Elsevier

The Lancet

Volume 389, Issue 10080, 29 April–5 May 2017, Pages 1730-1739
The Lancet

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

https://doi.org/10.1016/S0140-6736(17)30752-3Get rights and content

Summary

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 Luke's Hospital of Kansas City; and Paleocardiology Foundation.

Introduction

Large-scale population studies have identified conventional coronary artery disease risk factors as important to the clinical manifestation of coronary artery disease events, and might explain more than 90% of the attributable risk of coronary artery disease.1 These data are supported by findings that nearly 50% of coronary artery disease risk can be reduced on adoption of a heart-healthy lifestyle, even in individuals with a higher genetic susceptibility to coronary artery disease.2 Additionally, multiple primary prevention studies have conclusively shown that the control of risk factors including cholesterol, smoking, hypertension, and diabetes lead to significant, consistent, and dose-related reduction in major adverse cardiac events.3, 4, 5, 6 Populations with a lower prevalence of risk factors such as those that preceded modern lifestyles in industrialised settings should naturally show less prevalence of coronary disease.

Previous research by the HORUS Study Team on atherosclerosis in a pre-modern era has focused on mummies, observing peripheral atherosclerosis to be common in multiple ancient populations.7, 8 Atherosclerosis was confirmed by demonstration of calcific deposits in arterial beds. High inflammatory exposure from infection and presumptive abundance of risk factors was hypothesised to play a part in the pathogenesis of coronary artery disease in these populations.9 Conversely, contemporary pre-industrial populations have shown either lower prevalence of peripheral atherosclerosis,10, 11 or coronary risk factors.12, 13 On the basis of carotid and femoral ultrasound studies (Heart Attack Prevention Programme for You, HAPPY), atherosclerosis in a physically active, strictly vegetarian, non-smoking, and regularly meditating suburban population in India was encountered a decade and a half later than the comparable population in Texas, USA.10, 11 Similarly, the Tsimane Health and Life History Project team (THLHP) has been working with the indigenous Tsimane of Bolivia, a population of 16 000 individuals that live a pre-industrial lifestyle of hunting, gathering, fishing, and farming along the Maniqui River, an Amazon River tributary. The indirect measures of vascular ageing indicate that the Tsimane have low rates of hypertension and arterial stiffness.12, 13 Although the Tsimane have a low prevalence of coronary risk factors, they are similar to ancestral subsistence populations in their high infectious burden associated with high levels of biomarkers of inflammation.

Research in context

Evidence before this study

We searched both PubMed and Google Scholar for articles with terms “coronary calcium” and “CAC” (coronary calcium scoring) published after 1990 with no language restrictions. We searched for all population-based studies of coronary artery disease using CAC to determine whether data have been published on prevalence and severity of disease in small-scale subsistence populations and to integrate all available data. We included studies that were either population-representative or of very large sample size with explicit sampling methodologies described.

Added value of this study

The findings of the present study show that, in comparison to existing evidence, Tsimane indigenous South Americans have the lowest prevalence of coronary atherosclerosis of any population yet studied. This was achieved despite a high infectious inflammatory burden.

Implications of all the available evidence

The available evidence suggests that a lifetime with very low LDL cholesterol, a subsistence diet of wild game, fish, and high-fibre carbohydrates that are very low in saturated fat, combined with physical activity throughout much of the day sets a new target in the prevention of coronary atherosclerosis. Although consuming a subsistence diet is generally not feasible in urban industrialised populations, adoption of certain aspects of subsistence lifestyles could benefit individuals in sedentary industrialised populations. Urbanisation and the elimination of a subsistence diet and lifestyle might represent a novel risk factor for coronary artery disease. The general lack of prediction of CAC by inflammatory biomarkers in this study suggests the potential of a threshold effect for either degree of coronary atherosclerosis or LDL cholesterol level required for inflammation to either cause or predict coronary artery disease. Alternatively, inflammation secondary to infection might not be causal.

To better understand the association between the pre-industrial lifestyle and low prevalence of coronary artery disease risk factors, the HORUS Study Team and THLHP joined to collaboratively examine the hypothesis that an active subsistence lifestyle, resembling an era before sedentary urbanisation and large-scale economic specialisation, would be associated with low levels of manifest coronary artery disease, despite high inflammation from parasites and pathogens. To do so, we used direct coronary artery visualisation by CT for quantification of extent, severity, and location of coronary artery calcium (CAC) in 705 Tsimane adults. CAC scoring is a safe, non-invasive test commonly done by CT that enables quantification of CAC extent, severity and location; CAC scoring can now be accomplished with minimal radiation burden.14 An array of population-based and observational cohort registries have proved the prognostic usefulness of CAC scores beyond traditional coronary artery disease risk factors and non-coronary measures of peripheral atherosclerosis.15

Section snippets

Study design and participants

The THLHP has been working with the Tsimane population since 2002, and in 2011, expanded its coverage to 85 Tsimane villages, sampling individuals aged 40 years or older in a cohort-based panel design. This cross-sectional sample includes all individuals who met the inclusion criteria of self-identifying as Tsimane and who were aged 40 years or older (see appendix for age estimation methods). The THLHP makes regularly scheduled visits to Tsimane villages every 18 months, during which clinical

Results

Between July 2, 2014, and Sept 10, 2015, 705 individuals were included in this study. Individuals older than 60 years who were not sampled had either recently migrated between communities after major flooding (n=49), did not wish to participate because they were hunting, working in their fields, or engaged in childcare (n=15), or refused to participate (n=2). Only one individual refused to participate because of poor health or inability to travel (recovering from a hernia surgery; figure 1). To

Discussion

In this population-based study of the indigenous Tsimane population of Bolivia, we observed a very low prevalence of coronary atherosclerosis, as measured by CAC scoring. The low prevalence of atherosclerosis extends to the older ages wherein up to 31 (65%) Tsimane octogenarians were free from atherosclerosis; only four (8%) of octogenarians showed moderately elevated CAC scores. This makes the Tsimane the population with the least reported coronary atherosclerosis. This contrasts starkly with

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