<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03228459</url>
  </required_header>
  <id_info>
    <org_study_id>The ILERVAS project</org_study_id>
    <nct_id>NCT03228459</nct_id>
  </id_info>
  <brief_title>The ILERVAS Project: Assessing the Prevalence of Subclinical Vascular Disease and Hidden Kidney Disease</brief_title>
  <acronym>ILERVAS</acronym>
  <official_title>Randomized Intervention Study to Assess the Prevalence of Subclinical Vascular Disease and Hidden Kidney Disease and Its Impact on Morbidity and Mortality: The ILERVAS Project</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institut de Recerca Biomèdica de Lleida</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Diputació de Lleida</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Jaume Arnó Renal Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Unit of Detection and Treatment of Atherothrombotic diseases (UDETMA)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Lleida Primary health care</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Institut de Recerca Biomèdica de Lleida</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      BACKGROUND AND OBJECTIVES:&#xD;
&#xD;
      Cardiovascular disease is the leading cause of death despite huge primary and secondary&#xD;
      prevention policies with a strong economic burden. The primary objectives of the ILERVAS&#xD;
      project are: (i) to identify unknown factors involved in the presence of atherosclerosis,&#xD;
      metabolic syndrome, pre-diabetes and hidden kidney disease in a low/moderate cardiovascular&#xD;
      risk population; (ii) to identify unknown factors involved in the progression of&#xD;
      atherosclerosis, metabolic syndrome, pre-diabetes and hidden kidney disease in a low/moderate&#xD;
      cardiovascular risk population; (iii) to Assess of the impact of arterial ultrasound on&#xD;
      cardiovascular events and mortality in a low/moderate cardiovascular risk population.&#xD;
&#xD;
      METHODS:&#xD;
&#xD;
      Randomized intervention study. From 2015 to 2018, 16,660 participants (8,330 in the&#xD;
      intervention group (Mobile Unit Follow-up Group) and 8,330 in the no intervention group&#xD;
      (Electronic Medical History Follow-up Group )) aged between 45 and 70 years without a&#xD;
      previous history of cardiovascular disease and with at least one cardiovascular risk factor&#xD;
      will be randomly selected across the province of Lleida, Spain.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      STUDY DESIGN AND POPULATION:&#xD;
&#xD;
      Randomized interventional study. From 2015 to 2018, 16,660 participants (8,330 in the&#xD;
      intervention group (Mobile Unit Follow-up Group) and 8,330 in the no intervention group&#xD;
      (Electronic Medical History Follow-up Group)) aged between 45 and 70 years without a previous&#xD;
      history of cardiovascular disease and with at least one cardiovascular risk factor will be&#xD;
      randomly selected across the province of Lleida, Spain. The Ethics Committee of the&#xD;
      University Hospital Arnau de Vilanova in Lleida (Spain) approved the protocol. All patients&#xD;
      signed informed consent. The study was conducted according to the principles of the&#xD;
      Declaration of Helsinki.&#xD;
&#xD;
      SOURCE OF INFORMATION AND INSTRUMENTS FOR DATA COLLECTION:&#xD;
&#xD;
      In the Mobile Unit (MU), clinical, sociodemographic and anthropometric data will be recorded.&#xD;
      Patients will be evaluated with artery ultrasound (carotid, femoral, transcranial and&#xD;
      abdominal aorta), ankle-brachial index, pulse wave velocity, spirometry, determination of&#xD;
      advanced glycation-end products, atrial fibrillation screening, dried blood spot test and&#xD;
      urine analysis. Moreover, DNA, RNA, Saliva, blood and urine samples will be collected and&#xD;
      stored in the biobank to identify new biomarkers using omic studies. Additionally, climate,&#xD;
      air pollutant and airborne pollen data form the entire province of Lleida will be registered.&#xD;
      In addition, variables such as physical exercise, diet and daytime will be collected.&#xD;
&#xD;
      In the no intervention group (Electronic Medical History Follow-up Group), participants will&#xD;
      be followed through their electronic medical records. Sociodemographic (age, sex, race,&#xD;
      marital status, education and labour status), clinical and anthropometric data and will be&#xD;
      electronically collected.&#xD;
&#xD;
      PARTICIPANT SELECTION:&#xD;
&#xD;
      From a total of 410,246 people with an open history in the e-CAP (in October 24, 2014), the&#xD;
      study population that meets the inclusion criteria will be identified. Of these, a total of&#xD;
      16,660 people (8,330 in the intervention group and 8,330 in the no intervention group) will&#xD;
      be selected through simple randomization without replacement, within clusters defined by&#xD;
      basic healthcare area, primary care (PC) centre or doctor's office, in accordance with the&#xD;
      total number of people who may be visited in the MU during one year period. The participants&#xD;
      of the selected intervention group will be informed of the study objectives and the&#xD;
      diagnostic tests.&#xD;
&#xD;
      FOLLOW-UP PERIOD:&#xD;
&#xD;
      A minimum 10-year follow-up period has been established to observe the onset of CV events. In&#xD;
      the Mobile Unit Follow-up group, a second visit will be performed after four year of&#xD;
      recruitment.&#xD;
&#xD;
      CARDIOVASCULAR EVENTS AND CKD PROGRESSION:&#xD;
&#xD;
      The onset of a CV event will be recorded according to the 10th version of the International&#xD;
