Although heart disease is common today, it was likely a far less frequent cause of death than predatory assaults among our prehistoric ancestors. Anyone reading this article is the fortunate descendant of an unbroken lineage of organisms that escaped or survived predatory attacks before reproducing.

The responses that help us survive predatory attacks are collectively called the fight-or-flight system. This system drives three major vascular responses to injury: coagulation (to counter blood loss), vasoconstriction (also to counter blood loss), and inflammation (to combat microorganisms and to promote wound healing). Together they helped our predecessors survive a predator’s bite. These responses are called upon reflexively no matter what the source of injury.

However, modern humans rarely encounter predatory danger. Far more common causes of vascular injury include smoking, diabetes, stress, and high blood pressure. Unfortunately, the human body doesn’t distinguish these modern triggers of vascular injury from that of predators, and thus executes the same factory-setting responses fashioned during the prehistoric age.

As a result, patients who are stressed, smoke, diabetic, or have high blood pressure are prone to vasoconstriction, coagulation, and inflammation. That’s essentially what atherosclerosis, or hardening of the arteries, is. Therefore, atherosclerosis represents a maladaptation of the vascular injury responses that once promoted fitness during antiquity.

To look closer, a narrowed vessel impedes oxygen delivery to downstream tissues. In prehistoric times, this interruption of oxygen flow was likely precipitated by a predator-related injury, not atherosclerosis. Once upon a time it made sense that a reduced oxygen supply, known as hypoxia, promoted a necessary fight-or-flight response. While this life-saving response is still important in rare moments of real danger, people today are chronically triggering hypoxia due to poor habits and modern day stress. Thus, a vicious cycle occurs, sometimes referred to as sympathetic bias.

Unfortunately, this Darwinian perspective has eluded the medical profession in the treatment of heart disease. Tight, inflamed, and obstructed arteries have been viewed as a plumbing problem that needs to be opened up. Beginning in the 1960s, expanding pressure balloons were deployed in narrow portions of an artery – a procedure called angioplasty.

While angioplasty improved downstream flow, the injury caused by the balloon upon the artery re-starts the cascade of vasoconstriction, inflammation, and coagulation, potentially undoing the benefit over time and sometimes making matters even worse.

The recurrence of arterial narrowing at the site of angioplasty is called restenosis. It would be hard to distinguish whether the artery re-narrowed due to underlying disease or because the vessel had been injured. High rates of restenosis after angioplasty led to the development of stents – tiny metal cages designed to keep the vessel propped open.

Unfortunately, stents are deployed by expanding pressure balloons, and in the long run the vessel often re-narrows and collapses the stent – a condition called in-stent restenosis. Again, was the disease meant to recur or was it induced by the injury related to the procedure? The field’s response to growing rates of in-stent restenosis was to add toxins or radiation to stents.

In contrast to the Sisyphean loop the field of interventional cardiology has been mired in for half a century, evolutionary thinking yields different approaches to the causes and therefore treatment of chronic and acute heart disease. Since sympathetic bias is the maladaptive mechanism behind heart disease, reducing the fight-or-flight response then, may be a better approach.

Indeed a patient who seems to be having an acute heart attack demonstrates all the hallmarks of someone in fight-or-fight overload: this includes high levels of adrenaline, aldosterone, angiotensin-converting enzyme, and low heart rate variability. Beta blockers, which counter fight-or-fight response, were once considered counterproductive in patients showing signs of a heart attack, but now are considered standard care in the treatment of such patients.

The reduction of sympathetic bias will be a key focus area in development of novel treatments for heart disease.

(Originally published in This View of Life on December 27th, 2012)