The ILERVAS Project: Assessing the Prevalence of Subclinical Vascular Disease and Hidden Kidney Disease

NCT03228459 | Active Not Recruiting

• 1 other identifier: The ILERVAS project
• Study Type: interventional
• Target: 16,660
• Locations: 1 country
• Sites: 3

Brief Summary

BACKGROUND AND OBJECTIVES: Cardiovascular disease is the leading cause of death despite huge primary and secondary prevention policies with a strong economic burden. The primary objectives of the ILERVAS project are: (i) to identify unknown factors involved in the presence of atherosclerosis, metabolic syndrome, pre-diabetes and hidden kidney disease in a low/moderate cardiovascular risk population; (ii) to identify unknown factors involved in the progression of atherosclerosis, metabolic syndrome, pre-diabetes and hidden kidney disease in a low/moderate cardiovascular risk population; (iii) to Assess of the impact of arterial ultrasound on cardiovascular events and mortality in a low/moderate cardiovascular risk population. METHODS: Randomized intervention study. From 2015 to 2018, 16,660 participants (8,330 in the intervention group (Mobile Unit Follow-up Group) and 8,330 in the no intervention group (Electronic Medical History Follow-up Group )) aged between 45 and 70 years without a previous history of cardiovascular disease and with at least one cardiovascular risk factor will be randomly selected across the province of Lleida, Spain.

Conditions

Atherosclerosis; Chronic Kidney Diseases; Metabolic Syndrome; PreDiabetes; Subclinical Disease and/or Syndrome

Keywords

Kidney Diseases; Subclinical Disease and/or Syndrome; Atherosclerosis; Biomarkers; Prevention; Lung capacity; Early diagnosis; Advanced glycation-end products; Atrial fibrillation; Diabetes; Arterial ultrasound

Outcome Measures

Primary Outcomes (4)

• Identification of sociodemographic, lifestyle, clinical, anthropometric, laboratory, climate and air pollutants factors involved in atherosclerosis, in a low/moderate cardiovascular risk population.

  The presence of atherosclerosis will be identified as an intima-media thickness higher than 1.5 mm.

  4 years

• Identification of sociodemographic, lifestyle, clinical, anthropometric, laboratory, climate and air pollutants factors involved in pre-diabetes, in a low/moderate cardiovascular risk population.

  The percentage of glycated hemoglobin (Hb A1c) will be determined with a Cobas b 101® machine (Roche). Values lower than 5.7% are normal, \> 5.7-6.5% indicate pre-diabetes; and ≥ 6.5% indicate diabetes.

  4 years

• Identification of sociodemograpic, lifestyle, clinical, anthropometric, laboratory, climate and air pollutants factors involved in chronic kidney disease, in a low/moderate cardiovascular risk population.

  The prevalence of hidden chronic kidney disease will be assessed with a urine spot test that determines the albumin/creatinine ratio (ACR). Values lower than 30 mg/g are normal; 30-300 mg/g indicate microalbuminuria; and values higher than 300 indicate macroalbuminuria.

  4 years

• Assessment of the impact of arterial ultrasound on cardiovascular events and mortality in a low/moderate cardiovascular risk population.

  The onset of a cardiovascular event will be recorded according to the tenth version of the International Statistical Classification of Diseases (ICD-10). Cardiovascular events and mortality in the intervention group will be compared to the control group during a during a 10-year follow-up period.

  10 years

Secondary Outcomes (12)

• Prevalence of atherosclerosis in a low/moderate cardiovascular risk population

  4 years

• Prevalence of hidden chronic kidney disease in a low/moderate cardiovascular risk population.

  4 years

• Prevalence of pre-diabetes and undiagnosed diabetes in a low/moderate cardiovascular risk population.

  4 years

• Correlation of skin autofluorescence with atherosclerosis in a low/moderate cardiovascular risk population.

  4 years

• Correlation of adherence to the Mediterranean diet with atherosclerosis in a low/moderate cardiovascular risk population.

