Homocysteine and Early Diastolic Dysfunction in Newly Diagnosed Hypertension

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.

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