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The inflammatory theory of atherosclerosis may explain the discrepancies between traditional risk factors and observed phenomena in current literature. Following the divergence from chimpanzees several millennia ago, loss of function mutations in immune regulatory genes and changes in gene expression have resulted in an overactive human immune system. The ubiquity of atherosclerosis in the modern era may reflect a selective pressure that enhanced the innate immune response at the cost of atherogenesis and other chronic disease states. Evidence provided from the fields of genetics, evolutionary biology, and paleoanthropology demonstrates a sort of circular dependency between inflammation, immune system functioning, and evolution at both a species and cellular level. More recently, the role of proinflammatory stimuli, somatic mutations, and the gene-environment effect appear to be underappreciated elements in the development and progression of atherosclerosis. Neurobiological stress, metabolic syndrome, and traditional cardiovascular risk factors may instead function as intermediary links between inflammation and atherosclerosis. Therefore, considering evolution as a mechanistic process and atherosclerosis as part of the inertia of evolution, greater insight into future preventative and therapeutic interventions for atherosclerosis can be gained by examining the past. <\/jats:p>","DOI":"10.1152\/ajpheart.00744.2023","type":"journal-article","created":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T15:20:51Z","timestamp":1706887251000},"page":"H821-H831","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Atherosclerosis as the Damocles\u2019 sword of human evolution: insights from nonhuman ape-like primates, ancient human remains, and isolated modern human populations"],"prefix":"10.1152","volume":"326","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4895-3954","authenticated-orcid":false,"given":"Annora Ai-Wei","family":"Kumar","sequence":"first","affiliation":[{"name":"Medical School, The University of Western Australia, Crawley, 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