{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:01:57Z","timestamp":1790251317630,"version":"4.1.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004047","name":"Karolinska Institutet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p>The microvasculature forms the interface for nutrient exchange and signaling between the blood and tissues. Its dysfunction is increasingly recognized as a key mechanism underlying various cardiovascular diseases, including heart failure, ischemic heart disease, atherosclerosis, stroke and vascular dementia. Early detection of these subclinical processes using non-invasive assessments could facilitate timely interventions and provide mechanistic insights to prevent disease progression. SCAPIS 2 Spectrum is a prospective cross-sectional phenotyping sub study of the Swedish Cardiopulmonary Bioimage Study, recruiting up to 900 participants aged 58\u201375 years. The study is organized into four overlapping phenotype groups: (1) those with obstructive coronary artery disease, (2) angina with non-obstructive coronary arteries, (3) metabolic syndrome with type 2 diabetes, and (4) those with diastolic dysfunction, each compared with controls drawn from the same cohort. All participants undergo a comprehensive skin microvascular assessment at rest and following various local provocations and those without exclusion criteria or obstructive coronary artery disease will also undergo stress cardiovascular magnetic resonance imaging to assess myocardial perfusion. Descriptive statistics, association analysis, multivariable regression and exploratory modelling will be employed to investigate associations between device-derived parameters in skin microcirculation and myocardial perfusion. Circulating biomarkers will be incorporated as candidate features in exploratory analysis. Ethical approval has been obtained from the Swedish Ethical Review Authority and the Swedish Medical Products Agency (CIV-ID 23-12-045355). Study results will be disseminated through peer-reviewed publications, national and international conference presentations.<\/jats:p>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/clinicaltrials.gov\/study\/NCT07359768?term=scapis%202%20spectrum&amp;amp;viewType=Card&amp;amp;rank=1&amp;amp;tab=study<\/jats:ext-link>\n                      , ClinicalTrials.gov ID: NCT07359768.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcvm.2026.1899591","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T11:03:08Z","timestamp":1790247788000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["SCAPIS 2 spectrum: rationale, objectives and design of a microvascular dysfunction sub-study within the Swedish CArdioPulmonary bioImage study."],"prefix":"10.3389","volume":"13","author":[{"given":"Jacob","family":"Widaeus","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet","place":["Stockholm, Sweden"]},{"name":"Department of Medical Specialties, Danderyd Hospital","place":["Stockholm, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin Wel\u00e9n","family":"Schef","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet","place":["Stockholm, Sweden"]},{"name":"Department of Cardiology, Danderyd Hospital","place":["Stockholm, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Jernberg","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet","place":["Stockholm, Sweden"]},{"name":"Department of Cardiology, Danderyd Hospital","place":["Stockholm, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattias","family":"Wind\u00e5","sequence":"additional","affiliation":[{"name":"Neko Health AB","place":["Stockholm, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrik","family":"Salomonsson","sequence":"additional","affiliation":[{"name":"Neko Health AB","place":["Stockholm, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Johansson","sequence":"additional","affiliation":[{"name":"Neko Health AB","place":["Stockholm, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jannike","family":"Nickander","sequence":"additional","affiliation":[{"name":"Department of Clinical Physiology, Karolinska University Hospital","place":["Stockholm, Sweden"]},{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet","place":["Stockholm, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helge","family":"Brandberg","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet","place":["Stockholm, Sweden"]},{"name":"Department of Cardiology, Danderyd Hospital","place":["Stockholm, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Cronhjort","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet","place":["Stockholm, Sweden"]},{"name":"Department of Anaesthesia and Intensive Care, Danderyd