| 1. |
- Chadalavada, Sucharitha, et al.
(författare)
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Diabetes and heart failure associations in women and men : Results from the MORGAM consortium
- 2023
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Ingår i: Frontiers in Cardiovascular Medicine. - 2297-055X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Diabetes and its cardiovascular complications are a growing concern worldwide. Recently, some studies have demonstrated that relative risk of heart failure (HF) is higher in women with type 1 diabetes (T1DM) than in men. This study aims to validate these findings in cohorts representing five countries across Europe.Methods: This study includes 88,559 (51.8% women) participants, 3,281 (46.3% women) of whom had diabetes at baseline. Survival analysis was performed with the outcomes of interest being death and HF with a follow-up time of 12 years. Sub-group analysis according to sex and type of diabetes was also performed for the HF outcome.Results: 6,460 deaths were recorded, of which 567 were amongst those with diabetes. Additionally, HF was diagnosed in 2,772 individuals (446 with diabetes). A multivariable Cox proportional hazard analysis showed that there was an increased risk of death and HF (hazard ratio (HR) of 1.73 [1.58–1.89] and 2.12 [1.91–2.36], respectively) when comparing those with diabetes and those without. The HR for HF was 6.72 [2.75–16.41] for women with T1DM vs. 5.80 [2.72–12.37] for men with T1DM, but the interaction term for sex differences was insignificant (p for interaction 0.45). There was no significant difference in the relative risk of HF between men and women when both types of diabetes were combined (HR 2.22 [1.93–2.54] vs. 1.99 [1.67–2.38] respectively, p for interaction 0.80).Conclusion: Diabetes is associated with increased risks of death and heart failure, and there was no difference in relative risk according to sex.
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| 2. |
- 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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| 3. |
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| 4. |
- Doimo, Sara, et al.
(författare)
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Tissue-tracking in the assessment of late gadolinium enhancement in myocarditis and myocardial infarction
- 2020
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Ingår i: Magnetic Resonance Imaging. - : Elsevier BV. - 0730-725X. ; 73, s. 62-69
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To test the diagnostic performance of cardiovascular magnetic resonance (CMR) tissue-tracking (TT) to detect the presence of late gadolinium enhancement (LGE) in patients with a diagnosis of myocardial infarction (MI) or myocarditis (MYO), preserved left ventricular ejection fraction (LVEF) and no visual regional wall motion abnormalities (RWMA). Methods: We selected consecutive CMR studies of 50 MI, 50 MYO and 96 controls. Receiving operating characteristic (ROC) curve and net reclassification index (NRI) analyses were used to assess the predictive ability and the incremental diagnostic yield of 2D and 3D TT-derived strain parameters for the detection of LGE and to measure the best cut-off values of strain parameters. Results: Overall, cases showed significantly reduced 2D global longitudinal strain (2D-GLS) values compared with controls (−20.1 ± 3.1% vs −21.6 ± 2.7%; p = 0.0008). 2D-GLS was also significantly reduced in MYO patients compared with healthy controls (−19.7 ± 2.9% vs −21.9 ± 2.4%; p = 0.0001). 3D global radial strain (3D-GRS) was significantly reduced in MI patients compared with controls with risk factors (34.3 ± 11.8% vs 40.3 ± 12.5%, p = 0.024) Overall, 2D-GLS yielded good diagnostic accuracy for the detection of LGE in the MYO subgroup (AUROC 0.79; NRI (95% CI) = 0.6 (0.3, 1.02) p = 0.0004), with incremental predictive value beyond risk factors and LV function parameters (p for AUROC difference = 0.048). In the MI subgroup, 2D-GRS (AUROC 0.81; NRI (95% CI) = 0.56 (0.17, 0.95) p = 0.004), 3D-GRS (AUROC 0.82; NRI (95% CI) = 0.57 (0.17, 0.97) p = 0.006) and 3D global circumferential strain (3D-GCS) (AUROC 0.81; NRI (95% CI) = 0.62 (0.22, 1.01) p = 0.002) emerged as potential markers of disease. The best cut-off for 2D-GLS was −21.1%, for 2D- and 3D-GRS were 39.1% and 37.7%, respectively, and for 3D-GCS was −16.4%. Conclusions: At CMR-tissue tracking analysis, 2D-GLS was a significant predictor of LGE in patients with myocarditis but preserved LVEF and no visual RWMA. Both 2D- and 3D-GRS and 2D-GCS yielded good diagnostic accuracy for LGE detection in patients with previous MI but preserved LVEF and no visual RWMA.
