| 1. |
- Glasbey, JC, et al.
(author)
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- 2021
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swepub:Mat__t
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| 2. |
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| 3. |
- Postmus, I., et al.
(author)
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Meta-analysis of genome-wide association studies of HDL cholesterol response to statins
- 2016
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In: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 53:12, s. 835-45
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Journal article (peer-reviewed)abstract
- Background In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Interindividual variation in HDL-C response to statins may be partially explained by genetic variation. Methods and results We performed a meta-analysis of genome-wide association studies (GWAS) to identify variants with an effect on statin-induced high density lipoprotein cholesterol (HDL-C) changes. The 123 most promising signals with p<1x10(-4) from the 16 769 statin-treated participants in the first analysis stage were followed up in an independent group of 10 951 statin-treated individuals, providing a total sample size of 27 720 individuals. The only associations of genome-wide significance (p<5x10(-8)) were between minor alleles at the CETP locus and greater HDL-C response to statin treatment. Conclusions Based on results from this study that included a relatively large sample size, we suggest that CETP may be the only detectable locus with common genetic variants that influence HDL-C response to statins substantially in individuals of European descent. Although CETP is known to be associated with HDL-C, we provide evidence that this pharmacogenetic effect is independent of its association with baseline HDL-C levels.
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| 4. |
- Postmus, Iris, et al.
(author)
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Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.
- 2014
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5
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Journal article (peer-reviewed)abstract
- Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response.
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| 5. |
- Meijs, Loek P. B., et al.
(author)
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An electrocardiographic sign of ischemic preconditioning
- 2014
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In: American Journal of Physiology: Heart and Circulatory Physiology. - : American Physiological Society. - 1522-1539 .- 0363-6135. ; 307:1, s. 80-87
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Journal article (peer-reviewed)abstract
- Ischemic preconditioning is a form of intrinsic cardioprotection where an episode of sublethal ischemia protects against subsequent episodes of ischemia. Identifying a clinical biomarker of preconditioning could have important clinical implications, and prior work has focused on the electrocardiographic ST segment. However, the electrophysiology biomarker of preconditioning is increased action potential duration (APD) shortening with subsequent ischemic episodes, and APD shortening should primarily alter the T wave, not the ST segment. We translated findings from simulations to canine to patient models of preconditioning to test the hypothesis that the combination of increased [delta (Delta)] T wave amplitude with decreased ST segment elevation characterizes preconditioning. In simulations, decreased APD caused increased T wave amplitude with minimal ST segment elevation. In contrast, decreased action potential amplitude increased ST segment elevation significantly. In a canine model of preconditioning (9 mongrel dogs undergoing 4 ischemia-reperfusion episodes), ST segment amplitude increased more than T wave amplitude during the first ischemic episode [Delta T/Delta ST slope = 0.81, 95% confidence interval (CI) 0.46 -1.15]; however, during subsequent ischemic episodes the T wave increased significantly more than the ST segment (Delta T/Delta ST slope = 2.43, CI 2.07-2.80) (P = 0.001 for interaction of occlusions 2 vs. 1). A similar result was observed in patients (9 patients undergoing 2 consecutive prolonged occlusions during elective percutaneous coronary intervention), with an increase in slope of Delta T/Delta ST of 0.13 (CI = 0.15 to 0.42) in the first occlusion to 1.02 (CI 0.31-1.73) in the second occlusion (P = 0.02). This integrated analysis of the T wave and ST segment goes beyond the standard approach to only analyze ST elevation, and detects cellular electrophysiology changes of preconditioning.
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| 7. |
- Kraja, Aldi T., et al.
(author)
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New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475000 Individuals
- 2017
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In: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 1942-325X .- 1942-3268. ; 10:5
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Journal article (peer-reviewed)abstract
- Background - Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association.Methods and Results - Here, we augment the sample with 140886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one in individuals of European, South Asian, African, and Hispanic descent (pan-ancestry, approximate to 475000), and the other in the subset of individuals of European descent (approximate to 423000). Twenty-one SNVs were genome-wide significant (P<5x10(-8) ) for BP, of which 4 are new BP loci: rs9678851 (missense, SLC4A1AP), rs7437940 (AFAP1), rs13303 (missense, STAB1), and rs1055144 (7p15.2). In addition, we identified a potentially independent novel BP-associated SNV, rs3416322 (missense, SYNPO2L) at a known locus, uncorrelated with the previously reported SNVs. Two SNVs are associated with expression levels of nearby genes, and SNVs at 3 loci are associated with other traits. One SNV with a minor allele frequency <0.01, (rs3025380 at DBH) was genome-wide significant.Conclusions - We report 4 novel loci associated with BP regulation, and 1 independent variant at an established BP locus. This analysis highlights several candidate genes with variation that alter protein function or gene expression for potential follow-up.
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| 8. |
- Pahlm, Olle, et al.
