GlycOxiTOD: Multimodal Vascular and Target-Organ Damage Registry

BACKGROUND AND PURPOSE

GlycOxiTOD is an ambispective observational registry designed to characterize vascular and other target-organ damage in adults evaluated for increased cardiovascular risk. The registry is coordinated at the Complejo Hospitalario Universitario de Santiago de Compostela and is designed to support collaborative and multicenter studies conducted under the corresponding ethical and institutional approvals.

The registry was initially developed to study the relationship between glycation, oxidative stress, arterial biomechanics, and target-organ damage. Its scope has subsequently expanded to provide a common clinical research platform integrating hemodynamic assessment, vascular imaging, biochemical markers, optical signals, and the technical and methodological evaluation of non-invasive cardiovascular devices.

The registry does not assign treatments or alter usual clinical care. Clinical decisions remain under the responsibility of the treating health care team.

SCIENTIFIC FRAMEWORK

Cardiovascular target-organ damage includes structural or functional abnormalities affecting the arterial system, heart, kidneys, retina, and other organs. These abnormalities may develop before symptomatic cardiovascular disease and may not be fully identified by conventional risk-factor assessment alone.

GlycOxiTOD evaluates the hypothesis that target-organ damage results from the interaction of several biological and mechanical processes, including:

* Blood pressure load and variability * Abnormal arterial biomechanics * Atherosclerotic and arteriosclerotic changes * Glycation and advanced glycation processes * Oxidative and inflammatory imbalance * Metabolic abnormalities * Changes in vascular optical and pulse-wave signals

The registry is intended to identify clinically meaningful phenotypes rather than to study a single biomarker or device in isolation.

REGISTRY ASSESSMENTS

Assessments are selected according to the participant's clinical characteristics, the applicable protocol, and the objectives of each nested study. They may include the following domains.

Clinical and hemodynamic assessment:

* Demographic, anthropometric, epidemiological, and clinical variables * Cardiovascular risk factors and relevant medical history * Current cardiovascular and metabolic treatments * Office blood pressure and heart rate * Ambulatory blood pressure monitoring * Pulse pressure, blood pressure variability, circadian patterns, and orthostatic response * Clinical cardiovascular-risk estimation

Laboratory and biochemical assessment:

* Routine metabolic, renal, inflammatory, and cardiovascular laboratory variables * Glycated hemoglobin, fructosamine, glycated albumin, and related glycation markers * Advanced glycation and glycoxidation markers * Oxidative stress and antioxidant-system markers * Plasma and urinary redox biomarkers * Additional biomarkers included in approved nested studies

Vascular and target-organ assessment:

* Carotid and peripheral vascular ultrasound * Carotid intima-media thickness and plaque assessment * Arterial structural and biomechanical measurements * Quantitative vascular-image analysis * Ankle-brachial and other non-invasive vascular indices, when available * Renal, cardiac, retinal, or other target-organ variables obtained during clinical evaluation * Retinal imaging, when available and applicable

Optical and signal-based assessment:

* Non-invasive photoplethysmographic recordings * Peripheral and cervical optical pulse signals * Red, infrared, or other approved optical acquisition modalities * Pulse-wave morphology, amplitude, timing, stability, and derived signal features * Comparison of signals obtained from different vascular territories * Integration of signal-derived markers with clinical, biochemical, and imaging findings

Skin advanced glycation end products may also be assessed non-invasively using validated fluorescence-based devices when available.

CORE REGISTRY DATASET AND OPTIONAL MODULES

The registry distinguishes between a minimum core dataset and optional nested-study modules.

The minimum core dataset includes informed consent, demographic and clinical information, major cardiovascular risk factors, current treatments, office blood pressure, routine metabolic and renal laboratory data, and the protocol-defined core vascular assessment.

Additional modules may include ambulatory blood pressure monitoring, advanced glycation and glycoxidative biomarkers, skin autofluorescence, retinal imaging, quantitative vascular imaging, photoplethysmography, and device-validation procedures.

Module-specific eligibility criteria, procedures, quality requirements, and evaluable denominators are prespecified for each nested study. Participants are not classified as having a normal result when the corresponding module was not performed or did not meet technical quality criteria.

TECHNICAL AND METHODOLOGICAL VALIDATION OF DEVICES

An additional purpose of the registry is to support the technical and methodological validation of devices and measurement procedures used within the research line.

These evaluations may include devices for:

* Office, ambulatory, wearable, or cuff-based blood pressure measurement * Vascular ultrasound and quantitative image analysis * Photoplethysmographic and other optical cardiovascular recordings * Arterial-function and biomechanical assessment * Skin advanced glycation measurement * Retinal imaging * Other non-invasive cardiovascular measurements included in approved nested studies

Depending on the device and research question, validation procedures may assess:

* Technical feasibility * Proportion of valid and interpretable measurements * Signal and image quality * Agreement with an established clinical or technical reference method * Within-session repeatability * Between-session reproducibility * Interobserver and intraobserver variability * Device-to-device or operator-related variability * Sensitivity to positioning, contact pressure, motion, and acquisition conditions * Calibration and measurement stability * Robustness of signal-processing or image-analysis algorithms * Diagnostic or discriminative performance, when supported by an appropriate sample and reference standard

Repeated measurements may be performed after repositioning the device or repeating the acquisition procedure. Technical failures, uninterpretable measurements, repeat acquisitions, acquisition time, and reasons for exclusion are recorded whenever relevant.

Device-derived variables and algorithms are evaluated according to prespecified technical criteria. Exploratory results are clearly distinguished from confirmatory validation analyses.

INDEPENDENT ASSESSMENT AND BLINDING

For diagnostic and device-validation studies, index-test processing and reference-standard assessment are performed independently whenever feasible.

Investigators processing photoplethysmography signals, quantitative image features, or investigational device outputs are blinded to the reference vascular classification during prespecified confirmatory analyses. Investigators assessing the reference standard are blinded to investigational signal-derived results.

Algorithm versions, preprocessing steps, exclusion rules, technical quality thresholds, and analysis populations are documented and locked before confirmatory validation.

NESTED STUDIES

GlycOxiTOD functions as a shared registry from which specific observational and methodological studies may be developed.

Nested studies may focus on:

• Vascular Target-Organ Damage Burden [Time frame: At the baseline vascular assessment]
• Presence of Renal Target-Organ Damage [Time frame: At the baseline laboratory assessment]
• Presence of Cardiac Target-Organ Damage [Time frame: At the baseline cardiovascular assessment]
• Presence of Retinal Target-Organ Damage [Time frame: At the baseline retinal assessment]
• Presence of Other Target-Organ Damage [Time frame: At the baseline registry assessment]
• Overall Target-Organ Damage Burden [Time frame: At the baseline registry assessment]
• Association Between Ambulatory Blood Pressure Phenotypes and Target-Organ Damage [Time frame: At the baseline ambulatory blood pressure and target-organ assessment]
• Association Between Glycation Markers and Vascular Target-Organ Damage [Time frame: At the baseline laboratory, skin glycation, and vascular assessment]
• Association Between Glycoxidative and Redox Markers and Vascular Target-Organ Damage [Time frame: At the baseline laboratory and vascular assessment]
• Proportion of Technically Valid Photoplethysmography Recordings [Time frame: During the initial photoplethysmography assessment]
• Diagnostic Performance of Photoplethysmography for Vascular Target-Organ Damage [Time frame: At the baseline photoplethysmography and vascular assessment]
• Technical Validity and Reproducibility of Non-Invasive Cardiovascular Devices [Time frame: During the device-specific assessment, from the first measurement through completion of prespecified repeat measurements]