| 51. |
- Hallberg, Pär, et al.
(författare)
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The CYP2C9 genotype predicts the blood pressure response to irbesartan : results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs Atenolol (SILVHIA) trial
- 2002
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Ingår i: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 20:10, s. 2089-2093
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The cytochrome P450 CYP2C9 enzyme (CYP2C9) metabolizes many clinically important drugs, for example, phenytoin, warfarin and the angiotensin II type 1 (AT(1)) receptor antagonists, losartan and irbesartan. Single nucleotide polymorphisms in the CYP2C9 gene result in the expression of three important variants, CYP2C9*1(wild-type), CYP2C9*2 and CYP2C9*3, the last two exhibiting reduced catalytic activity compared with the wild-type. The CYP2C9 genotype is known to determine sensitivity to and dose requirements for both warfarin and phenytoin, and also the rate of metabolism of losartan. However, its influence on clinical response to treatment with the AT(1) receptor antagonist, irbesartan, has not been investigated. OBJECTIVE: To determine whether the CYP2C9genotype influences the blood pressure-decreasing response to antihypertensive treatment with irbesartan. DESIGN AND METHODS: One hundred and two patients with essential hypertension and left ventricular hypertrophy were allocated randomly to groups to receive double-blind treatment with either irbesartan (n = 49) or the beta(1)-adrenergic receptor blocker, atenolol ( n= 53). Blood pressure was measured before and after 12 weeks of treatment. genotyping was performed using solid-phase minisequencing. RESULTS: The diastolic blood pressure (DBP) response differed in relation to the CYP2C9 genotype in patients given irbesartan: the reduction in patients with genotype CYP2C9*1/CYP2C9*1 (n = 33) was 7.5% and that with CYP2C9*1/CYP2C9*2 (n = 12) was 14.4% ( P= 0.036). A similar trend was seen for systolic blood pressure. In contrast, no relation was seen between the CYP2C9 genotype and blood pressure response to atenolol, a drug not metabolized via CYP2C9. CONCLUSIONS: The CYP2C9 genotype seems to predict the DBP response to irbesartan, but not to atenolol, in patients with essential hypertension.
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| 52. |
- Hallberg, Pär, et al.
(författare)
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Transforming growth factor beta1 genotype and change in left ventricular mass during antihypertensive treatment : results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA)
- 2004
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Ingår i: Clinical Cardiology. - : Wiley. - 0160-9289 .- 1932-8737. ; 27:3, s. 169-73
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Angiotensin II, via the angiotensin II type 1 (AT1) receptor, may mediate myocardial fibrosis and myocyte hypertrophy seen in hypertensive left ventricular (LV) hypertrophy through production of transforming growth factor beta1 (TGF-beta1); AT1-receptor antagonists reverse these changes. The TGF-beta1 G + 915C polymorphism is associated with interindividual variation in TGF-beta1 production. No study has yet determined the impact of this polymorphism on the response to antihypertensive treatment. HYPOTHESIS: We aimed to determine whether the TGF-beta1 G + 915C polymorphism was related to change in LV mass during antihypertensive treatment with either an AT1-receptor antagonists or a beta1-adrenoceptor blocker. The polymorphism was hypothesized to have an impact mainly on the irbesartan group. METHODS: We determined the association between the TGF-beta1 genotype and regression of LV mass in 90 patients with essential hypertension and echocardiographically diagnosed LV hypertrophy, randomized in a double-blind study to receive treatment for 48 weeks with either the AT1-receptor antagonist irbesartan or the beta1-adrenoceptor blocker atenolol. RESULTS: Irbesartan-treated patients who were carriers of the C-allele, which is associated with low expression of TGF-beta1, responded with a markedly greater decrease in LV mass index (LVMI) than subjects with the G/G genotype (adjusted mean change in LVMI -44.7 g/m2 vs. -22.2 g/m2, p = 0.007), independent of blood pressure reduction. No association between genotype and change in LVMI was observed in the atenolol group. CONCLUSIONS: The TGF-beta1 G + 915C polymorphism is related to the change in LVMI in response to antihypertensive treatment with the AT1-receptor antagonist irbesartan.
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| 53. |
- Hayashi, Shirley Yumi, et al.
