| 1. |
- Green, Anna, 1973-, et al.
(författare)
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Copy number variants in familial hypercholesterolemia genes using targeted NGS, validated through optical genome mapping
- 2024
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Ingår i: European Journal of Human Genetics. - : Nature Portfolio. - 1018-4813 .- 1476-5438. ; 32:Suppl. 1, s. 159-159
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background/Objectives: Familial hypercholesterolemia (FH) is a common genetic disorder which is primarily caused by pathogenic variants in the LDLR, APOB, and PCSK9 genes. Approximately 10% of pathogenic variants in LDLR may be CNVs. Here, we combine NGS, MLPA, and Optical Genome Mapping (OGM) to investigate CNVs in LDLR.Methods: A NGS panel was designed for whole gene sequencing (8 genes) of 100 FH patients using Twist technology and Illumina platform. CNVs were detected using CNVexpo, and an in-house pipeline for base-resolved normalized coverage. Identified CNVs were validated using MLPA and OGM. Bionano Services Lab performed the OGM procedure. Purified gDNA was labeled using Direct Label and Stain DNA Labeling Kit. Saphyr chip was run aiming for 100X coverage. De novo assembly and Variant Annotation pipelines were executed on Bionano Solve v3.7. Bionano Access v1.7 was used for CNV reporting and visualization.Results: In five out of 100 samples NGS and MLPA data showed heterozygous deletions in LDLR. Three deletions, affecting different exons, was analyzed and confirmed using OGM. In two samples, OGM better defined the breakpoints as well as the size of the event, which expanded far beyond the gene of interest. In one sample, an additional CNV of SLCO1B1, a pharmaco-gene, important for transport of statins used for FH treatment was identified.Conclusion: CNVs in FH genes in FH patients could be detected using targeted NGS, which was further confirmed by MLPA and characterized using OGM.
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| 2. |
- Lindblad, L., et al.
(författare)
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Risk factors for mortality of medical causes within 30 days of electroconvulsive therapy
- 2023
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Ingår i: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 320, s. 527-533
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Electroconvulsive therapy (ECT) is used to treat severe psychiatric disorders and is associated with reduced risk of suicide and all-cause mortality in patients with severe depression. We investigated the causes of death occurring shortly after ECT and identified potential risk factors for medical causes of death.METHODS: Patients treated with ECT between 2012 and 2018 were included in this Swedish register-based study. Multivariate binary logistic regression was used to calculate odds ratios for covariates to determine potential predictors of 30-day mortality.RESULTS: Of the 20,225 included patients, 93 (0.46 %) died of suicide and 123 (0.61 %) died of medical causes after ECT. Cardiovascular disease was the most common medical cause of death (n = 49, 40 %). An older age, a Charlson Comorbidity Index of 1 or more, atrial fibrillation, kidney disease, reflux disease, dementia, and cancer were associated with increased risk of death by medical causes.LIMITATIONS: Real-life observational studies based on registry data may demonstrate associations, but cannot determine causality. If medical records had been available, we would be better able to determine if deaths were due to the ECT, anesthesia, pre-existing medical conditions, or the mental disorder.CONCLUSIONS: ECT appears to be a low-risk medical procedure. Older individuals with severe somatic diseases have the highest risk of death and extra measures should be considered to optimize their medical health during the pre-ECT workup, and during and after ECT.
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| 3. |
- Nordenskjöld, Axel, 1977-, et al.
(författare)
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Major adverse cardiovascular events following electroconvulsive therapy in depression : A register-based nationwide Swedish cohort study with 1-year follow-up
- 2022
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Ingår i: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 296, s. 298-304
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The cardiovascular response during electroconvulsive therapy (ECT) could induce major adverse cardiovascular events (MACE) in the short-term, while reduced depression could decrease the risk of MACE in the long-term. The balance between these potential effects has not been thoroughly investigated.METHODS: This nationwide, registry-based cohort study included all patients admitted to Swedish hospitals due to moderate or severe unipolar depression between 2011 and 2018. Patients were divided into an ECT group and a non-ECT group, and followed for 1 year. Patients were matched by risk factors for cardiovascular disease by propensity score matching. Cox regression was used to examine the association between ECT and MACE.RESULTS: Out of a total of 28 584 inpatients, 5476 patients who had received ECT were matched to 5476 non-ECT patients. ECT was associated with reduced risk of MACE within 90 days and 1 year. Within 1 year after admission, a total of 127 patients (2.3%) in the non-ECT group and 82 patients (1.4%) in the ECT group had at least one MACE (hazard ratio [HR], 0.65; 95% confidence interval, 0.49-0.85).LIMITATIONS: Real-life observational studies carry risk for residual confounding.CONCLUSIONS: ECT in patients hospitalized for depression was not associated with any significant short-term risks of cardiovascular events. Instead, ECT was associated with a reduced risk of MACE within 1 year after admission compared with patients not treated with ECT. This association may be explained by reduced depressive symptoms after ECT, improved risk factor management in the ECT-group or by residual confounding by indication.
