José Pablo Werba
@ccfm.it
Unit of Prevention of Atherosclerosis
Centro Cardiologico Monzino IRCCS
Scopus Publications
Scopus Publications
Kanika Inamdar Dharmayat, Antonio J. Vallejo-Vaz, Christophe A.T. Stevens, Julia M. Brandts, Alexander R.M. Lyons, Urh Groselj, Marianne Abifadel, Carlos A. Aguilar-Salinas, Khalid Alhabib, Mutaz Alkhnifsawi,et al.
Elsevier BV
Janneke W. C. M. Mulder, Tycho R. Tromp, Mutaz Al-Khnifsawi, Dirk J. Blom, Krysztof Chlebus, Marina Cuchel, Laura D’Erasmo, Antonio Gallo, G. Kees Hovingh, Ngoc Thanh Kim,et al.
American Medical Association (AMA)
ImportanceHomozygous familial hypercholesterolemia (HoFH) is a rare genetic condition characterized by extremely increased low-density lipoprotein (LDL) cholesterol levels and premature atherosclerotic cardiovascular disease (ASCVD). Heterozygous familial hypercholesterolemia (HeFH) is more common than HoFH, and women with HeFH are diagnosed later and undertreated compared to men; it is unknown whether these sex differences also apply to HoFH.ObjectiveTo investigate sex differences in age at diagnosis, risk factors, lipid-lowering treatment, and ASCVD morbidity and mortality in patients with HoFH.Design, Setting, and ParticipantsSex-specific analyses for this retrospective cohort study were performed using data from the HoFH International Clinical Collaborators (HICC) registry, the largest global dataset of patients with HoFH, spanning 88 institutions across 38 countries. Patients with HoFH who were alive during or after 2010 were eligible for inclusion. Data entry occurred between February 2016 and December 2020. Data were analyzed from June 2022 to June 2023.Main Outcomes and MeasuresComparison between women and men with HoFH regarding age at diagnosis, presence of risk factors, lipid-lowering treatment, prevalence, and onset and incidence of ASCVD morbidity (myocardial infarction [MI], aortic stenosis, and combined ASCVD outcomes) and mortality.ResultsData from 389 women and 362 men with HoFH from 38 countries were included. Women and men had similar age at diagnosis (median [IQR], 13 [6-26] years vs 11 [5-27] years, respectively), untreated LDL cholesterol levels (mean [SD], 579 [203] vs 596 [186] mg/dL, respectively), and cardiovascular risk factor prevalence, except smoking (38 of 266 women [14.3%] vs 59 of 217 men [27.2%], respectively). Prevalence of MI was lower in women (31 of 389 [8.0%]) than men (59 of 362 [16.3%]), but age at first MI was similar (mean [SD], 39 [13] years in women vs 38 [13] years in men). Treated LDL cholesterol levels and lipid-lowering therapy were similar in both sexes, in particular statins (248 of 276 women [89.9%] vs 235 of 258 men [91.1%]) and lipoprotein apheresis (115 of 317 women [36.3%] vs 118 of 304 men [38.8%]). Sixteen years after HoFH diagnosis, women had statistically significant lower cumulative incidence of MI (5.0% in women vs 13.7% in men; subdistribution hazard ratio [SHR], 0.37; 95% CI, 0.21-0.66) and nonsignificantly lower all-cause mortality (3.0% in women vs 4.1% in men; HR, 0.76; 95% CI, 0.40-1.45) and cardiovascular mortality (2.6% in women vs 4.1% in men; SHR, 0.87; 95% CI, 0.44-1.75).Conclusions and RelevanceIn this cohort study of individuals with known HoFH, MI was higher in men compared with women yet age at diagnosis and at first ASCVD event were similar. These findings suggest that early diagnosis and treatment are important in attenuating the excessive cardiovascular risk in both sexes.
Manuela Casula, Marta Gazzotti, Maria Elena Capra, Elena Olmastroni, Federica Galimberti, Alberico L. Catapano, Cristina Pederiva, Adriano Anesi, Marcello Arca, Renata Auricchio,et al.
Elsevier BV
Patrizia Amadio, Benedetta Porro, Viviana Cavalca, Marta Zarà, Sonia Eligini, Leonardo Sandrini, José Pablo Werba, Nicola Cosentino, Paolo Olivares, Arianna Galotta,et al.