(författare)
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Improvement of cardiac function after haemodialysis : Quantitative evaluation by colour tissue velocity imaging
- 2004
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Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 19:6, s. 1497-1506
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Tidskriftsartikel (refereegranskat)abstract
- Background. Overhydration and accumulation of uraemic toxins may influence the myocardial function in haemodialysis (HD) patients. To evaluate cardiac function and the effects of fluid and solute removal during a single session of HD, colour tissue velocity imaging (TVI) was used. This new technique, which is less load dependent than conventional echocardiography, allows an objective quantitative assessment of myocardial contractility, contraction and relaxation. Methods. Conventional echocardiographic and TVI images were recorded before and after a single HD session in 13 clinically stable HD patients (62 +/- 10 years, six males) and in 13 sex- and age-matched healthy controls. Myocardial tissue velocities (v; cm/s) for isovolumetric contraction (IVC), peak systole (PS), early (E) and late (A') diastolic filling and strain rate (SR) were measured. Results. Left ventricular hypertrophy (LVH) was present in 12 patients. TVI gave additional information in comparison with conventional echocardiography. Before HD, PS (5.0 +/- 0.8 vs 6.0 +/- 1.2 cm/s, P < 0.05), E' (5.7 +/- 1.7 vs 7.3 +/- 2.0 cm/s, P < 0.05) and A' (6.6 +/- 1.7 vs. 8.3 +/- 2.9 cm/s, P < 0.05) velocities were lower in the patients than in the controls, indicating systolic and diastolic dysfunction. The HD session increased IVCv (4.0 +/- 1.7 to 5.5 +/- 1.9 cm/s; P < 0.001), PSv (5.0 +/- 0.8 to 5.7 +/- 0.8 cm/s; P < 0.05) and SR (0.7 +/- 0.2 to 0.9 +/- 0.2 1/s; P < 0.05) and decreased E/E' (16.7 +/- 7.7 to 12.2 +/- 4.0, P < 0.05), indicating improved systolic function and decreased LV filling pressure, respectively. Linear regression analysis demonstrated a dependency of systolic contraction (PSv) and contractility (IVCv) upon plasma levels of phosphate (r(2) = 0.70, P < 0.005, r(2) = 0.33, P < 0.01). Conclusions. Using TVI, HD patients demonstrate myocardial dysfunction, which is found less frequently when using conventional echocardiography. The systolic function seems to be impaired by high plasma levels of phosphate and an increased Ca x P product. One single session of HD improved systolic function as indicated by increases in IVCv, PSv and SR. Further studies are needed to clarify if this effect of HD is due to the acute removal of fluid, the removal of solutes or both.
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| 54. |
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| 55. |
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| 56. |
- Holmlund, A., et al.
(författare)
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Soluble intercellular adhesion molecule-1 is related to endothelial vasodilatory function in healthy individuals
- 2002
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Ingår i: Atherosclerosis. - 0021-9150 .- 1879-1484. ; 165:2, s. 271-276
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the associations between markers of systemic and vascular inflammation, and indicators of vascular morphology and function. METHODS: In 59 apparently healthy individuals, we measured serum levels of highly sensitive C-reactive protein (hsCRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin. Endothelium-dependent (EDV) and -independent (EIDV) vasodilatation was evaluated in the forearm by venous occlusion plethysmography and local infusions of methacholine and sodium nitroprussid. Endothelial function index (EFI) was expressed as the EDV/EIDV ratio. The intima-media thickness (IMT) of the common carotid artery was investigated with ultrasound (far wall). RESULTS: EFI was inversely related only to ICAM-1 (r=-0.31, P<0.02) by univariate analysis. This association remained significant after adjustment for age, sex, blood pressure, smoking and serum cholesterol. EFI did not relate to hsCRP, VCAM-1 or E-selectin. Neither hsCRP, nor the adhesion molecules were significantly related to carotid artery IMT. CONCLUSION: ICAM-1 was related to endothelial vasodilatory function, but not to IMT, suggesting that endothelial inflammatory activation is related to an impaired vascular relaxation in apparently healthy individuals.
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| 57. |
- Hänni, Arvo, et al.
(författare)
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Systolic blood pressure alterations during hyperinsulinemia are related to changes in ionized calcium status
- 2001
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Ingår i: American Journal of Hypertension. - 0895-7061 .- 1941-7225. ; 14:11 Pt 1, s. 1106-1111
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A correlation between changes in ionized calcium status and changes in systolic blood pressure (BP) has previously been observed during induced euglycemic hyperinsulinemia in patients with essential hypertension. The objective of this study was to evaluate associations between alterations in ion status and BP changes during euglycemic hyperinsulinemia in healthy normotensive subjects. METHODS: Ion status in plasma and BP were measured before and at the end of euglycemic hyperinsulinemic clamp tests performed in 41 healthy normotensive volunteers. RESULTS: During euglycemic hyperinsulinemia plasma sodium increased by 1% (P < .0001), ionized calcium (iCa) by 5% (P < .0001), and ionized magnesium (iMg) by 4% (P < .01), whereas potassium decreased by 10% (P < .0001). The changes in plasma iCa and iMg correlated significantly to changes in systolic BP (r = -0.38, P < .02; r = -0.32, P < .05, respectively), but the correlation between changes in iMg and changes in systolic BP did not remain significant in a multiple regression model. The glucose infusion rate correlated inversely to the change in iMg (r = -0.39, P < .01). CONCLUSIONS: The group mean systolic BP was unaltered during induced euglycemic hyperinsulinemia in healthy normotensive subjects; however, a more pronounced increase in the circulating iCa concentration was associated with a greater decline in systolic BP, which is in accordance with previous observations in patients with essential hypertension. The group mean diastolic BP was decreased; however, the lowered diastolic BP was not correlated to changes in ion status.
