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

Guangzhou Institute of Respiratory Disease

Status: Completed

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

Study type: Observational

Funder types: Other

Identifiers

NCT06622304

YYKC-2021-01-102

Details and patient eligibility

About

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.

Full 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.

Enrollment: 250,736 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.