The Implications of Greater Amounts of Remnant Cholesterol in the Bloodstream

Atherosclerosis is a condition in which fatty lesions form to narrow and weaken blood vessels. It causes a sizable percentage of all deaths in old age, via stroke or heart attack when lesions rupture. Much of the focus in the medical and research communities is on cholesterol in the bloodstream as a contributing factor to the condition, but atherosclerosis should be thought of as being primarily caused by the dysfunction of the macrophage cells responsible for removing cholesterol from blood vessel tissues, handing it off to HDL particles to return to the liver. In youth these cells function just fine, and young people don't develop lesions. In old age, however, it is a different story.

Macrophages are vulnerable to oxidized cholesterol and to the signaling of chronic inflammation. Both can degrade their ability to transport cholesterol, and they can develop into senescent foam cells that make the local environment even more inflammatory. They also die in large numbers, overwhelmed by cholesterol, and the debris of cell death expands the lesion that the macrophages should be helping to remove. It is because oxidized cholesterol is important in this process that reductions in overall cholesterol in the bloodstream can slow the progression of atherosclerosis. Treatments such as statins have become widely used as a result, but they do not lead to significant reversal of existing lesions.

Scientists here note that most of the work on atherosclerosis to date focuses on reducing LDL cholesterol in the bloodstream, which is to say cholesterol attached to an LDL particle. But other forms of cholesterol are also present in the blood stream, the so-called remnant cholesterol, and the research community has underestimated its presence and contribution to atherosclerosis. This has implications for the various approaches taken to try to control the condition, and further demonstrates that perhaps it is a better idea to focus on the macrophages rather than on the cholesterol. If macrophages can be made resilient to oxidized cholesterol, either by removing that cholesterol in a targeted way, by preventing it from being created in the first place, or by giving the macrophages additional capabilities, as we're working on at Repair Biotechnologies, then this should go a long way towards the goal of reversal of atherosclerosis.

Levels of 'Ugly Cholesterol' in the Blood are Much Higher than Previously Imagined

Three quarters of the Danish population have moderately elevated levels of cholesterol. If cholesterol levels are too high, risk of cardiovascular disease is increased. Often, LDL cholesterol, the so-called bad cholesterol, is considered the culprit. However, new research shows that a completely different type of cholesterol may be more responsible than previously assumed. What we are talking about is remnant cholesterol To their surprise, the researchers have discovered that the amount of remnant cholesterol in the blood of adult Danes is much higher than previously believed. From the age of 20 until the age of 60, the amount in the blood is constantly increasing, and for many people it remains at a high level for the rest of their lives.

"Our results show that the amount of remnant cholesterol in the blood of adult Danes is just as high as the amount of the bad LDL cholesterol. We have previously shown that remnant cholesterol is at least as critical as LDL cholesterol in relation to an increased risk of myocardial infarction and stroke, and it is therefore a disturbing development." The results are based on data from people from the Copenhagen General Population Study. A total of 9,000 individuals had cholesterol in their fat particles in the blood measured by metabolomic techniques. "Previous studies from the Copenhagen General Population Study show that overweight and obesity are the main cause of the very high amount of remnant cholesterol in the blood of adult Danes. In addition, diabetes, hereditary genes and lack of exercise play a part."

In 2018, a large international, controlled clinical trial was published that clearly showed that when triglycerides and thus remnant cholesterol were reduced by the help of medication in people with elevated levels in the blood, the risk of cardiovascular disease was reduced by 25%. "Our findings point to the fact that prevention of myocardial infarction and stroke should not just focus on reducing the bad LDL cholesterol, but also on reducing remnant cholesterol and triglycerides. So far, both cardiologists and GPs have focused mostly on reducing LDL cholesterol, but in the future, the focus will also be on reducing triglycerides and remnant cholesterol."

A third of nonfasting plasma cholesterol is in remnant lipoproteins: Lipoprotein subclass profiling in 9293 individuals

Increased concentrations of calculated remnant cholesterol in triglyceride-rich lipoproteins are observationally and genetically, causally associated with increased risk of ischemic heart disease; however, when measured directly, the fraction of plasma cholesterol present in remnant particles is unclear. We tested the hypothesis that a major fraction of plasma cholesterol is present in remnant lipoproteins in individuals in the general population.

