10 Pitfalls of Using LDL Cholesterol to Assess Risk

Blood levels of low-density lipoprotein cholesterol (LDL-C), commonly termed the “bad cholesterol” are widely used to assess the risk of future heart disease.

A traditional lipid panel measures total cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-C). These numbers are then used to calculate LDL-C which has been found to be strongly correlated with the risk of cardiovascular disease (CVD).

10 Pitfalls of Using LDL Cholesterol to Assess Risk

 

For the past 25 years, LDL-C has been the primary lipid parameter for risk stratification and goal-directed therapy. Lifestyle measures to lower LDL-C are generally recommended, and statins (cholesterol-lowering drugs) are used by millions of healthy people worldwide in order lower LDL-C numbers.  Nonetheless, relying on LDL-C may be misleading.

Many individuals with high LDL-C have an excellent prognosis and low risk of CVD, while many with normal or low LDL-C may be at high risk. Furthermore, low levels of total cholesterol and LDL-C are often associated with an increased risk of death. Therefore, it is important to understand the pitfalls of LDL-C measurements in clinical practice. Indeed, scientific evidence suggests that the role of LDL-C as a risk factor may be overestimated.

1. LDL-C Is a Calculated Variable

LDL-C is a measure of the amount of cholesterol carried within low-density lipoprotein particles. However, LDL-C is a calculated number. LDL-C is usually not measured directly in blood. To be able to calculate LDL-C we need to know the total concentration of cholesterol in blood, triglyceride (TG) concentration and HDL-cholesterol (the “good cholesterol”).  By using the Friedewald formula we can get an estimate of LDL-C.

Here is how LDL-C is calculated:

If mg/dl is your unit, like in the United States the formula looks like this:

LDL-C = [Total cholesterol] – [HDL-cholesterol] – [TG]/5

If mmol/l is your unit like in Australia, Canada, and Europe the formula looks like this:

LDL-C= [Total cholesterol] – [HDL-cholesterol] – [TG]/2.2

The formula relies on the assumption that the ratio of triglyceride to cholesterol is constant, which is not always the case. Therefore, LDL-C calculations may have limitations when blood triglyceride levels are either high or low. For example, the Friedewald equation cannot be used if TG levels are above 400 mg/dL (4.52 mmol/L).

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2. The Association Between LDL-C and Mortality is Controversial

The relationship between measurements of total cholesterol and mortality was addressed in the Framingham Study. Under age 50, cholesterol levels were directly related to 30-year overall mortality and mortality from CVD. After age 50 there was no increased overall mortality with either high or low serum cholesterol levels. It was proposed that after age 50 the association of mortality with cholesterol values is confounded by people whose cholesterol levels are falling, perhaps due to diseases predisposing to death.

Serum cholesterol is generally considered a strong predictor of coronary heart disease and all-cause mortality in middle-aged populations. Data from the MRFIT trial showed increased overall mortality among men in the top 10-15% cholesterol levels. Among the other 85 percent, the difference in mortality was very small when those with high and low levels were compared, although mortality seemed to increase in a linear fashion with elevated LDL-C levels.

However, those with the lowest cholesterol levels had an increased mortality. The J-shaped curve is typical when describing the association between cholesterol levels and overall mortality. When it comes to total mortality, some data indicate that optimal levels of serum cholesterol may be between 210 and 230 mg/dl (5.4 and 5.9 mmol/l).

10 Pitfalls of Using LDL Cholesterol to Assess Risk
When it comes to total mortality, some data indicate that optimal levels of serum cholesterol may be between 210 and 230 mg/dL (5.4 and 5.9 mmol/L)

A large Italian study published 2005 showed that the risk of total mortality in women and fatal heart failure in both sexes decreased with higher LDL-C. Nonetheless, higher LDL-C levels were associated with an increased risk of heart attack (myocardial infarction).

The association between blood cholesterol and mortality was also studied among middle-aged and elderly individuals in the Honolulu Heart Program. The study results indicate that lower cholesterol levels are associated with increased mortality.

The authors concluded that their results lent support to previous findings that low serum cholesterol imparts a poor outlook when compared with higher concentrations of cholesterol in elderly people. Their data also suggested that those individuals with a low serum cholesterol maintained over a 20-year period had the worst outlook for all-cause mortality

A Norwegian study found an inverse relationship between cholesterol levels and mortality among women, for whom (according to the authors) moderately elevated cholesterol (by current standards) may prove to be not only harmless but even beneficial.

Thus, although high LDL-C may be associated with increased risk of heart disease, low levels are associated with increased risk of death. Among elderly individuals there appears to be an inverse relationship between cholesterol levels and mortality, indicating that high cholesterol levels are protective or reflect better health. Furthermore, the relationship between cholesterol levels and disease may be different for men and women.

