{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T10:20:49Z","timestamp":1779099649205,"version":"3.51.4"},"reference-count":40,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T00:00:00Z","timestamp":1778976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Healthcare"],"abstract":"<jats:p>Background and Aims: Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of mortality worldwide, with lipid abnormalities playing a central role in disease development. While the causal role of low-density lipoprotein cholesterol (LDL-C) in ASCVD is well-established, the long-term population impact of combined lipid profiles, particularly the HDL-C\/LDL-C ratio, remains less clearly quantified. This study aimed to estimate the lifetime burden of cardiovascular outcomes associated with different lipid risk profiles using a patient-level simulation framework. Methods: The authors analyzed projected lifetime ASCVD events across four HDL-C\/LDL-C risk strata, ranging from low (\u22650.45) to very high (&lt;0.25), using the National Health Model Database of Projected and Estimated Outcomes (NHM-DPEO)\u2014a digital twin of national healthcare systems built from multiple data sources, including national health and demographic statistics and estimates from the relevant literature. The framework is structured as a patient-level simulation model that projects individual health trajectories over a lifetime horizon. Model outputs were assessed for plausibility by comparison with published epidemiological estimates. Results: The NHM simulation revealed a strong, graded relationship between lipid profiles and cardiovascular survival. Life expectancy declined from 80.2 years in the lowest risk group (HDL-C\/LDL-C \u2265 0.45) to 63.0 years in the very-high-risk group (HDL-C\/LDL-C &lt; 0.25), a reduction of 17.2 years, with 13.7 fewer QALYs. Similarly, participants with LDL-C &gt; 5.0 mmol\/L had a life expectancy 13.4 years shorter than those with LDL-C &lt; 3.1 mmol\/L. The burden of ASCVD increased exponentially with worsening lipid ratios: MI events rose from 5000 to 73,090 per 100,000 births, with onset in the highest risk group occurring as early as age 20. Ischaemic heart disease followed a similar pattern, showing up to 92% of events attributable to elevated lipid risk. While ischaemic stroke risk displayed a more complex pattern due to earlier MI mortality in high-risk groups, overall cardiovascular mortality and lifetime event burden were dominated by LDL-driven disease. These findings demonstrate that sustained LDL-C reduction and balanced HDL-C\/LDL-C ratios confer substantial survival benefits across both sexes and all age groups. Conclusions: This study shows that lipid balance has a decisive influence on cardiovascular survival. Sustained LDL-C reduction and favourable HDL-C\/LDL-C ratios markedly extend life expectancy and delay the onset of MI and IHD. The magnitude of this survival benefit highlights the need for early and continuous lipid control as a cornerstone of ASCVD prevention. The NHM quantifies these lifetime effects, offering valuable insights for targeted strategies that improve both longevity and quality of life.<\/jats:p>","DOI":"10.3390\/healthcare14101371","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T08:56:27Z","timestamp":1779094587000},"page":"1371","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Complex Relationship Between HDL\/LDL Cholesterol, Stroke and Cardiovascular Disease"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6007-0842","authenticated-orcid":false,"given":"Mark","family":"Parker","sequence":"first","affiliation":[{"name":"ZEM Solutions, 11050 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanja","family":"Novakovi\u0107","sequence":"additional","affiliation":[{"name":"ZEM Solutions, 11050 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milica","family":"Krga Rastovi\u0107","sequence":"additional","affiliation":[{"name":"ZEM Solutions, 11050 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0399-8008","authenticated-orcid":false,"given":"Vanesa","family":"Benkovi\u0107","sequence":"additional","affiliation":[{"name":"School of Public Health, Faculty of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4080-7963","authenticated-orcid":false,"given":"I\u00f1aki","family":"Gutierrez-Ibarluzea","sequence":"additional","affiliation":[{"name":"OSTEBA\u2014Basque Office for Health Technology Assessment, Health Research and Innovation Directorate, Ministry for Health, Basque Government, 01010 Vitoria-Gasteiz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/s41569-021-00607-3","article-title":"Epidemiology of cardiovascular disease in Europe","volume":"19","author":"Townsend","year":"2022","journal-title":"Nat. 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