GlycOxiTOD: Multimodal Vascular and Target-Organ Damage Registry (GlycOxiTOD)

Multimodal Vascular Phenotyping and Target-Organ Damage Using Vascular Imaging, Glyco-Oxidative Biomarkers, and Photoplethysmography in Adults at Increased Cardiovascular Risk: The GlycOxiTOD Observational Registry

The goal of the GlycOxiTOD observational registry is to improve the early detection and characterization of vascular and other target-organ damage in adults at increased cardiovascular risk.

Target-organ damage (TOD) means changes in the arteries, heart, kidneys, or other organs that may develop before cardiovascular symptoms or events occur. The registry studies how blood pressure, arterial function, vascular imaging, metabolic and glycoxidative markers, and non-invasive optical signals are related to this early damage.

The main questions are:

• Which clinical, blood pressure, imaging, and laboratory markers are associated with vascular and other target-organ damage?
• Can photoplethysmography, a non-invasive optical technique that records changes in blood flow, identify abnormal arterial features?
• Are new devices, measurement procedures, and signal-analysis methods technically valid, reliable, and reproducible when compared with established clinical methods?
• Can combinations of clinical, imaging, laboratory, and device-derived measurements improve cardiovascular risk assessment?
• How do vascular abnormalities and target-organ damage change during follow-up?

Researchers will not assign any treatment as part of this observational registry. Participants will receive assessments that may include:

• Clinical and cardiovascular risk evaluation
• Office and 24-hour ambulatory blood pressure measurements
• Blood and urine tests for metabolic, glycation, oxidative stress, and inflammatory markers
• Non-invasive vascular ultrasound and arterial function measurements
• Optical photoplethysmography recordings from peripheral or cervical arterial sites
• Skin measurement of advanced glycation end products
• Retinal imaging, when available
• Repeated measurements to assess the reliability and reproducibility of selected devices and procedures
• Follow-up using clinical visits and medical records to identify changes in target-organ damage and cardiovascular events

The registry provides a shared clinical research platform for studies on hypertension, vascular imaging, arterial biomechanics, biomarkers, optical technologies, and the technical and methodological validation of non-invasive cardiovascular devices. Its overall aim is to support the development of reliable tools for early cardiovascular risk assessment and prevention.

Study Overview

• Status: Recruiting
• Conditions: Hypertension; Atherosclerosis; Vascular Stiffness; Heart Disease Risk Factors; Target Organ Damage
• Intervention / Treatment: Diagnostic test: Multimodal Cardiovascular Phenotyping

Detailed Description

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:

• Hypertension and ambulatory blood pressure phenotypes
• Early vascular target-organ damage
• Carotid imaging and plaque characterization
• Arterial biomechanics
• Glycation, oxidative stress, and inflammatory pathways
• Non-invasive biomarkers
• Photoplethysmography and optical vascular sensing
• Validation of cardiovascular devices and analytical procedures
• Diagnostic and risk-stratification models
• Longitudinal changes in vascular or target-organ damage
• Cardiovascular outcomes during follow-up

Each nested study must be scientifically justified and conducted within the scope of the applicable ethical approval, participant information, consent, data-protection requirements, and institutional governance procedures.

FOLLOW-UP

Participants may be followed through scheduled clinical assessments and review of available medical records. Follow-up may be used to identify changes in cardiovascular risk factors, vascular abnormalities, target-organ damage, treatments, hospital use, and cardiovascular events.

The duration and specific content of follow-up depend on the applicable protocol and the objectives of each nested analysis. The registry does not require all participants to undergo every available procedure.

EVENT VERIFICATION AND ADJUDICATION

Potential cardiovascular events are verified against source medical records using prespecified definitions.

Event date, event type, source documentation, and certainty of classification are recorded separately. Where required by a nested study, events are independently reviewed according to a written adjudication charter, and disagreements are resolved by an additional reviewer.

Investigators adjudicating clinical outcomes do not use investigational photoplethysmography or novel biomarker results to classify events.

DATA QUALITY AND REGISTRY PROCEDURES

The registry uses a quality-assurance framework covering participant identification, data collection, data entry, source verification, data management, analysis, and change control.

A structured data dictionary defines the main registry variables, including:

• Variable name and definition
• Source of information
• Unit of measurement
• Permitted values and coding rules
• Clinically plausible ranges
• Missing-data categories
• Derivation rules for calculated variables
• Device or laboratory method, when relevant

Data-entry controls include predefined range and consistency rules. These checks are used to identify values that are missing, duplicated, outside an expected range, or inconsistent with related variables.

