| 1. |
- Hallberg, Pär, et al.
(författare)
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Adipocyte-derived leucine aminopeptidase genotype and response to antihypertensive therapy
- 2003
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261 .- 1471-2261. ; 18:3, s. 11-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAdipocyte-derived leucine aminopeptidase (ALAP) is a recently identified member of the M1 family of zinc-metallopeptidases and is thought to play a role in blood pressure control through inactivation of angiotensin II and/or generation of bradykinin. The enzyme seems to be particularly abundant in the heart. Recently, the Arg528-encoding allele of the ALAP gene was shown to be associated with essential hypertension.MethodsWe evaluated the influence of this polymorphism on the change in left ventricular mass index in 90 patients with essential hypertension and echocardiographically diagnosed left ventricular hypertrophy, randomised in a double-blind study to receive treatment with either the angiotensin II type I receptor antagonist irbesartan or the beta1-adrenoceptor blocker atenolol for 48 weeks. Genyotyping was performed using minisequencing.ResultsAfter adjustment for potential covariates (blood pressure and left ventricular mass index at baseline, blood pressure change, age, sex, dose and added antihypertensive treatment), there was a marked difference between the Arg/Arg and Lys/Arg genotypes in patients treated with irbesartan; those with the Arg/Arg genotype responded on average with an almost two-fold greater regression of left ventricular mass index than patients with the Lys/Arg genotype (-30.1 g/m2 [3.6] vs -16.7 [4.5], p = 0.03).ConclusionsThe ALAP genotype seems to determine the degree of regression of left ventricular hypertrophy during antihypertensive treatment with the angiotensin II type I receptor antagonist irbesartan in patients with essential hypertension and left ventricular hypertrophy. This is the first report of a role for ALAP/aminopeptidases in left ventricular mass regulation, and suggests a new potential target for antihypertensive drugs.
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| 2. |
- Bhadani, Kanishk, 1991, et al.
(författare)
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CDIO Course Development for Faculty in Raw Materials Programmes
- 2017
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Ingår i: The 13th International CDIO Conference Proceedings, Calgary, Canada. - 1796-9964. - 9780889533998 ; , s. 315-326
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Konferensbidrag (refereegranskat)abstract
- In Europe, the existing MSc programmes which are linked to the thematic Raw Material content often focus mainly on technical knowledge in itself, and students graduate as professionals who know how to solve pre-defined technical problems. Students in such programmes seldom practice entrepreneurial, communication and innovation skills at a level that is needed in working life. On the other hand, the CDIO Initiative has developed a framework for modernizing engineering education by introducing such skills and thinking into the technical programmes and courses. It is widely discussed in the CDIO community that one of the constraints in implementing CDIO is faculty staff professional development. CDIO standards 9 and 10 focus on the faculty development and competencies both in terms of pedagogic as well as learning methods to deal with personal and interpersonal skills, and product, process, and system building skills. In order to bring a change and implement CDIO into the Raw Materials programmes in Europe, a modular course for training in CDIO was developed and delivered for the faculty member in the Raw Materials sector. This paper accounts for the development of the faculty training course, and provides a unique perspective on the implementation of CDIO into raw materials related programmes capturing the different models of implementation from different universities’ programmes and courses. The various universities involved provide programmes and courses across the entire value chain of raw materials from mining and minerals processing to materials design, sustainability and recycling. This paper will serve as a reference for the educators to develop and implement CDIO education methods in specific disciplines as illustrated here in the field of raw materials related programmes.
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| 3. |
- Conradsson, Mia, et al.
(författare)
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Berg Balance Scale : intrarater test-retest reliability among older people dependent in activities of daily living and living in residential care facilities
- 2007
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Ingår i: Physical Therapy. - : Oxford University Press (OUP). - 0031-9023 .- 1538-6724. ; 87:9, s. 1155-1163
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Tidskriftsartikel (refereegranskat)abstract
- The Berg Balance Scale (BBS) is frequently used to assess balance in older people, but knowledge is lacking about the absolute reliability of BBS scores. The aim of this study was to investigate the absolute and relative intrarater test-retest reliability of data obtained with the BBS when it is used among older people who are dependent in activities of daily living and living in residential care facilities. The participants were 45 older people (36 women and 9 men) who were living in 3 residential care facilities. Their mean age was 82.3 years (SD=6.6, range=68-96), and their mean score on the Mini Mental State Examination was 17.5 (SD=6.3, range=4-30). The BBS was assessed twice by the same assessor. The intrarater test-retest reliability assessments were made at approximately the same time of day and with 1 to 3 days in between assessments. Absolute reliability was calculated using an analysis of variance with a 95% confidence level, as suggested by Bland and Altman. Relative reliability was calculated using the intraclass correlation coefficient (ICC). The mean score was 30.1 points (SD=15.9, range=3-53) for the first BBS test and 30.6 points (SD=15.6, range=4-54) for the retest. The mean absolute difference between the 2 tests was 2.8 points (SD=2.7, range=0-11). The absolute reliability was calculated as being 7.7 points, and the ICC was calculated to .97. Despite a high ICC value, the absolute reliability showed that a change of 8 BBS points is required to reveal a genuine change in function among older people who are dependent in activities of daily living and living in residential care facilities. This knowledge is important in the clinical setting when evaluating an individual's change in balance function over time in this group of older people.
