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The Cholesterol Mistake Everyone Is Making

Article at-a-glance:

  • Heart disease is the leading cause of death in the United States, killing someone in the U.S. every 90 seconds.
  • For decades we’ve all heard how important health cholesterol levels are for preventing heart disease, but that advice was mostly wrong. 
  • Like other chronic diseases, boiling it down to one cause (eg, LDL cholesterol) is an oversimplification that bears little resemblance to reality.
  • The prevention heart disease rests in testing for and reducing systemic inflammation.

by Dr. John Neustadt

Heart disease is the leading cause of death in the United States. Someone in the U.S. dies from heart disease about every 90 seconds,1 killing over 375,000 people a year. That’s 1 in every 7 deaths. The costs of heart disease are staggering as well: $200 billion a year—including healthcare, medications, and lost productivity.2

When I talk to people about heart disease, typically one of the first things they mention is their cholesterol. For decades we’ve all heard how important health cholesterol levels are for preventing heart disease. Over 102 million Americans (20 years or older) have total cholesterol levels at or above 200 mg/dL, which the Centers for Disease Control (CDC) considers too high.3 High cholesterol is said to be a major risk factor for heart disease, and one type of cholesterol in particular—Low Density Lipoprotein (LDL) or “bad” cholesterol—has been vilified as the bad guy we all need to be worried about. 

Cholesterol is a fat. As such, it doesn’t dissolve well in the blood, which makes transporting it around the body difficult. But the body has created an ingenious solution. It packages cholesterol into particles called lipoproteins. And it’s these lipoproteins, such as LDL cholesterol, that are measured.4

While there are different types of lipoproteins, historically the main focus has been on lowering LDL cholesterol to reduce heart disease risk. But has it worked? For years doctors have prescribed statin medications such as lovastatin and simvastatin to lower LDL cholesterol and more than 35 million Americans currently take statins.5 

But the idea that high LDL cholesterol is, all by itself, an accurate predictor of cardiovascular disease is a gross oversimplification. Heart disease is a chronic condition. Like other chronic diseases, boiling it down to one cause (eg, LDL cholesterol) is an oversimplification that bears very little resemblance to reality and has not been shown to be particularly good at preventing a first heart attack. Researchers have concluded that in people who have never had a heart attack, statin therapy that lowers LDL cholesterol is of “doubtful benefit.”6 

Guilt by Association

To understand how this emphasis on lowering LDL cholesterol came about, we have to go back to the early 1900s. Scientists noticed that fats in our diet seemed to correlate with cardiovascular disease. That is, they noticed that people who had heart disease also had high cholesterol. But in research, as in medicine, it’s important to understand that correlation does not mean causation. 

Making researchers believe they found the underlying cause were additional observations after World War II that Americans were eating more saturated fat and cholesterol-rich foods (such as eggs, butter and whole milk), while the incidence of cardiovascular disease was increasing.7 So, for decades, doctors advised patients to reduce dietary cholesterol and saturated fat, and yet more and more people were still having heart attacks.

We now understand that dietary cholesterol on its own doesn’t have a major influence on the development of heart disease8 and reducing cholesterol to normal or low levels hasn’t had the hoped-for impact on heart attacks. Half of patients with ideal cholesterol levels actually have dangerous plaque build-up and are at risk for a heart attack or stroke.9 

In addition, the work of Uffe Ravnskov at the University of Lund, Sweden has called into question the predictive power of LDL cholesterol in heart disease. Ravnskov and colleagues reviewed 19 studies looking at nearly 70,000 individuals and concluded that elderly people with high LDL cholesterol live as long or longer than those with low LDL cholesterol. “Our analysis,” the authors write, “provides reason to question the validity of the cholesterol hypothesis.10 

More recently, in 2018, Ravnskov and colleagues threw down the gauntlet once again, publishing a paper that stated: “For half a century, a high level of total cholesterol (TC) or low-density lipoprotein cholesterol (LDL-C) has been considered to be the major cause of atherosclerosis and cardiovascular disease (CVD), and statin treatment has been widely promoted for cardiovascular prevention. However, there is an increasing understanding that the mechanisms are more complicated and that statin treatment, in particular when used as primary prevention, is of doubtful benefit.”11 

The war waged against cholesterol all too often overlooks all the benefits of this important lipid. Cholesterol is essential for the normal function of all cells in the body. Cholesterol is a building block for hormones like cortisol, estrogen and testosterone, as well as vitamin D. Cholesterol helps maintain the integrity of the membranes that surround every cell, as well as the gut lining12 and it is critical for brain function.13 Cholesterol is critical for liver function, as it is contained in bile salts, which help us digest our food and move toxins out of the body.