Hospital","place":["Stockholm, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Tehrani","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet","place":["Stockholm, Sweden"]},{"name":"Department of Medical Specialties, Danderyd Hospital","place":["Stockholm, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1016\/j.amjmed.2022.04.006","article-title":"Microvascular dysfunction as a systemic disease: a review of the evidence","volume":"135","author":"Feuer","year":"2022","journal-title":"Am J Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"H1","DOI":"10.1152\/ajpheart.00581.2016","article-title":"Functional vascular contributions to cognitive impairment and dementia: mechanisms and consequences of cerebral autoregulatory dysfunction, endothelial impairment, and neurovascular uncoupling in aging","volume":"312","author":"Toth","year":"2017","journal-title":"American Journal of Physiology Heart and Circulatory Physiology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1007\/s00395-020-0798-y","article-title":"Microvascular and lymphatic dysfunction in HFpEF and its associated comorbidities","volume":"115","author":"Cuijpers","year":"2020","journal-title":"Basic Res Cardiol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"e010805","DOI":"10.1161\/CIRCHEARTFAILURE.123.010805","article-title":"Coronary microvascular dysfunction in patients with heart failure: characterization of patterns in HFrEF versus HFpEF","volume":"17","author":"Paolisso","year":"2024","journal-title":"Circulation Heart Failure"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1042\/CS20200279","article-title":"Microvascular disease in chronic kidney disease: the base of the iceberg in cardiovascular comorbidity","volume":"134","author":"Querfeld","year":"2020","journal-title":"Clinical Science (London, England: 1979)"},{"key":"B6","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1161\/01.HYP.34.4.655","article-title":"Rarefaction of skin capillaries in borderline essential hypertension suggests an early structural abnormality","volume":"34","author":"Antonios","year":"1999","journal-title":"Hypertension (Dallas, Tex: 1979)"},{"key":"B7","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1136\/heart.89.2.175","article-title":"Rarefaction of skin capillaries in normotensive offspring of individuals with essential hypertension","volume":"89","author":"Antonios","year":"2003","journal-title":"Heart (British Cardiac Society)"},{"key":"B8","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1093\/cvr\/cvaa085","article-title":"Endothelial function in cardiovascular medicine: a consensus paper of the European Society of Cardiology working groups on atherosclerosis and vascular biology, aorta and peripheral vascular diseases, coronary pathophysiology and microcirculation, and thrombosis","volume":"117","author":"Alexander","year":"2021","journal-title":"Cardiovasc Res"},{"key":"B9","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1111\/joim.12384","article-title":"The Swedish CArdioPulmonary BioImage study: objectives and design","volume":"278","author":"Bergstr\u00f6m","year":"2015","journal-title":"J Intern Med"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1016\/S0140-6736(07)61602-X","article-title":"The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies","volume":"370","author":"Von Elm","year":"2007","journal-title":"Lancet (London, England)"},{"key":"B11","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1161\/CIRCULATIONAHA.121.055340","article-title":"Prevalence of subclinical coronary artery atherosclerosis in the general population","volume":"144","author":"Bergstr\u00f6m","year":"2021","journal-title":"Circulation"},{"key":"B12","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1001\/archinte.1971.00310240115015","article-title":"Angina pectoris and the rose questionnaire","volume":"128","author":"Heyden","year":"1971","journal-title":"Arch Intern Med"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1450","DOI":"10.1136\/heartjnl-2023-322345","article-title":"Prevalence of angina pectoris and association with coronary atherosclerosis in a general population","volume":"109","author":"Wel\u00e9n Schef","year":"2023","journal-title":"Heart (British Cardiac Society)"},{"key":"B14","doi-asserted-by":"publisher","first-page":"S27","DOI":"10.2337\/dc25-S002","article-title":"Diagnosis and classification of diabetes: standards of care in diabetes-2025","volume":"48","author":"ElSayed","year":"2025","journal-title":"Diabetes Care"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1640","DOI":"10.1161\/CIRCULATIONAHA.109.192644","article-title":"Harmonizing the metabolic syndrome: a joint interim statement of the international diabetes federation task force on epidemiology and prevention; national heart, lung, and blood institute; American Heart