3. Lifestyle Measures that Lower LDL-C Have Not Been Shown to Cut Risk

The largest controlled intervention trial on diet and heart disease to date, the Women’s Health Initiative randomly assigned more than 48 thousand women, 50 – 79 years old, to a low-fat intervention or a comparison group.

Saturated fat intake was lower in the intervention group as was dietary polyunsaturated fat. Dietary carbohydrates were higher in the intervention group.

LDL-C was significantly lowered in the intervention group compared to the comparison group. Nonetheless, after six years of follow-up, there were no differences between the groups in the incidence of coronary heart disease and stroke.

The MRFIT trial evaluated 12,866 high-risk middle-aged men who were randomly assigned either to a special intervention program consisting of stepped-care treatment for high blood pressure, counseling for cigarette smoking, and dietary advice for lowering blood cholesterol levels or to their usual sources of health care in the community. LDL-C was significantly lowered in the special intervention group compared to the “usual care” group. However, during a follow-up of seven years, there was no significant difference in total death rates between the groups and no differences in the number of deaths from heart disease.

The results of these two large trials strongly indicate that lifestyle measures aimed at lowering LDL-C do not improve survival or reduce mortality from CVD. Therefore, one has to wonder why such lifestyle measures are generally recommended by public health authorities.

4. LDL-C Can Underestimate Risk in People With the Metabolic Syndrome

An epidemic of obesity and metabolic syndrome has evolved in many countries over the past few decades, mostly due to changes in diet and lifestyle. Approximately one-third of U.S. adults currently suffer from metabolic syndrome.

Individuals with metabolic syndrome, overweight or obesity often have a lipid profile with elevated triglyceride-rich remnant lipoproteins, characteristic of insulin resistance.

These lipoproteins include very-low-density lipoproteins (VLDL) and their remnants, intermediate-density lipoproteins, and chylomicron remnant particles.

This lipid profile is much better accounted for by measuring non–HDL Cholesterol than LDL-C. Indeed, relying on LDL-C to assess risk in these individuals may be misleading and could underestimate risk. Furthermore, recommendations or treatment aimed at lowering LDL-C may not be the best therapeutic option under these circumstances. Measures aimed at reducing insulin resistance, lowering triglycerides and elevating HDL cholesterol could be more important.

5. LDL-C Does Not Reflect the Concentration of Atherogenic Particles

It is important to emphasize, that it is lipoprotein that interacts with the arterial wall and starts the cascade of events that leads to atherosclerosis. Cholesterol is only one of many components of lipoproteins.  Therefore, measurements of total cholesterol are only indirect measurements of the lipoproteins that transport the bulk of cholesterol. Indeed, measurements of the number of LDL-particles (LDL-P) seem more predictive of risk than the measurements of the cholesterol mass within these particles, reflected by LDL-C.

Due to the fact that LDL-C has traditionally been used for so many years to reflect the number of LDL particles, LDL-C and LDL have become almost synonymous. This is quite misleading because the cholesterol content of LDL particles varies greatly. Thus, LDL-C is a surrogate measure that only provides an estimate of LDL levels. Studies indicate that the risk for atherosclerosis is more related to the number or concentration of LDL-particles than the total amount of cholesterol within these particles.

6. LDL-C Does Not Reflect LDL Particle Size

It has been known for a couple of decades that the size of LDL particles may influence the risk of atherosclerosis. Studies suggest that small, dense LDL doesn’t travel alone, it typically comes along with low HDL-C and high triglycerides. This pattern has been called “lipoprotein pattern B”. Its opposite is “lipoprotein pattern A” where LDL particles are large, HDL-C often high and triglycerides low.

Interestingly, studies have shown that diets rich in saturated fat seem to increase LDL-particle size. Therefore, in theory, such diets could improve the lipid profile of individuals with small, dense LDL particles which is often associated with the metabolic syndrome. However, public health guidelines generally recommend avoidance of saturated fats as the may elevate LDL-C.

10 Pitfalls of Using LDL Cholesterol to Assess Risk
Almost half of patients admitted to hospital for coronary artery disease in the U.S. don’t have elevated LDL cholesterol
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7. A Large Proportion of Patients with Coronary Artery Disease Don’t Have Elevated LDL-C

An often cited study published in 2009 reported lipid measurements among 232.000 patients with coronary artery disease admitted to hospitals in the U.S. between 2000 and 2006. Almost half of these individuals had LDL-C levels less than 100 mg/dl (2.6 mmol/l) which is relatively low. However, almost 55 percent of these patients had very low levels of HDL-C (less than 40 mg/dl or 1.0 mmol/l).

The study is a reminder that low LDL-C according to current definitions does not prevent coronary artery disease. Although some scientists claim that further lowering is needed, this has still not been proven.

The current evidence, therefore, indicates that when it comes to lipids and cardiovascular prevention, relying on LDL-C is an oversimplification and will not solve any problems in the long run. Many other factors have to be taken into account. Overemphasizing the role of LDL-C in order to increase the use of statin drugs is misleading and has to stop.

