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- 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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| 37. |
- Lindgren, P., et al.
(författare)
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Cost-effectiveness of atorvastatin for the prevention of coronary and stroke events: an economic analysis of the Anglo-Scandinavian Cardiac Outcomes Trial--lipid-lowering arm (ASCOT-LLA)
- 2005
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Ingår i: Eur J Cardiovasc Prev Rehabil. - : Oxford University Press (OUP). - 1741-8267. ; 12:1, s. 29-36
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of this study is to assess the cost-effectiveness of the lipid-lowering arm of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT-LLA) where patients from seven countries with hypertension and no history of coronary heart disease (CHD) were randomized to receive 10 mg atorvastatin or placebo. DESIGN: Economic analysis of a randomized controlled trial. METHODS: Data on resource use were aggregated for all patients during the entire trial period (median 3.3 years) and multiplied with unit costs for Sweden and the UK. The total number of cardiovascular events and procedures avoided was used as the measure of effectiveness. RESULTS: Patients treated with atorvastatin had an additional net costs of 449 euro (4114 SEK) in Sweden and 414 euro (260 pounds sterling) in the UK, but fewer events per patient (0.097 compared to 0.132). The incremental cost-effectiveness ratios were 12673 euro (116119 SEK) and 11693 euro (7349 pounds sterling) per event avoided. CONCLUSION: Based on comparisons with the WOSCOPS and 4S studies, atorvastatin at 10 mg to treat patients as in the ASCOT study, appears to be a cost-effective strategy.
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| 40. |
- Lindgren, P., et al.
(författare)
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The lifetime cost effectiveness of amlodipine-based therapy plus atorvastatin compared with atenolol plus atorvastatin, amlodipine-based therapy alone and atenolol-based therapy alone: results from ASCOT1
- 2009
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Ingår i: Pharmacoeconomics. - 1170-7690. ; 27:3, s. 221-30
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) showed in hypertensive patients that blood pressure-lowering treatment with an amlodipine-based regimen reduces events compared with an atenolol-based regimen and that atorvastatin was more effective than placebo. OBJECTIVE: To assess the cost effectiveness of four alternative treatment strategies in patients with hypertension and three or more cardiovascular risk factors in the UK (from the UK NHS perspective) or Sweden (from the societal perspective): amlodipine-based plus atorvastatin, atenolol-based plus atorvastatin, amlodipine-based alone and atenolol-based alone. METHODS: Based on the trial data, a Markov model was constructed where the risk of myocardial infarction, revascularization procedures and stroke and the long-term costs, quality of life and mortality associated with these events were estimated. Transition probabilities and costs (euro, 2007 values) were based on the patient-level trial data. Outcomes were reported as life-years gained and QALYs. In the latter case, utility reduction from events was based on a substudy in ASCOT patients. Treatment was applied for the duration of the lipid-lowering arm of the trial (3 years) and patients were then followed to the end of their life. RESULTS: Amlodipine-based therapy plus atorvastatin was the most expensive but also most effective treatment. Compared with amlodipine-based therapy alone, the cost to gain one QALY was euro 11,965 in the UK and euro 8,591 in Sweden. The incremental cost effectiveness of amlodipine-based therapy compared with atenolol-based therapy was euro 9,548 and euro 3,965 per QALY gained in the UK and Sweden, respectively. Atenolol-based therapy plus atorvastatin was eliminated through extended dominance. Applying the threshold values used by the National Institute for Health and Clinical Excellence (NICE) and the Swedish National Board of Health and Welfare, a combination of amlodipine-based therapy and atorvastatin appears to be cost effective in patients with hypertension and three or more additional risk factors.
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