Examples include checks for:

• Chronological consistency between dates
• Physiologically implausible clinical or laboratory values
• Incompatible combinations of diagnoses, treatments, or measurements
• Incomplete device or imaging records
• Differences between recorded status and source documentation
• Duplicate participant identifiers or repeated records

Potential inconsistencies generate a data query or are reviewed by an authorized member of the research team. Corrections are made using the source record and are documented according to the applicable data-management procedure.

SOURCE DATA VERIFICATION

Selected registry variables are verified against source documentation, including:

• Electronic medical records
• Clinical reports
• Laboratory information systems
• Ambulatory blood pressure reports
• Ultrasound and imaging files
• Device-generated raw data
• Study worksheets or electronic case-report forms

Verification may be complete for critical variables and sample-based for other variables, depending on the nested study and available resources.

Critical variables may include participant eligibility, dates, target-organ damage classification, reference-standard results, principal device-derived measures, and major cardiovascular outcomes.

PERIODIC REVIEW AND MONITORING

The research team performs periodic reviews of data completeness, consistency, and protocol adherence. Reviews may include:

• Recruitment and follow-up status
• Missing or pending assessments
• Quality of imaging and signal recordings
• Consistency of derived variables
• Resolution of outstanding queries
• Completeness of critical outcomes
• Compliance with the applicable standard operating procedures

Where required by the sponsor, institution, funding body, or applicable regulation, the registry may also be subject to institutional monitoring, audit, or external review.

Quality is based on institutional governance, source verification, predefined rules, documented procedures, and periodic review.

STANDARD OPERATING PROCEDURES

Written procedures are used, when applicable, for:

• Participant recruitment and identification
• Informed-consent procedures
• Clinical and hemodynamic measurements
• Ambulatory blood pressure monitoring
• Vascular ultrasound acquisition
• Image selection and quantitative analysis
• Photoplethysmographic acquisition and signal-quality assessment
• Device positioning and repeated measurements
• Laboratory-sample collection, processing, storage, and analysis
• Data entry and source verification
• Management of missing or inconsistent data
• Dataset locking and version control
• Statistical analysis
• Reporting of incidents related to research procedures
• Protocol and data-dictionary amendments
• Documentation of analytical-code and algorithm versions

Changes affecting variable definitions, acquisition methods, or analytical procedures are documented to preserve traceability across registry versions.

DATA CONFIDENTIALITY AND GOVERNANCE

Participants are assigned a coded study identifier. Direct identifiers are kept separately from the research dataset and access is restricted to authorized personnel.

Research data are handled according to applicable European and Spanish data-protection legislation and institutional policies. Access to registry data is role-based and limited to the information necessary for each approved activity.

Use of registry data for a nested study requires scientific, ethical, and institutional authorization when applicable. Data are not made available to external collaborators without the corresponding governance, data-protection, and contractual arrangements.

MISSING AND UNINTERPRETABLE DATA

The registry distinguishes between different reasons for unavailable information, including:

• Not collected
• Not clinically indicated
• Participant unable or unwilling to complete the assessment
• Technical acquisition failure
• Uninterpretable signal or image
• Source data unavailable
• Value outside prespecified quality criteria
• Lost to follow-up

Missing or uninterpretable data are not automatically replaced during primary data entry.

The analytical approach to missing data depends on the objective, variable type, amount of missingness, and assumptions about the missing-data mechanism. Analyses may include complete-case analysis, multiple imputation, sensitivity analysis, or other appropriate methods.

Device-derived or imaging variables that fail predefined quality criteria are generally classified as non-interpretable rather than imputed, unless a specific and justified analytical procedure has been prespecified.

SAMPLE SIZE

The registry is intended to support continued recruitment and multiple scientific questions. For this reason, the overall registry size is not based on a single effect estimate.

Each confirmatory nested study includes a specific sample-size or precision assessment based on its primary objective, design, expected effect, prevalence, paired or unpaired structure, reference standard, and anticipated proportion of non-interpretable measurements.

Early technical studies may use smaller feasibility samples to evaluate whether procedures can be completed and whether usable measurements can be obtained. These studies are not used to claim diagnostic validity or clinical effectiveness.

STATISTICAL ANALYSIS

Analyses are selected according to the objectives of each nested study and are described in the corresponding statistical analysis plan.