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| 4. |
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| 5. |
- Djekic, Demir, 1989-
(författare)
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Novel and Traditional Risk Factors for Coronary Artery Disease : Role of Coronary Artery Calcium, Lipidomics, Psychosocial Factors and Diet
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The aim of the research reported in this thesis was to determine the association of novel and traditional risk factors with coronary artery calcium (CAC), a marker of subclinical coronary artery disease (CAD) in healthy individuals. In addition, we investigated the effects of a vegetarian, compared to a meat diet, on novel and traditional risk factors in patients with diagnosed CAD.Methods: Studies I-II evaluated the inter-laboratory reproducibility of liquid chromatography-mass spectrometry (LC-MS) lipid analysis and the association of serum lipidome with CAC in a cohort of 70 patients. Studies III and IV analysed data of 1067 participants in the pilot study of the Swedish CArdioPulmonary bioImage Study to determine associations of psychosocial (residential area, education, housing, and social support) and traditional risk factors with CAC. Cardiac computed tomography was used to obtain a coronary artery calcium score (CACS) (Studies I–IV). Study V employed a crossover design in which 31 patients with CAD were randomly allocated to a four-week vegetarian diet alternating with four weeks of an isocaloric meat diet. Enzyme-linked immunosorbent assay was used to measure oxidised LDL-cholesterol. Plasma metabolome, including choline, trimethylamine N-oxide, L-carnitine, and acetyl-carnitine, as well as plasma lipidome were determined with LC-MS. Gut microbiota and faecal short- and branched-chain fatty acids were analysed with 16S rRNA gene sequencing and gas chromatography-MS, respectively.Results: In Study I, two laboratories independently identified six lipids in common that differentiated serum of patients with CACS >250 from that of those with CACS=0. Study II, revealed higher levels of phosphatidylcholine(PC)(16:0/20:4) and lower levels of PC(18:2/18:2), PC(36:3) and phosphatidylethanolamine (PE)(20:0/18:2) in patients with CACS >250 than found in those with CACS=0. Study III showed a CACS >0 prevalence of 46.3% and 36.6% in low and high socioeconomic residential areas, respectively, but the traditional risk factor–adjusted odds ratio for CACS >0 was not significantly higher in subjects living in low socioeconomic areas. In Study III, the traditional risk factor–adjusted odds ratio for CACS >100 relative to CACS=0 was significantly higher in women with low education level and living in a rented apartment. Studies III and IV showed traditional risk factor–adjusted odds ratios for CACS >0 to be significantly higher in women with a family history of premature cardiovascular disease and low social support. No relationship of psychosocial factors with CAC was observed in men. The vegetarian diet implemented in Study V significantly lowered mean oxidized LDL-cholesterol (-2.73 U/L), total cholesterol (-0.13 mmol/L), LDL-cholesterol (-0.10 mmol/L), and body mass index (-0.21 kg/m2), as well as the relative abundance of PCs, PEs, and several microbial genera compared with the meat diet. The effect of the vegetarian diet on oxidized LDL-C was associated with higher relative abundance of Ruminococcaceae genera and of Barnesiella and reduced abundance of Flavonifractor. The vegetarian diet lowered the relative abundance of ceramide(d18:1/16:0) and triacylglycerols with saturated fatty acyl chains and raised the relative abundance of triacylglycerols with high carbon and polyunsaturated fatty acyl chains compared with the meat diet.Conclusions: Novel and traditional cardiovascular risk factors are associated with subclinical CAD. Psychosocial factors are associated with subclinical CAD in women, but not in men. Short-term intervention with a vegetarian diet in individuals with CAD can positively impact novel and traditional factors that have been associated with risk of future cardiovascular events.
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| 6. |
- Eggers, Kai, et al.
