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Aging, genetics, inflammation among possible explanations for atherosclerosis in ancient cultures
A series of original investigations and review articles published by the Horus research team in Global Heart offer several hypotheses for the presence of atherosclerosis in mummies from five continents, including aging, genetics, inflammation, exposure to cooking fires and protein mutations.
In 2013, the Horus team reported the presence of atherosclerosis dating back as far as 4,000 years. The presence of atherosclerosis could not be explained by modern diets and lifestyles, which are often, and perhaps erroneously, assumed to be the exclusive causes of atherosclerosis in modern humans.
L. Samuel Wann
In an editorial, Gregory S. Thomas, MD, MPH, medical director of MemorialCare Heart and Vascular Institute at Long Beach Memorial, Long Beach, Calif., L. Samuel Wann, MD, MACC, FESC, cardiologist at Columbia-St. Mary’s Healthcare, Milwaukee, and Jagat Narula, MD, DM, PhD, FACC, associate dean for global affairs and professor of cardiology and radiology at Mount Sinai Hospital, wrote that investigators “have yet to find a culture that did not have preclinical atherosclerosis” and that a continued multidisciplinary evaluation of atherosclerosis is warranted. Wann and Narula are members of the Cardiology Today Editorial Board.
Correlation to age
In one investigation, Adel H. Allam, MD, professor of cardiology at Al-Azhar University, Cairo, Egypt, and colleagues performed whole-body CT scans on 76 Egyptian mummies dating from 3600 B.C. to 364 A.D. and 178 modern Egyptians to compare the presence and extent of vascular calcifications.
While vascular calcifications were more prevalent in the modern group than in the mummies (60.7% vs. 38.2%; P<.001), the calcifications strongly correlated to age in both groups. None of the mummies were estimated to be older than 60 years at death. When the researchers excluded modern Egyptians exceeding 60 years of age, they found that the prevalence and severity of atherosclerosis were comparable among the modern group and the mummies.
Other similarities between the groups were that the number of arterial beds with atherosclerosis correlated with age, and calcifications were seen in aortoiliac beds approximately a decade before they appeared in the coronary and carotid beds. This information about aortoiliac beds “could be used as an important screening tool for effective preventive [CV] strategies,” Allam and colleagues wrote.
An Egyptian mummy prepped to undergo scanning.
Source: L. Samuel Wann, MD
Genetic factors
At least one genetic predisposition to atherosclerosis was observed in a mummy, according to a review by Albert Zink, PhD, director of the Institute for Mummies and the Iceman at the European Academy of Bolzano/Bozen, Bolzano/Bozen, Italy, and colleagues.
Sequencing of the genome of Ötzi the Iceman, a mummy found in the Ötztal Alps in 1991 who lived around 3300 B.C., revealed “a strong genetic predisposition for increased risk for CHD,” Zink and colleagues wrote. This was consistent with CT scans that showed major calcification in the carotid arteries, distal aorta and right iliac artery.
The Iceman was homozygous for the GG allele of rs10757274, a known strong genetic predictor of MI, making him the first ancient human in which a genetic predisposition of CVD was detected, according to the researchers.
“Further studies are planned that will include a detailed [single nucleotide polymorphism] analysis of [CV] risk factors and possible identification of new or currently unrecognized genetic polymorphisms that are no longer present in modern-day patients,” they wrote. “Even though our human ancestors lived far different lives than we do, their environment and lifestyles were not protecting them against the development of atherosclerosis. What was similar between now and then is … our genome.”
Inflammation and other factors
Randall C. Thompson
Atherosclerosis was present in the mummified remains of people from five different cultures on five different continents, despite having very different diets and lifestyles from modern humans and each other, according to a review article by Randall C. Thompson, MD, of St. Luke’s Mid America Heart Institute, Kansas City., Mo., and colleagues.
One thing the cultures might have had in common, however, was high levels of inflammation. “Chronic inflammation from infections and parasites was likely common, and this inflammatory state might have contributed to atherogenesis,” Thompson and colleagues wrote.
“These ancient people were unaware of the germs lurking in the unhygienic environments in which they lived, animals and people living side by side, inadequate sewage, contaminated water,” Thomas, who was a co-author on the paper, said in a press release. “They did not know that the germs amongst which they lived caused infection after infection. In addition to frequent bacterial and viral infections, the ancients likely suffered from lifelong parasitic infestations. Modern medicine, knowledge and antibiotics had not yet arrived.”
Another possible cause of atherosclerosis in ancient people is “considerable exposure to smoke from cooking and heating fires,” Thompson and colleagues wrote. They noted that in some cultures, atherosclerosis was more prevalent in women than in men, and women spent more time than men around cooking fires. “This cooking fire smoke, like tobacco smoke, might be atherogenic.” Ötzi the Iceman also had blackened lungs suggesting smoke inhalation.
Given the possible importance of these nontraditional risk factors, “further study of genetic and environmental risk factors for atherosclerosis in ancient people may offer insights into this common modern disease,” they wrote.
A possible role for progerin
The finding of atherosclerosis in ancient humans has “stimulated interest in the underlying biological processes that might impart to humans an inherent predisposition to the development of atherosclerosis,” Michael I. Miyamoto, MD, FACC, of Mission Heritage Medical Group, St. Joseph Heritage Health, Mission Viejo, Calif., and colleagues wrote in a review.
Clues might be found in accelerated aging syndromes such as Hutchinson-Gilford progeria syndrome, which includes premature aging phenotypes such as dramatically premature accelerated atherosclerosis, they wrote.
The culprit in that syndrome is progerin, a mutant form of the nuclear structural protein lamin A. Smaller amounts of progerin are present in people without Hutchinson-Gilford progeria syndrome, which suggests that progerin may play a role in age-related vascular disease, and could be a factor as to why atherosclerosis was observed in ancient people without modern risk factors, they wrote.
“The development of atherosclerosis in humans is an inexorable process, perhaps in part related to progressive, age-related progerin and/or other abnormal lamin A expression and accumulation,” Miyamoto and colleagues wrote.
For more information:
Allam AH. Global Heart. 2014;9:197-202.
Miyamoto MI. Global Heart. 2014;9:211-218.
Thomas GS. Global Heart. 2014;9:185-186.
Thompson RC. Global Heart. 2014;9:187-196.
Zink A. Global Heart. 2014;9:203-209.
Disclosure: See the full studies for a list of the researchers’ relevant financial disclosures.