Conceived and designed the experiments: MDG HK CEF EC. Performed the experiments: DER. Analyzed the data: MDG SV JKK. Contributed reagents/materials/analysis tools: MDG JW CEF EC. Wrote the paper: MDG.
The authors have declared that no competing interests exist.
Arterial aging is well characterized in industrial populations, but scantly described in populations with little access to modern medicine. Here we characterize health and aging among the Tsimane, Amazonian forager-horticulturalists with short life expectancy, high infectious loads and inflammation, but low adiposity and robust physical fitness. Inflammation has been implicated in all stages of arterial aging, atherogenesis and hypertension, and so we test whether greater inflammation associates with atherosclerosis and CVD risk. In contrast, moderate to vigorous daily activity, minimal obesity, and low fat intake predict minimal CVD risk among older Tsimane.
Peripheral arterial disease (PAD), based on the Ankle-Brachial Index (ABI), and hypertension were measured in Tsimane adults, and compared with rates from industrialized populations. No cases of PAD were found among Tsimane and hypertension was comparatively low (prevalence: 3.5%, 40+; 23%, 70+). Markers of infection and inflammation were much higher among Tsimane than among U.S. adults, whereas HDL was substantially lower. Regression models examine associations of ABI and BP with biomarkers of energy balance and metabolism and of inflammation and infection. Among Tsimane, obesity, blood lipids, and disease history were not significantly associated with ABI. Unlike the Tsimane case, higher cholesterol, C-reactive protein, leukocytes, cigarette smoking and systolic pressure among North Americans are all significantly associated with lower ABI.
Inflammation may not always be a risk factor for arterial degeneration and CVD, but instead may be offset by other factors: healthy metabolism, active lifestyle, favorable body mass, lean diet, low blood lipids and cardiorespiratory health. Other possibilities, including genetic susceptibility and the role of helminth infections, are discussed. The absence of PAD and CVD among Tsimane parallels anecdotal reports from other small-scale subsistence populations and suggests that chronic vascular disease had little impact on adult mortality throughout most of human evolutionary history.
We report the first systematic study of peripheral arterial disease (PAD), hypertension and cardiovascular risk factors in a population with both high infectious and parasitic burden but low adiposity and robust physical fitness. The Tsimane are a population of 9,000 forager-horticulturalists in the Bolivian Amazon. Their recent life expectancy at birth of 43 years resembles much of Europe in the mid-nineteenth century, with half of documented deaths by infectious and parasitic disease
Prevalence of PAD and hypertension was measured in Tsimane adults and compared with representative samples from seven countries spanning the Americas, Asia, Africa and Europe. PAD was assessed with the Ankle-Brachial Pressure Index (ABI), a simple, non-invasive and recommended form of PAD diagnosis
Cardiovascular disease (CVD) and stroke account for the majority of adult deaths in the industrialized world, and are now major causes of morbidity and mortality in the developing world
Recent research considers chronic inflammation in the onset and progression of CVD. Many studies associate inflammatory markers and CVD morbidity and mortality after controlling for risk factors
Atherosclerosis and CVD are caused by a complex interaction of lifestyle factors (diet, energy balance, smoking, exercise) and inflammatory pathways. Elevated cholesterol and other risk factors predict less than half of heart attacks annually