The Real Problem, Inflammation

New research points to inflammation as a key driver of cardiovascular disease. The prevention of chronic diseases, including heart disease, rests in controlling systemic inflammation.14

Cholesterol itself is not dangerous. It becomes problematic, however, in the presence of inflammation. Inflammation creates free radicals, which damages cholesterol and other fats. This activates the immune system and starts a cascade of events that ultimately creates plaques in the arteries, causing atherosclerosis. 

Uncontrolled inflammation makes plaques unstable and vulnerable to rupture, which can lead to a heart attack or a thrombosis (a blood clot). Plaques can dislodge and cause strokes or blockages in the lungs (pulmonary embolism). When plaques occur in arteries other than those in the heart, it is called peripheral arterial disease.15 This can cause impotence in men, among other disorders.16

The link between chronic inflammatory diseases and cardiovascular disease is of great significance. For example, individuals suffering from rheumatoid arthritis, a chronic inflammatory autoimmune disease, are at significantly increased risk of dying from heart disease.17

In contrast, lifestyle modifications such as diet, stress reduction, sufficient sleep and regular exercise can reduce chronic inflammation, oxidative stress, and hypercoagulation (excessive tendency to form blood clots), all of which are implicated in cardiovascular disease.18

For a More Accurate Assessment Order These Nine Tests

To get a more accurate picture of your heart disease risk, it’s important to test more than just total and LDL cholesterol. High Density Lipoprotein (HDL) cholesterol is another type of cholesterol, which is important to test. Triglycerides, a type of fat, is also important. HDL Cholesterol is often called the “good” cholesterol because it transports cholesterol back to the liver, while LDL cholesterol takes cholesterol from the liver and transports it to other areas in the body.  

Routine lipid panels run ordered by doctors will typically test the following:

Total Cholesterol

HDL Cholesterol

Triglycerides

LDL Cholesterol 

Cholesterol/HDL Ratio 

LDL/HDL Ratio 

Non-HDL Cholesterol 

The big mistake doctors are making is that they aren’t testing for direct free radical damage to cholesterol. What the standard lipid panels miss are two markers of inflammation and free radical damage that can be included on a more comprehensive panel. They are:

Hs-CRP

Oxidized Low-density Lipoprotein (oxLDL)

Oxidized LDL (oxLDL) has been studied for more than 30 years. Since the discovery of oxidized LDL, over 5,000 articles have appeared on the topic. Oxidized low-density lipoprotein (OxLDL) can promote inflammation and lipid deposition in the arterial wall.19 OxLDL has emerged as a risk factor for heart disease, fatty liver and cancer, and is associated with a pro-inflammatory Western Diet (the Standard American Diet).20,21 OxLDL is also implicated in playing a principal role in diabetes complications.22 Running an oxLDL test provides important additional information about your risk. 

C-reactive Protein (CRP) is produced by the liver and increases in the blood in response to inflammation, infection, and following a heart attack or trauma. High-sensitivity CRP (hs-CRP) is used in the evaluation of inflammatory disorders and infections. A positive test indicates the presence of inflammation but not the cause of the inflammation. CRP levels are strong predictors of cardiovascular disease, including heart attacks, stroke, sudden cardiac death, unstable angina and peripheral arterial disease.23,24,25 

How to Reduce Your Risk

Next time you get your cholesterol levels tested, get a lipid panel that includes all the lipid measures mentioned above as well as a CRP and oxidized LDL test to get a better idea of your risk. You could ask your healthcare provider for the test.

Or to save money and time, order your advanced lipid panel directly from NBI. We supply the doctor’s order. Your lab requisition form is ready within seconds of checking out. You then simply take the lab test order form into one of our more than 2,000 testing centers around the country for your blood draw. Results are ready within days by email (if you opt-in to receiving results by email) or simply by logging into your NBI account to view them.

