Michael I. Miyamoto

Atherosclerosis across 4000 years of human history: the Horus study of four ancient populations

BACKGROUNDnAtherosclerosis is thought to be a disease of modern human beings and related to contemporary lifestyles. However, its prevalence before the modern era is unknown. We aimed to evaluate preindustrial populations for atherosclerosis.nnnMETHODSnWe obtained whole body CT scans of 137 mummies from four different geographical regions or populations spanning more than 4000 years. Individuals from ancient Egypt, ancient Peru, the Ancestral Puebloans of southwest America, and the Unangan of the Aleutian Islands were imaged. Atherosclerosis was regarded as definite if a calcified plaque was seen in the wall of an artery and probable if calcifications were seen along the expected course of an artery.nnnFINDINGSnProbable or definite atherosclerosis was noted in 47 (34%) of 137 mummies and in all four geographical populations: 29 (38%) of 76 ancient Egyptians, 13 (25%) of 51 ancient Peruvians, two (40%) of five Ancestral Puebloans, and three (60%) of five Unangan hunter gatherers (p=NS). Atherosclerosis was present in the aorta in 28 (20%) mummies, iliac or femoral arteries in 25 (18%), popliteal or tibial arteries in 25 (18%), carotid arteries in 17 (12%), and coronary arteries in six (4%). Of the five vascular beds examined, atherosclerosis was present in one to two beds in 34 (25%) mummies, in three to four beds in 11 (8%), and in all five vascular beds in two (1%). Age at time of death was positively correlated with atherosclerosis (mean age at death was 43 [SD 10] years for mummies with atherosclerosis vs 32 [15] years for those without; p<0·0001) and with the number of arterial beds involved (mean age was 32 [SD 15] years for mummies with no atherosclerosis, 42 [10] years for those with atherosclerosis in one or two beds, and 44 [8] years for those with atherosclerosis in three to five beds; p<0·0001).nnnINTERPRETATIONnAtherosclerosis was common in four preindustrial populations including preagricultural hunter-gatherers. Although commonly assumed to be a modern disease, the presence of atherosclerosis in premodern human beings raises the possibility of a more basic predisposition to the disease.nnnFUNDINGnNational Endowment for the Humanities, Paleocardiology Foundation, The National Bank of Egypt, Siemens, and St Lukes Hospital Foundation of Kansas City.

Why Did Ancient People Have Atherosclerosis?: From Autopsies to Computed Tomography to Potential Causes

Computed tomographic findings of atherosclerosis in the ancient cultures of Egypt, Peru, the American Southwest and the Aleutian Islands challenge our understanding of the fundamental causes of atherosclerosis. Could these findings be true? Is so, what traditional risk factors might be present in these cultures that could explain this apparent paradox? The recent computed tomographic findings are consistent with multiple autopsy studies dating as far back as 1852 that demonstrate calcific atherosclerosis in ancient Egyptians and Peruvians. A nontraditional cause of atherosclerosis that could explain this burden of atherosclerosis is the microbial and parasitic inflammatory burden likely to be present in ancient cultures inherently lacking modern hygiene and antimicrobials. Patients with chronic systemic inflammatory diseases of today, including systemic lupus erythematosus, rheumatoid arthritis, and human immunodeficiency virus infection, experience premature atherosclerosis and coronary events. Might the chronic inflammatory load of ancient times secondary to infection have resulted in atherosclerosis? Smoke inhalation from the use of open fires for daily cooking and illumination represents another potential cause. Undiscovered risk factors could also have been present, potential causes that technologically cannot currently be measured in our serum or other tissue. A synthesis of these findings suggests that a gene-environmental interplay is causal for atherosclerosis. That is, humans have an inherent genetic susceptibility to atherosclerosis, whereas the speed and severity of its development are secondary to known and potentially unknown environmental factors.

