Why Hearts Attack

The pendulum is swinging back, Cholesterol is taking a backseat to chronic Inflammation as the driver of heart disease and cancer. It is difficult to pin it only on cholesterol when half of heart attack events occur in individuals with cholesterol levels considered safe (within acceptable levels). article ref ref ref  (C-Reactive Protein indicates inflammation somewhere in body)

NEW UPDATE BELOW

Here is everything and more you would ever want to know about cholesterol, a vital ingredient for health. And the chart that says it all. Next is info the Medical Profession uses to support more statin use. ref Someone has to justify this with these facts. ref  And NOW, 2015, the US Government makes startling admission on dietary cholesterol. ref

Insight: Here are the results of a large analysis of dietary patterns on CVD from 42 Countries. Interesting results. Saturated fat is taking a back seat.

The body uses EPA, an omega 3 fat, as the controller of the inflammatory process through messengers it produces and sends out to stop the enzyme processing of both Omega 3 and Omega 6 pathway cascades, especially of Omega 6 into Arachadonic Acid (AA). AA produces messengers that participate in pro-inflammatory actions. A healthy ratio is needed between these factors which a balanced diet (before 20th century) maintained. It is now known that there is a very profound balance needed between Omega 3 EPA and DHA and omega 6 AA that not only influences fatty acid balance and messenger production, but also on transcription factors that help regulate inflammatory gene expression. Most notably NF-kB. This one you will hear more about as new cancer theories put it front and center in cancer promotion and growth. ref

This important research from almost 28,000 Women's Health Study shows chronic inflammation connected to fatty acid profile balance between omega 6 and omega 3 is vital to controlling and preventing chronic inflammatory caused heart and stroke conditions. 

"BACKGROUND  (study referenced above copied here in case link is lost)

Both C-reactive protein and low-density lipoprotein (LDL) cholesterol levels are elevated in persons at risk for cardiovascular events. However, population-based data directly comparing these two biologic markers are not available.

Full Text of Background...

METHODS

C-reactive protein and LDL cholesterol were measured at base line in 27,939 apparently healthy American women, who were then followed for a mean of eight years for the occurrence of myocardial infarction, ischemic stroke, coronary revascularization, or death from cardiovascular causes. We assessed the value of these two measurements in predicting the risk of cardiovascular events in the study population.

Full Text of Methods...

RESULTS

Although C-reactive protein and LDL cholesterol were minimally correlated (r=0.08), base-line levels of each had a strong linear relation with the incidence of cardiovascular events. After adjustment for age, smoking status, the presence or absence of diabetes mellitus, categorical levels of blood pressure, and use or nonuse of hormone-replacement therapy, the relative risks of first cardiovascular events according to increasing quintiles of C-reactive protein, as compared with the women in the lowest quintile, were 1.4, 1.6, 2.0, and 2.3 (P<0.001), whereas the corresponding relative risks in increasing quintiles of LDL cholesterol, as compared with the lowest, were 0.9, 1.1, 1.3, and 1.5 (P<0.001). Similar effects were observed in separate analyses of each component of the composite end point and among users and nonusers of hormone-replacement therapy. Overall, 77 percent of all events occurred among women with LDL cholesterol levels below 160 mg per deciliter (4.14 mmol per liter), and 46 percent occurred among those with LDL cholesterol levels below 130 mg per deciliter (3.36 mmol per liter). By contrast, because C-reactive protein and LDL cholesterol measurements tended to identify different high-risk groups, screening for both biologic markers provided better prognostic information than screening for either alone. Independent effects were also observed for C-reactive protein in analyses adjusted for all components of the Framingham risk score.

Full Text of Results...

CONCLUSIONS

These data suggest that the C-reactive protein level is a stronger predictor of cardiovascular events than just the LDL cholesterol level and that it adds prognostic information to that conveyed by the Framingham risk score." --end of copy

UPDATE: A new enzyme has been associated with inflammation in arteries. Adding measurements of this enzyme to CRP levels in chest pain patients gives even greater alert to the likelihood of a pending heart attack. The enzyme myeloperoxidase, or MPO, is made in white blood cells. This enzyme is produced and at higher concentrations when arteries are inflamed and have rupture-prone fatty deposits. ref

Remember, inflammation and resulting C-Reative Protein are present in all cases of artery diease, BUT not all people with high C-Reative Protein and inflammation have artery diesease. MPO represents one additional key to explaining why this is so. 

