Homocysteine and Early Diastolic Dysfunction in Newly Diagnosed Hypertension (HHT-EDD)

Relationship Between Elevated Homocysteine Levels and Early Diastolic Dysfunction in Newly Diagnosed Hypertensive Patients

This prospective single-center observational study aims to evaluate the relationship between elevated plasma homocysteine levels and early echocardiographic abnormalities in patients with newly diagnosed essential hypertension. Adult patients diagnosed with essential hypertension within the previous 6 months will undergo clinical assessment, ambulatory blood pressure monitoring, electrocardiography, laboratory testing, and comprehensive transthoracic echocardiography including diastolic function assessment and strain analysis when image quality is adequate. Participants will be classified according to plasma homocysteine level using, and patients with elevated and normal homocysteine levels will be compared with respect to diastolic dysfunction and left ventricular and left atrial global longitudinal strain parameters. Clinical, laboratory, and echocardiographic data will also be used to develop a machine-learning based model for prediction of H-type hypertension.

Study Overview

• Status: Recruiting
• Conditions: Diastolic Dysfunction; Hyperhomocysteinemia; Hypertension (HTN)
• Intervention / Treatment: Diagnostic test: Homocysteine Measurement and Echocardiography

Detailed Description

Hypertension may lead to subclinical myocardial dysfunction before overt structural heart disease becomes evident. Homocysteine has been associated with endothelial dysfunction, oxidative stress, vascular remodeling, and myocardial impairment. However, the association between elevated homocysteine and early diastolic dysfunction in newly diagnosed hypertensive patients has not been fully characterized.

This prospective, single-center, observational cohort study will enroll at least 500 adults with newly diagnosed essential hypertension within the preceding 6 months. Peripheral venous blood samples will be collected, and plasma homocysteine levels will be measured in batches after enrollment of a predefined number of participants. All participants will undergo standardized clinical and laboratory evaluation, ambulatory blood pressure monitoring, electrocardiography, and comprehensive transthoracic echocardiography. Echocardiographic assessment will include conventional chamber measurements, mitral inflow Doppler parameters, tissue Doppler septal and lateral e' velocities, left ventricular ejection fraction and volumes, and left ventricular and left atrial strain analysis where feasible.

Participants will be categorized into elevated homocysteine and normal homocysteine groups using a threshold of 15 µmol/L. The first-stage objective of the study is to determine whether elevated homocysteine is associated with early diastolic dysfunction and impaired ventricular and atrial longitudinal deformation in newly diagnosed hypertension. A secondary objective is to assess clinical, laboratory, and echocardiographic correlates of elevated homocysteine and to develop a machine-learning based prediction model for H-type hypertension. Long-term follow-up is planned as a future second phase of the project.

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: yunus emre yavuz, MD; Phone Number: +903322235976 +90 5306069194; Email: eyavuz@erbakan.edu.tr

Study Locations

• Turkey (Türkiye)
  • Meram
    • Konya, Meram, Turkey (Türkiye), 42080
      • Recruiting
      • Necmettin Erbakan University Meram Faculty of Medicine
      • Contact: YUNUS EMRE YAVUZ, MD; Phone Number: +905306069194; Email: eyavuz@erbakan.edu.tr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adults with newly diagnosed essential hypertension evaluated at a single tertiary care center, who undergo clinical assessment, laboratory testing, ambulatory blood pressure monitoring, electrocardiography, and echocardiographic evaluation including diastolic function and strain analysis.

