Adel H. Allam

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

BACKGROUND Atherosclerosis 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. METHODS We 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. FINDINGS Probable 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). INTERPRETATION Atherosclerosis 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. FUNDING National Endowment for the Humanities, Paleocardiology Foundation, The National Bank of Egypt, Siemens, and St Lukes Hospital Foundation of Kansas City.

Atherosclerosis in ancient Egyptian mummies: the Horus study.

OBJECTIVES The purpose of this study was to determine whether ancient Egyptians had atherosclerosis. BACKGROUND The worldwide burden of atherosclerotic disease continues to rise and parallels the spread of diet, lifestyles, and environmental risk factors associated with the developed world. It is tempting to conclude that atherosclerotic cardiovascular disease is exclusively a disease of modern society and did not affect our ancient ancestors. METHODS We performed whole body, multislice computed tomography scanning on 52 ancient Egyptian mummies from the Middle Kingdom to the Greco-Roman period to identify cardiovascular structures and arterial calcifications. We interpreted images by consensus reading of 7 imaging physicians, and collected demographic data from historical and museum records. We estimated age at the time of death from the computed tomography skeletal evaluation. RESULTS Forty-four of 52 mummies had identifiable cardiovascular (CV) structures, and 20 of these had either definite atherosclerosis (defined as calcification within the wall of an identifiable artery, n = 12) or probable atherosclerosis (defined as calcifications along the expected course of an artery, n = 8). Calcifications were found in the aorta as well as the coronary, carotid, iliac, femoral, and peripheral leg arteries. The 20 mummies with definite or probable atherosclerosis were older at time of death (mean age 45.1 ± 9.2 years) than the mummies with CV tissue but no atherosclerosis (mean age 34.5 ± 11.8 years, p < 0.002). Two mummies had evidence of severe arterial atherosclerosis with calcifications in virtually every arterial bed. Definite coronary atherosclerosis was present in 2 mummies, including a princess who lived between 1550 and 1580 BCE. This finding represents the earliest documentation of coronary atherosclerosis in a human. Definite or probable atherosclerosis was present in mummies who lived during virtually every era of ancient Egypt represented in this study, a time span of >2,000 years. CONCLUSIONS Atherosclerosis is commonplace in mummified ancient Egyptians.

Current worldwide nuclear cardiology practices and radiation exposure: results from the 65 country IAEA Nuclear Cardiology Protocols Cross-Sectional Study (INCAPS)

Aims To characterize patient radiation doses from nuclear myocardial perfusion imaging (MPI) and the use of radiation-optimizing ‘best practices’ worldwide, and to evaluate the relationship between laboratory use of best practices and patient radiation dose. Methods and results We conducted an observational cross-sectional study of protocols used for all 7911 MPI studies performed in 308 nuclear cardiology laboratories in 65 countries for a single week in March–April 2013. Eight ‘best practices’ relating to radiation exposure were identified a priori by an expert committee, and a radiation-related quality index (QI) devised indicating the number of best practices used by a laboratory. Patient radiation effective dose (ED) ranged between 0.8 and 35.6 mSv (median 10.0 mSv). Average laboratory ED ranged from 2.2 to 24.4 mSv (median 10.4 mSv); only 91 (30%) laboratories achieved the median ED ≤ 9 mSv recommended by guidelines. Laboratory QIs ranged from 2 to 8 (median 5). Both ED and QI differed significantly between laboratories, countries, and world regions. The lowest median ED (8.0 mSv), in Europe, coincided with high best-practice adherence (mean laboratory QI 6.2). The highest doses (median 12.1 mSv) and low QI (4.9) occurred in Latin America. In hierarchical regression modelling, patients undergoing MPI at laboratories following more ‘best practices’ had lower EDs. Conclusion Marked worldwide variation exists in radiation safety practices pertaining to MPI, with targeted EDs currently achieved in a minority of laboratories. The significant relationship between best-practice implementation and lower doses indicates numerous opportunities to reduce radiation exposure from MPI globally.