Understanding the interaction of diet, energy balance, physical activity and inflammation is hampered by the populations studied: mainly well-fed in developed nations, or experimental animals fed
Though arterial aging in the form of elastin fragmentation and medial fibrosis may be an inevitable outcome of aging, the role of atherosclerosis in adult morbidity before the 20th century remains unclear. Studying arterial disease and CVD in indigenous populations is illuminating for three reasons. First, new light is shed on the roles and interactions of diet, exercise and inflammation on disease etiology. Second, subsistence populations with minimal medical access are characteristic of our evolutionary past, and may be informative about the role of vascular disease in the biology of aging during the long course of human evolution. Third, infectious disease is most prevalent in tropical regions of the developing world where the synergistic mix of risk factors and infectious causes are expected to bring a “gigantic epidemic of heart disease” in the coming decades
Existing research provides contradictory findings and lacks important information on relevant variables. Traditional populations often show negligible CVD prior to acculturation to western diets and sedentary lifestyles
PAD is absent (ABI<0.9) among all 258 Tsimane in our sample (see
The absence of PAD among Tsimane contrasts with patterns observed in national samples, especially South African blacks (
Data sources for ABI: urban China
Systolic BP was low among Tsimane young adults and climbed to moderately higher values among older adults (
Body size / lipids / lifestyle | Inflammation | Pressure | ||||||||||||
Age group | BMI | Trig | Chol | HDL | LDL | Cig. Pack Yrs | CRP | WBC | ESR | Hyper- tension (%) | ||||
≥30 | ≥200 | >240 | <40 | ≥160 | ≥25 | ≥3 | ≥10800 | >20 or 13 | (Stage I/II) | |||||
3.1 | 15.5 | 0.0 | 59.7 | 0.0 | 0.0 | 49.0 | 21.5 | 74.9 | 1.3 | 0.0 | ||||
(0.2) | (0.4) | (0.0) | (0.5) | (0.0) | (0.0) | (0.1) | (0.0) | (0.0) | (0.0) | (0.0) | ||||
8.3 | 12.0 | 0.0 | 68.1 | 0.0 | 0.0 | 45.1 | 15.0 | 87.6 | 3.7 | 1.9 | ||||
(0.3) | (0.3) | (0.0) | (0.5) | (0.0) | (0.0) | (0.1) | (0.0) | (0.0) | (0.0) | (0.0) | ||||
2.3 | 13.3 | 0.0 | 57.7 | 0.0 | 0.0 | 60.0 | 11.9 | 88.5 | 6.8 | 1.1 | ||||
(0.1) | (0.3) | (0.0) | (0.5) | (0.0) | (0.0) | (0.1) | (0.0) | (0.0) | (0.0) | (0.0) | ||||
1.9 | 3.8 | 0.0 | 68.2 | 0.0 | 0.0 | 53.8 | 11.5 | 92.0 | 15.7 | 7.8 | ||||
(0.1) | (0.2) | (0.0) | (0.5) | (0.0) | (0.0) | (0.1) | (0.0) | (0.0) | (0.1) | (0.0) | ||||
Age group | BMI | Trig | Chol | HDL | LDL | Cig. Pack Yrs | CRP Mean/ median | WBC | ESR | SBP | DBP | |||
23.9 | 137 | 144 | 37 | 80 | 0.4 | 9.9/2.7 | 8,968 | 30.1 | 111 | 68 | ||||
(0.2) | (8) | (3) | (1) | (2) | (0.1) | (2.0) | (177) | (1.4) | (1) | (1) | ||||
24.4 | 142 | 144 | 37 | 79 | 0.4 | 6.8/2.7 | 8,244 | 38.1 | 115 | 71 | ||||
(0.4) | (11) | (4) | (1) | (4) | (0.1) | (1.7) | (251) | (2.3) | (1) | (1) | ||||
23.2 | 116 | 136 | 37 | 76 | 0.7 | 7.2/4.0 | 8,218 | 38.6 | 118 | 70 | ||||
(0.3) | (15) | (4) | (1) | (3) | (0.2) | (1.5) | (241) | (2.7) | (2) | (1) | ||||
22.1 | 121 | 134 | 35 | 72 | 0.5 | 15.1/3.4 | 8,074 | 47.1 | 121 | 70 | ||||
(0.4) | (8) | (5) | (2) | (3) | (0.2) | (6.1) | (296) | (3.9) | (3) | (2) | ||||
N = | 477 | 203 | 203 | 172 | 170 | 463 | 205 | 480 | 436 | 472 |
Note: Triglycerides and LDL are based on non-fasting samples for Tsimane (a 6+ hours fasting sample was used for US). Units for variables are the following: triglycerides, cholesterol, HDL and LDL (mg/dL), BMI (kg/m2), cigarette pack years (# cigarette packs smoked per day, where 1 pack-year is equal to smoking 1 pack per day for 1 year), CRP (mg/L), WBC (cells/mm3), ESR (mm/hr), SBP and DBP (mm Hg). For ESR, 20 is cutoff for women and 13 for men. Hypertension prevalence refers to 140≤SBP<160 and/or 90≤DBP<100 (Stage I) and SBP≥160 and/or DBP≥100.
