Tag Archives: cholesterol

Does Eating Saturated Fat Lower Your Risk of Stroke and Dying?: Humility and Conscience in Nutritional Guidelines

A study presented at the European Society of Cardiology  meetings in Barcelona and simultaneously published in The Lancet earlier this month caught the attention of many of my readers. Media headlines trumpeted  “Huge New Study Casts Doubt On Conventional Wisdom About Fat And Carbs” and “Pure Shakes Up Nutritional Field: Finds High Fat Intake Beneficial.”

Since I’ve been casting as much doubt as possible on the  conventional nutritional wisdom  to cut saturated fat, they reasoned, I should be overjoyed to see such results.

What Did the PURE Study Find?

The Prospective Urban Rural Epidemiology (PURE) study, involved more than 200 investigators who collected data on more than 135000 individuals from 18 countries across five continents for over 7 years.

There were three high-income (Canada, Sweden, and United Arab Emirates), 11 middle-income (Argentina, Brazil, Chile, China, Colombia, Iran, Malaysia, occupied Palestinian territory, Poland, South Africa, and Turkey) and four low-income countries (Bangladesh, India, Pakistan, and Zimbabwe)

This was the largest prospective observational study to assess the association of nutrients (estimated by food frequency questionnaires) with cardiovascular disease and mortality in low-income and middle-income populations,

The PURE team reported that:

Higher carbohydrate intake was associated with an increased risk of total mortality but not with CV disease or CV disease mortality.

This finding meshes well with one of my oft-repeated themes here, that added sugar is the major toxin in our diet (see here and here.)

Higher fat intake was associated with lower risk of total mortality.

Each type of fat (saturated, unsaturated, mono unsaturated ) was associated with about the same lower risk of total mortality. 

 

These findings are consistent with my observations that it is becoming increasingly clear that cutting back on  fat and saturated fat as the AHA and the Dietary Guidelines for Americans have been telling you to do for 30 years is not universally helpful (see here and  here ).

When you process the fat out of dairy and eliminate meat from your diet although your LDL (“bad”) cholesterol drops a little your overall cholesterol (atherogenic lipid) profile doesn’t improve (see here).

Another paper from the PURE study shows this nicely and concluded:

Our data are at odds with current recommendations to reduce total fat and saturated fats. Reducing saturated fatty acid intake and replacing it with carbohydrate has an adverse effect on blood lipids. Substituting saturated fatty acids with unsaturated fats might improve some risk markers, but might worsen others. Simulations suggest that ApoB-to-ApoA1 ratio probably provides the best overall indication of the effect of saturated fatty acids on cardiovascular disease risk among the markers tested. Focusing on a single lipid marker such as LDL cholesterol alone does not capture the net clinical effects of nutrients on cardiovascular risk.

Further findings from PURE:

-Higher saturated fat intake was associated with a lower risk of stroke

-There was no association between total fat or saturated fat or unsaturated fat with risk of heart attack or dying from heart disease.

Given that most people still believe that saturated fat causes heart disease and are instructed by most national dietary guidelines to cut out animal and dairy fat this does indeed suggest that

Global dietary guidelines should be reconsidered …”

Amen!

Because the focus of dietary guidelines on reducing total and saturated fatty acid intake “is largely based on selective emphasis on some observation and clinical data despite the existence of several randomizesed trials and observational studies that do not support these conclusions.”

Pesky Confounding Factors

We cannot infer causality from PURE because like all obervational studies, the investigators do not have control over all the factors influencing outcomes. These confounding factors are legion in a study that is casting such a broad net across different countries with markedly different lifestyles and socioeconomic status.

The investigators did the best job they could taking into account household wealth and income, education, urban versus rural location and the effects of study centre on the outcomes.

In an accompanying editorial, Christopher E Ramsden and Anthony F Domenichiello, prominent NIH researchers,  ask:

“Is PURE less confounded by conscientiousness than observational studies done in Europe and North American countries?

 

“Conscientiousness is among the best predictors of longevity. For example, in a Japanese population, highly and moderately conscientious individuals had 54% and 50% lower mortality, respectively, compared with the least conscientious tertile.”

“Conscientious individuals exhibit numerous health-related behaviours ranging from adherence to physicians’ recommendations and medication regimens, to better sleep habits, to less alcohol and substance misuse. Importantly, conscientious individuals tend to eat more recommended foods and fewer restricted foods.Since individuals in European and North American populations have, for many decades, received in influential diet recommendations, protective associations attributed to nutrients in studies of these populations are likely confounded by numerous other healthy behaviours. Because many of the populations included in PURE are less exposed to in influential diet recommendations, the present findings are perhaps less likely to be confounded by conscientiousness.”

It is this pesky conscientiousness factor (and other unmeasured confounding variables) which limit the confidence in any conclusions we can make from observational studies.

I agree wholeheartedly with the editorial’s conclusions:

Initial PURE findings challenge conventional diet–disease tenets that are largely based on observational associations in European and North American populations, adding to the uncertainty about what constitutes a healthy diet. This uncertainty is likely to prevail until well designed randomised controlled trials are done. Until then, the best medicine for the nutrition field is a healthy dose of humility.

 

Ah, if only the field of nutrition had been injected with a healthy dose of humility and a nagging conscience thirty years ago when its experts declared confidently that high dietary fat and cholesterol consumption was the cause of heart disease.!

Current nutritional experts and the guidelines they write will  benefit from a keen awareness of the unintended consequences of recommendations which they make based on weak and insufficient evidence  because such recommendations influence the food choices  (and thereby the quality of life and the mechanisms of death) of hundreds of millions of people.

PUREly Yours,

ACP

Sheepshead Fish: Vulnerable and Gender Fluid Yet Mighty Tasty

The skeptical cardiologist and his Eternal Fiancee’ have escaped dreary and oceanopenic St. Louis and are spending a week in allegedly sunny and definitely beachy San Diego.

Upon arrival we took in a Farmer’s Market in Little Italy and stumbled into Ironside Fish and Oyster.screen-shot-2017-01-22-at-9-07-04-am
Always in search of heart-healthy, unique and local fish dishes, I spotted on the menu a luncheon special of sheepshead fish.

Kelly Fukushima is the local fisherman who caught my fish
Kelly Fukushima is the local fisherman who caught my fish.