Elsevier BV
M. Arca, Maurizio Averna, C. Borghi, M. Lettino, Pasquale Perrone Filardi, Antonia Alberti, Claudio Bilato, P. Calabrò, Francesca Carubbi, M. Ciccone,et al.
Atherosclerotic cardiovascular diseases remain the main cause of mortality worldwide, due to a poor control of modifiable risk factors for atherosclerosis. High levels of low-density lipoprotein cholesterol represent the most relevant actor in the development of atherosclerotic cardiovascular diseases, as well as the main target of prevention strategies. Although lipid-lowering treatments were shown to be effective for cardiovascular prevention, several barriers (e.g. clinician reluctance to prescribe an intensive treatment, poor adherence of patients to therapy, high pharmacotherapy burden of high-risk patients and the fear for adverse events potentially associated with statins) still prevent therapy optimization. Such issues will be addressed in this review article, taking into account possible strategies for their solution, through an integrated approach including both management interventions and a larger use of the available pharmacologic options.
Damiano Baldassarre, Licia Iacoviello, Roberta Baetta, Maria Carla Roncaglioni, Gianluigi Condorelli, Giuseppe Remuzzi, Gianfranco Gensini, Luigi Frati, Walter Ricciardi, Pier Giulio Conaldi,et al.
BMJ
IntroductionPrevention of cardiovascular disease (CVD) is of key importance in reducing morbidity, disability and mortality worldwide. Observational studies suggest that digital health interventions can be an effective strategy to reduce cardiovascular (CV) risk. However, evidence from large randomised clinical trials is lacking.Methods and analysisThe CV-PREVITAL study is a multicentre, prospective, randomised, controlled, open-label interventional trial designed to compare the effectiveness of an educational and motivational mobile health (mHealth) intervention versus usual care in reducing CV risk. The intervention aims at improving diet, physical activity, sleep quality, psycho-behavioural aspects, as well as promoting smoking cessation and adherence to pharmacological treatment for CV risk factors. The trial aims to enrol approximately 80 000 subjects without overt CVDs referring to general practitioners’ offices, community pharmacies or clinics of Scientific Institute for Research, Hospitalization and Health Care (Italian acronym IRCCS) affiliated with the Italian Cardiology Network. All participants are evaluated at baseline and after 12 months to assess the effectiveness of the intervention on short-term endpoints, namely improvement in CV risk score and reduction of major CV risk factors. Beyond the funded life of the study, a long-term (7 years) follow-up is also planned to assess the effectiveness of the intervention on the incidence of major adverse CV events. A series of ancillary studies designed to evaluate the effect of the mHealth intervention on additional risk biomarkers are also performed.Ethics and disseminationThis study received ethics approval from the ethics committee of the coordinating centre (Monzino Cardiology Center; R1256/20-CCM 1319) and from all other relevant IRBs and ethics committees. Findings are disseminated through scientific meetings and peer-reviewed journals and via social media. Partners are informed about the study’s course and findings through regular meetings.Trial registration numberNCT05339841.
Alessandra Romandini, Damiano Baldassarre, Stefano Genovese, Stefano Capri, Giulio Pompilio, Marco Scatigna, and José Pablo Werba
MDPI AG
Innovative lipid-modifying agents are valuable resources to improve the control of atherogenic dyslipidemias and reduce the lipid-related residual cardiovascular risk of patients with intolerance or who are not fully responsive to a consolidated standard of care (statins plus ezetimibe). Moreover, some of the upcoming compounds potently affect lipid targets that are thus far considered “unmodifiable”. The present paper is a viewpoint aimed at presenting the incremental metabolic and cardiovascular benefits of the emerging lipid-modulating agents and real-life barriers, hindering their prescription by physicians and their assumption by patients, which need to be worked out for a more diffuse and appropriate drug utilization.
Andrea Poli, Alberico L. Catapano, Alberto Corsini, Enzo Manzato, José Pablo Werba, Gabriele Catena, Irene Cetin, Arrigo F.G. Cicero, Andrea Cignarella, Furio Colivicchi,et al.
Elsevier BV
Elena Olmastroni, Marta Gazzotti, Maurizio Averna, Marcello Arca, Patrizia Tarugi, Sebastiano Calandra, Stefano Bertolini, Alberico L. Catapano, Manuela Casula, Marcello Arca,et al.
