From a purely physiological perspective, the heart is essentially a bag of muscle that pumps blood around the body. In certain circumstances, the heart’s pumping action can weaken, ultimately resulting in what is usually termed ‘heart failure’. Symptoms of this can include fatigue, breathlessness and fluid retention.
I was interested in a study recently published in the journal Cardiology that assessed the relationship between LDL-cholesterol levels and health outcomes in a group of 212 elderly individuals with known heart failure [1]. These individuals were split into 3 groups according to their LDL-cholesterol levels.
1. < 90 mg/dl
2. 90-115 mg/dl (2.3-3.0 mmol/l)
3. >115 mg/dl
Over an average of 3.7 years, the individuals in the 1st group (with then lowest LDL levels) fared worst. Those in group 3 (with the highest LDL levels) fared the best. 58 per cent of people in group 3 lived at least 50 months compared to just 34 per cent in group 1. These results were in spite of the fact that at the start of the study this group had a disproportionate number of people with severe heart failure in it.
Some argue that any relationship between low cholesterol and worsened health outcomes is most likely due to the fact that long-standing illness can lead to weight loss from poor nutritional status, and that cholesterol levels fall as a result. In other words, it’s poor health that is causing lower cholesterol levels, not the other way round.
However, in this study, the subjects started out with what appeared to be broadly identical nutritional status, which suggests that the explanation above is not valid here. According to the authors, “LDL-[cholesterol] may be considered an independent predictor of mortality.”
Why might low LDL-cholesterol levels be a risk factor for mortality? The authors point out that cholesterol can alter the functioning of certain inflammatory substances (including C-reactive protein and cytokines), and therefore low-cholesterol might lead to a more inflammatory state (which is not healthy).
One very interesting thing about this study was that it found that mortality across the groups was no different in individuals not treated with statins. What this suggests is that statins might be having a direct effect that is harmful to the hearts and health of individuals with heart failure.
If I was to hazards a guess as to what this might be, I’d suggest it could have something to do with the fact that statins are known to have the capacity to deplete the body of the substance Coenzyme Q10. Statins reduce cholesterol by inhibiting an enzyme in the liver known as ‘HMG-CoA reductase’ which ‘drives’ cholesterol production. But HMG-CoA reductase also facilitates the production of coenzyme Q10, which itself participates in the production of what is known as ‘adenosine triphosphate’ (ATP) – the most basic unit of energy ‘fuel’ in the body. In other words, Coenzyme Q10 is critical to energy production in the heart muscle and therefore heart function.
Taking statins has been proven to have the capacity to lower levels of CoQ10 in the body [2]. A while back, I came across a review of the evidence for statin-inducted CoQ10 depletion in both humans and animals [3]. Here’s what its authors had to say in their concluding remarks:
Statin-induced CoQ10 deficiency is completely preventable with supplemental CoQ10 with no adverse impact on the cholesterol lowering or anti-inflammatory properties of the statin drugs. We are currently in the midst of a congestive heart failure epidemic in the United States, the cause or causes of which are unclear. As physicians, it is our duty to be absolutely certain that we are not inadvertently doing harm to our patients by creating a wide-spread deficiency of a nutrient critically important for normal heart function.
And here’s the conclusion from the Cardiology study:
Low LDL-[cholesterol] levels are association with a reduced survival in elderly patients with clinically controlled moderate and severe [heart failure]. Statins were independently and significantly associated with a higher risk of mortality.
The underlying message here appears to be that in individuals with heart failure, statins are contraindicated. Some doctors may be aware of this, but others may need to be educated regarding this by their patients or patients’ carers.
References:
1. Charach G, et al. Low levels of low-density lipoprotein cholesterol: a negative predictor of survival in elderly patients with advanced heart failure. Cardiology 2014;127(1):45-50.
2. Passi S, et al. Statins lower plasma and lymphocyte ubiquinol/ubiquinone without affecting other antioxidants and PUFA. Biofactors 2003;18(1-4):113-24.
3. Langsjoen PH, et al. The clinical use of HMG CoA-reductase inhibitors and the associated depletion of coenzyme Q10. A review of animal and human publications. Biofactors 2003;18(1-4):101-11.
Excellent article. However I’d like to take issue with the “from a purely physiological perspective, the heart is essentially a bag of muscle”. This perspective stops at mechanics and biochemistry. It does not take into account electro-magnetism or signalling through pathways as yet not properly defined (connective tissue matrices, fluid state semiconductor effects, meridians etc..). I know I venture into “unchartered” territory and i know that notwithstanding my observation the point you are making in this article remains perfectly valid. I also understand that these “extra” perspectives are not mainstream. However some day we are going to accept that physics underlies chemistry and that in order to fully comprehend the physiological meaning of organs (and, yes, i use the word meaning very consciously to express purpose in function) we are going to have to take into account effects for which we currently do not have devices to measure 100% and for which we do not have the full scientific training or perspective to appreciate. Physiology remains more than mechanics and biochemistry. Nevertheless great article. I hope that doesn’t read like a back handed compliment. I honestly feel you do great work… A subject to discuss sometime…?