Association; world heart federation; international atherosclerosis society; and international association for the study of obesity","volume":"120","author":"Alberti","year":"2009","journal-title":"Circulation"},{"key":"B16","doi-asserted-by":"publisher","first-page":"e0119582","DOI":"10.1371\/journal.pone.0119582","article-title":"Prevalence, pharmacological treatment, and control of cardiometabolic risk factors among older people in central Stockholm: a population-based study","volume":"10","author":"Wang","year":"2015","journal-title":"PLoS One"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1111\/j.1464-5491.2005.01648.x","article-title":"The gap between guidelines and reality: type 2 diabetes in a national diabetes register 1996\u20132003","volume":"22","author":"Eliasson","year":"2005","journal-title":"Diabetic Medicine: a Journal of the British Diabetic Association"},{"key":"B18","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s44156-024-00051-2","article-title":"The assessment of left ventricular diastolic function: guidance and recommendations from the British society of echocardiography","volume":"11","author":"Robinson","year":"2024","journal-title":"Echo Res Pract"},{"key":"B19","doi-asserted-by":"publisher","first-page":"e069937","DOI":"10.1136\/bmjopen-2022-069937","article-title":"Association between self-reported alcohol consumption and diastolic dysfunction: a cross-sectional study","volume":"13","author":"Daka","year":"2023","journal-title":"BMJ Open"},{"key":"B20","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/S0195-668X(02)00428-1","article-title":"Prevalence of left ventricular diastolic dysfunction in the community: results from a Doppler echocardiographic-based survey of a population sample","volume":"24","author":"Fischer","year":"2003","journal-title":"Eur Heart J"},{"key":"B21","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1093\/eurjhf\/hfs052","article-title":"Prevalence of preclinical and clinical heart failure in the elderly. A population-based study in central Italy","volume":"14","author":"Mureddu","year":"2012","journal-title":"Eur J Heart Fail"},{"key":"B22","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1097\/MCA.0000000000000055","article-title":"Impairment of systemic microvascular endothelial and smooth muscle function in individuals with early-onset coronary artery disease: studies with laser speckle contrast imaging","volume":"25","author":"Souza","year":"2014","journal-title":"Coron Artery Dis"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1727","DOI":"10.1016\/j.amjcard.2005.12.069","article-title":"Microvascular function, metabolic syndrome, and novel risk factor status in women with cardiac syndrome X","volume":"97","author":"Jadhav","year":"2006","journal-title":"Am J Cardiol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1161\/ATVBAHA.114.304591","article-title":"Metabolic syndrome individuals with and without type 2 diabetes mellitus present generalized vascular dysfunction: cross-sectional study","volume":"35","author":"Walther","year":"2015","journal-title":"Arterioscler, Thromb, Vasc Biol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1016\/j.ejheart.2007.06.003","article-title":"Differences in arterial compliance, microvascular function and venous capacitance between patients with heart failure and either preserved or reduced left ventricular systolic function","volume":"9","author":"Balmain","year":"2007","journal-title":"Eur J Heart Fail"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v042.i08","article-title":"Matchit: nonparametric preprocessing for parametric causal inference","volume":"42","author":"Ho","year":"2011","journal-title":"J Stat Softw"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.1109\/10.790500","article-title":"Wavelet analysis of oscillations in the peripheral blood circulation measured by laser Doppler technique","volume":"46","author":"Stefanovska","year":"1999","journal-title":"IEEE Transactions on Bio-Medical Engineering"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1117\/1.JBO.24.9.095002","article-title":"Validation of speed-resolved laser Doppler perfusion in a multimodal optical system using a blood-flow phantom","volume":"24","author":"Jonasson","year":"2019","journal-title":"J Biomed Opt"},{"key":"B29","doi-asserted-by":"publisher","first-page":"036007","DOI":"10.1117\/1.JBO.28.3.036007","article-title":"Speed-resolved perfusion imaging using multi-exposure laser speckle contrast imaging and machine learning","volume":"28","author":"Hultman","year":"2023","journal-title":"J Biomed Opt"},{"key":"B30","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.mvr.2003.12.003","article-title":"A protocol for iontophoresis of acetylcholine and sodium nitroprusside