  4 years

Study Arms (2)

Mobile Unit Follow-up Group

EXPERIMENTAL

In the Mobile Unit (MU), clinical, sociodemographic and anthropometric data will be recorded. Patients will be evaluated with artery ultrasound (carotid, femoral, transcranial and abdominal aorta), ankle-brachial index, pulse wave velocity, spirometry, determination of advanced glycation-end products, atrial fibrillation screening, dried blood spot test and urine analysis. Moreover, DNA, RNA, Saliva, blood and urine samples will be collected and stored in the biobank to identify new biomarkers using omic studies. Additionally, climate, air pollutant and airborne pollen data form the entire province of Lleida will be registered. Finally, a report with the exploration results and recommendations based on the current guidelines will be uploaded to the e-CAP history for the Primary care evaluation.

Diagnostic Test: Dried blood spot test; Diagnostic Test: Urine test; Diagnostic Test: Artery ultrasound; Diagnostic Test: Ankle-brachial index; Diagnostic Test: Spirometry; Diagnostic Test: Determination of advanced glycation-end products; Diagnostic Test: Atrial fibrillation screening; Other: Biological sample collection; Other: Result and recommendation report; Diagnostic Test: Pulse wave velocity

Electronic Medical History Follow-up Group

NO INTERVENTION

Participants will be followed through their electronic medical records. Sociodemographic (age, sex, race, marital status, education and labour status), clinical and anthropometric data and will be electronically collected.

Interventions

Artery ultrasound DIAGNOSTIC_TEST

Carotid and femoral artery ultrasound for atheroma plaque diagnosis. Abdominal aorta ultrasound for early diagnosis of aortic aneurism. Transcranial ultrasound for cerebral arterial blood flow alterations.

Mobile Unit Follow-up Group

Ankle-brachial index DIAGNOSTIC_TEST

Systolic blood pressure measurement in the brachial artery, posterior tibial artery and dorsalis pedis artery in both limbs. The ratios between tibial and pedal systolic blood pressure in each leg and the higher brachial blood pressure will be calculated.

Mobile Unit Follow-up Group

Spirometry DIAGNOSTIC_TEST

Spirometry will be used to assess lung capacity. It will be performed by the same nurse who will measure forced vital capacity (FVC); forced expiratory volume in one second (FEV1); the ratio between FEV1 and FVC and the lower limit of normality, as a percentage.

Mobile Unit Follow-up Group

Determination of advanced glycation-end products DIAGNOSTIC_TEST

These will be measured using skin autofluorescence (SAF) in the forearm with the AGE Reader® system (Diagnostics, the Netherlands). SAF is measured using spectrophotometry which is calculated as the relationship of the intensity of reflected light compared to refracted light.

Mobile Unit Follow-up Group

Atrial fibrillation screening DIAGNOSTIC_TEST

The presence of atrial fibrillation is assessed with a device (SRA, EVINA Health Solutions) during one hour in the mobile unit.

Mobile Unit Follow-up Group

Biological sample collection OTHER

Blood samples from a peripheral vein of the hand or forearm to obtain serum, plasma, DNA and RNA will be collected. Moreover, a saliva sample will be collected.These samples will be prepared in aliquots following a standardized protocol, and sent frozen (dry ice) to a centralized biobank (IRBLleida Biobank, Spain) for processing and storage for subsequent studies of CV, inflammatory and mineral-metabolism biomarkers and genetic polymorphisms. Urine samples will be frozen and stored in a biobank for subsequent study of biomarkers.

Mobile Unit Follow-up Group

Result and recommendation report OTHER

A report with exploration results and recommendations based on the current guidelines will be uploaded to the e-CAP history for the Primary care evaluation.

Mobile Unit Follow-up Group

Pulse wave velocity DIAGNOSTIC_TEST

Pulse wave velocity (PWV) will be used as an indicator of arterial stiffness. It will be measured non-invasively with the carotid to femoral PWV (cfPWV) according to standard protocols.

