Atherosclerosis, Inflammation, and Genetics – And you Thought it Was Just LDL-cholesterol

As the twentieth century unfolded, based on numerous epidemiological observations and intervention trials, cardiovascular risk factors were identified and targeted with the aim of decreasing cardiovascular disease burden worldwide. Along the centuries, changes in human eating patterns, a progressive decrease in physical activity, and a higher prevalence of obesity, all of which are contributing factors to the alarming rates of diabetes, hypertension, and hypercholesterolemia we see in our daily practice, have led us to assume that atherosclerosis-related disorders (myocardial infarction, ischemic cardiomyopathy, stroke, and peripheral artery disease) are an inevitable consequence of the evolutionary process we have to face in present times. However, due to advances in noninvasive imaging of the vascular system, atherosclerotic lesions in the aorta and coronary and carotid arteries happen to be found in mummies from ancient Egypt, whose estimated mean age at the time of death was only 45 years.

If the so-called “classical risk factors” were less prevalent in ancient times, different, non-traditional factors must have played a significant role in the development and progression of atherosclerosis. Microbial and parasitic inflammatory burdens that were likely present in ancient cultures inherently lacking modern hygiene and antimicrobials could have evoked a chronic inflammatory status. Given that patients with today’s chronic systemic inflammatory diseases, including human immunodeficiency virus infection, systemic lupus erythematosus, and rheumatoid arthritis experience early-onset atherosclerosis and coronary events, is it possible that the chronic inflammatory load secondary to infection resulted in atherosclerosis in ancient times? Moreover, atherosclerosis is a complex, multifactorial biological process, and, as such, it is also subject to gene-environment interplay; therefore, although the contribution of today’s classical risk factors to the development of atherosclerosis is inquestionable, their role in the appearance of atherosclerotic lesions in the vascular tree involves not only inflammation and activation of the immune system but also genetic factors that facilitate or oppose the formation of lipid accumulation in the arterial wall.

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