California sheepshead (Semicossyphus pulcher), the existence of which I was previously unaware, turned out to be a fascinating and most delicious fish.

casheepshead

Before I could order it, I had to verify that I wasn’t contributing to the extinction of a species.  The IUCN Red List of Threatened species lists the CS as “vulnerable” because:

“The natural history of this species, including its limited geographic range along inshore habitat, the likely increasing interest in the fishery and the currently unsustainable fishing levels (according to the models of Alonzo et al. 2004), together with the difficulties in enforcing existing regulations strongly suggest that this species will continue to decline if stronger protective action is not put into place. “

After learning the CS was vulnerable, I had to make a critical decision: should I eat it before it disappeared, robbing me of a chance to ever taste it, or should I order something that wasn’t vulnerable, thus contributing to the preservation of the continuing biodiversity of the planet. I elected to taste it.

Gender Fluid Fish

Further research revealed that the CS transitions from a reproductively functional female at birth, to a functional male during the course of a lifespan in response to social factors (?reverse Bruce Jenner).

According to evolution.berkeley.edu this is termed sequential hermaphroditism:

In some sequentially hermaphroditic fish species, animals develop first as male and then switch to female (a condition called protandry), and in others, the individuals develop first as female and then switch to male (protogyny).

Clownfish (as in Finding Nemo) do the opposite of the sheepshead and are protandrous:

This species lives within sea anemones in groups of two large fish and many small fish. The two large fish are the only sexually mature fish and are a male and female breeding pair. All of the smaller fish are male. If the large breeding female is removed, her male mate changes sex to female and the next largest fish in the group rapidly increases in size and takes over the role as the sexually mature male.

While waiting for the vulnerable and sequentially hermaphroditic sheepshead to arrive, I sampled an equally

img_8160stupendous and heart-healthy side of cannelloni bean cassoulet. Chock full of Mediterranean diet essentials including kale, beans and mustard seeds, it worked really well as an appetizer.

 

Do not make the mistake of looking at this youtube video while waiting for your sheepshead entree’ as I did. The disturbing human-like teeth will not be part of your meal.

Finally, the 4 ounces of CS arrived, perfectly prepared a la plancha,

img_8162with an accompanying lemon butter sauce that was divine. Although butter is not officially a big part of the Mediterranean diet, frequent readers of the skepcard know that dairy fat does not make you fat or promote heart disease, and is fine (in moderation of course) as part of a heart-healthy diet.

Speaking of lingering bad dietary advice, if you investigate the nutritional content of sheepshead at a site like SELF Nutrition, the screen-shot-2017-01-22-at-10-18-54-amold canard that we should be limiting our dietary cholesterol raises its ugly head. Because sheepshead contain significant amounts of cholesterol (presumably from carnivorously munching on shellfish with its scary human-like choppers), the misguided nutritionists at SELF Nutrition and other would-be nutritionistas pronounce it as not optimally healthy.

Semiccossyphusilly Yours

-ACP

PS. If you’d really like to get your nerd on about sequential hermaphroditism check out this graphic showing the independent evolution of this feature across different phylogenetic lineages!

hermaphroditismtree

 

 

 

 

What Happens To Cholesterol Levels When You Switch To Low Or Non Fat Dairy

When individuals  discover that they have abnormal  cholesterol readings they are often told to initiate  lifestyle changes to try to correct them.

Based on what physicians and patients have been taught  over the last twenty years, the likely dietary change recommended and the easy , first step is likely  to be to cut back on dairy fat.

IMG_6135
Yoplait Original-25% Less Sugar.(but still with 18 grams per 6 oz serving). A typical supermarket/doctor’s lounge yogurt with lots of ingredients added in (sugar, modified corn starch, Vitamin A Acetate, Vitamin D3)to replace the natural good taste and nutrients found in dairy fat.
IMG_6272 (1)
Traders Point Creamery plain yogurt. Ingredients= milk and cultures. Taste =fantastic. Grams of sugar=zero.

After all, it’s a pretty easy transition to start using skim milk and non fat yogurt because these line the supermarket shelves and have been filled with chocolate or added sugar to taste more palatable.

You might miss the great taste that butter adds to bread or cooking but for your health you would be willing to switch to non butter spreads and cut down on the cheese in your diet because  based on what you have heard from numerous media sources this is a giant step toward reducing your cholesterol numbers.

 

 

 

 


 

Unfortunately, it is a horribly misguided  step.

Although, the switch to low or non fat dairy lowers your cholesterol numbers, it is  not lower cholesterol numbers that you want: what you want is a lower risk of developing stroke or heart attack or the other complications of atherosclerosis.

Let me repeat: Don’t worry about your cholesterol numbers, worry about your overall risk of developing heart attack or stroke.

Due to 30 years of misinformation, the concept that lowering your cholesterol means lower risk of heart disease has become firmly entrenched in the public’s consciousness-but in the case of dietary intervention this has never been documented.

I take care of a 69 year old woman who has an abnormal heart rhythm and chest pain. As part of her evaluation for chest pain we performed a coronary CT angiogram (CCTA) which showed advanced but not obstructive atherosclerotic plaque in her right and left anterior descending coronary arteries.

This lady was not overweight, followed a healthy diet and exercised regularly. Her mother, a sedentary, heavy smoker, suffered a heart attack at age 54.

Her PCP had obtained lipid values on her 6 months before I saw her which were abnormal but the patient had been reluctant to start the recommended statin drug because of concerns about side effects.

After seeing her CCTA I advised that she begin atorvastastin 10 mg daily and aspirin to help reduce her long term risk of heart attack, stroke.

She decided without telling me not to take the statin, again due to side effect concerns, but started the aspirin, and began to pursue what she felt were healthy dietary changes.

When I saw her back in the office she told me  “I don’t eat butter or cheese anymore and I’ve switched to skim milk.” She had substituted olive oil for butter.

Here are her lipid values before and after her dietary changes (TC=total cholesterol, LDL= bad cholesterol, HDL=good cholesterol, trigs=triglycerides)

Date              TC             LDL       HDL   trigs            ASCVd 10 year risk

3/2015         275          173       72       149                         7.9%

10/2015      220           122       43      274                         8.3%

At first glance, and especially if we focus only on the total and bad cholesterol, this appears to be a successful response to dietary changes:  a 29% reduction in the bad cholesterol and a 25% drop in the total cholesterol.

However, although the LDL or bad cholesterol has dropped a lot, the HDL or good cholesterol has dropped by  more: 40%!

This is the typical change when patients cut out dairy fat-the overall ratio of bad  to good cholesterol actually rises.

In addition, the pattern she has now, with a low HDL and high triglycerides is typical of the metabolic syndrome which is recognized as likely to contribute to early  atherosclerosis: so-called “atherogenic dyslipidemia.”

When I plugged both sets of numbers into the ASCVD 10 year risk calculator app (see here) her estimated 10 year risk of heart attack and stroke had actually increased from 7.9% to 8.3%.