Blood indicators suggest high levels of inflammation and infection among Tsimane (
Mean levels of (A) C-reactive protein (CRP, mg/L), (B) white blood cell (WBC) count (cells/mm3), (C) body mass index (BMI,kg/m2), (D) total and HDL cholesterol (mg/dL). Total cholesterol correlates strongly with low-density lipoprotein (LDL) among both Tsimane (r = .82, p<.0001) and US (r = .91, p<.0001), and with triglycerides (Tsimane: r = .48, p<.0001; US: r = .43, p<.0001), and so are not illustrated here. See
Body size / lipids / lifestyle | Inflammation | Pressure | ||||||||
Age group | BMI | Trig | Chol | HDL | LDL | Cig. Pack Yrs | CRP | WBC≥ | Hyper- Tension (%) | |
≥30 | ≥200 | >240 | <40 | ≥160 | ≥25 | ≥3 | 10800 | (Stage I/II) | ||
33.9 | 17.8 | 19.1 | 21.4 | 15.2 | 16.3 | 36.3 | 5.7 | 12.7 | 3.0 | |
(1.3) | (1.6) | (1.1) | (1.0) | (1.6) | (1.1) | (1.2) | (0.5) | (1.0) | (0.5) | |
35.1 | 23.4 | 22.5 | 19.9 | 17.5 | 24.7 | 41.2 | 5.5 | 17.1 | 5.8 | |
(1.6) | (2.0) | (1.2) | (1.3) | (1.6) | (1.0) | (1.5) | (0.6) | (1.1) | (0.7) | |
38.2 | 26.3 | 22.7 | 19.5 | 16.8 | 32.0 | 45.6 | 4.7 | 23.6 | 11.7 | |
(1.0) | (1.7) | (1.0) | (1.0) | (1.4) | (1.1) | (1.5) | (0.6) | (1.2) | (1.0) | |
25.7 | 19.0 | 18.9 | 17.0 | 12.4 | 25.3 | 43.3 | 4.3 | 29.3 | 23.7 | |
(1.2) | (1.5) | (0.8) | (0.9) | (1.1) | (0.8) | (1.2) | (0.4) | (1.0) | (1.3) | |
Age group | BMI | Trig | Chol | HDL | LDL | Cig. Pack Yrs | CRP | WBC | SBP | DBP |
29 | 159 (7.1) | 208 | 52 | 125 | 9.6 | 4.1/2.0 | 7196 | 121 | 76 | |
(0.2) | (1.3) | (0.5) | (1.4) | (0.5) | (0.2) | (60.7) | (0.5) | (0.3) | ||
29 | 174 | 214 | 53 | 128 | 15.1 | 4.6/2.4 | 7082 | 127 | 76 | |
(0.2) | (8.3) | (1.2) | (0.5) | (1.6) | (0.6) | (0.2) | (76.9) | (0.6) | (0.4) | |
29 | 162 | 214 | 53 | 128 | 20.3 | 5.2/2.7 | 7032 | 135 | 72 | |
(0.1) | (3.5) | (1.1) | (0.5) | (1.7) | (0.8) | (0.2) | (64.3) | (0.6) | (0.4) | |
27 | 151 | 208 | 55 | 120 | 17.1 | 5.52.6 | 7227 | 144 | 65 | |
(0.1) | (2.4) | (0.9) | (0.5) | (1.1) | (0.6) | (0.2) | (57.1) | (0.8) | (0.5) | |
N = | 8761 | 3871 | 8564 | 8562 | 3818 | 8641 | 8620 | 8744 | 8619 |
Note: Triglycerides and LDL are based on 6+ hours fasting sample for US (a non-fasting sample was used for Tsimane). Units for variables are the following: triglycerides, cholesterol, HDL and LDL (mg/dL), BMI (kg/m2), cigarette pack years (# cigarette packs smoked per day, where 1 pack-year is equal to smoking 1 pack per day for 1 year), CRP (mg/L), WBC (cells/mm3), ESR (mm/hr), SBP and DBP (mm Hg). For ESR, 20 is cutoff for women and 13 for men. Hypertension prevalence refers to 140≤SBP<160 and/or 90≤DBP<100 (Stage I) and SBP≥160 and/or DBP≥100.