      Statistical Classification of Diseases (ICD-10), which includes: angina pectoris, myocardial&#xD;
      infarction, transient ischemic attack, cerebrovascular accident, heart failure, arrhythmia,&#xD;
      peripheral artery disease, aortic aneurysm, revascularization and angioplasty of any artery&#xD;
      region. Likewise, the patient's cause of death, whether of CV origin (myocardial infarction,&#xD;
      arrhythmia, heart failure, cerebrovascular accident, aortic aneurysm, mesenteric infarction&#xD;
      or sudden death) or of non-CV origin (infections, cancers, accident or kidney disease) will&#xD;
      be recorded. The information sources used to identify CV events will be: review of medical&#xD;
      records (through the e-CAP) and consultation of the Catalonia mortality registry. CKD&#xD;
      progression is defined as a doubling of creatinine or entry into renal replacement therapy,&#xD;
      and will also be collected through the e-CAP.&#xD;
&#xD;
      CLINICAL AND BIOCHEMICAL DATA:&#xD;
&#xD;
      The following variables will be recorded: weight, height, waist circumference and neck&#xD;
      circumference, body mass index in kg/m2, hours of fasting, systolic blood pressure, diastolic&#xD;
      blood pressure and pulse pressure (mmHg). Blood pressure will be measured 3 times (Omron 6®)&#xD;
      at 2-min intervals and the mean of the last 2 will be collected. Dried capillary blood&#xD;
      testing (fingertip puncture) will be used to determine creatinine, uric acid and total&#xD;
      cholesterol, using the reflotron® Plus system (Roche). In cases in which total cholesterol is&#xD;
      greater than 200 mg/dl, the complete lipid profile (HDL cholesterol, LDL cholesterol and&#xD;
      triglycerides) will be determined using Cobas B 101® system, Roche. Non-HDL cholesterol&#xD;
      levels, glycated hemoglobin (Cobas B 101 system, Roche), the CKD-EPI glomerular filtration&#xD;
      rate will be determined as well. Albuminuria and albumin/creatinine ratio will be determined&#xD;
      in urine sample from spontaneous micturition collected in the MU using Clinitek Microalbumin&#xD;
      2 Reagent Strips and a Siemens Clinitek Status® analyzer.&#xD;
&#xD;
      ARTERY ULTRASOUND:&#xD;
&#xD;
      The examination and reading will be performed by 2 nurses specialized in vascular imaging&#xD;
      diagnostics, following a standardized protocol with the patient in supine decubitus. The&#xD;
      VIVID I version BT12 ultrasound system (GE Healthcare) will be used. The system has a&#xD;
      12L-RS/4-13 MHz linear probe (carotid and femoral arteries), a 4C-RS/1.5-6 MHz convex probe&#xD;
      (abdominal aorta) and a 3SRS/ 1.5-2.5 MHz sector probe (transcranial). It also has a module&#xD;
      for measuring intima-media thickness and pulsed Doppler ultrasound to assess hemodynamic&#xD;
      abnormalities in the case that atheromatous plaques are present, and also to analyze the&#xD;
      intracranial circulation. The DICOM network connectivity system will be used to record the&#xD;
      results and ultrasound images online in the e-CAP.&#xD;
&#xD;
      Carotid arteries: a total of 8 vascular regions will be analyzed (common carotid, bifurcation&#xD;
      or bulb, internal carotid and external carotid), with the patient in supine decubitus and the&#xD;
      head turned 45º towards the opposite side in the examination.&#xD;
&#xD;
      Femoral arteries: with the patient in supine decubitus, the presence of plaque will be&#xD;
      examined in the common femoral artery (1 cm proximal to the bifurcation) and the superficial&#xD;
      femoral artery on both sides. The plaque definition follows the same previous criteria.&#xD;
&#xD;
      Abdominal aorta: in men age 60 and older. With the patient in supine decubitus, the abdominal&#xD;
      aorta will be examined in the midline of the abdomen from the base of the sternum until the&#xD;
      bifurcation the iliac arteries. In an axial section, at the points where a greater diameter&#xD;
      is observed, 2 images of the aorta will be captured, and 2 measurements will be made&#xD;
      (anterior-posterior and lateral-lateral). An aortic aneurysm will be considered to be present&#xD;
      when the diameter is greater than 3 cm.&#xD;
&#xD;
      Transcranial ultrasound: the arteries of the Willis circle and their branches will be&#xD;
      insonated through the transtemporal and transforaminal acoustic windows. The Doppler spectrum&#xD;
      of each intracranial artery will be determined using the colour-coded signal. Flow direction,&#xD;
      peak systolic velocity, mean flow velocity and diastolic flow velocity will be established.&#xD;
      The intracranial carotid artery, the medial cerebral artery in the M1 and M2 segments, the&#xD;
      anterior cerebral artery (segment A1) and the posterior cerebral artery in segments P1 and P2&#xD;
      will be studied through the transtemporal acoustic window. The V4 segment of the vertebral&#xD;
      arteries and the basilar artery will be studied through the transforaminal acoustic window.&#xD;
      In each patient, the number, location and severity of stenosis will be recorded.&#xD;
      Baumgartner's criteria will be used to establish the severity of the stenosis based on peak&#xD;
      systolic wave velocity (moderate to serious stenosis, if it is ≥155/ 220 cm/s for the medial&#xD;
      cerebral artery, ≤120/≥155 cm/s for the anterior cerebral artery, ≥100/≥145 cm/s for the&#xD;
      posterior cerebral artery and the basilar artery, and ≥90/≥120 cm/s for the vertebral&#xD;
      artery).&#xD;
&#xD;
      ANKLE-BRACHIAL INDEX:&#xD;
&#xD;
