Functional Health Services for Your Well Being

A Tale of Three Lipid Panels

by Alex Boersma

I get questions all the time about blood work. Invariably these questions arise after a friend or client has been advised by their doctor that their LDL cholesterol is too high and that perhaps they should entertain the idea of going on a statin.  Invariably I ask what their HDL and triglyceride levels are.  Invariably they don’t know.

Now don’t get me wrong.  I’m not against statins.  Ok, well, maybe just a little bit.  No, really, I do believe that statins have a role to play for people with established heart disease.  You know, people who have actually had a heart attack!  What I am against is the indiscriminate prescription of statins in situations where their efficacy has not been established or where their benefit is so minimal that, in my opinion, it fails to outweigh the possible down side.  Here’s what one reviewof the evidence for people in this category concluded:
    

In conclusion, based on aggregate data on 65 229 men and women from 11 studies, yielding approximately 244 000 person-years of follow- up and 2793 deaths, we observed that statin therapy for an average period of 3.7 years had no benefit on all-cause mortality in a high-risk primary prevention (primary prevention means people with risk factors but no established heart disease) population.  Current prevention guidelines endorse statin therapy for subjects at high global risk of incident CVD as a means to reduce fatal and nonfatal vascular events. Consideration is needed in applying statin therapy in lower-risk primary prevention populations.

Having read many such reviews, I have become somewhat of a statin skeptic.  So when somebody tells me they are being advised to take a statin, I generally suggest that they determine just how high their risk of heart disease really is.  I tell them that in order to make an informed decision, they will need to know a lot more than just the status of their LDL cholesterol.  I tell them to go back to their doctor and find out, at a minimum, what their HDL and triglyceride levels are as well as what their total cholesterol/HDL ratio is.

To illustrate the significance of acquiring this additional information, I am offering below a comparison of three lipid panels.  Although I will not reveal their names, rest assured that these are real people.  The first belongs to a woman in her 40’s who is slightly overweight, a smoker and has a history of heart disease in her family.  The second belongs to a woman in her mid 70’s who has been on a statin for more than 15 years despite having no risk factors other than high total cholesterol (at the time, her total cholesterol was high but it was mostly because her good cholesterol (HDL) was very high, as it still is).  The third belongs to me, a 48 year old with only a family history (my dad had a heart attack in his 50s) as an added risk factor.  I will also include a list of the recommendations for blood lipids on the Canadian Heart and Stroke website for reference.

LIPID PANEL

 

The bottom row shows the triglyceride/HDL ratio, which is not mentioned in the Heart and Stroke literature, even though a recent paper on the subject concluded:

“Nearly all routinely assessed lipid variables were associated with the extent of coronary disease, but only the ratio of triglycerides to HDL were robustly associated with disease extent.  Elevation in the ratio of TG to HDL was the single most powerful predictor of extensive coronary heart disease among all the lipid variables examined”

Not sure how many doctors are familiar with the TG/HDL ratio, but it sounds like something you might want to know before you sentence somebody to a lifetime on statins.  Seems that the TG/HDL ratio is an excellent indicator of whether or not your LDL is small and dense (the killer kind) or light and fluffy (the innocuous kind).  Although there is no established norm for the TG/HDL ratio, lower seems to be better, with <2 being pretty good and <1 being excellent.

So what does it all mean?  Let’s take a look on a line by line basis:

  • LDL Cholesterol (the “bad” stuff)

The Heart and Stroke Foundation wants your LDL “bad” cholesterol to be under 3.5.  However, they add the caveat that for people with other established risk factors for heart disease, they would rather see it below 3.  All three of us have at least one added risk factor, so a number above 3 should at least draw the attention of our doctors.  Subject #1 has three added risk factors and the highest LDL, so her doctor is right to be concerned.

Having said that, keep in mind that the medical establishment is preoccupied with LDL.  Many doctors are entirely uninterested in the complexity of lipid bio-markers.  When subject #1 asked her doctor for her HDL and triglyceride levels, she responded with “Those numbers are inconsequential – only LDL is important.”  Subject#2, as we have seen,  spent 15 years on a statin despite having only marginally elevated LDL.  Despite having exemplary HDL and TC/LDL.  And despite having complained for years about muscle pain, brain fog and low energy (three common side effects of statins). 