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| 4. |
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| 5. |
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| 6. |
- Conradsson, Mia, et al.
(författare)
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The Berg Balance Scale : Intra-rater reliability in older people dependent in ADL and living in residential care facilities
- 2006
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Aim: The aim of this study was to investigate the absolute and the relative intra-rater reliability of the Berg Balance Scale (BBS) among older people who are dependent in activities of daily living (ADL) and living in residential care facilities.Methods: The participants were 45 older people, 36 females and 9 men, who were dependent in ADL and living in three residential care facilities. Their mean age ± SD was 82.3 ± 6.6 (range 68-96) and mean ± SD of Mini Mental State Examination score was 17.5 ± 6.3 (range 4-30). The BBS was assessed twice by the same assessor, at approximately the same time of day, and with 1-3 days in between. The absolute reliability for the difference in score between the two test occasions was calculated with the Bland and Altman analysis of variance with 95 % confidence level. The relative reliability was calculated with Intraclass Correlation Coefficient (ICC).Results: For the first test of the BBS, mean ± SD was 30.1 ± 15.9 (range 3-53) points and for the retest 30.6 ± 15.6 (range 4-54). The absolute difference between the two test occasions was in mean ± SD 2.8 ± 2.7 (range 0-11) points. The absolute intra-rater reliability was calculated to 7.7 points and the ICC value was 0.97. Conclusions: Despite a high ICC value, the result of the absolute reliability show that a change of 8 BBS points is required to reveal a genuine change of function among older people who are dependent in ADL and living in residential care facilities. This knowledge is important in the clinical setting when evaluating an individual's change in balance function over time.
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| 7. |
- Falk, Johan, et al.
(författare)
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Exponential Roadmap: Scaling 36 Solutions to Halve Emissions by 2030
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The 2019 Exponential Roadmap focuses on moving from incremental to exponential climate action in the next decade. It presents 36 economically- viable solutions to cut global greenhouse gas emissions 50% by 2030 and the strategies to scale this transformation. The roadmap is consistent with the Paris Agreement’s goal to keep global average temperature “well below 2°C” and aiming for 1.5°C above pre- industrial levels. The 2019 roadmap is the second in the series. Each new roadmap updates solutions that have proven potential to scale and charts progress towards exponential scaling. The roadmap, based on the carbon law (see box) is a collaboration between academia, business and civil society. The roadmap is complemented with a high-ambition narrative, Meeting the 1.5°C Ambition, that presents the case why holding global average temperature increase to just 1.5°C above pre-industrial levels is important. Since the first roadmap, the Intergovernmental Panel on Climate Change (IPCC) published its special report on 1.5°C. The report concluded that the economic and humanitarian risks of a 2°C world are significantly higher than 1.5°C. The remaining emissions budget for 1.5°C is small, and will be exceeded within ten to fifteen years at current emission rates. The window of feasibility is closing rapidly. The global economic benefit of a low-carbon future is estimated at US$26 trillion by 2030 compared with staying on the current high-carbon pathway. The scale of transformation – halving emissions by 2030 – is unprecedented but the speed is not. Some cities and companies can transform significantly faster. Developed nations with significant historic emissions have a responsibility to reduce emissions faster. Greenhouse gas emissions, and the solutions to reduce them, are grouped by six sectors: energy, industry, transport, buildings, food consumption, nature-based solutions (sources and sinks). Meeting the 1.5°C goal means implementing solutions in parallel across all sectors. The solutions must scale exponentially. The roadmap identifies four levers required to scale the transformation as well as necessary actions for each: policy, climate leadership and movements, finance and exponential technology. Implementation must be fair and just or risk deep resistance.
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| 8. |
- Hallberg, Pär, et al.