Ovid Technologies (Wolters Kluwer Health)
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 <0.0001); however, subjects with FH/M− and lp(a) score ≥1 had higher mean (SD) pretreatment low‐density lipoprotein cholesterol levels (223.47 [50.40] mg/dL) compared with subjects with FH/M− and lp(a) score=0 (219.38 [54.54] mg/dL for), although not statistically significant. The adjustment of low‐density lipoprotein cholesterol levels based on lp(a) concentration reduced from 68% to 42% the proportion of subjects with low‐density lipoprotein cholesterol level ≥190 mg/dL (or from 68% to 50%, considering a more conservative formula). Conclusions Our study supports the importance of measuring lp(a) to perform the diagnosis of FH appropriately and to exclude that the observed phenotype is driven by elevated levels of lp(a) before performing the genetic test for FH.
Oreste Lanza, Nicola Cosentino, Claudia Lucci, Marta Resta, Mara Rubino, Valentina Milazzo, Monica De Metrio, Filippo Trombara, Jeness Campodonico, José Pablo Werba,et al.
MDPI AG
Background: Prior statin therapy has a cardioprotective effect in patients undergoing elective or urgent percutaneous coronary intervention (PCI). However, data on patients with ST-elevation myocardial infarction (STEMI) undergoing primary PCI are still controversial. We retrospectively evaluated the effect of prior statin therapy on in-hospital clinical outcomes in consecutive STEMI patients undergoing primary PCI. Methods: A total of 1790 patients (mean age 67 ± 11 years, 1354 men) were included. At admission, all patients were interrogated about prior (>6 months) statin therapy. The primary endpoint of the study was the composite of in-hospital mortality, acute pulmonary edema, and cardiogenic shock in patients with or without prior statin therapy. Results: A total of 427 patients (24%) were on prior statin therapy. The incidence of the primary endpoint was similar in patients with or without prior statin therapy (15% vs. 16%; p = 0.38). However, at multivariate analysis, prior statin therapy was associated with a lower risk of the primary endpoint, after adjustment for major prognostic predictors (odds ratio 0.61 [95% CI 0.39–0.96]; p = 0.03). Conclusions: This study demonstrated that prior statin therapy is associated with a better in-hospital clinical outcome in patients with STEMI undergoing primary PCI compared to those without prior statin therapy.
Marta Gazzotti, Manuela Casula, Stefano Bertolini, Maria Elena Capra, Elena Olmastroni, Alberico Luigi Catapano, Cristina Pederiva, and
Frontiers Media SA
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.
Sonia Eligini, Benedetta Porro, José Pablo Werba, Nicolò Capra, Stefano Genovese, Arianna Greco, Viviana Cavalca, and Cristina Banfi
MDPI AG
The effects of the oral glucose tolerance test (OGTT) on red blood cells (RBCs) have not been thoroughly investigated, although it is known that the ingestion of 75 g of glucose during OGTT results in a systemic state of inflammation and oxidative stress. Therefore, we evaluated the effect of OGTT on oxidative stress and L-arginine/Nitric Oxide (L-Arg/NO) metabolic pathway in RBCs obtained from patients with prediabetes. Blood samples were collected from all participants before (T0) and at 10 (T1), 20 (T2), 30 (T3), 60 (T4), 90 (T5), 120 (T6), 150 (T7), and 180 (T8) minutes after glucose loading. Results showed a significant increase in oxidative stress status characterized by a rise in the GSSG/GSH ratio at T4 and T6 that increased in parallel with a reduction of NO production in RBCs. In addition, in this time frame, increased exposure of phosphatidylserine on RBCs membrane was observed. These metabolic modifications were rescued at T8, together with an increase in activated RBC NO synthase expression. These findings provide a possible explanation of the phenomena occurring after glucose loading and suggest that, even in the early stages of diabetes, it may be important to avoid acute variations in glycemia in order to prevent diabetic complications.
José P. Werba, Monica G. Giroli, Niccolò Simonelli, Lorenzo Vigo, Alessandra Gorini, Alice Bonomi, Fabrizio Veglia, and Elena Tremoli
Elsevier BV
José Pablo Werba, Alice Bonomi, Monica Giroli, Manuela Amato, Lorenzo Vigo, Marco Agrifoglio, Francesco Alamanni, Laura Cavallotti, Samer Kassem, Moreno Naliato,et al.