Tsimane clinical history is consistent with high cumulative exposure to acute infection. About 55% of those 40+ had at least one gastrointestinal illness in two prior medical exams and one third had respiratory illnesses. Two-thirds carried helminthic parasites. Infection and concomitant high inflammation are prevalent
Other CVD risk factors are low: mean±SD total cholesterol, 138±29 mg/dL and LDL, 75±22 mg/dL. However, high density lipoprotein (HDL) and triglycerides are exceptions: HDL is low at 37±9 mg/dL and trigylcerides moderately high at 130±73 mg/dL. Over half of Tsimane adults show unfavorable HDL levels by American Heart Association standards (<40 for men, <45 for women). Whereas no Tsimane show high risk levels of total cholesterol and LDL, 20% of U.S. adults have elevated levels of each blood lipid, even though many Americans use lipid-lowering medications. The prevalence of high triglycerides for most age groups in the U.S. is double that of the Tsimane. There is little indication of age increases in these measures among Tsimane. Values are similar across ages after 40 and do not show increased CVD risk at older ages in any parameter (
Obesity is 8–10 times more common in the US than among Tsimane (
The main CVD risk factors greater among Tsimane than U.S. adults are markers of infection. Low HDL prevalence is also common, being about 3-fold greater among Tsimane, although the clinical significance of low HDL in energy-limited populations has not been established. Inflammatory markers (CRP, ESR, and WBC counts) were significantly higher among Tsimane (
The links between CVD risk factors and ABI, SBP and DBP were examined in multiple regressions controlling for age, age2 and gender in both Tsimane and U.S. populations to explore whether risk factors show similar associations in both populations.
Regression results indicate that Tsimane men have higher ABI than women (
Tsimane | United States | ||||||||
Variables | beta | std err | N | beta | std err | N | |||
Sex (ref = female) | 0.009 | 0.145 | 258 | 0.003 | 0.095 | 7571 | |||
Age | 0.004 | 0.001 | |||||||
Age2 | <.001 | 0.000 | |||||||
Total cholesterol (mg/dL) | <0.001 | 0.000 | 0.17 | 127 | 0.000 | 0.098 | 7219 | ||
Triglycerides (mg/dL) | <0.001 | 0.000 | 0.171 | 127 | <0.001 |
0.000 | 0.087 | 3343 | |
estimated LDL (mg/dL) | 0.001 | 0.000 | 0.135 | 110 | <0.001 |
0.000 | 0.083 | 3209 | |
HDL (mg/dL) | −0.001 | 0.001 | 0.126 | 110 | 0.000 | 0.097 | 7218 | ||
Body Mass Index (kg/m2) | −0.001 | 0.001 | 0.141 | 255 | <0.001 |
0.000 | 0.093 | 7467 | |
CRP (mg/L) | −0.004 | 0.004 | 0.165 | 129 | −0.001 | 0.003 | 0.105 | 7261 | |
WBC count (#/mm3) | 0.000 | 0.000 | 0.163 | 232 | <0.001 | 0.000 | 0.107 | 7353 | |
ESR (mm/hr) | 0.003 | 0.173 | 234 | ||||||
Cigarette pack-years | <.001 | 0.002 | 0.145 | 257 | 0.000 | 0.120 | 7163 | ||
Systolic BP (mmHg) | 0.000 | 0.154 | 258 | 0.000 | 0.125 | 7360 | |||
Diastolic BP (mmHg) | 0.000 | 0.175 | 258 | <0.001 |
0.000 | 0.097 | 7360 |
p<.1.
p<.05.
p<.01.
p<.001.
