Publications by authors named "Francesco Cipollone"

115 Publications

Sex-Specific Association of Endogenous PCSK9 With Memory Function in Elderly Subjects at High Cardiovascular Risk.

Front Aging Neurosci 2021 11;13:632655. Epub 2021 Mar 11.

Department of Medicine and Aging and Center for Advanced Studies and Technology, Chieti, Italy.

Growing evidence indicates that cognitive decline and cardiovascular diseases (CVDs) share common vascular risk factors. Protease proprotein convertase subtilisin/kexin type 9 (PCSK9) is associated with CV disease risk and has been also involved in neuronal differentiation. Evaluate whether in patients at high CV risk cognitive function is related to PCSK9 levels. . One hundred sixty-six patients (67 female) were enrolled. A detailed neuropsychological (NP) assessment was performed. PCSK9 levels were measured with ELISA. Men had significantly higher short-term memory, executive function, and praxic and mental representation skills, as reflected by Forward Digit Span (FDS) ( = 0.005), Trail Making Test-A (TMT-A) ( = 0.047), Clock Drawing Test (CDT) (0.016). Endogenous PCSK9 levels were higher in female ( = 0.005). On linear regression analysis PCSK9 predicts short term memory only in females (Beta = 0.408, = 0.001), with an interaction between PCSK9 and gender ( = 0.004 for interaction PCSK9 by sex). The association of PCSK9 with FDS in female was partially mediated by waist circumference (mediation effect 8.5%). In patients at high CV risk short term memory was directly related to PCSK9 levels only in women, revealing the relevance of sex in this relationship. The association of PCSK9 with memory function may be mediated, at least in part, by waist circumference.
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http://dx.doi.org/10.3389/fnagi.2021.632655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990768PMC
March 2021

Clinical outcome with different doses of low-molecular-weight heparin in patients hospitalized for COVID-19.

J Thromb Thrombolysis 2021 Mar 1. Epub 2021 Mar 1.

Azienda Ospedaliero-Universitaria Maggiore della Carità, Novara, Italy.

A pro-thrombotic milieu and a higher risk of thrombotic events were observed in patients with CoronaVirus disease-19 (COVID-19). Accordingly, recent data suggested a beneficial role of low molecular weight heparin (LMWH), but the optimal dosage of this treatment is unknown. We evaluated the association between prophylactic vs. intermediate-to-fully anticoagulant doses of enoxaparin and in-hospital adverse events in patients with COVID-19. We retrospectively included 436 consecutive patients admitted in three Italian hospitals. Outcome according to the use of prophylactic (4000 IU) vs. higher (> 4000 IU) daily dosage of enoxaparin was evaluated. The primary end-point was in-hospital death. Secondary outcome measures were in-hospital cardiovascular death, venous thromboembolism, new-onset acute respiratory distress syndrome (ARDS) and mechanical ventilation. A total of 287 patients (65.8%) were treated with the prophylactic enoxaparin regimen and 149 (34.2%) with a higher dosing regimen. The use of prophylactic enoxaparin dose was associated with a similar incidence of all-cause mortality (25.4% vs. 26.9% with the higher dose; OR at multivariable analysis, including the propensity score: 0.847, 95% CI 0.400-0.1.792; p = 0.664). In the prophylactic dose group, a significantly lower incidence of cardiovascular death (OR 0.165), venous thromboembolism (OR 0.067), new-onset ARDS (OR 0.454) and mechanical intubation (OR 0.150) was observed. In patients hospitalized for COVID-19, the use of a prophylactic dosage of enoxaparin appears to be associated with similar in-hospital overall mortality compared to higher doses. These findings require confirmation in a randomized, controlled study.
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http://dx.doi.org/10.1007/s11239-021-02401-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919624PMC
March 2021

Plasma microRNA signature associated with retinopathy in patients with type 2 diabetes.

Sci Rep 2021 Feb 18;11(1):4136. Epub 2021 Feb 18.

Department of Medicine and Aging Science, "G. d'Annunzio" University, Chieti, Italy.

Diabetic retinopathy (DR) is a leading cause of vision loss and disability. Effective management of DR depends on prompt treatment and would benefit from biomarkers for screening and pre-symptomatic detection of retinopathy in diabetic patients. MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression which are released in the bloodstream and may serve as biomarkers. Little is known on circulating miRNAs in patients with type 2 diabetes (T2DM) and DR. Here we show that DR is associated with higher circulating miR-25-3p (P = 0.004) and miR-320b (P = 0.011) and lower levels of miR-495-3p (P < 0.001) in a cohort of patients with T2DM with DR (n = 20), compared with diabetic subjects without DR (n = 10) and healthy individuals (n = 10). These associations persisted significant after adjustment for age, gender, and HbA1c. The circulating levels of these miRNAs correlated with severity of the disease and their concomitant evaluation showed high accuracy for identifying DR (AUROC = 0.93; P < 0.001). Gene ontology analysis of validated targets revealed enrichment in pathways such as regulation of metabolic process (P = 1.5 × 10), of cell response to stress (P = 1.9 × 10), and development of blood vessels (P = 2.7 × 10). Pending external validation, we anticipate that these miRNAs may serve as putative disease biomarkers and highlight novel molecular targets for improving care of patients with diabetic retinopathy.
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http://dx.doi.org/10.1038/s41598-021-83047-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892881PMC
February 2021

Chest Imaging of Patients with Sarcoidosis and SARS-CoV-2 Infection. Current Evidence and Clinical Perspectives.

Diagnostics (Basel) 2021 Jan 27;11(2). Epub 2021 Jan 27.

COVID-19 Medicine Unit and Geriatrics Clinic, "SS Annunziata" Hospital of Chieti, Department of Medicine and Science of Aging and CAST, "G D'Annunzio" University of Chieti, 66100 Chieti, Italy.