that minimises nonspecific vasodilatory effects","volume":"67","author":"Droog","year":"2004","journal-title":"Microvasc Res"},{"key":"B31","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1111\/j.1549-8719.2011.00129.x","article-title":"Non-invasive assessment of skin microvascular function in humans: an insight into methods","volume":"19","author":"Roustit","year":"2012","journal-title":"Microcirculation (New York, NY: 1994)"},{"key":"B32","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1111\/j.1549-8719.2010.00037.x","article-title":"Characterization of the non-invasive assessment of the cutaneous microcirculation by laser Doppler perfusion scanner","volume":"17","author":"Keymel","year":"2010","journal-title":"Microcirculation (New York, NY: 1994)"},{"key":"B33","doi-asserted-by":"publisher","first-page":"e34807","DOI":"10.1371\/journal.pone.0034807","article-title":"Diabetic neuropathy and axon reflex-mediated neurogenic vasodilatation in type 1 diabetes","volume":"7","author":"Nabavi Nouri","year":"2012","journal-title":"PLoS One"},{"key":"B34","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1002\/mus.21333","article-title":"C-fiber function assessed by the laser Doppler imager flare technique and acetylcholine iontophoresis","volume":"40","author":"Green","year":"2009","journal-title":"Muscle Nerve"},{"key":"B35","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1002\/(SICI)1097-0258(19980115)17:1<101::AID-SIM727>3.0.CO;2-E","article-title":"Sample size and optimal designs for reliability studies","volume":"17","author":"Walter","year":"1998","journal-title":"Stat Med"},{"key":"B36","doi-asserted-by":"publisher","first-page":"e61320","DOI":"10.1371\/journal.pone.0061320","article-title":"Reproducibility of non-invasive assessment of skin endothelial function using laser Doppler flowmetry and laser speckle contrast imaging","volume":"8","author":"Puissant","year":"2013","journal-title":"PLoS One"},{"key":"B37","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s12968-017-0355-5","article-title":"Myocardial perfusion cardiovascular magnetic resonance: optimized dual sequence and reconstruction for quantification","volume":"19","author":"Kellman","year":"2017","journal-title":"Journal of Cardiovascular Magnetic Resonance: Official journal of the Society for Cardiovascular Magnetic Resonance"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1768","DOI":"10.1002\/mrm.24389","article-title":"Gadgetron: an open source framework for medical image reconstruction","volume":"69","author":"Hansen","year":"2013","journal-title":"Magn Reson Med"},{"key":"B39","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1161\/01.RES.65.4.997","article-title":"Blood-tissue exchange via transport and transformation by capillary endothelial cells","volume":"65","author":"Bassingthwaighte","year":"1989","journal-title":"Circ Res"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1958","DOI":"10.1016\/j.jcmg.2018.12.022","article-title":"Automated pixel-wise quantitative myocardial perfusion mapping by CMR to detect obstructive coronary artery disease and coronary microvascular dysfunction: validation against invasive coronary physiology","volume":"12","author":"Kotecha","year":"2019","journal-title":"JACC: Cardiovascular Imaging"},{"key":"B41","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1016\/j.jcmg.2020.10.015","article-title":"High-resolution cardiac magnetic resonance imaging techniques for the identification of coronary microvascular dysfunction","volume":"14","author":"Rahman","year":"2021","journal-title":"JACC: Cardiovascular Imaging"},{"key":"B42","doi-asserted-by":"publisher","first-page":"10380","DOI":"10.1038\/s41598-020-67196-y","article-title":"Females have higher myocardial perfusion, blood volume and extracellular volume compared to males - an adenosine stress cardiovascular magnetic resonance study","volume":"10","author":"Nickander","year":"2020","journal-title":"Sci Rep"},{"key":"B43","doi-asserted-by":"publisher","first-page":"22094","DOI":"10.1038\/s41598-023-49223-w","article-title":"Reduced stress perfusion in myocardial infarction with nonobstructive coronary arteries","volume":"13","author":"Steffen Johansson","year":"2023","journal-title":"Sci Rep"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2026.1899591\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T11:03:09Z","timestamp":1790247789000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2026.1899591\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,24]]},"references-count":43,"alternative-id":["10.3389\/fcvm.2026.1899591"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2026.1899591","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,24]]},"article-number":"1899591"}}