Servizio di Diabetologia, e Malattie Metaboliche, Pederzoli, Ospedale P., Peschiera del Garda, and Verona, Italy.

Subjects
genetic diagnosis, clinical diagnosis, familial hypercholesterolemia, cardiovascular genetics, pathology register, pediatric cohort, Settore BIO/14 - Farmacologia, Genetics, Molecular Medicine, Genetics (clinical)
Abstract

Pathology registers can be a useful tool to overcome obstacles in the identification and management of familial hypercholesterolemia since childhood. In 2018, the LIPIGEN pediatric group was constituted within the Italian LIPIGEN study to focus on FH subjects under 18 years. This work aimed at discussing its recent progress and early outcomes. Demographic, biochemical, and genetic baseline characteristics were collected, with an in-depth analysis of the genetic defects. The analysis was carried out on 1,602 children and adolescents (mean age at baseline 9.9 ± 4.0 years), and almost the whole cohort underwent the genetic test (93.3%). Overall, the untreated mean value of LDL-C was 220.0 ± 97.2 mg/dl, with an increasing gradient from subjects with a negative (N = 317; mean untreated LDL-C = 159.9 ± 47.7 mg/dl), inconclusive (N = 125; mean untreated LDL-C = 166.4 ± 56.5 mg/dl), or positive (N = 1,053; mean untreated LDL-C = 246.5 ± 102.1 mg/dl) genetic diagnosis of FH. In the latter group, the LDL-C values presented a great variability based on the number and the biological impact of involved causative variants. The LIPIGEN pediatric group represents one of the largest cohorts of children with FH, allowing the deepening of the characterization of their baseline and genetic features, providing the basis for further longitudinal investigations for complete details.

Published
2022
Full Text
View/download PDF

19. Lipoprotein(a) and family history for cardiovascular disease in paediatric patients: A new frontier in cardiovascular risk stratification. Data from the LIPIGEN paediatric group

Author

Cristina Pederiva, Maria Elena Capra, Giacomo Biasucci, Giuseppe Banderali, Enrico Fabrizi, Marta Gazzotti, Manuela Casula, Alberico L. Catapano, Marcello Arca, Maurizio Averna, Stefano Bertolini, Sebastiano Calandra, Alberico Luigi Catapano, Patrizia Tarugi, Fabio Pellegatta, Andrea Bartuli, Claudio Borghi, Paolo Calabrò, Francesca Carubbi, Francesco Cipollone, Nadia Citroni, Maria Del Ben, Giuliana Fortunato, Ornella Guardamagna, Arcangelo Iannuzzi, Gabriella Iannuzzo, Lorenzo Iughetti, Giuseppe Mandraffino, Lorenzo Maroni, Giuliana Mombelli, Sandro Muntoni, Gianfranco Parati, Angelina Passaro, Livia Pisciotta, Arturo Pujia, Francesco Purrello, Anna Rita Roscini, Riccardo Sarzani, Patrizia Suppressa, Josè Pablo Werba, Sabina Zambon, Maria Grazia Zenti, Massimiliano Allevi, Renata Auricchio, Davide Baldera, Patrizia Bruzzi, Marco Bucci, Paola Sabrina Buonuomo, Angelo Baldassarre Cefalù, Giuseppe Covetti, Sergio D'Addato, Maria Donata Di Taranto, Roberto Franceschi, Fabio Fimiani, Simonetta Genovesi, Liliana Grigore, Graziana Lupattelli, Sara Madaghiele, Giulia Massini, Ilenia Minicocci, Tiziana Montalcini, Fabio Nascimbeni, Chiara Pavanello, Francesco Massimo Perla, Gaia Peroni, Elena Sani, Roberto Scicali, Arianna Toscano, Giovanni Battista Vigna, Alberto Zambon, Federica Galimberti, Elena Olmastroni, and Veronica Zampoleri

Subjects
Male, Adolescent, Family history, High cardiovascular risk, Paediatric FH, Lp(a), Children/adolescents, Premature CVD, Cholesterol, LDL, Hyperlipoproteinemia Type II, Cardiovascular Diseases, Heart Disease Risk Factors, Risk Factors, Humans, Female, Cardiology and Cardiovascular Medicine, Child, Lipoprotein(a)
Abstract

Little is known about the role of Lp(a) in the assessment of cardiovascular risk in the paediatric population. Trying to clarify the clinical relevance of Lp(a) in risk stratification, the aim of the study is to evaluate the association between Lp(a) plasma levels in children with familial hypercholesterolaemia (FH) and positive family history for premature cardiovascular disease (pCVD) in first- and second-degree relatives.653 Caucasian children and adolescents (334 females and 319 males), aged 2-17 years, with diagnosis of FH from a paediatric cohort included in the LIPIGEN Network, were selected. We compared family history of pCVD, lipid and genetic profile in two groups based on Lp(a) levels below or above 30 mg/dL. To determine the independent predictors of pCVD, a multivariate logistic regression was used, with all clinical characteristics and blood measurements as predictors.Subjects with Lp(a) 30 mg/dl more frequently reported positive family history of pCVD compared to subjects with Lp(a)≤30 mg/dl (69.90% vs 36.66%, p 0.0001), while did not show differences in terms of median [interquartile range] LDL-cholesterol level (153.00 [88.00 vs 164.50 [90.25] mg/dL, p = 0.3105). In the regression analysis, Lp(a) 30 mg/dl was an independent predictor of family history of pCVD. Comparing subjects with or without family history of pCVD, we reported significant differences for Lp(a) 30 mg/dl (46.25% vs 17.65%, p 0.0001), FH genetic mutation (50.48% vs 40.75%, p = 0,0157), as well as for LDL-cholesterol (p = 0.0013) and total cholesterol (p = 0.0101).Children/adolescents with FH and Lp(a) 30 mg/dl where more likely to have a positive family history of pCVD. Lp(a) screening in children and adolescents with FH may enhance risk assessment and help identify those subjects, children and relatives, at increased pCVD risk.

Published
2021

20. Pentraxin 3 deficiency protects from the metabolic inflammation associated to diet-induced obesity

Author

A. Moregola, Rémi Porte, Alberico L. Catapano, Fabio Pellegatta, Liliana Grigore, Andrea Baragetti, Marina Sironi, Cecilia Garlanda, Fabrizia Bonacina, Alice Salatin, Alberto Mantovani, Giuseppe Danilo Norata, Barbara Bottazzi, Eduardo Bonavita, Elisa Barbati, and Martina Molgora

Subjects
Male, 0301 basic medicine, Physiology, Cell Plasticity, Adipose tissue, 030204 cardiovascular system & hematology, Weight Gain, 0302 clinical medicine, Glucose homeostasis, Cells, Cultured, Adiposity, Mice, Knockout, 2. Zero hunger, Adipogenesis, PTX3, Middle Aged, 3. Good health, Serum Amyloid P-Component, C-Reactive Protein, Phenotype, Obesity, Abdominal, Female, Inflammation Mediators, medicine.symptom, Cardiology and Cardiovascular Medicine, Signal Transduction, medicine.medical_specialty, Subcutaneous Fat, Neovascularization, Physiologic, Nerve Tissue Proteins, Inflammation, Intra-Abdominal Fat, Diet, High-Fat, 03 medical and health sciences, Immune system, Physiology (medical), Internal medicine, medicine, Animals, Humans, Obesity, Aged, business.industry, Macrophages, Lipid metabolism, medicine.disease, Immunity, Innate, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, Endocrinology, Haplotypes, Metabolic syndrome, Energy Metabolism, business, Weight gain
Abstract

AimsLow-grade chronic inflammation characterizes obesity and metabolic syndrome. Here, we aim at investigating the impact of the acute-phase protein long pentraxin 3 (PTX3) on the immune-inflammatory response occurring during diet-induced obesity.Methods and resultsPTX3 deficiency in mice fed a high-fat diet for 20 weeks protects from weight gain and adipose tissue deposition in visceral and subcutaneous depots. This effect is not related to changes in glucose homeostasis and lipid metabolism but is associated with an improved immune cell phenotype in the adipose tissue of Ptx3 deficient animals, which is characterized by M2-macrophages polarization and increased angiogenesis. These findings are recapitulated in humans where carriers of a PTX3 haplotype (PTX3 h2/h2 haplotype), resulting in lower PTX3 plasma levels, presented with a reduced prevalence of obesity and decreased abdominal adiposity compared with non-carriers.ConclusionOur results support a critical role for PTX3 in the onset of obesity by promoting inflammation and limiting adipose tissue vascularization and delineate PTX3 targeting as a valuable strategy for the treatment of adipose tissue-associated inflammatory response.