      A continuous Doppler (Hadecco ES100X MiniDop®), sphygmomanometer and blood pressure cuffs&#xD;
      (Riester minimus III®) will be used. Systolic blood pressure will be measured in the brachial&#xD;
      artery, posterior tibial artery and dorsalis pedis artery in both limbs. The ratios between&#xD;
      tibial and pedal systolic blood pressure in each leg and the higher brachial blood pressure&#xD;
      will be calculated. The final value for each limb will be the lower value of those obtained&#xD;
      between tibial and pedal blood pressure. An ankle-brachial index value &lt;0.9 will be&#xD;
      considered to be suggestive of stenosis; a value &lt;0.7 will be considered to be stenosis and a&#xD;
      value ≥1.4 will be considered to be suggestive of arterial rigidity.&#xD;
&#xD;
      SPIROMETRY:&#xD;
&#xD;
      Spirometry will be used to assess lung capacity. It will be performed by the same nurse who&#xD;
      will measure forced vital capacity (FVC); forced expiratory volume in one second (FEV1); the&#xD;
      ratio between FEV1 and FVC and the lower limit of normality, as a percentage.&#xD;
&#xD;
      DETERMINATION OF ADVANCED GLYCATION-END PRODUCTS:&#xD;
&#xD;
      They will be measured using skin autofluorescence (SAF) in the forearm with the AGE Reader&#xD;
      system® (Diagnostics, the Netherlands). SAF is measured using spectrophotometry which is&#xD;
      calculated as the relationship of the intensity of reflected light compared to refracted&#xD;
      light. The result obtained will be divided into 4 CV risk groups, taking into account age and&#xD;
      sex.&#xD;
&#xD;
      ATRIAL FIBRILLATION SCREENING:&#xD;
&#xD;
      The presence of atrial fibrillation will be assessed with the SRA device® (EVINA Health&#xD;
      Solutions) for one hour in the MU.&#xD;
&#xD;
      PULSE WAVE VELOCITY:&#xD;
&#xD;
      Pulse wave velocity (PWV) will be used as an indicator of arterial stiffness. It will be&#xD;
      measured non-invasively with the carotid to femoral PWV (cfPWV) according to standard&#xD;
      protocols.&#xD;
&#xD;
      BIOLOGICAL SAMPLE COLLECTION:&#xD;
&#xD;
      Blood samples from a peripheral vein of the hand or forearm to obtain serum, plasma, DNA and&#xD;
      RNA will be collected. Moreover, a saliva sample will be collected.These samples will be&#xD;
      prepared in aliquots following a standardized protocol, and sent frozen (dry ice) to a&#xD;
      centralized biobank (IRBLleida Biobank, Spain) for processing and storage for subsequent&#xD;
      studies of CV, inflammatory and mineral-metabolism biomarkers and genetic polymorphisms.&#xD;
      Urine samples will be frozen and stored in a biobank for subsequent study of biomarkers.&#xD;
&#xD;
      STATISTICAL ANALYSIS:&#xD;
&#xD;
      Descriptive analysis will include absolute and relative frequencies for the qualitative&#xD;
      variables, means and standard deviations for the continuous variables that follow a normal&#xD;
      distribution, and median and interquartile range in the cases that do not follow a normal&#xD;
      distribution. Their distribution will be analyzed with the chi-squared test, in the case of&#xD;
      qualitative variables, and Student's t test or ANOVA for quantitative variables with a normal&#xD;
      distribution, or, failing this, non-parametric Mann-Whitney U or Kruskal-Wallis tests will be&#xD;
      used for those without a normal distribution. The correlation between quantitative variables&#xD;
      will be analyzed using Pearson's or Spearman's test, depending on the distribution. The&#xD;
      existence of collinearity between 2 variables will be analyzed to enter the variable that&#xD;
      better predicts the result variable in the multivariate model. Multivariate analysis will be&#xD;
      performed using logistic regression if the dependent variable is qualitative or linear&#xD;
      regression if it is quantitative. Beta regression coefficients, odds ratios (ORs) and their&#xD;
      respective 95% confidence intervals will be estimated as measures of association. In the&#xD;
      longitudinal study, the incidence of CV morbidity and mortality and mortality due to any&#xD;
      cause will be analyzed, based on the diagnostic tests used in the MU and the biomarkers&#xD;
      studied using Cox regression. Statistical significance will be set at a p value &lt; 0.05.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 15, 2015</start_date>
  <completion_date type="Anticipated">December 31, 2028</completion_date>
  <primary_completion_date type="Actual">December 31, 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>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.</intervention_model_description>
    <primary_purpose>Screening</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Identification of sociodemographic, lifestyle, clinical, anthropometric, laboratory, climate and air pollutants factors involved in atherosclerosis, in a low/moderate cardiovascular risk population.</measure>
    <time_frame>4 years</time_frame>
    <description>The presence of atherosclerosis will be identified as an intima-media thickness higher than 1.5 mm.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Identification of sociodemographic, lifestyle, clinical, anthropometric, laboratory, climate and air pollutants factors involved in pre-diabetes, in a low/moderate cardiovascular risk population.</measure>
    <time_frame>4 years</time_frame>
    <description>The percentage of glycated hemoglobin (Hb A1c) will be determined with a Cobas b 101® machine (Roche). Values lower than 5.7% are normal, &gt; 5.7-6.5% indicate pre-diabetes; and ≥ 6.5% indicate diabetes.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Identification of sociodemograpic, lifestyle, clinical, anthropometric, laboratory, climate and air pollutants factors involved in chronic kidney disease, in a low/moderate cardiovascular risk population.</measure>
