Exploring the Effects of Antihypertensive and Lipid-Lowering Drugs on Inflammatory Cytokine Levels

NCT ID: NCT06622304

Last Updated: 2024-10-03

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 250736 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-04-01
• Study Completion Date: 2024-09-11

Brief Summary

This study investigates the causal relationships between antihypertensive and lipid-lowering drugs and inflammatory cytokines using a drug-targeted Mendelian randomization approach. By leveraging genome-wide association studies (GWAS) and expression quantitative trait loci (eQTL) data, the study evaluates the effects of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), HMG-CoA reductase inhibitors, PCSK9 inhibitors, and NPC1L1 inhibitors on key inflammatory cytokines such as IL-1β, TNF-α, CRP, and MCP-1. The findings aim to provide insights into the prevention and control of excessive inflammatory responses, particularly in patients with hypertension and dyslipidemia, by assessing the causal effects of these therapies.

Detailed Description

This observational study focuses on elucidating the causal relationships between commonly prescribed antihypertensive drugs (ACEIs and ARBs) and lipid-lowering drugs (HMG-CoA reductase inhibitors, PCSK9 inhibitors, and NPC1L1 inhibitors) with various inflammatory cytokines, including IL-1β, TNF-α, CRP, MCP-1, and IFN-γ, using a drug-targeted Mendelian randomization (MR) framework. The study employs large-scale genetic data from European populations, drawing from genome-wide association studies (GWAS) and expression quantitative trait loci (eQTL) datasets, to construct instrumental variables that mimic the effects of drug exposure.

The primary aim is to explore how these pharmaceutical interventions influence inflammatory pathways at the molecular level. The use of MR methods enables causal inference by utilizing genetic variants within or near drug-target genes, allowing for the estimation of downstream effects similar to those produced by actual drug interventions. Key statistical methods, including inverse variance weighting and sensitivity analyses, are applied to ensure robustness and validity of the results.

This research provides critical evidence for the selection of antihypertensive and lipid-lowering therapies that not only manage cardiovascular risk factors but also modulate inflammation, contributing to personalized medicine strategies for patients with chronic inflammatory conditions. Furthermore, the findings have broader implications for drug repurposing and the development of new therapeutic targets aimed at mitigating inflammatory processes that underlie various chronic diseases.

Conditions

Hypertension; Dyslipidemias; Inflammatory Response; Chronic Inflammation; Inflammatory Cytokines

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• Participants aged 18 years or older.
• Diagnosed with hypertension, coronary artery disease, or dyslipidemia.
• Availability of complete genome-wide data and inflammatory cytokine levels.
• Willingness to participate in the study and provide the required clinical data.

Exclusion Criteria

• Participants under the age of 18.
• Individuals with severe chronic diseases or other conditions that may significantly influence inflammatory responses.
• Individuals unwilling or unable to provide necessary clinical or genomic data.
• Pregnant or breastfeeding women.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine

OTHER

Sponsor Role: collaborator

Guangzhou Institute of Respiratory Disease

OTHER

Sponsor Role: lead

Responsible Party

Zhibin Xu

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Guangzhou Institute of Respiratory Diseases, the First Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, China

Countries

China

References

Xin J, Xu Z, Zhang F, Sun Y, Wang X, Wu C, Zhao L. Mendelian randomization-based observational cohort study on drug targets: Impact of antihypertensive and lipid-lowering therapies on inflammatory cytokines. Medicine (Baltimore). 2025 Mar 7;104(10):e41771. doi: 10.1097/MD.0000000000041771.

Reference Type: DERIVED

PMID: 40068040 (View on PubMed)

Other Identifiers

YYKC-2021-01-102

Identifier Type: -

Identifier Source: org_study_id