The recent COVID-19 pandemic has dramatically changed the world in the last months, leading to a serious global emergency related to a novel coronavirus infection that affects both sexes of all ages ubiquitously. Advanced age, cardiovascular comorbidity, and viral load have been hypothesized as some of the risk factors for severity, but their role in patients affected with other diseases, in particular immune disorders, such as sarcoidosis, and the specific interaction between these two diseases remains unclear. The two conditions might share similar imaging findings but have distinctive features that are here described. The recent development of complex imaging softwares, called deep learning techniques, opens new scenarios for the diagnosis and management.
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http://dx.doi.org/10.3390/diagnostics11020183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911338PMC
January 2021

Efficacy of canakinumab in mild or severe COVID-19 pneumonia.

Immun Inflamm Dis 2021 Jan 19. Epub 2021 Jan 19.

Department of Medicine and Science of Aging, Clinic of Infectious Diseases, University "G. d'Annunzio" Chieti-Pescara, Chieti, Italy.

Background: Clinicians all around the world are currently experiencing a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several therapeutic strategies have been used until now but, to date, there is no specific therapy to treat SARS-CoV-2 infection. In this study, we used canakinumab, a human monoclonal antibody targeting interleukin-1 beta to improve respiratory function and laboratory parameters compared with standard therapy (hydroxycloroquine plus lopinavir/ritonavir).

Methods: We enrolled 34 patients with mild or severe non intensive care unit (ICU) coronavirus disease 2019 (COVID-19): 17 patients treated with standard therapy and 17 patients treated with a subcutaneous single dose of canakinumab 300 mg. We collected data about oxygen supports and laboratory parameters such as inflammation indices and hemogasanalysis. We compared the data collected before the administration of canakinumab (T0), 3 days after T0 (T1) and 7 days after T0 (T2) with the same data from patients taking the standard therapy.

Results: We observed a reduction in inflammation indices and a significant and rapid increase in P/F ratio in canakinumab group, with improvement of 60.3% after the administration. We reported a significant reduction in oxygen flow in patients treated with canakinumab (-28.6% at T1 vs. T0 and -40.0% at T2 vs. T1). Conversely, the standard group increased the supply of high oxygen at T1 versus T0 (+66.7%), but reduced oxygen flows at T2 versus T1 (-40.0%).

Conclusion: In hospitalized adult patients with mild or severe non ICU COVID-19, canakinumab could be a valid therapeutic option. Canakinumab therapy causes rapid and long-lasting improvement in oxygenation levels in the absence of any severe adverse events.
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http://dx.doi.org/10.1002/iid3.400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013503PMC
January 2021

Prognostic value of daytime and nighttime blood pressure in treated hypertensive patients according to age and sex.

J Clin Hypertens (Greenwich) 2020 11 10;22(11):2014-2021. Epub 2020 Sep 10.

Department of Medical, Oral and Biotechnological Sciences, University "Gabriele d'Annunzio," Chieti-Pescara, Chieti, Italy.

The authors assessed the prognostic value of daytime and nighttime blood pressure (BP) in adult (≤65 years) or old (> 65 years) women or men with treated hypertension. Cardiovascular outcomes were evaluated in 2264 patients. During the follow-up (mean 10 years), 523 cardiovascular events occurred. After adjustment for covariates, both daytime and nighttime systolic BP were always associated with outcomes, that is, hazard ratio (95% confidence interval per 10 mm Hg increment) 1.22 (1.04-1.43) and 1.20 (1.04-1.37), respectively, in adult women, 1.30 (1.18-1.43) and 1.21 (1.10-1.33), respectively, in adult men, 1.21 (1.10-1.33) and 1.18 (1.07-1.31), respectively, in old women, and 1.16 (1.01-1.33) and 1.28 (1.14-1.44), respectively, in old men. When daytime and nighttime systolic BP were further and mutually adjusted, daytime and nighttime BP had comparable prognostic value in adult and old women, daytime BP remained associated with outcomes in adult men (hazard ratio 1.40, 95% confidence interval 1.13-1.74 per 10 mm Hg increment), and nighttime BP remained associated with outcomes in old men (hazard ratio 1.35, 95% confidence interval 1.11-1.64 per 10 mm Hg increment). Daytime and nighttime systolic BP have similar prognostic impact in adult and old women with treated hypertension, whereas daytime BP is a stronger predictor of risk in adult men and nighttime BP is a stronger predictor of risk in old men.
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http://dx.doi.org/10.1111/jch.14028DOI Listing
November 2020

Role of shear-wave and strain elastography to differentiate malignant vs benign subpleural lung lesions.

Medicine (Baltimore) 2021 Jan;100(1):e24123

Unit of Ultrasound in Internal Medicine, Department of Medicine and Science of Aging, "G. d'Annunzio" University.

Abstract: Elastosonography is a non-invasive diagnostic method to evaluate tissue stiffness. The aim of our study was to demonstrate the applicability and efficacy of elastosonography to differentiate benign vs malignant subpleural lung lesions compared to clinical, radiological and histological findings.We performed both strain and shear wave velocity (SWV) elastosonography on subpleural lung lesions. Moreover, we elaborated a composite score called "elasto index".Fourteen patients, 10 males and 4 females were recruited. On strain elastography, 9 lesions showed a hard pattern (type 3), 3 lesions showed an intermediate pattern (type 2), and 2 lesions a soft pattern (type 1). All lesions showed a mean SWV value of 4.46 ± 2.37 m/second. The mean SWV for malignant lesions (n = 6) was 5.92 ± 2.8 m/second. The mean SWV for benign lesions (n = 8) was 3.36 ± 1.20 m/second. SWV shows an area under the curve (AUC) of 0.792, and the Youden index shows a value of 3.6 m/second. The ROC curve elaborated for the diagnosis of malignancy by strain elastography showed an AUC of 0.688. ROC curve for the diagnosis of malignancy by elasto index demonstrated an AUC of 0.802.SWV values obtained by ARFI elastosonographic method are higher in malignant lung lesions (mean SWV: 5.92 m/second) than in benign ones (mean SWV: 3.36); a composite score (elasto index) is characterized by better statistical significance for the differentiation of the lesions.
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http://dx.doi.org/10.1097/MD.0000000000024123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793371PMC
January 2021

Heparin in COVID-19 Patients Is Associated with Reduced In-Hospital Mortality: the Multicenter Italian CORIST Study.