Hopefully, this anecdote will reinforce what population studies show:

  • There is NO evidence that dairy fat consumption increases risk of cardiovascular disease (see here)
  • Current recommendations to consume non or low fat dairy (often  accompanied by increase in added sugars) are not supported by scientific studies.

Finally, my patient is another example of an inherited tendency to development of premature atherosclerosis: her diet, exercise, body weight were all optimal and could not be tweaked to lower her risk.

Such patients must deal with the cardiovascular cards they have been dealt. If they have advanced atherosclerosis, as much as they may dislike taking medications, statins are by far the most effective means of reducing their long term risk of heart attack and stroke.

 

 

 

Why Is The American College of Cardiology Distorting The 2015 Dietary Guidelines for Americans?

The 2015-2020 Dietary Guidelines for Americans (DGA) have finally been released and I’m sure that most of you could care less what they say. You may think that they can’t be trusted because you believe the original science-based recommendations have been altered by political, food and agribusiness forces.  Perhaps you don’t trust science to guide us in food choices. Perhaps, like the skeptical cardiologist, you realize that the DGA has created, in the past, more problems than they have corrected.

This time, the skeptical cardiologist believes they have made a few strides forward, but suffer from an ongoing need to continue to vilify all saturated fats.

As such, the DGA no longer lists a recommended limit on daily cholesterol consumption (step forward) but persists in a recommendation to switch from full fat to non fat or low fat dairy products, which is totally unsubstantiated by science, (see my multiple posts on this topic here).

By now you should have gotten the message that a healthy diet consists of lots of fruits, vegetables, nuts, legumes, fish, olive oil and whole grains. The DGA emphasizes this.

There is general consensus that processed foods and added sugar should be limited.

Most of the controversy is about what to limit and how much to limit foods that are considered unhealthy.

Red meat and processed meat remain in the crosshairs of the DGA (although not stated explicitly), but eggs and cholesterol have gotten a pass, something which represents a significant change for the DGA and which I have strongly advocated (here and here).

But hold on, my professional organization, the American College of Cardiology says otherwise.

Misleading Information From the American College of Cardiology

The American College of Cardiology sent me an email and posted on their website the following horribly misleading title:

“2015 Dietary Guidelines Recommend Limited Cholesterol Intake”

The first paragraph of the ACC post reads as follows:

“Physiological and structural functions of the body do not require additional intake of dietary cholesterol according to the 2015 Dietary Guidelines released on Jan. 7 by the U.S. Departments of Health and Human Services (HHS) and of Agriculture (USDA). As such, people should practice healthy eating patterns consuming as little dietary cholesterol as possible. – ”

While technically these statements can be found in the document (by digging way down) the executive summary (infographic below) says nothing about limiting cholesterol.

healthy eating pattern includes

The “Key Recommendations” list eggs as included under a “healthy eating pattern” along with other protein foods.

 

Screen Shot 2016-01-09 at 1.31.18 PM

In addition, there is no mention of cholesterol under what a healthy pattern limits.

 

 

In the same section on cholesterol that the ACC inexplicably has chosen to emphasize, is this sentence:

“More research is needed regarding the dose-response relationship between dietary cholesterol and blood cholesterol levels. Adequate evidence is not available for a quantitative limit for dietary cholesterol specific to the Dietary Guidelines.”

So the DGA recommends no specific limit on dietary cholesterol.

This is consistent with what the DG advisory committee recommended when they wrote “dietary cholesterol is no longer a nutrient of concern.”

The DGA goes on to state:

“A few foods, notably egg yolks and some shellfish, are higher in dietary cholesterol but not saturated fats. Eggs and shellfish can be consumed along with a variety of other choices within and across the subgroup recommendations of the protein foods group.”

The Vegan Agenda

I have a theory on why the ACC went so wildly astray in reporting this information: they are led by a vegan.

The current president of the ACC, Kim Williams, is an evangelical vegan, unrepentant, as this NY times article points out. Apparently, he tries to convert all his patients to the “plant-based diet.”

He is quoted extensively in the ACC blurb on the DGA and is clearly attempting to put a bizarre vegan spin on the new guidelines, ignoring the evidence and the progressive shift from the 2010 guidelines.

Can any information from the ACC be trusted if such basic and important science reporting was so heavily distorted by its President?

No wonder Americans tune out dietary advice: it can so easily be manipulated by those with an agenda.

-May the forks and knives be with you

-ACP

 

 

 

 

Saturated Fat: Traditionalists versus Progressives

Why is death from coronary heart disease declining in the US at the same time that obesity and diabetes rates are climbing?

Two editorials recently published in The Lancet show the widely varying opinions on the optimal diet for controlling obesity , diabetes and coronary heart disease that experts on nutrition, diabetes and heart disease hold.

fats
Typical innocent and usual suspects rounded up in the war on fat: Cheese-data show it lower heart disease risk Full fat yogurt (Trader’s Point Creamery)-data show it is associated with lower heart disease risk Butter-Delicious. Used in moderation not a culprit.

The first paper contains what I would  consider the saturated fat “traditionalist” viewpoint. This is a modification of the misguided concept that was foisted on the American public in the 1980s and resulted in the widespread consumption of industrially produced trans-fats and high sugar junk food that was considered heart healthy.

The traditionalists have shifted from condemning all fats to vilifying only saturated and trans fats. They would like to explain at least part of the reduction in coronary heart mortality as due to lower saturated fat consumption and the accompanying lowering of LDL (“bad”) cholesterol.

The SFA traditionalists fortunately are in decline and more and more in the last five years, prominent thinkers, researchers and scientists working on the connection between diet and the heart believe saturated fats are neutral but sugar and refined carbohydrates are harmful in the diet.

Darius Mozzafarian, a highly respected cardiologist and epidemiologist, who is dean of the School of Nutrition Science and Policy at Tufts, wrote the second editorial and is what I would term a saturated fatty acid (SFA) progressive.

He makes the following points which are extremely important to understand and which I have covered in previous posts. I’ve included his supporting references which can be accessed here.

Fat Doesn’t Make You Fat, Refined Starches And Sugar Do

"Foods rich in refined starches and sugars—not fats—seem to be the primary culprits for weight gain and, in turn, risk of type 2 diabetes. To blame dietary fats, or even all   calories, is incorrect
Although any calorie is energetically equivalent for short-term weight loss, a food's long-term obesogenicity is modified by its complex effects on satiety, glucose–insulin responses, hepatic fat synthesis, adipocyte function, brain craving, the microbiome, and even metabolic expenditure Thus, foods rich in rapidly digestible, low-fibre carbohydrates promote long-term weight gain, whereas fruits, non-starchy vegetables, nuts, yoghurt, fish, and whole grains reduce       long-term weight gain.123
Overall, increases in refined starches, sugars, and other ultraprocessed foods; advances in food industry marketing; decreasing physical activity and increasing urbanisation in developing nations; and possibly maternal–fetal influences and reduced sleep may be the main drivers of obesity and diabetes worldwide".