(author)
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Scientific MALT and STAFF meetings - past, present, and future
- 2016
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In: Journal of Electrocardiology. - : Elsevier BV. - 0022-0736. ; 49:3, s. 259-262
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Research review (peer-reviewed)abstract
- The scientific STAFF and MALT meetings were created around the turn of the century for scientists engaged in enhancing the role of the 12-lead ECG for detection and quantification of involved myocardium in patients with acute coronary syndrome. These meetings were initially focused on computer processing of data from two single-center databases. The STAFF database was collected in the mid-nineties on patients with prolonged total coronary occlusion; high-resolution 12-lead ECGs were collected before, during, and after 5 minutes of occlusion. The MALT database was created in the early years of this century on consecutive patients with chest pain admitted to a large teaching hospital. Delayed enhancement magnetic resonance imaging and electrocardiograms were recorded in these acutely ill patients. The paper highlights the first 2 decades of the STAFF and MALT meetings and details the meeting format.
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| 9. |
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| 10. |
- Pettersson, Jonas, et al.
(author)
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Changes in high-frequency QRS components are more sensitive than ST segment deviation for detecting acute coronary artery occlusion
- 2000
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In: Journal of the American College of Cardiology. - 0735-1097. ; 36:6, s. 1827-1834
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Journal article (peer-reviewed)abstract
- OBJECTIVES This study describes changes in high-frequency QRS components (HF-QRS) during percutaneous transluminal coronary angioplasty (PTCA) and compares the ability of these changes in HF-QRS and ST-segment deviation in the standard 12-lead electrocardiogram (ECG) to detect acute coronary artery occlusion. BACKGROUND Previous studies have shown decreased HF-QRS in the frequency range of 150–250 Hz during acute myocardial ischemia. It would be important to know whether the high-frequency analysis could add information to that available from the ST segments in the standard ECG. METHODS The study population consisted of 52 patients undergoing prolonged balloon occlusion during PTCA. Signal-averaged electrocardiograms (SAECG) were recorded prior to and during the balloon inflation. The HF-QRS were determined within a bandwidth of 150–250 Hz in the preinflation and inflation SAECGs. The ST-segment deviation during inflation was determined in the standard frequency range. RESULTS The sensitivity for detecting acute coronary artery occlusion was 88% using the high-frequency method. In 71% of the patients there was ST elevation during inflation. If both ST elevation and depression were considered, the sensitivity was 79%. The sensitivity was significantly higher using the high-frequency method, p < 0.002, compared with the assessment of ST elevation. CONCLUSIONS Acute coronary artery occlusion is detected with higher sensitivity using high-frequency QRS analysis compared with conventional assessment of ST segments. This result suggests that analysis of HF-QRS could provide an adjunctive tool with high sensitivity for detecting acute myocardial ischemia.
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| 11. |
- Ringborn, Michael, et al.
(author)
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Comparison of high-frequency QRS components and ST-segment elevation to detect and quantify acute myocardial ischemia.
- 2010
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In: Journal of Electrocardiology. - : Elsevier BV. - 1532-8430 .- 0022-0736. ; 43, s. 113-120
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Journal article (peer-reviewed)abstract
- OBJECTIVE: This study tests the ability of high-frequency components of the depolarization phase (HF-QRS) vs conventional ST-elevation criteria to detect and quantify myocardial ischemia. METHODS: Twenty-one patients admitted for elective percutaneous coronary intervention were included. Quantification of the ischemia was made by myocardial scintigraphy. High-resolution electrocardiogram before and during percutaneous coronary intervention was recorded and signal averaged. The HF-QRS were determined within the frequency band 150 to 250 Hz. ST-segment deviation was measured in the standard frequency range (<100 Hz). RESULTS: HF-QRS criteria were met by 76% of the patients, whereas 38% met the ST-elevation criteria (P = .008). Both HF-QRS reduction and ST elevation correlated significantly with the amount of ischemia (HF-QRS: r = 0.59, P = .005 for extent and r = 0.69, P = .001 for severity; ST elevation: r = 0.49, P = .023 for extent and r = 0.57, P = .007 for severity). CONCLUSIONS: This study suggests that HF-QRS analysis could provide valuable information both to detect acute ischemia and to quantify myocardial area at risk.
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| 12. |
- Ringborn, Michael, et al.
(author)
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The absence of high-frequency QRS changes in the presence of standard electrocardiographic QRS changes of old myocardial infarction
- 2001
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In: American Heart Journal. - : Elsevier BV. - 1097-6744 .- 0002-8703. ; 141:4, s. 573-579
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Journal article (peer-reviewed)abstract
- BACKGROUND: This study compares the high-frequency QRS components (HF-QRS) in patients with and without standard electrocardiogram (ECG) changes indicative of old myocardial infarction (MI). Previous studies have indicated that patients with an old MI differ in their HF-QRS compared with healthy subjects. The HF-QRS has been reported to be decreased during acute coronary occlusion and increased after reperfusion. However, there is controversy about the appearance of HF-QRS after the acute phase of MI. METHODS: A total of 154 patients were included, 57 with and 97 without QRS changes of old MI on the standard ECG. The patients with old MI were divided into subgroups on the basis of the MI location indicated by the standard ECG. Signal-averaged ECGs from the 12 standard leads were recorded. The root-mean-square values of the HF-QRS were determined within two frequency bands: 150 to 250 Hz and 80 to 300 Hz. RESULTS: There was a large interindividual variation in HF-QRS in patients without MI as well as in those with different MI locations. There were no significant differences between the groups in the summed HF-QRS of all 12 leads or in the pattern of lead distribution of the HF-QRS. Not even the patients with the greatest QRS changes of old MI could be differentiated from those without any changes of old MI on the standard ECG. The results were the same in both analyzed frequency bands. CONCLUSIONS: This study shows, contrary to previous studies, that analysis of HF-QRS cannot differentiate between patients with and without old MI.
