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  • 1
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    Abstract 17744: In Vivo Platelet Activation and Aspirin Responsiveness in Type 1 Diabetes Mellitus
    Ovid Technologies (Wolters Kluwer Health) ; 2014
    In:  Circulation Vol. 130, No. suppl_2 ( 2014-11-25)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 130, No. suppl_2 ( 2014-11-25)
    Abstract: Introduction: While reduced responsiveness to low-dose aspirin has been associated with type 2 diabetes mellitus (T2DM), aspirin responsiveness remains unexplored in T1DM. Hypothesis: We investigated in vivo platelet activation, as reflected by the urinary excretion of 11-dehydro-TXB2 (TXM) and platelet COX-1 inhibition, as assessed by serum TXB2 (sTXB2), in uncomplicated, normotensive, normolipidemic T1DM subjects on insulin therapy. Methods: Upon informed consent, we enrolled 40 T1DM patients (26M, age 35±11yr, disease duration 16±11yr, BMI 24±2 kg/m2) and 10 healthy controls (6M, age 33±7yr). In 9 patients we assessed the stability of TXM excretion on 3 different visits. Thirty-one patients and all controls were given 100 mg daily aspirin for 21 days, and urinary TXM and sTXB2 were measured before and 24h after stopping aspirin. To assess the influence of glycemic variability on aspirin response, 26 patients underwent continuous glucose monitoring (CGM) for the first 24h after drug withdrawal. Results: TXM excretion in T1DM was significantly higher than in controls (930 [659-1358] vs 568 [385-619] pg/mg creatinine; p 〈 0.001) and quite stable across repeated sampling (p for linear trend = 0.755). By multivariate analysis, urinary TXM was associated with microalbuminuria (β=0.23; p=0.042) at baseline. The degree of inhibition at 24h after aspirin dosing was similar in T1DM and controls for both sTXB2 (98.2% vs 98.6%, p=0.607) and urinary TXM (68.8% vs 68.4%, p=0.962). CGM-derived mean and standard deviation glucose were not associated with sTXB2 or TXM inhibition at 24h. Conclusions: We conclude that enhanced platelet activation in T1DM is independent of glycemic control and associated with kidney/endothelial damage. Moreover, in contrast to T2DM, the response to aspirin is unchanged, suggesting that the metabolic disturbance per se is not responsible for altered pharmacodynamics.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.130.suppl_2.17744
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2014
    detail.hit.zdb_id: 1466401-X
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  • 2
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    Abstract 17186: In Vivo Platelet Activation in Impaired Glucose Tolerance and During Progression of Type 2 Diabetes: a Cross-sectional and Longitudinal Study
    Ovid Technologies (Wolters Kluwer Health) ; 2014
    In:  Circulation Vol. 130, No. suppl_2 ( 2014-11-25)
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    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 130, No. suppl_2 ( 2014-11-25)
    Abstract: Introduction: Impaired glucose tolerance (IGT) reflects the progression from normoglycemia to type 2 diabetes mellitus (DM). IGT and DM are associated with high cardiovascular disease (CVD) morbidity and mortality. Hypothesis: Enhanced platelet activation has been previously reported in DM, but whether this pertains to IGT is unknown. Methods: We investigated in vivo platelet activation, as reflected by the urinary excretion of 11-dehydro-TXB2 (TXM), in IGT and DM patients with a diagnosis documented either 〈 12 months (new-DM) or ≥12 months (established-DM) from study entry. Patients were studied repeatedly up to 46 months to assess changes in platelet activation over time. Some patients were given standard 500 kcal meals at 8am, 1 and 6pm and TXM was measured repeatedly during a 12-hr period. Results: We enrolled 49 IGT patients (19M, age 56±9 yrs), 59 new-DM (36M, 61±10 yrs) and 61 established-DM (34M, 62±7 yrs, DM duration 9.7±6.1 yrs) patients diagnosed according to the ADA criteria, not on antiplatelet drugs. Median TXM values at study entry were comparably enhanced in the 3 groups (1,189 [897-1,503], 1,277 [897-1,870] , and 1,217 [885-1,494] pg/mg creatinine in IGT, new- and established-DM, respectively; p=0.39). Urinary TXM excretion showed limited intra-subject variability over time, as shown in the Figure. There was no convincing evidence of a circadian variation in TXM excretion. Two-hour, post-meal glucose variations (8-10am or 1-3pm) did not affect subsequent TXM values. Conclusions: We conclude that the potential benefits and risks of antiplatelet therapy should be considered in IGT management, because persistent platelet activation might contribute to CVD progression and its thrombotic complications. Given the stability of high TXM excretion in DM, this non-invasive biomarker of platelet activation should be tested as a predictor of vascular events during long-term follow-up.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.130.suppl_2.17186