8. Statin Drugs May Work Through Other Mechanisms than Lowering LDL-C

The Jupiter trial suggested that treatment with statins (cholesterol-lowering drugs) may have beneficial effects among people with relatively low levels of LDL-C. The individuals who participated in this trial all had elevated levels of hs-CRP which is a marker of inflammation.

The study raises the question whether cholesterol-lowering is only a byproduct, and whether the efficacy of statins is mediated through other mechanisms, such as reducing inflammation.

Statins are potent inhibitors of cholesterol biosynthesis. They are effective in secondary prevention of individuals with CVD. However, the overall benefits observed with statins appear to be greater than what might be expected from changes in lipid levels alone, suggesting effects beyond cholesterol lowering.

Indeed, recent studies indicate that some of the cholesterol-independent or “pleiotropic” effects of statins involve improving endothelial function, enhancing the stability of atherosclerotic plaques, decreasing oxidative stress and inflammation, and inhibiting blood clotting mechanisms.

9. Modern Risk Calculators Don’t Rely on LDL-C when Assessing Cardiovascular Risk

The new cardiovascular risk calculator provided by the American Heart Association (AHA) and The American College of Cardiology (ACC) does not rely on LDL-C when assessing the risk of CVD. The only lipid parameters the calculator uses when assessing risk are total cholesterol and HDL cholesterol.

However, the new AHA and ACC guidelines still believe that LDL-C is an important marker of risk. The guidelines recommend that all individuals with LDL-C above 190 mg/dL (4.9 mmol/L) should receive treatment with statin drugs.

10. It’s Unlikely that LDL-C Is Always Bad and Never Good

Low-density lipoprotein plays an important biologic role. It’s a carrier of different lipid molecules that are essential for many cells and tissues of the body, among these, are cholesterol and triglycerides.

Cholesterol plays an important role in cell membranes and it’s essential for the production of many hormones in our body. However, we don’t have to get cholesterol from the food we eat because the body is able to produce it. Cholesterol is mainly produced by liver cells.

The fact that cholesterol is an important substance for our body does not necessarily imply that it can’t be afflicted with atherosclerosis and heart disease.

In animal models, atherosclerosis does not occur in the absence of greatly elevated blood cholesterol.

Heart attacks have been shown to be uncommon in humans with very low LDL-C due to a sequence variation in the PCSK9 gene.

In cell cultures, according to Nobel prize winners Brown and Goldstein, cellular needs for cholesterol can be met with an LDL-C level of 25 mg/dl (0.65 mmol/L) which is very low.

Human newborns have an LDL-C in the range of 40-50 mg/dl (1.1-1.3 mmol/L). Healthy adult levels are 3-4 times higher.

The normal LDL cholesterol range is 50 to 70 mg/dl (1.3-1.5 mmol/L) for native hunter-gatherers, 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-C is lowered to <70 mg/dl (1.8 mmol/L). No major safety concerns have surfaced in studies that lowered LDL-C to the range of 50 to 70 mg/dl.

So, there is a lot of evidence suggesting that lowering LDL-C may be helpful and will not cause harm. However, we can’t ignore the fact the low-density lipoprotein, and the lipid molecules it carries play an important role in bodily function. Therefore, although lowering LDL-C may reduce the risk of heart disease, it may, in theory, have harmful effects, many of which may not yet be fully understood.

We know that statins have side effects, among them are muscle disorders, increased risk of diabetes and negative effects on cognitive function. This is not surprising because these drugs affect a biologic pathway that important for cells and tissues in our body. It would be naive to believe that such mechanisms can be blocked by chemicals without causing any harm.

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Hilary
Hilary
6 years ago

Hi Doc! Thanks for this interesting post. So it seems that a lowered LDL-P is a good thing, along side a higher HDL, lower triglycerides, and low dense LDL. Can you possibly advise us of your thoughts regarding the best diet and health-generating lifestyle strategies for us to focus on to achieve this without taking statins or other drugs (assuming no prior history of CVD or atherosclerosis)?

Doc's Opinion
Admin
Doc's Opinion
6 years ago
Reply to  Hilary

Hilary. This is not an easy task. It may depend on the individual. If you are dealing with obesity or the metabolic syndrome I’m generally in favor of carbohydrate restriction. Here are some general tips: Avoid refined and added sugars Avoid sweets and sugared beverages Eat vegetables every day, preferably few times a day Eat fruit (in moderation though if you’re trying to restrict carbs) Avoid refined foods in general Cook your own food and choose your ingredients wisely Avoid trans fats Eat red meat, animal and dairy fats in moderation (unless you´re restricting carbs) Eat fish at least a… Read more »

