The Evolution & Medicine Review

What factors should we blame most for the continuing pandemic of heart and artery disease throughout the Western world? The argument has endured more twists and turns than California Route 1. For years, the diet cholesterol hypothesis has held sway, with added blame attached to smoking and a couch potato lifestyle. Before the ascendency of the cholesterol hypothesis, cardiology favored inflammation as the main driving force for atherosclerosis, and interest in inflammation has returned thanks to studies suggesting C-reactive protein is a much better indicator of heart problems lying in wait for asymptomatic individuals than cholesterol levels or high blood pressure; a meta-analysis showing that dietary change has no impact on the risk of a heart attack; studies showing that atherogenic processes in arterial walls are driven by the immune system; and paleocardiology studies showing that pre-industrial and prehistoric societies had high levels of arterial plaque despite high exercise levels and a frugal diet low in saturated fat. i.e. that susceptibility to heart disease is not a modern phenomenon. Now, a study published last Friday in The Lancet, based on measurements taken from members of the Tsimane – a forager-horticulturalist population living in the Bolivian Amazon basin – dramatically switches the argument back again. The Tsimane have extraordinarily low rates of coronary artery disease, low blood pressure, low blood glucose, and low “bad” cholesterol (LDL), despite enduring chronic high levels of systemic inflammation due to the high pathogenic load they carry. It is infection that carries them off – not heart disease.

The paper, titled “Coronary atherosclerosis in indigenous South American Tsimane: a cross-sectional cohort study”, comes from a collaboration between two large research groups: the Tsimane Health and Life History Project team (THLHP), whose members include Michael Gurven, Hillard Kaplan and Benjamin Trumble, and who have been studying the Tsimane for over a decade; and the HORUS research team (named after the Egyptian god) who have based their research on the study of arterial plaque preserved in blood vessels in mummified remains from ancient Egypt, ancient Peru, ancestral Pueblans of southwest America, and the Unangans from the Aleutian islands. These team members include Randall C. Thompson, Caleb Finch, Gregory Thomas and Adel Allam.

The cross-sectional study sampled 705 individuals between 40 and 95 years of age from some 85 Tsimane villages. Coronary atherosclerosis was measured by estimating coronary artery calcification (CAC) via computed tomography. Blood lipids, blood pressure, and inflammatory biomarkers were measured at the same time. They discovered that the prevalence of coronary artery disease risk factors, including blood pressure, cholesterol and glucose concentrations, were low in all age groups measured and that the prevalence of smoking was also low. No differences, they say, were observed across age groups for hypertension, hyper-cholesterolaemia, obesity, or diabetes, and inflammation marker levels were similar across all age groups. The occurrence of atherosclerosis was astonishingly low. 85% of the participants had no coronary artery calcification whatsoever and age did not wither – 65% of Tsimane octogenarians were also free of arterial disease. The Tsimane have an approximately 25 year time lag before even low levels of calcification show up, compared with the multi-ethnic MESA study in the US. Their rate of progression to coronary artery disease is much slower. Typically, men have four times the levels of calcification than women, but in the Tsimane both sexes were protected against heart disease and Tsimane men had lower rates of calcification than Japanese women.

The Tsimane have low levels of LDL cholesterol, but they also have relatively low levels of “good” cholesterol (HDL) – thought to be a risk factor for heart disease – though the ratio of LDL to HDL was also low. To what possible extent is the Tsimane lifestyle athero-protective? They have a diet rich in un-refined carbohydrates in the form of rice, plantain, manioc, and corn, together with wild nuts and fruits, all of which have a high fiber content. Meat protein and fats are procured by hunting wild animals and fishing and there is no intake of trans fats. But their exercise levels might also be important. Most of a typical Tsimane day, the paper reports, involves the physical activity of farming, hunting, food preparation, household chores, and parenting. The average hunt lasts more than 8 hours and covers nearly 18 kilometers, while horticultural labour includes using metal
axes to chop large areas of primary forest. Men and women spend a mean of 6–7 hours and 4–6 hours per day engaged in physical activity. They are only sedentary for 10% of a day.

This study – on a live laboratory of Amazonian tribespeople – comes to opposite conclusions to those previously arrived at by the HORUS group. They set out to try and answer the question: When in the course of human history did atherosclerosis appear? Is it a disease of lifestyle? They found significant evidence of atherosclerosis in mummies from different cultures in very different geographical regions and over several epochs of time. Mummies from ancient Egypt, riddled with arterial plaque, were likely to be from high social caste and it has been argued that these individuals would have subsisted on a diet relatively high in saturated fat in the form of domesticated cattle and sheep and fowl. But the ancient Peruvians enjoyed a more prudent diet of corn, potato, tarxi, manioc, peanut, beans, bananas and hot peppers, augmented with lean meat from Andean deer, ducks, birds and frogs; while the ancestral Pueblans were transitioning from hunter-gathering to forage-farming growing corn and squash, while relying on meat from rabbits, rodents, deer and wild sheep. The Unangans took to the sea in kayaks and their marine diet consisted of seals, sea lions, otters, whales, fish, sea urchins, shell-fish and birds – all high in unsaturated fat. However, all populations, they concluded, would have lived with a chronic load of infectious pathogens which meant a chronic inflammatory regime in their bodies which would have been consistent with accelerated atherosclerosis. They concluded that atherosclerosis was common in all pre-industrial populations studied across a wide time span of human pre-history, suggesting, they said, that the disease is an inherent component of human aging and not characteristic of any specific diet or lifestyle. Or, as team leader Randall Thompson, was quoted as saying: “I think it’s fair to say people should feel less guilty about getting heart disease in modern times. We may have oversold the idea that a healthy lifestyle can completely eliminate your risk”.

The Tsimane study finds the HORUS group singing a different tune and falling into line with the THLHP. Leaving us to ponder whether the Tsimane represent a recipe for athero-protection that is generalisable to us all, or whether for some un-identified reason – the importance of low LDL or a quirk of genetics – they are a medical anomaly. The authors of this paper recognise the limitations of their study – it is unable to determine the weight or positive interaction between the number of mechanisms by which the Tsimane seem to be protected against coronary artery disease. Numerous potential explanations exist, they say, and might relate to coronary artery disease risk factors, subsistence lifestyle, genetics, and inflammation or immune regulation. Nevertheless, the team concludes that their findings suggest that coronary atherosclerosis can be avoided in most people by achieving a lifetime with low LDL, very low blood pressure, low glucose, normal BMI, no smoking, and plenty of physical activity. The relative contributions of each are still to be determined. In the modern Western world this is going to be much easier said than done!