Authors:
Augusto Di Castelnuovo Simona Costanzo Andrea Antinori Nausicaa Berselli Lorenzo Blandi Marialaura Bonaccio Roberto Cauda Giovanni Guaraldi Lorenzo Menicanti Marco Mennuni Giustino Parruti Giuseppe Patti Francesca Santilli Carlo Signorelli Alessandra Vergori Pasquale Abete Walter Ageno Antonella Agodi Piergiuseppe Agostoni Luca Aiello Samir Al Moghazi Rosa Arboretti Marinella Astuto Filippo Aucella Greta Barbieri Alessandro Bartoloni Paolo Bonfanti Francesco Cacciatore Lucia Caiano Laura Carrozzi Antonio Cascio Arturo Ciccullo Antonella Cingolani Francesco Cipollone Claudia Colomba Crizia Colombo Francesca Crosta Gian Battista Danzi Damiano D'Ardes Katleen de Gaetano Donati Francesco Di Gennaro Giuseppe Di Tano Gianpiero D'Offizi Massimo Fantoni Francesco Maria Fusco Ivan Gentile Francesco Gianfagna Elvira Grandone Emauele Graziani Leonardo Grisafi Gabriella Guarnieri Giovanni Larizza Armando Leone Gloria Maccagni Ferruccio Madaro Stefano Maitan Sandro Mancarella Massimo Mapelli Riccardo Maragna Rossella Marcucci Giulio Maresca Silvia Marongiu Claudia Marotta Lorenzo Marra Franco Mastroianni Maria Mazzitelli Alessandro Mengozzi Francesco Menichetti Marianna Meschiari Jovana Milic Filippo Minutolo Beatrice Molena Arturo Montineri Cristina Mussini Maria Musso Daniela Niola Anna Odone Marco Olivieri Antonella Palimodde Roberta Parisi Emanuela Pasi Raffaele Pesavento Francesco Petri Biagio Pinchera Venerino Poletti Claudia Ravaglia Andrea Rognoni Marco Rossato Marianna Rossi Vincenzo Sangiovanni Carlo Sanrocco Laura Scorzolini Raffaella Sgariglia Paola Giustina Simeone Eleonora Taddei Carlo Torti Roberto Vettor Andrea Vianello Marco Vinceti Alexandra Virano Laura Vocciante Raffaele De Caterina Licia Iacoviello

Thromb Haemost 2021 Jan 7. Epub 2021 Jan 7.

Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Isernia, Italy.

Introduction:  A hypercoagulable condition was described in patients with coronavirus disease 2019 (COVID-19) and proposed as a possible pathogenic mechanism contributing to disease progression and lethality.

Aim:  We evaluated if in-hospital administration of heparin improved survival in a large cohort of Italian COVID-19 patients.

Methods:  In a retrospective observational study, 2,574 unselected patients hospitalized in 30 clinical centers in Italy from February 19, 2020 to June 5, 2020 with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection were analyzed. The primary endpoint in a time-to event analysis was in-hospital death, comparing patients who received heparin (low-molecular-weight heparin [LMWH] or unfractionated heparin [UFH]) with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores.

Results:  Out of 2,574 COVID-19 patients, 70.1% received heparin. LMWH was largely the most used formulation (99.5%). Death rates for patients receiving heparin or not were 7.4 and 14.0 per 1,000 person-days, respectively. After adjustment for propensity scores, we found a 40% lower risk of death in patients receiving heparin (hazard ratio = 0.60; 95% confidence interval: 0.49-0.74; E-value = 2.04). This association was particularly evident in patients with a higher severity of disease or strong coagulation activation.

Conclusion:  In-hospital heparin treatment was associated with a lower mortality, particularly in severely ill COVID-19 patients and in those with strong coagulation activation. The results from randomized clinical trials are eagerly awaited to provide clear-cut recommendations.
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http://dx.doi.org/10.1055/a-1347-6070DOI Listing
January 2021

Smell and Taste in Severe CoViD-19: Self-Reported vs. Testing.

Front Med (Lausanne) 2020 2;7:589409. Epub 2020 Dec 2.

Neurophysiology, Olfaction and Chemoreception Laboratory, Physiology and Physiopathology Section, Neuroscience, Imaging and Clinical Sciences Department, 'G. d'Annunzio' University of Chieti-Pescara, Chieti, Italy.

One of the most striking reported symptoms in CoViD-19 is loss of smell and taste. The frequency of these impairments and their specificity as a potential central nervous system function biomarker are of great interest as a diagnostic clue for CoViD-19 infection as opposed to other similar symptomatologic diseases and because of their implication in viral pathogenesis. Here severe CoViD-19 was investigated by comparing self-report vs. testing of smell and taste, thus the objective severity of olfactory impairment and their possible correlation with other symptoms. Because a significant discrepancy between smell and taste testing vs. self-report results ( < 0.001) emerges in our result, we performed a statistical analysis highlighting disagreement among normosmia ( < 0.05), hyposmia, severe hyposmia, and anosmia ( < 0.001) and, in hypogeusia and severe hypogeusia, while no differences are observed in normogeusia and ageusia. Therefore, we analyzed the olfactory threshold by an objective test revealing the distribution of hyposmic (34%), severe hyposmic (48%), and anosmic (13%) patients in severe CoViD-19. In severe CoViD-19 patients, taste is lost in 4.3% of normosmic individuals, 31.9% of hyposmic individuals, 46.8% of severe hyposmic individuals, and 17% of anosmic individuals. Moreover, 95% of 100 CoViD-19 patients objectively tested were affected by smell dysfunction, while 47% were affected by taste dysfunction. Furthermore, analysis by objective testing also highlighted that the severity of smell dysfunction in CoViD-19 subjects did not correlate with age and sex. In conclusion, we report by objective testing that the majority of CoViD-19 patients report severe anosmia, that most of the subjects have olfactory impairment rather than taste impairment, and, finally, that the olfactory impairment correlate with symptom onset and hospitalization ( < 0.05). Patients who exhibit severe olfactory impairment had been hospitalized for about a week from symptom onset; double time has taken place in subjects with normosmia. Our results may be limited by the relatively small number of study participants, but these suggest by objective testing that hyposmia, severe hyposmia, and anosmia may relate directly to infection severity and neurological damage. The smell test assessment could be a potential screening symptom that might contribute to the decision to test suspected cases or guide quarantine instructions, further therapeutic approach, and evaluation of neurological damage.
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http://dx.doi.org/10.3389/fmed.2020.589409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745760PMC
December 2020

