Dataset Information

Cholesterol-lowering effect of statin therapy in a clinical HIV cohort: an application of double propensity score adjustment.

ABSTRACT:

Purpose

Propensity score matching (PSM) is often used to estimate the average treatment effect among the treated (ATT) using observational data. We demonstrate how the use of "double propensity score adjustment" can reduce residual confounding and avoid bias due to incomplete matching compared with traditional PSM methods.

Methods

The DC Cohort is an observational clinical HIV cohort in Washington, DC. We compared the mean percent change in non-high-density lipoprotein cholesterol (non-HDL-C) concentration after 3-12 months between participants treated and participants not treated with statin therapy between 2011 and 2018. We conducted traditional PSM procedures (optimal, nearest neighbor, and nearest neighbor caliper matching) and double propensity score adjustment.

Results

Among 202 treated and 1252 untreated participants, the ATT was -14.5% (95% CI: -18.4, -10.6) after optimal matching (202 matched pairs; 15/22 covariates balanced), -14.9% (-18.9, -11.0) after nearest neighbor matching (202 matched pairs; 17/22 covariates balanced), and -12.0% (-16.5, -7.5) after nearest neighbor caliper matching (153 matched pairs; 21/22 covariates balanced). After double propensity score adjustment, the ATT was -13.0% (-16.0, -10.1).

Conclusions

In PSM analyses, double propensity score adjustment is a readily accessible alternative approach for estimating ATTs when sufficient covariate balance between treatment groups cannot be achieved without excluding treated participants.

SUBMITTER: Levy ME

PROVIDER: S-EPMC7190432 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Publications

Cholesterol-lowering effect of statin therapy in a clinical HIV cohort: an application of double propensity score adjustment.

Levy Matthew E ME Ma Yan Y Magnus Manya M Younes Naji N Castel Amanda D AD

Annals of epidemiology 20200302

<h4>Purpose</h4>Propensity score matching (PSM) is often used to estimate the average treatment effect among the treated (ATT) using observational data. We demonstrate how the use of "double propensity score adjustment" can reduce residual confounding and avoid bias due to incomplete matching compared with traditional PSM methods.<h4>Methods</h4>The DC Cohort is an observational clinical HIV cohort in Washington, DC. We compared the mean percent change in non-high-density lipoprotein cholesterol ...[more]

PMID: 32204991

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Project description:Although statin drugs are generally efficacious for lowering plasma LDL-cholesterol levels, there is considerable variability in response. To identify candidate genes that may contribute to this variation, we used an unbiased genome-wide filter approach that was applied to 10,149 genes expressed in immortalized lymphoblastoid cell lines (LCLs) derived from 480 participants of the Cholesterol and Pharmacogenomics (CAP) clinical trial of simvastatin. The criteria for identification of candidates included genes whose statin-induced changes in expression were correlated with change in expression of HMGCR, a key regulator of cellular cholesterol metabolism and the target of statin inhibition. This analysis yielded 45 genes, from which RHOA was selected for follow-up because it has been found to participate in mediating the pleiotropic but not the lipid-lowering effects of statin treatment. RHOA knock-down in hepatoma cell lines reduced HMGCR, LDLR, and SREBF2 mRNA expression and increased intracellular cholesterol ester content as well as apolipoprotein B (APOB) concentrations in the conditioned media. Furthermore, inter-individual variation in statin-induced RHOA mRNA expression measured in vitro in CAP LCLs was correlated with the changes in plasma total cholesterol, LDL-cholesterol, and APOB induced by simvastatin treatment (40 mg/d for 6 wk) of the individuals from whom these cell lines were derived. Moreover, the minor allele of rs11716445, a SNP located in a novel cryptic RHOA exon, dramatically increased inclusion of the exon in RHOA transcripts during splicing and was associated with a smaller LDL-cholesterol reduction in response to statin treatment in 1,886 participants from the CAP and Pravastatin Inflamation and CRP Evaluation (PRINCE; pravastatin 40 mg/d) statin clinical trials. Thus, an unbiased filter approach based on transcriptome-wide profiling identified RHOA as a gene contributing to variation in LDL-cholesterol response to statin, illustrating the power of this approach for identifying candidate genes involved in drug response phenotypes.

Dataset Information

Cholesterol-lowering effect of statin therapy in a clinical HIV cohort: an application of double propensity score adjustment.

Purpose

Methods

Results

Conclusions

Publications

Cholesterol-lowering effect of statin therapy in a clinical HIV cohort: an application of double propensity score adjustment.

Similar Datasets

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