Oxford University Press (OUP)
Abstract Aims Patients with coronary heart disease (CHD) are at very high risk of recurrent events. A strategy to reduce excess risk might be to deliver structured secondary prevention programmes, but their efficacy has been mostly evaluated in the short term and in experimental settings. This is a retrospective case–control study aimed at assessing, in the real world, the efficacy of a secondary prevention programme in reducing long-term coronary event recurrences after coronary artery bypass surgery (CABG). Methods and results Programme participants (henceforth ‘cases’) were men and women aged &lt;75 years subjected to CABG between 2002 and 2014, living within 100 km of the hospital. Key programme actions included optimization of treatments according to the most updated European preventive guidelines, surveillance of therapy adherence, and customized lifestyle counselling. Controls were analogous patients not involved in the programme because living farther than 100 km away, matched 1:1 with cases for gender, age at CABG, and year of CABG. Both groups (n = 1248) underwent usual periodic cardiology follow-up at our centre. Data on symptomatic or silent CHD recurrences were obtained from the hospital electronic health records. Cox analysis (adjusted for baseline differences between groups) shows that programme participation was associated with a significantly lower incidence throughout 5 years post-CABG of symptomatic [hazard ratio (95% confidence interval): 0.59 (0.38–0.94)] and silent [0.53 (0.31–0.89)] coronary recurrences. Conclusion In a real-world setting, taking part in a structured longstanding secondary prevention programme, in addition to usual cardiology care, meaningfully lowers the risk of coronary recurrences.
Leonardo Sandrini, Patrizia Amadio, Alessandro Ieraci, Alessandro Malara, José P. Werba, Paolo M. Soprano, Alessandra Balduini, Marta Zarà, Alice Bonomi, Fabrizio Veglia,et al.
Elsevier BV
Depression is associated with thrombotic risk and arterial events, its proper management is strongly recommended in coronary artery disease (CAD) patients. We have previously shown that the Brain-Derived Neurotrophic Factor (BDNF)Val66Met polymorphism, related to depression, is associated with arterial thrombosis in mice, and with an increased risk of acute myocardial infarction in humans. Herein, expanding the previous findings on BDNFVal66Met polymorphism, we show that desipramine, a norepinephrine reuptake-inhibitor, rescues behavioral impairments, reduces the arterial thrombosis risk, abolishes pathological coagulation and platelet hyper-reactivity, normalizes leukocyte, platelet, and bone marrow megakaryocyte number and restores physiological norepinephrine levels in homozygous knock-in BDNF Val66Met (BDNFMet/Met) mice. The in vitro data confirm the enhanced procoagulant activity and the alpha2A-adrenergic receptor (α2A-ADR) overexpression found in BDNFMet/Met mice and we provide evidence that, in presence of Met variant, norepinephrine is crucial to up-regulate procoagulant activity and to enhance platelet generation. The α2-ADR antagonist rauwolscine rescues the prothrombotic phenotype in BDNFMet/Met mice and reduces procoagulant activity and platelet generation in cells transfected with BDNFMet plasmid or exposed to pro-BDNFMet peptide. Finally, we show that homozygous BDNFMet/Met CAD patients have hyper-reactive platelets overexpressing abundant α2A-ADR. The great proplatelet release from their megakaryocytes well reflects their higher circulating platelet number compared to BDNFVal/Val patients. These data reveal an unprecedented described role of Met allele in the dysregulation of norepinephrine/α2A-ADR pathway that may explain the predisposition to arterial thrombosis. Overall, the development of α2A-ADR inhibitors might represent a pharmacological treatment for depression-associated thrombotic conditions in this specific subgroup of CAD patients.
