Behaviorally modern humans evolved in Africa perhaps as early as 100 thousand years ago (kya) (1) and, by 50 kya, they began spreading throughout Eurasia and Australia. Since that evolutionary watershed, the human genome has changed little. For millions of years, human ancestors, like all other organisms, had responded to altered environmental circumstances solely through biological evolution (Table 16-1).However, during the past 50 millennia, humans have increasingly been able to adapt to new ambient circumstances through cultural innovation, in addition to the underlying (and slower) genetic change. Since agriculture and animal husbandry first appeared, perhaps 10,000 years ago, hemoglobinopathies and adult lactose tolerance are almost the only generally acknowledged genetic modifications. On the other hand, our lifestyle has changed radically: Nutrition, physical activity, reproductive experience, psychosocial relations, microbial interactions, and toxin/allergen exposure are all vastly different now from what they were for ancestral humans and prehumans during the period when our primary genetic makeup, including those factors relevant to endothelial health and disease, was selected.

The resulting discordance or mismatch between our genes and our modern lives is a likely contributor to many common chronic diseases and probably to various forms of endothelial dysfunction, so an appreciation of its potentially pertinent elements may further our understanding of pathophysiology. Also, awareness of the ancestral human lifestyle may suggest new avenues of prevention research applicable to the endothelium.

Reconstructing the biomedical circumstances of Stone Age humans is a fascinating, if sometimes frustrating endeavor. Several categories of data exist. Human skeletal remains are amenable to gross anatomical, microscopic, and biomechanical evaluation, as well as to radioisotopic analysis.