{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:29:24Z","timestamp":1791851364152,"version":"4.3.4"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"vor","delay-in-days":34,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["91718304"],"award-info":[{"award-number":["91718304"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cardiovasc Diabetol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Heart failure and peripheral artery disease (PAD) are the two most common cardiovascular diseases (CVD) in individuals with type 2 diabetes mellitus (T2DM). The T\n                      <jats:sub>50<\/jats:sub>\n                      calciprotein crystallization test measures the transformation of calciprotein particles type 1 (CPP1) into CPP2 in vitro and has been introduced as a low-cost biomarker for arterial calcification and CVD risk. We aimed to investigate the association between T\n                      <jats:sub>50<\/jats:sub>\n                      and (1) heart failure with preserved ejection fraction (HFpEF), (2) ankle-brachial index (ABI) as measure of PAD, (3) pulse wave velocity (PWV) as measure of central arterial stiffness and (4) arterial calcification in individuals with T2DM.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Cross-sectional data was used of 771 individuals with T2DM (64% men, 67 [63\u201371] years). T\n                      <jats:sub>50<\/jats:sub>\n                      was measured using nephelometry on non-fasting serum samples. Presence of HFpEF was assessed with echocardiography based on current guidelines. ABI was categorized as\u2009\u2264\u20090.9 (PAD), 0.9\u20131.4 (normal) and\u2009\u2265\u20091.4 (high). Central arterial stiffness was measured using carotid-femoral PWV. Lower-extremity and coronary calcification were measured using computed tomography and quantified using Agatston scores categorized into zero (reference category) and tertiles\u2009&gt;\u20090. Multivariable-adjusted Poisson, multinomial and linear regression analyses were used to study the associations with aforementioned surrogate CVD risk markers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Mean T\n                      <jats:sub>50<\/jats:sub>\n                      was 355\u2009\u00b1\u200955\u00a0min. HFpEF and PAD were present in 36.6% and 5.8% of the cohort, respectively. Mean cfPWV was 12.9\u2009\u00b1\u20092.5\u00a0m\/s. Median calcification scores in the coronary arteries and lower-extremities were 315 [40\u20131246] and 791 [64\u20133820] Agatston units, respectively. Every 60-min decrease in T\n                      <jats:sub>50<\/jats:sub>\n                      , indicating higher calcification risk, was associated with increased coronary arterial calcification (e.g. highest tertile OR\u2009=\u20091.63 [1.15\u20132.30],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.006), but not with lower-extremity arterial calcification (e.g. highest tertile OR\u2009=\u20091.28 [0.96\u20131.69],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.088). Moreover, T\n                      <jats:sub>50<\/jats:sub>\n                      \u2009\u2264\u2009330\u00a0min versus T\n                      <jats:sub>50<\/jats:sub>\n                      \u2009\u2265\u2009390\u00a0min was associated with PAD (OR\u2009=\u20093.04 [1.03\u20138.94],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.044). Finally, every 60-min decrease in T\n                      <jats:sub>50<\/jats:sub>\n                      was not associated with neither HFpEF (RR\u2009=\u20091.02 [0.90\u20131.17],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.736) nor cfPWV (\u03b2\u2009=\u2009\u2009\u2212\u20090.08 [\u2009\u2212\u20090.26\u20130.10],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.398).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Low T\n                      <jats:sub>50<\/jats:sub>\n                      was associated with increased risks of coronary arterial calcification and PAD (measured by ABI\u2009\u2264\u20090.9) in individuals with T2DM, but not with HFpEF, central arterial stiffness and lower-extremity arterial calcification. Further research is warranted to evaluate the additive value of T\n                      <jats:sub>50<\/jats:sub>\n                      in CVD risk stratification in clinical care.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12933-025-03016-9","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T08:16:49Z","timestamp":1765354609000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Calciprotein crystallization time (T50) and its association with surrogate cardiovascular disease risk markers in individuals with type 2 diabetes mellitus: the cross-sectional EARLY-HFpEF study"],"prefix":"10.1186","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4924-4458","authenticated-orcid":false,"given":"R.","family":"Meer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3656-7872","authenticated-orcid":false,"given":"A. 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The study was approved by the Medical Ethical Committee VUmc (METC VUmc, 2018.064\u2014EARLY-HFPEF).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Author AP is inventor of the T\n                      50\n                      test and both stock holder and president of Calciscon (Biel, Switzerland). All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"10"}}