David Brown
6 years ago
Reply to  Doc's Opinion

I suggest you add “Avoid omega-6 vegetable oils” to your tips list. Quote from page 191 of “The Modern Nutritional Diseases: and How to Prevent Them” by Fred and Alice Ottoboni. “BIOCHEMICAL LESSON: The significant point is that good health depends on regulating the D5D enzyme. High insulin levels due to dietary sugar and starch and high dietary omega-6 to omega-3 ratios, stimulate the D5D enzyme, and move the biochemical set point from normal toward inflammation. On the other hand, control of dietary sugar and starch, reduction of LA in the diet, and a daily supplement of fish oil to… Read more »

Hilary
Hilary
6 years ago
Reply to  Doc's Opinion

Hi Doc, great!! Thanks so much!! I really appreciate your time in responding so succinctly, and also for your knowledge and consideration of such a wide range of evidence. I am in good health and follow most of your principles already and am not overweight. This does take willpower and commitment in a world full of temptation!! However I do have some digestive and absorption issues. I read widely about general wellness, nutrition and supplementation and biochemistry (lately discovering methylation and gene activation) and I find it all fascinating even though it is difficult to determine what might be real… Read more »

Doc's Opinion
Admin
Doc's Opinion
6 years ago
Reply to  Hilary

Thanks Hilary. Appreciate your interest in my blog and hope you continue visiting.

Richard
Richard
6 years ago

Doc, where’s the controversy? LDL/TC is hardly alone, the predictive effect of nearly every single biomarker is confounded at later stages of life. Blood-pressure, BM, etc all show J-shaped curve in regards to total mortality. My own grandmother recently died to lung-cancer, the cancer wasn’t diagnosed until she was admitted to acute ward few days prior to her death. She was nearly anorectic the last ten years with very low cholesterol and blood-pressure (and obviously BMI). If only your scope would include even a tiny bit of global epidemiology, you’d see there’s not really much controversy out there. Elderly people… Read more »

Doc's Opinion
Admin
Doc's Opinion
6 years ago
Reply to  Richard

Richard. You cite some studies indicating an association between total cholesterol and mortality. I cited other studies that don’t support such an association. Then you ask: “Where’s the controversy?” Of course there is no controversy if you only look at the data that support your opinion. You refer to The Helsinki Businessmen Study. These were all men with relatively high cholesterol numbers. In fact, very few had total cholesterol lower than 155 mg/dL (4.0 mmol/l). By not including individuals with low cholesterol levels you will of course miss the J-shape of the curve. If the study had included individuals with… Read more »

Richard
Richard
6 years ago
Reply to  Doc's Opinion

Doc, there’s controversy once you pay attention to quality of the study. You enunciate that science is a some sort of show of hands or a democracy where every study has an equal value. I already mentioned the shortcomings of the Norwegian study. The Helsinki study is superior in every meaningful way, huge 46-year follow-up, quality control of the data, exclusion of people on statins and chronic disease. Nothing even close to this was achieved in the Norwegian paper, which was basically just a show of number crunching. What do you mean, there were no people with low-cholesterol in the… Read more »

Doc's Opinion
Admin
Doc's Opinion
6 years ago
Reply to  Richard

Richard. This is a quote from the Heslinki study publication where the authors discuss the limitations of their study: “Only one measured baseline serum cholesterol value was available, and the proportion of men with very low cholesterol levels (≤4 mmol/L, 154 mg/dl) at baseline was quite small (n = 22), because high cholesterol values were very common in Finland in the 1960s.” So, indeeed very few had low cholesterol levels. Your statement is interesting: “The association of low cholesterol at mid-life and decreased risk for dementia is most likely causal, whereas the link between low cholesterol at later stages of… Read more »

Richard
Richard
6 years ago
Reply to  Doc's Opinion

Thanks, Doc for sorting this out. There are limits with the Helsinki study, but the conclusions should be easy for us to accept. Those with famial hypobetalipoprotenemia usually have their life-long LDLs around 10-40mg/dl and live around 15 years more than their peers. The conclusion I made in regards to dementia, is a result of a careful line of thought. Do you suggest that low cholesterol levels cause dementia? I suggest that low cholesterol levels protect from dementia and other form of vascular disease. What about your optimal cholesterol levels indicated by your favorite studies; should we ask Okinawa islanders… Read more »

charles grashow
charles grashow
6 years ago

https://www.nytimes.com/2012/05/17/health/research/hdl-good-cholesterol-found-not-to-cut-heart-risk.html?_r=0 Now, a new study that makes use of powerful databases of genetic information has found that raising HDL levels may not make any difference to heart disease risk. People who inherit genes that give them naturally higher HDL levels throughout life have no less heart disease than those who inherit genes that give them slightly lower levels. If HDL were protective, those with genes causing higher levels should have had less heart disease. Researchers not associated with the study, published online Wednesday in The Lancet, found the results compelling and disturbing. Companies are actively developing and testing drugs that… Read more »

Doc's Opinion
Admin
Doc's Opinion
6 years ago

Thanks for the comment Charles. I often reject such lengthy “copy/pasting comments”. People usually don´t read them, unless it´s summarized into a clear message. Did you have a specific message you wanted to bring forward? I would prefer that, rather than such a pile of information.