Ambulatory blood pressure and risk of new-onset atrial fibrillation in treated hypertensive patients.

J Clin Hypertens (Greenwich) 2021 Jan 26;23(1):147-152. Epub 2020 Nov 26.

Department of Medical, Oral and Biotechnological Sciences, University "Gabriele d'Annunzio", Chieti, Italy.

The aim of this study was to evaluate the influence of clinic and ambulatory blood pressure (BP) on the occurrence of new-onset atrial fibrillation (AF) in treated hypertensive patients. We studied 2135 sequential treated hypertensive patients aged >40 years. During the follow-up (mean 9.7 years, range 0.4-20 years), 116 events (new-onset AF) occurred. In univariate analysis, clinic, daytime, nighttime, and 24-h systolic BP were all significantly associated with increased risk of new-onset AF, that is, hazard ratio (95% confidence interval) per 10 mm Hg increment 1.22 (1.11-1.35), 1.36 (1.21-1.53), 1.42 (1.29-1.57), and 1.42 (1.26-1.60), respectively. After adjustment for various covariates in multivariate analysis, clinic systolic BP was no longer associated with increased risk of new-onset AF, whereas daytime, nighttime, and 24-h systolic BP remained significantly associated with outcome, that is, hazard ratio (95% confidence interval) per 10 mm Hg increment 1.09 (0.97-1.23), 1.23 (1.10-1.39), 1.16 (1.03-1.31), and 1.22 (1.06-1.40), respectively. Daytime, nighttime, and 24-h systolic BP are superior to clinic systolic BP in predicting new-onset AF in treated hypertensive patients. Future studies are needed to evaluate whether a better control of ambulatory BP might be helpful in reducing the occurrence of new-onset AF.
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http://dx.doi.org/10.1111/jch.14112DOI Listing
January 2021

Risk of Atrial Fibrillation in Masked and White Coat Uncontrolled Hypertension.

Am J Hypertens 2020 Nov 13. Epub 2020 Nov 13.

Department of Medical, Oral and Biotechnological Sciences, University "Gabriele d'Annunzio", Chieti-Pescara, Chieti, Italy.

Background: Risk of atrial fibrillation (AF) in masked and white coat uncontrolled hypertension (MUCH and WUCH, respectively) has not yet been investigated. We assessed the risk of new-onset AF in MUCH and WUCH detected by ambulatory blood pressure (BP) monitoring.

Methods: The occurrence of AF was evaluated in 2135 treated hypertensive patients aged >40 years, with baseline sinus rhythm, by electrocardiogram. Controlled hypertension (CH) was defined as clinic BP <140/90 mmHg and daytime BP, regardless of nighttime BP, <135/85 mmHg, MUCH as clinic BP <140/90 mmHg and daytime BP ≥135 and/or ≥85 mmHg, WUCH as clinic BP >140 and/or >90 mmHg and daytime BP <135/85 mmHg and sustained uncontrolled hypertension (SUCH) as clinic BP >140 and/or >90 mmHg and daytime BP >135 and/or >85 mmHg.

Results: MUCH was identified in 203 patients (9.5% of all the population, 29% of those with normal clinic BP) and WUCH in 503 patients (23.5% of all the population, 35% of those with high clinic BP). During the follow-up (mean 9.7 years), 116 cases of AF occurred. After adjustment for covariates, patients with MUCH (hazard ratio (HR) 2.02, 95% confidence interval (CI) 1.06-3.85) and SUCH (HR 1.83, 95% CI, 1.04-3.21) had higher risk of new-onset AF than those with CH, whereas those with WUCH (HR 1.12, 95% CI, 0.59-2.13) did not.

Conclusions: When compared to patients with CH, those with MUCH and SUCH are at higher risk (approximately doubled) of new-onset AF, whereas those with WUCH are not.
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http://dx.doi.org/10.1093/ajh/hpaa185DOI Listing
November 2020

Low molecular weight heparin in COVID-19 patients prevents delirium and shortens hospitalization.

Neurol Sci 2021 Apr 13;42(4):1527-1530. Epub 2020 Nov 13.

Department of Neuroscience, Imaging and Clinical Sciences, University G. d'Annunzio of Chieti-Pescara, Chieti, Italy.

Background: COVID-19 patients present with delirium during their hospitalization.

Aims: To assess the incidence of delirium in hospitalized COVID-19 patients and analyze the possible association with demographic, clinical, laboratory, and pharmacological factors.

Methods: COVID-19 patients were assessed for clinical signs of delirium and administered the assessment test for delirium and cognitive impairment (4AT) and the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) scales.

Results: Out of the 56 patients of our cohort, 14 (25.0%) experienced delirium. The use of low molecular weight heparin (LMWH) (enoxaparin 1 mg/kg/daily) was less frequent in patients with delirium (p = 0.004) and was accompanied by lower C reactive protein (CRP) levels (p = 0.006).

Discussion: The use of LMWH was associated with absence of delirium, independently of comorbidities and age.