Published
2019
Full Text
View/download PDF

21. Gut Microbiota Functional Dysbiosis Relates to Individual Diet in Subclinical Carotid Atherosclerosis

Author

Andrea Baragetti, Marco Severgnini, Elena Olmastroni, Carola Conca Dioguardi, Elisa Mattavelli, Andrea Angius, Luca Rotta, Javier Cibella, Giada Caredda, Clarissa Consolandi, Liliana Grigore, Fabio Pellegatta, Flavio Giavarini, Donatella Caruso, Giuseppe Danilo Norata, and Alberico Luigi Catapano and Clelia Peano

Subjects
Atherosclerotic Cardiovascular Diseases, Gut Microbiota, next generation sequencing
Abstract

Gut Microbiota (GM) dysbiosis associates with Atherosclerotic Cardiovascular Diseases (ACVD), but whether this also holds true in subjects without clinically manifest ACVD represents a challenge of personalized prevention. We connected exposure to diet (self-reported by food diaries) and markers of Subclinical Carotid Atherosclerosis (SCA) with individual taxonomic and functional GM profiles (from fecal metagenomic DNA) of 345 subjects without previous clinically manifest ACVD. Subjects without SCA reported consuming higher amounts of cereals, starchy vegetables, milky products, yoghurts and bakery products versus those with SCA (who reported to consume more mechanically separated meats). The variety of dietary sources significantly overlapped with the separations in GM composition between subjects without SCA and those with SCA (RV coefficient between nutrients quantities and microbial relative abundances at genus level = 0.65, pvalue = 0.047). Additionally, specific bacterial species (Faecalibacterium prausnitzii in the absence of SCA and Escherichia coli in the presence of SCA) are directly related to over-representation of metagenomic pathways linked to different dietary sources (sulfur oxidation and starch degradation in absence of SCA, and metabolism of amino acids, syntheses of palmitate, choline, carnitines and Trimethylamine n-oxide in presence of SCA). These findings might contribute to hypothesize future strategies of personalized dietary intervention for primary CVD prevention setting.

Published
2021

22. Individual diet relates to gut microbiota functional dysbiosis since subclinical stages of atherosclerosis

Author

Liliana Grigore, E. Olmastroni, Fabio Pellegatta, Andrea Angius, Elisa Mattavelli, Andrea Baragetti, F. Giavarini, A.L. Catapano, Clarissa Consolandi, C. Conca Dioguardi, Clelia Peano, Donatella Caruso, D.G. Norata, Luca Rotta, Javier Cibella, and Marco Severgnini

Subjects
biology, Immunology, medicine, Gut flora, Cardiology and Cardiovascular Medicine, biology.organism_classification, medicine.disease, Dysbiosis, Subclinical infection
Published
2021
Full Text
View/download PDF

23. Genetically determined hypercholesterolaemia results into premature leucocyte telomere length shortening and reduced haematopoietic precursors

Author

A. Moregola, Fabio Pellegatta, Maurizio Averna, Alberico L. Catapano, V. Zampoleri, Rossella Spina, Angelo Baldassarre Cefalù, Fabrizia Bonacina, Lorenzo Da Dalt, Liliana Grigore, Andrea Baragetti, Giuseppe Danilo Norata, Angela Pirillo, Baragetti, Andrea, Bonacina, Fabrizia, Da Dalt, Lorenzo, Moregola, Annalisa, Zampoleri, Veronica, Pellegatta, Fabio, Grigore, Liliana, Pirillo, Angela, Spina, Rossella, Cefalù', Angelo Baldassare, Averna, Maurizio, Norata, Giuseppe D, and Catapano, Alberico L

Subjects
medicine.medical_specialty, Settore MED/09 - Medicina Interna, Cellular ageing, Epidemiology, Hypercholesterolemia, CD34, Cellular senescence, 030204 cardiovascular system & hematology, Hyperlipoproteinemia Type II, 03 medical and health sciences, Mice, 0302 clinical medicine, Internal medicine, Leukocytes, Medicine, Animals, Humans, Progenitor cell, Haematopoiesi, 030304 developmental biology, Ldl cholesterol, 0303 health sciences, business.industry, Cholesterol, LDL, Telomere, 3. Good health, Haematopoiesis, Increased risk, Endocrinology, medicine.anatomical_structure, CHD, Telomeres, Bone marrow, Cardiology and Cardiovascular Medicine, business, Familial hypercholesterolaemia
Abstract

Aims Leucocyte telomere length (LTL) shortening is a marker of cellular senescence and associates with increased risk of cardiovascular disease (CVD). A number of cardiovascular risk factors affect LTL, but the correlation between elevated LDL cholesterol (LDL-C) and shorter LTL is debated: in small cohorts including subjects with a clinical diagnosis of familial hypercholesterolaemia (FH). We assessed the relationship between LDL-C and LTL in subjects with genetic familial hypercholesterolaemia (HeFH) compared to those with clinically diagnosed, but not genetically confirmed FH (CD-FH), and normocholesterolaemic subjects. Methods and results LTL was measured in mononuclear cells-derived genomic DNA from 206 hypercholesterolaemic subjects (135 HeFH and 71 CD-FH) and 272 controls. HeFH presented shorter LTL vs. controls (1.27 ± 0.07 vs. 1.59 ± 0.04, P = 0.045). In particular, we found shorter LTL in young HeFH as compared to young controls ( Conclusions We found (i) shorter LTL in genetically determined hypercholesterolaemia, (ii) lower circulating haematopoietic precursors in HeFH subjects, and reduced bone marrow resident LT-HSPCs in LDLR-KO mice. We support early cellular senescence and haematopoietic alterations in subjects with FH.

Published
2020

24. LIPA gene mutations affect the composition of lipoproteins: Enrichment in ACAT-derived cholesteryl esters

Author

Alberico L. Catapano, Alice Ossoli, Alberto Corsini, Monica Gomaraschi, Lorenzo Arnaboldi, Samuela Castelnuovo, A. Granata, Chiara Pavanello, Liliana Grigore, Beatrice Arosio, Livia Pisciotta, Andrea Pasta, Andrea Baragetti, Eleonora Giorgio, Domenico Azzolino, Tiziano Lucchi, and Laura Calabresi

Subjects
0301 basic medicine, Male, Very low-density lipoprotein, 030204 cardiovascular system & hematology, Phosphatidylcholine-Sterol O-Acyltransferase, chemistry.chemical_compound, 0302 clinical medicine, High-density lipoprotein, Acetyl-CoA C-Acetyltransferase, Hypoalphalipoproteinemia, Cells, Cultured, Intermediate-density lipoprotein, Cholesterol Ester Storage Disease, Chemistry, Cholesteryl ester storage disease, Middle Aged, Phenotype, lipids (amino acids, peptides, and proteins), Female, Cholesterol Esters, Cardiology and Cardiovascular Medicine, Lipoproteins, Lysosomal acid lipase, Adult, medicine.medical_specialty, Adolescent, Sterol O-acyltransferase, Nitric Oxide, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Human Umbilical Vein Endothelial Cells, Humans, Genetic Predisposition to Disease, Triglycerides, Aged, Cholesterol, Cholesterol, HDL, Cholesterol ester storage disease, Cholesterol, LDL, Sterol Esterase, medicine.disease, 030104 developmental biology, Endocrinology, Case-Control Studies, Mutation, Biomarkers, Lipoprotein
Abstract

Background and aims Cholesteryl ester storage disease (CESD) due to LIPA gene mutations is characterized by hepatic steatosis, hypercholesterolemia and hypoalphalipoproteinemia, exposing affected patients to an increased cardiovascular risk. Further insights into the impact of LIPA gene mutations on lipid/lipoprotein metabolism are limited. Aim of the study was to investigate the effect of carrying one or two mutant LIPA alleles on lipoprotein composition and function. Methods Lipoproteins were isolated from 6 adult CESD patients, 5 relatives carrying one mutant LIPA allele (carriers) and 12 sex/age matched controls. Lipid profile, lipoprotein mass composition and the fatty acid distribution of cholesteryl esters (CEs) were assessed. HDL function was evaluated as the ability to promote nitric oxide release by endothelial cells. Results Despite the lipid-lowering therapy, total cholesterol, LDL-cholesterol and triglycerides were increased in CESD patients compared to controls, while HDL-cholesterol was reduced. Carriers also displayed elevated total and LDL-cholesterol. Very low and intermediate density lipoproteins from CESD patients and carriers were enriched in CEs compared to the control ones, with a concomitant reduction of triglycerides. Fatty acid composition of CEs in serum and lipoproteins showed a depletion of linoleate content in CESD patients, due to the reduced LCAT activity. In CESD HDL, fatty acid distribution of CEs was shifted towards saturated ones, if compared to control HDL. The changes in HDL composition did not affect HDL ability to promote nitric oxide release by endothelial cells. Conclusions LIPA gene mutations significantly affected plasma levels and lipid composition of lipoproteins, likely contributing to the increased cardiovascular risk of affected patients.