Richard
Richard
6 years ago

Doc, it seems to me that you are not willing to accept the LDL theory because it does not cope well with your predetermined idea’s of multi-faceted nature of CHD. That’s the feeling I get. Although, I’d like hear your take on this. However, you must at least acknowledge that the truth can be very simple, this is one possibility, after all. If you look at the Norwegian study in a bit more detailed manner, you’d understand that the authors did not exercise any kind of quality control over their data, no exclusion of people on statins or other chronic… Read more »

Doc's Opinion
Admin
Doc's Opinion
6 years ago
Reply to  Richard

Again Richard: The main focus of my article was to highlight some important issues that have to be kept in mind when using LDL-C for risk assessment. I was not saying that LDL-C is useless. However, clinicians and people in general should know the limitations of using this measure to assess risk and guide therapy. You´re right. I believe there is more to atherosclerosis and coronary heart disease than cholesterol. It seems that whatever I write you jump up in defense of the cholesterol hypothesis. I was not rejecting it with this particular post. You can’t go on like this… Read more »

bob
bob
6 years ago
Reply to  Richard

Egad, there’s so much wrong with what you’re saying it’s hard to know where to being. For one, we’re not monkeys. Thus, a study with monkeys pretty much has little relevance to humans. Two, if it were “easy” to determine that “mutagenic cholesterol elevating animal foods” (which are what, by the way?) are “behind” coronary disease, then there wouldn’t be literally hundreds of studies that disagree with this notion. See, for instance, this one: https://chriskresser.com/new-study-puts-final-nail-in-the-saturated-fat-causes-heart-disease-coffin Now, that’s a meta-analysis, but there are many others (including Mrfit, as one of the “risk factors” was fat intake, and the Women’s Health Initiative,… Read more »

FrankG
FrankG
6 years ago

Nicely balanced piece. Thanks Dr. Sigurdsson. Such open-mindedness on this topic, by a practicing Cardiologist is encouraging. Shame that any talk of “cholesterol” inevitably seems to lead to an outpouring of verbal diarrhoea from vegan trolls — perhaps I can recommend a good herbicide? 😛 Great that you emphasised the key differences between LDL and LDL-C. It seems that too many try to “dumb it down” so as to obscure the reality of the situation — makes me suspicious of their motivation; when there is so much financial gain at stake, in the marketing of drugs which specifically lower LDL-C… Read more »

Doc's Opinion
Admin
Doc's Opinion
6 years ago
Reply to  FrankG

Thanks for the comment Frank.

You´re right. LDL-C is not included when defining the metabolic syndrome. Only triglycerides and HDL-C are This indeed reflects the fact that LDL-C is not the main issue in this situation. As pointed out in my paper, today one third of U.S adults suffer from the metabolic syndrome. One more reason to stop overemphasizing LDL-C 🙂

Richard
Richard
6 years ago

Doc, BTW, thanks for sharing this link; very useful, great material. Lipoprotein Management in Patients With Cardiometabolic Risk Consensus statement from the American Diabetes Association and the American College of Cardiology Foundation “The dramatic success of cholesterol-lowering therapy might suggest that low cholesterol levels would be all that is required to prevent the development of atherosclerotic disease or halt or reverse established disease. This might be true if plasma cholesterol concentration could be reduced to very low levels long before the usual time of development of clinical disease” “Experimental studies directly support the central role of LDL in atherogenesis. Current… Read more »

charles grashow
charles grashow
6 years ago

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1906578/ I then learned the major differences between carnivores and herbivores, and humans clearly come down on the herbivore side. The teeth of carnivores are sharp and those of herbivores, more flat; the intestinal tract of carnivores is short (about 3 times body length), whereas that of herbivores is long (about 12 times body length); carnivores cool their bodies by panting, herbivores, who can also pant, do so mainly by sweating (carnivores cannot sweat); carnivores lap their fluids, herbivores sip them; carnivores make their own vitamin C, herbivores obtain that vitamin only from their diet. Brown and Goldstein in the… Read more »

Doc's Opinion
Admin
Doc's Opinion
6 years ago

Charles. I appreciate your comments, but I can´t continue to accept this type of lengthy copy/pasting comments. You even include the reference numbers from the articles you’re copying. Please 🙁

Charles Grashow
Charles Grashow
6 years ago
Reply to  Doc's Opinion

I don’t understand your comment. I attach the link to the whole article and paste in the necessary portions. Your statement – ” I often reject such lengthy “copy/pasting comments”. People usually don´t read them, unless it´s summarized into a clear message. Did you have a specific message you wanted to bring forward? I would prefer that, rather than such a pile of information.” Are you saying that your readers are lazy? Are piles of information that much of a burden for them to read? Okay – here’s my “clear message” – I believe that the preponderance of evidence supports… Read more »

Doc's Opinion
Admin
Doc's Opinion
6 years ago

That’s great Charles. This lipid profile should be associated with a very low risk of cardiovascular disease.

