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

NCT06622304 | Completed

• 1 other identifier: YYKC-2021-01-102
• Study Type: observational
• Target: 250,736
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Antihypertensive Drugs; Lipid-Lowering Drugs; Mendelian Randomization; ACE Inhibitors; ARBs; HMG-CoA Reductase Inhibitors; PCSK9 Inhibitors; NPC1L1 Inhibitors; IL-1β; TNF-α; CRP; MCP-1; Inflammatory Pathways; Genetic Association Studies; Causal Inference

Outcome Measures

Primary Outcomes (8)

• Reduction in IL-1β Levels Due to ACE Inhibitors

  The primary outcome is the reduction in plasma levels of IL-1β due to exposure to ACE inhibitors (ACEIs). The study evaluates the causal relationship between ACEIs and IL-1β levels using Mendelian randomization.（Unit: pg/mL）

  Baseline to 12 months

• Reduction in TNF-α Levels Due to ACE Inhibitors

  The primary outcome is the reduction in plasma levels of TNF-α due to exposure to ACE inhibitors (ACEIs). The study evaluates the causal relationship between ACEIs and TNF-α levels using Mendelian randomization.（Unit: pg/mL）

  Baseline to 12 months

• Reduction in CRP Levels Due to ACE Inhibitors

  The primary outcome is the reduction in plasma levels of CRP due to exposure to ACE inhibitors (ACEIs). The study evaluates the causal relationship between ACEIs and CRP levels using Mendelian randomization.（Unit: mg/L）

  Baseline to 12 months

• Modulation of MCP-1 Levels Due to Statin Therapy

  The primary outcome is the modulation of plasma levels of MCP-1 in patients treated with statins (HMG-CoA reductase inhibitors). The study investigates the effect of statins on MCP-1 levels.（Unit: pg/mL）

  Baseline to 12 months

• Modulation of MIP-1α Levels Due to Statin Therapy

  The primary outcome is the modulation of plasma levels of MIP-1α in patients treated with statins (HMG-CoA reductase inhibitors).（Unit: pg/mL）

  Baseline to 12 months

• Modulation of MIP-1β Levels Due to Statin Therapy

  The primary outcome is the modulation of plasma levels of MIP-1β in patients treated with statins (HMG-CoA reductase inhibitors).（Unit: pg/mL）

  Baseline to 12 months

• Reduction in IL-1β Levels Due to PCSK9 Inhibitors

  The primary outcome is the reduction in plasma levels of IL-1β in individuals exposed to PCSK9 inhibitors.（Unit: pg/mL）

  Baseline to 12 months

• Reduction in IL-6 Levels Due to PCSK9 Inhibitors

  The primary outcome is the reduction in plasma levels of IL-6 in individuals exposed to PCSK9 inhibitors.（Unit: pg/m）

  Baseline to 12 months

Secondary Outcomes (5)

• Reduction in Cardiovascular Events Due to Antihypertensive Therapy

  Baseline to 24 months

• Changes in LDL-C Levels Due to Statin Therapy

  Baseline to 24 months

• Changes in HDL-C Levels Due to Statin Therapy

  Baseline to 24 months

• Reduction in IL-1β Levels Due to PCSK9 Inhibitors

  Baseline to 24 months

• Changes in Cardiometabolic Outcomes Due to PCSK9 Inhibitors

  Baseline to 24 months

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population includes adult patients diagnosed with hypertension, coronary artery disease, or dyslipidemia. These participants have genome-wide data collected through genome-wide association studies (GWAS) and include measurements of inflammatory cytokines. The study focuses on the effect of drug interventions on inflammatory biomarkers.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Guangzhou Institute of Respiratory Disease: lead
• Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine: collaborator

Study Sites (1)

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

Guangzhou, Guangdong, 510120, China

Location

Related Publications (1)

• 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.

  PMID: 40068040 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

No biospecimen retention. The study utilizes existing genome-wide association study (GWAS) and expression quantitative trait loci (eQTL) data, with no collection of new biological specimens.

MeSH Terms

Conditions

Hypertension; Dyslipidemias

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 29, 2024
• First Posted: October 2, 2024
• Study Start: April 1, 2024
• Primary Completion: August 1, 2024
• Study Completion: September 11, 2024
• Last Updated: October 3, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: The data will be available starting 6 months after publication and will be accessible for a period of 5 years.
• Access Criteria: Researchers requesting access to the data will need to submit a detailed study proposal and obtain approval from the study's governing ethics board.

Locations

CN (1)