Published
2020

25. Prevalence and relationship between metabolic syndrome and risk of cardiovascular disease: Evidence from two population-based studies

Author

Fabio Pellegatta, Alexandra Konradi, Asiiat Alieva, Elena Tragni, Oxana Rotar, Olga V. Reutova, Andrea Baragetti, Alberico L. Catapano, Evgeny Shlyakhto, E. Olmastroni, Manuela Casula, and Liliana Grigore

Subjects
Male, medicine.medical_specialty, Waist, Population, Disease, 030204 cardiovascular system & hematology, Lower risk, Risk Assessment, Russia, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Epidemiology, Diabetes Mellitus, Prevalence, Internal Medicine, medicine, Humans, 030212 general & internal medicine, education, Metabolic Syndrome, education.field_of_study, business.industry, Public health, Smoking, Cholesterol, LDL, General Medicine, Middle Aged, medicine.disease, Cholesterol, Cross-Sectional Studies, Italy, Cardiovascular Diseases, Hypertension, Cohort, Female, Waist Circumference, Metabolic syndrome, business, Cardiology and Cardiovascular Medicine
Abstract

Background and aim The metabolic syndrome (MetS) has become one of the most important clinical issues in the cardiovascular field for this decade because of the marked increase in cardiovascular (CV) risk associated with a clustering of risk factors. The aim of the current study was to evaluate the relationship between MetS and its components and cardiovascular disease (CVD). Methods This population-based cross-sectional study was based on data from two studies carried out in Russia (ESSE-RF) and Italy (PLIC). One sample from each cohort was selected, matching individuals by sex and age. A comparison between samples of MetS components distribution and CV risk, according to SCORE chart, has been conducted. Results A total of 609 individuals (mean [SD] age 55 [8] years, about 39% males) for each cohort were selected. Almost half of PLIC cohort participants belonged to the moderate CV risk group (47% vs 27%), while in ESSE-RF cohort a relatively higher prevalence of individuals classified in the high and very high risk group was observed (19% vs 11%, 21% vs 6%, respectively). Overall, 43% of ESSE-RF participants were diagnosed with MetS, compared with the 27% of PLIC members (the difference in prevalence becomes 37% vs 21%, considering a more conservative cut-off for waist circumference). Both cohorts showed a trend towards the increase of MetS components moving from the lowest to the highest CV risk class, with a high prevalence of patients with four or five MetS determinants allocated in the high/very high CV risk group. Conclusions Developing effective public health strategies for the prevention, detection and treatment of MetS should be an urgent priority to reduce the burden of CVD, not only in subjects at high/very high CV risk, but also in those characterized by a lower risk, as even rare CV events that come from low risk group bring a tangible burden to healthcare systems.

Published
2021
Full Text
View/download PDF

26. Association between dietary inflammatory index and subclinical carotid atherosclerosis in the general population

Author

Liliana Grigore, Cristina Tidone, A.L. Catapano, Fabio Pellegatta, Elisa Mattavelli, Andrea Baragetti, R. Domenighini, Laura Redaelli, and V. Zampoleri

Subjects
Carotid atherosclerosis, education.field_of_study, medicine.medical_specialty, Index (economics), business.industry, Internal medicine, Population, medicine, Cardiology, Cardiology and Cardiovascular Medicine, education, business, Subclinical infection
Published
2021
Full Text
View/download PDF

29. PCSK9 deficiency results in increased ectopic fat accumulation in experimental models and in humans

Author

Alberico L. Catapano, Giuseppina Pisano, Anna Ludovica Fracanzani, G. Balzarotti, Andrea Baragetti, Uliano Guerrini, Silvia Fargion, Liliana Grigore, Fabio Pellegatta, and Giuseppe Danilo Norata

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Time Factors, Genotype, Epidemiology, Receptor expression, Adipose tissue, 030204 cardiovascular system & hematology, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Loss of Function Mutation, Internal medicine, Animals, Humans, Medicine, Adiposity, Mice, Knockout, business.industry, PCSK9, Cholesterol, LDL, medicine.disease, Phenotype, 030104 developmental biology, Endocrinology, Adipose Tissue, Italy, Kexin, Android fat distribution, Proprotein Convertase 9, Steatosis, Cardiology and Cardiovascular Medicine, business, Body mass index, Lipoprotein
Abstract

Background Proprotein convertase subtilisin kexin type 9 (PCSK9) regulates low-density lipoprotein and very low-density lipoprotein receptor expression in several tissues. Here we evaluated whether PCSK9 may modulate the handling of triglycerides in the liver and peripheral tissues. Methods Subjects from the PLIC cohort were genotyped for the loss-of-function PCSK9 R46L variant and characterized for clinical and biochemical parameters, total and android fat mass, hepatic steatosis and epicardial fat thickness. Visceral adipose tissue and subcutaneous adipose tissue in PCSK9 KO and wild type mice were quantified by nuclear magnetic resonance imaging. Results Carriers of the R46L variant ( n = 13) had lower low-density lipoprotein cholesterol levels, higher body mass index and increased percentage of total and android fat masses compared with non-carriers ( n = 521). R46L variant associated with a two-fold increase prevalence of hepatic steatosis and higher epicardial fat thickness. These observations were replicated in PCSK9 KO mice, which showed increased visceral adipose tissue (but not subcutaneous adipose tissue) when fed chow or high-fat diet for 20 weeks, compared with wild type mice. Conclusions These data suggest that genetically determined PCSK9 deficiency might be associated with ectopic fat accumulation.

Published
2017
Full Text
View/download PDF

30. How to implement clinical guidelines to optimise familial hypercholesterolaemia diagnosis and treatment

Author

Masa-aki Kawashiri, Michel Farnier, Olivier S. Descamps, Fernando Civeira, Brano Vohnout, and Liliana Grigore

Subjects
medicine.medical_specialty, Statin, medicine.drug_class, MEDLINE, Disease, Cascade screening, 030204 cardiovascular system & hematology, Hyperlipoproteinemia Type II, 03 medical and health sciences, 0302 clinical medicine, Ezetimibe, Risk Factors, Internal Medicine, medicine, Humans, 030212 general & internal medicine, Medical diagnosis, Intensive care medicine, Hypolipidemic Agents, business.industry, Genetic disorder, General Medicine, Atherosclerosis, medicine.disease, Cholesterol, Practice Guidelines as Topic, Physical therapy, Statin therapy, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiology and Cardiovascular Medicine, business, Biomarkers, medicine.drug
Abstract

Background and aims Familial hypercholesterolaemia (FH) is a genetic disorder associated with significantly elevated plasma low-density lipoprotein cholesterol (LDL-C) and premature coronary heart disease (CHD). Optimal management of FH relies on early identification and treatment with statins alone or in combination with other lipid-lowering therapies. A lack of awareness of FH and its manifestations among primary care physicians and specialists has led to many individuals being misdiagnosed in the early stages of the disease, further increasing the risk of CHD and requiring much more intensive lipid-lowering strategies. Therefore, implementing clinical guidelines to optimise the diagnosis and treatment of FH is essential. Methods A working group of clinical experts managing FH patients in their daily practice collaborated in order to provide healthcare professionals with a practical evidence-based guide to streamline early diagnosis and treatment of FH. Results Following thorough evaluation of available data and clinical guidelines, the expert working group provided recommendations on how to detect patients with a suspicion of FH; criteria for clinical and genetic diagnoses of FH; how to assess atherosclerosis in primary care and identify patients at the highest risk; follow-up approaches for patients' families; the most optimal treatment combinations; and when to start lipid-lowering therapy in children with FH. Conclusions The expert working group placed great importance on an individualised approach in the management of FH and highlighted the unmet need for both improved education and communication with the laboratory for physicians when LDL-C levels are significantly elevated. Screening high-risk individuals, or cascade screening, is the most cost-effective way of identifying FH cases and initiating adequate statin therapy alone or in combination with other lipid-lowering therapies. In the case of severe FH, where plasma LDL-C levels remain high following maximum-tolerated statin and ezetimibe treatment, PCSK9 inhibitors should be considered.