TSIMANE | ABI (n = 126), R2 = 0.178 | SBP (n = 260), R2 = 0.176 | DBP (n = 260), R2 = 0.084 | |||
Variable | Beta | s.e. | beta | s.e. | beta | s.e. |
Intercept | 0.825 |
0.162 | 69.703 |
6.864 | 43.965 |
5.213 |
Male (reference = female) | 0.014 | 1.475 | 0.692 | 1.121 | ||
Age | 0.005 | 0.052 | 0.039 | |||
Age2 | <.001 | – | – | – | – | |
BMI | <−.001 | 0.002 | 0.236 | 0.179 | ||
CRP (mg/L) | −0.000 | 0.000 | 0.040 | 0.030 | ||
Total cholesterol | <.001 | <.001 | 0.035 | 0.025 | 0.026 | 0.019 |
Cigarette Pack-Years | 0.003 | 0.010 | −1.023 | 0.638 | −0.555 | 0.484 |
UNITED STATES | ABI (n = 6746), R2 = 0.130 | SBP (n = 7476), R2 = 0.214 | DBP (n = 7476), R2 = 0.132 | |||
Variable | Beta | s.e. | beta | s.e. | beta | s.e. |
Intercept | 0.039 | 5.773 | 3.951 | |||
Male (reference = female) | 0.004 | 1.088 | 0.651 | 0.371 | ||
Age | 0.001 | 0.199 | 0.143 | |||
Age2 | 0.000 | 0.002 | 0.002 | 0.001 | ||
BMI | 0.000 | 0.000 | 0.048 | 0.030 | ||
CRP (mg/L) | 0.000 | 0.018 | 0.032 | −0.022 | 0.026 | |
Total cholesterol | 0.000 | 0.007 | 0.005 | |||
Cigarette Pack-Years | 0.000 | 0.012 | 0.007 |
p<.1.
p<.05.
p<.01.
p<.001.
Aside from sex, the strongest predictor of both SBP and DBP among Tsimane is BMI (standardized estimate = 0.178, 0.170, respectively). The magnitude of the effect, however, is not very large: an increase in BMI by 5 kg/m2 increases SBP by 4 mm and DBP by 3 mm (
Systolic BP | Diastolic BP | ||||||
N | beta | std err | beta | std err | |||
Male (reference = female) | 1262 | 1.910 | 0.131 | 1.430 | 0.048 | ||
Age | 0.034 | 0.025 | |||||
Sex |
0.047 | −0.024 | 0.035 | ||||
Male (reference = female) | 13399 | 0.964 | 0.294 | 0.811 | 0.015 | ||
Age | 0.018 | −0.016 | 0.012 | ||||
Sex |
0.022 | 0.015 | 0.017 | ||||
Total cholesterol (mg/dL) | 383 | 0.019 | 0.135 | 0.015 | 0.048 | ||
Triglycerides (mg/dL) | 383 | 0.008 | 0.135 | 0.006 | 0.038 | ||
estimated LDL (mg/dL) | 331 | 0.041 | 0.029 | 0.114 | 0.023 | 0.033 | |
HDL (mg/dL) | 331 | −0.026 | 0.071 | 0.108 | 0.064 | 0.056 | 0.026 |
Body Mass Index (BMI kg/m2) | 1257 | 0.116 | 0.144 | 0.086 | 0.076 | ||
CRP (mg/L) | 386 | −0.005 | 0.028 | 0.126 | −0.136 | 0.222 | 0.027 |
WBC count (#/mm3) | 1000 | 0.000 | 0.000 | 0.114 | 0.000 | 0.036 | |
ESR (mm/hr) | 1005 | 0.018 | 0.123 | 0.013 | 0.05 | ||
Mean Cigarette Pack-Years | 788 | 0.361 | 0.099 | 0.264 | 0.041 | ||
Total cholesterol (mg/dL) | 12641 | 0.005 | 0.27 | 0.004 | 0.034 | ||
Triglycerides (mg/dL) | 5758 | 0.003 | 0.002 | 0.259 | 0.002 | 0.023 | |
estimated LDL (mg/dL) | 5566 | 0.007 | 0.263 | 0.006 | 0.034 | ||
HDL (mg/dL) | 12640 | −0.012 | 0.014 | 0.267 | −0.012 | 0.012 | 0.016 |
Body Mass Index (BMI kg/m2) | 13035 | 0.034 | 0.284 | 0.022 | 0.031 | ||
CRP (mg/dL) | 12705 | 0.022 | 0.263 | 0.006 | 0.016 | 0.015 | |
WBC count (#/mm3) | 12844 | 0.000 | 0.268 | 0.000 | 0.019 | ||
Mean Cigarette Pack Yrs | 12430 | 0.011 | 0.270 | 0.006 | 0.017 |
p<.1.
