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 Gandolifini’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”.
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.