Cardiovascular Disease
Cardiovascular disease, otherwise commonly called heart disease and stroke, are the largest single cause of mortality.
According to the World Health Organization and Center For Disease Control and Prevention, of the 56.9 million deaths globally in 2016, 15.2 million (26%) were due to heart disease and stroke. In contrast, a mere 1.4 million (2.4%) were due to road injuries[1] [2] [3]. Nearly every year, cardiovascular diseases are the number one cause of death. Over the years there have been many proposed mechanisms and likely candidates for causation. One of the most studied is cholesterol, and due both to that and the contentious nature of cholesterol on online health circles (particularly alt-med and health trends) it is the main focus of this article.
Contents
Relevance to Veganism
Vegetarians and vegans are consistently found to have lower risk for cardiovascular disease, and this makes up a large part of the health argument against meat. It makes a strong argument for at least reduction of most animal product consumption and incorporating more healthy plant-based foods, though as discussed elsewhere the health argument doesn't strictly recommend veganism, since very small amounts of animal products are probably not significant and it's hard to make any compelling case for health against leather, fur, or animal tested cosmetics which vegans typically avoid. Regardless of the degree of reduction it compels, any reduction in animal products is a reduction in animal suffering too which is an important goal of veganism (not just making people vegan). There are concerns for unintended consequences that have to be kept in mind, see health argument and one step for more.
Causes
Saturated Fat
Over the years there have been many proposed mechanisms and likely candidates for causation. With death and cardiovascular disease on the rise in the 1950s, research was undertaken to determine the best course of preventive action. Work on rabbits and other mammals found that feeding certain lipids induced atherosclerosis. Correlations in population (epidemiology) research showed a correlation with total fat and rates of heart disease. Later this research was criticized by researchers Yerushalmy and Hilaboe. They found that animal protein showed an even stronger association casting doubt on whether fat was really to blame. However, this makes sense given this was before it was known that saturated fat was uniquely damaging to heart health, and so animal protein would show a stronger association than total fat. In the following years a scientific consensus has formed to keep saturated fat below 5-10% of total calories for the prevention of cardiovascular disease. For a full article on why this is, and an exploration of arguments skeptics use, see the full article on Saturated Fatty Acids
Cholesterol
The main mechanism by which saturated fatty acids raise heart disease risk, is by increasing cholesterol; a fatty molecule in the blood strongly linked to increased plaque formation. The more of it one has, the higher their risk of the disease. Some of the most transformative work in this regard came from Mike Brown and Joe Goldstein, who had been performing various experiments on cholesterol metabolism. Brown and Goldstein found that those with a genetic condition characterized by elevated LDL-cholesterol (familial hypercholesterolemia) had LDL that would not bind to the rate-controlling enzyme of cholesterol synthesis known as, HMG-CoA reductase [1]. HMG-CoA reductase is the main target of the class of cholesterol controlling statin medication used today. Ultimately, their work lead to the discovery of the LDL receptor, earning them the Nobel Prize in Physiology and Medicine in 1985 (A. G. Motulsky,. 1986). Brown and Goldstein paved the way and were paramount in understanding cholesterol in the later years. Today, and thirteen Nobel Prizes later, there is a near-unanimous scientific agreement on the role of cholesterol in heart disease [2]. There is high-quality evidence that demonstrates this, and medications such as statins and PCSK9 inhibitors have been created with the intent of saving lives and preventing the disease. For the reasons why this is, see the full article on Cholesterol
"The disease mechanisms elicited by LDL and the other causal factors are multifaceted as discussed below, involving lipoprotein retention, inflammatory cell recruitment, foam cell formation, apoptosis and necrosis, smooth muscle cell (SMC) proliferation and matrix synthesis, calcification, angiogenesis, arterial remodeling, fibrous cap rupture, thrombosis, and more." [3]The way LDL cholesterol increases risk of CVD is by lodging in the arterial walls, accumulating over time.
This causes the radius where blood can move freely in the artery to decrease (image 1), leading to a higher risk of cardiac events.
If enough HDL cholesterol is available, it will latch onto the LDL cholesterol in the artery wall, lug it back into the bloodstream, and carry it to the liver. Since cholesterol is taken out of arterial cells, the process is sometimes known as cholesterol efflux. Since cholesterol is returned to the liver (where it was assembled in the first place), reverse transport is another name for the process. By either name, it's good for vascular health, since the liver collects cholesterol from the HDL particles, packages it into bile salts and bile acids, and dumps it into the intestines for excretion in the feces. [4]
After LDL cholesterol is deposited in the artery, the body fights back by sending immune system cells called macrophages that ingest LDL particles. [5]
LDL-laden macrophages become foam cells, that promote inflammation and further the development of atherosclerotic plaques.
This process triggers muscle cells in the artery wall to multiply and form a 'cap' over the area, enclosing the plaque.
The soft plaque beneath the cap is dangerous. If the blood pressure spikes, it puts pressure on the thin wall of the plaque, which can break open, form a clot, and cause a stroke or a heart attack. When the wall breaks, blood cell fragments, called platelets, stick to the site of the injury. They may clump together to form blood clots. Clots narrow the arteries even more, limiting the flow of oxygen-rich blood to your body. Depending on which arteries are affected, blood clots can worsen angina (chest pain) or cause a heart attack or stroke.
"Depending on their age and lifestyle, most people have small inflammations in the walls of their blood vessels. These can develop in different ways. In people who have high LDL cholesterol, the phagocytes (scavenger cells) in blood “eat” more cholesterol particles. This means that cholesterol is more likely to stick to the walls of affected blood vessels.
Inflammations can also weaken the blood vessel wall, which might then tear. If blood suddenly comes into contact with the cholesterol-rich deposits as a result, a blood clot might form. That is because our bodies try to seal the wound in the blood vessel wall, just like when scabs form if you cut your skin.
If this happens, the consequences will depend on various things, including how big the blood clot is. A big clot can completely block the blood vessel, causing a heart attack or stroke. But the blood clots that form are often only small – they fix the damage in the blood vessel wall and do not have any noticeable consequences. Then the cut heals on its own. This can lead to scarring and calcification of the blood vessel wall, which can gradually make the blood vessel narrower without blocking it completely. The blood vessel wall becomes thicker and stiffer. The medical term for the hardening of blood vessel walls is arteriosclerosis.
Inflammations can develop in any artery in the body. They are particularly dangerous in the large arteries that carry blood to the brain and heart. Narrow coronary blood vessels can cause chest pain (pectoral angina) during physical strain. If a coronary blood vessel becomes blocked, blood will no longer flow to part of the heart muscle, which might result in a heart attack. If a blood vessel in the brain becomes blocked, it might lead to a stroke." [6]
It's not exactly certain why LDL cholesterol accumulates in the arterial walls, but it's thought to be because a protein called SR-B1 'ferries' LDL particles into and then across the endothelial cells that line arteries. It was also found that a second protein called DOCK4 partners with SR-B1 and is necessary for the process.
In fact, higher levels of SR-B1 and DOCK4 were found in the disease-prone regions long before atherosclerotic plaques formed.
SR-B1 is not well understood, as it would seem to help the transport of cholesterol back to the liver. [7] [8]
"SR-B1 also facilitates the efflux of cholesterol from peripheral tissues, including macrophages, back to liver."A level of LDL cholesterol going over the threshold of 50 to 70 mg/dl has been associated with incrementally increased risk of atherosclerosis (image 2). [9] [10]