Computed tomographic assessment of atherosclerosis in ancient Egyptian mummies.

occurred within the first few weeks after spinal interbody fusion procedures assisted with BMP, have been clinically insignificant in some patients, but in others have resulted in serious complications (spacer subsidence, loss of correction, spacer dislodgement, and failure of spinal fusion). In the study by Tumialán et al, no end plate resorption was reported. In contrast, a study by Vaidya et al, using the same interbody spacer and even smaller doses of BMP, reported 100% incidence of end plate resorption, resulting in subsidence of disc space in 40.5% of cervical levels. Improved surgical technique was emphasized by Tumialán et al as a reason for lack of resorption in their study, avoiding cortical end plate violations and therefore preventing contact between BMP and cancellous vertebral body, which can lead to osteolysis. However, a study by Slosar et al confirmed end plate violation during lumbar interbody fusions (interbody spacers were placed slightly deep and angulated) assisted with an even higher dose of BMP; no resorption and no subsidence was reported. Besides dosing and containment of BMPs in spinal fusion procedures, there are other unidentified causes of important discrepancies in reported results, incidences of adverse effects, and clinical consequences. We agree with Cahill et al on the need for refined guidelines for BMP use and further study of the long-term risks and benefits of BMP.

Assessing the need for nuclear cardiology and other advanced cardiac imaging modalities in the developing world

BackgroundIn 2005, 80% of cardiovascular disease (CVD) deaths occurred in low- to middle-income countries (i.e., developing nations). Cardiovascular imaging, such as myocardial perfusion SPECT, is one method that may be applied to detect and foster improved detection of at-risk patients. This document will review the availability and utilization for nuclear cardiology procedures worldwide and propose strategies to devise regional centers of excellence to achieve quality imaging around the world.MethodsAs a means to establish the current state of nuclear cardiology, International Atomic Energy Agency member and non-member states were queried as to annual utilization of nuclear cardiology procedures. Other sources for imaging statistics included data from medical societies (American Society of Nuclear Cardiology, European Society of Cardiology, and the European Association of Nuclear Medicine) and nuclear cardiology working groups within several nations. Utilization was calculated by dividing annual procedural volume by 2007 population statistics (/100,000) and categorized as high (>1,000/100,000), moderate-high (250-999/100,000), moderate (100-249/100,000), low-moderate (50-99/100,000) and low (<50/100,000).ResultsHigh nuclear cardiology utilization was reported in the United States, Canada, and Israel. Most Western European countries, Australia, and Japan reported moderate-high utilization. With the exception of Argentina, Brazil, Colombia and Uruguay, South America had low usage. This was also noted across Eastern Europe, Russia, and Asia. Utilization patterns generally mirrored each country’s gross domestic product. However, nuclear cardiology utilization was higher for developing countries neighboring moderate-high “user” countries (e.g., Algeria and Egypt); perhaps the result of accessible high-quality training programs.ConclusionsWorldwide utilization patterns for nuclear cardiology vary substantially and may be influenced by physician access to training and education programs. Development of regional training centers of excellence can guide utilization of nuclear cardiology through the application of guideline- and appropriateness-driven testing, training, continuing education, and quality assurance programs aiding developing nations to confront the epidemics of CVD.

Coronary atherosclerosis in indigenous South American Tsimane: a cross-sectional cohort study

