Non-invasive Microvascular Assessment in Individuals at High Risk of Cardiovascular Disease From the SCAPIS2 Study

SCAPIS 2 - Spectrum Study -CVD Risk Based on Microvascular Dysfunction

Microvascular dysfunction, particularly endothelial dysfunction, is increasingly recognized as a key mechanism underlying various cardiovascular diseases (CVD), including heart failure, ischemic heart disease, atherosclerosis, stroke, dementia, and kidney failure. Chronic low-grade inflammation linked to metabolic syndrome may further drive systemic microvascular impairment. Early detection of these subclinical processes using non-invasive assessments could facilitate timely interventions to prevent disease progression.

SCAPIS 2 Spectrum is a prospective observational sub-study of the Swedish Cardiopulmonary Bioimage Study (SCAPIS-2), recruiting approximately 900 subjects aged 60-75 years. The study is organized into five arms-obstructive coronary artery disease (O-CAD), angina with nonobstructive coronary arteries (ANOCA), metabolic syndrome with diabetes, left ventricular systolic dysfunction, and left ventricular diastolic dysfunction-each defined by specific inclusion and exclusion criteria. Participants will undergo a comprehensive microvascular assessment using investigational devices (including Perimed Periflux EPOS, PeriCam MultiFlow, and TCI P4) alongside stress cardiac magnetic resonance imaging (stress-CMR) for cardiac-specific evaluation.

Study Overview

• Status: Recruiting
• Conditions: Cardiovascular Diseases; Microvascular Complications

Detailed Description

Non-invasive microvascular Assessment A comprehensive microvascular evaluation is performed using three investigational devices designed to capture detailed information on dermal perfusion. The Perimed Periflux 6000 EPOS employs diffuse reflectance spectroscopy (DRS) and laser Doppler flowmetry (LDF) for a single-point multi-modal assessment. The PeriCam MultiFlow performs imaging of dermal perfusion using multi-exposure laser contrast imaging (MELSCI) and measures blood oxygen saturation via multispectral imaging (MSI). Additionally, the TCI P4 utilizes spatial frequency domain imaging technology for quantification of perfusion and chromophore concentrations in the skin. Functional methods, including Post-Occlusive Reactive Hyperemia (PORH), Flow-Motion Analysis, and Thermal Provocation, are applied to assess dynamic microvascular responses.

Cardiac Magnetic Resonance Imaging (CMR) Stress#CMR is conducted using adenosine infusion and contrast enhancement to evaluate cardiac-specific microvascular function. This approach includes first-pass perfusion imaging and quantitative myocardial blood flow analyses, which allow for calculation of myocardial perfusion reserve.

• Study Type: Observational
• Enrollment (Estimated): 900

Contacts and Locations

• Study Contact: Name: Mattias Windå, Chief Science and Innovation Officer; Phone Number: +46703169040; Email: mattias@nekohealth.com

Study Locations

• Sweden
  • Danderyd
    • Stockholm, Danderyd, Sweden
      • Recruiting
      • Danderyd Hospital
      • Contact: Sara Tehrani, Principal Investigator, MD, Ph.D; Phone Number: +46736797074; Email: sara.tehrani@regionstockholm.se

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

SCAPIS 2 General cohort

Description

Inclusion Criteria:

• Participated in the SCAPIS baseline (SCAPIS 1 study, 10 years ago)
• Cohort specific inclusion criteria apply, as stated in 'groups' section
• Has been invited to SCAPIS 2 core Singed informed consent to SCAPIS 2 core

Exclusion Criteria:

• Scarring, tattoos, or amputations that preclude device examination
• Cohort specific exclusion criteria apply, as stated in 'groups' section

