{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T08:28:34Z","timestamp":1781857714215,"version":"3.54.5"},"reference-count":124,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T00:00:00Z","timestamp":1716508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>The role of cholesterol, mainly low-density lipoproteins (LDL-C), as a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) is now established and accepted by the international scientific community. Based on this evidence, the European and American guidelines recommend early risk stratification and \u201crapid\u201d achievement of the suggested target according to the risk estimation to reduce the number of major cardiovascular events. Prolonged exposure over the years to high levels of LDL-C is one of the determining factors in the development and progression of atherosclerotic plaque, on which the action of conventional risk factors (cigarette smoking, excess weight, sedentary lifestyle, arterial hypertension, diabetes mellitus) as well as non-conventional risk factors (gut microbiota, hyperuricemia, inflammation), alone or in combination, favors the destabilization of the atherosclerotic lesion with rupture\/fissuration\/ulceration and consequent formation of intravascular thrombosis, which leads to the acute clinical manifestations of acute coronary syndromes. In the current clinical practice, there is a growing number of cases that, although extremely common, are emblematic of the concept of long-term exposure to the risk factor (LDL hypercholesterolemia), which, not adequately controlled and in combination with other risk factors, has favored the onset of major cardiovascular events. The triple concept of \u201cgo lower, start earlier and keep longer!\u201d should be applied in current clinical practice at any level of prevention. In the present manuscript, we will review the current evidence and documents supporting the causal role of LDL-C in determining ASCVD and whether it is time to remove it from any score.<\/jats:p>","DOI":"10.3390\/life14060679","type":"journal-article","created":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T11:17:52Z","timestamp":1716549472000},"page":"679","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Evolving Concepts of the SCORE System: Subtracting Cholesterol from Risk Estimation: A Way for a Healthy Longevity?"],"prefix":"10.3390","volume":"14","author":[{"given":"Francesco","family":"Natale","sequence":"first","affiliation":[{"name":"Vanvitelli Cardiology Unit, Monaldi Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Franzese","sequence":"additional","affiliation":[{"name":"Vanvitelli Cardiology Unit, Monaldi Hospital, 80131 Naples, Italy"},{"name":"Department of Translational Medical Sciences, Section of Cardiology, University of Campania Luigi Vanvitelli, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Marotta","sequence":"additional","affiliation":[{"name":"Vanvitelli Cardiology Unit, Monaldi Hospital, 80131 Naples, Italy"},{"name":"Department of Translational Medical Sciences, Section of Cardiology, University of Campania Luigi Vanvitelli, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noemi","family":"Mollo","sequence":"additional","affiliation":[{"name":"Vanvitelli Cardiology Unit, Monaldi Hospital, 80131 Naples, Italy"},{"name":"Department of Translational Medical Sciences, Section of Cardiology, University of Campania Luigi Vanvitelli, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achille","family":"Solimene","sequence":"additional","affiliation":[{"name":"Vanvitelli Cardiology Unit, Monaldi Hospital, 80131 Naples, Italy"},{"name":"Department of Translational Medical Sciences, Section of Cardiology, University of Campania Luigi Vanvitelli, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ettore","family":"Luisi","sequence":"additional","affiliation":[{"name":"Vanvitelli Cardiology Unit, Monaldi Hospital, 80131 Naples, Italy"},{"name":"Department of Translational Medical Sciences, Section of Cardiology, University of Campania Luigi Vanvitelli, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmine","family":"Gentile","sequence":"additional","affiliation":[{"name":"Vanvitelli Cardiology Unit, Monaldi Hospital, 80131 Naples, Italy"},{"name":"Department of Translational Medical Sciences, Section of Cardiology, University of Campania Luigi Vanvitelli, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco S.","family":"Loffredo","sequence":"additional","affiliation":[{"name":"Vanvitelli Cardiology Unit, Monaldi Hospital, 80131 Naples, Italy"},{"name":"Department of Translational Medical Sciences, Section of Cardiology, University of Campania Luigi Vanvitelli, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6260-4576","authenticated-orcid":false,"given":"Paolo","family":"Golino","sequence":"additional","affiliation":[{"name":"Vanvitelli Cardiology Unit, Monaldi Hospital, 80131 Naples, Italy"},{"name":"Department of Translational Medical Sciences, Section of Cardiology, University of Campania Luigi Vanvitelli, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3802-7052","authenticated-orcid":false,"given":"Giovanni","family":"Cimmino","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, Section of Cardiology, University of Campania Luigi Vanvitelli, 80131 Naples, Italy"},{"name":"Cardiology Unit, AOU Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1093\/eurheartj\/ehz962","article-title":"Low-density lipoproteins cause atherosclerotic cardiovascular disease: Pathophysiological, genetic, and therapeutic insights: A consensus statement from the European Atherosclerosis Society Consensus Panel","volume":"41","author":"Boren","year":"2020","journal-title":"Eur. 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