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2014
    detail.hit.zdb_id: 1466401-X
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  • 3
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    Impact of Glycemic Variability on Chromatin Remodeling, Oxidative Stress, and Endothelial Dysfunction in Patients With Type 2 Diabetes and With Target HbA1c Levels
    American Diabetes Association ; 2017
    In:  Diabetes Vol. 66, No. 9 ( 2017-09-01), p. 2472-2482
    Details
    In: Diabetes, American Diabetes Association, Vol. 66, No. 9 ( 2017-09-01), p. 2472-2482
    Abstract: Intensive glycemic control (IGC) targeting HbA1c fails to show an unequivocal reduction of macrovascular complications in type 2 diabetes (T2D); however, the underlying mechanisms remain elusive. Epigenetic changes are emerging as important mediators of cardiovascular damage and may play a role in this setting. This study investigated whether epigenetic regulation of the adaptor protein p66Shc, a key driver of mitochondrial oxidative stress, contributes to persistent vascular dysfunction in patients with T2D despite IGC. Thirty-nine patients with uncontrolled T2D (HbA1c & gt;7.5%) and 24 age- and sex-matched healthy control subjects were consecutively enrolled. IGC was implemented for 6 months in patients with T2D to achieve a target HbA1c of ≤7.0%. Brachial artery flow-mediated dilation (FMD), urinary 8-isoprostaglandin F2α (8-isoPGF2α), and epigenetic regulation of p66Shc were assessed at baseline and follow-up. Continuous glucose monitoring was performed to determine the mean amplitude of glycemic excursion (MAGE) and postprandial incremental area under the curve (AUCpp). At baseline, patients with T2D showed impaired FMD, increased urinary 8-isoPGF2α, and p66Shc upregulation in circulating monocytes compared with control subjects. FMD, 8-isoPGF2α, and p66Shc expression were not affected by IGC. DNA hypomethylation and histone 3 acetylation were found on the p66Shc promoter of patients with T2D, and IGC did not change such adverse epigenetic remodeling. Persistent downregulation of methyltransferase DNMT3b and deacetylase SIRT1 may explain the observed p66Shc-related epigenetic changes. MAGE and AUCpp but not HbA1c were independently associated with the altered epigenetic profile on the p66Shc promoter. Hence, glucose fluctuations contribute to chromatin remodeling and may explain persistent vascular dysfunction in patients with T2D with target HbA1c levels.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db17-0294
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2017
    detail.hit.zdb_id: 1501252-9
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  • 4
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    The additional value of lung cancer screening program in identifying unrecognized diseases
    Springer Science and Business Media LLC ; 2022
    In:  BMC Pulmonary Medicine Vol. 22, No. 1 ( 2022-12)
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    In: BMC Pulmonary Medicine, Springer Science and Business Media LLC, Vol. 22, No. 1 ( 2022-12)
    Abstract: A systematic examination of low-dose CT (LDCT) scan, beside lung nodules, may disclose the presence of undiagnosed diseases, improving the efficacy and the cost/efficacy of these programs. The study was aimed at evaluating the association between LDCT scan findings and non-oncologic and oncologic diseases. Methods The LDCT scan of participants to the “Un Respiro per la vita” ® lung cancer screening program were checked and abnormal findings, beside lung nodules, recorded. First admission to the acute care because of cardiovascular (CD), respiratory (RD) and oncological diseases (OD) in the following three years were retrieved. The association of LDCT scan abnormal findings with CD, RD and OD was assessed through univariable and multivariable logistic regression models. Results Mean age of 746 participants was 62 years (SD:5), 62% were male. 11 (1.5%) received a diagnosis of lung cancer. 16.1% participants were admitted to the acute care in the following three years: 8.6% for CD, 4.3% for RD and 5.2% for OD. Valve calcification (OR 2.02, p:0.02) and mucus plugs (OR 3.37, p:0.04) were positively associated with CD, while sub-pleural fibrosis had a protective role (OR 0.47, p:0.01). Lung nodules  〉  8 mm (OR 5.54, p:  〈  0.01), tracheal deviation (OR 6.04, p:0.01) and mucus plugs (OR 4.00, p:0.04) were positively associated with OD admissions. Centrilobular emphysema OR for RD admissions was 1.97 (p:0.06). Conclusions The observed association between selected LDCT findings and ensuing CD, RD and OD suggests that the information potential of LCDT goes beyond the screening of lung cancer.