And all this despite the fact that neither total nor LDL cholesterol has ever been proven causative of or even significantly correlated with heart disease.  As you can see from the graph below, there is very little difference in heart disease risk between the extremes of LDL concentrations within the normal population.  It is only when HDL levels are low that LDL levels begin to predict heart disease significantly.

ldl hdl good

*adapted from Gordon T. et al, American Journal of Medicine, 1977;62;707-714

You tell me.  Is HDL inconsequentialal?

  • HDL Cholesterol (the “good” stuff)

Heart and Stroke wants HDL kept above 1.3mmo/l.  That’s OK, but from the chart above we can see that an HDL of 1.3, even at the lowest levels of LDL , still leaves you with a much higher risk of heart disease than would an HDL greater than 2 with just about any level of LDL!  All three of us are above the 1.3 mark, but, as you can see, this is a number which appears to get better and better the higher it gets.  Why it takes a back seat to LDL in the doctor’s office is beyond me.

  • Total Cholesterol/HDL Ratio

Heart and Stroke wants the TC/HDL ratio below 5, although it should be mentioned that other conventional medical authorities want the ratio even lower.  The Mayo Clinic, for example, sets the bar at 4.  One of HDL’s primary roles is to prevent the oxidation of LDL.  Oxidized LDL tends to turn into small, dense LDL.  Small dense LDL is most definitely atherogenic – even the American Heart Association admits this.  So if you have a lot of cholesterol, but a significant percentage of it is associated with HDL, the likelihood of the rest getting oxidized is relatively small.  If you don’t have much HDL, though, you’d better hope that you don’t have much LDL either.  High LDL in the context of low HDL, as we can see from the graph above, will certainly increase your chances of becoming athlerosclerotic.

  • Triglycerides

Triglyceride levels also associate well with heart disease.  In fact, one recent meta-analysis claims that each 1mmo/l increase in triglycerides is associated with a 37% increase in risk of heart disease for women.  If this is correct, then it suggests that the Heart and Stroke recommendation of <1.7 may be overly conservative. 

Triglycerides are basically a measure of the amount of fat in your blood.  Although the fact that high triglycerides are associated with disease would seem to condemn dietary fat, this is far from the case.  The truth is, the fats associated with hypertriglyceridemia are made in the liver, primarily when carbohydrate consumption is high.  The mechanism behind this is not fully understood, but it is related to an over-production of fat in the liver and/or an inability to clear this fat from the blood.  The inability to clear fat from the blood, as I explain in my series on diabetes, is indicative of insulin resistance.  Insulin resistance causes high blood sugars and hyperinsulinemia, both of which contribute to inflammation, oxidation and arterial damage.  And, despite the advice of conventional medicine to eat a low fat diet, it is quite clear that eating a high carbohydrate diet will raise triglycerides.

  •  Triglyceride/HDL Ratio

As I explained above, TG/HDL ratio is an excellent predictor of severity of heart disease.  When researchers measure the amount of plaque in people’s arteries and compare that to blood lipids, the TG/HDL ratio seems to be most impressive in determining the extent of arterial damage.  The table below, taken from this paper, shows just how well the numbers correlate.

hdl trigly numbers 

Notice that for Total Cholesterol and LDL, the relationship to coronary disease is not linear.  Having low LDL or Total cholesterol will give you almost as much risk for heart disease as having high LDL or TC.  Tell that to the statinators who seem to believe that lower is always better! 

On the other hand, notice that there is a clear linear relationship between HDL, Triglycerides and TG/HDL with extent of heart disease.  The more TG you have, the more heart disease you have.  The more HDL you have, the less heart disease you have.  Consequently, the higher your ratio of TG to HDL, the more risk of heart disease you have.

How much does your risk of heart disease go up when your TG/HDL ratio is elevated?  This study found that the people with the highest TG/HDL ratio had 16 times the risk for heart disease as the people with the lowest ratio.  Mind you, these people had, on average, a TG/HDL of over 7.5.  However, even the second quartile of participants, with an average TG/HDL of 2.3 had a 4-fold increase in risk of heart disease.

  

SO WHAT DOES IT ALL MEAN FOR THE THREE OF US?