A new drug, Lovaza, made of a highly refined fish oil is showing promise in protecting against heart attacks. The omega 3 fats in fish oil protect the cell membranes covering plaque and prevent rupture through an interactive process acting between platelets in the blood and intestinal wall cell membrane integrity. Lowering triglyceride levels might be one mechanism responsible for these omega 3 actions.  ref   Plus, omega 3 fish oils also increase the LDL particle sizes. Larger is better.

This again brings back into play the dietary ratio of omega 6 to omega 3 fatty acids, or at least the level of omega 3 at sufficient amounts to offer protection against and modulate the pro-inflammatory cascade effect. Trans-fats are especially damaging here and the falling heart attack rate from the 1970s onward might in large part be influenced by the health food industry offering healthier alternatives and generating awareness. This change in heart attack rate direction started about 10 years BEFORE statins were introduced. The downward decline did not change or vary after Statin introduction. The Scientific talk of late has been about the anti-inflammation effects of Statins rather than about cholesterol lowering. The facts now overwhelmingly support this.

Very Interesting!  A complete index to references for the many inflammatory markers in the body. Notice CRP, Fibrinogen, and Hyaluronate. Here is a research study showing statins also have an effect on fibrin formation that helps CVD outcome. Copied from this study, "the inhibitory effect of statins on the mevalonate pathway is involved in the regulation of some key steps of coagulation and fibrinolysis processes."  

This next very techno reference reveals Statins interfere with the PAL-1 pathway that is involved in inflammation and wound healing.(1) ref  This is very new research and will need many years of duplication and testing before any public exposure erupts. The vital piece of info here is that PAL-1 triggers PXR and PXR triggers PAL-1, and PXR is involved with Drug resistance and cancer spreading. This is one of the pathways cancer cells might hyjack and use to protect against chemotherapeutic drugs and speed the proliferation of new cancer cells. (2) ref

Copied from above (1) ref: Plasminogen activator inhibitor type 1 (PAI-1) is a multifunctional protein that has important roles in inflammation and wound healing. Its aberrant regulation may contribute to many disease processes such as heart disease. The PAI-1 promoter is responsive to multiple inputs including cytokines, growth factors, steroids and oxidative stress. The statin drugs, atorvastatin, mevastatin and rosuvastatin, increased basal and stimulated expression of the PAI-1 promoter 3-fold.  Copied from (2) ref: PXR is expressed in several cancer tissues and the accumulating evidence strongly points to the differential role of PXR in cancer growth and progression as well as in chemotherapy outcome. In cancer cells, besides regulating the gene expression of enzymes and proteins involved in drug metabolism and transport, PXR also regulates other genes involved in proliferation, metastasis, apoptosis, anti-apoptosis, inflammation, and oxidative stress. In this review, we focus on the differential role of PXR in a variety of cancers, including prostate, breast, ovarian, endometrial, and colon.

Interesting History of heart disease here (<moved page, searching for another) Heart disease was almost unknown before the 1900's.

NEW UPDATED RESEARCH

Please read the abstract for the above study. It reveals a possible eplanation for sudden heart attacks when other observable evidence is not found. Phosphate tocivity. Here are the foods that are high in phosphates: article

High-phosphorus foods to avoid or limit:

• Dairy foods.
• Beans.
• Lentils.
• Nuts.
• Bran cereals.
• Oatmeal.
• Colas and other drinks with phosphate additives.
• Some bottled ice tea.

Since many of these foods have other valubale nutrients, moderation is the key. Plus, grains and legumes also contain phytes which bind with phosphorus to limit absorption. This is another reason Vegetables are used since they do not contain phosphates. Balance between calcium, phosphorus, and magnesium gain significance with this concept. ref  Kidneys play a large role in this balance. Also of consideration are the functions of vitamin D and K to direct and control the placement of these minerals in the proper body structures and not in soft tissues or artery walls.