    Type of Medium: Online Resource
    ISSN: 1471-2466
    URL: Article
    DOI: 10.1186/s12890-022-01826-1
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2059871-3
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  • 5
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    Platelet mean volume, distribution width, and count in type 2 diabetes, impaired fasting glucose, and metabolic syndrome: a meta‐analysis
    Wiley ; 2015
    In:  Diabetes/Metabolism Research and Reviews Vol. 31, No. 4 ( 2015-05), p. 402-410
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    In: Diabetes/Metabolism Research and Reviews, Wiley, Vol. 31, No. 4 ( 2015-05), p. 402-410
    Abstract: Platelet activation contributes to cardiovascular disease (CVD), the main complication of type 2 diabetes mellitus (T2DM) and pre‐diabetic conditions. Mean platelet volume is an easy‐to‐measure platelet parameter that has been associated with CVD. We sought to assess mean platelet volume, platelet distribution width, and platelet count in T2DM, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and metabolic syndrome. Methods Web‐based literature search (PubMed, EMBASE, and Web of Science) of studies published in English through June 2014 was performed to select case–control and cross‐sectional studies that reported data on mean platelet volume, platelet distribution width, or platelet count in cases (subjects with T2DM, IFG, IGT, or metabolic syndrome) and noncases. Descriptive and quantitative information was extracted, and within‐study standardized mean difference was estimated from means and standard deviations. Standardized mean differences across studies were synthesized using a random random‐effects model, and subgroup analyses were performed on pre‐specified study‐level characteristics. Results Thirty‐nine studies were included. Compared with controls, mean platelet volume was significantly higher in T2DM (standardized mean difference, 95% confidence interval: 0.70, 0.50–0.91; N  = 24 245), IFG (0.14, 0.02–0.26; N  = 17 389) but not in metabolic syndrome (0.15, −0.24 to 0.55; N  = 14 990). Platelet distribution width was wider in T2DM (0.93, 0.09–1.76; N  = 471). Platelet count resulted higher in IFG (0.18, 0.12–0.24; N  = 3960) and metabolic syndrome (0.39, 0.01–0.78; N  = 4070). Only two studies included IGT. Conclusions Available data suggest that T2DM subjects tend to have higher mean platelet volume and platelet distribution width values, but nondifferent platelet count as compared with subjects without T2DM. Whether and how these morphometric changes contribute to CVD of T2DM or can be used as CVD biomarker awaits further investigation. Copyright © 2014 John Wiley & Sons, Ltd.
