| 1. |
- De Innocentiis, Carlo, et al.
(författare)
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Athlete’s Heart : Diagnostic Challenges and Future Perspectives
- 2018
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Ingår i: Sports Medicine. - : Springer Science and Business Media LLC. - 0112-1642 .- 1179-2035. ; 48:11, s. 2463-2477
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Forskningsöversikt (refereegranskat)abstract
- Distinguishing between adaptive and maladaptive cardiovascular response to exercise is crucial to prevent the unnecessary termination of an athlete’s career and to minimize the risk of sudden death. This is a challenging task essentially due to the substantial phenotypic overlap between electrical and structural changes seen in the physiological athletic heart remodeling and pathological changes seen in inherited or acquired cardiomyopathies. Stress testing is an ideal tool to discriminate normal from abnormal cardiovascular response by unmasking subtle pathologic responses otherwise undetectable at rest. Treadmill or bicycle electrocardiography, transthoracic echocardiography, and cardiopulmonary exercise testing are common clinical investigations used in sports cardiology, specifically among participants presenting with resting electrocardiographic abnormalities, frequent premature ventricular beats, or non-sustained ventricular arrhythmias. In this setting, as well as in cases of left ventricular hypertrophy or asymptomatic left ventricular dysfunction, stress imaging and myocardial tissue characterization by cardiovascular magnetic resonance show promise. In this review, we aimed to reappraise current diagnostic schemes, screening strategies and novel approaches that may be used to distinguish adaptive remodeling patterns to physical exercise from early phenotypes of inherited or acquired pathological conditions commanding prompt intervention.
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| 2. |
- Johansson, Madeleine, et al.
(författare)
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Inflammatory biomarker profiling in classical orthostatic hypotension : Insights from the SYSTEMA cohort
- 2018
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 259, s. 192-197
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the inflammatory biomarker signature associated with classical orthostatic hypotension (OH). Methods: A cross-sectional study including 778 patients with unexplained syncope and/or orthostatic intolerance undergoing head-up tilt test (HUT) and supine blood sampling. Of these, 98 met diagnostic criteria of classical OH and 181 demonstrated normal haemodynamic response during HUT. Blood plasma samples were analysed by antibody-based Proximity Extension Assay technique simultaneously measuring 57 inflammatory and cancer-related human protein biomarkers. The discovery algorithm was a sequential two-step process of biomarker signature identification by multivariate principal component analysis (PCA), and verification by univariate ANOVA with Bonferroni correction. Results: Patients with classical OH were older (68 vs. 60 years; p < 0.001) and more likely to be men (58 vs. 41%; p < 0.001). PCA and Bonferroni-adjusted ANOVA identified midkine (MK), immunoglobulin-like transcript 3 (ILT-3), regenerating islet-derived protein 4 (REG-4), and tartrate-resistant acid phosphatase type 5 (TR-AP) as the most robust targeted biomarker signature for OH. In multivariate regression analysis adjusting for age, sex, cardiovascular disease and risk factors, the results remained significant for ILT-3 (p = 0.036), MK (p = 0.008) and REG-4 (p = 0.024), but not for TR-AP. Conclusions: Targeted protein profiling in classical orthostatic hypotension reveals a biomarker signature associated with immunoregulatory functions and vascular inflammation. Circulating levels of midkine, immunoglobulin-like transcript-3, regenerating islet-derived protein-4 are elevated in orthostatic hypotension, suggesting a complex interplay among inflammation, autonomic dysfunction and atherothrombosis.
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| 3. |
- Johansson, Madeleine, et al.
