Berglund G

References (2)

Title : Polymorphisms associated with cholesterol and risk of cardiovascular events - Kathiresan_2008_N.Engl.J.Med_358_1240
Author(s) : Kathiresan S , Melander O , Anevski D , Guiducci C , Burtt NP , Roos C , Hirschhorn JN , Berglund G , Hedblad B , Groop L , Altshuler DM , Newton-Cheh C , Orho-Melander M
Ref : N Engl J Med , 358 :1240 , 2008
Abstract : BACKGROUND: Common single-nucleotide polymorphisms (SNPs) that are associated with blood low-density lipoprotein (LDL) or high-density lipoprotein (HDL) cholesterol modestly affect lipid levels. We tested the hypothesis that a combination of such SNPs contributes to the risk of cardiovascular disease. METHODS: We studied SNPs at nine loci in 5414 subjects from the cardiovascular cohort of the Malmo Diet and Cancer Study. We first validated the association between SNPs and either LDL or HDL cholesterol and subsequently created a genotype score on the basis of the number of unfavorable alleles. We used Cox proportional-hazards models to determine the time to the first cardiovascular event in relation to the genotype score. RESULTS: All nine SNPs showed replication of an association with levels of either LDL or HDL cholesterol. With increasing genotype scores, the level of LDL cholesterol increased from 152 mg to 171 mg per deciliter (3.9 to 4.4 mmol per liter), whereas HDL cholesterol decreased from 60 mg to 51 mg per deciliter (1.6 to 1.3 mmol per liter). During follow-up (median, 10.6 years), 238 subjects had a first cardiovascular event. The genotype score was associated with incident cardiovascular disease in models adjusted for covariates including baseline lipid levels (P<0.001). The use of the genotype score did not improve the clinical risk prediction, as assessed by the C statistic. However, there was a significant improvement in risk classification with the use of models that included the genotype score, as compared with those that did not include the genotype score. CONCLUSIONS: A genotype score of nine validated SNPs that are associated with modulation in levels of LDL or HDL cholesterol was an independent risk factor for incident cardiovascular disease. The score did not improve risk discrimination but did modestly improve clinical risk reclassification for individual subjects beyond standard clinical factors.
ESTHER : Kathiresan_2008_N.Engl.J.Med_358_1240
PubMedSearch : Kathiresan_2008_N.Engl.J.Med_358_1240
PubMedID: 18354102

Title : Collaborative meta-analysis of individual participant data from observational studies of Lp-PLA2 and cardiovascular diseases - Ballantyne_2007_Eur.J.Cardiovasc.Prev.Rehabil_14_3
Author(s) : Ballantyne C , Cushman M , Psaty B , Furberg C , Khaw KT , Sandhu M , Oldgren J , Rossi GP , Maiolino G , Cesari M , Lenzini L , James SK , Rimm E , Collins R , Anderson J , Koenig W , Brenner H , Rothenbacher D , Berglund G , Persson M , Berger P , Brilakis E , McConnell JP , Sacco R , Elkind M , Talmud P , Cannon CP , Packard C , Barrett-Connor E , Hofman A , Kardys I , Witteman JC , Criqui M , Corsetti JP , Rainwater DL , Moss AJ , Robins S , Bloomfield H , Collins D , Wassertheil-Smoller S , Ridker P , Danesh J , Gu D , Nelson JJ , Thompson S , Zalewski A , Zariffa N , Di Angelantonio E , Kaptoge S , Thompson A , Walker M , Watson S , Wood A
Ref : Eur J Cardiovasc Prev Rehabil , 14 :3 , 2007
Abstract : BACKGROUND: A large number of observational epidemiological studies have reported generally positive associations between circulating mass and activity levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) and the risk of cardiovascular diseases. Few studies have been large enough to provide reliable estimates in different circumstances, such as in different subgroups (e.g., by age group, sex, or smoking status) or at different Lp-PLA2 levels. Moreover, most published studies have related disease risk only to baseline values of Lp-PLA2 markers (which can lead to substantial underestimation of any risk relationships because of within-person variability over time) and have used different approaches to adjustment for possible confounding factors. OBJECTIVES: By combination of data from individual participants from all relevant observational studies in a systematic 'meta-analysis', with correction for regression dilution (using available data on serial measurements of Lp-PLA2), the Lp-PLA2 Studies Collaboration will aim to characterize more precisely than has previously been possible the strength and shape of the age and sex-specific associations of plasma Lp-PLA2 with coronary heart disease (and, where data are sufficient, with other vascular diseases, such as ischaemic stroke). It will also help to determine to what extent such associations are independent of possible confounding factors and to explore potential sources of heterogeneity among studies, such as those related to assay methods and study design. It is anticipated that the present collaboration will serve as a framework to investigate related questions on Lp-PLA2 and cardiovascular outcomes. METHODS: A central database is being established containing data on circulating Lp-PLA2 values, sex and other potential confounding factors, age at baseline Lp-PLA2 measurement, age at event or at last follow-up, major vascular morbidity and cause-specific mortality. Information about any repeat measurements of Lp-PLA2 and potential confounding factors has been sought to allow adjustment for possible confounding and correction for regression dilution. The analyses will involve age-specific regression models. Synthesis of the available observational studies of Lp-PLA2 will yield information on a total of about 15 000 cardiovascular disease endpoints.
ESTHER : Ballantyne_2007_Eur.J.Cardiovasc.Prev.Rehabil_14_3
PubMedSearch : Ballantyne_2007_Eur.J.Cardiovasc.Prev.Rehabil_14_3
PubMedID: 17301621
Gene_locus related to this paper: human-PLA2G7