    Type of Medium: Online Resource
    ISSN: 1520-7552 , 1520-7560
    URL: Issue
    URL: Article
    DOI: 10.1002/dmrr.v31.4
    DOI: 10.1002/dmrr.2625
    Language: English
    Publisher: Wiley
    Publication Date: 2015
    detail.hit.zdb_id: 2001565-3
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  • 6
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    Outcomes after cryoballoon ablation of paroxysmal atrial fibrillation with the PolarX or the Arctic Front Advance Pro: a prospective multicentre experience
    Oxford University Press (OUP) ; 2023
    In:  EP Europace Vol. 25, No. 3 ( 2023-03-30), p. 873-879
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    In: EP Europace, Oxford University Press (OUP), Vol. 25, No. 3 ( 2023-03-30), p. 873-879
    Abstract: The aim of this study was to compare procedural efficacy and safety, including 1-year freedom from AF recurrence, between the novel cryoballoon system PolarX (Boston Scientific) and the Arctic Front Advance Pro (AFA-Pro) (Medtronic), in patients with paroxysmal AF undergoing PVI. Methods and results This multicentre prospective observational study included 267 consecutive patients undergoing a first cryoablation procedure for paroxysmal AF (137 PolarX, 130 AFA-Pro). Kaplan-Meier curves with the log-rank test was used to compare the 1-year freedom from AF recurrence between both groups. Multivariate Cox model was performed to evaluate whether the type of procedure (PolarX vs. AFA-Pro) had an impact on the occurrence of AF recurrences after adjustment on potentially confounding factors. The PolarX reaches lower temperatures than the AFA-Pro (LSPV 52 ± 5, vs. 59 ± 6; LIPV 49 ± 6 vs. 56 ± 6; right superior pulmonary vein: 49 ± 6 vs. 57 ± 7; right inferior pulmonary vein: 52 ± 6 vs. 59 ± 6; P & lt; 0.0001). A higher rate of transient phrenic nerve palsy was found in patients treated with the PolarX system (15% vs. 7%, P = 0.05). After a mean follow-up of 15 ± 5 months, 20 patients (15%) had recurrences in AFA-Pro group and 27 patients (19%) in PolarX group (P = 0.35). Based on survival analysis, no significant difference was observed between both groups with a 12-month free of recurrence survival of 91.2% (85.1–95.4%) vs. 83.7% (76.0%–89.1%) (log-rank test P = 0.11). In multivariate Cox model hazard ratio of recurrence for PolarX vs. AFA-Pro was not significant [HR = 1.6 (0.9–2.8), P = 0.12]. Conclusion PolarX and AFA-Pro have comparable efficacy and safety profiles for pulmonary veins isolation in paroxysmal atrial fibrillation.
    Type of Medium: Online Resource
    ISSN: 1099-5129 , 1532-2092
    URL: Article
    DOI: 10.1093/europace/euad005
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2002579-8
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  • 7
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    In Vivo Platelet Activation and Aspirin Responsiveness in Type 1 Diabetes
    American Diabetes Association ; 2016
    In:  Diabetes Vol. 65, No. 2 ( 2016-02-01), p. 503-509
    Details
    In: Diabetes, American Diabetes Association, Vol. 65, No. 2 ( 2016-02-01), p. 503-509
    Abstract: Platelet activation is persistently enhanced, and its inhibition by low-dose aspirin is impaired in type 2 diabetes mellitus. We investigated in vivo thromboxane (TX) and prostacyclin (PGI2) biosynthesis and their determinants, as well as aspirin responsiveness, in young adult subjects with type 1 diabetes mellitus (T1DM) without overt cardiovascular disease and stable glycemic control. The biosynthesis of TXA2 was persistently increased in subjects with T1DM versus matched healthy subjects, with females showing higher urinary TX metabolite (TXM) excretion than male subjects with T1DM. Microalbuminuria and urinary 8-iso-PGF2α, an index of in vivo oxidative stress, independently predicted TXM excretion in T1DM. No homeostatic increase in PGI2 biosynthesis was detected. Platelet COX-1 suppression by low-dose aspirin and the kinetics of its recovery after drug withdrawal were similar in patients and control subjects and were unaffected by glucose variability. We conclude that patients with T1DM and stable glycemic control display enhanced platelet activation correlating with female sex and microvascular and oxidative damages. Moreover, aspirin responsiveness is unimpaired in T1DM, suggesting that the metabolic disturbance per se is unrelated to altered pharmacodynamics. The efficacy and safety of low-dose aspirin in T1DM warrant further clinical investigation.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db15-0936
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2016
    detail.hit.zdb_id: 1501252-9
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