Heart Attack and Sudden Death. “It’s the particles stupid”.

Actor James Gandolfini’s sudden and tragic passing has cruelly reminded us about the seriousness and unpredictability of cardiovascular disease. Sudden death in middle age is most often caused by underlying coronary heart disease (CHD). One has to wonder, in light of current knowledge and modern technology, why we can not prevent such devastating events. One explanation may be the fact that CHD often is a very unpredictable disorder. In some cases, serious disturbances of heart rhythm (ventricular fibrillation) leading to sudden death is the first symptom. This is usually caused by an abrupt blockage of one of the coronary arteries that supply blood to the muscle of the left ventricle of the heart.

Recently, on the website Lecturepad, Thomas Dayspring MD and James A Underberg MD reflected on the teachable moment G

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andolifini’s untimely demise presents.  Lecturepad is one of my favourite websites for medical information. It needs a registration, but I presume everyone can have one, and it is definitively worthwhile. Their educational material is top class and up to date.

Dayspring and Underberg suggest that “if modern diagnostic blood tests were routinely performed and any discovered abnormalities were treated with proper lifestyle and appropriate pharmacological intervention, premature death from CHD would likely disappear”.

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The Dreaded Plaque Rupture

In their article, Dayspring and Underberg point out that “humans do not die from severely narrowed or blocked coronary arteries or pipes” as we have often been lead to believe. “The fact is that the real cause of heart attack is the presence of small, obstructive cholesterol laden plaques that suddenly rupture and rapidly induce blood clots that obstruct the artery, which causes blood flow to the heart to be blocked, leading to injury or death of heart muscle”.

They don’t go into details about what cause plaque formation and why plaques rupture. A plaque that is prone to rupture can not be detected by a blood sample, an electrocardiogram (ECG), an exercise test, an ultrasound of the heart or a coronary calcium scan. Even coronary angiography usually can not differ between a rupture-prone plaque and a stable plaque. One of the biggest questions in cardiology today is how we can detect plaques that are prone to rupture from those who are not. Dayspring and Underberg on the other hand point out that “the only absolute requirement for plaque development is the presence of cholesterol in the artery: although there are additional heart risk factors like smoking, hypertension, obesity, family history, diabetes, kidney disease, etc., none of those need to be present”.

Cholesterol and Risk

Measurements of blood cholesterol have traditionally been used for risk testing. In particular, blood levels of low density lipoprotein cholesterol (LDL-C) are used to assess risk and to guide therapy. Lowering LDL-C is considered an important target to reduce the risk of future CHD, and among patients with known cardiovascular disease.

However, measuring cholesterol levels in the blood may be misleading, because cholesterol circulating in our blood will not cause plaque unless it settles in the arterial wall. According to Doctors Dayspring and Underberg ” The graveyard and coronary care units are filled with individuals whose pre-death cholesterol levels were perfect. We now understand that the major way cholesterol gets into the arteries is as a passenger, in protein-enwrapped particles, called lipoproteins”. They believe that we have much better biomarkers than blood cholesterol to assess cardiovascular risk.

They write: “Particle entry into the artery wall is driven by the amount of particles (particle number) not by how much cholesterol they contain. CHD is very often found in those with normal total or LDL cholesterol levels in the presence of a high LDL particle number (LDL–P). By far, the most common underlying condition that increases LDL particle concentration is insulin resistance, or prediabetes, a state where the body actually resists the action of the sugar controlling hormone insulin. This is the most common scenario where patients have significant heart attack risk with perfectly normal cholesterol levels. The good news is that we can easily fix this, sometimes without medication.”

The Role of Sugar and Carbohydrates

In general, most methods that lower LDL-C have some ability to lower LDL-P. However, there are some differences.  In order to lower LDL-C, most doctors will recommend eating less fat and cholesterol from meat and dairy products. Statin therapy significantly lowers LDL-C. Therapies may affect the LDL particle number differently. Interventions that will lower LDL-C more than LDL-P include statins, estrogen replacement therapy, some antiretrovirals, and a low-fat, high-carbohydrate diet. Interventions that lower LDL-P more than LDL-C include fibrates, niacin, pioglitazone, omega-3 fatty acids, exercise, and Mediterranean and low-carbohydrate diets.

Patients with high levels of triglycerides and low high-density lipoprotein cholesterol (HDL-C) are likely to have high LDL-P despite normal or low LDL-C. Such a lipid profile is typical for individuals with overweight, obesity and the metabolic syndrome. Studies indicate that carbohydrate restriction reduces LDL particle number among these individuals.