Published
2017
Full Text
View/download PDF

32. Treatment with fibrates is associated with higher LAL activity in dyslipidemic patients

Author

Chiara Pavanello, Monica Gomaraschi, Adriana Branchi, Alberico L. Catapano, Andrea Baragetti, Liliana Grigore, Eleonora Giorgio, Laura Calabresi, and Samuela Castelnuovo

Subjects
0301 basic medicine, Adult, Male, medicine.medical_specialty, 03 medical and health sciences, chemistry.chemical_compound, Ezetimibe, Internal medicine, Diabetes mellitus, Medicine, Humans, Aged, Dyslipidemias, Hypolipidemic Agents, Pharmacology, chemistry.chemical_classification, business.industry, Cholesterol, Fibric Acids, Metabolism, Middle Aged, Sterol Esterase, medicine.disease, 030104 developmental biology, Endocrinology, chemistry, lipids (amino acids, peptides, and proteins), Female, Liver function, Metabolic syndrome, business, Dyslipidemia, Polyunsaturated fatty acid, medicine.drug
Abstract

Lysosomal acid lipase (LAL) is responsible for the hydrolysis of cholesteryl esters (CE) and triglycerides (TG) within the lysosomes; generated cholesterol and free fatty acids (FFA) are released in the cytosol where they can regulate their own synthesis and metabolism. When LAL is not active, as in case of genetic mutations, CE and TG accumulate in the lysosomal compartment, while the lack of release of cholesterol and FFA in the cytosol leads to an upregulation of their synthesis. Thus, LAL plays a central role in the intracellular homeostasis of lipids. Since there are no indications about the effect of different lipid-lowering agents on LAL activity, aim of the study was to address the relationship between LAL activity and the type of lipid-lowering therapy in a cohort of dyslipidemic patients. LAL activity was measured on dried blood spot from 120 patients with hypercholesterolemia or mixed dyslipidemia and was negatively correlated to LDL-cholesterol levels. Among enrolled patients, ninety-one were taking one or more lipid-lowering drugs, as statins, fibrates, ezetimibe and omega-3 polyunsaturated fatty acids. When patients were stratified according to the type of lipid-lowering treatment, i.e. untreated, taking statins or taking fibrates, LAL activity was significantly higher in those with fibrates, even after adjustment for sex, age, BMI, lipid parameters, liver function, metabolic syndrome, diabetes and statin use. In a subset of patients tested after 3 months of treatment with micronized fenofibrate, LAL activity raised by 21%; the increase was negatively correlated with baseline LAL activity. Thus, the use of fibrates is independently associated with higher LAL activity in dyslipidemic patients, suggesting that the positive effects of PPAR-α activation on cellular and systemic lipid homeostasis can also include an improved LAL activity.

Published
2019

34. Progression of conventional cardiovascular risk factors and vascular disease risk in individuals: insights from the PROG-IMT consortium

Author

Wiek H. van Gilst, Fabrizio Veglia, Folkert W. Asselbergs, Matthias Sitzer, Gerald S. Berenson, Lars Lind, Joseph F. Polak, Tatjana Rundek, Jackie F. Price, Tomi-Pekka Tuomainen, Christos Savopoulos, Oscar H. Franco, Stefan Kiechl, Matthieu Plichart, Holger Poppert, Alberico L. Catapano, Peter Willeit, Helmuth Steinmetz, Damiano Baldassarre, Frank P. Brouwers, Marcus Dörr, Maryam Kavousi, Apostolos I. Hatzitolios, Martin Bahls, Lu Gao, Stefan Agewall, Stela McLachlan, Henry Völzke, Johann Willeit, Göran Bergström, Michael H. Olsen, Albert Hofman, Jussi Kauhanen, Eric de Groot, Ellisiv B. Mathiesen, Pierre Ducimetière, Dirk Sander, Heiko Uthoff, Horst Bickel, Michiel L. Bots, Kazuo Kitagawa, Liliana Grigore, Matthias W. Lorenz, Ralph L. Sacco, Caroline Schmidt, Giuseppe Danilo Norata, M. Arfan Ikram, Coen D.A. Stehouwer, Simon G. Thompson, Jean Philippe Empana, Moïse Desvarieux, Ulf Schminke, Michael R. Skilton, George Ntaios, Stein Harald Johnsen, PROG-IMT Study Group, Radiotherapy, Cardiology, Graduate School, APH - Personalized Medicine, APH - Methodology, Gastroenterology and Hepatology, Public and occupational health, MUMC+: Centrum voor Chronische Zieken (3), MUMC+: MA Med Staf Artsass Interne Geneeskunde (9), RS: Carim - V01 Vascular complications of diabetes and metabolic syndrome, MUMC+: MA Reumatologie (9), MUMC+: MA Nefrologie (9), MUMC+: MA Medische Oncologie (9), MUMC+: MA Hematologie (9), MUMC+: MA Maag Darm Lever (9), MUMC+: MA Endocrinologie (9), MUMC+: HVC Pieken Maastricht Studie (9), Interne Geneeskunde, MUMC+: MA Interne Geneeskunde (3), Cardiovascular Centre (CVC), Epidemiology, Neurology, and Radiology & Nuclear Medicine

Subjects
Carotid Artery Diseases, Male, Time Factors, BASE-LINE, Epidemiology, Myocardial Infarction, Blood Pressure, 030204 cardiovascular system & hematology, Carotid Intima-Media Thickness, INTIMA-MEDIA THICKNESS, 0302 clinical medicine, Clinical endpoint, Medicine, Cardiac and Cardiovascular Systems, Myocardial infarction, Prospective cohort study, Aged, 80 and over, Kardiologi, Hazard ratio, Middle Aged, Prognosis, VDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710, ddc, DIASTOLIC BLOOD-PRESSURE, Cholesterol, DENSITY-LIPOPROTEIN CHOLESTEROL, Cardiovascular Diseases, Hypertension, Disease Progression, Cardiology, Female, lipids (amino acids, peptides, and proteins), CAROTID-ARTERY INTIMA, Cardiology and Cardiovascular Medicine, STROKE, Adult, medicine.medical_specialty, 610 Medicine & health, risk factor progression, Lower risk, Risk Assessment, Young Adult, 03 medical and health sciences, Predictive Value of Tests, 360 Social problems & social services, Internal medicine, Journal Article, Humans, CORONARY-HEART-DISEASE, ddc:610, METAANALYSIS, Aged, Dyslipidemias, business.industry, Vascular disease, Cholesterol, HDL, VDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710, Cholesterol, LDL, medicine.disease, Blood pressure, MYOCARDIAL-INFARCTION, ATHEROSCLEROSIS, Intima-media thickness, Risk factors, Heart Disease Risk Factors, CVD biomarker, business, Biomarkers, 030217 neurology & neurosurgery
Abstract

AimsAveraged measurements, but not the progression based on multiple assessments of carotid intima-media thickness, (cIMT) are predictive of cardiovascular disease (CVD) events in individuals. Whether this is true for conventional risk factors is unclear.Methods and resultsAn individual participant meta-analysis was used to associate the annualised progression of systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with future cardiovascular disease risk in 13 prospective cohort studies of the PROG-IMT collaboration ( n = 34,072). Follow-up data included information on a combined cardiovascular disease endpoint of myocardial infarction, stroke, or vascular death. In secondary analyses, annualised progression was replaced with average. Log hazard ratios per standard deviation difference were pooled across studies by a random effects meta-analysis. In primary analysis, the annualised progression of total cholesterol was marginally related to a higher cardiovascular disease risk (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.00 to 1.07). The annualised progression of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol was not associated with future cardiovascular disease risk. In secondary analysis, average systolic blood pressure (HR 1.20 95% CI 1.11 to 1.29) and low-density lipoprotein cholesterol (HR 1.09, 95% CI 1.02 to 1.16) were related to a greater, while high-density lipoprotein cholesterol (HR 0.92, 95% CI 0.88 to 0.97) was related to a lower risk of future cardiovascular disease events.ConclusionAveraged measurements of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol displayed significant linear relationships with the risk of future cardiovascular disease events. However, there was no clear association between the annualised progression of these conventional risk factors in individuals with the risk of future clinical endpoints.

