For much of history, there were three great threats to human survival: infections, injuries and starvation. By striking early and often, all three prevented us from fulfilling the most important reason for our existence: reproduction. Humans, therefore, evolved mechanisms to stave off these life-limiters.

These days most of us die of heart disease. The reason our species finds itself in the ever-constricting clutches of atherosclerosis — the insidious buildup of cholesterol-filled plaques in blood vessels leading to heart attacks and stroke — might be that human evolution inadvertently led us into its labyrinthine lair. If that is true, is it possible for us find our way out?

While it’s hard to recreate ancient human life and find a causative link, the Tsimane, a remote people living in the Bolivian rain forest, provide a sneak peek. The Tsimane, who have minimal atherosclerosis, are under relentless assault by infectious organisms. Ancient humans predating the Tsimane were under even greater siege. The only human beings who could survive were those with a vigilant immune system, always on the lookout for foreign invaders.

In response to infections, the immune system unleashes a powerful response called inflammation. In extreme forms, such as after catching the flu, inflammation can set the body ablaze and is our best means to keep us sterile and free of infection. Inflammation also plays an important role when someone gets hurt and the barrier between the body and the world outside is breached. Inflammatory cells unleash a cascade that results in blood clots forming to quickly plug nicks and cuts. As species have evolved, they have also developed stronger mechanisms of clot formation.

After the institution of better public hygiene, our great guardian, inflammation, no longer busy with outsiders, turned its menacing guns inward. Inflammation is responsible for every important step in the story of atherosclerosis, from its birth as fatty streaks in the lining of the blood vessels, to the dramatic eruption of cholesterol-laden plaques in blood vessels supplying the heart, brain and legs, that activate our clotting cascade, leading to blockages that cause heart attacks, strokes and blood-choked limbs needing amputation.

The third threat to ancient human survival, starvation, existed because of the long intervals that could occur between generous meals. The brain only feeds on sugar, specifically glucose, and therefore it was necessary to maintain glucose in the blood to nourish the brain during thrifty times. And what hormone lowers glucose levels in the blood? Insulin. Therefore, it is hypothesized inconclusively that genes that reduced the effectiveness of insulin were positively selected, raising the glucose levels in the body and now contributing to the pandemic of diabetes. It is also controversially theorized that high cholesterol levels, one of the most important risk factors for atherosclerosis, could have conferred a longer life in prior generations because of a theoretical protective function against infections. These days, however, the lower the cholesterol, the better.

Evolution has a hand in another important driver of heart disease — obesity. Not only did we develop mechanisms to store nutrition to prepare for the inevitable famine around the corner, obesity actually conferred another advantage — it overcharged inflammation. Not only does inflammation cause atherosclerosis, it also accelerates the development of other risk factors for heart disease such as diabetes and high blood pressure.

Evolution may have affected African-Americans even more adversely, as they are very prone to high blood pressure from salt consumption. Natives of Africa had very little salt in their diets and risked losing most of it in their sweat. There is evidence that those that held onto salt in the body were positively selected through evolution. Salt intake in modern societies is several-fold that of what we had consumed for thousands of years. Mechanisms developed to hold onto a previously rare nutrient might be contributing to high blood pressure at a time when salt is ubiquitous. Hypertension, in fact, is much more common in black Americans compared to both white Americans and foreign-born blacks in the United States.

How can we have a chance at reversing these evolutionary mechanisms? Anti-inflammatory drugs repurposed from other conditions such as rheumatoid arthritis have shown mixed results in treating atherosclerosis. Greater benefits could be achieved from anti-inflammatory therapies specifically designed to treat atherosclerosis.

Perhaps the most important evolutionary mechanisms behind the emergence of atherosclerosis is that protection from our ancient adversaries — infection, injury and starvation — now allows us to live long enough to gain prolonged deadly exposure from our modern lifestyles. “Because we adapted so well to these other threats, we now live long enough to be exposed to risk that we haven’t had time to genetically accommodate to,” said Dr. Clyde Yancy, a professor at Northwestern University and Chief of Cardiology at Northwestern Memorial Hospital in Chicago. “Is it possible that lifestyle changes can overcome the inclinations we have developed?”

We need to stop testing ourselves with lifestyles and diets that put our body’s defenses at odds with our well-being. Atherosclerosis has always been around, even in the blood vessels of one of the oldest mummified humans, Ötzi the Iceman, who was found in a block of ice from 5,300 years ago. Yet, the reason atherosclerosis rarely killed was because our lifestyles were not at odds with our biology. Recent dramatic reductions in heart disease are proof that through lifestyle improvements and medical therapy, we can exert real agency over our fitness, and that we are not beholden to our genetic biology. While the DASH and Mediterranean diets have the best evidence for heart health, the problem seems to be not too much of either fat, salt, sugar or meat in our diets, but too much of everything. The density of calories available to us coupled with the minimal effort required to obtain them is a toxic recipe.

The solution is not to live like the Tsimane or crumble in nihilism. The solution is to transform our lifestyles so that we can come up to speed with evolutionary mechanisms set in motion millenniums ago. Heart disease is still a new disease, and if we respect our evolution, adapt accordingly and follow evidence-based medical advice, we can revert it to a speck in the history of mankind.

Haider Warraich (@haiderwarraich) is joining the faculty of Brigham and Women’s Hospital, the Boston VA and Harvard Medical School in the fall. He is the author of the new book: “State of the Heart: Exploring the History, Science and Future of Cardiac Disease.”

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