Conclusions: The use of LMWH may help preventing the occurrence of delirium in COVID-19 patients, with possible reduction of length of stay in the hospital and sequelae.
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http://dx.doi.org/10.1007/s10072-020-04887-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664586PMC
April 2021

SARS-CoV-2 and Oral Manifestation: An Observational, Human Study.

J Clin Med 2020 Oct 7;9(10). Epub 2020 Oct 7.

Clinica Medica Institute, Department of Medicine and Aging Sciences, University "Gabriele d'Annunzio", Chieti-Pescara, 66100 Chieti, Italy.

The correlation between SARS-CoV-2 and oral manifestations is still controversial. The aim of this observational study was to determine the oral manifestation of the hospitalized patients for COVID-19. A total of 20 patients met the inclusion criteria and gave their signed informed consent. A questionnaire of 32 questions regarding the oral and systemic health condition was administrated to these patients during the convalescence. A descriptive statistic was performed. Data were analysed through the use of χ test, to assess the statistical significance. A statistically significant increase of about 30% of reporting xerostomia during hospitalization was observed ( = 0.02). Meanwhile, a decrease of oral hygiene was observed during the hospitalization, even if a non-statistically significant difference was shown between the two study time points (before and after hospitalization). During the hospitalization period, 25% of patients reported impaired taste, 15% burning sensation, and 20% difficulty in swallowing. An interesting result was that among the systemic conditions, hypertension was observed in 39% of patients and mostly in female patients (62.5%). Further studies are necessary to better understand the symptoms of this new virus in order to faster detect its presence in humans. Probably, a multidisciplinary team following the COVID-19 patients could be of key importance in treating this disease.
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http://dx.doi.org/10.3390/jcm9103218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600761PMC
October 2020

CT Findings in Pulmonary and Abdominal Sarcoidosis. Implications for Diagnosis and Classification.

J Clin Med 2020 Sep 20;9(9). Epub 2020 Sep 20.

Geriatrics Clinic, Department of Medicine and Science of Aging, "G. D'Annunzio" University of Chieti, 66100 Chieti, Italy.

Sarcoidosis is a granulomatous disorder of unknown etiology characterized by noncaseating granulomas virtually in every organ and tissue. This finding represents the most important diagnostic clue to reach a correct definition of sarcoidosis, although the biopsy is invasive and has several risk procedures. Several efforts are made to suspect the diagnosis of sarcoidosis by combining noninvasive elements, in particular from imaging, though these findings are often nonspecific and reflect the wide multifactorial pathogenesis. Every effort should be made to obtain a detailed radiological picture that, if associated with a suggestive clinical picture, could avoid the need of biopsy in some specific cases. In this narrative review, we aim to describe main computed tomography (CT) features of pulmonary and abdominal sarcoidosis, by reporting strengths and limits of this technique, in particular for the identification of extrapulmonary, isolated disease.
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http://dx.doi.org/10.3390/jcm9093028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565100PMC
September 2020

Common cardiovascular risk factors and in-hospital mortality in 3,894 patients with COVID-19: survival analysis and machine learning-based findings from the multicentre Italian CORIST Study.

Authors:
Augusto Di Castelnuovo Marialaura Bonaccio Simona Costanzo Alessandro Gialluisi Andrea Antinori Nausicaa Berselli Lorenzo Blandi Raffaele Bruno Roberto Cauda Giovanni Guaraldi Ilaria My Lorenzo Menicanti Giustino Parruti Giuseppe Patti Stefano Perlini Francesca Santilli Carlo Signorelli Giulio G Stefanini Alessandra Vergori Amina Abdeddaim Walter Ageno Antonella Agodi Piergiuseppe Agostoni Luca Aiello Samir Al Moghazi Filippo Aucella Greta Barbieri Alessandro Bartoloni Carolina Bologna Paolo Bonfanti Serena Brancati Francesco Cacciatore Lucia Caiano Francesco Cannata Laura Carrozzi Antonio Cascio Antonella Cingolani Francesco Cipollone Claudia Colomba Annalisa Crisetti Francesca Crosta Gian B Danzi Damiano D'Ardes Katleen de Gaetano Donati Francesco Di Gennaro Gisella Di Palma Giuseppe Di Tano Massimo Fantoni Tommaso Filippini Paola Fioretto Francesco M Fusco Ivan Gentile Leonardo Grisafi Gabriella Guarnieri Francesco Landi Giovanni Larizza Armando Leone Gloria Maccagni Sandro Maccarella Massimo Mapelli Riccardo Maragna Rossella Marcucci Giulio Maresca Claudia Marotta Lorenzo Marra Franco Mastroianni Alessandro Mengozzi Francesco Menichetti Jovana Milic Rita Murri Arturo Montineri Roberta Mussinelli Cristina Mussini Maria Musso Anna Odone Marco Olivieri Emanuela Pasi Francesco Petri Biagio Pinchera Carlo A Pivato Roberto Pizzi Venerino Poletti Francesca Raffaelli Claudia Ravaglia Giulia Righetti Andrea Rognoni Marco Rossato Marianna Rossi Anna Sabena Francesco Salinaro Vincenzo Sangiovanni Carlo Sanrocco Antonio Scarafino Laura Scorzolini Raffaella Sgariglia Paola G Simeone Enrico Spinoni Carlo Torti Enrico M Trecarichi Francesca Vezzani Giovanni Veronesi Roberto Vettor Andrea Vianello Marco Vinceti Raffaele De Caterina Licia Iacoviello

Nutr Metab Cardiovasc Dis 2020 10 31;30(11):1899-1913. Epub 2020 Jul 31.

Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, IS, Italy; Department of Medicine and Surgery, University of Insubria, Varese, Italy. Electronic address:

Background And Aims: There is poor knowledge on characteristics, comorbidities and laboratory measures associated with risk for adverse outcomes and in-hospital mortality in European Countries. We aimed at identifying baseline characteristics predisposing COVID-19 patients to in-hospital death.