Mobile Unit Follow-up Group

Dried blood spot test DIAGNOSTIC_TEST

Dried capillary blood testing creatinine, uric acid and total cholesterol (reflotron® Plus system, Roche). Determination of the complete lipid profile in cases in which total cholesterol is greater than 200 mg/dl: HDL cholesterol (mg/dl), LDL cholesterol (mg/dl) and triglycerides (mg/dl) (Cobas B 101® system, Roche). Calculation of non-HDL cholesterol levels. Glycated haemoglobin will be analysed with the Cobas B 101 system,Roche. The CKD-EPI glomerular filtration rate will be determined.

Mobile Unit Follow-up Group

Urine test DIAGNOSTIC_TEST

A urine sample from spontaneous micturition will be collected and analyzed using Clinitek Microalbumin 2 Reagent Strips and a Siemens Clinitek Status® analyzer. It will be determined albuminuria (mg/l) and albumin/creatinine ratio (mg/g).

Mobile Unit Follow-up Group

Eligibility Criteria

• Age: 45 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• women (50-70 years) and men ( 45-65 years) with at least one cardiovascular risk factor (hypertension, dyslipidemia, obesity (BMI \>30 Kg/m2), current smoking habit or former smoker (\<10 years), first-degree family history of early cardiovascular disease).

You may not qualify if:

• Prior medical history of cardiovascular disease.
• Diabetes.
• Glomerular filtration rate (CKD-EPI \< 60 ml/min/1.73m2).
• Active neoplasm or acute disease.
• A life expectancy \< 18 months.
• Pregnancy.

Sponsors & Collaborators

• Diputació de Lleida: collaborator
• Jaume Arnó Renal Foundation: collaborator
• Lleida Primary health care: collaborator
• Unit of Detection and Treatment of Atherothrombotic diseases (UDETMA): collaborator
• Institut de Recerca Biomèdica de Lleida: lead

Study Sites (3)

Fundació Renal Jaume Arnò

Lleida, Lleida, 25006, Spain

Location

Primary Care centre

Lleida, Lleida, 25007, Spain

Location

Institut de recerca Biomèdica de Lleida

Lleida, Lleida, 25198, Spain

Location

Related Publications (13)

• Betriu A, Farras C, Abajo M, Martinez-Alonso M, Arroyo D, Barbe F, Buti M, Lecube A, Portero M, Purroy F, Torres G, Valdivielso JM, Fernandez E. Randomised intervention study to assess the prevalence of subclinical vascular disease and hidden kidney disease and its impact on morbidity and mortality: The ILERVAS project. Nefrologia. 2016 Jul-Aug;36(4):389-96. doi: 10.1016/j.nefro.2016.02.008. Epub 2016 Apr 1. English, Spanish.

  PMID: 27044887 RESULT

• Sanchez E, Lecube A, Betriu A, Hernandez C, Lopez-Cano C, Gutierrez-Carrasquilla L, Kerkeni M, Yeramian A, Purroy F, Pamplona R, Farras C, Fernandez E, Barbe F, Simo R; ILERVAS project; Hernandez M, Rius F, Polanco D, de la Torre MS, Torres G, Godoy P, Portero-Otin M, Jove M, Colas-Compas L, Benabdelhak I, Miquel E, Ortega M, Valdivielso JM, Bermudez M, Martinez-Alonso M. Subcutaneous advanced glycation end-products and lung function according to glucose abnormalities: The ILERVAS Project. Diabetes Metab. 2019 Dec;45(6):595-598. doi: 10.1016/j.diabet.2018.04.002. Epub 2018 Apr 13. No abstract available.