We examined 9293 individuals from the Copenhagen General Population Study using nuclear magnetic resonance spectroscopy measurements of total cholesterol, free- and esterified cholesterol, triglycerides, phospholipids, and particle concentration. Fourteen subclasses of decreasing size and their lipid constituents were analysed: six subclasses were very low-density lipoprotein (VLDL), one intermediate-density lipoprotein (IDL), three low-density lipoprotein (LDL), and four subclasses were high-density lipoprotein (HDL). Remnant lipoproteins were VLDL and IDL combined.

Mean nonfasting cholesterol concentration was 72 mg/dL for remnants, 78 mg/dL for LDL, and 71 mg/dL for HDL, equivalent to remnants containing 32% of plasma total cholesterol. Of 14 lipoprotein subclasses, large LDL and IDL were the ones containing most of plasma cholesterol. The plasma concentration of remnant cholesterol was from 54 mg/dL at age 20 to 74 mg/dL at age 60. Corresponding values for LDL cholesterol were from 58 mg/dL to 81 mg/dL. Thus, using direct measurements, one third of total cholesterol in plasma was present in remnant lipoproteins, that is, in the triglyceride-rich lipoproteins IDL and VLDL.

Comments

I am under impression that high remnants = high triglycerides = metabolic syndrome = hyperinsulinemia and the best way to treat is to reverse underling cause = metabolic syndrome

Posted by: Andriy at August 8th, 2019 3:33 AM

Confusing because there appears to be more than one definition of Remnant. Regardless unless you are paying $100+ premium for direct measurement of LDL the estimated LDL in the standard lipid panel can vary +-10, which is not a big deal as to the LDL number itself, but results in a huge variable to the Remnant calculation. Aside: I have had very good success with my Ezetimbe mono therapy experiment. Been on one month, 2.5mg per day. LDL, APOb, LDL particle number all down 30%, LPa down 10%, HDL actually increased a little, (my triglycerides were already very low).

Posted by: JohnD at August 8th, 2019 12:26 PM

Hey there! Just a 2 cents.

''In youth these cells function just fine, and young people don't develop lesions. In old age, however, it is a different story.''

Yes, in general, but...there are exceptions and, indeed, yougn people also develop lesions.
I am the living proof.

With that said, it depends on your family genetics and your lifestyle - it does not matter if you are 30 years old or 90 years old...lesions will come and atherosclerosis will then happen, as it happened to me.

If your body cannot control HDL:LDL levels correctly, and in this study 'remnant cholesterol' blood levels'...then, yes, you will have atherosclerosis, I guarantee it. A blood clot will form in your arteries as plaque builds up - young or old. It takes about a decade or 2, and then it hits you, young or old. The only solution is if you do something about it, changing lifestyle/foods...etc cutting cholesterol, taking supplements or medications (statins etc). Whether you are 90 or 30.

I sometimes read people say : ''I eat eggs eveyday, foie gras/fatty liver, cholesterol-fried burgers, high-fructose corn syrup maize products, super salty meals, doughnuts and a mint with that...''
''I feel great''.

I don't know what to say them... a part of me is anger and a part of me is 'we choose what we choose/nobody decides for nobody's choices' and 'live of it' (or, die of it).

If their health does not decline and they check their blood.....then, all the power to them, they are forces of nature, nothing can kill them (obviously, others do not have this luxury/gene protection).

Just a 2 cents.

PS: Note aside not related....I saw the video you spoke about aging/your website/company and I was very impressed....it'S incredible the resemblance between you/Reson and Aubrey de Grey; I thought for a second...my god..is Aubrey his brother/cousin or twin (both of you are UK British/accent and the similary is there, only difference is the John Lennon circle Brit-glasses, both pale, same accent, same facial structure and the AdG huge red beard, but of you are red head/blond of same age (late 40s/mid 50). both British keeping their accent. Anyway, it's great!

Posted by: CANanonymity at August 8th, 2019 5:36 PM

This is a very important study. But it is not new. We have known for well over 20-30 years that triglycerides are a significant risk factor. Where the entire medical community is focused on "cholesterol." The categorization of "remnant cholesterol" Is both confusing and essentially imprecise. It is much more rational and reasonable to simply label this as triglycerides and VLDL.

The seminal example is Tim Russert. He died of a massive heart attack with "normal" cholesterol. But it is known that he had very high triglycerides. Similarly, the longest medical study, the Framingham study, has shown that well over 50 percent of heart attacks occur in the setting of "normal" cholesterol.

So the previous comment is quite correct. High triglycerides are associated with a Pattern B, metabolic syndrome and nonalcoholic fatty infiltration of liver (NAFLD or NASH).

So the importance of this study is simply to highlight what we have already known for so long.

Posted by: Philip Lee Miller at August 11th, 2019 4:03 PM

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