There Are Many Different Kinds of Saturated Fats With Markedly Different Health Effects: It Makes No Sense to Lump Them All Together 

"SFAs are heterogeneous, ranging from six to 24 carbon atoms and having dissimilar biology. For example, palmitic acid (16:0) exhibits in vitro adverse metabolic effects, whereas medium-chain (6:0–12:0), odd-chain (15:0, 17:0), and very-long-chain (20:0–24:0) SFAs might have metabolic benefits.4 This biological and metabolic diversity belies the wisdom of grouping of SFAs based on a single common chemical characteristic—the absence of double bonds. Even for any single SFA, physiological effects are complex: eg, compared with carbohydrate, 16:0 raises blood LDL cholesterol, while simultaneously raising HDL cholesterol, reducing triglyceride-rich lipoproteins and remnants, and having no appreciable effect on apolipoprotein B,  5 the most salient LDL-related characteristic. Based on triglyceride-lowering effects, 16:0 could also reduce apolipoprotein CIII, an important modifier of cardiovascular effects of LDL and HDL cholesterol. SFAs also reduce concentrations of lipoprotein(a) ,6 an independent risk factor for coronary heart disease."

The Effects of Dietary Saturated Fats Depend on Complex Interactions With The Other Ingredients in Food

"Dietary SFAs are also obtained from diverse foods, including cheese, grain-based desserts, dairy desserts, chicken, processed meats, unprocessed red meat, milk, yoghurt, butter, vegetable oils, and nuts. Each food has, in addition to SFAs, many other ingredients and characteristics that modify the health effects of that food and perhaps even its fats. Judging the long-term health effects of foods or diets based on macronutrient composition is unsound, often creating paradoxical food choices and product formulations. Endogenous metabolism of SFAs provide further caution against oversimplified inference: for example, 14:0 and 16:0 in blood and tissues, where they are most relevant, are often synthesised endogenously from dietary carbohydrate and correlate more with intake of dietary starches and sugars than with intake of meats and dairy.4"

Dietary Saturated Fat Should Not Be a Target for Health Promotion

"These complexities clarify why total dietary SFA intake has little health effect or relevance as a target. Judging a food or an individual's diet as harmful because it contains more SFAs, or beneficial because it contains less, is intrinsically flawed. A wealth of high-quality cohort data show largely neutral cardiovascular and metabolic effects of overall SFA intake.7 Among meats, those highest in processing and sodium, rather than SFAs, are most strongly linked to coronary heart disease.7Conversely, higher intake of all red meats, irrespective of SFA content, increases risk of weight gain and type 2 diabetes; the risk of the latter may be linked to the iron content of meats.28 Cheese, a leading source of SFAs, is actually linked to no difference in or reduced risk of coronary heart disease and type 2 diabetes.910 Notably, based on correlations of SFA-rich food with other unhealthy lifestyle factors, residual confounding in these cohorts would lead to upward bias, causing overestimation of harms, not neutral effects or benefits. To summarise, these lines of evidence—no influence on apolipoprotein B, reductions in triglyceride-rich lipoproteins and lipoprotein(a), no relation of overall intake with coronary heart disease, and no observed cardiovascular harm for most major food sources—provide powerful and consistent evidence for absence of appreciable harms of SFAs."

Dietary Saturated Fats May Raise LDL cholesterol But This Is Not Important: Overall Effects On Obesity and Atherosclerosis Are What Matters

"a common mistake made by SFA traditionalists is to consider only slices of data—for example, effects of SFAs on LDL cholesterol but not their other complex effects on lipids and lipoproteins; selected ecological trends; and expedient nutrient contrasts. Reductions in blood cholesterol concentrations in Western countries are invoked, yet without systematic quantification of whether such declines are explained by changes in dietary SFAs. For example, whereas blood total cholesterol fell similarly in the USA and France between 1980 and 2000, changes in dietary fats explain only about 20% of the decline in the US and virtually none of that which occurred in France.11Changes in dietary fats11 simply cannot explain most of the reductions in blood cholesterol in Western countries—even less so in view of the increasing prevalence of obesity. Medication use also can explain only a small part of the observed global trends in blood cholesterol and blood pressure. Whether decreases in these parameters are caused by changes in fetal nutrition, the microbiome, or other unknown pathways remains unclear, thus highlighting a crucial and greatly underappreciated area for further investigation."

Dietary Saturated Fats Are Neutral For Coronary heart Disease Risk

Finally, SFA traditionalists often compare the effects of SFAs only with those of vegetable polyunsaturated fats, one of the healthiest macronutrients. Total SFAs, carbohydrate, protein, and monounsaturated fat each seem to be relatively neutral for coronary heart disease risk, likely due to the biological heterogeneity of nutrients and foods within these macronutrient categories.7Comparisons of any of these broad macronutrient categories with healthy vegetable fats would show harm,12 so why isolate SFAs? Indeed, compared with refined carbohydrates, SFAs seem to be beneficial.7

The overall evidence suggests that total SFAs are mostly neutral for health—neither a major nutrient of concern, nor a health-promoting priority for increased intake. 

Focusing On Reducing Saturated Fats Leads To Unhealthy Dietary Choices

I’ve written about this a lot. The most baffling aspect of this is the promotion of low or non-fat dairy.

There is no evidence that low fat dairy products are  healthier than full fat dairy products.

Non-fat yogurt filled with sugar should be considered a dessert, not a healthy food.

"Continued focus on modifying intake of SFAs as a single group is misleading—for instance, US schools ban whole milk but allow sugar-sweetened skim milk; industry promotes low-fat foods filled with refined grains and sugars; and policy makers censure healthy nut-rich snacks because of SFA content.13 "

It is extremely hard to change most people’s opinions on dietary fat.

My patients have been hearing the SFA traditionalist dogma for decades and thus it has become entrenched in their minds.

When I present to them the new progressive and science-based approach to fat and saturated fat some find it so mind boggling that they become skeptical of the skeptical cardiologist!

Hopefully, in the next few years, the progressive SFA recommendations will become the norm and maybe , some day in the not too distant future, the inexplicable recommendations for low-fat or non fat dairy will disappear.

As more data accumulates we may become SFA enthusiasts!

Saturatingly Yours,

-ACP

For another viewpoint (?from an SFA enthusiast) and  a detailed description of both editorials see Axel Sigurdsson’s excellent post here.