  PMID: 29706471 RESULT

• Montserrat-Capdevila J, Seminario MA, Godoy P, Marsal JR, Ortega M, Pujol J, Castan MT, Alseda M, Betriu A, Lecube A, Portero M, Purroy F, Valdivielso JM, Barbe F. Prevalence of chronic obstructive pulmonary disease (COPD) not diagnosed in a population with cardiovascular risk factors. Med Clin (Barc). 2018 Nov 21;151(10):383-389. doi: 10.1016/j.medcli.2017.12.018. Epub 2018 Mar 7. English, Spanish.

  PMID: 29525115 RESULT

• Gutierrez-Carrasquilla L, Sanchez E, Hernandez M, Polanco D, Salas-Salvado J, Betriu A, Gaeta AM, Carmona P, Purroy F, Pamplona R, Farras C, Lopez-Cano C, Fernandez E, Lecube A. Effects of Mediterranean Diet and Physical Activity on Pulmonary Function: A Cross-Sectional Analysis in the ILERVAS Project. Nutrients. 2019 Feb 3;11(2):329. doi: 10.3390/nu11020329.

  PMID: 30717453 RESULT

• Sanchez E, Betriu A, Yeramian A, Fernandez E, Purroy F, Sanchez-de-la-Torre M, Pamplona R, Miquel E, Kerkeni M, Hernandez C, Simo R, Lecube A; ILERVAS project; ILERVAS Project:; Hernandez M, Rius F, Polanco D, Barbe F, Torres G, Suarez G, Portero-Otin M, Jove M, Colas-Campas L, Benabdelhak I, Farras C, Ortega M, Manuel Valdivielso J, Bermudez-Lopez M, Martinez-Alonso M. Skin Autofluorescence Measurement in Subclinical Atheromatous Disease: Results from the ILERVAS Project. J Atheroscler Thromb. 2019 Oct 1;26(10):879-889. doi: 10.5551/jat.47498. Epub 2019 Mar 6.

  PMID: 30842389 RESULT

• Sanchez E, Gutierrez-Carrasquilla L, Barbe F, Betriu A, Lopez-Cano C, Gaeta AM, Purroy F, Pamplona R, Ortega M, Fernandez E, Hernandez C, Lecube A, Simo R; ILERVAS Project. Lung function measurements in the prediabetes stage: data from the ILERVAS Project. Acta Diabetol. 2019 Sep;56(9):1005-1012. doi: 10.1007/s00592-019-01333-6. Epub 2019 Apr 15.

  PMID: 30989377 RESULT

• Sanchez E, Betriu A, Salas-Salvado J, Pamplona R, Barbe F, Purroy F, Farras C, Fernandez E, Lopez-Cano C, Mizab C, Lecube A; ILERVAS project investigators. Mediterranean diet, physical activity and subcutaneous advanced glycation end-products' accumulation: a cross-sectional analysis in the ILERVAS project. Eur J Nutr. 2020 Apr;59(3):1233-1242. doi: 10.1007/s00394-019-01983-w. Epub 2019 May 7.

  PMID: 31065845 RESULT

• Sanchez M, Sanchez E, Hernandez M, Gonzalez J, Purroy F, Rius F, Pamplona R, Farras-Salles C, Gutierrez-Carrasquilla L, Fernandez E, Bermudez-Lopez M, Salvador J, Salas-Salvado J, Lecube A; ILERVAS project collaborators. Dissimilar Impact of a Mediterranean Diet and Physical Activity on Anthropometric Indices: A Cross-Sectional Study from the ILERVAS Project. Nutrients. 2019 Jun 17;11(6):1359. doi: 10.3390/nu11061359.

  PMID: 31212934 RESULT

• Leon-Mengibar J, Malagon MM, Bermudez-Lopez M, Valdivielso JM, Pamplona R, Torres G, Mauricio D, Castro E, Fernandez E, Caixas A, Hernandez M, Lopez-Cano C, Gordon A, Guzman-Ruiz R, Cusi K, Lecube A. Association of estimated liver fibrosis with carotid but not femoral atherosclerotic burden: the ILERVAS cohort. Front Endocrinol (Lausanne). 2026 Jan 6;16:1651689. doi: 10.3389/fendo.2025.1651689. eCollection 2025.