Description

Inclusion Criteria:

• Adults aged 18 years or older
• Newly diagnosed essential hypertension within the previous 6 months
• Ability and willingness to provide informed consent
• Availability for clinical evaluation, laboratory testing, ambulatory blood pressure monitoring, electrocardiography, and transthoracic echocardiography

Exclusion Criteria:

• Resistant hypertension
• Secondary hypertension
• Acute coronary syndrome within the previous 6 months
• Major surgery within the previous 6 months
• Known heart failure
• Pulmonary hypertension
• Congenital heart disease
• Atrial fibrillation or atrial flutter
• Moderate or severe valvular heart disease
• Chronic kidney disease
• Anemia
• Current folate, vitamin B12, or vitamin B6 supplementation or treatment
• Inadequate echocardiographic image quality for strain analysis
• Known systemic conditions that may significantly affect plasma homocysteine levels

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Elevated Homocysteine Group; Patients with newly diagnosed essential hypertension and plasma homocysteine levels greater than 15 µmol/L.	Diagnostic test: Homocysteine Measurement and Echocardiography; Peripheral venous blood sampling for plasma homocysteine measurement and comprehensive transthoracic echocardiography including diastolic function assessment and strain analysis.
Normal Homocysteine Group; Patients with newly diagnosed essential hypertension and plasma homocysteine levels less than or equal to 15 µmol/L.	Diagnostic test: Homocysteine Measurement and Echocardiography; Peripheral venous blood sampling for plasma homocysteine measurement and comprehensive transthoracic echocardiography including diastolic function assessment and strain analysis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of Early Left Ventricular Diastolic Dysfunction	Presence of early left ventricular diastolic dysfunction based on predefined echocardiographic diastolic function criteria assessed by transthoracic echocardiography at baseline, compared between patients with elevated homocysteine levels and normal homocysteine levels.	Baseline assessment at enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mitral Inflow Doppler E/A Ratio by Transthoracic Echocardiography	Comparison of mitral inflow Doppler E/A ratio assessed by transthoracic echocardiography between patients with elevated homocysteine levels and normal homocysteine levels at baseline.	Baseline assessment at enrollment
Septal Mitral Annular e' Velocity by Tissue Doppler Imaging Echocardiography	Comparison of septal mitral annular e' velocity assessed by tissue Doppler imaging echocardiography between patients with elevated homocysteine levels and normal homocysteine levels at baseline.	Baseline assessment at enrollment
Lateral Mitral Annular e' Velocity by Tissue Doppler Imaging Echocardiography	Comparison of lateral mitral annular e' velocity assessed by tissue Doppler imaging echocardiography between patients with elevated homocysteine levels and normal homocysteine levels at baseline.	Baseline assessment at enrollment
Average E/e' Ratio by Doppler Echocardiography	Comparison of average E/e' ratio assessed by Doppler echocardiography between patients with elevated homocysteine levels and normal homocysteine levels at baseline.	Baseline assessment at enrollment
Left Ventricular Global Longitudinal Strain by Speckle-Tracking Echocardiography	Comparison of left ventricular global longitudinal strain assessed by speckle-tracking echocardiography between patients with elevated homocysteine levels and normal homocysteine levels at baseline.	Baseline assessment at enrollment
Left Atrial Global Longitudinal Strain by Speckle-Tracking Echocardiography	Comparison of left atrial global longitudinal strain assessed by speckle-tracking echocardiography between patients with elevated homocysteine levels and normal homocysteine levels at baseline.	Baseline assessment at enrollment

Collaborators and Investigators

• Sponsor: Necmettin Erbakan University
• Investigators: Principal Investigator: yunus emre yavuz, MD, Necmettin Erbakan University

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: March 6, 2026
• First Submitted That Met QC Criteria: March 14, 2026
• First Posted (Actual): March 18, 2026

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 20, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Echocardiography; Diastolic dysfunction; Homocysteine; Machine learning; H-type hypertension; Left ventricular global longitudinal strain; Left atrial global longitudinal strain
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Nutrition Disorders; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Malabsorption Syndromes; Amino Acid Metabolism, Inborn Errors; Avitaminosis; Deficiency Diseases; Malnutrition; Vitamin B Deficiency; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Hypertension; Hyperhomocysteinemia; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Imaging; Diagnostic Techniques, Cardiovascular; Heart Function Tests; Cardiac Imaging Techniques; Ultrasonography; Echocardiography
• Other Study ID Numbers: 2025-5720-HHT-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No