Richard
Richard
6 years ago
Reply to  Doc's Opinion

Bill Roberts is the editor in chief of American Journal of Cardiology; he is in his 80s, seems to be great health, still groin’ strong and working full-days. He spoke recently at McDougall Program and seems to fully in the plant-based bandwagon. Doc needs to read his landmark review: The Cause of Atherosclerosis https://ncp.sagepub.com/content/23/5/464.extract Every single top-notch atherosclerotic expert I’ve communicated seems to believe we need to keep LDL as low as possible, and get it down to the floor very quickly. I recently talked about this with young PhD student in vascular chemistry. “It’s the cholesterol stupid”. Many of… Read more »

Doc's Opinion
Admin
Doc's Opinion
6 years ago
Reply to  Richard

Richard. Dr. Roberts starts his lanmark review you cited with these words: “Most physicians, I believe, consider atherosclerosis to be a multifactorial disease, and the greater the number of atherosclerotic risks factors present, the greater the chance of having an atherosclerotic event. I am in the minority in believing atherosclerosis to be a unifactorial disease, the result of abnormal serum or plasma cholesterol levels.” Dr. Roberts obviously considers himself to belong to the minority of experts that don’t believe that atherosclerosis is a multifactorial disease. So, according to him, the Doc’s there with the majority. By the way, Icelanders are… Read more »

Charles GRashow
Charles GRashow
6 years ago
Reply to  Doc's Opinion

@Doc What are your thoughts on Dr William Davis (Wheat Belly)? In his book Track Your Plaque he lays out this https://pi-bill-articles.blogspot.com/2011/03/track-your-plaque-program-by-william.html Track Your Plaque Program Details – Attain the Following Targets: a) Reduction of LDL to 60 mg/dl (LDL should be measured directly, not calculated) b) Reduction of triglycerides to 60 mg/dl. c) Raising HDL to 60 mg/dl. d) Correction of hidden causes of plaque on Lipoprotein profile such as total number of small LDL particles, IDL, and Lp(a). e) Achieving normal blood pressure (<130/80)  Even a small elevation of blood pressure in diseased arteries can cause increased mortality. … Read more »

Doc's Opinion
Admin
Doc's Opinion
6 years ago

Charles. I haven’t read Wheat Belly. I’ve given it a try a couple of times but somehow the book didn’t appeal to me. I’m planning on giving it another go.

I’m a bit skeptical about serial CAT scans to assess coronary calcium score. I don’t know of any scientific studies favoring such an approach. The targets are interesting. However, probably very difficult to reduce LDL-C to 60 mg/dl and at the same time elevate HDL-C to 60 mg/dl. A lipid profile where HDL-C is higher than LDL-C is difficult to attain.

DN
DN
3 years ago
Reply to  Doc's Opinion

I realize this post is a bit old however I just recently found it :)…Doc, I’m just curious if you could elaborate on the reasons for skepticism on CAT scan/coronary calcium score. Many thanks, great blog!!!

Axel F Sigurdsson
Axel F Sigurdsson
3 years ago
Reply to  DN

Hi DN. I think what I meant to say was that I’m sceptical about using CCS as a screening tool for everybody. However, I think it can be very helpful as an additional tool when needed.

Charles GRashow
Charles GRashow
6 years ago
Reply to  Doc's Opinion

Dr Roberts also says

” If dyslipidemia is present, then systemic hypertension, diabetes mellitus, cigarette smoking, inactivity, and excessive body weight increase the likelihood of an atherosclerotic event, but none of them in and of themselves is required for severe atherosclerosis to occur. In contrast, atherosclerosis does not occur if dyslipidemia is not present, irrespective of the blood pressure level, blood glucose level, the degree of obesity, the degree of activity, or the number of cigarettes smoked daily.

Jennifer
Jennifer
6 years ago

I thought the ‘humans as herbivores hypothesis’ was pretty neatly debunked by the relative belly sizes of primates versus humans. If we were indeed built to eat only vegetable matter then we would have a much larger gut designed to break down all of that woodsy material. We also need the nutrients that animals provide. Though I do have much respect for anyone who chooses to eschew meat for moral reasons.

JeffryGerberMD
6 years ago

Dr. Axel – thanks for pointing out that the new primary prevention risk calculator is using a better tool to predict risk: non-HDL-C instead of LDL-C. However, the new calculator recommends that more than twice as many should take statins based on a new lower 10 year risk threshold: >7.5% vs >20%, yuk! On what basis has the threshold been lowered? Look more like speculation!