    <time_frame>4 years</time_frame>
    <description>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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Assessment of the impact of arterial ultrasound on cardiovascular events and mortality in a low/moderate cardiovascular risk population.</measure>
    <time_frame>10 years</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Prevalence of atherosclerosis in a low/moderate cardiovascular risk population</measure>
    <time_frame>4 years</time_frame>
    <description>The presence of atherosclerosis will be identified as an intima-media thickness higher than 1.5 mm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prevalence of hidden chronic kidney disease in a low/moderate cardiovascular risk population.</measure>
    <time_frame>4 years</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prevalence of pre-diabetes and undiagnosed diabetes in a low/moderate cardiovascular risk population.</measure>
    <time_frame>4 years</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation of skin autofluorescence with atherosclerosis in a low/moderate cardiovascular risk population.</measure>
    <time_frame>4 years</time_frame>
    <description>Skin autofluorescence will be analyzed with the AGE reader™ device (DiagnOptics Technologies, Groningen, The Netherlands). Values range from 1-24 units.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation of adherence to the Mediterranean diet with atherosclerosis in a low/moderate cardiovascular risk population.</measure>
    <time_frame>4 years</time_frame>
    <description>Adherence to the Mediterranean diet will be evaluated with the Mediterranean Diet Adherence screener (MEDAS). Values are from 0 to 14 and categorize subjects according to their level of adherence: high (score &gt;11 points), moderate (7-10 points), and low (&lt;6 points).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation of physical exercise with atherosclerosis in a low/moderate cardiovascular risk population.</measure>
    <time_frame>4 years</time_frame>
    <description>Physical exercise will be evaluated with the International Physical Activity Questionnaire (IPAQ). Values are from vigorous, moderate, and low physical activity. Low activity corresponds to no activity or some activity but not enough to meet moderate category. Moderate corresponds to 3 or more days of walking for at least 30 minutes. Vigorous activity corresponds to 5 or more days of walking for at least 60 minutes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prevalence of atrial fibrillation in a low/moderate cardiovascular risk population.</measure>
    <time_frame>4 years</time_frame>
    <description>The presence of atrial fibrillation is assessed with stroke risk analysis device (SRA, EVINA Health Solutions).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation of spirometry alterations with atherosclerosis in a low/moderate cardiovascular risk population</measure>
    <time_frame>4 years</time_frame>
    <description>Forced vital capacity (FVC) will be measured as liters (l).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation of advanced glycation end-products (AGEs) and cardiovascular events in a low/moderate cardiovascular risk population.</measure>
    <time_frame>10 years</time_frame>
    <description>AGES will be analyzed with the AGE reader™ device (DiagnOptics Technologies, Groningen, The Netherlands). Values range from 1-24 units.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation of adherence to the Mediterranean diet and cardiovascular events in a low/moderate cardiovascular risk population.</measure>
    <time_frame>10 years</time_frame>
    <description>Adherence to the Mediterranean diet will be evaluated with the Mediterranean Diet Adherence screener (MEDAS). Values are from 0 to 14 and categorize subjects according to their level of adherence: high (score &gt;11 points), moderate (7-10 points), and low (&lt;6 points).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation of physical exercise and cardiovascular events in a low/moderate cardiovascular risk population.</measure>
    <time_frame>10 years</time_frame>
    <description>Physical exercise will be evaluated with the International Physical Activity Questionnaire (IPAQ). Values are from vigorous, moderate, and low physical activity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Association of spirometry alterations and cardiovascular events in a low/moderate cardiovascular risk population</measure>
    <time_frame>10 years</time_frame>
    <description>Forced vital capacity (FVC) will be measured as liters (l).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">16660</enrollment>
  <condition>Atherosclerosis</condition>
  <condition>Chronic Kidney Diseases</condition>
  <condition>Metabolic Syndrome</condition>
  <condition>PreDiabetes</condition>
  <condition>Subclinical Disease and/or Syndrome</condition>
  <arm_group>
    <arm_group_label>Mobile Unit Follow-up Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Electronic Medical History Follow-up Group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Dried blood spot test</intervention_name>
    <description>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.</description>
    <arm_group_label>Mobile Unit Follow-up Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Urine test</intervention_name>
    <description>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).</description>