(författare)
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Diagnostic value of serial measurement of cardiac markers in patients with chest pain : limited value of adding myoglobin to troponin I for exclusion of myocardial infarction
- 2004
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 148:4, s. 574-581
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Despite improved laboratory assays for cardiac markers and a revised standard for definition of myocardial infarction (AMI), early detection of coronary ischemia in unselected patients with chest pain remains a difficult challenge.METHODS:Rapid measurements of troponin I (TnI), creatine kinase MB (CK-MB), and myoglobin were performed in 197 consecutive patients with chest pain and a nondiagnostic electrocardiogram for AMI. The early diagnostic performances of these markers and different multimarker strategies were evaluated and compared. Diagnosis of AMI was based on European Society of Cardiology/American College of Cardiology criteria.RESULTS:At a given specificity of 95%, TnI yielded the highest sensitivity of all markers at all time points. A TnI cutoff corresponding to the 10% coefficient of variation (0.1 microg/L) demonstrated a cumulative sensitivity of 93% with a corresponding specificity of 81% at 2 hours. The sensitivity was considerably higher compared to CK-MB and myoglobin, even considering patients with a short delay until admission. Using the 99th percentile of TnI results as a cutoff (0.07 microg/L) produced a cumulative sensitivity of 98% at 2 hours, but its usefulness was limited due to low specificities. Multimarker strategies including TnI and/or myoglobin did not provide a superior overall diagnostic performance compared to TnI using the 0.1 microg/L cutoff.CONCLUSION:A TnI cutoff corresponding to the 10% coefficient of variation was most appropriate for early diagnosis of AMI. A lower TnI cutoff may be useful for very early exclusion of AMI. CK-MB and in particular myoglobin did not offer additional diagnostic value.
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| 7. |
- Eggers, Kai Marten, et al.
(författare)
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Analytic Performance of a Point-of-Care Instrument for Measurement of Cardiac Markers : An Evaluation Under Clinical Conditions
- 2003
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Ingår i: Point of Care. - : Lippincott Williams & Wilkins. - 1533-029X .- 1533-0303. ; 2:4, s. 235-242
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Tidskriftsartikel (refereegranskat)abstract
- Point-of-care testing of cardiac markers has been widely introduced into clinical practice. In this study, the authors examined the analytic qualities and the feasibility of a point-of-care device—the Stratus CS STAT Fluorometric Analyzer—under clinical conditions. Measurements of myoglobin, creatine kinase–MB (CK-MB), and troponin I (TnI) were performed in 197 consecutive patients admitted to the coronary care unit because of chest pain suggestive of a myocardial infarction. Additionally, all cardiac markers were determined on the AxSYM analyzer used as a comparative device. The Stratus CS demonstrated an average analytic imprecision (or coefficient of variation [CV]) of 4.0 to 5.1% for the TnI assay, 2.9 to 5.5% for CK-MB, and 3.7 to 4.7% for myoglobin. This was superior to CVs of AxSYM measurements, in particular concerning the lower range of TnI concentrations. The method comparison showed 17 to 22% lower Stratus CS myoglobin results and 24 to 29% lower Stratus CS CK-MB results. For TnI, Stratus CS results were factor 5 or factor 10 lower compared with AxSYM measurements and showed a great dispersion of values as a result of the higher CV of the AxSYM TnI assay. The diagnostic sensitivities and specificities of all 3 markers correlated well on both test systems. In conclusion, the Stratus CS showed an overall good performance, with analytic qualities and clinical performance as least as good as those of the AxSYM analyzer.A large number of patients are admitted to coronary care units (CCUs) with chest pain suggestive of an acute coronary syndrome (ie, unstable angina or acute myocardial infarction [AMI]). The diagnosis of AMI is immediately established only in case of ST elevation in the electrocardiogram (EKG). The large majority of chest pain patients, however, will have a nondiagnostic EKG for AMI. In those patients, confirmation of AMI is mainly dependent on serial testing of biochemical markers of myocardial damage, which currently is a time-consuming procedure.Fast evaluation of patients with chest pain leads to several advantages. First, tests or procedures for establishing a definite or alternative diagnosis can be initiated earlier or avoided in appropriate circumstances. Second, rapid identification of patients suitable for treatment aimed at reducing morbidity and mortality (eg, percutaneous coronary intervention or Gp IIb/IIIa receptor antagonist treatment) may be possible. Furthermore, considerable economic gains might be achieved by early identification of patients who are at sufficiently low risk to be discharged or transferred from the CCU to a less resource-demanding unit. 1–3To achieve fast assessment of chest pain patients, a short-assay turnaround time (TAT) is necessary. Normally, TAT includes the delay in the delivery of the sample to the laboratory, the preanalytic steps necessary to prepare the sample, the analysis time itself, and the effort it takes to deliver results to the ordering physician. To reach a TAT of less than 30 minutes, point-of-care (POC) instruments for analysis of cardiac markers have been developed, combining advantages such as near-patient assessment, a short sample-to-diagnosis time, and reasonable costs.The aim of the current study was to examine and validate the feasibility of such a POC instrument—the Stratus CS STAT Fluorometric Analyzer (Dade Behring, Deerfield, IL)—in a routine setting of patients presenting with chest pain suggestive of an AMI but without confirming EKG changes. The analytic qualities and clinical performance of the assays of the commonly used cardiac markers troponin I (TnI), creatine kinase–MB (CK-MB), and myoglobin were studied and compared with results obtained from the central laboratory. Additionally, clinical characteristics such as user friendliness and TAT were evaluated.