Methods And Results: Retrospective observational study on 3894 patients with SARS-CoV-2 infection hospitalized from February 19th to May 23rd, 2020 and recruited in 30 clinical centres distributed throughout Italy. Machine learning (random forest)-based and Cox survival analysis. 61.7% of participants were men (median age 67 years), followed up for a median of 13 days. In-hospital mortality exhibited a geographical gradient, Northern Italian regions featuring more than twofold higher death rates as compared to Central/Southern areas (15.6% vs 6.4%, respectively). Machine learning analysis revealed that the most important features in death classification were impaired renal function, elevated C reactive protein and advanced age. These findings were confirmed by multivariable Cox survival analysis (hazard ratio (HR): 8.2; 95% confidence interval (CI) 4.6-14.7 for age ≥85 vs 18-44 y); HR = 4.7; 2.9-7.7 for estimated glomerular filtration rate levels <15 vs ≥ 90 mL/min/1.73 m; HR = 2.3; 1.5-3.6 for C-reactive protein levels ≥10 vs ≤ 3 mg/L). No relation was found with obesity, tobacco use, cardiovascular disease and related-comorbidities. The associations between these variables and mortality were substantially homogenous across all sub-groups analyses.

Conclusions: Impaired renal function, elevated C-reactive protein and advanced age were major predictors of in-hospital death in a large cohort of unselected patients with COVID-19, admitted to 30 different clinical centres all over Italy.
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http://dx.doi.org/10.1016/j.numecd.2020.07.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833278PMC
October 2020

Duration of COVID-19: Data from an Italian Cohort and Potential Role for Steroids.

Microorganisms 2020 Aug 31;8(9). Epub 2020 Aug 31.

"Clinica Medica" Institute, Department of "Medicine and Science of Aging", "G. d'Annunzio" University, 66100 Chieti, Italy.

The diffusion of SARS-CoV-2, starting from China in December 2019, has led to a pandemic, reaching Italy in February 2020. Previous studies in Asia have shown that the median duration of SARS-CoV-2 viral shedding was approximately 12-20 days. We considered a cohort of patients recovered from COVID-19 showing that the median disease duration between onset and end of COVID-19 symptoms was 27.5 days (interquartile range (IQR): 17.0-33.2) and that the median duration between onset of symptoms and microbiological healing, defined by two consecutive negative nasopharyngeal swabs, was 38 days (IQR: 31.7-50.2). A longer duration of COVID-19 with delayed clinical healing (symptom-free) occurred in patients presenting at admission a lower PaO/FiO ratio ( < 0.001), a more severe clinical presentation ( = 0.001) and a lower lymphocyte count ( = 0.035). Moreover, patients presenting at admission a lower PaO/FiO ratio and more severe disease showed longer viral shedding ( = 0.031 and = 0.032, respectively). In addition, patients treated with corticosteroids had delayed clinical healing ( = 0.013).
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http://dx.doi.org/10.3390/microorganisms8091327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564504PMC
August 2020

Canakinumab in a subgroup of patients with COVID-19.

Lancet Rheumatol 2020 Aug 4;2(8):e457-ee458. Epub 2020 Jun 4.

Clinic of Infectious Diseases, Department of Medicine and Science of Aging, G. d'Annunzio University of Chieti-Pescara, Chieti 66100, Italy.

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http://dx.doi.org/10.1016/S2665-9913(20)30167-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272172PMC
August 2020

Is Albumin Predictor of Mortality in COVID-19?

Antioxid Redox Signal 2020 Jun 22. Epub 2020 Jun 22.

Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.

Coronavirus 2019 (COVID-19) is a pandemic associated with a high risk of mortality. Human serum albumin (HSA) is an acute phase reactant with antioxidant property; however, its behavior and impact on survival in COVID-19 patients have never been studied so far. Among 319 COVID-19 patients followed up for a median of 19 days, 64 died. Compared with survivors, nonsurvivors had more prevalence of intensive care unit (ICU) admission, chronic obstructive pulmonary disease (COPD), heart failure, elevated levels of D-dimer, high-sensitivity C reactive protein (hs-CRP) and troponins, and lower values of albumin. At the Cox regression analysis, albumin (hazard ratio [HR]: 0.38, 95% confidence interval [CI]: 0.23-0.63,  < 0.001) and age (HR: 1.03, 95% CI: 1.01-1.06,  = 0.001) were independently associated with mortality, irrespective of adjustment for gender, ICU admission, heart failure, COPD, and hs-CRP levels. Our observation leads to the hypothesis that HSA analysis may be used to identify patients at higher risk of death in COVID-19 patients.
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http://dx.doi.org/10.1089/ars.2020.8142DOI Listing
June 2020

Long-term Positivity to SARS-CoV-2: A Clinical Case of COVID-19 with Persistent Evidence of Infection.

Eur J Case Rep Intern Med 2020 11;7(6):001707. Epub 2020 May 11.

Internal Medicine, Department of Medicine and Science of Aging, 'G. D'Annunzio' University, Chieti, Italy.

In December 2019, an outbreak of a new coronavirus (SARS-CoV-2) was reported in Hubei province in China. The disease has since spread worldwide and the World Health Organization declared it a pandemic on 11 March 2020. We describe the case of a 65-year-old woman who clinically recovered from COVID-19 but showed persistent infection with SARS-CoV-2 for 51 days.

Learning Points: A case of persistent infection with SARS-CoV-2 is described.Some tests may pick up viral RNA fragments, giving a false positive result.The quarantining of infected patients to limit possible SARS-CoV-2 spread is important.
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http://dx.doi.org/10.12890/2020_001707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279900PMC
May 2020

Prognostic Value of Masked Uncontrolled Hypertension Defined by Different Ambulatory Blood Pressure Criteria.

Am J Hypertens 2020 08;33(8):726-733

Department of Medical, Oral and Biotechnological Sciences, University "Gabriele d'Annunzio", Chieti-Pescara, Chieti, Italy.

