Clinical trial NCT06622304: Exploring the Effects of Antihypertensive and Lipid-Lowering Drugs on Inflammatory Cytokine Levels
Official title: Mendelian Randomization Analysis of Drug Targets: Exploring the Impact of Antihypertensive and Lipid-Lowering Therapies on Inflammatory Cytokines
Study type: OBSERVATIONAL
Overall status: COMPLETED
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
Lead sponsor: Guangzhou Institute of Respiratory Disease
Sponsor class: OTHER
Collaborators: name: Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine
First posted: 2024-10-02
Enrollment: 250736
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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.

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.

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.

Primary outcomes:
measure: Reduction in IL-1β Levels Due to ACE Inhibitors
timeFrame: Baseline to 12 months
measure: Reduction in TNF-α Levels Due to ACE Inhibitors
timeFrame: Baseline to 12 months
measure: Reduction in CRP Levels Due to ACE Inhibitors
timeFrame: Baseline to 12 months
measure: Modulation of MCP-1 Levels Due to Statin Therapy
timeFrame: Baseline to 12 months
measure: Modulation of MIP-1α Levels Due to Statin Therapy
timeFrame: Baseline to 12 months
measure: Modulation of MIP-1β Levels Due to Statin Therapy
timeFrame: Baseline to 12 months
measure: Reduction in IL-1β Levels Due to PCSK9 Inhibitors
timeFrame: Baseline to 12 months
measure: Reduction in IL-6 Levels Due to PCSK9 Inhibitors
timeFrame: Baseline to 12 months
Secondary outcomes:
measure: Reduction in Cardiovascular Events Due to Antihypertensive Therapy
timeFrame: Baseline to 24 months
measure: Changes in LDL-C Levels Due to Statin Therapy
timeFrame: Baseline to 24 months
measure: Changes in HDL-C Levels Due to Statin Therapy
timeFrame: Baseline to 24 months
measure: Reduction in IL-1β Levels Due to PCSK9 Inhibitors
timeFrame: Baseline to 24 months
measure: Changes in Cardiometabolic Outcomes Due to PCSK9 Inhibitors
timeFrame: Baseline to 24 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Guangzhou Institute of Respiratory Diseases, the First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
Study officials:
References: