Metapopulation dynamics of SARS-CoV-2 transmission in a small-scale Amazonian society.

The severity of infectious disease outbreaks is governed by patterns of human contact, which vary by geography, social organization, mobility, access to technology and healthcare, economic development, and culture. Whereas globalized societies and urban centers exhibit characteristics that can heighten vulnerability to pandemics, small-scale subsistence societies occupying remote, rural areas may be buffered. Accordingly, voluntary collective isolation has been proposed as one strategy to mitigate the impacts of COVID-19 and other pandemics on small-scale Indigenous populations with minimal access to healthcare infrastructure. To assess the vulnerability of such populations and the viability of interventions such as voluntary collective isolation, we simulate and analyze the dynamics of SARS-CoV-2 infection among Amazonian forager-horticulturalists in Bolivia using a stochastic network metapopulation model parameterized with high-resolution empirical data on population structure, mobility, and contact networks. Our model suggests that relative isolation offers little protection at the population level (expected approximately 80% cumulative incidence), and more remote communities are not conferred protection via greater distance from outside sources of infection, due to common features of small-scale societies that promote rapid disease transmission such as high rates of travel and dense social networks. Neighborhood density, central household location in villages, and household size greatly increase the individual risk of infection. Simulated interventions further demonstrate that without implausibly high levels of centralized control, collective isolation is unlikely to be effective, especially if it is difficult to restrict visitation between communities as well as travel to outside areas. Finally, comparison of model results to empirical COVID-19 outcomes measured via seroassay suggest that our theoretical model is successful at predicting outbreak severity at both the population and community levels. Taken together, these findings suggest that the social organization and relative isolation from urban centers of many rural Indigenous communities offer little protection from pandemics and that standard control measures, including vaccination, are required to counteract effects of tight-knit social structures characteristic of small-scale populations.

Applying an evolutionary mismatch framework to understand disease susceptibility.

Noncommunicable diseases (NCDs) are on the rise worldwide. Obesity, cardiovascular disease, and type 2 diabetes are among a long list of "lifestyle" diseases that were rare throughout human history but are now common. The evolutionary mismatch hypothesis posits that humans evolved in environments that radically differ from those we currently experience; consequently, traits that were once advantageous may now be "mismatched" and disease causing. At the genetic level, this hypothesis predicts that loci with a history of selection will exhibit "genotype by environment" (GxE) interactions, with different health effects in "ancestral" versus "modern" environments. To identify such loci, we advocate for combining genomic tools in partnership with subsistence-level groups experiencing rapid lifestyle change. In these populations, comparisons of individuals falling on opposite extremes of the "matched" to "mismatched" spectrum are uniquely possible. More broadly, the work we propose will inform our understanding of environmental and genetic risk factors for NCDs across diverse ancestries and cultures.

Prevalence of dementia and mild cognitive impairment in indigenous Bolivian forager-horticulturalists.

INTRODUCTION: We evaluated the prevalence of dementia and mild cognitive impairment (MCI) in indigenous Tsimane and Moseten, who lead a subsistence lifestyle. METHODS: Participants from population-based samples ≥ 60 years of age (n = 623) were assessed using adapted versions of the Modified Mini-Mental State Examination, informant interview, longitudinal cognitive testing and brain computed tomography (CT) scans. RESULTS: Tsimane exhibited five cases of dementia (among n = 435; crude prevalence = 1.2%, 95% confidence interval [CI]: 0.4, 2.7); Moseten exhibited one case (among n = 169; crude prevalence = 0.6%, 95% CI: 0.0, 3.2), all age ≥ 80 years. Age-standardized MCI prevalence was 7.7% (95% CI: 5.2, 10.3) in Tsimane and 9.8% (95% CI: 4.9, 14.6) in Moseten. Cognitive impairment was associated with visuospatial impairments, parkinsonian symptoms, and vascular calcification in the basal ganglia. DISCUSSION: The prevalence of dementia in this cohort is among the lowest in the world. Widespread intracranial medial arterial calcifications suggest a previously unrecognized, non-Alzheimer's disease (AD) dementia phenotype.

Mother's social status is associated with child health in a horticulturalist population.

High social status is often associated with greater mating opportunities and fertility for men, but do women also obtain fitness benefits of high status? Greater resource access and child survivorship may be principal pathways through which social status increases women's fitness. Here, we examine whether peer-rankings of women's social status (indicated by political influence, project leadership, and respect) positively covaries with child nutritional status and health in a community of Amazonian horticulturalists. We find that maternal political influence is associated with improved child health outcomes in models adjusting for maternal age, parental height and weight, level of schooling, household income, family size, and number of kin in the community. Children of politically influential women have higher weight-for-age (B = 0.33; 95% CI = 0.12-0.54), height-for-age (B = 0.32; 95% CI = 0.10-0.54), and weight-for-height (B = 0.24; 95% CI = 0.04-0.44), and they are less likely to be diagnosed with common illnesses (OR = 0.48; 95% CI = 0.31-0.76). These results are consistent with women leveraging their social status to enhance reproductive success through improvements in child health. We discuss these results in light of parental investment theory and the implications for the evolution of female social status in humans.

Preserving quantifiable ethnographic records of disappearing human lifeways.

The human evolutionary sciences place high value on quantitative data from traditional small-scale societies that are rapidly modernizing. These data often stem from the sustained ethnographic work of anthropologists who are today nearing the end of their careers. Yet many quantitative ethnographic data are preserved only in summary formats that do not reflect the rich and variable ethnographic reality often described in unpublished field notes, nor the deep knowledge of their collectors. In raw disaggregated formats, such data have tremendous scientific value when used in conjunction with modern statistical techniques and as part of comparative analyses. Through a personal example of longitudinal research with Batek hunter-gatherers that involved collaboration across generations of researchers, we argue that quantifiable ethnographic records, just like material artifacts, deserve high-priority preservation efforts. We discuss the benefits, challenges, and possible avenues forward for digitizing, preserving, and archiving ethnographic data before it is too late.

Does exposure to parasites modify relationships between diurnal cortisol and leukocytes among Honduran women?

BACKGROUND: Altered hypothalamic-pituitary-adrenal (HPA) function and related changes in circulating glucocorticoids have been implicated in the pathogenesis of numerous diseases that involve dysregulated immune function. Glucocorticoid hormones have both direct and indirect modulatory effects on both pro- and anti-inflammatory aspects of the immune system, including granulocytic and lymphocytic leukocyte subsets. However, past findings are complicated by inconsistencies across studies in how glucocorticoids and immune markers interact and relate to disease risk. Some incongruencies are likely due to an overreliance on single-unit (e.g., HPA or one immune marker) measures, and a failure to consider ecological exposures that may shape the base levels or correspondence between these systems. Here, we test single-unit and diurnal measures of HPA axis and immune system interactions in a less-industrial ecological setting with relatively high parasite loads. METHODS: In a sample of 114 Honduran women (mean age = 36 years), morning and evening blood samples were analyzed to quantify granulocytes, lymphocytes, and immunoglobulin-E (IgE). Saliva was collected over 2 days (8 samples per woman) to measure peak cortisol, cumulative cortisol, and slope of decline. These repeated measures of saliva and venous blood were used to investigate associations between single-point and diurnal salivary cortisol and leukocytes, under variable levels of past parasite exposure (proxied by IgE). RESULTS: Individuals with less of a decline in cortisol (i.e., "flatter" decline) show less of an increase in lymphocytes (2.27% increase in cells/µL/hr; 95% CI: 0.91-7.29; p = .01) across the day compared to those with steeper cortisol decline (7.5% increase in lymphocytes; 95% CI: 5.79-9.34; p < .001). IgE levels did not modify this association. Interestingly, IgE did moderate relationships between measures of cortisol and granulocytes: diurnal cortisol was positively associated with granulocytes, only in individuals with high previous exposure to parasites. There were no consistent relationships between single-unit measures of cortisol, lymphocytes or granulocytes, regardless of past parasite exposure. DISCUSSION: Results demonstrate that the relationship between HPA function and immune modulation cannot be fully understood without an understanding of local disease ecology. These results highlight the importance of research that seeks to identify etiologies of disease across environmental contexts.

Relationship of sanitation, water boiling, and mosquito nets to health biomarkers in a rural subsistence population.

OBJECTIVES: Throughout human evolutionary history, parasites and pathogens were a major cause of mortality-modern urban life with public health infrastructure has changed disease exposure. We examine associations between boiling water, using latrines, mosquito net usage, and biomarkers among the Tsimane, a nonindustrial subsistence population with little public health infrastructure. METHODS: We conducted cross sectional surveys on water, latrines, and bed nets among 507 heads of households (aged 18-92 years, median age 41 years). Regression models estimated associations between behaviors and health biomarkers (ie, white blood cell count [WBC], hemoglobin, eosinophil count, and erythrocyte sedimentation rate) adjusting for age, sex, body mass index, wealth, schooling, and distance to the nearby market town. RESULTS: Latrine use is associated with 6.5% lower WBC count (ß = -679.6, P = .031, SE = 314.1), 17.4% lower eosinophil counts (ß = -244.7, P = .023, SE = 107.2), and reduced odds of eosinophilia (adjusted OR = 0.40, P < .019, 95% CI = 0.18-0.86). Boiling water and mosquito net use are not significantly associated with any biomarkers measured. CONCLUSIONS: In a subsistence population currently undergoing epidemiological transition, we find that latrine use was associated with several objective measures of health. This suggests that relatively low cost and low maintenance public health interventions may wish to focus on latrine use, as there is unmet need and potential health benefits for those who use latrines. Additionally, while the cost is higher, public health organizations aimed at improving sanitation may be able to use minimally invasive field-collected biomarkers as a diagnostic to objectively test the efficacy of interventions with greater specificity than anthropometric measurements.

Old friends and friendly fire: Pregnancy, hookworm infection, and anemia among tropical horticulturalists.

OBJECTIVES: Despite public health concerns about hookworm infection in pregnancy, little is known about immune profiles associated with hookworm (Necator americanus and Ancylostoma duodenale) infection during pregnancy. Fetal tolerance requirements may constrain maternal immune response to hookworm, thereby increasing susceptibility to new infections or increasing hemoglobin loss. To explore this possibility, we study systemic immune response and hemoglobin levels in a natural fertility population with endemic helminthic infection. METHODS: We used Bayesian multilevel models to analyze mixed longitudinal data on hemoglobin, hookworm infection, reproductive state, eosinophils, and erythrocyte sedimentation rate (ESR) to examine the effects of pregnancy and hookworm infection on nonspecific inflammation, cellular parasite response, and hemoglobin among 612 Tsimane women aged 15-45 (1016 observations). RESULTS: Pregnancy is associated with lower eosinophil counts and lower eosinophil response to hookworm, particularly during the second and third trimesters. Both hookworm and pregnancy are associated with higher ESR, with evidence for an interaction between the two causing further increases in the first trimester. Pregnancy is moderately associated with higher odds of hookworm infection (OR: 1.23, 95% CI: 0.83 to 1.83). Pregnancy and hookworm both decrease hemoglobin and may interact to accentuate this effect in the first-trimester of pregnancy (Interaction: ß: -0.30 g/dL; CI: -0.870 to 0.24). CONCLUSIONS: Our findings are consistent with a possible trade-off between hookworm immunity and successful pregnancy, and with the suggestion that hookworm and pregnancy may have synergistic effects, particularly in the first trimester.

Hunter-gatherer residential mobility and the marginal value of rainforest patches.

The residential mobility patterns of modern hunter-gatherers broadly reflect local resource availability, but the proximate ecological and social forces that determine the timing of camp movements are poorly known. We tested the hypothesis that the timing of such moves maximizes foraging efficiency as hunter-gatherers move across the landscape. The marginal value theorem predicts when a group should depart a camp and its associated foraging area and move to another based on declining marginal return rates. This influential model has yet to be directly applied in a population of hunter-gatherers, primarily because the shape of gain curves (cumulative resource acquisition through time) and travel times between patches have been difficult to estimate in ethnographic settings. We tested the predictions of the marginal value theorem in the context of hunter-gatherer residential mobility using historical foraging data from nomadic, socially egalitarian Batek hunter-gatherers (n = 93 d across 11 residential camps) living in the tropical rainforests of Peninsular Malaysia. We characterized the gain functions for all resources acquired by the Batek at daily timescales and examined how patterns of individual foraging related to the emergent property of residential movements. Patterns of camp residence times conformed well with the predictions of the marginal value theorem, indicating that communal perceptions of resource depletion are closely linked to collective movement decisions. Despite (and perhaps because of) a protracted process of deliberation and argument about when to depart camps, Batek residential mobility seems to maximize group-level foraging efficiency.

Locomotor constraints favour the evolution of the human pygmy phenotype in tropical rainforests.

The convergent evolution of the human pygmy phenotype in tropical rainforests is widely assumed to reflect adaptation in response to the distinct ecological challenges of this habitat (e.g. high levels of heat and humidity, high pathogen load, low food availability, and dense forest structure), yet few precise adaptive benefits of this phenotype have been proposed. Here, we describe and test a biomechanical model of how the rainforest environment can alter gait kinematics such that short stature is advantageous in dense habitats. We hypothesized that environmental constraints on step length in rainforests alter walking mechanics such that taller individuals are expected to walk more slowly due to their inability to achieve preferred step lengths in the rainforest. We tested predictions from this model with experimental field data from two short-statured populations that regularly forage in the rainforest: the Batek of Peninsular Malaysia and the Tsimane of the Bolivian Amazon. In accordance with model expectations, we found stature-dependent constraints on step length in the rainforest and concomitant reductions in walking speed that are expected to compromise foraging efficiency. These results provide the first evidence that the human pygmy phenotype is beneficial in terms of locomotor performance and highlight the value of applying laboratory-derived biomechanical models to field settings for testing evolutionary hypotheses.

Tree climbing and human evolution.

Paleoanthropologists have long argued--often contentiously--about the climbing abilities of early hominins and whether a foot adapted to terrestrial bipedalism constrained regular access to trees. However, some modern humans climb tall trees routinely in pursuit of honey, fruit, and game, often without the aid of tools or support systems. Mortality and morbidity associated with facultative arboreality is expected to favor behaviors and anatomies that facilitate safe and efficient climbing. Here we show that Twa hunter-gatherers use extraordinary ankle dorsiflexion (>45°) during climbing, similar to the degree observed in wild chimpanzees. Although we did not detect a skeletal signature of dorsiflexion in museum specimens of climbing hunter-gatherers from the Ituri forest, we did find that climbing by the Twa is associated with longer fibers in the gastrocnemius muscle relative to those of neighboring, nonclimbing agriculturalists. This result suggests that a more excursive calf muscle facilitates climbing with a bipedally adapted ankle and foot by positioning the climber closer to the tree, and it might be among the mechanisms that allow hunter-gatherers to access the canopy safely. Given that we did not find a skeletal correlate for this observed behavior, our results imply that derived aspects of the hominin ankle associated with bipedalism remain compatible with vertical climbing and arboreal resource acquisition. Our findings challenge the persistent arboreal-terrestrial dichotomy that has informed behavioral reconstructions of fossil hominins and highlight the value of using modern humans as models for inferring the limits of hominin arboreality.

Could plant extracts have enabled hominins to acquire honey before the control of fire?

Honey is increasingly recognized as an important food item in human evolution, but it remains unclear whether extinct hominins could have overcome the formidable collective stinging defenses of honey bees during honey acquisition. The utility of smoke for this purpose is widely recognized, but little research has explored alternative methods of sting deterrence such as the use of plant secondary compounds. To consider whether hominins could have used plant extracts as a precursor or alternative to smoke, we review the ethnographic, ethnobotanical, and plant chemical ecology literature to examine how humans use plants in combination with, and independently of, smoke during honey collection. Plant secondary compounds are diverse in their physiological and behavioral effects on bees and differ fundamentally from those of smoke. Plants containing these chemicals are widespread and prove to be remarkably effective in facilitating honey collection by honey hunters and beekeepers worldwide. While smoke may be superior as a deterrent to bees, plant extracts represent a plausible precursor or alternative to the use of smoke during honey collection by hominins. Smoke is a sufficient but not necessary condition for acquiring honey in amounts exceeding those typically obtained by chimpanzees, suggesting that significant honey consumption could have predated the control of fire.

Lagged effects of early-season herbivores on valley oak fecundity.

The seasonal match between folivore and leaf phenology affects the annual success of arboreal folivore populations because many folivores exploit developing leaves, which are an ephemeral resource. One strategy for folivores to exploit early-season leaves is to anticipate their emergence. The consequence of this behavior for trees is that individuals that set leaves earlier may experience greater rates of folivore damage, with potential negative fitness consequences. To test this hypothesis, we surveyed the early-season phenology, insect folivore damage, and acorn crop of a population of valley oaks (Quercus lobata) over a 3-year period. We found that trees that set leaves earlier experienced greater rates of folivore damage than trees that set leaves later in the season. In addition, we observed a lagged effect of folivore damage on acorn production, whereby trees with greater leaf damage produced fewer acorns in the subsequent year. These results indicate potential negative fitness consequences of earlier leaf phenology. Our study suggests that folivore pressure may be one factor that affects the optimal timing of leaf set in oaks.

A natural history of human tree climbing.

Walking and running have dominated the literature on human locomotor evolution at the expense of other behaviors with positive and negative fitness consequences. For example, although modern hunter-gatherers frequently climb trees to obtain important food resources in the canopy, these behaviors are seldom considered within the existing framework of primate positional behavior. As a result, inferences about the arboreal performance capabilities of fossil hominins based on a resemblance to humans may be more complicated than previously assumed. Here we use ethnographic reports of human tree climbing to critically evaluate hypotheses about the performance capabilities of humans in trees compared with other primates. We do so by reviewing the ecological basis of tree climbing behavior among hunter-gatherers and the diversity of human climbing techniques and styles. Results suggest that the biological and adaptive significance of human climbing has been underestimated, and that some humans are surprisingly competent in trees, particularly during vertical climbing and activities in the central core of trees. We conclude that while hominins evolved enhanced terrestrial locomotor performance through time, such shifts may have imposed only minor costs on vertical climbing abilities. The diversity of the locomotor repertoire of modern humans must therefore be taken into account when making form-function inferences during the behavioral reconstruction of fossil hominins.

Poor Oral Health Is Associated With Inflammation, Aortic Valve Calcification, and Brain Volume Among Forager-Farmers.

Poor oral health is associated with cardiovascular disease and dementia. Potential pathways include sepsis from oral bacteria, systemic inflammation, and nutritional deficiencies. However, in post-industrialized populations, links between oral health and chronic disease may be confounded because the lower socioeconomic exposome (poor diet, pollution, and low physical activity) often entails insufficient dental care. We assessed tooth loss, caries, and damaged teeth, in relation to cardiovascular and brain aging among the Tsimane, a subsistence population living a relatively traditional forager-horticulturalist lifestyle with poor dental health, but minimal cardiovascular disease and dementia. Dental health was assessed by a physician in 739 participants aged 40-92 years with cardiac and brain health measured by chest computed tomography (CT; n = 728) and brain CT (n = 605). A subset of 356 individuals aged 60+ were also assessed for dementia and mild cognitive impairment (n = 33 impaired). Tooth loss was highly prevalent, with 2.2 teeth lost per decade and a 2-fold greater loss in women. The number of teeth with exposed pulp was associated with higher inflammation, as measured by cytokine levels and white blood cell counts, and lower body mass index. Coronary artery calcium and thoracic aortic calcium were not associated with tooth loss or damaged teeth. However, aortic valve calcification and brain tissue loss were higher in those who had more teeth with exposed pulp. Overall, these results suggest that dental health is associated with indicators of chronic diseases in the absence of typical confounds, even in a population with low cardiovascular and dementia risk factors.

Phenotypic plasticity of climbing-related traits in the ankle joint of great apes and rainforest hunter-gatherers.

The "negrito" and African "pygmy" phenotypes are predominately exhibited by hunter-gatherers living in rainforest habitats. Foraging within such habitats is associated with a unique set of locomotor behaviors, most notably habitual vertical climbing during the pursuit of honey, fruit, and game. When performed frequently, this behavior is expected to correlate with developmentally plastic skeletal morphologies that respond to mechanical loading. Using six measurements in the distal tibia and talus that discriminate nonhuman primates by vertical climbing frequency, we tested the prediction that intraspecific variation in this behavior is reflected in the morphology of the ankle joint of habitually climbing human populations. First, to explore the plasticity of climbing-linked morphologies, we made comparisons between chimpanzees, gorillas, and orangutans from wild and captive settings. The analysis revealed significant differences in two climbing-linked traits (anterior expansion of the articular surface of the distal tibia and increased degree of talar wedging), indicating that these traits are sensitive to climbing behavior. However, our analyses did not reveal any signatures of climbing behavior in the ankles of habitually climbing hunter-gatherers. These results suggest that the detection of fine-grained differences in human locomotor behaviors at the ankle joint, particularly those associated with arboreality, may be obscured by the functional demands of terrestrial bipedalism. Accordingly, it may be difficult to use population-level characteristics of ankle morphology to make inferences about the climbing behavior of hominins in the fossil record, even when facultative arborealism is associated with key fitness benefits.

Female cooperative labour networks in hunter-gatherers and horticulturalists.

Cooperation in food acquisition is a hallmark of the human species. Given that costs and benefits of cooperation vary among production regimes and work activities, the transition from hunting-and-gathering to agriculture is likely to have reshaped the structure of cooperative subsistence networks. Hunter-gatherers often forage in groups and are generally more interdependent and experience higher short-term food acquisition risk than horticulturalists, suggesting that cooperative labour should be more widespread and frequent for hunter-gatherers. Here we compare female cooperative labour networks of Batek hunter-gatherers of Peninsular Malaysia and Tsimane forager-horticulturalists of Bolivia. We find that Batek foraging results in high daily variation in labour partnerships, facilitating frequent cooperation in diffuse networks comprised of kin and non-kin. By contrast, Tsimane horticulture involves more restricted giving and receiving of labour, confined mostly to spouses and primary or distant kin. Tsimane women also interact with few individuals in the context of hunting/fishing activities and forage mainly with spouses and primary kin. These differences give rise to camp- or village-level networks that are more modular (have more substructure when partitioned) among Tsimane horticulturalists. Our findings suggest that subsistence activities shape the formation and extent of female social networks, particularly with respect to connections with other women and non-kin. We discuss the implications of restricted female labour networks in the context of gender relations, power dynamics and the adoption of farming in humans. This article is part of the theme issue 'Cooperation among women: evolutionary and cross-cultural perspectives'.

Repercussions of patrilocal residence on mothers' social support networks among Tsimane forager-farmers.

