Pathologists early in the 20th century recognized by macro and micro observation, that inflammation accompanied the atheroma lesions and later cholesterol like crystals. Inflammation then suggested infection of some type was involved. Review of the 19th century literature, commencing in 1852 saw Rokitansky, Virchow,Huchard, Weisel, Klotz, and Osler either postulating or suggesting their data indicated an infectious cause for Atherosclerosis. Most childhood infections were implicated including Typhoid, Streptococcus, Measles, Scarlet fever, Coxsackie B4 and Mareks Virus.That was pathologically rational at that time. The presence of cholesterol crystals or a lipid type material, although un-explained, was not considered a culprit component until later in the evolution of the lesion. This sequence meant cholesterol was not the initiating factor. Cholesterol was not present in the early childhood lesions of ‘fatty streak’, described as such as they looked fatty, but had none. Complete occlusion of coronary arteries was not described at autopsy by pathologists until later in the 1920-30’s . Then Dudley White in the mid 1930’s, made the clinical diagnosis of occlusion, heart attack for the first time in the USA.
An infective agent was not found until the later 1980’s and then it was components of some Herpes viruses and Chlamydia pneumonia. Antibodies to these infectious species were recognized first and they were not always present with infectious fragments in the atheroma. There are potential reasons why this may arise. But the means to measure chronic inflammation in these patients with antibodies in the case of the Herpes Virus, Cytomegalovirus, showed an association of previous infection, with ongoing chronic inflammation,(CRP) was a strong indicator of atheroma and coronary artery disease. Did these agents initiate lesions or were they secondary invaders? Did they contribute to the maintenance of the lesion, inflammation, did they make the lesion unstable and likely to fissure, rupture later with thrombus clot occlusion?Cytomegalovirus can remain inactive, latent for long periods.
The most interesting infective agent is Cytomegalovirus for several reasons. It is a ‘latent’ virus, meaning after infection it remains in situ and may survive the life time of the patient. So if it is involved with atheroma lesions, it could potentially be a problem for a lifetime. Authors working in this area believe that continuing inflammation with this virus is necessary for it to be a culprit agent. Its found in the atheroma lesions of the coronary arteries of rejected transplanted hearts and is considered to be a culprit there.
Does inflammation from other sources contribute like Insulin resistance with obesity, diabetes, chronic dental disease, autoimmune disease hypertension etc.,? Another contributing feature of this virus is that it is ubiquitous on this planet and amongst the socio-economically deprived, those in poverty, the bulk of homosapiens on the planet, are infected. Mothers pass the virus to their progeny.In an Indigenous study in Queensland, amongst 803 adults and 74 children, conducted with a colleague Tom Lynch, all participants were CMV antibody positive and most to the highest titre. The Australian Indigenous die 20 years prematurely with coronary heart disease. Does chronic inflammation from dental and periodontal disease with skin infection contribute to Indigenous CHD also?
Over six decades ago Velican and Velican, demonstrated arterial lesions in the fetus, newborn and child and many others subsequently. They were seen as cushions at branches and described pathologically as fatty streaks and fibrous plaques. They have subsequently been accepted as the fore-runners of atheroma lesions. Interestingly these lesions have been found in Indigenous populations that had no evidence of adult coronary disease in Africa.This suggests these early lesions are stage one in the evolution of the atheroma lesion and don’t evolve to more advanced lesions and clinical events. Smoking, OWOB, diabetes and hypertension if avoided, as was the case with Indigenous populations and hunter gatherer’s, do not develope obstructive lesions and are atheroma free clinically as adults.It seems the early lesions need a life practice, life nutrition to effect chronic inflammation, via these risk factors. Indigenous hunter gatherers studied did not have symptomatic CHD, although I would speculate they may have had the early lesions.
Autopsy studies of airmen in WWI, British forces in WWII, Americans in the Korean and Vietnam wars revealed surprising levels of atheroma, some occlusions, evidence of evolution from fatty streaks, fibrous plaques to mature lesions, in this ‘young’ cohort, less than 35 years. Then, 4-5 decades ago, symptomatic presentation occurred later, but now it is much younger with attendant risk factors. Korean soldiers autopsied, showed few lesions.Why?
Does this mean that there are several stages in the evolution of atheroma? Could infection such as CMV initiate lesions such as fatty streak and fibrous plaque, which would be extensive amongst homosapiens disadvantaged, in poverty, because it is ubiquitous? These lesions could remain benign unless new aspects or factors were super-imposed on them, like inflammatory states from other infections or metabolic diseases, so called risk factors.
From population studies and reviewing past early evidence, it seems CHD prevalence exploded in the mid 20th century. I suspect it is a very old disease that arose minimally when the template was laid at the Neolithic Period. Why now? What has changed, what could be responsible for this recent epidemic?
I believe we have evidence, that we as a species underwent metabolic and structural changes with the change of nutrition and life practice at the Neolithic Period. We know carbohydrate in a new form was increasingly consumed and we have MRI evidence of arterial lesions consistent with atheroma in > 3000 year old Mummies in Egypt, the planets largest wheat and beer producer for thousands of years.There was evidence in these skeletons of protein and micronutrient depletion, a malnutrition for impaired immunity.
Atheroma did not first turn up in early 20th century, it was ‘fertilised’ by a major increase in consumption of processed carbohydrate and sugar, in our ‘Period of Decadence’from WWII. At the same time smoking was promoted as being good for your ‘nerves’and women male identified, after being used as male substitutes during the war.The nutritional template was set at the Neolithic period.
The result is homosapiens has ‘overdosed’ on processed carbohydrate, produced a further inflammatory state with obesity, pre and diabetes, after the saturated fat and cholesterol ‘con’, such that, any in place template lesions, like the fatty streak and fibrous plaque, can evolve into larger and more complex lesions. Abdominal omental fat is often missed in assessment and is just as ‘endocrine active’ as fat elsewhere or more so.
Does infection influence the end stage in the life cycle of an atheroma lesion? Since I was a Cardiology & CCU registrar in 1973 and before, it was known that most atheroma occlusive events, heart attacks arose when the repiratory viruses were active, usually winter and spring. Why? Did these viruses during their systemic phase infect atheroma lesions, make them unstable, leak and have healing clot contribute to partial or complete occlusion?We also back then knew that less than 50% of patients with acute myocardial infarction(heart attack) had serum raised total cholesterol. We also knew of Prior’s and Hunters work in the Tokelau Study.
Because most populations studied anywhere, show low levels of Vitamin D, mainly in winter, would it be rational to attempt to become eu-vitamin D? You will have some idea why we fail to produce this critical hormone (not vitamin). Perhaps the simplest, like so much of our evolution, is we evolved as a species in Central Africa with copious UV light. We decided to migrate; I believe it was voluntary, unnecessary, like the Neolithic decision. Arguably these were survival mistakes for the species with time, examples of my modified Newton’s Third Law of Motion. Was this in turn a result of Encephalisation? If we last long enough, perhaps we will finally synthesise our own vitamin D, like we did with cholesterol, because it is critical for our survival. Statin drugs have a pleotropic effect on CHD, indipendant of their effect on cholesterol its believed. Two decades ago studies suggested this effect may be due to statins attaching to Vitamin D receptors. This data has not been determined with certainty yet. It would be interesting if we found Vitamin D and statins were competing for the same receptor sites!
My two, three stage theory of the life cycle of the atheroma lesion in homosapiens is just that, a theory, sprinkled or brush-stroked with pieces of evidence.I have a post on the possible cytomegalovirus research evidence in atheroma, as well as the potential for vaccination.