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| 58. |
- Jensen, J., et al.
(författare)
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Deterioration in peak systolic velocity is closely related to ischaemia during angioplasty : a vectorcardiographic and tissue Doppler imaging study
- 2001
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Ingår i: Clinical Science. - : Portland Press Ltd.. - 0143-5221 .- 1470-8736. ; 100:2, s. 137-143
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Tidskriftsartikel (refereegranskat)abstract
- We tested the hypothesis that the extent of signs of ischaemia detected by vectorcardiography (VCG) during elective coronary angioplasty (percutaneous transluminal coronary angioplasty: PTCA) is related to systolic and diastolic myocardial velocities, as determined by tissue Doppler echocardiography. A total of 15 patients undergoing PTCA (12 men/three women; age 61 +/- 9 years), without prior myocardial infarction and with an election fraction of > 50%, were included. The balloon inflation was repeated three times, with minimum intervals of 2 min between inflations. Tissue Doppler echocardiography was performed. in an apical two- or four-chamber view, before and at the end of each inflation. Peak systolic velocity, time-to-peak systolic velocity (TTP), peak early (E-m) and late (A(m)) diastolic velocities, the E-m/A(m) ratio and jsovolumic relaxation time were measured in the basal segments of the left ventricle. VCG recordings were carried out during the whole procedure. ST vector magnitude (ST-VM) and ST change vector magnitude (STC-VM) were monitored. The total duration and area of each VCG change during inflation were calculated for each patient. Isovolumic relaxation time, peak E-m and A(m) values and the E-m/A(m) ratio did not change significantly during inflation. Peak systolic velocity decreased (6.7+/-2.0 to 5.3 +/- 1.9 cm/s; P < 0.001) and TTP increased (157 +/- 60 to 192 +/- 60 ms; P<0.01) during inflation. Both STC-VM rime (r = -0.68, P<0.01) and STC-VM area (r = -0.68, P < 0.01) were related to peak systolic velocity during inflation. STC-VM time was also related (r = 0.55, P < 0.05) to the difference in peak systolic velocity during compared with before inflation. ST-VM was less closely related to peak systolic velocity. Thus the duration and degree of ischaemia, as measured by VCG, are related to peak systolic velocity in the basal segments of the left ventricle.
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| 59. |
- Johansson, Kristina, et al.
(författare)
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Effects of blockade of alpha- and beta-adrenoceptors and neuropeptide Y(1) receptors, as well as brachial plexus blockade, on endothelium-dependent vasodilation in the human forearm
- 2002
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Ingår i: Clinical and experimental pharmacology & physiology. - : Wiley. - 0305-1870 .- 1440-1681. ; 29:7, s. 603-607
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Tidskriftsartikel (refereegranskat)abstract
- 1. The aim of the present study was to investigate the effects of alpha-adrenoceptor blockade (phentolamine), beta-adrenoceptor blockade (propranolol), neuropeptide Y(1) receptor blockade and neurogenic blockade (brachial plexus) on endothelium-dependent vasodilation (EDV) in the human forearm. 2. Forty-four young healthy volunteers underwent forearm blood flow (FBF) measurements, using venous occlusion plethysmography, during local intra-arterial infusions of methacholine (MCh; inducing EDV) and sodium nitroprusside (SNP; inducing endothelium-independent vasodilation (EIDV)). These measurements were undertaken at baseline and were repeated with either concomitant local intra-arterial infusion of phentolamine (n = 8), propranolol (n = 7) or saline (n = 6) in the forearm, neuropeptide Y(1) receptor blockade (n = 12) given i.v. or during axillary plexus blockade (n = 11). 3. Both alpha-adrenoceptor blockade and neurogenic blockade induced an upward shift in the dose-response curve for both EDV and EIDV. beta-Adrenoceptor blockade did not change resting FBF or EIDV, but induced a significant decrease in EDV (P = 0.015). Neuropeptide Y(1) receptor blocker induced no significant changes in resting FBF, EDV and EIDV and neither did saline. No changes in blood pressure or heart rate were induced by any of the blockades. 4. Whereas beta-adrenoceptor blockade impaired EDV, alpha-adrenoceptor blockade and neurogenic blockade caused a general vasodilation that was not endothelium dependent. Neuropeptide Y does not seem to influence blood flow in the resting forearm.
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