Background: Masked uncontrolled hypertension (MUCH), that is, nonhypertensive clinic but high out-of-office blood pressure (BP) in treated patients is at increased cardiovascular risk than controlled hypertension (CH), that is, nonhypertensive clinic and out-of-office BP. Using ambulatory BP, MUCH can be defined as daytime and/or nighttime and/or 24-hour BP above thresholds. It is unclear whether different definitions of MUCH have similar prognostic information. This study assessed the prognostic value of MUCH defined by different ambulatory BP criteria.

Methods: Cardiovascular events were evaluated in 738 treated hypertensive patients with nonhypertensive clinic BP. Among them, participants were classified as having CH or daytime MUCH (BP ≥135/85 mm Hg) regardless of nighttime BP (group 1), nighttime MUCH (BP ≥120/70 mm Hg) regardless of daytime BP (group 2), 24-hour MUCH (BP ≥130/80 mm Hg) regardless of daytime or nighttime BP (group 3), daytime MUCH only (group 4), nighttime MUCH only (group 5), and daytime + nighttime MUCH (group 6).

Results: We detected 215 (29%), 357 (48.5%), 275 (37%), 42 (5.5%),184 (25%) and 173 (23.5%) patients with MUCH from group 1 to 6, respectively. During the follow-up (10 ± 5 years), 148 events occurred in patients with CH and MUCH. After adjustment for covariates, compared with patients with CH, the adjusted hazard ratio (95% confidence interval) for cardiovascular events was 2.01 (1.45-2.79), 1.53 (1.09-2.15), 1.69 (1.22-2.34), 1.52 (0.80-2.91), 1.15 (0.74-1.80), and 2.29 (1.53-3.42) from group 1 to 6, respectively.

Conclusions: The prognostic impact of MUCH defined according to various ambulatory BP definitions may be different.
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http://dx.doi.org/10.1093/ajh/hpaa078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402227PMC
August 2020

A Case of Coinfection with SARS-COV-2 and Cytomegalovirus in the Era of COVID-19.

Eur J Case Rep Intern Med 2020 11;7(5):001652. Epub 2020 Apr 11.

Internal Medicine, Department of Medicine and Science of Aging, 'G. D'Annunzio' University, Chieti, Italy.

The World Health Organization has declared novel coronavirus disease 2019 (COVID-19) an international public health emergency. We describe the case of a 92-year-old woman who was admitted to our unit with fever and chills with laboratory evidence of coinfection with SARS-CoV-2 and cytomegalovirus.

Learning Points: This is the first reported case of coinfection with SARS-CoV-2 and cytomegalovirus.
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http://dx.doi.org/10.12890/2020_001652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213827PMC
April 2020

COVID-19 and RAS: Unravelling an Unclear Relationship.

Int J Mol Sci 2020 Apr 24;21(8). Epub 2020 Apr 24.

Clinica Medica Institute, European Center of Excellence on Atherosclerosis, Hypertension and Dyslipidemia, "G. D'Annunzio" University of Chieti-Pescara, 66100 Chieti, Italy.

The renin-angiotensin system (RAS) plays a main role in regulating blood pressure and electrolyte and liquid balance. Previous evidence suggests that RAS may represent an important target for the treatment of lung pathologies, especially for acute respiratory distress syndrome and chronic fibrotic disease. The scientific community has recently focused its attention on angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor 1 (AT1R) inhibitors and their possible benefit/harms for patients infected by Coronavirus disease (COVID-19) who experience pneumonia, but there are still some doubts about the effects of these drugs in this setting.
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http://dx.doi.org/10.3390/ijms21083003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215550PMC
April 2020

Thoracic ultrasound and SARS-COVID-19: a pictorial essay.

J Ultrasound 2020 Jun 16;23(2):217-221. Epub 2020 Apr 16.

Internistic Ultrasound Unit, SS Annunziata Hospital, "G. d'Annunzio" University, via dei Vestini, 66100, Chieti, Italy.

Thoracic ultrasound seems to adapt to the screening for lung involvement of patients with suspected or ascertained SARS-COVID-19 infection due to its characteristics of easy applicability. It can be also a relevant method in monitoring patients. B lines are early finding of COVID-19, even in mild-symptomatic subjects; in the most serious cases such as pre-ARDS or ARDS, the B lines end up filling the ultrasound image almost completely, until it merges, so as to create a single hyperechoic image named as "white lung", with distortion and irregularity of the pleural line. In advanced stage, lung consolidations are present, representing pulmonary pathological areas that are no longer normally ventilated.
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http://dx.doi.org/10.1007/s40477-020-00458-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159975PMC
June 2020

Liraglutide improves memory in obese patients with prediabetes or early type 2 diabetes: a randomized, controlled study.

Int J Obes (Lond) 2020 06 21;44(6):1254-1263. Epub 2020 Jan 21.

Department of Medicine and Aging, Center of Aging Science and Translational Medicine (CESI-Met), Via Luigi Polacchi, Chieti, Italy.

Background/objectives: Diabetic subjects are at increased risk of subtle cognitive impairment since the disease early stages and of dementia later in life. In animal models, glucagon-like peptide-1 receptor agonizts (GLP1-RAs) have been shown to exert neuroprotective effects, expecially in the memory domain. We assessed whether treatment with a GLP1-RA might affect cognitive functions in type 2 diabetic subjects independently on the weight loss it might induce.

Subjects/methods: Forty metformin-treated obese subjects with prediabetes or newly diagnosed type 2 diabetes mellitus, received liraglutide (1.8 mg/d) (n = 20) or lifestyle counseling (dietary intervention and exercise training) (n = 20) until achieving a modest and comparable weight loss (-7% of initial body weight).

Interventions/methods: A detailed neuropsychological assessment before and after weight loss was completed in 16 patients per arm, who were administered a total of seven psychological tests, thus assessing three composite domain z-scores for attention, memory, and executive control.

Results: After comparable weight loss and superimposable glycemic control and insulin sensitivity, a significant increase in short term memory (mean Digit Span Z score from -0.06 to 0.80, p = 0.024) and memory composite z-score (mean memory z-score from -0.67 to 0.032, p = 0.0065) was observed in the liraglutide exposed subjects (between group p = 0.041 and p = 0.033, respectively).