Published
2019
Full Text
View/download PDF

35. Subclinical atherosclerosis is associated with Epicardial Fat Thickness and hepatic steatosis in the general population

Author

Anna Ludovica Fracanzani, Liliana Grigore, Alberico L. Catapano, G. Pisano, Katia Garlaschelli, Silvia Fargion, Andrea Baragetti, Cristina Bertelli, and Giuseppe Danilo Norata

Subjects
Carotid Artery Diseases, Male, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), 030204 cardiovascular system & hematology, Carotid Intima-Media Thickness, Ventricular Dysfunction, Left, Absorptiometry, Photon, 0302 clinical medicine, Risk Factors, Odds Ratio, 030212 general & internal medicine, Abdominal obesity, Adiposity, Subclinical infection, Metabolic Syndrome, education.field_of_study, Nutrition and Dietetics, Ultrasound, Middle Aged, Plaque, Atherosclerotic, Adipose Tissue, Cardiology, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, Pericardium, medicine.medical_specialty, Population, Aortic Diseases, 03 medical and health sciences, Sex Factors, Insulin resistance, Predictive Value of Tests, Internal medicine, medicine, Humans, Obesity, Vascular Calcification, education, Aged, Chi-Square Distribution, business.industry, Atherosclerosis, medicine.disease, Echocardiography, Doppler, Color, Fatty Liver, Logistic Models, Endocrinology, Asymptomatic Diseases, Multivariate Analysis, Linear Models, Metabolic syndrome, Steatosis, business
Abstract

Abdominal obesity and hepatic steatosis are ectopic fat depots associated with Metabolic Syndrome (MetS). Epicardial Fat Thickness (EFT) is a newly discovered one, increasing with obesity, insulin resistance and MetS. Therefore we studied whether different ectopic fat markers, and EFT in particular, are associated with MetS and markers of subclinical cardiovascular disease.868 subjects from the PLIC Study were included, EFT, aortic calcifications, carotid Intima-Media Thickness (c-IMT) and echocardiographic parameters were determined by ultrasound; extra-cardiac atherosclerotic lesions were defined in presence of plaques at both carotid and aortic levels. Hepatic steatosis degrees were defined according to a scoring system. Abdominal adiposity was determined using Dual X-ray Absorbimetry (DEXA). Independently from age, women showed higher EFT versus men (4.5 (0.20-9.00) mm vs 4.00 (0.10-8.00) mm, p = 0.013); EFT was thicker in post-menopausal women (independently from hormone-replacement therapy). EFT, liver steatosis and abdominal adiposity increased with MetS (p0.001). EFT was the only ectopic fat marker associated with cardiac dysfunction (OR = 1.340 [1.088-1.651 95% C.I., p = 0.006); liver steatosis and EFT were associated with extra-cardiac plaques (OR = 2.529 [1.328-4.819] 95% C.I., p0.001 and OR = 1.195 [1.008-1.299] 95% C.I., p = 0.042; respectively). On top of cardiovascular risk factors, only EFT improved the discrimination of subjects with cardiac dysfunction and atherosclerotic plaques.EFT is associated with left ventricular dysfunction and subclinical atherosclerosis. Our data suggest that EFT may represent an additional tool for the stratification of cardiovascular risk.

Published
2016
Full Text
View/download PDF

36. Normative values for carotid intima media thickness and its progression: Are they transferrable outside of their cohort of origin?

Author

J.M. Dekker, Matthias Sitzer, Gerald S. Berenson, Joseph F. Polak, Sathanur R. Srinivasan, Ulf Schminke, Jing Liu, Kuo-Liong Chien, Jackie F. Price, Matthias W. Lorenz, Dong Zhao, Ximing Liao, Oscar H. Franco, Ralph L. Sacco, Stein Harald Johnsen, Marcus Dörr, Stefan Kiechl, Hung-Ju Lin, Giel Nijpels, Alfonsa Friera, Ellisiv B. Mathiesen, Dirk Sander, Coen D.A. Stehouwer, Tomi-Pekka Tuomainen, Horst Bickel, Holger Poppert, Alberico L. Catapano, Ta-Chen Su, Simon G. Thompson, David Yanez, Giuseppe Danilo Norata, Kimmo Ronkainen, Liliana Grigore, Jean Philippe Empana, Moïse Desvarieux, Helmuth Steinmetz, Lena Bokemark, Marat V. Ezhov, Wuxiang Xie, Matthieu Plichart, Carmen Suárez, Tatjana Rundek, Stela McLachlan, Maya S. Safarova, Pierre Ducimetière, Albert Hofman, Caroline Schmidt, Rafael Gabriel, Bernhard Iglseder, Peter Willeit, Johann Willeit, Henry Völzke, M. Arfan Ikram, Maryam Kavousi, Lars Lind, T.V. Balakhonova, Christine Robertson, Göran Bergström, Jussi Kauhanen, General practice, EMGO - Lifestyle, overweight and diabetes, Epidemiology and Data Science, Dermatology, MUMC+: HVC Pieken Maastricht Studie (9), RS: CARIM - R3.01 - Vascular complications of diabetes and the metabolic syndrome, Interne Geneeskunde, MUMC+: MA Interne Geneeskunde (3), Epidemiology, Neurology, and Radiology & Nuclear Medicine

Subjects
cardiovascular risk, Percentile, Epidemiology, Population, 030204 cardiovascular system & hematology, Global Health, Carotid Intima-Media Thickness, hazard ratio, 03 medical and health sciences, 0302 clinical medicine, Reference Values, Risk Factors, Humans, Medicine, cardiovascular diseases, 030212 general & internal medicine, education, geographic, education.field_of_study, normal value, Proportional hazards model, business.industry, Incidence, Incidence (epidemiology), Hazard ratio, Atherosclerosis, Random effects model, Intima media thickness, Intima-media thickness, Cohort, Disease Progression, cardiovascular system, ethnicity, Cardiology and Cardiovascular Medicine, business, Demography
Abstract

Background The clinical use of carotid intima media thickness (cIMT) requires normal values, which may be subject to variation of geographical factors, ethnicity or measurement details. The influence of these factors has rarely been studied. The aim of this study was to determine whether normative cIMT values and their association with event risk are generalizable across populations. Design Meta-analysis of individual participant data. Method From 22 general population cohorts from Europe, North America and Asia we selected subjects free of cardiovascular disease. Percentiles of cIMT and cIMT progression were assessed separately for every cohort. Cox proportional hazards models for vascular events were used to estimate hazard ratios for cIMT in each cohort. The estimates were pooled across Europe, North America and Asia, with random effects meta-analysis. The influence of geography, ethnicity and ultrasound protocols on cIMT values and on the hazard ratios was examined by meta-regression. Results Geographical factors, ethnicity and the ultrasound protocol had influence neither on the percentiles of cIMT and its progression, nor on the hazard ratios of cIMT for vascular events. Heterogeneity for percentiles of cIMT and cIMT progression was too large to create meaningful normative values. Conclusions The distribution of cIMT values is too heterogeneous to define universal or regional population reference values. CIMT values vary widely between different studies regardless of ethnicity, geographic location and ultrasound protocol. Prediction of vascular events with cIMT values was more consistent across all cohorts, ethnicities and regions.

Published
2016
Full Text
View/download PDF

37. Optimizing the method of plasma lipoprotein isolation for elucidating their differential association to proprotein convertase subtilisin/kexin 9 (PCSK9)

Author

Stefano Bellosta, Patrizia Uboldi, A.L. Catapano, V. Zampoleri, A.M. Malvandi, L. Canclini, Andrea Baragetti, Liliana Grigore, and Alberto Zambon

Subjects
Plasma lipoprotein, Proprotein Convertase Subtilisin/Kexin 9, Biochemistry, Isolation (health care), Chemistry, PCSK9, Cardiology and Cardiovascular Medicine
Published
2020
Full Text
View/download PDF

38. Gut microbiota composition and functional relevance in subclinical carotid atherosclerosis

Author

Liliana Grigore, Giada Caredda, Luca Rotta, Marco Severgnini, Andrea Angius, A.L. Catapano, Clelia Peano, C. Conca Dioguardi, D.G. Norata, E. Olmastroni, Andrea Baragetti, and Fabio Pellegatta

Subjects
Carotid atherosclerosis, biology, business.industry, Immunology, Medicine, Gut flora, Cardiology and Cardiovascular Medicine, business, biology.organism_classification, Subclinical infection
Published
2020
Full Text
View/download PDF

39. Low Plasma Lecithin: Cholesterol Acyltransferase (LCAT) Concentration Predicts Chronic Kidney Disease

Author

Andrea Baragetti, Liliana Grigore, Alberico L. Catapano, Ivano Baragetti, Laura Calabresi, Fabio Pellegatta, Alice Ossoli, Sara Simonelli, Arianna Strazzella, and Giuseppe Danilo Norata

Subjects
high-density lipoproteins, medicine.medical_specialty, food.ingredient, lecithin:cholesterol acyltransferase, Population, Sterol O-acyltransferase, lcsh:Medicine, Renal function, 030204 cardiovascular system & hematology, urologic and male genital diseases, Lecithin, Article, 03 medical and health sciences, Basal (phylogenetics), 0302 clinical medicine, food, Internal medicine, medicine, education, 030304 developmental biology, 0303 health sciences, education.field_of_study, business.industry, lcsh:R, Hazard ratio, General Medicine, medicine.disease, Endocrinology, Cohort, lipids (amino acids, peptides, and proteins), business, chronic kidney disease, Kidney disease
Abstract