PCSK9: The canine that escalates Your LDL

Yes. PCSK9 is a factor in escalating LDL cholesterol levels. The point was brought home as I rode the escalator up from the first to the top pcsk9floor of the San Diego Convention Center at this year’s American College of Cardiology meetings. I suspsect if I had taken an elevator I would have seen a sign proclaming that PCSK9 is a factor in elevating cholesterol levels.
And PCSK9 signage is everywhere in this meeting.

 

 

Proprotein convertase subtilisin/kexin type 9, also known as PCSK9, is an enzyme that appears to degrade LDL receptors.

If you are born with a mutation that produces less active PCSK9 you have more LDL receptors and consequently more LDL is taken out of circulation leading to lower LDL levels.

Mutations leading to gain of PCSK9 function result in lower LDL receptors, higher LDL levels and substantial clinical evidence for premature atherosclerosis.

Amgen has produced all the PCSK9 signs that abound at the ACC meetings because they have produced a fully humanized monoclonal antibody (utilizing Chinese hamster ovaries) that inhibits PCSK9 and does a great job of lowering LDL without significant adverse effects.

At a late-breaking clinical trial session, results of longer term follow up of the company’s Osler randomized trials were presented and simultaneously published here.

The results were remarkably good. Not only did evolocumab drop LDL by 61% (from 120 down to 48) it showed significant improvement in cardiovascular outcomes.

“The rate of cardiovascular events at 1 year was reduced from 2.18% in the standard-therapy group to 0.95% in the evolocumab group (hazard ratio in the evolocumab group, 0.47; 95% confidence interval, 0.28 to 0.78; P=0.003).”

According to the biotech website fiercebiotech:

“The antibody is expected to win FDA approval by Aug. 27, trailing Sanofi ($SNY) and Regeneron’s ($REGN) alirocumab, which, thanks to some regulatory opportunism, is likely to hit the market a month or so before. Pfizer ($PFE) is in third place, working through Phase III with its bococizumab. Analysts say each treatment could bring in more than $3 billion a year at its peak…”

More study is needed of these drugs before approval in my opinion for a number of reasons. There is evidence of a small, but significant increase in neurocognitive side effects for one.

Although with evolocumab these were not related to the level of LDL achieved, there are concerns that extremely low LDL levels may interfere with neural development and such effects may not manifest for years.

The study authors did a good job of pointing out other limitations including small number of events, open-label design and patients selected who were free of adverse events. Hopefully, the FOURIER study will resolve these issues.

This post was also posted at SERMO, the physician social network. I would encourage physicians to join in the robust discussions on medicine and other topics at this site.

Skeptically Yours,

ACP

Since Dietary Cholesterol Isn’t Important Can I Stop Taking My Cholesterol Drug

A year ago one of my patients began experiencing  chest pain when he walked up hills. Subsequent evaluation revealed that atherosclerotic plaque (95% narrowing of a major coronary artery ) was severely reducing the blood flow to his heart muscle and was the cause of his chest pain. When this blockage was opened up with a stent he no longer had the pain.

Along with other medications (aspirin and plavix to keep his stent open) I had him start atorvastatin, the generic version of Lipitor, a powerful statin drug that has been shown to prevent progression of atherosclerotic plaque and thereby reduce subsequent heart attacks, strokes and death in patients like him

I saw him in the office the other day in follow up and he was feeling great . He asked me “Doc I read  your post yesterday.s Since you say that cholesterol in the diet doesn’t matter anymore, does that mean I don’t have to take my cholesterol drug anymore.?”

His question gets at the heart of the  “diet-heart hypothesis”. The concept that dietary modification, with reduction of cholesterol and fat consumption can reduce coronary heart disease.

The science supporting this hypothesis has never been strong but the concept was foisted on the American public and was widely believed. It was accepted I would  say because it has a beautiful simplicity which can be summarized as follows:

“If you eat cholesterol and fat it  will enter  your blood stream and raise cholesterol levels. This excess cholesterol will then  deposit in your arteries, creating fatty plaque , clogging them and leading to a heart attack.”

This concept was really easy to grasp and simplified the public health recommendations.

However, cholesterol blood levels are determined more by cholesterol synthesized in the liver and predicting  how dietary modifications will effect these levels is not easy.

Since the public has had the diet-heart hypothesis fed to them for decades and given its beautiful simplicity it is hard to reverse this dogma. My patient’s question reflects a natural concern that if science/doctors got this crucial question so wrong, is everything we know about cholesterol treatment and heart disease wrong?

In other words, are doctors promoting a great cholesterol hoax?

Evidence Strongly Supports Statins in Secondary Prevention 

For my patient the science supporting taking a  cholesterol-lowering statin drug is very solid. There are multiple excellent studies showing that in patients with established coronary artery disease taking a statin drug substantially reduces their risk of heart attack and dying.

These studies are the kind that provide the most robust proof: randomized, prospective and blinded.

level of evidenceWhen cardiologists rate the strength of evidence for a certain treatment (as done for lifestyle intervention here) we use  a system that categorizes the evidence as Level A, B, or C quality.

LeveleA quality (or strong) evidence consists of multiple,large, well-done, randomized trials such as exist for statins in patients with coronary heart disease.

Level B Evidence comes from a single randomized trial or nonrandomized studies.

Level C evidence is the weakest and comes from “consensus opinion of experts, case studies or standard of care.”

When treatment recommendations are based on Level C evidence they are often reversed as more solid data is obtained. Level A recommendations almost always hold up over time.

The level of evidence supporting restricting dietary cholesterol and fat to reduce heart attacks and strokes has always been at or below Level C and now it is clear that it is insufficient and should be taken out of guideline recommendations.

Evidence Strongly Supports Atherogenic Cholesterol is Related to Coronary Heart Disease

There are other lines of evidence that strongly support  the concept that  LDL cholesterol (bad cholesterol) or an atherogenic form of LDL cholesterol is strongly related to the development of atherosclerosis. If you are born with really high levels you are at very high risk for coronary heart disease, conversely if you are born with mutations that cause extremely low levels you are highly unlikely to get coronary heart disease.

Thus, the cholesterol hypothesis as it relates to heart disease is very much till intact although the diet-heart hypothesis is not.

Conflating the Diet-Heart Hypothesis and the Cholesterol Hypothesis

There is an abundance of misinformation on the internet that tries to conflate these two concepts. Sites with titles like “The Great Cholesterol Lie” , “The”  Cholesterol Hoax”, The Cholesterol Scam”  abound .

These sites proclaim that cholesterol is a vital component of cell membranes (it is) and that any attempt by diet or drugs to lower levels will result in severe side effects with no benefit

Doctors, according to these types of sites, in collusion with Big Pharma, have inflated the benefits of statin drugs and overlooked the side effects in the name of profit. Often, a “natural” alternative to statins is promoted.  In all cases a book is promoted.