Is atherosclerosis fundamental to human aging? Lessons from ancient mummies

Case reports from Johan Czermak, Marc Ruffer, and others a century or more ago demonstrated ancient Egyptians had atherosclerosis three millennia ago. The Horus study team extended their findings, demonstrating that atherosclerosis was prevalent among 76 ancient Egyptian mummies and among 61 mummies from each of the ancient cultures of Peru, the American Southwest, and the Aleutian Islands. These findings challenge the assumption that atherosclerosis is a modern disease caused by present day risk factors. An extensive autopsy of an ancient Egyptian teenage male weaver named Nakht found that he was infected with four parasites: Schistosoma haematobium, Taenia species, Trichinella spiralis, and Plasmodium falciparum. Modern day patients with chronic inflammatory disease such as rheumatoid arthritis, systemic lupus erythematosus, and human immunodeficiency virus experience premature atherosclerosis. Could the burden of chronic inflammatory disease have been a risk factor for atherosclerosis in these ancient cultures? The prevalence of atherosclerosis in four diverse ancient cultures is consistent with atherosclerosis being fundamental to aging. The impact of risk factors in modern times, and potentially in ancient times, suggests a strong gene-environmental interplay: human genes provide a vulnerability to atherosclerosis, the environment determines when and if atherosclerosis becomes manifest clinically.

Genomic correlates of atherosclerosis in ancient humans.

Paleogenetics offers a unique opportunity to study human evolution, population dynamics, and disease evolution in situ. Although histologic and computed x-ray tomographic investigations of ancient mummies have clearly shown that atherosclerosis has been present in humans for more than 5,000 years, limited data are available on the presence of genetic predisposition for cardiovascular disease in ancient human populations. In a previous whole-genome study of the Tyrolean Iceman, a 5,300-year-old glacier mummy from the Alps, an increased risk for coronary heart disease was detected. The Icemans genome revealed several single nucleotide polymorphisms that are linked with cardiovascular disease in genome-wide association studies. Future genetic studies of ancient humans from various geographic origins and time periods have the potential to provide more insights into the presence and possible changes of genetic risk factors in our ancestors. The study of ancient humans and a better understanding of the interaction between environmental and genetic influences on the development of heart diseases may lead to a more effective prevention and treatment of the most common cause of death in the modern world.

Atherosclerotic cardiovascular disease in Egyptian women: 1570 BCE–2011 CE

BACKGROUNDnAtherosclerotic cardiovascular disease is often thought of as a disease of modernity, a disease affecting primarily men and a disease primarily affecting members of affluent Western societies.nnnMETHODSnWe reviewed CT scans for evidence of vascular calcification as a manifestation of atherosclerosis in ancient Egyptian female mummies and compared the results to clinical features of contemporary Egyptian women, who are suffering from an epidemic of atherosclerotic cardiovascular disease.nnnRESULTSnThe common assumption that atherosclerosis is strictly a modern disease which spares women, mainly affecting men, is not true. We report the CT examination of an ancient Egyptian woman who lived more than 3000 years ago, finding calcified atherosclerotic plaque in her systemic arteries and other abnormalities probably due to prior myocardial infarction. We also confirmed recent reports of a virtual epidemic of atherosclerotic cardiovascular disease in contemporary Egyptian women.nnnCONCLUSIONSnAtherosclerosis, both ancient and contemporary, is common in women as well as in men, and is related to both a genetic predisposition and to environmental factors including diet, exercise, obesity and exposure to smoke and other toxins.

Atherosclerosis in Ancient Humans, Accelerated Aging Syndromes and Normal Aging: Is Lamin A Protein a Common Link?

Imaging studies of ancient human mummies have demonstrated the presence of vascular calcification that is consistent with the presence of atherosclerosis. These findings have stimulated interest in the underlying biological processes that might impart to humans an inherent predisposition to the development of atherosclerosis. Clues to these processes may possibly be found in accelerated aging syndromes, such as Hutchinson-Gilford progeria syndrome (HGPS), an ultra-rare disorder characterized by premature aging phenotypes, including very aggressive forms of atherosclerosis, occurring in childhood. The genetic defect in HGPS eventuates in the production of a mutant form of the nuclear structural protein lamin A, called progerin, which is thought to interfere with normal nuclear functioning. Progerin appears to be expressed in vascular cells, resulting in vessel wall cell loss and replacement by fibrous tissue, reducing vessel compliance and promoting calcification, leading to the vascular dysfunction and atherosclerosis seen in HGPS. Interestingly, vascular progerin is detectable in lower levels, in an age-related manner, in the general population, providing the basis for further study of the potential role of abnormal forms of lamin A in the atherosclerotic process of normal aging.