(författare)
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B2 bradykinin receptor (B2BKR) polymorphism and change in left ventricular mass in response to antihypertensive treatment : results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial
- 2003
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Ingår i: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 21:3, s. 621-4
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Hypertension is associated with a number of adverse morphologic and functional changes in the cardiovascular system, including left ventricular (LV) hypertrophy. Studies have demonstrated that bradykinin, through the B2 bradykinin receptor (B2BKR), mediates important cardiovascular effects that may protect against LV hypertrophy. Recently, a +9/-9 exon 1 polymorphism of the B2BKR was shown to be strongly associated with LV growth response among normotensive males undergoing physical training. We aimed to clarify whether the processes found in exercise-induced LV growth in normotensive people also occur in pathological LV hypertrophy. DESIGN AND METHODS: We determined the B2BKR genotype of 90 patients with essential hypertension and echocardiographically diagnosed LV hypertrophy, included in a double-blind study to receive treatment for 48 weeks with either the angiotensin II type 1 (AT1) receptor antagonist irbesartan or the beta1-adrenoceptor antagonist atenolol. RESULTS: B2BKR +9/+9 genotypes responded poorly in LV mass regression, independent of blood pressure reduction or treatment, as compared to the other genotypes (adjusted mean change in LV mass index = -10.0 +/- 4.6 versus -21.6 +/- 2.2 g/m2, P = 0.03). CONCLUSIONS: Our results suggest an impact of the B2BKR polymorphism on LV mass regression during antihypertensive treatment.
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| 9. |
- Hallberg, Pär, et al.
(författare)
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Gender-specific association between preproendothelin-1 genotype and reduction of systolic blood pressure 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. ; 27:5, s. 287-290
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Studies suggest that endothelin-1 contributes to the pathogenesis of hypertension. A G5665T gene polymorphism of preproendothelin-1 has been shown to be associated with higher blood pressure in overweight patients. No study has yet determined the effect of this polymorphism on the change in blood pressure during antihypertensive treatment.HYPOTHESIS:This study aimed to determine this effect in hypertensive patients with left ventricular (LV) hypertrophy during antihypertensive treatment with either irbesartan or atenolol.METHODS: We determined the preproendothelin-1 genotype using minisequencing in 102 patients with essential hypertension and LV hypertrophy verified by echocardiography, randomized in a double-blind fashion to treatment with either the AT1-receptor antagonist irbesartan or the beta1-adrenoceptor antagonist atenolol.RESULTS:The change in systolic blood pressure (SBP) after 12 weeks of treatment was related to the preproendothelin-1 genotype in men; after adjustment for potential covariates (age, blood pressure, and LV mass index at study entry, dose of irbesartan/atenolol, and type of treatment), those carrying the T-allele responded on average with a more than two-fold greater reduction than those with the G/G genotype (-21.9 mmHg [13.9] vs. -8.9 [2.3], p = 0.007). No significant differences in blood pressure change between G/G and carriers of the T-allele were seen among women.CONCLUSIONS:Our finding suggests a gender-specific relationship between the G5665T preproendothelin-1 polymorphism and change in SBP in response to antihypertensive treatment with irbesartan or atenolol, suggesting the endothelin pathway to be a common mechanism included in the hypertensive action of the drugs.
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| 10. |
- 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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| 11. |
- 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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| 12. |
- Karlsson, Julia, et al.
(författare)
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Beta1-adrenergic receptor gene polymorphisms and response to beta1-adrenergic receptor blockade in patients with essential hypertension
- 2004
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Ingår i: Clinical Cardiology. - : Wiley. - 0160-9289 .- 1932-8737. ; 27:6, s. 347-350
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Studies suggest that the Ser49Gly and Arg389Gly polymorphisms in the beta1-adrenergic receptor might be of functional importance for the cardiovascular system. Both have been associated with altered receptor activity in vitro, and with hypertension and cardiac failure in vivo. HYPOTHESIS: The aim of this study was to test whether these polymorphisms were associated with the change in heart rate or blood pressure in patients with essential hypertension and left ventricular (LV) hypertrophy treated with the beta1-adrenergic receptor blocker atenolol. METHODS: Blood pressure and heart rate were measured in 101 hypertensive patients with echocardiographically verified LV hypertrophy, randomized in a double-blind study to treatment with either the beta1-adrenergic receptor blocker atenolol or the angiotensin II type I receptor antagonist irbesartan. Changes in blood pressure and heart rate were evaluated after 12 weeks. Beta1-adrenergic receptor genotyping was performed using polymerase chain reaction and restriction fragment length polymorphism. RESULTS: We found no significant associations between the changes in the measured variables and either of the two polymorphisms. However, carriers of the 49Gly allele showed a tendency toward a greater reduction in heart rate compared with patients with the Ser/Ser49 genotype (p = 0.06). CONCLUSIONS: The Ser49Gly and Arg389Gly beta1-adrenergic receptor polymorphisms do not seem to exert a major effect on the changes in heart rate and blood pressure during 12 weeks of treatment with atenolol in patients with essential hypertension and LV hypertrophy.