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| 5. |
- 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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| 6. |
- 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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| 7. |
- Laudette, Marion, et al.
(författare)
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Cardiomyocyte-specific PCSK9 deficiency compromises mitochondrial bioenergetics and heart function
- 2023
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Ingår i: Cardiovascular Research. - : Oxford University Press (OUP). - 0008-6363 .- 1755-3245. ; 119:7, s. 1537-1552
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Tidskriftsartikel (refereegranskat)abstract
- Aims Pro-protein convertase subtilisin-kexin type 9 (PCSK9), which is expressed mainly in the liver and at low levels in the heart, regulates cholesterol levels by directing low-density lipoprotein receptors to degradation. Studies to determine the role of PCSK9 in the heart are complicated by the close link between cardiac function and systemic lipid metabolism. Here, we sought to elucidate the function of PCSK9 specifically in the heart by generating and analysing mice with cardiomyocyte-specific Pcsk9 deficiency (CMPcsk9−/− mice) and by silencing Pcsk9 acutely in a cell culture model of adult cardiomyocyte-like cells. Methods and results Mice with cardiomyocyte-specific deletion of Pcsk9 had reduced contractile capacity, impaired cardiac function, and left ventricular dilatation at 28 weeks of age and died prematurely. Transcriptomic analyses revealed alterations of signalling pathways linked to cardiomyopathy and energy metabolism in hearts from CM-Pcsk9−/− mice vs. wild-type littermates. In agreement, levels of genes and proteins involved in mitochondrial metabolism were reduced in CM-Pcsk9−/− hearts. By using a Seahorse flux analyser, we showed that mitochondrial but not glycolytic function was impaired in cardiomyocytes from CM-Pcsk9−/− mice. We further showed that assembly and activity of electron transport chain (ETC) complexes were altered in isolated mitochondria from CM-Pcsk9−/− mice. Circulating lipid levels were unchanged in CM-Pcsk9−/− mice, but the lipid composition of mitochondrial membranes was altered. In addition, cardiomyocytes from CM-Pcsk9−/− mice had an increased number of mitochondria–endoplasmic reticulum contacts and alterations in the morphology of cristae, the physical location of the ETC complexes. We also showed that acute Pcsk9 silencing in adult cardiomyocyte-like cells reduced the activity of ETC complexes and impaired mitochondrial metabolism. Conclusion PCSK9, despite its low expression in cardiomyocytes, contributes to cardiac metabolic function, and PCSK9 deficiency in cardiomyocytes is linked to cardiomyopathy, impaired heart function, and compromised energy production.
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| 8. |
- 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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| 9. |
- Medic Spahic, Jasmina, et al.
(författare)
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Proteomic analysis reveals sex-specific biomarker signature in postural orthostatic tachycardia syndrome
- 2020
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 20
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is a variant of cardiovascular (CV) autonomic disorder of unknown etiology characterized by an excessive heart rate increase on standing and orthostatic intolerance. In this study we sought to identify novel CV biomarkers potentially implicated in POTS pathophysiology.METHODS: We conducted a nested case-control study within the Syncope Study of Unselected Population in Malmö (SYSTEMA) cohort including 396 patients (age range, 15-50 years) with either POTS (n = 113) or normal hemodynamic response during passive head-up-tilt test (n = 283). We used a targeted approach to explore changes in cardiovascular proteomics associated with POTS through a sequential two-stage process including supervised principal component analysis and univariate ANOVA with Bonferroni correction.RESULTS: POTS patients were younger (26 vs. 31 years; p < 0.001) and had lower BMI than controls. The discovery algorithm identified growth hormone (GH) and myoglobin (MB) as the most specific biomarker fingerprint for POTS. Plasma level of GH was higher (9.37 vs 8.37 of normalised protein expression units (NPX); p = 0.002), whereas MB was lower (4.86 vs 5.14 NPX; p = 0.002) in POTS compared with controls. In multivariate regression analysis, adjusted for age and BMI, and stratified by sex, lower MB level in men and higher GH level in women remained independently associated with POTS.CONCLUSIONS: Cardiovascular proteomics analysis revealed sex-specific biomarker signature in POTS featured by higher plasma level of GH in women and lower plasma level of MB in men. These findings point to sex-specific immune-neuroendocrine dysregulation and deconditioning as potentially key pathophysiological traits underlying POTS.
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| 10. |
- 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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