Great article and reply. And is the heart even a pump? (As an example, blood leaves the heart at the same speed it enters the heart.) Malcolm Kendrick, cardiologist, argues that low Heart Rate Variability (HRV) – beat-beat-beat without variation – is the best predictor of heart attack/sudden death. If the heart is communicating with trillions of cells in capillary beds at all times, greater beat-to-beat variability suggests the heart is less a mechanical pump and more a vital bio-electric communications hub for overall metabolism.
Just a repost in case anyone missed it when originally posted – it refers to the knowledge that Big Pharma had of the link between CoQ10 depletion and statins as long ago as 1989.
Nigel John 27 November 2009 at 8:05 pm #
Sorry Margaret salt has no effect on Cholesterol synthesis, and has very little impact if any on normal non-hypertensive patients.
Statins – I have been on Lipitor for nearly 10 years and gradual age related increase in chol levels were addressed last year by an increase to 40mg, as a runner (probably now just a jogger to be honest) I started suffering calf muscle pulls that crippled me for days and prevented running for a month at a time. Eventually I overcame my skepticism and ordered some 100mg CoQ10. Six months on and no further muscle pulls, so it might be circumstantial but I dare not stop! I found a patent application by Merck&Co filed in 1989 2 years before they launched Zocor (simvastatin) which was for simvastatin plus CoQ10 combination (application number 07/298535) indicating a concern at the time of their phase III trials!
To my understanding, statins works by decreasing the LDL and also the number of small LDL particles. It’s supposed to be the small particles that is bad for the heart and arteries.
Guess what, by eating a low carb diet with a high fat content, the number of small LDL particles decreases but not the large and healthy particles. Also the good HDL increases. The effect is thus twofold in the correct direction.
Supplementing with a good antioxidant will also decrease the number of small LDL particles and be good for heart disease without any ill effects. This should be the doctors choice instead of statins.
All other things being equal, if there is something of an age related trend to be witnessed in lipoprotein profiles, if levels of ‘cholesterol’ do indeed rise with age, and if pure cholesterol or other constituency of lipoproteins can be considered in some way anti-inflammatory then the age-related rise in cholesterol may be evidence of an adaptive, rather than maladaptive, eventuality.
Here’s a question for you Dr Briffa:
If we get a bad cold, influenza, or a bout of man-flu, we feel listless and deprived of energy. Very probably the response of certain white blood cells to an infection of this kind is to release an oxidative burst of reactive oxygen species (ROS, or ‘free radicals’) who are the first responders of the immune system tasked with impeding proliferation of the virus. It’s the action of white blood cells, releasing ROS as part of an oxidative burst and invoking inflammation that has us feel listless and depleted of energy and not the effect of the virus itself. So how does the process result in the effects we feel? Are the ROS making up the oxidative burst interfering with the action of CoQ10 or ATP in any way? Or does the red alert and general inflammatory response to an infection of this kind impede the legi timate mobility of metabolites to sites (cells) as a consequence of trying to impede. perhaps, mobility of the virus?
The thing about CoQ10 is that risks of congestive heart failure (CHF) rise as levels of CoQ10 fall, and it is generally uncontested that CoQ10 availability declines with ageing, so HMG-CoA reductase inhibitors that impede the natural biosynthesis of CoQ10 would raise the risks of CHF. However the rationale for prescribing HMG-CoA reductase inhibitors (statins) is that they impede the biosynthesis of cholesterol, alter the profiles (counts) of lipoproteins, and so (as conventions has it) decrease risks of atherogenesis.
For those of your readers who may not know ‘atherogenesis’ describes the process that is the formation of fatty or calciferous plaques in the endothelial layer of the arterial walls close to heart. Atherogenesis is the progressive side to coronary heart disease (CHD) that results in the plaques, ‘atheroscleroisis’ that convention says may eventually lead to heart attack or stroke. Hence according to convention the supposed (multiple) lifestyle and environmental risk factors for CHD must converge upon the process of atherogenesis.
As far back as 1974 Imai and colleagues established and reported that pure cholesterol is not all atherogenic, however oxidised cholesterols are. So if the natural and pure cholesterol circulating our bodies becomes subject to oxidative stress and is commuted to, and contaminated by, oxycholesterols then the altered behaviour of cells in, or in proximity to, the endothelial layer of the arterial wall then atherosclerosis is a growing risk. Cholestane triol is one of three possible variations upon oxycholesterols and it is branded with being the most potent atherogen among them.
Other than oxycholesterols one other biochmical that could get access close to the scene of the crime has been identified for its capacity to potentate atheogenesis; its homoscyteine. Homeocysteine looks to be the most potent oxidising agent capable of converting molecules of pure cholesterol to oxycholesterols including cholestane triol. Homocyteinme levels can rise under a number of circumstances, elevated or arrhythmic cortisol being one. this points to a notional causal axis involving cortisol, homocysteine, and oxycholesterol (CHO).