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| 13. |
- Kurland, Lisa, et al.
(författare)
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Aldosterone synthase (CYP11B2) -344 C/T polymorphism is related to antihypertensive response : result from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial
- 2002
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Ingår i: American Journal of Hypertension. - : Elsevier. - 0895-7061 .- 1941-7225. ; 15:5, s. 389-93
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Our aim was to determine whether the aldosterone synthase (CYP11B2) -344 C/T polymorphism was associated with the blood pressure (BP)-lowering response to antihypertensive treatment. METHODS: Patients with mild-to-moderate primary hypertension and left ventricular hypertrophy were randomized in a double-blind study to receive treatment with either the angiotensin II type 1 (AT1) receptor antagonist irbesartan (n = 43), or the beta1-adrenergic receptor blocker atenolol (n = 43). The aldosterone synthase (CYP11B2) -344 C/T polymorphism was analyzed using solid-phase minisequencing and related to BP reduction after 3 months treatment. Serum aldosterone levels were measured. RESULTS: After 3 months treatment the mean reductions in BP were similar for both treatment groups. When assessing the systolic BP reduction in the irbesartan group, patients with the TT variant had a more pronounced reduction (-21 +/- 19 SD mm Hg, n = 17) than both the TC (-14 +/- 18 mm Hg, n= 18) and CC (0 +/- 17 mm Hg, n = 8) genotypes (P = .04). There was no association between this polymorphism and the diastolic BP response. The -344 C/T polymorphism was not associated with the BP response to atenolol. Nor was it related to the baseline serum aldosterone level. CONCLUSIONS: The aldosterone synthase -344 C/T polymorphism was related to the BP-lowering response in hypertensive patients treated with the AT1-receptor antagonist irbesartan.
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| 14. |
- Kurland, Lisa, et al.
(författare)
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Angiotensin converting enzyme gene polymorphism predicts blood pressure response to angiotensin II receptor type 1 antagonist treatment in hypertensive patients
- 2001
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Ingår i: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 19:10, s. 1783-1787
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To determine whether polymorphisms in the renin-angiotensin system can predict blood pressure-lowering response to antihypertensive treatment; more specifically, in response to treatment with irbesartan or atenolol. DESIGN AND METHODS: Eighty-six patients with hypertension were randomized to double-blind treatment with either the angiotensin II type 1 receptor antagonist irbesartan or the beta1 adrenergic receptor blocker atenolol and followed for 3 months. We analysed angiotensinogen T174M and M235T, angiotensin converting enzyme (ACE) I/D and angiotensin II type 1 receptor A1166C polymorphisms and related them to blood pressure reduction. RESULTS: The mean reductions in blood pressure were similar for both treatments. In the irbesartan group, individuals homozygous for the ACE gene I allele showed a greater reduction in diastolic blood pressure, exceeding those with the D allele (-18 +/- 11 SD versus -7 +/- 10 mmHg, P = 0.0096). This was not the case during treatment with atenolol, and the interaction term between type of treatment and ACE II genotype was significant (P = 0.0176). The angiotensinogen and angiotensin II type 1 receptor polymorhisms were not related to the response to treatment. CONCLUSIONS: ACE genotyping predicted the blood pressure-lowering response to antihypertensive treatment with irbesartan but not atenolol. Thus, specific genotypes might predict the response to specific antihypertensive treatment.
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| 15. |
- Kurland, Lisa, 1960-, et al.
