Collaborative meta-analysis of individual participant data from observational studies of Lp-PLA2 and cardiovascular diseases.
Lp-PLA2 Studies Collaboration None., 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., Koenig W., Sacco R., Elkind M., Talmud P., Rimm E., 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., Packard C., Wassertheil-Smoller S., Ridker P., Ballantyne C., Cannon CP., Cushman M., Danesh J., Gu D., Hofman A., Nelson JJ., Thompson S., Zalewski A., Zariffa N., Di Angelantonio E., Kaptoge S., Thompson A., Thompson S., Walker M., Watson S., Wood A.
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.