p<.05.
p<.01.
p<.001.
Contrary to expectations, higher WBC and ESR associate with
Despite their high levels of inflammation, we find no evidence of advanced atherosclerosis among Tsimane adults. This is consistent with subjective clinical evaluation of arterial hardening: only 3 out of 570 individuals aged 40+ showed signs of augmented tension in the radial and humeral arteries. The presence of mild hypertension in older adults is, however, consistent with some age-related arterial stiffening. Tsimane show several clinical indicators for CVD: high blood CRP, low HDL and moderately elevated triglycerides, which are established risk factors in well-nourished populations. Tsimane diet includes salt in acculturated villages, and Tsimane consume moderate amounts of alcohol in the form of fermented manioc and maize. Nevertheless, we found little evidence for the most common risk conditions of atherosclerosis and CVD: no PAD and little hypertension. These results are consistent with reports of low CVD among traditional foraging and small-scale farming populations
Though body mass, total cholesterol, and triglycerides predict higher blood pressure among Tsimane, the magnitude of these separate effects is small, and combined do not put Tsimane at high risk. Cholesterol and triglyceride elevations of 30 mg/dL coupled with 15 kg weight gain and 20% body fat percentage increase together add <6 mm SBP and 5 mm DBP.
We propose several possible hypotheses to explain the low atherosclerosis and CVD prevalence among Tsimane, and other traditional foraging and horticultural populations living under similar conditions. The combination of low LDL and high physical exertion is a common feature in many of these populations. The Tsimane diet contains wild game and fish, is low in saturated fat, and high in potassium (K). Plantains provide ∼1,500 mg K/day. Low BMI and LDL, and sparse tobacco consumption may be protective factors trumping the risk factors of atherosclerosis and CVD. Oxidized LDL is implicated in inflammatory cascades leading to endothelial dysfunction, plaque maturation and rupture; therefore some argue that atherosclerosis and CVD are avoidable when LDL is maintained <70 mg/dL
The physically demanding Tsimane lifestyle may be central for maintaining healthy metabolism and favorable body mass, blood lipids and cardiorespiratory health. Subsistence hunting, fishing and slash and burn farming require extensive daily physical activity, consistent with high VO2max values found using a variation of the Harvard Step Test on a subsample. Using equations of total energy expenditure with body weights and physical activity levels (PALs) for Tsimane and relatively sedentary U.S. adults
These results are consistent with evidence for the cardioprotective value of exercise. Exercise reduces oxidative load in muscle, levels of inflammatory cytokines, SBP, macrophage-rich fat and improves insulin sensitivity
Several alternative explanations may also be responsible for the low CVD risk profile of Tsimane, and merit future investigation. Tsimane and other Amerindians should be comprehensively investigated for distinct inflammation profiles due to genetic variability in loci affecting expression of CRP
One preliminary attempt to assess the implications of genetic differences between Tsimane and other populations is to consider atherosclerosis and CVD risk among Amerindians in the U.S. A study among 13 North Amerindian groups revealed a low rate of PAD (5.3%) among adults aged 45–74, little difference in PAD prevalence among the groups, and significant predictive effects of LDL, BMI, cigarette pack-years and fibrinogen