    <arm_group_label>Mobile Unit Follow-up Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Artery ultrasound</intervention_name>
    <description>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.</description>
    <arm_group_label>Mobile Unit Follow-up Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Ankle-brachial index</intervention_name>
    <description>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.</description>
    <arm_group_label>Mobile Unit Follow-up Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Spirometry</intervention_name>
    <description>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.</description>
    <arm_group_label>Mobile Unit Follow-up Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Determination of advanced glycation-end products</intervention_name>
    <description>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.</description>
    <arm_group_label>Mobile Unit Follow-up Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Atrial fibrillation screening</intervention_name>
    <description>The presence of atrial fibrillation is assessed with a device (SRA, EVINA Health Solutions) during one hour in the mobile unit.</description>
    <arm_group_label>Mobile Unit Follow-up Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Biological sample collection</intervention_name>
    <description>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.</description>
    <arm_group_label>Mobile Unit Follow-up Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Result and recommendation report</intervention_name>
    <description>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.</description>
    <arm_group_label>Mobile Unit Follow-up Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Pulse wave velocity</intervention_name>
    <description>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.</description>
    <arm_group_label>Mobile Unit Follow-up Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  women (50-70 years) and men ( 45-65 years) with at least one cardiovascular risk&#xD;
             factor (hypertension, dyslipidemia, obesity (BMI &gt;30 Kg/m2), current smoking habit or&#xD;
             former smoker (&lt;10 years), first-degree family history of early cardiovascular&#xD;
             disease).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior medical history of cardiovascular disease.&#xD;
&#xD;
          -  Diabetes.&#xD;
&#xD;
          -  Glomerular filtration rate (CKD-EPI &lt; 60 ml/min/1.73m2).&#xD;
&#xD;
          -  Active neoplasm or acute disease.&#xD;
&#xD;
          -  A life expectancy &lt; 18 months.&#xD;
&#xD;
          -  Pregnancy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>45 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Elvira Fernández Giráldez, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Fundació Renal Jaume Arnò</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Marcelino Bermúdez López, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Institut de Recerca Biomèdica de Lleida</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Fundació Renal Jaume Arnò</name>
      <address>
        <city>Lleida</city>
        <zip>25006</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Primary Care centre</name>
      <address>
        <city>Lleida</city>
        <zip>25007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut de recerca Biomèdica de Lleida</name>
      <address>
        <city>Lleida</city>
        <zip>25198</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <link>
    <url>http://www.elbusdelasalut.cat/</url>
    <description>Study website</description>
  </link>
  <results_reference>
    <citation>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.</citation>
    <PMID>27044887</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>29706471</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>29525115</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>30717453</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>30842389</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>30989377</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>31065845</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>31212934</PMID>
  </results_reference>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>July 17, 2017</study_first_submitted>
  <study_first_submitted_qc>July 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 25, 2017</study_first_posted>
  <last_update_submitted>August 7, 2022</last_update_submitted>
  <last_update_submitted_qc>August 7, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 9, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Institut de Recerca Biomèdica de Lleida</investigator_affiliation>
    <investigator_full_name>Elvira Fernández Giráldez</investigator_full_name>
    <investigator_title>Study Chair</investigator_title>
  </responsible_party>
  <keyword>Kidney Diseases</keyword>
  <keyword>Subclinical Disease and/or Syndrome</keyword>
  <keyword>Atherosclerosis</keyword>
  <keyword>Biomarkers</keyword>
  <keyword>Prevention</keyword>
  <keyword>Lung capacity</keyword>
  <keyword>Early diagnosis</keyword>
  <keyword>Advanced glycation-end products</keyword>
  <keyword>Atrial fibrillation</keyword>
  <keyword>Diabetes</keyword>
  <keyword>Arterial ultrasound</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Renal Insufficiency, Chronic</mesh_term>
    <mesh_term>Atherosclerosis</mesh_term>
    <mesh_term>Vascular Diseases</mesh_term>
    <mesh_term>Metabolic Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03228459
org study id: The ILERVAS project
nct id: NCT03228459
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
STUDY DESIGN AND POPULATION:

      Randomized interventional 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. The Ethics Committee of the
      University Hospital Arnau de Vilanova in Lleida (Spain) approved the protocol. All patients
      signed informed consent. The study was conducted according to the principles of the
      Declaration of Helsinki.

      SOURCE OF INFORMATION AND INSTRUMENTS FOR DATA COLLECTION:

      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.
      In addition, variables such as physical exercise, diet and daytime will be collected.

      In the no intervention group (Electronic Medical History Follow-up Group), 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.

      PARTICIPANT SELECTION:

      From a total of 410,246 people with an open history in the e-CAP (in October 24, 2014), the
      study population that meets the inclusion criteria will be identified. Of these, a total of
      16,660 people (8,330 in the intervention group and 8,330 in the no intervention group) will
      be selected through simple randomization without replacement, within clusters defined by
      basic healthcare area, primary care (PC) centre or doctor's office, in accordance with the
      total number of people who may be visited in the MU during one year period. The participants
      of the selected intervention group will be informed of the study objectives and the
      diagnostic tests.

      FOLLOW-UP PERIOD:

      A minimum 10-year follow-up period has been established to observe the onset of CV events. In
      the Mobile Unit Follow-up group, a second visit will be performed after four year of
      recruitment.

      CARDIOVASCULAR EVENTS AND CKD PROGRESSION:

      The onset of a CV event will be recorded according to the 10th version of the International
      Statistical Classification of Diseases (ICD-10), which includes: angina pectoris, myocardial
      infarction, transient ischemic attack, cerebrovascular accident, heart failure, arrhythmia,
      peripheral artery disease, aortic aneurysm, revascularization and angioplasty of any artery
      region. Likewise, the patient's cause of death, whether of CV origin (myocardial infarction,
      arrhythmia, heart failure, cerebrovascular accident, aortic aneurysm, mesenteric infarction
      or sudden death) or of non-CV origin (infections, cancers, accident or kidney disease) will
      be recorded. The information sources used to identify CV events will be: review of medical
      records (through the e-CAP) and consultation of the Catalonia mortality registry. CKD
      progression is defined as a doubling of creatinine or entry into renal replacement therapy,
      and will also be collected through the e-CAP.

      CLINICAL AND BIOCHEMICAL DATA:

      The following variables will be recorded: weight, height, waist circumference and neck
      circumference, body mass index in kg/m2, hours of fasting, systolic blood pressure, diastolic
      blood pressure and pulse pressure (mmHg). Blood pressure will be measured 3 times (Omron 6®)
      at 2-min intervals and the mean of the last 2 will be collected. Dried capillary blood
      testing (fingertip puncture) will be used to determine creatinine, uric acid and total
      cholesterol, using the reflotron® Plus system (Roche). In cases in which total cholesterol is
      greater than 200 mg/dl, the complete lipid profile (HDL cholesterol, LDL cholesterol and
      triglycerides) will be determined using Cobas B 101® system, Roche. Non-HDL cholesterol
      levels, glycated hemoglobin (Cobas B 101 system, Roche), the CKD-EPI glomerular filtration
      rate will be determined as well. Albuminuria and albumin/creatinine ratio will be determined
      in urine sample from spontaneous micturition collected in the MU using Clinitek Microalbumin
      2 Reagent Strips and a Siemens Clinitek Status® analyzer.

      ARTERY ULTRASOUND:

      The examination and reading will be performed by 2 nurses specialized in vascular imaging
      diagnostics, following a standardized protocol with the patient in supine decubitus. The
      VIVID I version BT12 ultrasound system (GE Healthcare) will be used. The system has a
      12L-RS/4-13 MHz linear probe (carotid and femoral arteries), a 4C-RS/1.5-6 MHz convex probe
      (abdominal aorta) and a 3SRS/ 1.5-2.5 MHz sector probe (transcranial). It also has a module
      for measuring intima-media thickness and pulsed Doppler ultrasound to assess hemodynamic
      abnormalities in the case that atheromatous plaques are present, and also to analyze the
      intracranial circulation. The DICOM network connectivity system will be used to record the
      results and ultrasound images online in the e-CAP.

      Carotid arteries: a total of 8 vascular regions will be analyzed (common carotid, bifurcation
      or bulb, internal carotid and external carotid), with the patient in supine decubitus and the
      head turned 45º towards the opposite side in the examination.

      Femoral arteries: with the patient in supine decubitus, the presence of plaque will be
      examined in the common femoral artery (1 cm proximal to the bifurcation) and the superficial
      femoral artery on both sides. The plaque definition follows the same previous criteria.

      Abdominal aorta: in men age 60 and older. With the patient in supine decubitus, the abdominal
      aorta will be examined in the midline of the abdomen from the base of the sternum until the
      bifurcation the iliac arteries. In an axial section, at the points where a greater diameter
      is observed, 2 images of the aorta will be captured, and 2 measurements will be made
      (anterior-posterior and lateral-lateral). An aortic aneurysm will be considered to be present
      when the diameter is greater than 3 cm.