It appears that both low and high phosphate blood levels are associated with higher risk for caridac events. ref

This represents another situation where Health Agencies are failing to protect Public Health. While food processors are adding phosphates to many propared foods, even those not considered high in phosphates, science is finding upset balance in minerals as the cause of or associated with numerous diseases.

Plaque Attack

Heart Attacks have long been attributed to the development of plaque in artery walls. This plaque is a combination of cholesterol and calcium and usually builds up inside the artery lining cell walls. When the plaque gets large, it can either begin to block blood flow or if the covering cell membranes rupture exposing the plaque, a small piece can break off and travel in the blood stream until it reaches a narrowing vessel where it gets stuck and blocks blood flow. If the blockage is in the heart, it is called a heart attack, and if it is in the brain, a stroke.

Of Interest: Even old research, look at the year, didn't support the dietary cholesterol effect on heart disease in older people. Yet medicine did not correct the critical impression created in the media concerning cholesterol intake on mortality. ref  article

This works for most heart attacks in older people, but fails to satisfy heart attacks in younger people who don't exhibit hardly any plaque build-up. This dilemma needs another explanation. The membranes do not so much tear apart as just exhibit an abrasion looking effect. ref   ref 

Regardless of initiation, what has to be addressed is first, why does plaque develop and can this process be modified or eliminated? Next, how can the body be protected after plaque is present to prevent rupture and clots? How might vitamins play a role? And fundamentally, is plaque build up a defensive mechanism of the body to protect the integrity of arteries once they are injured? Is the body trying to strengthen the artery wall to prevent a rupture at a damaged or injured weak spot?

These are the areas under consideration:

• Clotting ability of blood, includes Fibrinogen levels
• Thickness of blood or the stickiness or clumping of red blood cellls
• Fat profile (includes cholesterol) in blood
• Oxidation rate of fats in blood
• Artery Wall elasticity on blood pressure
• Artery wall cell membrane integrity
• inflammatory state of artery wall cells
• Markers or elements in blood related to inflammation

FACT: There are dietary nutritional vitamins, minerals, enzymes, and other phyto-nutrients in foods that have an influence over many if not all of these conditions. Magnesium> ref

IMPACT OF DIETARY CALCIUM  

Here is what the Harvard newsletter says about this topic:

"Cardiovascular calcification

Calcium can accumulate in the arterial plaque that develops after an injury to the vessel wall. The plaque is usually soft to begin with, but eventually tends to harden and become calcified. In addition, blood vessel cells themselves sometimes convert into bone-forming osteoblasts, producing extra calcium on the spot. (Well! Not really producing calcium, but directing it's placement in the plaque inside the artery cell wallls).

Coronary arteries. People with arterial calcifications are more likely to develop heart disease, but it's unclear whether calcified plaque is more likely than soft plaque to rupture and cause a heart attack.

The risk of coronary artery disease can be predicted by the amount of calcium in the coronary arteries, as measured by CT scanning — even after correction for other heart disease risk factors. But the American Heart Association does not recommend these heart scans if you can tell by your medical history or other risk factors that you are at low or high risk for heart disease. If you are at intermediate risk (a 10% to 20% chance of a heart attack in the next 10 years), a coronary artery calcium scan may help your doctor determine how aggressively to pursue therapies such as statins.

If you develop chest pain, scanning for coronary artery calcium may help determine whether heart disease is the cause. Echocardiography — a procedure that uses sound waves to create moving pictures of the beating heart — may reveal calcification of the aortic valve, which greatly raises the risk for coronary artery disease.

Brain-related arteries. In most patients who undergo brain CT scans, for whatever reason, the carotid (neck) and vertebral (spine) arteries show signs of calcification. These calcifications may be an independent risk factor for stroke: a 2007 study found that calcifications are especially common in people who have had a clot-related (ischemic) stroke.