Doc's Opinion
Admin
Doc's Opinion
6 years ago
Reply to  JeffryGerberMD

I agree Jeff. I don’t really know why they chose 7.5%. It’s almost like an arbitrary decision. Interestingly, age counts very strongly as a risk factor. So if you feed the calculator with very healthy numbers, average blood pressure and no other risk factors, all men will reach 7.5% risk at age 58 and all women at age 70. So according to the guidelines, all healthy men 58 years and older, and all women 70 years and older should be offered statins, nonwithstanding
other risk factors.

JeffryGerberMD
6 years ago
Reply to  Doc's Opinion

Dr Axel; I exchanged emails today with Dr. Donald M Lloyd-Jones the principle who worked on the CV risk calculator. Based on primary prevention trials, they pushed the primary prevention treatment threshold down as low as possible to 7.5% while keeping diabetes risk as low as possible. With an even lower threshold like 5% the diabetes risk went up. This is explained in the guidelines section 4.6, but it was not obvious to me. https://circ.ahajournals.org/content/early/2013/11/11/01.cir.0000437738.63853.7a/ At least the panel believes that a 1-2% absolute risk reduction is enough to warrant such prolific use of statins for primary prevention.

Doc's Opinion
Admin
Doc's Opinion
6 years ago
Reply to  JeffryGerberMD

Thanks Jeff. That’s very interesting. I still believe that 1-2% absolute risk reduction is very low considering treatment with potential side effects. If you look at it from a different angle (assuming your risk of cardiovascular event is 8% over ten years), the likelihood of not having a cardiovascular event in the next ten years will be 92% if you don´t take statins, but 93-94% if you take statins. That´s not a huge difference.

JeffryGerberMD
6 years ago
Reply to  Doc's Opinion

Many are questioning the role of statins for primary prevention!

charles grashow
charles grashow
6 years ago

Getting More People on Statins William Clifford Roberts, MD Editor in Chief Baylor Heart & Vascular Institute Baylor University Medical Center Dallas, Texas “But what serum cholesterol numbers are necessary to prevent atherosclerotic plaques from forming. The evidence is substantial that if over decades the serum total cholesterol is <150 mg/dl, the LDL cholesterol <100mg/dl, and the high-density lipoprotein (HDL) cholesterol 〉20 mg/dl, the chances of forming atherosclerotic plaques are slim. (I realize that many readers will be shocked by the mention of an HDL-cholesterol of only 〉20 mg/dl. But this number is only when the total cholesterol is <150… Read more »

Richard
Richard
6 years ago

BTW, Doc.

The American Association of Clinical Endocrinologists decided not to promote these new guidelines by AHH/ACC. National Lipid Association withdrew their support already at the initial stage.
https://login.medscape.com/login/sso/getlogin?urlCache=aHR0cDovL3d3dy5tZWRzY2FwZS5jb20vdmlld2FydGljbGUvODE3ODEw&ac=401

It seems that every single lipid expert knows that lower the LDL, the better and quicker the better.

Anyways, pay attention to the new report by AHA/ACC, they set the upper limit for SFA at 5-7%.

FrankG
FrankG
6 years ago
Reply to  Richard

So, in short we should ignore these new guidelines by AHH/ACC because the “National Lipid Association withdrew their support already”

BUT simultaneously, we should pay attention to these new guidelines by AHH/ACC because they set an upper limit for SFA?

Not to mention that humans — who apparently are herbivores (I can’t help but wonder what my ice-age European ancestors would have to say about that) — are all suffering from an acute shortage of statins!

Every single lipid expert…? Every, single one… ALL of them… seriously?!?

LOL 😛

Is it any wonder that your comments lack credibility?

FrankG
FrankG
6 years ago
Reply to  Richard

And who exactly is the National Lipid Association and why should we listen to them anyway? With their next “Clinical Lipid Update”, Spring 2014 in Maui Hawaii..! Book soon for the early bird special prices! Are they yet another self-appointed group of people with (I suspect) strong ties to the pharmaceutical industry like the NCEP – ATP III Committee? ATP III Update 2004: Financial Disclosure of NCEP members… https://www.nhlbi.nih.gov/guidelines/cholesterol/atp3upd04_disclose.htm Out of the eight member (self-selected) committee, there were seventy two potential financial conflicts of interest… “Imagine if eight Supreme Court judges, ruling on any issue, had seventy two direct financial… Read more »

Norma Gallagher
6 years ago

Your total cholesterol level is in the Desirable range, but your level of “bad” LDL cholesterol is borderline high. If your LDL goes higher, your total cholesterol level could become Borderline High. Consider reducing the amount of foods you eat with saturated fats and increasing physical activity. If you get more exercise, your level of “good” HDL cholesterol may increase, which could also help to keep your levels of LDL and total cholesterol in check.