Another unexplored potential explanation highlights the hypothesized cardioprotective effects of chronic helminthic infection. Polarized Th-2 immune activation associated with helminthic infection modifies cytokine profiles, whereby anti-inflammatory IL-4, IL-10 and IL-13 protect vessel walls from oxidized LDL-induced monocyte injury in the endothelium, and downregulate fibrinogen synthesis
Though our characterization of arterial disease is provisional pending ultrasonographic studies, our study provides evidence that chronic low-grade inflammation in the absence of several other risk factors is not a determinant of CVD in a subsistence population. Inflammation and infection may not accelerate arterial degeneration in the context of restricted caloric intake, parasitism, and daily physical activity that maintains low BMI. We observed low levels of atherosclerosis and associated CVD among Tsimane, suggesting that these conditions may have been rare throughout pre-industrial human history. However, as indigenous populations like the Tsimane rapidly acculturate to western lifestyles, rates of CVD among older adults may rise considerably. Transitioning populations exhibiting western lifestyles but relatively high pathogen load are likely to suffer the double burden of chronic and infectious disease morbidity and mortality
Informed consent was obtained for all protocols at three levels: 1)
Data were collected during annual medical exams of the Tsimane Health and Life History Project co-directed by MG and HK (
Variable | Tsimane | United States (NHANES) | ||||||
40+ ABI sample | 20+ BP sample | 40+ ABI sample | 20+ BP sample | |||||
Mean | N | Mean | N | Mean | N | Mean | N | |
Sex (%) | 51.6 | 258 | 50.8 | 809 | 51.7 | 7571 | 51.6 | 13399 |
Age (yrs) | 53.1 | 258 | 37.6 | 1604 | 56.2 | 7571 | 46.1 | 13399 |
Height (cm) | 156.8 | 257 | 156.1 | 1280 | 168.7 | 7479 | 169.0 | 13137 |
Weight (kg) | 62.2 | 257 | 58.8 | 1280 | 80.8 | 7530 | 80.2 | 13149 |
BMI (kg/m2) | 25.2 | 256 | 23.7 | 1266 | 28.3 | 7467 | 28.0 | 13035 |
Systolic BP | 113.2 | 258 | 110.6 | 1262 | 128.7 | 7360 | 123.6 | 13399 |
Diastolic BP | 71.1 | 258 | 67.4 | 1263 | 73.4 | 7360 | 71.7 | 13399 |
ABI | 1.13 | 258 | 1.13 | 242 | 1.13 | 7571 | 1.13 | 7360 |
CRP (mg/L) | 8.47 | 129 | 9.35 | 430 | 4.4 | 7260 | 4.2 | 12705 |
median | 2.33 | 2.64 | 2.30 | 2.10 | ||||
Total Chol (mg/dL) | 146.5 | 127 | 137.6 | 427 | 210.7 | 7219 | 202.8 | 12641 |
HDL (mg/dL) | 38.1 | 110 | 36.7 | 369 | 53.2 | 7218 | 52.2 | 12640 |
LDL (mg/dL) | 80.6 | 108 | 74.8 | 366 | 126.1 | 3209 | 121.2 | 5566 |
Triglyceride (mg/dL) | 134.9 | 127 | 129.8 | 427 | 162.2 | 3343 | 148.2 | 5758 |
Cigarette pack-yrs | 0.4 | 257 | 0.4 | 800 | 14.5 | 7162 | 10.3 | 12429 |
In-field blood analysis of nonfasting venous samples provided estimates of WBC and ESR. Blood measures exist for 234 ABI and 1,000 BP samples. CRP, total cholesterol, HDL and triglycerides were analyzed separately on a subset of serum samples by TriCore Laboratories (Albuquerque, NM). ABI exists for >110 of the 203 (age 40+), and blood pressure for 383 of the 427 (age 20+) samples with blood lipids, CRP and antibodies. Non-fasting LDL is estimated using the Friedewald formula (total cholesterol – HDL – triglycerides/5). CRP, ESR, and WBC are biomarkers of inflammation and infection.
