| 1. |
- Glasbey, JC, et al.
(författare)
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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.
(författare)
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Meta-analysis of genome-wide association studies of HDL cholesterol response to statins
- 2016
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Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 53:12, s. 835-45
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Tidskriftsartikel (refereegranskat)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.
(författare)
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Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.
- 2014
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5
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Tidskriftsartikel (refereegranskat)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.
(författare)
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An electrocardiographic sign of ischemic preconditioning
- 2014
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Ingår i: American Journal of Physiology: Heart and Circulatory Physiology. - : American Physiological Society. - 1522-1539 .- 0363-6135. ; 307:1, s. 80-87
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Tidskriftsartikel (refereegranskat)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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| 6. |
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| 7. |
- Kraja, Aldi T., et al.
(författare)
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New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475000 Individuals
- 2017
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Ingår i: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 1942-325X .- 1942-3268. ; 10:5
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Tidskriftsartikel (refereegranskat)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.
(författare)
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Scientific MALT and STAFF meetings - past, present, and future
- 2016
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Ingår i: Journal of Electrocardiology. - : Elsevier BV. - 0022-0736. ; 49:3, s. 259-262
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Forskningsöversikt (refereegranskat)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.
(författare)
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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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Ingår i: Journal of the American College of Cardiology. - 0735-1097. ; 36:6, s. 1827-1834
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Tidskriftsartikel (refereegranskat)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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