Consumption connection? Evidence is limited, but calcium intake doesn't appear to increase the risk of calcification in coronary arteries. In fact, a high level of calcium in the diet is usually thought to be beneficial to heart health, because it's associated with lower blood pressure and lower weight. However, there have been some worrisome findings.** Some studies (but not all) have found an increased risk of heart attacks among women taking calcium supplements. Researchers involved in 15 randomized trials of calcium supplements for various conditions are pooling their data on adverse events among almost 12,000 people to look for any association."  -end of article copy.

Check this out, even though in Type 2 Diabetics, still some insight. Both low and high calcium intake harmful. ref

**It is now quite clear that both low and high amounts of dietary calcium increase all cause mortality and cardiovascular disease in Women. ref  The safest total intake for calcium per day exhibiting the lowest mortality rate is between 600 mg and 1000 mg. This includes the amount from diet and supplements.

A Sticky Point: If the cholesterol theory was correct, one would expect to find artery damage throughout the entire artery system. BUT, damaged arteries are mainly found, or at greater degrees, at points where arteries turn or split into two channels. This generates a greater dynamic fluid turbulence leading to increased stresses on vessel walls from the blood flow. If the cells in the walls are not healthy enough, they will begin to break down or sustain an injury to the usually non-delicate membrane lining the inside of the arteries.This damaged area then prompts the body to go into a repair mode. Packing calcium and cholesterol into this damaged tissue area might simply be part of this repair attempt. Oxidized LDL is definitely a player along with inflammatory issues and these may be another source of initiation, or act as a contributer. 

Vitamins have Heart

Do vitamin supplements support a healthy HEART?  Here is a Physicians Journal report for Vitamins E & C. From the CHAOS, Chambridge Heart Anti-Oxidant Study, a 71% reduction in second heart attacks was discovered in the group taking vitamin E during the test period. Review of studies. ref

Check out this report that tocotrienols have greater cardiovascular protection than just vitamin E as d' or dL' alpha tocopherol. Alpha tocopherol is the form mainly used in most research studies with mixed results. D' alpha represents the natural form while dL' alpha is the synthetic configuration. The L stands for the half of the synthetic molecules that form to the Left while the natural d' alpha molecules all form to the the Right. Could it be that vitamin E is more effective as a family group rather than just as d' or dL' alpha by itself? article

VITAMIN D

This is a gem of a study. When the heart is stressed and has to overwork, it enlarges and turns fibrous. A 2008 study shows that in animals, the hormone form of vitamin D prevents this enlarging and keeps out fibrous tissues. ref  Fibrous tissues are probably formed to hold the heart together and help it withstand the increased stress from overworking.  article

VITAMIN K

Vitamin K is involved in preventing artery stiffness and of course, blood coagulation. article

VITAMIN E

Vitamin E has of late found negative research on heart disease compared to many years of positive findings mainly from higher dietary levels of vitamin E. Perhaps the fact that research only used one form of E may be influencing negative results.  article

Here is a review study on many vitamins including vitamin E on vascular calcificaton. Test subjects that added vitamin E supplements, largely just alpha tocopherol, exhibited increased cardio vascular calcification above the subjects with just higher dietary vitamin E levels (mixed also present in food). ref 

What influence would taking the whole vitamin E family at lower dosages have on vascular calcifications? It is already known that vitamin K and magnesium have positive actions. Calcification is of course the incorporation of calcium forms into artery walls. The process is similar to bone building, just in the wrong area. Vitamin K activates osteocalcin produced by vitamin D to combine with calcium and other bone minerals and deposit them into bone. Vitamin K forms, especially K2, also activate a Matrix GLA protein in artery walls that prevents calcificaton. Magnesium helps control calcium movement in and out of cells.

Fish oils influence can be found here. article 

Cholesterol- Friend or Foe?

Answer: You would not survive very long without the functions cholesterol performs. Found in every cell in the body, cholesterol manufactures Hormones, fights infections, aids fat digestion and absorption of fat soluble vitamins A, D, E, & K, produces Vitamin D from sunshine, maintains cell membrane integrity especially for water balance and nutrient transport (by this function cholesterol is linked to every cell function needing outside nutrients to enter cells), plus cholesterol helps prevent virus attachment onto cell membranes. Perhaps one of the most vital functions getting attention right now is that cholesterol supports learning and memory with important roles in the health of nerve tissues.