General analytical principles may include:

• Description of participant characteristics and data completeness
• Assessment of variable distributions and measurement quality
• Correlation and association analyses
• Multivariable regression
• Longitudinal and repeated-measures models
• Paired analyses comparing vascular territories within the same participant
• Agreement analysis
• Intraclass correlation coefficients and coefficients of variation
• Bland-Altman analysis
• Diagnostic-discrimination analysis
• Receiver operating characteristic curves
• Calibration and internal validation of predictive models
• Sensitivity analyses for missing data and technical exclusions
• Adjustment for clinically relevant confounding variables

Analyses involving device or algorithm performance distinguish between development, exploratory assessment, and validation. Training and validation datasets are separated when sample size and study design permit.

Results from very small feasibility samples are reported descriptively and are not interpreted as definitive evidence of diagnostic accuracy.

REGISTRY OUTPUTS

The registry is expected to generate:

• Observational studies of cardiovascular and vascular phenotypes
• Technical and methodological validation studies
• Studies of non-invasive biomarkers
• Imaging and signal-processing methods
• Diagnostic and prognostic models
• Procedures for standardized cardiovascular phenotyping
• Collaborative and multicenter research projects
• Scientific publications, training activities, and potential translational developments

The overall purpose is to build a clinically grounded and methodologically robust platform for the early characterization of cardiovascular risk and target-organ damage.

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Nestor Vazquez-Agra, PhD; Phone Number: 0034981951256; Email: nestor.vazquez.agra@sergas.es

Study Locations

• Spain
  • A Coruña
    • Santiago de Compostela, A Coruña, Spain, 15706
      • Recruiting
      • Complejo Hospitalario Universitario de Santiago de Compostela
      • Principal Investigator: Nestor Vazquez-Agra, PhD
      • Sub-Investigator: Ana-Teresa Marques-Afonso, MD
      • Sub-Investigator: Sofia Barbosa-Gouveia, PhD
      • Sub-Investigator: Anton Cruces-Sande, PhD
      • Sub-Investigator: Carla Diaz-Louzao, PhD
      • Sub-Investigator: Iago Carballo, PhD
      • Sub-Investigator: Lucia Barrera-Lopez, MD
      • Sub-Investigator: Alvaro Hermida-Ameijeiras, PhD
      • Sub-Investigator: Arturo Gonzalez-Quintela, PhD
      • Sub-Investigator: Antonio Pose-Reino, PhD
      • Sub-Investigator: Francisco Gude-Sampedro, PhD
      • Contact: Nestor Vazquez Agra, PhD; Phone Number: 0034981951256; Email: nestor.vazquez.agra@sergas.es
      • Sub-Investigator: Oscar Seoane-Casqueiro, MD
      • Sub-Investigator: Emma Lopez-Prado, MD
      • Sub-Investigator: Jose-Enrique Lopez-Paz, PhD
      • Sub-Investigator: Vanesa Alende-Castro, PhD
      • Sub-Investigator: Monica Real-Alvarez, MD

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Participants will be selected from adults evaluated in outpatient Internal Medicine, Hypertension, and Cardiovascular Risk clinics at the Complejo Hospitalario Universitario de Santiago de Compostela, A Coruña, Spain.

The source population includes people referred from primary care or other hospital services for assessment of elevated blood pressure, hypertension, cardiovascular risk factors, suspected subclinical target-organ damage, or non-invasive vascular evaluation.

Eligible participants are enrolled consecutively whenever possible. The registry reflects routine clinical practice and may include both newly evaluated participants and individuals previously characterized under the applicable protocol who have provided the required informed consent.

Description

INCLUSION CRITERIA

• Age 18 years or older.
• Written informed consent to participate in the registry.
• Undergoing cardiovascular risk or hypertension assessment in a primary-prevention setting.