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| 13. |
- Schlegel, Todd T., et al.
(author)
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Accuracy of advanced versus strictly conventional 12-lead ECG for detection and screening of coronary artery disease, left ventricular hypertrophy and left ventricular systolic dysfunction
- 2010
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In: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 10
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Journal article (peer-reviewed)abstract
- Background: Resting conventional 12-lead ECG has low sensitivity for detection of coronary artery disease (CAD) and left ventricular hypertrophy (LVH) and low positive predictive value (PPV) for prediction of left ventricular systolic dysfunction (LVSD). We hypothesized that a similar to 5-min resting 12-lead advanced ECG test ("A-ECG") that combined results from both the advanced and conventional ECG could more accurately screen for these conditions than strictly conventional ECG. Methods: Results from nearly every conventional and advanced resting ECG parameter known from the literature to have diagnostic or predictive value were first retrospectively evaluated in 418 healthy controls and 290 patients with imaging-proven CAD, LVH and/or LVSD. Each ECG parameter was examined for potential inclusion within multi-parameter A-ECG scores derived from multivariate regression models that were designed to optimally screen for disease in general or LVSD in particular. The performance of the best retrospectively-validated A-ECG scores was then compared against that of optimized pooled criteria from the strictly conventional ECG in a test set of 315 additional individuals. Results: Compared to optimized pooled criteria from the strictly conventional ECG, a 7-parameter A-ECG score validated in the training set increased the sensitivity of resting ECG for identifying disease in the test set from 78% (72-84%) to 92% (88-96%) (P < 0.0001) while also increasing specificity from 85% (77-91%) to 94% (88-98%) (P < 0.05). In diseased patients, another 5-parameter A-ECG score increased the PPV of ECG for LVSD from 53% (41-65%) to 92% (78-98%) (P < 0.0001) without compromising related negative predictive value. Conclusion: Resting 12-lead A-ECG scoring is more accurate than strictly conventional ECG in screening for CAD, LVH and LVSD.
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| 14. |
- ter Haar, C. Cato, et al.
(author)
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Difference vectors to describe dynamics of the ST segment and the ventricular gradient in acute ischemia
- 2013
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In: Journal of Electrocardiology. - : Elsevier BV. - 1532-8430 .- 0022-0736. ; 46:4, s. 302-311
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Journal article (peer-reviewed)abstract
- Background: The ECG is important in the diagnosis and triage of the acute coronary syndrome (ACS), especially in the hyperacute phase, the "golden hours," during which myocardial salvage possibilities are largest. An important triaging decision to be taken is whether or not a patient requires primary PCI, for which, as mentioned in the guidelines, the presence of an ST elevation (STE) pattern in the ECG is a major criterion. However, preexisting non-zero ST amplitudes (diagnostic, but also non-diagnostic) can obscure or even preclude this diagnosis. Methods: In this study, we investigated the potential diagnostic possibilities of ischemia detection by means of changes in the ST vector, Delta ST, and changes in the VG (QRST integral) vector, Delta VG. We studied the vectorcardiograms (VCGs) synthesized of the ECGs of 84 patients who underwent elective PTCA. Mean +/- SD balloon occlusion times were 260 +/- 76 s. The ECG ischemia diagnosis (ST elevation, STE, or non-ST-elevation, NSTE), magnitudes and orientations of the ST and VG vectors, and the differences Delta ST and Delta VG with the baseline ECG were measured after 3 min of balloon occlusion. Results: Planar angles between the Delta ST and Delta VG vectors were 14.9 +/- 14.0 degrees. Linear regression of Delta VG on Delta ST yielded Delta VG = 324. Delta ST (r = 0.85; P < 0.0001, Delta ST in mV). We adopted Delta ST > 0.05 mV, and the corresponding Delta VG > 16.2 mV.ms as ischemia thresholds. The classical criteria characterized the ECGs of 46/84 (55%) patients after 3 min of occlusion as STE ECGs. Combined application of the Delta ST and Delta VG criteria identified 73/84 (87%) of the patients as ischemic. Conclusion: Differential diagnosis by Delta ST and Delta VG (requiring an earlier made non-ischemic baseline ECG) could dramatically improve ECG guided detection of patients who urgently require catheter intervention. (C) 2013 Elsevier Inc. All rights reserved.
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