The Great Cholesterol Truths

It’s unfortunate that nutritional guidelines have promoted restriction of cholesterol and fat for so long. These guidelines (like most of nutritional science)  were based on flawed observational studies. They should not have been made public policy without more consensus from the scientific community.  The good news is that ultimately the truth prevails when enough good scientific studies are done.

It is right to question the flimsy foundation of nutritional recommendations on diet and heart disease but the evidence for statin benefits in patients with established coronary heart disease is rock solid.

Hopefully, the less long-winded explanation I provided my patient in the office will persuade him to keep on taking his atorvastatin pills while simultaneously allowing him to eat eggs, shrimp and full fat dairy without guilt.

Cioppino and Cholesterol in the City by the Bay

IMG_2812
Crab cioppino from Sotto Mare. The crab is quartered and you must use utensils to get at it.

The other night  I had the best cioppino I have ever had. I’ve had variations of this wonderful tomato-based seafood stew  all over the world (including the legendary bouillabaisse in Marseilles) but I left my heart with the Dungeness crab cioppino served at Sotto Mare Oysteria and Seafood restaurant in North Beach, San Francisco. It makes sense, since cioppino was invented by Genoan fishermen from the SF Bay Area in the 19th century who threw together the freshest catch from their day at sea.

The recipe for Sotto Mare’s cioppino is actually available online as follows:
¼ cup olive oil
1 tsp. crushed red chile flakes
8 cloves garlic, finely chopped
3 cups fish stock
1 ½ cups whole peeled tomatoes in juice, crushed
10 leaves basil
1 lb. cod, cut into 2″ chunks
1 lb. cleaned calamari, bodies cut into ½″-wide rings
12 oz. medium shrimp, deveined
12 oz. bay scallops
16 clams, cleaned
16 mussels, cleaned
2 2-lb. Dungeness crabs or snow crab legs, halved
Kosher salt and freshly ground black pepper, to taste

It involves a lot of shellfish: calamari, shrimp, scallop, clams, mussels, crabs and I think a large part of what made it so good was the freshness of the shellfish obtained from the nearby Pacific Ocean.

Shellfish, Dietary Cholesterol and Cardiovascular Risk

Shellfish contain a lot of cholesterol and many of my patients have been told to minimize or avoid shellfish, especially shrimp, due to concerns they will exceed the (completely arbitrary) 300 mg daily limit suggested by the American Heart Association and the USDA nutritional guidelines.

There is no scientific basis for being concerned about the amount of cholesterol one consumes when eating shellfish (or for any food for that matter, as I previously wrote about with regard to eggs here)

But there are definitely warnings out there on the internet and traditional new media from seemingly responsible authorities.

This blurb from  the Physician Committee for Responsible Medicine is typical of the misinformation:

“Since our bodies make plenty of cholesterol for our needs,we do not need to add any in our diet. Cholesterol is found in all foods that come from animals: red meat, poultry, fish, eggs, milk, cheese, yogurt, and every other meat and dairy product. Choosing lean cuts of meat is not enough; the cholesterol is mainly in the lean portion. Many people are surprised to learn that chicken contains as much cholesterol as beef. Every four-ounce serving of beef or chicken contains 100 milligrams of cholesterol. Also, most shellfish are very high in cholesterol. All animal products should be avoided for this reason. “

The Physician Committee for Responsible Medicine appears to be a front for vegan-promotion. They go on to state that every 100 mg of cholesterol you consume raises your cholesterol by 5 mg/dl and that

“Every time you reduce your cholesterol level by 1 percent, you reduce your risk of heart disease by 2 percent.  For example, a reduction from 300 mg/dl to 200 mg/dl (i.e., a one-third reduction) will yield a two-thirds reduction in the risk of a heart attack”

A Fox News publication simultaneously extolls the virtues of shrimp consumption (noting that “three ounces of shrimp (or about seven medium-sized shrimp) has a mere 84 calories, 1g of fat, and an impressive 18g of lean protein” and that they are a great source of selenium, “an antioxidant that fights cancer-causing free radicals in your body”) and warns you against eating it (“If you are watching your cholesterol, it’s best to go easy on shrimp because four large shrimp have 42.5mg of cholesterol”)

Other publications advise those with high cholesterol or higher risk of heart disease to choose low-cholesterol varieties of shellfish over shrimp.

The Science Supporting Shrimp

Let’s look at what is actually known about consuming shrimp and shellfish.
A study of over 13,000 subjects (the ARIC study) found no increased risk of cardiovascular disease in the high shellfish consumers versus the low shellfish consumers.

A study in 1996 compared consuming a diet with 300 grams (about 10 oz.)  of steamed shrimp/day (providing 590 mg of cholesterol daily) versus a baseline diet of 107 mg/ cholesterol in 18 individuals without cholesterol problems.  The shrimp consumers compared to baseline had a 7% higher LDL or bad cholesterol but a 12% higher HDL or good cholesterol. Thus, the ratio of total to good cholesterol went down. We now know that this ratio is a much more important risk marker for cardiovascular disease than the total cholesterol. Triglycerides dropped significantly when subjects were consuming shrimp versus the baseline, low cholesterol diet.

A 1990 study looked at multiple different types of shellfish substituted for meat, cheese and eggs, and found that oyster, clam, crab and mussel diets (with lower cholesterol and higher omega-3 fatty acid profiles) lowered VLDL triglycerides and VLDL cholesterol.  These shellfish diets, except for the mussel diet, also lowered LDL and total cholesterol. Shrimp and squid had no effect on the lipid profiles.

 Benefits of Shrimp and Shellfish Consumption

I’ve focused on shrimp in this post because it has the highest cholesterol content of all shellfish and therefore is the most likely to be considered bad for heart patients or patients with high cholesterol. I’m presuming if I can convince you that shrimp are heart healthy, then you will believe that all shellfish are.

shrimp contentsTake a look at this chart of the nutrient composition of shrimp and you can understand that, once you eliminate  unsubstantiated fears of the cholesterol content, this a great food.

I am not a big advocate of examining the macronutrient composition of foods in order to predict their health benefits. This approach to nutritional science resulted in the development of highly processed low-fat monstrosities that currently sit in boxes and bags and line the most prominent parts of supermarket shelves. The overall effect of foods on the cardiovascular system depends on an incredibly complicated interaction of food components, bacteria in the gut and genetic predispositions: areas we are only beginning to understand. However, for those readers who are concerned about such things there is reassurance.

Start with the fact that there are no carbohydrates in shellfish: since carbs and added sugar are likely the biggest culprits in our obesity epidemic, shrimp and shellfish are great tools in helping to manage weight.  Shrimp have a very high percentage and quality of protein content for muscle building.