• At least one of the following cardiovascular risk conditions:

  • Confirmed hypertension requiring specialist cardiovascular assessment.
  • A SCORE2 estimated 10-year cardiovascular risk of 2% or higher in participants aged 40 to 69 years, when SCORE2 is applicable.
  • A SCORE2-OP estimated 10-year cardiovascular risk of 2% or higher in participants aged 70 to 89 years, when SCORE2-OP is applicable.
  • Type 2 diabetes with at least moderate cardiovascular risk according to SCORE2-Diabetes in participants within its validated age range, or according to guideline-defined clinical risk criteria when SCORE2-Diabetes is not applicable.
  • Chronic kidney disease confirmed for at least 3 months, defined by an estimated glomerular filtration rate below 60 mL/min/1.73 m², a urinary albumin-to-creatinine ratio of 30 mg/g or higher, or another persistent marker of kidney damage.
  • Hypertension-mediated target-organ damage or subclinical atherosclerotic vascular disease documented by clinical, laboratory, imaging, or functional assessment.
  • Confirmed or probable familial hypercholesterolemia.
  • For participants aged 18 to 39 years or older than 89 years, a documented major cardiovascular risk condition, such as hypertension, type 2 diabetes, chronic kidney disease, familial hypercholesterolemia, or target-organ damage.

EXCLUSION CRITERIA

• Inability or unwillingness to provide written informed consent.
• Established clinical cardiovascular disease requiring secondary-prevention management, including previous myocardial infarction, acute coronary syndrome, stroke, transient ischemic attack, coronary or peripheral revascularization, symptomatic peripheral artery disease, or other established symptomatic cardiovascular disease.
• Acute or clinically unstable illness that prevents completion of the baseline registry assessment.
• A medical, technical, cognitive, or logistical condition that prevents completion of the minimum required registry procedures.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

GlycOxiTOD Registry Cohort; Adults enrolled in the GlycOxiTOD observational registry during evaluation for increased cardiovascular risk. The cohort includes participants undergoing cardiovascular risk assessment and evaluation of vascular or other target-organ damage. Participants may be followed through clinical visits and medical-record review to assess changes in cardiovascular risk factors, target-organ damage, treatments, health care use, and cardiovascular events. No treatment is assigned by the registry.