Doctors Dayspring and Underberg believe that it is possible to reduce the risk of CHD among individuals with high LDL-P despite normal or close to normal LDL-C: “The key to understanding how comes with the knowledge that the driving forces are dietary carbohydrates, especially fructose and high-fructose corn syrup. In the past, we’ve often been told that elimination of saturated fats from the diet would help solve the problem. That was bad advice. The fact is that until those predisposed to insulin resistance drastically reduce their carbohydrate intake, sudden deaths from coronary heart disease and the exploding diabetes epidemic will continue to prematurely kill those so afflicted. While obesity and insulin resistance often co-exist, 1 out of 5, or (20%), of afflicted patients have a normal body mass index (BMI). That is why testing and correctly interpreting the right blood tests are so important. And for goodness’ sake, if you want to live longer, start reducing the amount of dietary carbohydrates, including bread, potatoes, rice, soda and sweetened beverages (including fruit juices), cereal, candy – the list is large”.

“It’s the Particles Stupid”

These are Dayspring’s and Underberg’s final remarks: “James Gandolfini’s death is a tragedy, and if history is our guide, our guess is that we will find that his passing was likely preventable.  It’s important for both doctors and families to learn these lessons so that similar tragedies are prevented from occurring in our own families.  Bill Clinton (also a victim of a preventable heart attack) won the 1992 election with the slogan, “It’s the economy stupid.”  When it comes to heart disease, a similar quip is equally as powerful and important: “It’s the particles, stupid.”

Here is an article explaining the difference between LDL-C and LDL-P.

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Ken
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Ken

Fantastic article (one of your best)! As my wife and I have been living a Paleo+ lifestyle for almost a year, we have come to see very clear evidence of that which you speak. Carbs (other than plant-based, non-grain) have been rather painlessly removed from our diet, and our bloodwork shows the phenomenal benefits. Hopefully the word will spread and the AMA and AHA will finally get on board.
Thank you for your wonderful newsletter. If ever in Iceland we hope to say ‘hello.’

Axel F Sigurdsson
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Axel F Sigurdsson

Thanks Ken. Appreciate your interest and hope you continue to follow my blog and share your thoughts.

Art Ford
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Art Ford

Although particles are likely to have an important role, I think it’s a mistake to confer on them the ‘holy grail’ of all CHD. This same mistake was first made with TC, then LDL, and now Dayspring has become the new Ancel Keys, only now its the “particles,” stupid. There are likely additional factors at work in CHD, which if ignored by patients the more cardio event deaths will occur. Unfortunately, the bombastic and singular-minded Dayspring is doing the public a disservice by performing just like Keys. Before people dedicate their total focus (and unhealthy obsessions) solely on particle reduction,… Read more »

Axel F Sigurdsson
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Axel F Sigurdsson

You’re right Art. Coronary artery disease is a multifactorial disorder. Many different mechansims contribute to atherosclerosis. However, if we’re stuck on a sideroad, it may take strong words and unilateral efforts to get us back on track.

Mie
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Mie

Although I cannot totally agree with Art’s comments on the “mistakes” of LDL – since I really don’t know what he means by that – I agree with the idea the Dayspring and Underberg are oversimplifying matters. 1) “Dayspring and Underberg on the other hand point out that “the only absolute requirement for plaque development is the presence of cholesterol in the artery: although there are additional heart risk factors like smoking, hypertension, obesity, family history, diabetes, kidney disease, etc., none of those need to be present”.” Yes, it takes elevated LDL levels for fatty streaks (the first step toward… Read more »

Annette
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Annette

I see no mention that a lack of magnesium in the body can also cause this. By allowing calcium free rein in the body it will deposit in the heart and any other soft tissues. The sad diet is lacking in magnesium. Up the magnesium and ditch the grains and the bad oils.

jake3_14
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jake3_14

There are multiple co-factors for calcium assimilation: magnesium, boron, silica, and vit. K2. It’s vit. K2 that catalyzes the movement of calcium into bones and prevents its buildup in vascular tissue.

jake3_14
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jake3_14

Calcium requires multiple co-factors for proper assimilation: magnesium, boron, silica, and vit. K2. It’s vit. K2’s role, not magnesium’s, to activate matrix-Gla protein, which prevents calcification of blood vessels and organs. In addition, K2 activates osteocalcin to transports calcium to the bones, where K2 solidifies this calcium into the bone matrix.

Axel F Sigurdsson
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Axel F Sigurdsson

Thanks Annette. The issue on magnesium is interesting. There is so much we don´t know about this mineral and so much indicating that magnesium deficiency is more common than we have been lead to believe. Do you know if there are any scientific studies relating magnesium deficiency to acute heart attack?