Some avid shrimp promoters insist that shrimp should be consumed regularly to reduce the risk of both cancer and heart disease.  The fat in shrimp is mostly polyunsaturated fat with a high ratio of omega-3 to omega-6 which is considered optimal . Eating 100 ounces of shrimp daily gives you 180 mg of EPA and DHA (considered the most important of the omega-3 fish oils for heart health) daily, close to the 250 mg daily the USDA recommends for most adults.

Astaxanthin has been found to be a potent natural antioxidant, exceeding ten times the antioxidant activity of β-carotene and 500 times that of α-tocopherol. The astaxanthin level of wild shrimps has been reported to vary between 740 and 1400 μg/100 g in edible meat portions.

If I were a vegan or vegetarian I would consider slipping shrimp into my dishes instead of tofu.

Adulterated Shrimp

The cioppino recipe above doesn’t add a lot to the shellfish and fish: a little olive oil and tomatoes, basil and garlic-these things are not going to jack up the calories, sugar or fat content.

Depending on how you cook shrimp, the resulting dish will have markedly different nutrient composition compared to the raw nutrients listed above.

Breading and deep frying the shrimp takes 3 oz from 60 calories to 206 and the fat grams from 1 to 10.  I suspect that you or your body will figure this out and eat less later. Given the fairly low fat and carbohydrate content of the Sotto Mare cioppino, I am ashamed to admit, I ate that whole bowl pictured above (which the menu said could be shared between two).

The SOSC doesn’t share my love of cioppino; she ordered the linguine with clam sauce. Three ounces of clams have only 26 mg of cholesterol but it seems to me the majority of calories in this dish are coming from the carbs in the pasta and whatever the composition of the sauce is. In any event, the SOSC pronounced it the best she has ever had.

Mercury in Shellfish

The level of mercury is a concern in all the fish that we consume.  Fortunately a recent study from Maine University found that shrimp is very low in mercury.mercury by type of shrimp This included varieties from Thai shrimp farms, Maine shrimp farms and the Gulf of Mexico. In comparison to other types of fish, shellfish are universally on the low end of the mercury level graph as shown below.mercury in fish

 

 

 

Fear neither the  cholesterol nor the mercury in shrimp and consume your cioppino with gusto and without guilt!

 

Should All Men Over Sixty Take a Statin Drug?

The updated AHA/ACC Cardiovascular Prevention Guidelines (CPG) which include the   excessively wordy “The Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults Risk” were published late last year and immediately were the center of controversy.

After working with them for 9 months and using the iPhone app to calculate my patients’ 10 year risk of atherosclerotic cardiovascular disease (ASCVD, primarily heart attacks and strokes) it has become clear to me that the new guidelines will recommend statin therapy to almost all males over the age of 60 and females over the age of 70.

As critics have pointed out, this immediately adds about 10 million individuals to the 40 million or so who are currently taking statins.

Should we be starting all elderly Americans on statin drugs?

My simple answer is no. It doesn’t make sense to do this, because clearly not all elderly individuals have atherosclerosis or will ever develop its consequences of heart attack and stroke. Many have inherited the genes that allowed their parents to live free of heart disease into their 90s and will not benefit at all from long term statin therapy; they may actually suffer the expense and side effects instead.

How can we better decide who among the elderly will benefit from statin therapy?

If you have read my previous posts on searching for subclinical atherosclerosis here and here you probably know the answer. Let’s look at a specific case and apply those principles.

Robert is 69 years old. I see him because, in 2010, the posterior leaflet of his mitral valve ruptured, resulting in the mitral valve becoming severely incompetent at its job of preventing back flow from the left ventricle into the left atrium. I sent him to a cardiac surgeon who repaired the ruptured leaflet. Although he has a form of “heart disease,” this is a form that has nothing to do with cholesterol, hypertension or diabetes and is not associated with ASCVD.

However, it is my job to assess in him, like all individuals, the risk of developing coronary heart disease or ASCVD.

He has no family history of ASCVD and he feels great since the surgery, exercising aerobically 4-5 times per week.

His BMI is 23.87 which is in the normal range. His BP runs 116/80.

His total cholesterol is 210 and LDL or bad cholesterol is 142. Good or HDL cholesterol is 56 and triglycerides 59. The total and LDL cholesterol levels are considered “high,” but they could be perfectly acceptable for this man.

When I ran his 10 year ASCVD risk (risk of developing a heart attack or stroke over the next 10 years), it came back as 14%. The new guidelines would suggest having a conversation with him about starting a statin if his risk is over 7.5%. His risk is double this and statins are definitely recommended in this intermediate risk range. Interestingly, I cannot enter a cholesterol level or blood pressure for a man of this age that yields a risk less than 7.5%.

When I had my discussion with him about his risk for ASCVD, I plugged his numbers into my iPhone and showed him the results and gave him the guideline recommendation.

Lifestyle Changes to Lower Cholesterol

The new Cardiovascular Prevention Guidelines have a section devoted to Lifestyle Management to Reduce Cardiovascular Risk. Unfortunately, none of the lifestyle changes they recommend have been shown to reduce ASCVD risk in an individual like Robert. He already exercises the recommended amount, is at his ideal body weight and eats a healthy diet. If we were to tighten up on his diet by, say reducing red meat, eggs and high fat dairy, all we would accomplish would be to lower his LDL and HDL cholesterol levels and make his life and meals less satisfying. The lower total cholesterol and LDL cholesterol would not lower his risk of ASCVD and the calculated 10 year ASCVD risk would still be in the range where statins are recommended.

Therefore, I am not going to tell Robert that he should reduce his saturated fat consumption (he already has incorporated that into his diet since he’s been bombarded with the low fat mantra for 30 years).

Searching for Subclinical Atherosclerosis

I’m going to tell Robert that we need to know if he has atherosclerosis, the disease that we are attempting to modify.

We started with an ultrasound to look at the lining of the large arteries in his neck that supply blood to the brain, the carotid arteries (a process I describe in more detail here). Although severe atherosclerotic blockages in these arteries put one at risk of a stroke, I was much more interested in the subtle changes in the arteries that precede symptoms and are an early harbinger of atherosclerosis.

Careful ultrasound recording and measurement of the main common carotid arteries from both the left and right side showed that the IMT or thickness was lower than average for his age, gender and ethnicity. His carotid IMT was at the average for a 60 year old, therefore, his so-called vascular age was 60 years, younger than his chronological age. If I plug that age into the ASCVD risk estimator, I get an 8.2% 10 year risk, just barely above the statin treatment cut-off.