Diagnostic test: Multimodal Cardiovascular Phenotyping; Multimodal cardiovascular phenotyping may include clinical and anthropometric assessment; office and 24-hour ambulatory blood pressure monitoring; vascular ultrasound and arterial-function measurements; blood and urine biomarkers related to metabolism, glycation, oxidative stress, and inflammation; skin advanced glycation assessment; retinal imaging; and peripheral or cervical photoplethysmography. Selected measurements may be repeated to assess technical feasibility, agreement with reference methods, repeatability, reproducibility, and signal or image quality of non-invasive devices and analytical procedures. Assessments depend on the applicable protocol or nested study, and not all participants undergo every procedure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of Baseline Vascular Target-Organ Damage or Subclinical Vascular Disease	Number and proportion of participants with baseline vascular target-organ damage or subclinical vascular disease, defined by at least one of the following: carotid plaque according to Mannheim criteria; femoral plaque according to prespecified ultrasound criteria; mean carotid intima-media thickness of 0.9 mm or greater; carotid-femoral pulse wave velocity greater than 10 m/s, or validated brachial-ankle pulse wave velocity greater than 14 m/s; or resting ankle-brachial index of 0.90 or lower. An ankle-brachial index greater than 1.40 is non-compressible. Components are recorded separately. Photoplethysmography-derived measures, investigational image-texture features, and device-estimated pulse wave velocity are excluded from the reference outcome. A participant is positive if any criterion is met; negative only when carotid/femoral imaging, validated pulse wave velocity, and ankle-brachial index are all evaluable and below threshold; otherwise indeterminate.	At the baseline vascular assessment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vascular Target-Organ Damage Burden	Number of affected vascular domains among: structural atherosclerotic damage (carotid or femoral plaque, or mean carotid intima-media thickness of 0.9 mm or greater); large-artery stiffness (carotid-femoral pulse wave velocity greater than 10 m/s or validated brachial-ankle pulse wave velocity greater than 14 m/s); and lower-extremity arterial disease (ankle-brachial index of 0.90 or lower). The score ranges from 0 to 3. It is calculated only when all three domains are evaluable; otherwise, affected and evaluable domains are reported separately. An ankle-brachial index greater than 1.40 is classified as non-compressible and not normal.	At the baseline vascular assessment
Presence of Renal Target-Organ Damage	Number and proportion of participants with renal target-organ damage, defined by an estimated glomerular filtration rate below 60 mL/min/1.73 m², a urinary albumin-to-creatinine ratio of 30 mg/g or higher, or another persistent protocol-defined marker of kidney damage. Chronic kidney disease criteria require evidence of persistence when applicable. Participants without sufficient renal data are classified as indeterminate.	At the baseline laboratory assessment
Presence of Cardiac Target-Organ Damage	Number and proportion of participants with cardiac target-organ damage according to prespecified electrocardiographic or echocardiographic criteria. The primary cardiac component is left ventricular hypertrophy, defined using protocol-specified sex-specific thresholds. Additional structural or functional cardiac abnormalities are recorded separately when available. Participants without an evaluable cardiac assessment are classified as indeterminate.	At the baseline cardiovascular assessment
Presence of Retinal Target-Organ Damage	Number and proportion of participants with retinal target-organ damage based on retinal imaging, ophthalmologic examination, or validated clinical documentation. Hypertensive retinopathy and other prespecified retinal microvascular abnormalities are classified using the protocol-defined grading system. The denominator is limited to participants with an evaluable retinal assessment.	At the baseline retinal assessment
Presence of Other Target-Organ Damage	Number and proportion of participants with at least one protocol-defined cardiac, renal, or retinal target-organ abnormality. Each organ domain is also recorded separately. Participants without sufficient information to assess any of these domains are classified as indeterminate rather than as having no target-organ damage.	At the baseline registry assessment
Overall Target-Organ Damage Burden	Number of affected target-organ domains among vascular, renal, cardiac, and retinal domains. The score ranges from 0 to 4 when all domains are evaluable, with higher values indicating greater overall target-organ damage burden. If one or more domains are unavailable, the numbers of affected and evaluable domains are reported separately. Missing domains are not treated as normal.	At the baseline registry assessment
Association Between Ambulatory Blood Pressure Phenotypes and Target-Organ Damage	Association of prespecified 24-hour ambulatory blood pressure measures with baseline vascular and overall target-organ damage. Measures include mean 24-hour, daytime, and nighttime systolic and diastolic blood pressure; pulse pressure; short-term blood pressure variability; and nocturnal dipping pattern. Each exposure is analyzed separately. Results are reported using adjusted effect estimates with 95% confidence intervals.	At the baseline ambulatory blood pressure and target-organ assessment
Association Between Glycation Markers and Vascular Target-Organ Damage	Associations between baseline glycation markers and vascular target-organ damage. Glycation markers may include glycated hemoglobin, fructosamine, glycated albumin, and non-invasive skin autofluorescence as a marker of advanced glycation end-product accumulation. Each marker is analyzed separately using its assay-specific unit. Associations are reported using adjusted regression coefficients, odds ratios, or other appropriate effect estimates with confidence intervals.	At the baseline laboratory, skin glycation, and vascular assessment
Association Between Glycoxidative and Redox Markers and Vascular Target-Organ Damage	Associations between available plasma, serum, or urinary glycoxidative and redox biomarkers and vascular target-organ damage. Markers may include thiobarbituric acid-reactive substances, reduced thiols, catalase, glutathione peroxidase, superoxide dismutase, and other approved oxidative stress or antioxidant-system measurements. Each marker is analyzed separately. Only samples meeting prespecified collection, processing, and analytical quality criteria are included.	At the baseline laboratory and vascular assessment
Proportion of Technically Valid Photoplethysmography Recordings	Number and proportion of attempted peripheral or cervical photoplethysmography recordings that meet prespecified signal-quality and interpretability criteria. Results are reported for the first acquisition and, when applicable, after a permitted repeat acquisition. Reasons for invalid or uninterpretable recordings, including motion, poor contact, signal instability, or technical failure, are recorded separately.	During the initial photoplethysmography assessment
Diagnostic Performance of Photoplethysmography for Vascular Target-Organ Damage	Diagnostic performance of prespecified photoplethysmography-derived features or locked multivariable models for identifying the protocol-defined vascular target-organ damage reference outcome. Performance will be summarized using the area under the receiver operating characteristic curve with a 95% confidence interval. Sensitivity, specificity, positive and negative predictive values, and likelihood ratios may be reported at prespecified thresholds. Feature selection, signal preprocessing, quality criteria, and model version will be locked before confirmatory validation. Exploratory model development and confirmatory validation analyses will be reported separately.	At the baseline photoplethysmography and vascular assessment
Technical Validity and Reproducibility of Non-Invasive Cardiovascular Devices	Technical validity, agreement, repeatability, and reproducibility of selected non-invasive cardiovascular devices and measurement procedures. Device-specific analyses may include mean difference or measurement bias versus an established reference method, limits of agreement, intraclass correlation coefficients, coefficients of variation, intraobserver and interobserver variability, proportion of interpretable measurements, acquisition time, and reasons for technical failure. Results are reported separately for each device and measurement.	During the device-specific assessment, from the first measurement through completion of prespecified repeat measurements
Progression of Vascular Target-Organ Damage	Change in vascular target-organ damage between baseline and follow-up. Progression is defined as development of a new affected vascular domain, an increase of at least one point in the 0-to-3 vascular damage burden score, or a prespecified adverse change in a quantitative vascular measure within an approved nested study. Analyses are limited to participants with comparable evaluable assessments at both time points.	Baseline and 5 years after enrollment
Time to First Major Cardiovascular Event	Time from enrollment to the first occurrence of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, or arterial revascularization. Each component is also recorded separately. Potential events are verified against source medical records and classified according to a written event-definition and adjudication procedure. Participants without an event are censored at the date of their last available follow-up.	From enrollment through 5 years of follow-up