(författare)
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Angiotensinogen gene polymorphisms : relationship to blood pressure response to antihypertensive treatment. Results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs Atenolol (SILVHIA) trial
- 2004
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Ingår i: American Journal of Hypertension. - : Oxford University Press (OUP). - 0895-7061 .- 1941-7225. ; 17:1, s. 8-13
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) is important for the development of hypertension, and several antihypertensive drugs target this system. Our aim was to determine whether specific single nucleotide polymorphisms (SNPs) in RAAS genes were related to the blood pressure (BP) lowering effect of antihypertensive treatment. METHODS: Patients with mild to moderate primary hypertension and left ventricular hypertrophy were randomized in a double-blind fashion to treatment with either the angiotensin II type 1 receptor antagonist irbesartan (n = 48) or the beta(1)-adrenergic receptor blocker atenolol (n = 49) as monotherapy. A microarray-based minisequencing system was used to genotype 30 SNPs in seven genes in the RAAS. These polymorphisms were related to the antihypertensive response after 12 weeks treatment. RESULTS: The BP reductions were similar in the atenolol and the irbesartan groups. Presence of the angiotensinogen (AGT) -6A allele or the AGT 235T allele were both associated with the most pronounced systolic BP response to atenolol treatment (P =.001 when -6 AA+AG was compared with GG and P =.008 for presence of the 235T variant compared with 235 MM). CONCLUSIONS: We found that SNPs in the angiotensinogen gene were associated with the BP lowering response to atenolol. This study is limited by a relatively small sample size, and the results should therefore be viewed as preliminary. Despite this limitation, these results illustrate the potential of using SNP genotyping as a pharmacogenetic tool in antihypertensive treatment.
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| 16. |
- Kurland, Lisa, 1960-, et al.
(författare)
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Polymorphisms in the angiotensinogen and angiotensin II type 1 receptor gene are related to change in left ventricular mass during antihypertensive treatment : results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial
- 2002
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Ingår i: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 20:4, s. 657-663
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Our aim was to determine if gene polymorphisms in the renin-angiotensin-aldosterone system (RAAS) were related to the degree of change in left ventricular hypertrophy (LVH) during antihypertensive treatment. METHODS AND RESULTS: Patients with essential hypertension and echocardiographically diagnosed LVH were included in a double-blind study to receive treatment with either the angiotensin II type 1 receptor (AT1-receptor) antagonist irbesartan (n = 41), or the beta-1 adrenergic receptor blocker atenolol (n = 43) as monotherapy for 3 months. The angiotensinogen T174M and M235T, the angiotensin-converting enzyme I/D, the AT1-receptor A1166C and the aldosterone synthase (CYP11B2) -344 C/T polymorphisms were analysed and related to the change in left ventricular mass (LVM). Patients with the angiotensinogen 174 TM genotype treated with irbesartan responded with the greatest reduction in LVM (-23 +/- 31SD g/m2 for TM and +0.5 +/- 18 g/m2 for TT, P = 0.005), independent of blood pressure reduction. Both the angiotensinogen 235 T-allele (P = 0.02) and the AT1-receptor 1166 AC genotype responded with the greatest reduction in LVM when treated with irbesartan (-0.1 +/- 19 g/m2 for AA and -18 +/- 30 g/m2 for AC, P = 0.02), independent of blood pressure reduction. These polymorphisms were not associated with the change in LVM during treatment with atenolol. DISCUSSION: The angiotensinogen T174M and M235T and the AT1-receptor A1166C polymorphisms were related to the change in LVH during antihypertensive treatment with an AT1-receptor antagonist; of these angiotensinogen T174M was the most powerful. This highlights the role of the RAAS for left ventricular hypertrophy and the potential of pharmacogenetics as a tool for guidance of antihypertensive therapy.
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| 17. |
- Liljedahl, Ulrika, et al.
(författare)
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Single nucleotide polymorphisms predict the change in left ventricular mass in response to antihypertensive treatment
- 2004
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Ingår i: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 22:12, s. 2321-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Our aim was to determine whether the change in left ventricular (LV) mass in response to antihypertensive treatment could be predicted by multivariate analysis of single nucleotide polymorphisms (SNPs) in candidate genes reflecting pathways likely to be involved in blood pressure control. METHODS: Patients with mild to moderate primary hypertension and LV hypertrophy were randomized in a double-blind fashion to treatment with either the angiotensin II type 1 receptor antagonist irbesartan (n = 48) or the beta1 adrenoreceptor blocker atenolol (n = 49). A microarray-based minisequencing system was used for genotyping 74 SNPs in 25 genes. These genotypes were related to the change in LV mass index by echocardiography, after 12 weeks treatment as monotherapy, using stepwise multiple regression analysis. RESULTS: The blood pressure reductions were similar and significant in both treatment groups. Two SNPs in two separate genes (the angiotensinogen T1198C polymorphism, corresponding to the M235T variant and the apolipoprotein B G10108A polymorphism) for those treated with irbesartan, and the adrenoreceptor alpha2A A1817G for those treated with atenolol, significantly predicted the change in LV mass. The predictive power of these SNPs was independent of the degree of blood pressure reduction. CONCLUSION: SNPs in the angiotensinogen, apolipoprotein B, and the alpha2 adrenoreceptor gene predicted the change in LV mass during antihypertensive therapy. These results illustrate the potential of using microarray-based technology for SNP genotyping in predicting individual drug responses.
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