Katy
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Katy

What about inflammation in the blood vessels, inflammation causes the cholesterol to build… From Dr. Dwight Lundell’s website “Simply stated, without inflammation being present in the body, there is no way that cholesterol would accumulate in the wall of the blood vessel and cause heart disease and strokes. Without inflammation, cholesterol would move freely throughout the body as nature intended. It is inflammation that causes cholesterol to become trapped”….

Mie
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Mie

And cholesterol itself can cause inflammation. See e.g. these

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3243497/

https://www.ncbi.nlm.nih.gov/pubmed/20428172

if you’re interested in the mechanism.

Katy
Guest
Katy

Thanks, Mie… Appreciate the input…

Axel F Sigurdsson
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Axel F Sigurdsson

You´re absolutely right Katy. Inflammation probably plays an important role in atherosclerosis and coronary heart disease. Interestingly, inflammation is associated with obesity, the metabolic syndrome and type 2 diabetes. For an obese patient, losing weight usually reduces markers of inflammation. Choosing carbohydrates with a low glycemic index (GI) is usually associated with less inflammation than those with a high GI. The Mediterranean diet is an example of a diet that has been shown to reduce inflammatory markers. There are ongoing clinical trials testing the efficacy of anti-inflammatory drugs in patients with coronary heart disease.

Katy
Guest
Katy

Thanks, appreciate the information… And also, appreciate your blog…

Donal O'Neill
Guest

Dr. Sigurdsson this is a brilliantly informative article which I am now sharing with our followers. Thank you! “Cereal Killers” – our new feature length documentary focuses on my own attempt to avoid a family history of CHD and type 2 diabetes (despite being v lean + apparently healthy), under the watchful eye of Prof Tim Noakes MD in Cape Town, South Africa. Cholesterol Particles and Carbohydrate Restriction feature strongly in the implementation and analysis of my 4 week medically supervised nutritional intervention – the results will astound many but not your good self I should think. The film will… Read more »

Axel F Sigurdsson
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Axel F Sigurdsson

Thanks Donal. Took a sneak peak at your movie. Highly interesting. I´m certainly looking forward to see it when it´s released in september. I´m impressed by your commitment and urge to look for answers. Thanks for sharing. Good luck with it all.

Peggy Holloway
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People just can’t get over the failed “lipid hypothesis” and simply won’t believe that saturated fat is one of the healthiest fats you can consume. After 14 years of low-carb, I have upped fat intake to about 85%, following a ketogenic plan, and just get healthier and healthier. Insulin resistance is rampant in my family and I have no doubt that without my dietary changes, I would be like my father at my age, fat, diabetic and with heart disease.

Mie
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Mie

Peggy, the so-called lipid hypothesis – which states that plasma cholesterol levels & CHD are connected – is way past the point of being a mere hypothesis. The evidence is as solid as … well, can be.

And there’s nothing healthy about saturated fat: higher intakes of it haven’t been shown to produce benefit in anything.

Nick
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Nick

Peggy don’t listen to Mie the evidence is far from solid and has many inconsistencies, the hypothesis has never been proven, associations have been shown using epidemiological studies but these have many flaws like poor dietary intake assessment, limited lifestyle assessments and miss classification of food types/ groups. So poor associations at best. This meta-analysis of RCTs (gold standard) showed that fat modification not reduction reduced the incidence of CHD episodes. Subgroup analysis showed reducing sat fat and replacing with starch creating a low fat diet showed no risk reduction. There was no difference in CHD mortality between groups. Results… Read more »

Mie
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Mie

Nick, please. Of course no one’s forcing you to be coherent here, but …You do realize that Peggy mentioned (and I answered her about) the lipid hypothesis? The so-called “diet-heart hypothesis” is a different thing.

Art Ford
Guest
Art Ford

Wanted to elaborate a little more on my earlier response. 1. Like others, I do think your article was good and informative. 2. As a blogger myself, I can understand the article’s headline and the use of James Gandolfini’s picture. But the fact remains, there is no evidence that his death was due to “particles.” 3. Based on his appearance/physique alone, and the type of food and beverage that he likely often ate (https://tinyurl.com/ktq5kwc), he was walking heart attack waiting to happen. 4. In every episode of the Sopranos, Gandolfini’s labored breathing was obvious – my impression was that he… Read more »

Axel F Sigurdsson
Admin
Axel F Sigurdsson

I do agree with you. Of course we can’t allow ourselves to only look at the LDL-particle count. There are a lot of other important risk factors, some of which you mention, like smoking and high blood pressure. Although Gandolfini’s death sparked my article, my intention was not to analyse his personal health nor his risk factors. I don’t know anything about his LDL particle count or his medical history in general. So, my intentionm was not to discuss Mr. Gandolfini’s health or trying to figure out the cause of his tragcic and sudden death. That’s up to other people… Read more »