Alessandra Gorini, Federica Galli, Mattia Giuliani, Antonia Pierobon, José Pablo Werba, Edvige Palazzo Adriano, and Daniela Trabattoni
MDPI AG
During an acute cardiac event, Takotsubo Syndrome (TTS) and Acute Coronary Syndrome (ACS) apparently share very similar clinical characteristics. Since only a few inconsistent studies have evaluated the psychological features that characterize these different patients, the aim of the present explorative research was to investigate if post-recovery TTS and ACS patients present different psychological profiles. We also investigated whether the occurrence of acute psychological stressful episodes that had occurred prior to the cardiac event could be found in either syndrome. Twenty TTS and twenty ACS female patients were recruited. All patients completed self-report questionnaires about anxiety and depressive symptoms, perceived stress, type-D personality and post-traumatic symptoms. Results showed that only three subscales of health anxiety (i.e., Fear of Death/Diseases, Interference and Reassurance) significantly differed between the two groups, while no differences were found in the other psychological measurements. Moreover, personality traits seem to not be associated with the impact of the cardiac traumatic event. Finally, only TTS patients reported the presence of a significant emotional trigger preceding the acute cardiac event. In conclusion, post-recovery TTS patients differ from ACS patients in their level of concern about their health and in their need of reassurance and information only, probably as a result of the different clinical characteristics of the two illnesses.
Antonio J. Vallejo-Vaz, Christophe A.T. Stevens, Alexander R.M. Lyons, Kanika I. Dharmayat, Tomas Freiberger, G. Kees Hovingh, Pedro Mata, Frederick J. Raal, Raul D. Santos, Handrean Soran,et al.
Elsevier BV
M. Casula, M. Gazzotti, F. Bonaiti, E. OImastroni, M. Arca, M. Averna, A. Zambon, A.L. Catapano, Marcello Arca, Anna Montali,et al.
Wiley
AIM
Statin associated muscle symptoms (SAMS) are a major determinant of poor treatment adherence and/or discontinuation, but a definitive diagnosis of SAMS is challenging. The PROSISA study was an observational retrospective study aimed to assess the prevalence of reported SAMS in a cohort of dyslipidaemic patients.
METHODS
Demographic/anamnestic data, biochemical values, and occurrence of SAMS were collected by 23 Italian Lipid Clinics. Adjusted logistic regression was performed to estimate odds ratio (OR) and 95% confidence intervals for association between probability of reporting SAMS and several factors.
RESULTS
Analyses were carried out on 16,717 statin-treated patients (mean±SD, age 60.5±12.0 years; 52.1% men). During statin therapy, 9.6% (N=1,599) of patients reported SAMS. Women and physically active subjects were more likely to report SAMS (OR 1.23 [1.10-1.37] and OR 1.35 [1.14-1.60], respectively), while age ≥65 (OR 0.79 [0.70-0.89]), presence of type 2 diabetes mellitus (OR 0.62 [0.51-0.74]), use of concomitant non-statin lipid-lowering drugs (OR 0.87 [0.76-0.99]), of high-intensity statins (OR 0.79 [0.69-0.90]), and of potential interacting drugs (OR 0.63 [0.48-0.84]) were associated with lower probability of reporting SAMS. Among patients reporting SAMS, 82.2% underwent dechallenge (treatment interruption) and/or rechallenge (change or restart of statin therapy), with reappearance of muscular symptoms in 38.4% (3.01% of the whole cohort).
CONCLUSIONS
The reported prevalence of SAMS was 9.6% of the whole PROSISA cohort, but only a third of patients still reported SAMS after dechallenge/rechallenge. These results emphasize the need for a better management of SAMS to implement a more accurate diagnosis and treatment re-evaluation.
Susanna Fiorelli, Andrea Anesi, Benedetta Porro, Nicola Cosentino, José P. Werba, Alessandro Di Minno, Chiara Maria Manega, Simone Barbieri, Gualtiero I. Colombo, Giancarlo Marenzi,et al.