  Subject #1

Of the three of us, subject #1 has the highest risk for heart disease.  Certainly, the combination of smoking and family history create a potent risk.  She also carries most of her extra weight around her mid-section, which is indicative of metabolic syndrome, making that weight more of an imposing risk factor.  According to the Canadian Framingham Risk Score her chance of developing heart disease in the next 10 years is 3%. Compared to other women of her own age, she has a 5% greater risk of developing heart disease than those who do not have her risk factors – whatever that means!  This estimate does not, of course, include the fact that her triglycerides are a bit high, her TG/HDL ratio is elevated, or that her weight is carried at her mid-section.  It is therefore – at least in my humble opinion – probably a conservative estimate. 

My guess is that if she continues her current lifestyle, her total cholesterol will continue to creep up, as will her triglycerides.  In the meantime, her HDL will creep down and she will probably develop at least a minimal level of insulin resistance.  I suspect she is already experiencing some level of systemic inflammation, which could be measured by tracking C-Reactive Protein. 

But should she take a statin?  Remember, she does not have heart disease, which means that taking a statin would be a form of primary prevention.  Her risk for heart disease is at best moderate.  So what does the science say about the use of statins for primary prevention?  Well, it depends who you ask.  If you ask the pharmaceutical companies, they will, of course, say that statin usage is useful in primary prevention.  However, even the most optimistic statinators get, at best, about 30% risk reduction over 5 years in primary prevention.  This means that,  according to the drug dealers who make the statins, subject #1 might be able to reduce her risk of heart disease from 3% to 1% over the next ten years.  If she was a man!   It turns out that although primary prevention statin therapy may show some minimal benefit in men, it is not at all clear that it has the same benefit in women.  A recent meta-analysis on the subject concluded: 

Our study showed that statin therapy reduced the risk of CHD events in men without prior cardiovascular disease, but not in women. Statins did not reduce the risk of total mortality both in men and women.”

More importantly, as we already discussed above, and is stated again here, there is absolutely no relationship between statin usage and improved all cause mortality in primary prevention!  So she may minimally reduce her risk of heart disease, but she isn’t going to live any longer anyway.  You make the call!

What about making lifestyle changes?  Doctors don’t put much stock in lifestyle changes.  This pessimistic attitude is justified by the fact that most people are not capable of sustaining long term changes to their lifestyle.  But let’s just play a game of pretend.  Let’s pretend that subject #1 is one of those super-human people with the fortitude to make and sustain significant changes to her lifestyle.  Then what?

What happens to blood lipids if you sustain weight loss for 2 years?  If you use a low fat diet, you lose about 4 or 5 pounds.  If you use a Mediterranean or Atkins diet, you lose about 8 to 10 lbs.  Here’s what happens to your blood lipids:

fat loss and lipids

Wow!  HDL goes up and triglycerides go down.  TC/HDL ratio goes down.  So does TG/HDL ratio.  If you care to read the paper, you will see that insulin resistance,  leptin resistance and markers of inflammation also improve.  Even LDL goes down, as long as you don’t use a low fat diet to get yourself slim.

Wonder what happens if you quit smoking?  This study found a 12% increase in HDL for people who managed to quit for a year.  And that was despite an average weight gain of about 8-10 pounds! 

What about regular exerciseThis study concluded that regular moderate aerobic exercise – about 30 minutes 3 or 4 times per week – for 7 weeks could significantly reduce triglyceride levels and marginally increase HDL levels.

Here’s the thing.  Statins interfere with your liver’s ability to make LDL.  They accomplish this task by inhibiting HMG co-enzyme A reductase, a crucial enzyme in what is called the mevalonate pathway. Now there’s a gaggle of words that don’t come up much at the dinner table!  Bear with me.  This is important.   Here’s a synopsis of what else happens downstream of HMG Co-A reductase:

The mevalonate pathway or HMG-CoA reductase pathway or mevalonate-dependent (MAD) route or isoprenoid pathway, is an important cellular metabolic pathway present in all higher eukaryotes and many bacteria. It is important for the production ofdimethylallyl pyrophosphate (DMAPP) and isopentenyl pyrophosphate (IPP), which serve as the basis for the biosynthesis of molecules used in processes as diverse as terpenoid synthesis, protein prenylationcell membrane maintenance, hormonesprotein anchoring, and N-glycosylation. It is also a part of steroid biosynthesis” (from wikipedia)