      Transcranial ultrasound: the arteries of the Willis circle and their branches will be
      insonated through the transtemporal and transforaminal acoustic windows. The Doppler spectrum
      of each intracranial artery will be determined using the colour-coded signal. Flow direction,
      peak systolic velocity, mean flow velocity and diastolic flow velocity will be established.
      The intracranial carotid artery, the medial cerebral artery in the M1 and M2 segments, the
      anterior cerebral artery (segment A1) and the posterior cerebral artery in segments P1 and P2
      will be studied through the transtemporal acoustic window. The V4 segment of the vertebral
      arteries and the basilar artery will be studied through the transforaminal acoustic window.
      In each patient, the number, location and severity of stenosis will be recorded.
      Baumgartner's criteria will be used to establish the severity of the stenosis based on peak
      systolic wave velocity (moderate to serious stenosis, if it is ≥155/ 220 cm/s for the medial
      cerebral artery, ≤120/≥155 cm/s for the anterior cerebral artery, ≥100/≥145 cm/s for the
      posterior cerebral artery and the basilar artery, and ≥90/≥120 cm/s for the vertebral
      artery).

      ANKLE-BRACHIAL INDEX:

      A continuous Doppler (Hadecco ES100X MiniDop®), sphygmomanometer and blood pressure cuffs
      (Riester minimus III®) will be used. Systolic blood pressure will be measured 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. The final value for each limb will be the lower value of those obtained
      between tibial and pedal blood pressure. An ankle-brachial index value <0.9 will be
      considered to be suggestive of stenosis; a value <0.7 will be considered to be stenosis and a
      value ≥1.4 will be considered to be suggestive of arterial rigidity.

      SPIROMETRY:

      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.

      DETERMINATION OF ADVANCED GLYCATION-END PRODUCTS:

      They 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. The result obtained will be divided into 4 CV risk groups, taking into account age and
      sex.

      ATRIAL FIBRILLATION SCREENING:

      The presence of atrial fibrillation will be assessed with the SRA device® (EVINA Health
      Solutions) for one hour in the MU.

      PULSE WAVE VELOCITY:

      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.

      BIOLOGICAL SAMPLE COLLECTION:

      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.

      STATISTICAL ANALYSIS:

      Descriptive analysis will include absolute and relative frequencies for the qualitative
      variables, means and standard deviations for the continuous variables that follow a normal
      distribution, and median and interquartile range in the cases that do not follow a normal
      distribution. Their distribution will be analyzed with the chi-squared test, in the case of
      qualitative variables, and Student's t test or ANOVA for quantitative variables with a normal
      distribution, or, failing this, non-parametric Mann-Whitney U or Kruskal-Wallis tests will be
      used for those without a normal distribution. The correlation between quantitative variables
      will be analyzed using Pearson's or Spearman's test, depending on the distribution. The
      existence of collinearity between 2 variables will be analyzed to enter the variable that
      better predicts the result variable in the multivariate model. Multivariate analysis will be
      performed using logistic regression if the dependent variable is qualitative or linear
      regression if it is quantitative. Beta regression coefficients, odds ratios (ORs) and their
      respective 95% confidence intervals will be estimated as measures of association. In the
      longitudinal study, the incidence of CV morbidity and mortality and mortality due to any
      cause will be analyzed, based on the diagnostic tests used in the MU and the biomarkers
      studied using Cox regression. Statistical significance will be set at a p value < 0.05.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: 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.
primary purpose: Screening
masking: None (Open Label)
measure: Identification of sociodemographic, lifestyle, clinical, anthropometric, laboratory, climate and air pollutants factors involved in atherosclerosis, in a low/moderate cardiovascular risk population.
time frame: 4 years
description: The presence of atherosclerosis will be identified as an intima-media thickness higher than 1.5 mm.
measure: Identification of sociodemographic, lifestyle, clinical, anthropometric, laboratory, climate and air pollutants factors involved in pre-diabetes, in a low/moderate cardiovascular risk population.
time frame: 4 years
description: 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.
measure: Identification of sociodemograpic, lifestyle, clinical, anthropometric, laboratory, climate and air pollutants factors involved in chronic kidney disease, in a low/moderate cardiovascular risk population.
time frame: 4 years
description: 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.
measure: Assessment of the impact of arterial ultrasound on cardiovascular events and mortality in a low/moderate cardiovascular risk population.
time frame: 10 years
description: 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.
measure: Prevalence of atherosclerosis in a low/moderate cardiovascular risk population
time frame: 4 years
description: The presence of atherosclerosis will be identified as an intima-media thickness higher than 1.5 mm.
measure: Prevalence of hidden chronic kidney disease in a low/moderate cardiovascular risk population.
time frame: 4 years
description: 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.
measure: Prevalence of pre-diabetes and undiagnosed diabetes in a low/moderate cardiovascular risk population.
time frame: 4 years
description: 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.
measure: Correlation of skin autofluorescence with atherosclerosis in a low/moderate cardiovascular risk population.
time frame: 4 years
description: Skin autofluorescence will be analyzed with the AGE reader™ device (DiagnOptics Technologies, Groningen, The Netherlands). Values range from 1-24 units.
measure: Correlation of adherence to the Mediterranean diet with atherosclerosis in a low/moderate cardiovascular risk population.
time frame: 4 years
description: Adherence to the Mediterranean diet will be evaluated with the Mediterranean Diet Adherence screener (MEDAS). Values are from 0 to 14 and categorize subjects according to their level of adherence: high (score >11 points), moderate (7-10 points), and low (<6 points).
measure: Correlation of physical exercise with atherosclerosis in a low/moderate cardiovascular risk population.
time frame: 4 years
description: Physical exercise will be evaluated with the International Physical Activity Questionnaire (IPAQ). Values are from vigorous, moderate, and low physical activity. Low activity corresponds to no activity or some activity but not enough to meet moderate category. Moderate corresponds to 3 or more days of walking for at least 30 minutes. Vigorous activity corresponds to 5 or more days of walking for at least 60 minutes.
measure: Prevalence of atrial fibrillation in a low/moderate cardiovascular risk population.
time frame: 4 years
description: The presence of atrial fibrillation is assessed with stroke risk analysis device (SRA, EVINA Health Solutions).
measure: Correlation of spirometry alterations with atherosclerosis in a low/moderate cardiovascular risk population
time frame: 4 years
description: Forced vital capacity (FVC) will be measured as liters (l).
measure: Correlation of advanced glycation end-products (AGEs) and cardiovascular events in a low/moderate cardiovascular risk population.
time frame: 10 years
description: AGES will be analyzed with the AGE reader™ device (DiagnOptics Technologies, Groningen, The Netherlands). Values range from 1-24 units.
measure: Correlation of adherence to the Mediterranean diet and cardiovascular events in a low/moderate cardiovascular risk population.
time frame: 10 years
description: Adherence to the Mediterranean diet will be evaluated with the Mediterranean Diet Adherence screener (MEDAS). Values are from 0 to 14 and categorize subjects according to their level of adherence: high (score >11 points), moderate (7-10 points), and low (<6 points).
measure: Correlation of physical exercise and cardiovascular events in a low/moderate cardiovascular risk population.
time frame: 10 years
description: Physical exercise will be evaluated with the International Physical Activity Questionnaire (IPAQ). Values are from vigorous, moderate, and low physical activity.
measure: Association of spirometry alterations and cardiovascular events in a low/moderate cardiovascular risk population
time frame: 10 years
description: Forced vital capacity (FVC) will be measured as liters (l).
arm group label: Mobile Unit Follow-up Group
arm group type: Experimental
description: 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.
arm group label: Electronic Medical History Follow-up Group
arm group type: No Intervention
description: 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.
intervention type: Diagnostic Test
intervention name: Dried blood spot test
description: 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.
arm group label: Mobile Unit Follow-up Group
intervention type: Diagnostic Test
intervention name: Urine test
description: 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).
arm group label: Mobile Unit Follow-up Group
intervention type: Diagnostic Test
intervention name: Artery ultrasound
description: 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.
arm group label: Mobile Unit Follow-up Group
intervention type: Diagnostic Test
intervention name: Ankle-brachial index
description: 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.
arm group label: Mobile Unit Follow-up Group
intervention type: Diagnostic Test
intervention name: Spirometry
description: 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.
arm group label: Mobile Unit Follow-up Group
intervention type: Diagnostic Test
intervention name: Determination of advanced glycation-end products
description: 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.
arm group label: Mobile Unit Follow-up Group
intervention type: Diagnostic Test
intervention name: Atrial fibrillation screening
description: The presence of atrial fibrillation is assessed with a device (SRA, EVINA Health Solutions) during one hour in the mobile unit.
arm group label: Mobile Unit Follow-up Group
intervention type: Other
intervention name: Biological sample collection
description: 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.
arm group label: Mobile Unit Follow-up Group
intervention type: Other
intervention name: Result and recommendation report
description: 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.
arm group label: Mobile Unit Follow-up Group
intervention type: Diagnostic Test
intervention name: Pulse wave velocity
description: 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.
arm group label: Mobile Unit Follow-up Group
criteria: 
gender: All
minimum age: 45 Years
maximum age: 70 Years
healthy volunteers: No
last name: Elvira Fernández Giráldez, MD, PhD
role: Study Chair
affiliation: Fundació Renal Jaume Arnò
last name: Marcelino Bermúdez López, MD, PhD
role: Study Director
affiliation: Institut de Recerca Biomèdica de Lleida
facility: 
facility: 
facility: 
country: Spain
url: http://www.elbusdelasalut.cat/
description: Study website
citation: 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
citation: 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
citation: 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
citation: 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
citation: 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
citation: 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
citation: 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
citation: 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
responsible party type: Principal Investigator
investigator affiliation: Institut de Recerca Biomèdica de Lleida
investigator full name: Elvira Fernández Giráldez
investigator title: Study Chair
mesh term: Kidney Diseases
mesh term: Renal Insufficiency, Chronic
mesh term: Atherosclerosis
mesh term: Vascular Diseases
mesh term: Metabolic Syndrome
mesh term: Syndrome
sharing ipd: No