Computed tomographic evidence of atherosclerosis in the mummified remains of humans from around the world.

Although atherosclerosis is widely thought to be a disease of modernity, computed tomographic evidence of atherosclerosis has been found in the bodies of a large number of mummies. This article reviews the findings of atherosclerotic calcifications in the remains of ancient people-humans who lived across a very wide span of human history and over most of the inhabited globe. These people had a wide range of diets and lifestyles and traditional modern risk factors do not thoroughly explain the presence and easy detectability of this disease. Nontraditional risk factors such as the inhalation of cooking fire smoke and chronic infection or inflammation might have been important atherogenic factors in ancient times. Study of the genetic and environmental risk factors for atherosclerosis in ancient people may offer insights into this common modern disease.

Funerary Artifacts, Social Status, and Atherosclerosis in Ancient Peruvian Mummy Bundles☆

BACKGROUNDnEvidence of atherosclerotic plaques in ancient populations has led to the reconsideration of risk factors for heart disease and of the common belief that it is a disease of modern times.nnnMETHODSnFifty-one wrapped mummy bundles excavated from the sites of Huallamarca, Pedreros, and Rinconada La Molina from the Puruchuco Museum collection in Lima, Peru, were scanned using computed tomography to investigate the presence of atherosclerosis. Funerary artifacts contained within the undisturbed mummy bundles were analyzed as an attempt to infer the social status of the individuals to correlate social status with evidence of heart disease in this ancient Peruvian group. This work also provides an inventory of the museum mummy collection to guide and facilitate future research.nnnRESULTSnStatistical analysis concluded that there is little association between the types of grave goods contained within the bundles when the groups are pooled together. However, some patterns of artifact type, material, atherosclerosis, and sex emerge when the 3 excavation sites are analyzed separately.nnnCONCLUSIONSnFrom the current sample, it would seem that social class is difficult to discern, but those from Huallamarca have the most markers of elite status. We had hypothesized that higher-status individuals may have had lifestyles that would place them at a higher risk for atherogenesis. There seems to be some indication of this within the site of Huallamarca, but it is inconclusive in the other 2 archeological sites. It is possible that a larger sample size in the future could reveal more statistically significant results.

Atherosclerosis: a longue durée approach.

q This is an open access article under the CC BY-NCND license (http:// creativecommons.org/ licenses/by-nc-nd/3.0/). The authors report no relationships that could be construed as a conflict of interest. From the *Cardiovascular Physicians, Columbia St. Mary’s Healthcare, Milwaukee, WI, USA; ySaint Atherosclerosisq A Longue Durée Approach L. Samuel Wann*, Randall C. Thompsony, Adel H. Allamz, Caleb E. Finchx, Albert Zinkk, Bruno Frohlich{, Hillard Kaplan, Guido P. Lombardi**, M. Linda Sutherlandyy, James D. Sutherlandzz, Lucia Watsonxx, Samantha L. Coxkk,Michael I.Miyamoto{{, Alexandre F. R. Stewart, JagatNarula***, Gregory S.Thomasyyy,zzz

HOW BNP AND BODY WEIGHT CHANGES VARY IN HEART FAILURE WITH PRESERVED EJECTION FRACTION COMPARED TO REDUCED EJECTION FRACTION: SECONDARY RESULTS OF THE HABIT (HF ASSESSMENT WITH BNP IN THE HOME) TRIAL

In this subanalysis of the HF Assessment with Bnp In The Home (HABIT) trial, we examine the results of the home B-type natriuretic peptide (BNP) testing and weight monitoring in 160 patients with HFPEF and HFREF.nnThe study was a multi-center, single-arm double-blinded observational prospective