Wiley
Monocyte recruitment after vascular injury and their migration through the vessel wall represent crucial events in the initiation, progression, and destabilization of atherosclerotic plaque. Circulating monocytes are exposed to stimuli that alter their physiological state, and among them, lipids play a key role. Several studies investigated the mechanisms by which lipids affect monocyte functions promoting coronary atherosclerotic plaque initiation, but information on the relationship between lipid composition and function of monocyte is scant. We aimed at studying the migration of circulating monocytes isolated from patients with acute myocardial infarction (AMI) at hospital presentation and investigating its correlation with cellular lipid profile. The migration of monocytes was tested using both fetal bovine serum (FBS) and autologous serum as chemoattractant stimuli. Monocyte lipid profile was evaluated through an untargeted lipidomics approach, using a liquid chromatography/time-of-flight mass spectrometry platform. We observed that AMI patients' monocytes showed a significant increase in FBS and autologous serum-mediated migration compared to controls. Moreover, a different monocyte lipidomic profile between the two study groups was detected. In particular, AMI patients' monocytes showed an altered composition in ceramides, with an increase in lactosylceramide and in phospholipids (ie, phosphatidylethanolamine and lisophosphatidylethanolamine). Of note, a positive correlation between lactosylceramide levels and monocyte migration was observed. Furthermore, the lactosylceramide synthase inhibition significantly reduced FBS-induced monocyte migration. Our results highlight the influence of lactosylceramide on the monocyte migration capacity, pointing out a new possible mechanism of lipids in the onset of atherothrombosis and, hence, in AMI.
Patrizia Amadio, Benedetta Porro, Viviana Cavalca, Silvia Stella Barbieri, Sonia Eligini, Susanna Fiorelli, Alessandro Di Minno, Alessandra Gorini, Mattia Giuliani, Josè Pablo Werba,et al.
Elsevier BV
BACKGROUND
Takotsubo (TTS) syndrome is an acute cardiac condition characterized by transient and reversible left ventricle dysfunction that mainly affects postmenopausal women. Catecholamine burst is the most accredited mechanism underpinning TTS onset and leading to endothelial dysfunction and platelet activation. Even if the use of low dose acetylsalycilic acid (ASA) in this clinical setting is based on both clinical presentation and unfavorable long-term prognosis, its efficacy has been recently challenged.
AIM
This study was designed to assess endothelial function, residual thromboxane formation and platelet aggregation in TTS women on low-dose ASA treatment at long-term follow-up.
METHODS
Twenty-eight females with previously diagnosis of TTS syndrome were enrolled. Data were compared to those obtained from 23 coronary artery disease (CAD) women with a history of acute myocardial infarction, and 26 control subjects with no TTS or clinically evident CAD. Psychological and clinical profile were assessed in all study groups at the enrollment. Main metabolites involved in L-arginine/nitric oxide pathway, urinary prostacyclin, serum and urine thromboxane metabolites were measured by LCMS/MS methods. Thrombomodulin levels were quantified using an ELISA kit, and platelet aggregation, carried out on platelet rich-plasma, was induced by ADP or by epinephrine (EPI), norepinephrine (NORE) and TRAP-6, alone or in association with ADP and evaluated by Born's method.
RESULTS
In TTS women an endothelial derangement, characterized by reduced citrulline production and increased thrombomodulin concentration, with no perturbation in prostacyclin levels, was evidenced. In addition, despite ASA treatment, TTS displayed a higher residual thromboxane formation, in parallel with an enhanced platelet response to compared to CAD.
CONCLUSIONS
Our study highlighted the presence of endothelial perturbation in TTS patients even at long-term from the index event. The residual thromboxane production and platelet aggregation still leave open the question about the use of low dose ASA in this clinical setting.
Luca Piacentini, Claudio Saccu, Elisa Bono, Elena Tremoli, Rita Spirito, Gualtiero Ivanoe Colombo, and José Pablo Werba
Springer Science and Business Media LLC
Perivascular adipose tissue (PVAT) helps regulate arterial homeostasis and plays a role in the pathogenesis of large vessel diseases. In this study, we investigated whether the PVAT of aortic occlusive lesions shows specific gene-expression patterns related to pathophysiology. By a genome-wide approach, we investigated the PVAT transcriptome in patients with aortoiliac occlusive disease. We compared the adipose layer surrounding the distal aorta (atherosclerotic lesion) with the proximal aorta (plaque-free segment), both within and between patients with complete aortoiliac occlusion (Oc) and low-grade aortic stenosis (St). We found that PVAT of the distal versus proximal aorta within both Oc- and St-patients lacks specific, locally restricted gene-expression patterns. Conversely, singular gene-expression profiles distinguished the PVAT between Oc- and St-patients. Functional enrichment analysis revealed that these signatures were associated with pathways related to metabolism of cholesterol, vessel tone regulation, and remodeling, including TGF-β and SMAD signaling. We finally observed that gene-expression profiles in omental-visceral or subcutaneous fat differentiated between Oc- and St-patients, suggesting that the overall adipose component associates with a different atherosclerosis burden. Our work points out the role of PVAT and, likely, other adipose tissues play in the pathophysiological mechanisms underlying atherosclerotic disease, including the abdominal aortic occlusive forms.