Knowledge is power when it leads to action. Once you know your risks, you can modify them with lifestyle changes. Diet is very important. Research has shown much lower rates of cardiovascular disease and mortality in southern European citizens (such as those in Italy and Greece), where people eat a Mediterranean-style diet high in vegetables, fruits, herbs, nuts, beans and whole grains, as well as moderate amounts of seafood, dairy and eggs.26 Following a traditional Mediterranean dietary patterns reduces inflammatory markers such as CRP and oxLDL.27,28 A 10-year study published in 2015 that followed the dietary patterns of 32,921 women, concluded that those who adhere to a Mediterranean dietary pattern had a 26% reduced risk of heart attacks, 21% reduction in heart failure risk and a 22% lower risk for strokes.29 Vegetarian dietary patterns also reduce cardiovascular mortality and the risk of coronary heart disease (CHD) by 40%.30 

Exercise is a well-known “medicine” that can help prevent or reverse cardiovascular disease.31 Addressing depression and/or anxiety are important as well, since there is a well-established connection between depression, chronic stress, posttraumatic stress disorder (PTSD), anxiety and heart disease.32 Other risk factors, such as chronic sleep apnea and obesity, should also be addressed.33

Knowledge is power, and proper testing can provide valuable information to help you make more informed decisions about your health. The good news is that cardiovascular disease is largely preventable, and even reversible, through lifestyle changes. According to the CDC, 80% of cardiovascular disease is entirely preventable.34

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References

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2Centers for Disease Control. Heart Disease Fact Sheet. August 2017 [Report

3Centers for Disease Control and Prevention. September is National Cholesterol Education Month. [Report]

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5Fookes C. Statins for  high cholesterol: Are the benefits worth the risk? Sept 2018 [Report]

6Ravnskov U, de Lorgeril M, Diamond D et al. LDL-C does not cause cardiovascular disease: a comprehensive review of the current literature Expert Rev Clin Pharmacol. 2018 Oct;11(10):959-970. [Article]

7Püschel GP, Henkel J. Dietary cholesterol does not break your heart but kills your liver. Porto Biomed J. 2019 3(1):e12 [Article]

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9Fernández-Friera L, Fuster V, López-Melgar B et al. Normal LDL-Cholesterol levels are associated with subclinical atherosclerosis in the absence of risk factors. J Am Coll Cardiol. 2017 Dec, 70 (24) 2979-2991  [Article]

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14Tsoupras A, Lordan R, Zabetakis I. Inflammation, not cholesterol, is a cause of chronic disease. Nutrients. 2018 May 12;10(5). [Article]

15Mayo Clinic. Peripheral artery disease (PAD). Patient Care & Health Information: Diseases & Conditions [Report]

16Vaclav M. Arterial disease as a cause of impotence. Clinics in Endocrinology and Metabolism Volume 11, Issue 3, November 1982, Pages 725-748. [Article]

17England BR, Thiele GM, Anderson DR et al. Increased cardiovascular risk in rheumatoid arthritis: Mechanisms and implications. BMJ 2018, 361, k1036 [Article]

18Legein B, Temmerman L, Biessen EAL et al.  Inflammation and immune system interactions in atherosclerosis. Cellular Mol. Life Sci. 2013, 70, 3847–3869. [Article]

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20Bitorina AV, Oligschlaeger Y, Shiri-Sverdlov R et al. Low profile high value target: The role of OxLDL in cancer. Biochim Biophys Acta Mol Cell Biol Lipids. 2019 Dec;1864(12):158518. [Article]

21Ampuero J, Ranchal I, Gallego- Durán R et al. Oxidized low-density lipoprotein antibodies/high-density lipoprotein cholesterol ratio is linked to advanced non-alcoholic fatty liver disease lean patients. J Gastroenterol Hepatol. 2016 Sep;31(9):1611-8. [Article]

22Motamed M, Nargesi AA, Heidari B, Mirmiranpour H, Esteghamati A, Nakhjavani M. Oxidized Low-Density Lipoprotein (ox-LDL) to LDL Ratio (ox-LDL/LDL) and ox-LDL to High-Density Lipoprotein Ratio (ox-LDL/HDL). Clin Lab. 2016;62(9):1609-1617. [Article]

23Koenig W, Sund M, Fröhlich M et al. C-reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992. Circulation 1999;99:237– 42.3 [Article]

24Koenig W. C-Reactive protein and cardiovascular risk: will the controversy end after CANTOS? Clin Chem. 2017 63(12):1897–1898. [Article]

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