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- 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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- Liljedahl, Ulrika, et al.
(författare)
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Single nucleotide polymorphisms in the apolipoprotein B and low density lipoprotein receptor genes affect response to antihypertensive treatment
- 2004
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261 .- 1471-2261. ; 4:1, s. 16-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Dyslipidemia has been associated with hypertension. The present study explored if polymorphisms in genes encoding proteins in lipid metabolism could be used as predictors for the individual response to antihypertensive treatment. METHODS: Ten single nucleotide polymorphisms (SNP) in genes related to lipid metabolism were analysed by a microarray based minisequencing system in DNA samples from ninety-seven hypertensive subjects randomised to treatment with either 150 mg of the angiotensin II type 1 receptor blocker irbesartan or 50 mg of the beta1-adrenergic receptor blocker atenolol for twelve weeks. RESULTS: The reduction in blood pressure was similar in both treatment groups. The SNP C711T in the apolipoprotein B gene was associated with the blood pressure response to irbesartan with an average reduction of 19 mmHg in the individuals carrying the C-allele, but not to atenolol. The C16730T polymorphism in the low density lipoprotein receptor gene predicted the change in systolic blood pressure in the atenolol group with an average reduction of 14 mmHg in the individuals carrying the C-allele. CONCLUSIONS: Polymorphisms in genes encoding proteins in the lipid metabolism are associated with the response to antihypertensive treatment in a drug specific pattern. These results highlight the potential use of pharmacogenetics as a guide for individualised antihypertensive treatment, and also the role of lipids in blood pressure control.
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- Ruigomez, A, et al.
(författare)
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Risk of mortality in a cohort of patients newly diagnosed with chronic atrial fibrillation
- 2002
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261 .- 1471-2261. ; 2:5
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Tidskriftsartikel (refereegranskat)abstract
- Objective To estimate the mortality rate of patients newly diagnosed with chronic atrial fibrillation (AF) and compare it with the one in the general population. To evaluate the role of co-morbidity and other factors on the risk of dying among AF patients. Methods We used the General Practice Research Database in the UK to perform a retrospective cohort study. We followed a cohort of chronic AF patiens (N = 1,035) and an age and sex matched cohort of 5,000 subjects sampled from the general population. We used all deceased AF patients as cases (n = 234) and the remaining AF patients as controls to perform a nested case-control analysis. We estimated mortality risk associated with AF using Cox regression. We computed mortality relative risks using logistic regression among AF patients. Results During a mean follow-up of two years, 393 patients died in the general population cohort and 234 in the AF cohort. Adjusted relative risk of death in the cohort of AF was 2.5 (95%CI 2.1 – 3.0) compared to the general population. Among AF patients, mortality risk increased remarkably with advancing age. Smokers carried a relative risk of dying close to threefold. Ischaemic heart disease was the strongest clinical predictor of mortality with a RR of 3.0 (95% CI; 2.1–4.1). Current use of calcium channel blockers, warfarin and aspirin was associated with a decreased risk of mortality. Conclusions Chronic AF is an important determinant of increased mortality. Major risk factors for mortality in the AF cohort were age, smoking and cardiovascular co-morbidity, in particular ischaemic heart disease.
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- Alm, Rikard, et al.
(författare)
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Organ culture: a new model for vascular endothelium dysfunction.
- 2002
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Ingår i: BMC Cardiovascular Disorders. - 1471-2261. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Endothelium dysfunction is believed to play a role in the development of cardiovascular disease. The aim of the present study was to evaluate the suitability of organ culture as a model for endothelium dysfunction. METHODS: The isometric tension was recorded in isolated segments of the rat mesenteric artery branch, before and after organ culture for 20 h. Vasodilatation was expressed as % of preconstriction with U46619. The acetylcholine (ACh) induced nitric oxide (NO) mediated dilatation was studied in the presence of 10 &mgr;M indomethacin, 50 nM charybdotoxin and 1 &mgr;M apamin. Endothelium-derived hyperpolarising factor (EDHF) was studied in the presence of 0.1 mM L-NOARG and indomethacin. Prostaglandins were studied in the presence of L-NOARG, charybdotoxin and apamin. RESULTS: The ACh-induced NO and prostaglandin-mediated dilatations decreased significantly during organ culture (NO: 84% in control and 36% in cultured; prostaglandins: 48% in control and 16% in cultured). Notably, the total ACh-dilatation was not changed. This might be explained by the finding that EDHF alone stimulated a full dilatation even after organ culture (83% in control and 80% in cultured). EDHF may thereby compensate for the loss in NO and prostaglandin-mediated dilatation. Dilatations induced by forskolin or sodium nitroprusside did not change after organ culture, indicating intact smooth muscle cell function. CONCLUSIONS: Organ culture induces a loss in NO and prostaglandin-mediated dilatation, which is compensated for by EDHF. This shift in mediator profile resembles that in endothelium dysfunction. Organ culture provides an easily accessible model where the molecular changes that take place, when endothelium dysfunction is developed, can be examined over time.
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