Collaborative meta-analysis of individual participant data from observational studies of Lp-PLA2 and cardiovascular diseases.

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.

A trial of education, prompts, and opinion leaders to improve prescription of lipid modifying therapy by primary care physicians for patients with ischemic heart disease.

BACKGROUND: Recent clinical trials indicate that treatment with lipid modifying therapy improves outcomes in patients with ischemic heart disease (IHD) and low levels of high density lipoprotein (HDL) cholesterol. The results of these trials, however, have not been widely implemented in clinical practice. OBJECTIVES: To develop and test an intervention designed to increase the rate of prescription of lipid modifying therapy and to determine the relative effectiveness of three different prompts (progress notes, patient letters, or computer chart reminders). METHODS: The study was conducted in 11 US Department of Veterans Affairs Medical Centers. The effect of the intervention on the proportion of eligible patients receiving lipid modifying therapy was compared between five intervention sites and six matched control sites using a controlled before and after study design. Additionally, 92 providers within the intervention clinics were randomized to receive one of the three prompts. Data were analyzed using logistic regression modeling which incorporated terms to account for the clustered nature of the data. RESULTS: At the intervention sites the prescription rate increased from 8.3% during the pre-intervention period to 39.1% during the intervention (OR = 6.5, 95% CI 5.2 to 8.2, p<0.0001) but remained unchanged at the control sites. The interaction between group (control v intervention) and time period was highly significant (p<0.0001). The adjusted odds of receiving a prescription during the intervention period was 3.1 times higher at the intervention sites than at the control sites (95% CI 2.1 to 4.7). Overall, there was no significant difference in prescription rates among the three prompt groups. However, there was a significant interaction between prompt group and site, indicating that the efficacy of the prompts differed by site. CONCLUSION: An intervention for primary care providers consisting of an educational workshop, opinion leader influence, and prompts substantially increased the prescription rate of lipid modifying therapy.