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| 8. |
- Eggers, Kai M., 1962-, et al.
(författare)
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Clinical and prognostic implications of C-reactive protein levels in myocardial infarction with nonobstructive coronary arteries
- 2021
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Ingår i: Clinical Cardiology. - : John Wiley & Sons. - 0160-9289 .- 1932-8737. ; 44:7, s. 1019-1027
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Tidskriftsartikel (refereegranskat)abstract
- Background Myocardial infarction with nonobstructive coronary arteries (MINOCA) is a heterogeneous condition. Recent studies suggest that MINOCA patients may have a proinflammatory disposition. The role of inflammation in MINOCA may thus be distinct to myocardial infarction with significant coronary artery disease (MI-CAD). Hypothesis We hypothesized that inflammation reflected by C-reactive protein (CRP) levels might carry unique clinical information in MINOCA. Methods This retrospective registry-based cohort study (SWEDEHEART) included 9916 patients with MINOCA and 97 970 MI-CAD patients, used for comparisons. Multivariable-adjusted regressions were applied to investigate the associations of CRP levels with clinical variables, all-cause mortality and major cardiovascular events (MACE) during a median follow-up of up to 5.3 years. Results Median admission CRP levels in patients with MINOCA and MI-CAD were 5.0 (interquartile range 2.0-9.0) mg/dl and 5.0 (interquartile range 2.1-10.0 mg/dl), respectively. CRP levels in MINOCA exhibited independent associations with various cardiovascular risk factors, comorbidities and estimates of myocardial damage. The association of CRP with peripheral artery disease tended to be stronger compared to MI-CAD. The associations with female sex, renal dysfunction and myocardial damage were stronger in MI-CAD. CRP independently predicted all-cause mortality in MINOCA (hazard ratio 1.22 [95% confidence interval 1.17-1.26]), similar to MI-CAD (p interaction = 0.904). CRP also predicted MACE (hazard ratio 1.08 [95% confidence interval 1.04-1.12]) but this association was weaker compared to MI-CAD (p interaction<.001). Conclusions We found no evidence indicating the presence of a specific inflammatory pattern in acute MINOCA compared to MI-CAD. However, CRP levels were independently, albeit moderately associated with adverse outcome.
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| 9. |
- Eggers, Kai M., 1962-, et al.
(författare)
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Combining different biochemical markers of myocardial ischemia does not improve risk stratification in chest pain patients compared to troponin I alone
- 2005
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Ingår i: Coronary Artery Disease. - : Ovid Technologies (Wolters Kluwer Health). - 0954-6928 .- 1473-5830. ; 16:5, s. 315-9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Early evaluation of patients with chest pain is important not only for the detection of acute myocardial infarction (AMI) but also for identification of patients at high risk for future cardiac events. A multimarker strategy applying results of early measurements of different biochemical markers of cardiac necrosis in combination may improve risk prediction in chest pain patients. METHODS: Rapid measurements of troponin I (TnI), creatine kinase MB and myoglobin were performed in 191 consecutive patients with chest pain and a non-diagnostic electrocardiogram for AMI. The prognostic value of these markers and different multimarker strategies was evaluated and compared. RESULTS: Ten (5.2%) patients died during follow-up, which for eight (4.2%) patients was due to cardiac causes. Myocardial reinfarctions occurred in 17 (6.8%) patients. TnI was most predictive for cardiac mortality (TnI>or=0.1 microg/l, 10.7% event rate compared with TnI<0.1 microg/l, 0%, P<0.001) and myocardial reinfarction (14.9% compared with 1.7%, P<0.001). The other markers and multimarker strategies had a lower capacity for predicting adverse events apart from myoglobin and the combination of TnI or myoglobin regarding the endpoint of total mortality. CONCLUSION: The combinations of different markers were prognostically non-superior compared to TnI, which thus, should be preferred as a biochemical marker for risk stratification in patients with chest pain.
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| 10. |
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