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- Medic Spahic, Jasmina, et al.
(författare)
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Proconvertase furin is down regulated in postural orthostatic tachycardia syndrome
- 2019
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Ingår i: Frontiers in Neuroscience. - : Frontiers Media SA. - 1662-4548 .- 1662-453X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Postural Orthostatic Tachycardia Syndrome (POTS) is a cardiovascular autonomic disorder characterized by orthostatic intolerance and high prevalence among young women. The etiology of POTS is uncertain, though autoimmunity and inflammation may play an important role. We aimed to identify novel inflammatory biomarkers associated with POTS. Methods and Results: In the Syncope Study of Unselected Population in Malmö (SYSTEMA) cohort, we identified 396 patients (age range, 15–50 years) with either POTS (n = 113) or normal haemodynamic response during passive head-up-tilt test (n = 283). Blood samples were analyzed using antibody-based Proximity Extension Assay technique simultaneously measuring 57 inflammatory protein biomarkers. The discovery algorithm was a sequential two-step process of biomarker signature identification by supervised, multivariate, principal component analysis and verification by univariate ANOVA with Bonferroni correction. POTS patients were younger (26 vs. 31 years; p < 0.001) and there was no significant difference in sex distribution (74% vs. 67% females, p = 0.24). PCA and Bonferroni-adjusted ANOVA identified proconvertase furin as the most robust biomarker signature for POTS. Plasma level of proconvertase furin was lower (6.38 vs. 6.58 of normalized protein expression units (NPX); p < 0.001 in POTS, compared with the reference group. Proconvertase furin met Bonferroni-adjusted significance criteria in both uni- and multivariable regression analyses. Conclusion: Patients with POTS have lower plasma level of proconvertase furin compared with individuals with normal postural hemodynamic response. This finding suggests the presence of a specific autoimmune trait with disruption of immune peripheral tolerance in this hitherto unexplained condition. Further studies are needed for external validation of our results.
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- Renda, Giulia, et al.
(författare)
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CHA2DS2VASc score and adverse outcomes in middle-aged individuals without atrial fibrillation
- 2019
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Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4881 .- 2047-4873. ; 26:18, s. 1987-1997
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: The CHA2DS2VASc score is used to evaluate the risk of thromboembolic events in patients with non-valvular atrial fibrillation. We assessed the prognostic yield of CHA2DS2VASc for new-onset atrial fibrillation, cardiovascular morbidity and mortality in a non-atrial fibrillation population.METHODS: We analysed a population-based cohort of 22,179 middle-aged individuals with (n = 3542) and without (n = 18,367) a history of atrial fibrillation; we grouped the population into five CHA2DS2VASc strata (0-1-2-3-≥4), and compared the risk of major adverse cerebro-cardiovascular events and mortality. Furthermore, we analysed the annual incidence of atrial fibrillation across different CHA2DS2VASc strata.RESULTS: Over a median follow-up of 15 years, 1572 patients (6.9%) had ischaemic strokes, 2162 (9.5%) coronary events and 5899 (26%) died. The cumulative incidence of ischaemic stroke in CHA2DS2VASc ≥ 4 subjects without atrial fibrillation was similar to patients with atrial fibrillation and CHA2DS2VASc 2, with a 10-year crude incidence rate of 0.91 (95% confidence interval (CI) 0.68-1.19) and 1.13 (95% CI 0.93-1.36) ischaemic strokes per 100 patient-years, respectively. CHA2DS2VASc in a non-atrial fibrillation population showed higher predictive accuracy for ischaemic stroke compared with an atrial fibrillation population (area under the curve 0.60 vs. 0.56; P = 0.001). In multivariable Cox regression analysis, CHA2DS2VASc ≥ 2 was an independent predictor of all-cause death (adjusted hazard ratio (aHR) 2.58; 95% CI 2.42-2.76), cardiovascular death (aHR 3.40; 95% CI 2.98-3.89), ischaemic stroke (aHR 2.20; 95% CI 1.92-2.53) and coronary events (aHR 1.83; 95% CI 1.63-2.04). The cumulative incidence of atrial fibrillation was greater with increasing CHA2DS2VASc strata, with an absolute annual incidence of more than 2% per year if CHA2DS2VASc ≥ 4.CONCLUSION: The CHA2DS2VASc score is a sensitive tool for predicting new-onset atrial fibrillation and adverse outcomes in subjects both with and without atrial fibrillation.
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- Ricci, Fabrizio, et al.
(författare)
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Pulmonary blood volume index as a quantitative biomarker of haemodynamic congestion in hypertrophic cardiomyopathy
- 2019
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Ingår i: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2412 .- 2047-2404. ; 20:12, s. 1368-1376
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Tidskriftsartikel (refereegranskat)abstract
- AIMS : The non-invasive assessment of left ventricular (LV) diastolic function and filling pressure in hypertrophic cardiomyopathy (HCM) is still an open issue. Pulmonary blood volume index (PBVI) by cardiovascular magnetic resonance (CMR) has been proposed as a quantitative biomarker of haemodynamic congestion. We aimed to assess the diagnostic accuracy of PBVI for left atrial pressure (LAP) estimation in patients with HCM. METHODS AND RESULTS : We retrospectively identified 69 consecutive HCM outpatients (age 58 ± 11 years; 83% men) who underwent both transthoracic echocardiography (TTE) and CMR. Guideline-based detection of LV diastolic dysfunction was assessed by TTE, blinded to CMR results. PBVI was calculated as the product of right ventricular stroke volume index and the number of cardiac cycles for a bolus of gadolinium to pass through the pulmonary circulation as assessed by first-pass perfusion imaging. Compared to patients with normal LAP, patients with increased LAP showed significantly larger PBVI (463 ± 127 vs. 310 ± 86 mL/m2, P < 0.001). PBVI increased progressively with worsening New York Heart Association functional class and echocardiographic stages of diastolic dysfunction (P < 0.001 for both). At the best cut-off point of 413 mL/m2, PBVI yielded good diagnostic accuracy for the diagnosis of LV diastolic dysfunction with increased LAP [C-statistic = 0.83; 95% confidence interval (CI): 0.73-0.94]. At multivariable logistic regression analysis, PBVI was an independent predictor of increased LAP (odds ratio per 10% increase: 1.97, 95% CI: 1.06-3.68; P = 0.03). CONCLUSION : PBVI is a promising CMR application for assessment of diastolic function and LAP in patients with HCM and may serve as a quantitative marker for detection, grading, and monitoring of haemodynamic congestion.
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