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
O-CAD; O-CAD arm inclusion is based on burden of coronary atherosclerosis measure in computer tomography of coronary arteries (CCTA) as measured by coronary artery disease reporting and data system (CADRADS). If CAD-RADS is above or equal to 3, participant may be eligible for inclusion in O-CAD arm.
ANOCA; ANOCA arm inclusion is dictated by presence of cardiac angina as defined by the rose questionnaire and CAD-RADS <3. Exclusion criteria are similar as to those for stress-CMR.
Metabolic; Inclusion is dictated by prevalence of diabetes mellitus concomitantly present with metabolic syndrome with metabolic syndrome severity score higher than 4. Exclusion criteria are similar as to those for stress-CMR, alongside CAD RADS < 3 and no angina as defined by rose questionnaire.
Left ventricular diastolic dysfunction; Inclusion is dictated by diastolic dysfunction as defined by British Society of Echocardiography. Exclusion criteria are similar as to those for stress- CMR, alongside CAD RADS < 3 and no angina as defined by rose questionnaire.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between device-derived skin microcirculation variables and CCTA severity metrics including CAD-RADS (0-5) and plaque burden	Assess the correlation between skin microcirculation parameters measured by investigational devices (icluding PORH; 42°C local heat plateau; flow-motion endothelial-band power; iontophoresis acetylcholine response), coronary CT angiography (CCTA) severity metrics: CAD-RADS score, 0-5, zero is equivalent to no plaque and 5 indicates complete occlusionan (fully blocked) and Plaque burden indices (e.g., Segment Involvement Score [SIS]) The device-derived microcirculation parameters are: Baseline perfusion, Perfusion after provocation, Peak perfusion, Time to peak, Recovery time, Capillary recruitment and Oxygen saturation (StO₂) The goal is to determine if these microcirculation measurements reflect coronary disease severity.	Baseline
Discriminative performance of device-derived microcirculatory variables for significant coronary stenosis	Evaluate the ability of microcirculatory variables measured by investigational devices to discriminate between patients with and without significant coronary stenosis, defined as CAD-RADS ≥ 3 (≥50% luminal narrowing on coronary CT angiography).	Baseline
Proportion of ANOCA participants (CAD-RADS <3 with angina per Rose questionnaire) who meet CMD criteria on stress-cardiac MRI using perfusion assessment	Calculate the proportion of participants classified as ANOCA (defined as CAD-RADS < 3 and angina symptoms per Rose Angina Questionnaire) who fulfill criteria for coronary microvascular dysfunction (CMD) based on stress cardiac MRI perfusion assessment according to site-standard protocols	Baseline
Proportion of INOCA participants (CAD-RADS <3 with ishemia per Rose questionnaire) who meet CMD criteria on stress-cardiac MRI using perfusion assessment.	Calculate the proportion of participants classified as INOCA (CAD-RADS < 3 and objective ischemia evidence) who fulfill CMD criteria based on stress cardiac MRI perfusion assessment..	Baseline and at stress cardiac MRI- visit within 3 months
Proportion of ANOCA participants who have INOCA	Among participants identified with ANOCA (non-obstructive coronary artery disease on CT angiography), the proportion who demonstrate myocardial ischemia (INOCA) will be calculated. Ischemia will be assessed using cardiac MRI stress perfusion imaging, which is considered the gold standard for myocardial microcirculatory dysfunction	Baseline and at stress cardiac MRI- visit within 3 months
Assess whether peripheral microvascular function reflects myocardial perfusion abnormalities in CMD and mild CAD	This outcome examines whether skin microcirculation parameters measured by investigational devices correlate with quantitative/ semiquantitative myocardial perfusion metrics obtained from stress cardiac-MRI in participants with: Coronary Microvascular Dysfunction (CMD) Non-obstructive coronary disease (CAD-RADS <3)	Baseline and at stress cardiac MRI- visit within 3 months
Correlation between investigational device variables and presence of Coronary Microvascular Dysfunction (CMD).	Evaluate whether distinct cut-off values in device-derived microvascular parameters correlate with significant CMD. CMD will be defined by cardiac MRI stress perfusion imaging. The following variables will be assessed using investigational devices	Baseline and at stress cardiac MRI- visit within 3 months
Correlation of skin microcirculation variables with echocardiographic marker for diastolic function	Assess the general correlation between investigational device variables and E/é ratio (echocardiographic marker) to assess diastolic function. A high E/é ratio suggests elevated left atrial pressure and impaired relaxation (diastolic dysfunction). A low E/é ratio indicates normal filling pressures.	Baseline
Association of skin microcirculation variables with elevated echocardiographic marker for diastolic dysfunction.	Determine whether investigationnal device-derived variables correlate with E/é > 15, indicative of increased left ventricular filling pressures.	Baseline
Correlation of skin microcirculation variables with biomarker for cardiac stress	Assess general correlation between investigationnal device-derived variables and ProBNP as a biomarker of cardiac stress.	Baseline
Association of skin microcirculation variables with elevated biomarker for measuring cardiac stress	Assess general correlation between investigationnal device-derived variables s and ProBNP as a biomarker of cardiac stress.	Baseline
Identification of device variable thresholds predicting diastolic dysfunction/heart failure	Evaluate whether specific cut-off values of investigational device-derived microcirculation variables are associated with confirmed dysfunction/heart failure	Baseline and at stress cardiac MRI- visit within 3 months
Correlation of skin microcirculation variables with high levels of a biomarker for average blood glucose	Calculate the correlation between the respective variables of the investigational devices and the incidence of HbA1c being > 65 mmol/mol.	Baseline
Correlation of device-derived microcirculation variables with nephropathy	Calculate the correlation between the respective variables of the investigational devices and the incidence of nephropathy	Baseline
Correlation betweed device-derived microcirculatory variables with endothelial/glycocalyx/inflammation biomarkers	Correlation between microcirculatory variables from investigational devices and biomarker panels (thrombomodulin, circulating endothelial cells, VE-cadherin, syndecan-1, hyaluronan, hsCRP, IL-6, GlycA).	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of Myogenic Response with Cardiovascular Disease	Asses the association between myogenic response from device-derived variables and cardiovascular disease incidence; includes incidence of myogenic vs endothelial dysfunction.	Baseline
Association of Vascular Inflammation with Microcirculatory Variables	Correlation between systemic inflammation biomarkers (e.g., hsCRP, IL-6, GlycA) and device-derived microcirculatory measures; exploratory detection of early inflammatory alterations.	Baseline
Mechanisms of endothelial damage and Cardiovascular Disease devlopment	Analysis of biomarker panels (endothelial/glycocalyx damage: thrombomodulin, VE-cadherin, syndecan-1, hyaluronan) to identify progression patterns and explore the correlation with device-derived microcirculatory variables.	Baseline
Development of multi-modal Cardiovascular Disease risk score	Creation and validation of a composite risk score integrating microcirculatory variables derived from investigationa devices and biomarker data; evaluation of predictive performance for Cardiovascular Disease endpoints.	Baseline

Collaborators and Investigators

• Sponsor: HJN Sverige AB/Neko Health

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 29, 2026

Study Registration Dates

• First Submitted: January 13, 2026
• First Submitted That Met QC Criteria: January 13, 2026
• First Posted (Actual): January 22, 2026

Study Record Updates

• Last Update Posted (Actual): January 22, 2026
• Last Update Submitted That Met QC Criteria: January 13, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: microcirculation; non-invasive; cardiac magnetic resonance imaging; laser speckle contrast imaging; microvascular; spatial frequency domain imaging; laser doppler flowmetry
• Additional Relevant MeSH Terms: Cardiovascular Diseases
• Other Study ID Numbers: 2024-01937-01; CIV-23-12-045355 (Other Identifier: Swedish Medical Products Agency)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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