Physicians measured ABI after training by HK and MG according to standard protocol by the American Heart Association. The patient lies supine with feet uncovered while brachial and ankle systolic pressure measurements are made using a SummitDoppler L150 ultrasound machine. Systolic pressure is first measured in the posterior and anterior tibial arteries and the higher of these is selected as the ankle measurement for each foot. The cuffs are inflated on the ankle to roughly 30 mm Hg above the systolic pressure, then followed by a slow release until the first audible sound of systolic pressure is heard. Systolic pressure is then measured in each arm and the highest is chosen as the brachial pressure. The ratio of the left and right ankle pressures to the brachial pressure is the left and right ABI. ABI <0.9 indicates PAD. ABI between 0.5 and 0.9 corresponds to intermittent claudication in the lower limbs, whereas values <0.5 are associated with more severe symptoms such as resting pain, severe occlusion and critical ischemia. ABI values >1.3 suggest calcification of arterial walls and noncompressible vessels, and are therefore also symptomatic of severe PAD.
Systolic (SBP) and diastolic (DBP) pressure were measured during each visit with a Welch Allyn Tycos Aneroid 5090 sphygmomanometer and Littman stethoscope. The systolic brachial pressure using the Doppler highly correlates with aneuroidal SBP (r = 0.896, p<0.0001). Cumulative experience smoking cigarettes was measured in cigarette pack years based on interviews. One pack year is equal to a pack of cigarettes smoked per day for one year. Bolivian physicians using bilingual Tsimane assistants diagnosed illnesses and trauma presented by patients on annual visits since 09/2002. Diagnoses from the International Classification of Disease (ICD-10) are grouped into gastrointestinal, respiratory, and other infections, over the two most recent exams 10/2005–12/2007.
Age estimates are derived from demographic interviews conducted with all individuals aged 18+ (n = 1,098) and from missionary records. Years of birth were assigned based on methodologies employed by researchers among the !Kung
Tsimane health status was compared with NHANES data for the years 1999 to 2004 (N = 7,571 for adults age 40+, N = 14,213 for adults age 20+). The NHANES monitors the health and nutrition of a representative sample of the American noninstitutionalized population. Methods have been widely published and so are only briefly summarized here.
Lipid indicators include total, LDL and HDL cholesterol and triglycerides. Triglycerides and LDL were measured for approximately half of the sample that fasted for at least 6 hours. Total and HDL cholesterol and triglyceries were assayed using the Hitachi 704/717/912 Analyzer, Roche Diagnostics. Fasting LDL cholesterol was calculated using the Friedewald equation. CRP was determined by the latex-enhanced Behring Nephelometer. White blood cell differentials were determined using the Beckman Coulter® MAXM.
ABI was measured among the 40+ sample (N = 7,571) by trained technicians. People who had amputations, excessive obesity, or other conditions that inhibited examination were excluded. The procedure was the same as described for the Tsimane. Systolic and diastolic blood pressure was measured by physicians using a stethoscope and sphygmomanometer (Baumanometer® with a Calibrated® V-Lok® cuff, Latex Inflation Bulb, and an Air-Flo® Control Valve). SBP and DBP values are the average of three individual readings.
Multiple linear regression (PROC REG in SAS 9.1) was used for continuous values of ABI and blood pressure, as a function of demographic variables, risk factors and disease markers. Each risk factor is included separately in a baseline model that controls for sex, age and age2 for ABI, and sex, age and sex*age for BP. These results are reported in
Post-hoc power analysis for multiple regression assuming a 0.05 alpha level was performed to assess whether the absence of significant effects in the Tsimane analyses was due to small sample size. Given the observed
The authors thank the Tsimane for their cooperation, and Chris Kuzawa, Henry Harpending and two anonymous reviewers who provided helpful comments on an earlier draft.