The Cholesterol story is one that could sustain a season of weekly TV shows and remain entertaining until the end. Cholesterol testing in Rabbits alone would provide more entertainment than many CSI episodes. Scientists create artery disease in rabbits by feeding massive cholesterol amounts, but did not find that this always resulted in heart attacks. Rabbits never suffer from heart attacks on their normal diet. A very revealing fact might support this observation. Rabbits make their own vitamin C. Vitamin C builds collagen. ref  Collagen maintains artery wall membrane strength. Artery membranes separate cholesterol build up in artery walls from blood flow inside arteries. In humans this artery membrane tears open and pieces of the cholesterol laden plaque break off and float downstream until getting stuck when vessels narrow leading to a heart attack. This tearing of membranes did not happen in rabbits. 

Here is an interesting observation. Humans with higher cholesterol levels tend to have more heart disease while humans that measure low cholesterol tend to get more infectious diseases and cancers. ref ref

CHECK OUT THE GRAPH ON THIS WEBSITE. IT IS A THINK-TWICE WORLD PLOT OF MORTALITY TO CHOLESTEROL LEVELS. Sure looks like a target cholesterol level of about 210 (range 200-240) might be the safest amount from the lowest mortality point of view. Interestingly, it is exactly the same as the Korean men's study found. BUT, quite a bit more than the 160 advocated by USA health officials.

This means at 160 total cholesterol there might be less heart disease, BUT almost a 2.5 times higher overall death rate. While this is just an association, there are far too many other factors and studies not to see a trend. Seems like a very easy choice to pick life and a cholesterol level just over 200 (making sure HDL is 50-60), and then deal with lifestyle choices to reduce heart disease risk.

STATIN CRITICAL NEWS:

The link between cholesterol and Statins is one of immense interest and intrigue. Check out this next study for the relatinships expressed. Find out if there is a positive or negative association between Statin use and greater artery calcification.

Kaohsiung J Med Sci. 2021 Jul;37(7):624-631.

 doi: 10.1002/kjm2.12373. Epub 2021 Feb 26.

Statins, vascular calcification, and vitamin K-dependent proteins: Is there a relation?

Maria D Zhelyazkova-Savova 1, Yoto T Yotov 2, Miglena N Nikolova 3, Neshe F Nazifova-Tasinova 3, Deyana G Vankova 3, Atanas A Atanasov 2, Bistra Tz Galunska 3

Affiliations expand

• PMID: 33634559
 
• DOI: 10.1002/kjm2.12373

Free article

Abstract

The present cross-sectional clinical study aimed to examine the connection between statin exposure, coronary artery calcification (CAC), and vitamin K-dependent proteins (VKDPs) in patients with cardiovascular (CV) conditions. Two groups of patients were studied: patients with established CV disease (CVD) and healthy patients at moderate risk for CVD (a control group). The groups were also split into statin users and non-users. The following VKDPs were measured in plasma: uncarboxylated Matrix Gla-protein (ucMGP), undercarboxylated (ucOC), and carboxylated osteocalcin (cOC), Gla-rich protein (GRP). CAC score (CACS) was determined by multislice computed tomography. Among all the participants in the study, CACS was more pronounced in statin users compared to non-users; the same was found also among the CVD patients and among the controls. While the levels of ucMGP and GRP did not differ between statin users and non-users, ucOC and ucOC/cOC were significantly elevated in statin users, indicating vitamin K deficiency. There was a positive correlation between the levels of ucOC and CACS in the entire population and in the group of statin users, but not in statin non-users. No association was found between ucMGP or GRP and CACS. Statins had also an impact on the international normalized ratio and interacted with vitamin K antagonists (VKAs). Our results are in agreement with the existing evidence about positive association between statins and vascular calcification. They enlighten to a certain extent the possible mechanisms through which statins may enhance calcium accumulation in arterial wall, namely, by inhibition of vitamin K dependent proteins and functions involved in vascular protection.