Low high-density lipoprotein-cholesterol (HDL-c) is the most remarkable lipid trait both in mild-to-moderate chronic kidney disease (CKD) patients as well as in advanced renal disease stages, and we have previously shown that reduced lecithin:cholesterol acyltransferase (LCAT) concentration is a major determinant of the low HDL phenotype. In the present study, we test the hypothesis that reduced LCAT concentration in CKD contributes to the progression of renal damage. The study includes two cohorts of subjects selected from the PLIC study: a cohort of 164 patients with CKD (NefroPLIC cohort) and a cohort of 164 subjects selected from the PLIC participants with a basal estimated glomerular filtration rate (eGFR) &gt, 60 mL/min/1.73 m2 (PLIC cohort). When the NefroPLIC patients were categorized according to the LCAT concentration, patients in the 1st tertile showed the highest event rate at follow-up with an event hazard ratio significantly higher compared to the 3rd LCAT tertile. Moreover, in the PLIC cohort, subjects in the 1st LCAT tertile showed a significantly faster impairment of kidney function compared to subjects in the 3rd LCAT tertile. Serum from subjects in the 1st LCAT tertile promoted a higher reactive oxygen species (ROS) production in renal cells compared to serum from subjects in the third LCAT tertile, and this effect was contrasted by pre-incubation with recombinant human LCAT (rhLCAT). The present study shows that reduced plasma LCAT concentration predicts CKD progression over time in patients with renal dysfunction, and, even more striking, it predicts the impairment of kidney function in the general population.

Published
2020
Full Text
View/download PDF

40. Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk – Results from the PROG-IMT collaboration

Author

Sathanur R. Srinivasan, Christine Espinola-Klein, Albert Hofman, Jing Liu, Eric de Groot, Tomi-Pekka Tuomainen, Helmuth Steinmetz, Ta-Chen Su, Carmen Suárez, Maria Rosvall, Stela McLachlan, Raffaele Izzo, Marcus Dörr, Liliana Grigore, Gunnar Engström, Stein Harald Johnsen, David Yanez, Giel Nijpels, Giuseppe Danilo Norata, Fabrizio Veglia, Matthias W. Lorenz, Dong Zhao, Lu Gao, Wuxiang Xie, Damiano Baldassarre, Mauro Amato, Ellisiv B. Mathiesen, Michiel L. Bots, Dirk Sander, Joseph F. Polak, Matthieu Plichart, Holger Poppert, Matthias Sitzer, Ralph L. Sacco, Irene Schmidtmann, Heiko Uthoff, Manuel F. Landecho, Horst Bickel, Gerald S. Berenson, Oscar H. Franco, Bo Hedblad, Kazuo Kitagawa, Daniel Staub, Jackie F. Price, Caroline Schmidt, Alberico L. Catapano, Tatjana Rundek, Thapat Wannarong, M. Arfan Ikram, Kathrin Ziegelbauer, Alfonso Friera, Francesco Rozza, Kimmo Ronkainen, Jacqueline M. Dekker, Peter Willeit, Samuela Castelnuovo, Coen D.A. Stehouwer, Shuhei Okazaki, Pierre Ducimetière, Stefan Blankenberg, Johann Willeit, Oscar Beloqui, Maryam Kavousi, Henry Völzke, Kuo-Liong Chien, Grace Parraga, Bernhard Iglseder, Rafael Gabriel, Lena Bokemark, Stefan Kiechl, Cesare R. Sirtori, Göran Bergström, Jussi Kauhanen, Simon G. Thompson, Nicola De Luca, Lars Lind, Jean Philippe Empana, Moïse Desvarieux, Ulf Schminke, Hung-Ju Lin, Elena Tremoli, Lorenz, Matthias W, Gao, Lu, Ziegelbauer, Kathrin, Norata, Giuseppe Danilo, Empana, Jean Philippe, Schmidtmann, Irene, Lin, Hung-Ju, Mclachlan, Stela, Bokemark, Lena, Ronkainen, Kimmo, Amato, Mauro, Schminke, Ulf, Srinivasan, Sathanur R, Lind, Lar, Okazaki, Shuhei, Stehouwer, Coen D A, Willeit, Peter, Polak, Joseph F, Steinmetz, Helmuth, Sander, Dirk, Poppert, Holger, Desvarieux, Moise, Ikram, M Arfan, Johnsen, Stein Harald, Staub, Daniel, Sirtori, Cesare R, Iglseder, Bernhard, Beloqui, Oscar, Engström, Gunnar, Friera, Alfonso, Rozza, Francesco, Xie, Wuxiang, Parraga, Grace, Grigore, Liliana, Plichart, Matthieu, Blankenberg, Stefan, Su, Ta-Chen, Schmidt, Caroline, Tuomainen, Tomi-Pekka, Veglia, Fabrizio, Völzke, Henry, Nijpels, Giel, Willeit, Johann, Sacco, Ralph L, Franco, Oscar H, Uthoff, Heiko, Hedblad, Bo, Suarez, Carmen, Izzo, Raffaele, Zhao, Dong, Wannarong, Thapat, Catapano, Alberico, Ducimetiere, Pierre, Espinola-Klein, Christine, Chien, Kuo-Liong, Price, Jackie F, Bergström, Göran, Kauhanen, Jussi, Tremoli, Elena, Dörr, Marcu, Berenson, Gerald, Kitagawa, Kazuo, Dekker, Jacqueline M, Kiechl, Stefan, Sitzer, Matthia, Bickel, Horst, Rundek, Tatjana, Hofman, Albert, Mathiesen, Ellisiv B, Castelnuovo, Samuela, Landecho, Manuel F, Rosvall, Maria, Gabriel, Rafael, de Luca, Nicola, Liu, Jing, Baldassarre, Damiano, Kavousi, Maryam, de Groot, Eric, Bots, Michiel L, Yanez, David N, Thompson, Simon G, Lorenz, Matthias W [0000-0002-7565-1751], Apollo - University of Cambridge Repository, General practice, APH - Health Behaviors & Chronic Diseases, Epidemiology and Data Science, Interne Geneeskunde, RS: CARIM - R3.01 - Vascular complications of diabetes and the metabolic syndrome, MUMC+: HVC Pieken Maastricht Studie (9), MUMC+: MA Interne Geneeskunde (3), Epidemiology, Neurology, Radiology & Nuclear Medicine, Pirro, Matteo, and PROG-IMT study group

Subjects
Male, Myocardial Infarction, lcsh:Medicine, PROGRESSION, Cardiovascular Medicine, 030204 cardiovascular system & hematology, Vascular Medicine, Biochemistry, Carotid Intima-Media Thickness, Geographical locations, DISEASE, 0302 clinical medicine, Risk Factors, Germany, Medicine and Health Sciences, Medicine, Cardiac and Cardiovascular Systems, Myocardial infarction, skin and connective tissue diseases, lcsh:Science, ARTERY INTIMA, Stroke, Intersectoral Collaboration, POPULATION, Cardiovascular Diseases/diagnosis, METABOLIC SYNDROME, education.field_of_study, Kardiologi, Multidisciplinary, Agricultural and Biological Sciences(all), VDP::Medical disciplines: 700::Clinical medical disciplines: 750, Hazard ratio, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750, Middle Aged, Prognosis, Predictive value, 3. Good health, Europe, Neurology, Italy, Cardiovascular Diseases, HYPERTENSIVE MEN, Cardiology, cardiovascular system, Female, Research Article, medicine.medical_specialty, High cardiovascular risk, Cerebrovascular Diseases, Science, Population, 030209 endocrinology & metabolism, ATHEROSCLEROSIS RISK, Arbetsmedicin och miljömedicin, 03 medical and health sciences, Carotid intima media thickness (CIMT), Internal medicine, Humans, European Union, ddc:610, cardiovascular diseases, education, Aged, Sweden, Biochemistry, Genetics and Molecular Biology(all), Proportional hazards model, business.industry, lcsh:R, Health Risk Analysis, Correction, Occupational Health and Environmental Health, Atherosclerosis, medicine.disease, Confidence interval, Health Care, Intima-media thickness, MYOCARDIAL-INFARCTION, Medical Biophysics, lcsh:Q, VASCULAR RISK, sense organs, Carotid intima media thickness , Cardiovascular risk, People and places, Metabolic syndrome, business, FOLLOW-UP, 030217 neurology & neurosurgery, Genetics and Molecular Biology(all)
Abstract

