Is Lipid Level or Inflammation the Critical Factor for Cardiovascular Disease Risk?
No orthodoxy lacks accompanying heretics; it often seems that science is a business of proceeding abruptly and messily from one steady state consensus to another via the mechanism of heresy. It is of course worth bearing in mind that most heretics do turn out to be wrong, and are consequently forgotten by all but the most painstaking of scientific historians. In the paper I'll point out today, the orthodoxy of blood lipid levels as a cause of cardiovascular disease is challenged. The heresy is to suggest that it isn't the lipids at all, but all down to a matter of chronic inflammation.
This is a tough topic to arbitrate, because raised lipids, such as cholesterol, and raised inflammation go hand in hand. Dietary approaches to tackling cholesterol levels are minimally effective in the grand scheme of things, as dietary content is only a small factor in the lipid content of blood, but they also, inconveniently, tend to move the needle on inflammation as well. The calorie content of the diet, considered over the long-term, is linked to lipids and inflammation in equal measures via the amount of visceral fat tissue an individual carries. Therapies that are available and widely used to reduce blood cholesterol, such as statins, are shown to have anti-inflammatory effects. Therapies under development, such as delivery of the APOA1 protein that makes up the HDL particles responsible for dragging cholesterol out of vulnerable cells and transporting it to the liver, also have significant anti-inflammatory effects. You can probably see the challenge.
On the one hand, it doesn't seem completely unreasonable to mount the argument that lipid levels are a smokescreen, and we should be caring about chronic inflammation. We know that chronic inflammation is very damaging, and contributes to the progression of all of the common age-related diseases. When it comes to cardiovascular disease, and particularly atherosclerosis, it seems hard to write off a role for lipid levels in blood, however. Atherosclerosis is caused by oxidized lipids that overwhelm the cells sent to clean them up when they irritate blood vessel walls; the fatty deposits that narrow blood vessels are made up of lipids and dead cells. More lipids means more overwhelmed cells. Lower lipid levels means fewer oxidized lipids. But does that simple calculus hold up when looked at in detail? To answer that question, we need more data on highly effective therapies that are either anti-lipid or anti-inflammatory, but not both.
Inflammation, not Cholesterol, Is a Cause of Chronic Disease
According to the 'cholesterol hypothesis', high blood cholesterol is a major risk factor, while lowering cholesterol levels can reduce risk. Dyslipidaemias (i.e., hypercholesterolaemia or hyperlipidaemia) are abnormalities of lipid metabolism characterised by increased circulating levels of serum total cholesterol, LDL cholesterol, triglycerides, and decreased levels of serum HDL cholesterol. High levels of LDL cholesterol and non-HDL cholesterol have been associated with cardiovascular risk, while other cholesterol-related serum markers, such as the small dense LDL cholesterol, lipoprotein(a), and HDL particle measurements, have been proposed as additional significant biomarkers for cardiovascular disease (CVD) risk factors to add to the standard lipid profile.
HDL cholesterol has been considered as the atheroprotective 'good' cholesterol because of its strong inverse correlation with the progression of CVD; however, it is the functionality of HDL cholesterol, rather than its concentration that is more important for the preventative qualities of HDL cholesterol in CVD. In general, dyslipidaemias have been ranked as significant modifiable risk factors contributing to prevalence and severity of several chronic diseases including aging, hypertension, diabetes, and CVD. High serum levels of these lipids have been associated with an increased risk of developing atherosclerosis.
Furthermore, dyslipidaemias have been characterised by several studies not only as a risk factor but as a "well-established and prominent cause" of cardiovascular morbidity and mortality worldwide. Even though such an extrapolation is not adequate, it was, however, not surprising that this was made, because since the term arteriosclerosis was first introduced by pioneering pathologists of the 19th century, it has long been believed that atherosclerosis merely involved the passive accumulation of cholesterol into the arterial walls for the formation of foam cells. This process was considered the hallmark of atherosclerotic lesions and subsequent CVD.
Moreover, one-sided interpretations of several epidemiological studies, such as the Seven Countries Study (SCS), have highlighted outcomes that mostly concerned correlations between saturated fat intake, fasting blood cholesterol concentrations, and coronary heart disease mortality. Such epidemiological correlations between dyslipidaemias and atherosclerosis led to the characterisation of atherosclerosis as primarily a lipid disorder, and the "lipid hypothesis" was formed, which would dominate thinking for much of the 20th century.
On the other hand, since cholesterol is an essential biomolecule for the normal function of all our cells, an emerging question has recently surfaced: "how much do we need to lower the levels of cholesterol"? Furthermore, given the fact that cholesterol plays a crucial role in several of our cellular and tissue mechanisms, it is not surprising that there are several consequences due to the aggressive reduction of cholesterol levels in the body. Moreover, recent systematic reviews and meta-analyses have started to question the validity of the lipid hypothesis, as there is lack of an association or an inverse association between LDL cholesterol and both all-cause and CVD mortality in the elderly.
The principles of the Mediterranean diet and relevant data linked to the examples of people living in the five blue zones demonstrate that the key to longevity and the prevention of chronic disease development is not the reduction of dietary or serum cholesterol but the control of systemic inflammation. In this review, we present all the relevant data that supports the view that it is inflammation induced by several factors, such as platelet-activating factor (PAF), that leads to the onset of cardiovascular diseases (CVD) rather than serum cholesterol. The key to reducing the incidence of CVD is to control the activities of PAF and other inflammatory mediators via diet, exercise, and healthy lifestyle choices.
I guess we can design a study with mice who are injected high doses of LDL while they are young and probably on anti-inflammatory factors. And an opposing leg of the experiment is to induce inflammation and yet reduce LDL in another group. Poor mice...
The amount of money skimmed of Statins is more than enough to trigger fraudulent science by humans employed in that system.
I don't doubt lipids play a part but there is probably some much more robust way to check them.
@Cuberat
excellent idea; we have done this here
https://www.sciencedirect.com/science/article/pii/S0308814609013156
enjoy the paper :)
IZ
fyi
https://funfood16.blogspot.ie/2018/05/is-lipid-level-or-inflammation-critical.html
We can thus suggest that it is NOT the cholesterol but the anti-inflammatory impact of fish lipids.
IMO, blood lipids are the problem.
"The normal low-density lipoprotein (LDL) cholesterol range is 50 to 70 mg/dl for native hunter-gatherers, healthy human neonates, free-living primates, and other wild mammals (all of whom do not develop atherosclerosis). Randomized trial data suggest atherosclerosis progression and coronary heart disease events are minimized when LDL is lowered to <70 mg/dl. No major safety concerns have surfaced in studies that lowered LDL to this range of 50 to 70 mg/dl. The current guidelines setting the target LDL at 100 to 115 mg/dl may lead to substantial undertreatment in high-risk individuals."
https://www.sciencedirect.com/science/article/pii/S0735109704007168
https://nutritionfacts.org/video/optimal-cholesterol-level/