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- Malmqvist, K., et al.
(författare)
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Cardiac repolarization and its relation to ventricular geometry and rate in reverse remodelling during antihypertensive therapy with irbesartan or atenolol: results from the SILVHIA study
- 2007
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Ingår i: J Hum Hypertens. - 0950-9240.
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Tidskriftsartikel (refereegranskat)abstract
- Hypertensive left ventricular (LV) hypertrophy is associated with a substantial risk for malignant arrhythmias and sudden death. According to recent results, antihypertensive therapy with the angiotensin II type 1 receptor blocker irbesartan reverses both structural and electrical remodelling. However, the relation between the LV geometric pattern (concentric vs eccentric) and electrical reverse remodelling has not been characterized, neither has the relation between repolarization and rate (QT/RR and JT/RR relation), which presumably reflects the propensity for bradycardia-dependent ventricular arrhythmia. In this study, repeat echocardiographic and electrocardiographic measurements were performed in hypertensive patients with LV hypertrophy, randomized to double-blind therapy with irbesartan (n=44) or the beta(1)-adrenoceptor blocker atenolol (n=48) for 48 weeks; 53 patients had concentric and 39 eccentric LV hypertrophy. In addition, 37 matched hypertensive subjects without LV hypertrophy and no current therapy served as controls. Irbesartan induced structural and electrophysiological reverse remodelling, independent of LV geometry. In contrast, atenolol had similar beneficial effect only in patients with concentric LV hypertrophy, while the response in those with eccentric hypertrophy was unfavourable with both prolonged repolarization time and an increased QT/RR slope (suggesting reverse-use dependence). In conclusion, there is a significant geometry-related difference in the reverse remodelling processes induced by irbesartan and atenolol. Echocardiographic characterization of the geometry in hypertension-induced LV hypertrophy might become an important step in the selection of optimal antihypertensive therapy.Journal of Human Hypertension advance online publication, 19 July 2007; doi:10.1038/sj.jhh.1002250.
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- Mercke Odeberg, Johanna, et al.
(författare)
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UGT1A polymorphisms in a Swedish cohort and a human diversity panel, and the relation to bilirubin plasma levels in males and females
- 2006
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Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 62:10, s. 829-837
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The objective of this study was to investigate the prevalence of different polymorphisms and haplotypes associated with individual variations in pharmacokinetics and drug toxicity in the uridine-diphosphate glucuronosyl transferase (UGT) 1A gene in a Swedish cohort (248 healthy volunteers) and in 14 different ethnic groups. We also estimated UGT1A genotype-dependent glucuronidation efficiency using the endogenous substrate bilirubin as an indicator. Methods: Pyrosequencing-based genotyping assays were used to determine the different polymorphisms and haplotypes. Results: Haplotype analysis of the UGT1A1 (*1*28), UGT1A6 (*1*2), and UGT1A7(*1*2*3*4) allelic variants showed that three major haplotypes constituted 84% of the allelic variants in the cohort. We identified 15 haplotypes altogether from all groups, including previously undescribed haplotypes.Testing for the association of genotype and total bilirubin levels (nonfasting) in plasma disclosed that homozygous carriers of the TA allele, irrespective of haplotype combinations, had increased levels of bilirubin compared with noncarriers, but a gender-associated difference was observed. Conclusions: In a Swedish cohort, several genetic variants in the UGT1A gene are common, but prevalence in a population may differ because of ethnicity. A phenotype based on bilirubin levels has limitations in serving as an indicator of pharmacogenetic differences in glucuronidation due to the influence of gender. Because of possible substrate overlap regarding different UGT1A isoforms, determination of haplotypes of potential cis-acting polymorphisms in the UGT1A gene should be considered in pharmacogenetic association studies regarding drugs that undergo glucuronidation.
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- Mörtsell, David, et al.
(författare)
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Irbesartan reduces common carotid artery intima-media thickness in hypertensive patients when compared with atenolol : the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) study
- 2007
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 261:5, s. 472-479
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose. Angiotensin II promotes cell growth and has been implicated in the development and maintenance of left ventricular (LV) hypertrophy and of structural vascular changes. We wished to examine whether an angiotensin receptor blocker (ARB) would influence structural vascular changes beyond the effects of blood pressure reduction.Methods. Hypertensive patients with LV hypertrophy (age 55 ± 9 years, blood pressure 162 ± 19/104 ± 8 mmHg, LV mass index 148 ± 31 g m−2; mean ± SD) were randomized double-blind to the ARB irbesartan (n = 52) or the beta1 receptor blocker atenolol (n = 56) for 48 weeks. Ultrasonography of the left and right common carotid artery (CCA) and echocardiography were performed at week 0 and 48.Results. With similar reductions in blood pressure, CCA intima-media thickness (IMT) was reduced by irbesartan (from 0.92 ± 0.14 by 0.01 ± 0.10 mm, NS), whereas it was increased by atenolol (from 0.94 ± 0.21 by 0.03 ± 0.12 mm, P = 0.018; P = 0.002 between groups). CCA lumen diameter was less reduced by irbesartan than by atenolol. Thus, CCA intima-media area was reduced by irbesartan (from 21.3 ± 5.0 by 0.90 ± 2.45 mm2, P = 0.034) but not by atenolol (from 21.3 ± 6.1 by 0.18 ± 2.71 mm2, NS; P = 0.037 between groups). Changes in CCA IMT or area did not relate to changes in LV mass.Conclusions. The favourable effects by irbesartan on CCA IMT with an outward vascular remodelling suggest that angiotensin II mediates structural vascular changes, beyond the effects of blood pressure. This may be important in the prevention of cerebrovascular events.
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