Conclusions: Liraglutide might slow down memory function decline in diabetic patients in early, and possibly preclinical stages of the disease.
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http://dx.doi.org/10.1038/s41366-020-0535-5DOI Listing
June 2020

Co-occurrence of pain syndromes.

J Neural Transm (Vienna) 2020 04 29;127(4):625-646. Epub 2019 Nov 29.

Department of Medicine and Science of Aging and Ce.S.I.Met, Geriatrics Clinic, "G. D'Annunzio" University of Chieti, Chieti, Italy.

Many pain conditions in patients tend to co-occur, influencing the clinical expressions of each other in various ways. This paper summarizes the main concurrent pain conditions by analyzing the major interactions observed. In particular, co-occurrence will be examined in: visceral pain (especially ischemic heart disease, irritable bowel syndrome, dysmenorrhea/endometriosis and urinary pain), fibromyalgia, musculoskeletal pain and headache. Two concurrent visceral pains from internal organs sharing at least part of their central sensory projection can give rise to viscero-visceral hyperalgesia, i.e., enhancement of typical pain symptoms from both districts. Visceral pain, headache and musculoskeletal pains (myofascial pain from trigger points, joint pain) can enhance pain and hyperalgesia from fibromyalgia. Myofascial pain from trigger points can perpetuate pain symptoms from visceral pain conditions and trigger migraine attacks when located in the referred pain area from an internal organ or in cervico-facial areas, respectively. The pathophysiology of these pain associations is complex and probably multifactorial; among the possible processes underlying the mutual influence of symptoms recorded in the associations is modulation of central sensitization phenomena by nociceptive inputs from one or the other condition. A strong message in these pain syndrome co-occurrence is that effective treatment of one of the conditions can also improve symptoms from the other, thus suggesting a systematic and thorough evaluation of the pain patient for a global effective management of his/her suffering.
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http://dx.doi.org/10.1007/s00702-019-02107-8DOI Listing
April 2020

Cardiovascular Risk in Non-Alcoholic Fatty Liver Disease: Mechanisms and Therapeutic Implications.

Int J Environ Res Public Health 2019 08 26;16(17). Epub 2019 Aug 26.

Internal Medicine and Critical Subacute Care Unit, Medicine Geriatric-Rehabilitation Department and Department of Medicine and Surgery, University-Hospital of Parma, 43121 Parma, Italy.

New evidence suggests that non-alcoholic fatty liver disease (NAFLD) has a strong multifaceted relationship with diabetes and metabolic syndrome, and is associated with increased risk of cardiovascular events, regardless of traditional risk factors, such as hypertension, diabetes, dyslipidemia, and obesity. Given the pandemic-level rise of NAFLD-in parallel with the increasing prevalence of obesity and other components of the metabolic syndrome-and its association with poor cardiovascular outcomes, the question of how to manage NAFLD properly, in order to reduce the burden of associated incident cardiovascular events, is both timely and highly relevant. This review aims to summarize the current knowledge of the association between NAFLD and cardiovascular disease, and also to discuss possible clinical strategies for cardiovascular risk assessment, as well as the spectrum of available therapeutic strategies for the prevention and treatment of NAFLD and its downstream events.
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http://dx.doi.org/10.3390/ijerph16173104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747357PMC
August 2019

High dose rosuvastatin increases ABCA1 transporter in human atherosclerotic plaques in a cholesterol-independent fashion.

Int J Cardiol 2020 01 3;299:249-253. Epub 2019 Aug 3.

Clinical Research Center, Center of Excellence on Aging, Ce.S.I.-Me.T. "G. d'Annunzio University" Foundation, Chieti, Italy; Department of Medicine and Aging, "G. d'Annunzio" University, Chieti, Italy; Internal Medicine Department, European Center of Excellence on Atherosclerosis, Hypertension and Dyslipidemia, SS Annunziata Hospital, Chieti, Italy. Electronic address:

Background: ATP-binding cassette A1 (ABCA1) and G1 (ABCG1) mediate cholesterol efflux from lipid-laden macrophages, thus promoting anti-atherosclerotic outcomes. The mechanism(s) linking treatment with statins and ABCA1/ABCG1 in human atherosclerosis are not fully understood and require further investigation. Therefore, we studied whether short-term treatment with low- or high-dose rosuvastatin may affect ABCA1 and ABCG1 expression in human atherosclerotic plaques.

Methods: Seventy patients with severe stenosis of the internal carotid artery were randomized to receive low (10 mg/day) or high (40 mg/day) dose rosuvastatin for 12 weeks before elective endarterectomy. As controls, we analyzed a reference group of 10 plaques from subjects with hypercholesterolemia but not receiving statin treatment and an additional set of 11 plaques collected from normocholesterolemic patients. On atherosclerotic plaques, ABCA1 and ABCG1 expression was evaluated at RNA level by qPCR and at protein level by immunoblotting and immunohistochemistry.

Results: Both rosuvastatin doses were associated with lower plaque ABCA1 mRNA levels and with a trend toward reduction for ABCG1. However, ABCA1 protein was paradoxically higher in patients treated with high-dose rosuvastatin and was associated with lower levels of miR-33b-5p, a microRNA known as a regulator of ABCA1. Multivariate analyses showed that the effect is cholesterol-independent. Finally, no effects were found for ABCG1 protein.

Conclusions: High-dose rosuvastatin increases macrophage ABCA1 protein levels in human atherosclerotic plaque despite mRNA reduction in a mechanism unrelated to plasma cholesterol reduction and potentially involving miR-33b-5p. This pathway may reflect an additional feature contributing to the anti-atherosclerotic effect for high-dose rosuvastatin.

Trial Registration: ISRCTN16590640.
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http://dx.doi.org/10.1016/j.ijcard.2019.07.094DOI Listing
January 2020