  PMID: 41567808 DERIVED

• Leon-Mengibar J, Bermudez-Lopez M, Valdivielso JM, Pamplona R, Torres G, Mauricio D, Castro-Boque E, Fernandez E, Caixas A, Bueno M, Ciudin A, Hernandez M, Simo R, Hernandez C, Lecube A. Impact of the new EASO obesity definition on the detection of atheromatosis in subjects with low-to-moderate cardiovascular risk. Front Endocrinol (Lausanne). 2025 Oct 10;16:1689960. doi: 10.3389/fendo.2025.1689960. eCollection 2025.

  PMID: 41141356 DERIVED

• Bermudez-Lopez M, Marti-Antonio M, Castro-Boque E, Bretones MDM, Farras C, Torres G, Pamplona R, Lecube A, Mauricio D, Valdivielso JM, Fernandez E. Development and Validation of a Personalized, Sex-Specific Prediction Algorithm of Severe Atheromatosis in Middle-Aged Asymptomatic Individuals: The ILERVAS Study. Front Cardiovasc Med. 2022 Jul 14;9:895917. doi: 10.3389/fcvm.2022.895917. eCollection 2022.

  PMID: 35928938 DERIVED

• Bermudez-Lopez M, Martinez-Alonso M, Castro-Boque E, Betriu A, Cambray S, Farras C, Barbe F, Pamplona R, Lecube A, Mauricio D, Purroy F, Valdivielso JM, Fernandez E; ILERVAS project collaborators. Subclinical atheromatosis localization and burden in a low-to-moderate cardiovascular risk population: the ILERVAS study. Rev Esp Cardiol (Engl Ed). 2021 Dec;74(12):1042-1053. doi: 10.1016/j.rec.2020.09.015. Epub 2020 Nov 6. English, Spanish.

  PMID: 33162389 DERIVED

• Sanchez E, Betriu A, Lopez-Cano C, Hernandez M, Fernandez E, Purroy F, Bermudez-Lopez M, Farras-Salles C, Barril S, Pamplona R, Rius F, Hernandez C, Simo R, Lecube A; ILERVAS project collaborators. Characteristics of atheromatosis in the prediabetes stage: a cross-sectional investigation of the ILERVAS project. Cardiovasc Diabetol. 2019 Nov 15;18(1):154. doi: 10.1186/s12933-019-0962-6.

  PMID: 31729979 DERIVED

Related Links

• Study website

MeSH Terms

Conditions

Atherosclerosis; Renal Insufficiency, Chronic; Metabolic Syndrome; Prediabetic State; Kidney Diseases; Disease; Atrial Fibrillation; Diabetes Mellitus

Interventions

Urinalysis; Ultrasonography, Carotid Arteries; Ankle Brachial Index; Spirometry; Pulse Wave Analysis

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Renal Insufficiency; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Arrhythmias, Cardiac; Heart Diseases

Intervention Hierarchy (Ancestors)

Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Urological; Investigative Techniques; Ultrasonography; Diagnostic Imaging; Blood Pressure Determination; Diagnostic Techniques, Cardiovascular; Respiratory Function Tests; Diagnostic Techniques, Respiratory System

Study Officials

• Elvira Fernández Giráldez, MD, PhD

  Fundació Renal Jaume Arnò

  STUDY CHAIR

• Marcelino Bermúdez López, MD, PhD

  Institut de Recerca Biomèdica de Lleida

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Study Chair

Model Details: A randomized interventional study with 2 arms that will include 16,660 individuals with at least one cardiovascular risk factor from the province of Lleida, Spain. Patients will be recruited from January 2015 to December 2018. Patients will be followed for 10 years.

Study Record Dates

• First Submitted: July 17, 2017
• First Posted: July 25, 2017
• Study Start: January 15, 2015
• Primary Completion: December 31, 2018
• Study Completion (Estimated): December 31, 2028
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (3)