AIMS: Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk. METHODS AND RESULTS: From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies. In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95-1.02) in group A, 0.98 (0.93-1.04) in group B, and 0.95 (0.89-1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07-1.23) in group A, 1.13 (1.05-1.22) in group B, and 1.12 (1.05-1.20) in group C. CONCLUSIONS: We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals. The PROG-IMT project, which includes this publication, has been funded by the German Research Foundation (Deutsche Forschungsgemeinschaft, www.dfg.de) under the grants DFG Lo 1569/2-1 and DFG Lo 1569/2-3, received by MWL. The DFG had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Simon Thompson is supported by the British heart Foundation (CH/12/2/29428). Some of the contributing studies were funded by different parties, as listed in the acknowledgement section. Here, too, the funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Sí

Published
2018
Full Text
View/download PDF

41. Disease trends over time and CD4+CCR5+T-cells expansion predict carotid atherosclerosis development in patients with systemic lupus erythematosus

Author

Giuseppe A. Ramirez, Angelo A. Manfredi, Alvise Berti, Enrico Ammirati, Alberico L. Catapano, Martina Berteotti, Paolo G. Camici, Marco Magnoni, Enrica Bozzolo, Katia Garlaschelli, Isabella Scotti, Liliana Grigore, Andrea Baragetti, Giuseppe Danilo Norata, Baragetti, A., Ramirez, G. A., Magnoni, M., Garlaschelli, K., Grigore, L., Berteotti, M., Scotti, I., Bozzolo, E., Berti, A., Camici, P. G., Catapano, A. L., Manfredi, A. A., Ammirati, E., and Norata, G. D.

Subjects
medicine.medical_specialty, T cell, Endocrinology, Diabetes and Metabolism, Population, Adaptive immunity, Medicine (miscellaneous), Disease, Systemic lupus erythematosu, 030204 cardiovascular system & hematology, CXCR3, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Nutrition and Dietetic, Medicine, skin and connective tissue diseases, education, Prospective cohort study, 030203 arthritis & rheumatology, education.field_of_study, Nutrition and Dietetics, business.industry, Vascular disease, Incidence (epidemiology), Carotid atherosclerosi, medicine.disease, medicine.anatomical_structure, Predictive value of tests, Immunology, Cardiology, business, Cardiology and Cardiovascular Medicine
Abstract

Background and Aim Patients with Systemic Lupus Erythematosus (SLE) present increased cardiovascular mortality compared to the general population. Few studies have assessed the long-term development and progression of carotid atherosclerotic plaque in SLE patients. Our aim was to investigate the association of clinical and laboratory markers of disease activity and classical cardiovascular risk factors (CVRF) with carotid atherosclerosis development in SLE patients in a prospective 5-year study. Methods and results Clinical history and information on principal CVRFs were collected at baseline and after 5 years in 40 SLE patients (36 women, mean age 42 ± 9 years; 14.4 ± 7 years of mean disease duration) and 50 age-matched controls. Carotid Doppler ultrasonography was employed to quantify the atherosclerotic burden at baseline and at follow up. Clinimetrics were applied to assess SLE activity over time (SLEDAI). The association between basal circulating T cell subsets (including CD4+CCR5+; CD4+CXCR3+; CD4+HLADR+; CD4+CD45RA+RO−, CD4+CD45RO+RA− and their subsets) and atherosclerosis development was evaluated. During the 5-year follow up, 32% of SLE patients, developed carotid atherosclerosis compared to 4% of controls. Furthermore, considering SLEDAI changes over time, patients within the highest tertile were those with increased incidence of carotid atherosclerosis independently of CVRF. In addition, increased levels of CD4+CCR5+ T cells were independently associated with the development of carotid atherosclerosis in SLE patients. Conclusion Serial clinical evaluations over time, rather than a single point estimation of disease activity or CVRF burden, are required to define the risk of carotid atherosclerosis development in SLE patients. Specific T cell subsets are associated with long-term atherosclerotic progression and may further be of help in predicting vascular disease progression.

Published
2018

42. Post-Prandial Lipemia And Cd36

Author

A.L. Catapano, Laura Redaelli, Nico Mitro, Andrea Baragetti, S. Pedretti, D.G. Norata, Fabio Pellegatta, V. Zampoleri, Fabrizia Bonacina, and Liliana Grigore

Subjects
Post-prandial, medicine.medical_specialty, business.industry, Internal medicine, Cardiology, Medicine, Cardiology and Cardiovascular Medicine, business
Published
2019
Full Text
View/download PDF

43. Life-Style And Cardio-Metabolic Profile Of A Population Living In A Clustered Alpine Village (The Plic Chiesa Study): Comparison With An Urban Cohort (Plic Study)

Author

Laura Redaelli, E. Olmastroni, Andrea Baragetti, Liliana Grigore, A.L. Catapano, Elena Tragni, Cristina Tidone, V. Zampoleri, Manuela Casula, Fabio Pellegatta, and Paolo Magni

Subjects
education.field_of_study, Life style, business.industry, Cardio metabolic, Population, Cohort, Medicine, Cardiology and Cardiovascular Medicine, business, education, Demography
Published
2019
Full Text
View/download PDF

44. Genetically determined telomeres shortening is associated with carotid atherosclerosis progression and increased incidence of cardiovascular events

Author

Andrea Baragetti, Alberico L. Catapano, S. E. Humphries, Philippa J. Talmud, Jutta Palmen, Liliana Grigore, Katia Garlaschelli, and Giuseppe Danilo Norata

Subjects
Carotid Artery Diseases, 0301 basic medicine, Carotid atherosclerosis, medicine.medical_specialty, Pathology, Statistics as Topic, 030204 cardiovascular system & hematology, Carotid Intima-Media Thickness, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, Telomerase, Telomere Shortening, Asymptomatic Diseases, business.industry, Incidence, Disease progression, Membrane Proteins, Neoplasm Proteins, Telomere, 030104 developmental biology, Intima-media thickness, Cardiovascular Diseases, Disease Progression, Cardiology, RNA, Cardiology and Cardiovascular Medicine, business
Published
2016
Full Text
View/download PDF

45. Zc3h10 is a novel mitochondrial regulator

Author

Nico Mitro, Elisabetta Brioschi, Enrique Saez, Tiziana Bonaldi, Gaia Cermenati, Giuseppe R. Diaferia, Serena Ghisletti, Giuseppe Danilo Norata, Alberico L. Catapano, Alessandro Cuomo, Emma De Fabiani, Donatella Caruso, Andrea Baragetti, Matteo Audano, Liliana Grigore, Marina Mora, Fabrizia Bonacina, Maurizio Crestani, Franco Salerno, Silvia Pedretti, and Katia Garlaschelli

Subjects
0301 basic medicine, Male, Proteomics, Proteome, Cellular differentiation, Citric Acid Cycle, Muscle Fibers, Skeletal, Respiratory chain, Regulator, Gene Expression, Mitochondrion, Biochemistry, Cell Line, Myoblasts, 03 medical and health sciences, Mice, Genetics, Animals, Humans, Gene Silencing, Muscle, Skeletal, Molecular Biology, Aged, Zinc finger, Myogenesis, Chemistry, Gene Expression Profiling, Computational Biology, Cell Differentiation, Articles, Cell biology, Mitochondria, Citric acid cycle, 030104 developmental biology, Mitochondrial biogenesis, Mutation, Female, Carrier Proteins, Energy Metabolism
Abstract

Mitochondria are the energy-generating hubs of the cell. In spite of considerable advances, our understanding of the factors that regulate the molecular circuits that govern mitochondrial function remains incomplete. Using a genome-wide functional screen, we identify the poorly characterized protein Zinc finger CCCH-type containing 10 (Zc3h10) as regulator of mitochondrial physiology. We show that Zc3h10 is upregulated during physiological mitochondriogenesis as it occurs during the differentiation of myoblasts into myotubes. Zc3h10 overexpression boosts mitochondrial function and promotes myoblast differentiation, while the depletion of Zc3h10 results in impaired myoblast differentiation, mitochondrial dysfunction, reduced expression of electron transport chain (ETC) subunits, and blunted TCA cycle flux. Notably, we have identified a loss-of-function mutation of Zc3h10 in humans (Tyr105 to Cys105) that is associated with increased body mass index, fat mass, fasting glucose, and triglycerides. Isolated peripheral blood mononuclear cells from individuals homozygotic for Cys105 display reduced oxygen consumption rate, diminished expression of some ETC subunits, and decreased levels of some TCA cycle metabolites, which all together derive in mitochondrial dysfunction. Taken together, our study identifies Zc3h10 as a novel mitochondrial regulator.