battaggia
battaggia
6 years ago

Dear collegue, I agree with Your position. The theory “lower is better” is founded on the Cholesterol Treatment Trialists’ Collaborators work [1] : the results of their individual-data meta-analysies suffer nevertheless for several methodological pitfalls [2] and the parallel “dogma” of the LDL-Cholesterol targets [3] is moreover founded only on illustrious opinions with lack of any experimental evidence (=RCTs results based) regard the effectiveness of a certain “cholesterol target” about mayor cardiovascular end-points . In fact the most cited RCTs [4,5,6,7] from supporters of the “target theory” randomised drugs, not targets of LDL-CL, so that the dogma consists on a… Read more »

Flavor Seeker
6 years ago

Good Morning! I just stumbled across your blog and love it. I really enjoy your take on the whole fat and nutrition thing. So hard these days to determine what is the best way to navigate it all. I have moved to a more low carb high fat way of eating…just because that is what makes me feel good, I am the leanest/fittest I have ever been…However since trending this way my lipid profile has changed considerable and all though I read all the blogs that assure me this is ok, I am still of the non fat generation so… Read more »

Axel F Sigurdsson
Admin
Axel F Sigurdsson
6 years ago
Reply to  Flavor Seeker

@ Flavor Seeker Thanks for the comment and the kind words. Elevation of total cholesterol and LDL-cholesterol together with elevation of HDL-cholesterol is quite common on a low carb high fat diet. However, not all people respond in this way. Some experts believe this is nothing to worry about, partly because Triglyceride/HDL ratio improves together with many other metabolic abnormalities (such as insulin resistance for example). However, nobody knows whether LDL-cholesterol can be ignored under these circumstances. I usually recommend my patients to lower the intake of saturated fat (like the full fat dairy products in your case) under these… Read more »

Flavor Seeker
6 years ago

thank you!! I got the remaining results that make me feel a little better but I have switched from full fat yogurt to low fat..not sure I can give up my eggs though :0) Will see if this lowers my LDL-C.

The lipid subclass tests came back showing that I have more of the type a LDL( large buoyant) then the type B (dense) LDL.

My high-sensitivity CRP (marker of inflammation blood vessels)is still low at 0.3 (normal less than 1.0) and my homocystine level came back normal.

JustMEinT Musings
5 years ago

Always find your articles stimulating Axel
Have you seen???
https://www.sciencedaily.com/releases/2014/09/140904121247.htm

Axel F Sigurdsson
Admin
Axel F Sigurdsson
5 years ago

That’s interesting. Confirms that there is so much we don’t really know yet.

Georgianna Auzenne
Georgianna Auzenne
5 years ago

i just took my hdl test and it not good 49mg/dl. What do I need to do to raise it?

Axel F Sigurdsson
Admin
Axel F Sigurdsson
5 years ago

Georgianna
Take a look at my article on HDL cholesterol here.

Cal Chin
Cal Chin
5 years ago

Hi Dr Axel, I just turned 40. Height 1.78m 79kg. No family history of heart disease, At least one hour of exercise a day (mountain biking, martial arts, resistance training). In general good health. Diet is mainly low carb, high protein, and high fats (grass fed beef, grass fed butter, coconut and MCT oil) As an army reservist, I just went for my annual standard Lipid panel test: mmoL/L mg/dl Total Cholesterol 7.68 296.98 HDL Cholesterol 1.79 69.21 LDL-Cholesterol 5.25 203.01 Triglycerides 1.4 124.00 Cholesterol/ HDL ratio 4.29 Diabetes Mellitus profile: (Glucose fasting)- 5.1 mmol/L The attending doctor immediately downgraded… Read more »

pauljmey
pauljmey
4 years ago

Great post. I did want to comment on one thing. I think it would be more accurate to say the AHA calculator doesn’t rely solely on LDL-C. That said, using TC is even more questionable perhaps than using LDL-C in isolation since it adds together a score than you want to maximize (HDL) with one that should be minimized (triglycerides) with LCL-C (which may be low impact or inconsequential). It seems kind of crazy.

Matt
Matt
4 years ago

50 year old male; non-smoker
Family History: father had stroke due to A-Fib; mother has high blood pressure and CVD; CVD in grandparents on both sides
BP averages 125/70
Lift heavy 4 days per week; run 3 miles three times per week
5’7″ and 160lbs with a good bit of muscle
Total Cholesterol: 188
HDL: 48
LDL: 124
LDL-P: 1653
HDL-P: 32.3
Small LDL-P: 790
LDL Size: 20.9
Trig: 80
HDL Size: 8.7
LP-IR Score: 52
H1C always runs just under 6

Do I need a statin? If so, which one targets LDL-P?

lucy bakers
lucy bakers
2 years ago

Hi, I had a hemmoragic stroke. This was so tough for me because i never imagined myself in this way. I lost my speech and i was obviously useless because i could not perform any activity without any support, i could not walk, i use dto enjoy driving but none of this i could do again. I was totally paralyzed. The worst part was the emotional aspect of it. I cry very easily and have no control over it because all the doctors or physiotherapist iA met were not helpful at all. I am, however, very lucky that i was… Read more »

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