Dietary cholesterol and atherosclerosis.
Early observations that cholesterol is a key component of arterial plaques gave The relationship between LDL-C levels and risk for ASCVD is. Many autopsy studies have shown a relationship between blood cholesterol and the extent of atherosclerosis (4). Furthermore, accumulation of. establish this relationship is difficult. Extensive work has been done on blood cholesterol level in clinically diagnosed cases of atherosclerosis. Cases of.
Funding was provided by the Western Vascular Institute. Four of the study authors have previously written book s criticising "the cholesterol hypothesis". This is described as a group of scientists who "oppose…that animal fat and high cholesterol play a role [in heart disease]".
Dietary cholesterol and atherosclerosis.
If you were playing Devil's Advocate, you could argue that this represents a preconceived view of the authors regarding the role of cholesterol, rather than the open, unbiased mind you would hope for in the spirit of scientific enquiry. That said, many important scientific breakthroughs happened due to the efforts of individuals who challenged a prevailing orthodoxy of thinking. In general, the UK media provided fairly balanced reporting, presenting both sides of the argument — supporting the findings, but with critical views from other experts.
What kind of research was this? It has long been thought that cholesterol is a key cause of the fatty build-up in arteries atherosclerosis that causes heart disease. However, the researchers say there are contradictions to this view. Recent research has suggested that total cholesterol becomes less of a risk factor for all-cause or cardiovascular mortality the older people get. Less is known about LDL specifically and that's what this research aimed to look at.
A systematic review is the best way of gathering evidence from cohort studies that have looked at the link between an exposure or risk factor and an outcome. However, the strength of a review's findings is only as good as the studies they include. In cohort studies, it is often difficult to directly attribute an outcome to a specific cause, and there is always the potential that other factors are influencing the outcome. What did the research involve? The researchers searched one literature database PubMed in December to identify English-language cohort studies that had included a general population sample aged 60 and over.
Studies had to have taken baseline measures of LDL cholesterol and then followed participants up over time, looking at the link with all-cause or cardiovascular mortality.
Three authors reviewed potential studies and extracted data. From an initial 2, hits, 19 publications, covering 30 cohorts and including 68, participants, were included.
The majority of studies were excluded outright, as they didn't seem to contain anything relevant in the study title or abstract summary. The other reasons for exclusion were non-English language, participants not being representative of the general population, not measuring LDL cholesterol at baseline, and not giving separate data for older adults or looking at mortality outcomes.
What were the basic results? That is, as LDL cholesterol went down, all-cause mortality went up — higher LDL was apparently linked to lower all-cause mortality. In 14 of these 16, this was said to be a statistically significant link. The remaining 12 cohorts found no link with all-cause mortality.
Only nine of the identified cohorts specifically reported cardiovascular mortality. Seven found no link between LDL cholesterol and cardiovascular mortality. The other two found that those in the lowest fourth quartile of LDL levels actually had the highest cardiovascular mortality. How did the researchers interpret the results?
Low Density Lipoprotein (LDL) in Atherosclerosis and Heart Disease
The researchers concluded that, "High LDL-C is inversely associated with mortality in most people over 60 years". Increased permeability of the endothelium and increased intimal retention of LDL appear to play an important role in this process.
LDL particles interact with particular constituents of the intima, particularly the extracellular matrix. Small LDL particles are associated with high triglycerides 14low HDL cholesterol 15insulin resistance, metabolic syndrome 16and type 2 diabetes. The propensity of small LDL particles to be retained within the intima may explain why patients with the metabolic syndrome and type 2 diabetes are at heightened risk of coronary artery disease in the face of normal or average blood levels of LDL cholesterol.
At the most basic level, oxidation is the loss of electrons. When a compound is oxidized, its properties change. For example, unoxidized iron is a strong structurally sound metal, while oxidized iron, because of the loss of electrons, is a brittle reddish powder. Each LDL particle contains approximately molecules of phospholipids, molecules of free cholesterol, molecules of cholesterol esters, molecules of triglycerides, and one molecule of apoB. Both the protein and lipid moieties can undergo oxidative modification which is a very complex biochemical process.
Recent findings suggest that oxLDL begins to deposit in human coronary arteries before plaque formation and increasingly deposits with plaque growth OxLDL particles may promote atherosclerosis through several mechanisms. The discovery that vascular wall cells themselves can produce cytokines provided an important insight into the initiation of atherosclerosis.
Leukocyte recruitment to the arterial wall is an important initial step in the formation of atherosclerotic lesions. The circulating leukocytes that enter the vessel wall are called monocytes but within tissues, they are termed macrophages.
Typically, the endothelium resists adhesion of leukocytes derived from blood. However, when stimulated by pro-inflammatory cytokines, adhesion molecules on the surface of endothelial cells may capture leukocytes Cytokines may play a key role in recruiting inflammatory cells in the vascular wall. Failure of counter-regulatory mechanisms may also promote inflammation and oxidation in atherosclerosis.
For example, HDL particles may function as carriers for anti-inflammatory and anti-oxidant mediators HDL is an effective antioxidant. After reaching the intima, leukocytes macrophages take up modified lipoproteins.MEDICAL - How cholesterol clogs your arteries (atherosclerosis)
These-lipid laden white blood cells are called foam cells. Foam cells comprise the bulk of early atherosclerotic lesions often termed fatty streaks Foam cells play a critical role in the occurrence and development of atherosclerosis. The Vulnerable Plaque Rupture of the plaque surface, often with blood clotting thrombosis superimposed, frequently occurs during the evolution of coronary atherosclerotic lesions.
It is probably the most important mechanism underlying the sudden, rapid plaque progression responsible for acute coronary syndromes Plaque rupture is an important mechanism underlying most cases of acute heart attack and sudden cardiac death. The concept of plaque rupture was first reported at the autopsy of the celebrated neoclassical Danish artist Bertel Thorvaldsen, who died of sudden cardiac death in the Royal Theater in Copenhagen in Increased permeability of the endothelium and increased retention of LDL particles within the intima are important underlying mechanisms.
LDL particles may undergo chemical modification within the intima and become oxidized. Immune reactions and low-grade inflammation play a crucial role in the formation and progression of atherosclerotic plaques. Rupture of the plaque surface, often with blood clotting thrombosis superimposed, frequently occurs during the evolution of coronary atherosclerotic lesions.