The Causes of Heart Disease: Mostly Not Genetic

Some diseases such as chicken pox, TB, maple syrup urine disease and sleeping sickness are rooted in a single cause of a viral, bacterial, genetic and parasitic nature, respectively. But the two most common cardiovascular diseases, atherosclerosis and stroke, which combine to be the number-1 killer of humans worldwide, result from several factors, most of which are not genetic. Yet in too many minds the simplistic view that heart disease results from some pipe-clogging-like agent persists. The excessive focus has shifted from cholesterol to saturated fat and trans fats, while the potential of preventative medicine based on a fuller understanding of the causes of heart disease has been compromised.

Four completely different diseases, each brought on by a single cause. Heart diseases , unfortunately, do not fall under such a neat and tidy category.

As early as in the 1970s some medical researchers realised that dietary cholesterol was not cause of atherosclerosis and that the multifactorial nature of the disease was evident. In a 1977 Scientific American article on atherosclerosis, Earl P. Benditt wrote:

Moss and I fed cholesterol and administered estrogen to chickens and examined their vessels with the electron microscope. We found. first of all. that the lesions that cholesterol induced in the chickens did not resemble human atherosclerotic plaques. They appeared to be composed entirely of fat-filled cells derived from blood macrophages; there was no evidence of significant smooth-muscle-cell proliferation. And none of the lesions evolved into the raised plaques characteristic of the human disease.

Poring through recent review articles of the  medical and scientific literature, we observe that the current consensus on atherosclerosis is that’s an inflammatory disease characterised by intense immunological activity.  Moreover, as a November 2016 Nature Reviews Cardiology paper, Nature versus nurture in coronary atherosclerosis, points out:

“Lifestyle factors may powerfully modify risk of coronary artery disease regardless of the patient’s genetic risk profile.”

These findings are consistent with the modified response to injury theory of atherosclerosis. It identifies a number of “insults”, most of which are environmental or linked to lifestyle choices. The following factors trigger the intense immunological activities responsible for heart disease.

(1) Reactive oxygen species from smoking and/or air pollution

(2) High blood concentrations of “low density lipoprotein”(LDL) or “very low density lipoprotein” (VLDL), which contains more triglycerides.

(3) Chronically elevated levels of glucose

(4) Turbulent blood flow from arterial branching

(5) Stress from hypertension or elevated blood pressure

(6) Inherited metabolic defect that raises homocysteine levels, affecting the endothelium of tissue.

Until recently, it was not clear how air pollution led to heart disease. But Mark Miller and his team from Edinburg University and three Dutch institutes wondered whether tiny particles of soot migrate from the lung’s air sacs to the walls of blood vessels of the heart and brain.  Since they used human subjects in the study,  for ethical reasons, the researchers relied on gold, which is biochemically inert. Their patients were asked to inhale soot-sized particles of the precious metal. Within 15 minutes to 24 hours the gold showed up in the blood and urine, and three months later it was still in the body. When mice inhaled gold nanoparticles twice a week for 5 weeks, diseased arteries contained five times as much gold as healthy ones. Three human patients who were already scheduled for heart surgery and who inhaled the fine gold particles ended up concentrating them in their arterial plaques, just like the mice had done.

Small particles tend to get into the blood stream more easily than larger ones.  From ACS Open access

Upon examining the data, I also found it interesting that small gold particles (less than 10 nm) got into the blood stream far more efficiently than larger ones. This helps supports the current emphasis that environmental scientists place on PM 10 and PM 2.5 pollution, which are not only linked to heart disease but to lung cancer. Also, in the arterial plaque of mice, the gold particles were found within macrophages, suggesting that these may play a role in the translocation of the particles. How the gold is carried around is still not understood, but the authors point out that such knowledge is needed to assess the full impact that inhaled nanoparticles have on health.

Inhaled gold particles were found in immune system cells within arterial plaques of mice. From ACS open access