Oddly saturated fat and cholesterol do not really stack up as, or with, lifestyle, environmental, nor even the physiological risk factors for CHD. But there are several generally well accepted lifestyle and environmental risk factors that can be plausibly linked with the notion of the CHO-axis. Moreover, having cortisol placed in the causal chain that results in atherogenesis indicates some overlooked factors (at least two additional ones I know of) that can lead to arrhythmia in cortisol cycles and/or abnormal levels of cortisol persisting over time.
Here’s something Dr Kilmer McCully wrote on the topic some time back:
“Homocysteine catalyses oxidation of low-density lipoprotein in the presence of ferric ions in vitro. Cholestane triol is highly atherogenic cholesterol oxide that is produced by oxidation of low-density lipoprotein within the arterial wall. These and other observations led to the proposal of altered mitochondrial function in arteriosclerosis promoted by hyper-homocysteinemia” (elevated levels of homocysteine).
[Homocysteine and Vascular Disease (Developments in Cardiovascular Medicine) by Killian Robinson and K. Robinson (30 Apr 2000) ]
It kinda makes ya think. News can be slow to travel in the face of dogma and vested interests, eh?
Dear Christopher, I have a hypothesis that isn’t proved but might interest you.
It’s true that cholesterol level increases with age but why it increases seems not well known.
You might know that older peoples skin becomes less efficient at producing vitamin D from cholesterol with age. They also get low levels of vitamin D and my hypothesis is that the body simply up regulates the cholesterol level so more vitamin will be produced from UV light. However they do not stay long in the sun so it doesn’t really work as the body intended it to do.
There isn’t much real facts to support this hypothesis but I have found one study
that shows that supplementing D vitamin lowers the cholesterol level. Unfortunately it’s done in conjuction with statins so it is too weak in proving my point. Read about it here http://www.nature.com/clpt/journal/v85/n2/abs/clpt2008165a.html
If anyone has found a better study, please comment.
I’ve often wondered the same thing myself. And how it is all tied in with thyroid since low thyroid levels can also raise cholesterol.
This has been my experience a number of times with my patients. For example, at age 80, my mother-in-law was prescribed against my advice by her cardiologist a statin because she had, according to echocardiogram, suffered an MI. One year later, she was extremely short of breath and the cardiac echo showed a severe heart failure (less than 20% ejection fraction while her ejection fraction was normal at more than 50% one year before. Adding this to the severe myalgias she was suffering from, I stopped her statins and started her on Ubiquinol as per Dr Langsjoen’s suggestion. Myalgias have completely disappeared and she has no heart failure symptom anymore. Echocardiogram will confirm this soon. Big pharma is well aware of the myalgia and heart failure. They have a US patent combining CoQ10 and a statin, but decided not to put it on the market. Doing so would be the same as acknowledging what they have denied all along, that statin have major side effects in many, many people.
Pingo,
yes, as food for thought goes your hypothesis is excellent. I have wondered much the same. But there are confounding issues to bear in mind.
#1 much of the cholesterol in our bodies is biosynthesized in the liver, and enters circulation via lipoproteins.
#2 the majority of the cells of the body can synthesise cholesterol, and the brain has special cells called ‘glial’ cells tasked with this job
#3 the photosynthetic effect of ultraviolet light acting upon the skin converts cholesterol to vitamin D
#4 is the cholesterol that is destined to become vitamin D cholesterol that was synthesised in the liver and transported by the lipoproteins – or was produced by cells in proximity to the skin?
#5 the popular test for cholesterol, the lipid profile test, assess counts of lipoproteins, and does not measure cholesterol levels at all. As an indication of lipoprotein counts the lipid profile test is rudimentary and not at all sophisticated. lipoproteins get pigeon-holed into arbitrary groupings, and in reality they come in sizes that range in way that don’t conform to the discrete classifications. The lipid profile test is not a good measure or tool upon which to found a sound hypothesis.
#6 Lipoproteins convey a range of biochemical species, and its true cholesterol is a key constituent to be found in lipoproteins, but counts and profiles of counts, could be shifting for all manner of reasons.
#7 the lipid profile test, for all but the rarest instances is no more use than a chocolate fire-guard.
#8 despite the extensive grounds to say #7 there are professionals that will be deeply offended by the suggestion.
There are people who do not spend enough time in the sun, and in general ‘westerners’ do not get the kind of exposure that habituates them to the sun, and synthesis of vitamin D is challenged, leading to suboptimal levels of vitamin D, reason would have it.
Vitamin D is a powerful antioxidant that guards against corruption of DNA. I’d be more curious to wonder if vitamin D (or simply being out in the sun) can interfere with the atherogenic aspects of the cortisol-homocysteine-oxycholesterol (CHO) axis. Note B vitamin deficiency is the leading factor that accounts for the atherogenic risks of tied to homocysteine, as the present understanding has it.