(författare)
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Proteomic Profiling for Cardiovascular Biomarker Discovery in Orthostatic Hypotension
- 2018
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Ingår i: Hypertension. - 1524-4563. ; 71:3, s. 465-472
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Tidskriftsartikel (refereegranskat)abstract
- Orthostatic hypotension (OH) has been linked with higher incidence of cardiovascular disease, but little is known about the mechanisms behind this association. We aimed to identify cardiovascular disease biomarkers associated with OH through a proteomic profiling approach. Seven hundred seventy-eight patients with unexplained syncope or orthostatic intolerance underwent head-up tilt test and supine blood samples. Of these, 220 met diagnostic criteria of OH, and 179 demonstrated normal hemodynamic response during head-up tilt test. Blood samples were analyzed by antibody-based Proximity Extension Assay technique simultaneously measuring 92 cardiovascular disease-related human protein biomarkers. The discovery algorithm was a sequential 2-step process of biomarker signature identification by supervised, multivariate, principal component analysis and verification by univariate ANOVA with Bonferroni correction. Patients with OH were older (67 versus 60 years;P<0.001) and more likely to be women (48% versus 41%;P>0.001) but did not differ from OH-negative patients in medical history. Principal component analysis identified MMP-7 (matrix metalloproteinase-7), TM (thrombomodulin), MB (myoglobin), TIM-1 (T-cell immunoglobulin and mucin domain-1), CASP-8 (caspase-8), CXCL-1 (C-X-C motif chemokine-1), Dkk-1 (dickkopf-related protein-1), lectin-like LOX-1 (oxidized low-density lipoprotein receptor-1), PlGF (placenta growth factor), PAR-1 (proteinase-activated receptor-1), and MCP-1 (monocyte chemotactic protein-1) as the most robust proteomic signature for OH. From this proteomic feature selection, MMP-7 and TIM-1 met Bonferroni-adjusted significance criteria in univariate and multivariate regression analyses. Proteomic profiling in OH reveals a biomarker signature of atherothrombosis and inflammation. Circulating levels of MMP-7 and TIM-1 are independently associated with OH and may be involved in cardiovascular disease promotion.
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| 4. |
- Ricci, Fabrizio, et al.
(författare)
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Detection of inflammatory biomarkers associated with postural orthostatic tachycardia syndrome: insights from the SYSTEMA cohort
- 2018
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Ingår i: European Heart Journal, Supplement. - 1520-765X. ; 39:1, s. 889-889
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Konferensbidrag (refereegranskat)abstract
- Background: Postural Orthostatic Tachycardia Syndrome (POTS) is a cardiovascular dysautonomic condition affecting predominantly young women. POTS is defined as the presence of chronic symptoms of orthostatic intolerance associated with an increased heart rate ≥30 bpm, or heart rate exceeding 120 bpm, within 10 minutes of standing or head-up tilt in the absence of orthostatic hypotension. The etiology is still unknown though autoimmunity has been hypothesized to play an important role. Purpose: To investigate whether an inflammatory biomarker signature is associated with POTS. Methods: We performed a cross-sectional study enrolling 475 patients aged between 15 and 55 years with unexplained syncope or symptoms of orthostatic intolerance. Of these 118 have been diagnosed with POTS and 357 controls demonstrated normal hemodynamic response during passive phase of HUT i.e. no orthostatic hypotension or POTS. A total of 318 patients provided supine blood plasma samples that were analyzed through the antibody-based Proximity Extension Assay technique, simultaneously measuring 53 inflammatory and cancer-related human protein biomarkers. After excluding 5 biomarkers with low call rate <65% (VEstatin, LITAF, MYD88, MICA, CEA) and 9 patients with missing data, the final study sample consisted of 309 patients (POTS, n=78; no POTS n=231). The discovery algorithm was a sequential two-step process of biomarker signature identification by multivariate principal component analysis (PCA), and verification by univariate ANOVA with Bonferroni correction. Results: POTS patients were younger (28 vs. 35 years; p<0.001) compared with controls. PCA and Bonferroni-adjusted ANOVA identified furin and FADD as the most robust targeted biomarker signature for POTS. The plasma concentration of furin was significantly lower (6.39 (0.5) vs 6.64 (0.4), p<0.001), whereas FADD levels were significantly higher (2.37 (0.72) vs 2.14 (0.69), p=0.01) in POTS patients compared with controls. In multivariable regression analysis, adjusting for age and sex, the results remained significant. Conclusion: Targeted protein profiling in POTS revealed a biomarker signature associated with immunoregulatory functions. Circulating levels of furin were downregulated, whereas circulating levels of FADD were elevated in POTS, suggesting the presence of a characteristic inflammatory signature in this unexplained condition.
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