David
Guest
David

In looking at his last meal link from Art above, I can’t help but notice lots of fried food. I had my heart attack after fried falafel. I can still hear the sound of it hitting the deep fat fryer in the nearby restaurant kitchen. In her book “Deep Nutrition” by Dr. Cate Shanahan, she states that she has asked her heart attack patients if they had fried food before their heart attacks, and she says that “all” of them have said yes. I don’t have the book any more, but I believe she said something about the fried aspect… Read more »

Low-fat Richard
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Low-fat Richard

I agree with “Mi(k)e” here! Axel, Dr Dayspring idea’s about SFA avoidance being a failed public health measure is highly problematic based on pure mathematics. The IMPACT models by Simon Capewell show that the age-adjusted mortality in US has halved since the 1960s. The decline in mean serum cholesterol levels of Americans (from 240 to the current 200mg/dl), that occurred prior to statins, explains 25% of this reduction in CHD mortality. Much more dramatic findings have been observed in North-Europe and New Zealand. In Finland, the age-adjusted CHD mortality went down 80%. Decline in cholesterol levels explains 50% of this… Read more »

Mie
Guest
Mie

BTW, Richard: it’s “Mie”, not “Mike”. I’m not using my own name, but rather referring to a local dialect in Finland (which you, being from Finland too you recognize & possibly even appreciate).

Low-fat Richard
Guest
Low-fat Richard

Moreover, I find the way Dr Dayspring perceives heart disease highly problematic. Cholesterol is an issue of cumulative exposure. Whether someone has “normal” cholesterol at his/her last decades of the life span is less irrelevant. Besides, cholesterol levels start to plummet after the age of 65-70 due to metabolic changes in the intestine resulting lower absorption and synthesis of cholesterol. The cumulative exposure model was highlighted by the ATP-3 panel already in 2004: “Only in populations that maintain very low levels of serum cholesterol, e.g., total cholesterol <150 mg/dL (or LDL cholesterol <100 mg/dL) throughout life do we find a… Read more »

Dexter
Guest
Dexter

I am somewhat confused. As someone who has a LDL-C of 190 and LDL-P of 2100 with 9% of the 2100 being small dense, and a triglycerides of 28 and & HDL-C of 95…I thought I was healthy. But Dayspring & Underburg do not mention particle size as being a marker for CVD…only total particle number of LDL. The rupturing of plaque: “The fact is that the real cause of heart attack is the presence of small, obstructive cholesterol laden plaques that suddenly rupture and rapidly induce blood clots that obstruct the artery, which causes blood flow to the heart… Read more »

Peter
Guest
Peter

Dexter, your high NMR LDL-P is similar to mine, along w/ ideally low risk levels on all other lipid NMR markers and total absence of metabolic disorders. This seems to occur to some of the long-term LCHF eaters, anecdotally speaking. But for those eating the Standard-American-Diet (SAD), a high LDL-P seems to flag a CVD risk, even in those w/ normal LDL-C. And upon further examination, often cited by Dayspring’s discordant case analysis, these SAD usually have high TG & low HDL and accompanied by some metabolic syndromes. LDL-P seems like a valid proxy for CVD for SAD. Is high… Read more »

Judit Victor
Guest

DEFINITELY anecdotal only Peter! I have HeFH and went onto LCHF. Think I’m the only one in the world what dunnit! The more animal, coconut and olive fats I ate the lower my LDL got. BUT, of course, no-one cares, even though Lancet has all my astounding results. My son, who is a sportsman, refused LCHF, and over this past Christmas at 34 had quintuple bypass surger. I was floored. Now his hereditary condition has stabilised on high fat, although, he will not say a word of this to his cardiologist. He was prescribed 80 mg Crestor and almost died… Read more »

Low-fat Richard
Guest
Low-fat Richard

The problem with low-carbers is that they do not know the history nor the foundation of the diet-heart research. The eastern Finnish cohort in the 7CS showed highest CHD mortality in the world at the baseline and subsequent follow-ups. Abdominal obesity and metabolic syndrome was extremely infrequent in the cohort which was comprised mainly of very hard-working timbermen. The participants in the cohort had never visited MickeyDee’s nor ever had a can of coca-cola in their life. Second observation comes from the nomadic Kirghiz pastorals who ate lot of organic, grass fed beef and drank a lot of organic whole-milk.… Read more »

Ash
Guest

When it comes to heart disease, I get the sinking feeling that I have been sold an old nag for a premium price. Thank you so much much for debunking myths. Day by day, I realize more and more that there is no way to cheat on my diet and get away with it. I am reminded of Newton’s Law – “For every action there is an opposite and equal reaction.” In my diet, it seems poor choices accumulate despite all good signs to the contrary.

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