Study Roles of Heavy Metals and Essential Metal Dyshomeostasis in Pulmonary Arterial Hypertension Patients

Investigators plan to recruit 50 PAH patients from UofL PAH Clinic, with various degrees of severity (25 intermediate risk patients and 20 high risk patients) and 10 age and gender matched controls. PAH patients are evaluated at least every 6 months by the PAH Clinic and blood/urine samples will be obtained at each office visit. Blood, plasma and urine samples will be used to measure 31 metal levels including heavy metals (cadmium, arsenic, cobalt, lead etc.) and essential metals (calcium, copper, iron, zinc, potassium etc.) by the with ICP-MS via the service of ITEMFC. Interactions among the 31 metals in PAH patients, metal concentration differences between intermediate risk PAH, high risk PAH and control groups, the correlation between metal concentrations and the etiology, severity, duration, treatment, and progression of PAH/RV dysfunction over 12 months will be analyzed by CIEHS Biostatistics and Informatics Facility Core.

Study Overview

• Status: Recruiting
• Conditions: Pulmonary Hypertension; Metal Poison
• Intervention / Treatment: Diagnostic test: Metal level measurements

Detailed Description

Exposures to heavy metals such arsenic, lead, cadmium have been linked to increased incidence of cardiovascular disease (CVD). However, current studies suffer from multiple drawbacks, most studies were cross sectional in design, focused on individual metals without consideration of the joint effects of multiple metals, and did not examine the possible effects of essential metals in CVD. Especially, the relationship between heavy metals/essential metal dyshomeostasis and right ventricular (RV) dysfunction/pulmonary hypertension (PAH), is less investigated. Investigators hypothesize that increased toxic heavy metals and/or essential metal dyshomeostasis impact hypoxia response, endothelial dysfunction, perivascular inflammation and vascular remodeling of the pulmonary vasculature, and are important pathogenic initiators/stimulators during the progression of PAH and associated RV remodeling/dysfunction.

Investigators plan to recruit 50 PAH patients from UofL PAH Clinic, with various degrees of severity (25 intermediate risk patients and 20 high risk patients) and 10 age and gender matched controls. PAH patients are evaluated at least every 6 months by the PAH Clinic and blood/urine samples will be obtained at each office visit. Blood, plasma and urine samples will be used to measure 31 metal levels including heavy metals (cadmium, arsenic, cobalt, lead etc.) and essential metals (calcium, copper, iron, zinc, potassium etc.) by the with ICP-MS via the service of ITEMFC. Interactions among the 31 metals in PAH patients, metal concentration differences between intermediate risk PAH, high risk PAH and control groups, the correlation between metal concentrations and the etiology, severity, duration, treatment, and progression of PAH/RV dysfunction over 12 months will be analyzed by CIEHS Biostatistics and Informatics Facility Core.

Heavy metals have the potential of generating reactive oxygen species (ROS) and oxidative stress whenever the release of ROS exceeds endogenous antioxidant capacity. Therefore, investigators hypothesize that heavy metal/essential metal dyshomeostasis could induce oxidative stress responses, activate two key pulmonary vasculature regulators (endothelin 1 and hypoxia inducible factor (HIF) pathways), and in turn contributes to the PAH pathogenesis and RV dysfunction. Oxidative stress, endothelin 1 and HIF pathway markers in the blood will be measured with ELISA kits in both PAH and control groups. Investigators will perform comprehensive correlation analysis between metal levels, oxidative stress markers, endothelin 1 and HIF pathway markers, and quantitative clinical biomarkers such as hemodynamic, laboratory and functional data in PAH patients. Furthermore, investigators will perform correlation analysis between blood levels of oxidative stress, endothelin 1 and HIF pathway markers and the patients' dietary intake of antioxidant vegetables.

• Study Type: Observational
• Enrollment (Estimated): 110

Contacts and Locations

• Study Contact: Name: Jiapeng Huang, MD, PhD; Phone Number: 5028528157; Email: jiapeng.huang@louisville.edu

Study Locations

• United States
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • University of Louisville Health
      • Contact: Jiapeng Huang, MD, PhD; Phone Number: 5028528157; Email: jiapeng.huang@louisville.edu
      • Principal Investigator: Jiapeng Huang, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients with pulmonary hypertension

Description

Inclusion Criteria:

• All patients with the diagnosis of pulmonary hypertension
• Agree to the study protocol
• Healthy volunteers
• Age, gender matched controls

Exclusion Criteria:

• Younger than 18 years
• Refusal to participate

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Control; age and gender matched controls	Diagnostic test: Metal level measurements; Measure multiple metal levels
Pulmonary Hypertension Group; Pulmonary Hypertension Patients with Various Degree of Severity	Diagnostic test: Metal level measurements; Measure multiple metal levels

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metal levels in control and pulmonary hypertension groups	Metal levels in control and pulmonary hypertension groups	up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Right heart catheterization data	mean pulmonary artery pressure (mmHg)	up to 12 months
Pulmonary hypertension risk scores (Registry to Evaluate Early and Long-Term PAH Disease Management)	Pulmonary hypertension risk scores, 0-10, the higher score means a worse outcome.	up to 12 months
Mortality	death	up to 12 months

Collaborators and Investigators

• Sponsor: Jiapeng Huang

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2020
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: February 7, 2021
• First Submitted That Met QC Criteria: February 13, 2021
• First Posted (Actual): February 16, 2021

Study Record Updates

• Last Update Posted (Actual): May 30, 2025
• Last Update Submitted That Met QC Criteria: May 26, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Lung Diseases; Pulmonary Arterial Hypertension; Hypertension; Hypertension, Pulmonary
• Other Study ID Numbers: 20.0947

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No