Careful scrutiny with ultrasound of the entire visible carotid system in the neck on both sides did not reveal any early fatty plaques or calcium in the lining of the carotid arteries. He had no evidence for atherosclerosis, even very subtle early forms, in this large artery, a finding which is usually predictive of what is going on in the other large arteries in the body, including the coronary arteries, which supply blood to the heart.

At this point, I think, we could have stopped the search for subclinical atherosclerosis and agreed that no statin therapy was warranted. However, Robert wanted further reassurance that his coronary arteries were OK, therefore we set him up with a coronary calcium study (see my full description of this test here).

Searching for Subclinical Atherosclerosis: The Calcium Score

Robert’s coronary calcium score came back at 21 (all in the LAD coronary artery) , which put him at the 26th percentile compared to normal men of his age and gender. A score of 21 is average for a 59 year old man and 82% of men aged 69 have a score greater than zero. Robert had much less calcium in his coronaries than men his age, another factor putting him in a low risk category.

Given the low risk findings from both the vascular screening and the coronary calcium, I felt comfortable recommending no statin therapy and going against the guidelines.

Statins: Better Targets for The Two-edged Sword

This is not an unusual scenario; many of my older patients without heart attacks, strokes or diabetes fall into the risk category that would warrant statin therapy and if they have no clinical or subclinical evidence of atherosclerosis, I don’t advise statin therapy. My patients are free to follow the guidelines and take statin drugs after this advice, but most are very grateful that another pill (which they likely have heard bad things about on the internet or from friends with adverse experiences) can be avoided.

Statins are wonderful drugs when utilized in the right population, but they also carry a  9% increased risk of diabetes and about a 10% real world risk of developing muscle aches and weakness (myalgia).

I think it is essential to aim these two-edged swords at the right targets if we are to maximize the overall health benefits.

Statin Drugs Have Benefits Beyond Cholesterol Lowering

For most of the last 25 years I have told patients when I recommend  a statin drug to them that they should take it in order to lower their bad cholesterol (and raise the good cholesterol) thereby lowering their risk of future heart attacks.

I based this statement on my understanding of large statin trials which demonstrated reduction in heart attacks seemingly closely tied to drops in the bad cholesterol level.

Although I was aware of the so-called “pleiotropic” (meaning effecting multiple pathways leading to atherosclerosis) of statins it was easier to point to the cholesterol lowering effects and unify that message with the recommendation to reduce fat and cholesterol in the diet , thereby lowering cholesterol in the blood and arteries and cut heart attack risks.

Thus emerged a very simple (and likely false) paradigm: Fat in the diet causes fat in the blood which causes fat in the arteries which causes fatty plaques in the coronary arteries which causes heart attacks when they get too big and block off the blood flow.

I, like most cardiologists and lay people  mistakenly assumed that since lower bad cholesterol levels associated with taking a statin drug were associated with lower heart attack risks then dietary changes aimed at lowering bad cholesterol levels would also lower heart attack risk.

It turns out that we don’t really know how the statins reduce heart attacks . As a recent review points out:

 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 the thrombogenic response. Furthermore, statins have beneficial extrahepatic effects on the immune system, CNS, and bone. Many of these pleiotropic effects are mediated by inhibition of isoprenoids, which serve as lipid attachments for intracellular signaling molecules. In particular, inhibition of small GTP-binding proteins, Rho, Ras, and Rac, whose proper membrane localization and function are dependent on isoprenylation, may play an important role in mediating the pleiotropic effects of statins.

Supporting the non cholesterol lowering effects of statins on reducing CVD are the following observations

-Most heart attack victims don’t have elevated bad cholesterol levels and dietary reduction of bad cholesterol doesn’t seem very effective at preventing heart attacks.

-Drugs, like Zetia or ezetimibe which lower cholesterol level by other mechanisms don’t seem to prevent atherosclerosis even though they substantially lower bad cholesterol levels.

-Statin drugs reduce heart attacks in patients who have normal or low bad cholesterol levels

What Causes Atherosclerosis?

An article (Innate and adaptive inflammation as a Therapeutic Target in Vascular Disease) published in JACC recently by Tousoulis,et al. summarizes the current understanding of how atherosclerosis develops and the multiple ways that statins may affect that process. They write

Atherosclerosis, once thought to be a lipid storage disease, is now considered a chronic low-grade inflammatory condition that affects the vascular wall. It is characterized by the deposition of cholesterol and lipids followed by infiltration of T cells and macrophages, all as a result of an endothelial injury response.

I’m including this figure from the article to give you some idea of how incredibly complicated the process is.

atherosclerosis
Overview of Mechanisms Involved in Atherosclerosis Low-density lipoprotein (LDL) is oxidized in the presence of reactive oxygen species (ROS) and binds to proteoglycans (heparin sulfate) while simultaneously stimulating the endothelium, leading to adhesion molecule overexpression and increasing its permeability. Apart from this action, oxidized low-density lipoprotein (ox-LDL) inhibits nitric oxide (NO) production, prohibiting vasodilation. Furthermore, cytokines and other chemoattractant molecules, such as MCP-1, are secreted, favoring leukocyte adhesion. Leukocytes come into random contact with the activated endothelium and, due to interactions with adhesion molecules, roll and tether and are subsequently firmly arrested. In addition, leukocytes transmigrate into the subendothelial space, where they differentiate into macrophages, which in turn take up ox-LDL, forming foam cells. Ox-LDL antigens are presented by macrophage major histocompatibility complex class II (MHC-II) proteins and are recognized by CD4+ T cells. These preferentially differentiate into Th-1 cells, pro-inflammatory cytokine production. Finally, smooth muscle cell (SMC) proliferation and migration are induced as a result of cytokine and growth factor secretion.

Can you imagine trying to explain this to the average patient?

My eyes glazed over once I reached MCP-1.

Thus, doctors end up giving the simple, accepted conventional wisdom that we are “treating” high cholesterol by giving statin drugs. What we are really treating is atherosclerosis. And statins are the only effective drug treatment we have identified for this ubiqitous  and complex process.

It is entirely possible that the lower LDL cholesterol caused by statin drugs is totally unrelated to their ability to forestall atherosclerosis. The new cholesterol guidelines reflect this concept as they don’t recommend treating to an LDL target level.

I end with the closing comments from the article by Tousoulis, et al.

Given the fact that atherosclerosis is a multivariable disease, with several molecules involved in each stage, it is vey difficult to find an effective treatment. However, statins prove to be the most effective treatment so far because they interfere with most of the critical components of the atherosclerotic process and have been proven to have beneficial effects. Further to their well-established impact on nonspecific low-grade inflammation, statins also appear to have significant effects on innate and adaptive immunity that have been underestimated so far.