Even more big words!  Here’s the scoop.  Interfere with HMG Co-A reductase and you interfere with mevalonate.  Interfere with mevalonate and you interfere with cellular energy production, immune system regulation, cellular membrane integrity, the ability of proteins to attach themselves to cellular receptors, the synthesis of proteins and the synthesis of various hormones.  Do we really think that we can interfere with all these biological functions and not suffer long term metabolic consequences?  Do we really want to take the word of the pharmaceutical companies that statins are safe, when we know that none of their studies follow side-effects long term and few of them are empowered to study any of these complex systems even in the  short term?  Do we really want to take this risk simply in order to correct a single number (LDL) which isn’t even a particularly effective predictor of cardiovascular health and has certainly never proven to be causative of heart disease?

Subject #2

Before I start ranting, full disclosure.  I don’t know the full extent of this person’s health history at the time (15 years ago) when she was put on statins.  I don’t know what her LDL was.  I don’t know what her HDL was.  I don’t know what her triglycerides were.  I don’t know what her blood pressure was.  For all I know, her total cholesterol could have been 20 and her HDL 2, putting her at elevated risk for heart disease despite having high HDL.

Here’s what I do know.  I do know that statins have never proven to be the least bit effective for primary prevention of heart disease in women.  I do know that they have no long term positive effect on all cause mortality.  I do know that the muscle pain, lack of energy and brain fog she has been complaining of for years are well known side effects of statin usage.  I do know that it wasn’t until a rheumatologist (who she saw on account of her muscle pain) recognized her symptoms as side effects of statins that her doctor finally took her off them.  Only time will tell whether the accumulated cellular damage she probably sustained over 15 years of statin usage is reversible or not.  I have my doubts whether the pharmaceutical companies will ever do a study on that!

And then there’s me

I like my doctor.  He has never mentioned a statin, despite my LDL being slightly elevated- at least by conventional standards.  He recognizes that my HDL is stellar, my TC/HDL is ideal, my triglycerides are very low, my blood pressure is normal and I am not overweight. But here’s a funny story:

Last Spring I was experiencing some unfamiliar chest pain for a few weeks.  Coincidentally, I had already scheduled my annual physical, so I mentioned the issue to my doctor.  He immediately gave me an EKG and when the results were normal he re-assured me that it probably was nothing.  Just to be sure, though, he scheduled me for a full stress test with a cardiologist.  After an hour of testing, I sat down with the cardiologist who proclaimed that I had the healthiest heart he had seen in years.  Then he advised me to start taking a daily baby aspirin.  Guess he doesn’t read the Wall Stree Journal.  Here’s what Heartwire (an online heart disease newsletter targeted at physicians) had to say about giving aspirin to somebody like me who has low cardiovascular risk: 

“There needs to be better ways of educating primary-care physicians as to where it is clear that aspirin should be used, in secondary prevention and in diabetics with multiple risk factors, and very clear where aspirin should not be used, in people at low CV risk

The same article contains more comentary  worth quoting on the general topic of doctors and their advice on heart disease.

The aspirin findings speak to one of the overall conclusions of our PARADIGM study, and that is that unfortunately family doctors aren’t very good at doing risk assessment for primary prevention.”

So family doctors are not good at figuring out whether or not you have any risk of heart disease.  How do they figure out your risk?

“My suspicion,” he (Dr Milan Gupta, cardiologist and professor) continued “is that family doctors are eyeballing risk,”

Instead of weighing risk factors using sophisticated scientific practices (which, for the record, are out of date anyway) doctors are guessing.  Based on what?  Who knows, but apparently not based on current guidelines and evidence.  Gupta goes on to say:

“Most cardiologists in Canada, he adds, are not actively involved in primary prevention—this falls to primary-care physicians, who are slow to incorporate CVD prevention guideline evidence into practice.”

By the looks of it, my cardiologist is just as slow to incorporate CVD prevention guidline evidence as are the family doctors who think subject #1 and subject #2 should be taking statins.

(the chest pain never amounted to anything –  probably a muscle pull)

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