Collaborators and Investigators

• Sponsor: Complejo Hospitalario Universitario de Santiago
• Collaborators: Sociedad Española De Medicina Interna; Axencia Galega de Innovación (GAIN); Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS)

Publications and helpful links

General Publications

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• Van Bortel LM, Laurent S, Boutouyrie P, Chowienczyk P, Cruickshank JK, De Backer T, Filipovsky J, Huybrechts S, Mattace-Raso FU, Protogerou AD, Schillaci G, Segers P, Vermeersch S, Weber T; Artery Society; European Society of Hypertension Working Group on Vascular Structure and Function; European Network for Noninvasive Investigation of Large Arteries. Expert consensus document on the measurement of aortic stiffness in daily practice using carotid-femoral pulse wave velocity. J Hypertens. 2012 Mar;30(3):445-8. doi: 10.1097/HJH.0b013e32834fa8b0.
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• Benchimol EI, Smeeth L, Guttmann A, Harron K, Moher D, Petersen I, Sorensen HT, von Elm E, Langan SM; RECORD Working Committee. The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statement. PLoS Med. 2015 Oct 6;12(10):e1001885. doi: 10.1371/journal.pmed.1001885. eCollection 2015 Oct.
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Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2024
• Primary Completion (Estimated): March 31, 2031
• Study Completion (Estimated): December 31, 2035

Study Registration Dates

• First Submitted: March 16, 2024
• First Submitted That Met QC Criteria: March 16, 2024
• First Posted (Actual): March 22, 2024

Study Record Updates

• Last Update Posted (Actual): August 5, 2026
• Last Update Submitted That Met QC Criteria: August 3, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Oxidative Stress; Photoplethysmography; Ambulatory Blood Pressure Monitoring; Carotid Plaque; Carotid Intima-Media Thickness; Cardiovascular Biomarkers; Signal Processing; Advanced Glycation End Products; Vascular Imaging; Arterial Biomechanics; Cardiovascular Risk Assessment; Medical Device Validation; Noninvasive Vascular Assessment
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Hypertension; Atherosclerosis
• Other Study ID Numbers: 2021401/2023007; Juan Rodés Grant (JR23/00018) (Other Grant/Funding Number: Carlos III Health Institute (ISCIII)); IN607D2025/03 (Other Grant/Funding Number: Galician Innovation Agency (GAIN)); FEMI2024_C-0667 (Other Grant/Funding Number: Spanish Society of Internal Medicine (SEMI)); E-3210_HMOD (Other Identifier: Health Research Institute of Santiago de Compostela (IDIS))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data underlying published results from approved nested studies may be shared with qualified researchers. Data sharing will require approval of a scientifically sound proposal, confirmation that the proposed use is compatible with the informed consent and ethical approval, institutional authorization, and execution of a data-use agreement. Direct identifiers and the participant re-identification key will not be shared.
• IPD Sharing Time Frame: Beginning 12 months after publication of the primary results and completion of the prespecified secondary analyses for the corresponding nested study, whichever occurs later, and available for 5 years.
• IPD Sharing Access Criteria: Access will be considered for qualified researchers who submit a written scientific proposal, a prespecified analysis plan, evidence of ethical approval when required, and a commitment to secure data processing, confidentiality, and non-reidentification. Requests that substantially overlap with ongoing prespecified analyses by GlycOxiTOD investigators may be deferred until those analyses are completed or published. Requests will be reviewed by the GlycOxiTOD registry leadership and the applicable CHUS and FIDIS data-governance bodies. Approved requesters must sign a data-use agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

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