Published
2017

46. Myeloid apolipoprotein E controls dendritic cell antigen presentation and T cell activation

Author

Federica M. Marelli-Berg, Liliana Grigore, Alberico L. Catapano, Patrizia Uboldi, Maria P. Longhi, Guosu Wang, Donatella Caruso, Katia Garlaschelli, David Coe, Fabio Pellegatta, Giuseppe Danilo Norata, Nico Mitro, Silvia Gregori, Qingzhong Xiao, A. Moregola, Fabrizia Bonacina, Andrea Baragetti, Lorenzo Da Dalt, and Andrea Annoni

Subjects
0301 basic medicine, Apolipoprotein E, Male, Myeloid, T-Lymphocytes, Apolipoprotein E4, General Physics and Astronomy, Lymphocyte Activation, Major Histocompatibility Complex, Mice, Cell Movement, Myeloid Cells, lcsh:Science, Phospholipids, Mice, Knockout, Antigen Presentation, Mice, Inbred BALB C, Multidisciplinary, biology, Chemistry, Antigen processing, Fatty Acids, food and beverages, Cell Differentiation, Oxysterols, 3. Good health, Cell biology, medicine.anatomical_structure, Cholesterol, lipids (amino acids, peptides, and proteins), Female, T cell, Science, Antigen presentation, Hypercholesterolemia, Bone Marrow Cells, Major histocompatibility complex, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Immune system, Apolipoproteins E, medicine, Animals, Humans, fungi, Histocompatibility Antigens Class II, General Chemistry, Dendritic cell, Dendritic Cells, Hematopoietic Stem Cells, Mice, Inbred C57BL, 030104 developmental biology, biology.protein, lcsh:Q
Abstract

Cholesterol homeostasis has a pivotal function in regulating immune cells. Here we show that apolipoprotein E (apoE) deficiency leads to the accumulation of cholesterol in the cell membrane of dendritic cells (DC), resulting in enhanced MHC-II-dependent antigen presentation and CD4+ T-cell activation. Results from WT and apoE KO bone marrow chimera suggest that apoE from cells of hematopoietic origin has immunomodulatory functions, regardless of the onset of hypercholesterolemia. Humans expressing apoE4 isoform (ε4/3–ε4/4) have increased circulating levels of activated T cells compared to those expressing WT apoE3 (ε3/3) or apoE2 isoform (ε2/3–ε2/2). This increase is caused by enhanced antigen-presentation by apoE4-expressing DCs, and is reversed when these DCs are incubated with serum containing WT apoE3. In summary, our study identifies myeloid-produced apoE as a key physiological modulator of DC antigen presentation function, paving the way for further explorations of apoE as a tool to improve the management of immune diseases., Cholesterol homeostasis can modulate immunity via multiple pathways. Here the authors show that apolipoprotein E, an important regulator of cholesterol, produced by myeloid cells can regulate T cell activation by controlling the antigen presentation activity of dendritic cells in both humans and mice.

Published
2017

47. Telomere shortening over 6 years is associated with increased subclinical carotid vascular damage and worse cardiovascular prognosis in the general population

Author

Elena Tragni, Giuseppe Danilo Norata, Katia Garlaschelli, P.J. Talmud, Jutta Palmen, Alberico L. Catapano, Liliana Grigore, Andrea Baragetti, Fabio Pellegatta, and S. E. Humphries

Subjects
Carotid Artery Diseases, Male, medicine.medical_specialty, Population, Polymerase Chain Reaction, Interquartile range, Internal medicine, Internal Medicine, medicine, Humans, education, Subclinical infection, education.field_of_study, medicine.diagnostic_test, business.industry, Incidence (epidemiology), Hazard ratio, Telomere, Prognosis, Surgery, Blood pressure, ROC Curve, Intima-media thickness, Disease Progression, Cardiology, Female, Lipid profile, business
Abstract

Introduction Leucocyte telomere length (LTL) is an important determinant of telomere function and cellular replicative capacity. The aim of the present study was to examine prospectively the associations between telomere shortening (TS) and both the progression of atherosclerosis and the incidence of cardiovascular events (CVEs). Materials and methods Leucocyte telomere length was measured by quantitative polymerase chain reaction to determine the ratio of telomere length to single-copy gene (T/S) in 768 subjects (462 female and 306 male) enrolled in a large general population survey [the Progressione della Lesione Intimale Carotidea (PLIC study)]. Common carotid artery intima–media thickness was determined at baseline and after 6 years of follow-up, and the associations between TS and the progression of atherosclerosis and incidence of CVEs were evaluated. Results Mean LTL was 1.25 ± 0.92 T/S (median 1.14) at baseline and 0.70 ± 0.37 T/S (median 0.70) after 6 years of follow-up. Median 6-year LTL change was −0.46 T/S [interquartile range (IQR) −0.57 to 1.06], equating to −0.078 T/S [IQR(−0.092 to 0.176)] per year. Of note, telomere lengthening occurred in 30.4% of subjects. After adjustment for classical cardiovascular disease (CVD) risk factors (age, gender, smoking, physical activity, alcohol consumption, systolic blood pressure, glucose levels, lipid profile and therapies), TS was associated with incident subclinical carotid vascular damage [hazard ratio (HR) 5.19, 95% confidence interval (CI) 1.20–22.4, P = 0.028]. Finally, subjects in whom LTL shortened over time showed an increased risk of incident CVE, compared to those in whom LTL lengthened (HR 1.69, CI 1.02–2.78, P = 0.041). Conclusion These data indicate that TS is associated with increased risk of subclinical carotid vascular damage and increased incidence of CVEs beyond CVD risk factors in the general population, whereas LTL lengthening is protective.

Published
2014
Full Text
View/download PDF

48. Pentraxin 3 (PTX3) plasma levels and carotid intima media thickness progression in the general population

Author

Giuseppe Danilo Norata, Ivan Cuccovillo, Johann Willeit, Alberto Mantovani, Alberico L. Catapano, Barbara Bottazzi, Andrea Baragetti, Stefan Kiechl, Katia Garlaschelli, Michael Knoflach, Liliana Grigore, Manuela Casula, and Georg Wick

Subjects
Male, Pathology, medicine.medical_specialty, Carotid Artery, Common, Endocrinology, Diabetes and Metabolism, Population, Medicine (miscellaneous), Femoral artery, Carotid Intima-Media Thickness, Internal medicine, medicine.artery, medicine, Animals, Humans, Prospective Studies, cardiovascular diseases, Myocardial infarction, Common carotid artery, education, Aged, Aged, 80 and over, education.field_of_study, Nutrition and Dietetics, business.industry, Surrogate endpoint, PTX3, Middle Aged, medicine.disease, Serum Amyloid P-Component, C-Reactive Protein, Intima-media thickness, Cardiovascular Diseases, Heart failure, Disease Progression, cardiovascular system, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Biomarkers, Follow-Up Studies
Abstract

Background and aim Pentraxin 3 (PTX3) is an essential component of the humoral arm of innate immunity and, like C-reactive protein, is independently associated with the risk of developing vascular events. Aim of this study was to investigate, in two large population-based surveys, the Bruneck Study and the PLIC Study, whether PTX3 plasma levels predict the progression of common carotid artery intima–media thickness (CCA-IMT), a surrogate marker of atherosclerosis, in the general population during 5 or 6 years of follow-up. Results In the Bruneck Study, PTX3 plasma levels did not predict a faster progression of CCA-IMT either in the carotid artery or in the femoral artery. This finding was confirmed in the PLIC Study where subjects within the highest tertile of PTX3 did not show an increased progression of CCA-IMT. PTX3 plasma levels were also not associated with the fastest maximum IMT progression. In summary, in more than 2400 subjects from the general population, PTX3 plasma level is neither an independent predictor of progression of subclinical atherosclerosis in different arterial territories, including carotid and femoral arteries nor of incident cardiovascular events. Conclusion These findings support the relevance of investigating the predictive value of PTX3 plasma levels only in specific settings, like overt CVD, heart failure or acute myocardial infarction.

Published
2014
Full Text
View/download PDF

49. Leukocytes Telomere Length Shortening In Familial Hypercholesterolemia

Author

G. Norata Danilo, A. Catapano Luigi, Andrea Baragetti, Fabio Pellegatta, Liliana Grigore, V. Zampoleri, and S. Cicolari

Subjects
medicine.medical_specialty, Endocrinology, business.industry, Internal medicine, medicine, Familial hypercholesterolemia, Cardiology and Cardiovascular Medicine, medicine.disease, business, Telomere
Published
2019
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results