BACKGROUND Conventional coronary artery disease risk factors might potentially explain at least 90% of the attributable risk of coronary artery disease. To better understand the association between the pre-industrial lifestyle and low prevalence of coronary artery disease risk factors, we examined the Tsimane, a Bolivian population living a subsistence lifestyle of hunting, gathering, fishing, and farming with few cardiovascular risk factors, but high infectious inflammatory burden. METHODS We did a cross-sectional cohort study including all individuals who self-identified as Tsimane and who were aged 40 years or older. Coronary atherosclerosis was assessed by coronary artery calcium (CAC) scoring done with non-contrast CT in Tsimane adults. We assessed the difference between the Tsimane and 6814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). CAC scores higher than 100 were considered representative of significant atherosclerotic disease. Tsimane blood lipid and inflammatory biomarkers were obtained at the time of scanning, and in some patients, longitudinally. FINDINGS Between July 2, 2014, and Sept 10, 2015, 705 individuals, who had data available for analysis, were included in this study. 596 (85%) of 705 Tsimane had no CAC, 89 (13%) had CAC scores of 1-100, and 20 (3%) had CAC scores higher than 100. For individuals older than age 75 years, 31 (65%) Tsimane presented with a CAC score of 0, and only four (8%) had CAC scores of 100 or more, a five-fold lower prevalence than industrialised populations (p≤0·0001 for all age categories of MESA). Mean LDL and HDL cholesterol concentrations were 2·35 mmol/L (91 mg/dL) and 1·0 mmol/L (39·5 mg/dL), respectively; obesity, hypertension, high blood sugar, and regular cigarette smoking were rare. High-sensitivity C-reactive protein was elevated beyond the clinical cutoff of 3·0 mg/dL in 360 (51%) Tsimane participants. INTERPRETATION Despite a high infectious inflammatory burden, the Tsimane, a forager-horticulturalist population of the Bolivian Amazon with few coronary artery disease risk factors, have the lowest reported levels of coronary artery disease of any population recorded to date. These findings suggest that coronary atherosclerosis can be avoided in most people by achieving a lifetime with very low LDL, low blood pressure, low glucose, normal body-mass index, no smoking, and plenty of physical activity. The relative contributions of each are still to be determined. FUNDING National Institute on Aging, National Institutes of Health; St Lukes Hospital of Kansas City; and Paleocardiology Foundation.

The prevalence and predictive accuracy of quantitatively defined transient ischemic dilation of the left ventricle on otherwise normal SPECT myocardial perfusion imaging studies.

AimTID in the setting of otherwise normal MPI has been suggested as a marker of high risk CAD. In this study we estimate the variance of TID in a normal population and the statistical frequency of false positive TID. This will provide an indirect measurement of predictive accuracy (PA) in a mixed referral population.ObjectiveTo study the PA of TID in otherwise normal MPI.Methods688 consecutive patients were studied. We defined TID according to the standard method at 2 cut-off values; 1SD and 2SD, and also by a BSA normalized volume difference with gender-specific 2SD limits (NrVD).Results457 patients with otherwise normal MPI were analyzed. PA of TID at 1SD was 4% and 26% at 2SD. PA was slightly higher (42%) using the NrVD, however, still too low to be clinically useful as a high-risk marker. PA of TID in patients with perfusion abnormalities was 58% at 1SD, 80% at 2SD and slightly higher (93%) by NrVD.ConclusionsIn the setting of otherwise normal MPI, elevated TIDr has a low prevalence and poor predictive accuracy and should not be considered summarily as a marker of high risk CAD.

Gender Differences in Presentation, Management, and In-Hospital Outcomes for Patients with AMI in a Lower- Middle Income Country: Evidence from Egypt

Background Many studies in high-income countries have investigated gender differences in the care and outcomes of patients hospitalized with acute myocardial infarction (AMI). However, little evidence exists on gender differences among patients with AMI in lower-middle-income countries, where the proportion deaths stemming from cardiovascular disease is projected to increase dramatically. This study examines gender differences in patients in the lower-middle-income country of Egypt to determine if female patients with AMI have a different presentation, management, or outcome compared with men. Methods and Findings Using registry data collected over 18 months from 5 Egyptian hospitals, we considered 1204 patients (253 females, 951 males) with a confirmed diagnosis of AMI. We examined gender differences in initial presentation, clinical management, and in-hospital outcomes using t-tests and χ2 tests. Additionally, we explored gender differences in in-hospital death using multivariate logistic regression to adjust for age and other differences in initial presentation. We found that women were older than men, had higher BMI, and were more likely to have hypertension, diabetes mellitus, dyslipidemia, heart failure, and atrial fibrillation. Women were less likely to receive aspirin upon admission (p<0.01) or aspirin or statins at discharge (p = 0.001 and p<0.05, respectively), although the magnitude of these differences was small. While unadjusted in-hospital mortality was significantly higher for women (OR: 2.10; 95% CI: 1.54 to 2.87), this difference did not persist in the fully adjusted model (OR: 1.18; 95% CI: 0.55 to 2.55). Conclusions We found that female patients had a different profile than men at the time of presentation. Clinical management of men and women with AMI was similar, though there are small but significant differences in some areas. These gender differences did not translate into differences in in-hospital outcome, but highlight differences in quality of care and represent important opportunities for improvement.

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.