While it is commonly thought that patrilocality is associated with worse outcomes for women and their children due to lower social support, few studies have examined whether the structure of female social networks covaries with post-marital residence. Here, we analyse scan sample data collected among Tsimane forager-farmers. We compare the social groups and activity partners of 181 women residing in the same community as their parents, their husband's parents, both or neither. Relative to women living closer to their in-laws, women living closer to their parents are less likely to be alone or solely in the company of their nuclear family (odds ratio (OR): 0.6, 95% CI: 0.3-0.9), and more likely to be observed with others when engaging in food processing and manufacturing of market or household goods, but not other activities. Women are slightly more likely to receive childcare support from outside the nuclear family when they live closer to their parents (OR = 1.8, 95% CI 0.8-3.9). Their social group size and their children's probability of receiving allocare decrease significantly with distance from their parents, but not their in-laws. Our findings highlight the importance of women's proximity to kin, but also indicate that patrilocality per se is not costly to Tsimane women. This article is part of the theme issue 'Cooperation among women: evolutionary and cross-cultural perspectives'.

Evolutionary mismatch and the role of GxE interactions in human disease.

Globally, we are witnessing the rise of complex, non-communicable diseases (NCDs) related to changes in our daily environments. Obesity, asthma, cardiovascular disease, and type 2 diabetes are part of a long list of "lifestyle" diseases that were rare throughout human history but are now common. A key idea from anthropology and evolutionary biology-the evolutionary mismatch hypothesis-seeks to explain this phenomenon. It posits that humans evolved in environments that radically differ from the ones experienced by most people today, and thus traits that were advantageous in past environments may now be "mismatched" and disease-causing. This hypothesis is, at its core, a genetic one: it predicts that loci with a history of selection will exhibit "genotype by environment" (GxE) interactions and have differential health effects in ancestral versus modern environments. Here, we discuss how this concept could be leveraged to uncover the genetic architecture of NCDs in a principled way. Specifically, we advocate for partnering with small-scale, subsistence-level groups that are currently transitioning from environments that are arguably more "matched" with their recent evolutionary history to those that are more "mismatched". These populations provide diverse genetic backgrounds as well as the needed levels and types of environmental variation necessary for mapping GxE interactions in an explicit mismatch framework. Such work would make important contributions to our understanding of environmental and genetic risk factors for NCDs across diverse ancestries and sociocultural contexts.

Testosterone is positively associated with coronary artery calcium in a low cardiovascular disease risk population.

Background: In industrialized populations, low male testosterone is associated with higher rates of cardiovascular mortality. However, coronary risk factors like obesity impact both testosterone and cardiovascular outcomes. Here, we assess the role of endogenous testosterone on coronary artery calcium in an active subsistence population with relatively low testosterone levels, low cardiovascular risk and low coronary artery calcium scores. Methodology: In this cross-sectional community-based study, 719 Tsimane forager-horticulturalists in the Bolivian Amazon aged 40+ years underwent computed tomography (49.8% male, mean age 57.6 years). Results: Coronary artery calcium levels were low; 84.5% had no coronary artery calcium. Zero-inflated negative binomial models found testosterone was positively associated with coronary artery calcium for the full sample (Incidence Rate Ratio [IRR] = 1.477, 95% Confidence Interval [CI] 1.001-2.170, P = 0.031), and in a male-only subset (IRR = 1.532, 95% CI 0.993-2.360, P = 0.053). Testosterone was also positively associated with clinically relevant coronary atherosclerosis (calcium >100 Agatston units) in the full sample (Odds Ratio [OR] = 1.984, 95% CI 1.202-3.275, P = 0.007) and when limited to male-only sample (OR = 2.032, 95% CI 1.118-4.816, P = 0.024). Individuals with coronary artery calcium >100 had 20% higher levels of testosterone than those with calcium <100 (t = -3.201, P = 0.007). Conclusions and Implications: Among Tsimane, testosterone is positively associated with coronary artery calcium despite generally low normal testosterone levels, minimal atherosclerosis and rare cardiovascular disease (CVD) events. Associations between low testosterone and CVD events in industrialized populations are likely confounded by obesity and other lifestyle factors.