Mauro Amato, José Pablo Werba, Beatrice Frigerio, Daniela Coggi, Daniela Sansaro, Alessio Ravani, Palma Ferrante, Fabrizio Veglia, Elena Tremoli, and Damiano Baldassarre
MDPI AG
Background: The lack of specific vaccines or drugs against coronavirus disease 2019 (COVID-19) warrants studies focusing on alternative clinical approaches to reduce the spread of this pandemic disease. In this study, we investigated whether anti-influenza vaccination plays a role in minimizing the diffusion of COVID-19 in the Italian population aged 65 and over. Methods: Four COVID-19 outcomes were used: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence, hospitalizations for COVID-19 symptoms, admissions to intensive care units for reasons related to SARS-CoV-2, and deaths attributable to COVID-19. Results: At univariate analyses, the influenza vaccination coverage rates correlated negatively with all COVID-19 outcomes (Beta ranging from −134 to −0.61; all p < 0.01). At multivariable analyses, influenza vaccination coverage rates correlated independently with SARS-CoV-2 seroprevalence (Beta (95% C.I.): −130 (−198, −62); p = 0.001), hospitalizations for COVID-19 symptoms (Beta (95% C.I.): −4.16 (−6.27, −2.05); p = 0.001), admission to intensive care units for reasons related to SARS-CoV-2 (Beta (95% C.I.): −0.58 (−1.05, −0.12); p = 0.017), and number of deaths attributable to COVID-19 (Beta (95% C.I.): −3.29 (−5.66, −0.93); p = 0.010). The R2 observed in the unadjusted analysis increased from 82% to 159% for all the considered outcomes after multivariable analyses. Conclusions: In the Italian population, the coverage rate of the influenza vaccination in people aged 65 and over is associated with a reduced spread and a less severe clinical expression of COVID-19. This finding warrants ad hoc studies to investigate the role of influenza vaccination in preventing the spread of COVID-19.
Manuela Amato, Alice Bonomi, Federica Laguzzi, Fabrizio Veglia, Elena Tremoli, José P. Werba, and Monica G. Giroli
Elsevier BV
BACKGROUND AND AIM
Along with the increasing evidence of the cardioprotective effects of the Mediterranean Diet (MD), the scientific interest and advocacy of dietary variety as a potentially healthy eating habit gradually faded, until its complete oblivion in the latest European cardiovascular prevention guidelines. Our study aims to investigate whether dietary variety adds to the "Mediterranean-ness" of the diet in protecting against coronary heart disease (CHD).
METHODS AND RESULTS
In this case-control Italian study, data on eating habits were collected from 178 patients with CHD and 155 healthy controls, primarily males, frequency matched for age and gender, using the Food Frequency Questionnaire (FFQ) of the European Prospective Investigation into Cancer and Nutrition. Adherence to MD was estimated from FFQ by the Mediterranean Diet Score (MDS), an index developed by Trichopoulou (2003) ranging from 0 to 9, with higher scores indicating a stricter adherence. Overall dietary variety was computed from FFQ as a count of single food items consumed at least once a month. Associations between MDS or overall dietary variety and coronary status were evaluated by logistic regression models adjusted for BMI, physical activity, smoking, education, and caloric intake; the Odds Ratio (OR) for CHD for each 1.5-point increase in MDS was 0.76 [IC 95% 0.59; 0.98], whereas the OR for CHD for each 15-item increase in dietary variety was 0.62 [IC 95% 0.46; 0.84]. Remarkably, adherence to MD and overall dietary variety were independently associated with a significantly reduced chance of CHD.
CONCLUSION
Dietary Mediterranean-ness and overall dietary variety exhibit additive cardioprotective effects.
José Pablo Werba and Fabrizio Veglia
Ubiquity Press, Ltd.
An in-depth analysis of gathered data collected in several countries on the pre-infectious characteristics of patients who have developed severe forms of COVID-19 disease could be the basis for developing tools to estimate individual risk and tailor protective measures for a safer route through the Phase 2 of the pandemic.