Sunday, 23 April 2017

Cholesterol 101 and Oxidized LDL

Dr. Weeks’ Comment:   HDL is called “good” and LDL is called  “bad” but that is too simplistic and obfuscates the fact that both have a beneficial role and that heart disease itself is driven primarily by inflammation. For example, the well-known and oft ignored Cholesterol Paradox suggests that after a certain age, the lower your cholesterol greater the mortality.)   So testing the following non-lipid variables is critically important:   hs-CRP, (inflammation) fibrinogen (risk of stroke)  homocysteine (independent risk for heart attack) and lipoprotein panel including LP(a).  (Study more at this LINK). Total and good and bad cholesterol are less important. But if you do want to check your lipids,  know that that most dangerous lipid is the oxidized LDL cholesterol – a test rarely drawn unless your cardiologist is keeping up with the literature.  Share this with your cardiologist.

Here is where you can have this tested   or   here at LEF.org.

Oxidized LDL is an exciting new test, which was only available through Universities as part of scientific research, but is now available for everyone to access. Knowing your level of oxidzed LDL is a critical factor in determining your true cardiovascular risk!

Although routine lipid screening plays an important role in determining your risk for cardiovascular disease it does not provide information on the dangerous inflammation present in the walls of your arteries. Vascular disease actually begins as a malfunction of specialized cells that line your arteries, long before symptoms appear! These cells, called endothelial cells, are the key to atherosclerosis, a chronic inflammatory disease of the arterial wall.

Although LDL (low density lipoprotein) is usually thought of as “bad cholesterol”, non-oxidized LDL is just a protein carrying cholesterol and fats from the liver to the rest of the body. In order for LDL particles to cause disease, they have to be small and dense and capable of entering the wall of your arteries. Once inside the endothelium, fats in the LDL particles react with free radicals and Oxidized LDL (OxLDL) is formed.

As soon as LDL oxidizes it becomes pro-inflammatory, damaging to the arterial wall, and most importantly, capable of transforming immune cells called macrophages into foam cells, a major constituent of arterial plaque! Oxidation of LDL is one of the first steps in the development of vascular inflammation and the initiation of vulnerable plaque development. It’s also the reason OxLDLs are believed to be the most atherogenic forms of LDL!

Oxidized LDL may also play a role in increasing the amount of triglycerides your body produces, as well as increasing the amount of fat deposited…especially abdominal fat!  In turn, fat tissue can enhance the oxidation of LDL, creating a vicious cycle.

Let’s look at some statistics to see why you should have your Oxidized LDL levels checked:

  • Individuals with high levels of OxLDL are 4 times more likely to develop metabolic syndrome in the next five years.1
  • Increased OxLDL levels are associated with the presence of coronary artery disease2-4
  • Levels of OxLDL increase in a step-wise fashion as the severity of CAD increases.5

Fasting is not required for this blood test. Take all medications as prescribed.

References

  1. Holvoet P et al. Association between circulating oxidized low-density lipoprotein and incidence of the metabolic syndrome. JAMA. 2008; 299: 2287-2293
  2. Holvoet P et al. Circulating oxidized LDL is a useful marker for identifying patients with coronary artery disease. Arterioscler  Thromb Vasc Biol. 2001; 21: 844-848.
  3. Nishi K et al. Oxidized LDL in carotid plaques and plasma associates with plaquie instability. Aterioscler. Thromb Basc Biol. 2002; 22: 1649-1654
  4. Tsimikas S et al. Oxidized phospholipids, Lp(a) lipoprotein, and coronary artery diseae.  N Engl J Med, 2005; 353: 46-57
  5. Ehara D et al. Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary sndromes. Circulation, 2001: 103:1955-1960

 

more on Oxidized LDL

 

Association Between Circulating Oxidized Low-Density Lipoprotein and Incidence of the Metabolic Syndrome FREE

Paul Holvoet, PhD; Duk-Hee Lee, MD, PhD; Michael Steffes, MD, PhD; Myron Gross, PhD; David R. Jacobs, PhD
JAMA. 2008;299(19):2287-2293. doi:10.1001/jama.299.19.2287. 

Context Experimental data support the hypothesis that oxidized low-density lipoprotein (LDL) is associated with the metabolic syndrome. However, this hypothesis has not been tested in humans.

Objective To establish the relation of oxidized LDL with metabolic syndrome in the general community.

Design, Setting, and Participants The Coronary Artery Risk Development in Young Adults (CARDIA) study is a population-based, prospective, observational study. We studied 1889 participants who were between the ages of 18 and 30 years at the time of recruitment in 1985 and 1986 and living in 1 of 4 US metropolitan areas (41% African American; 56% women) and were seen both at year 15 (2000-2001, ages 33-45 years) and year 20 examinations (2005-2006).

Main Outcome Measure The longitudinal association of oxidized LDL and incident metabolic syndrome. Oxidized LDL was measured with a monoclonal antibody-based enzyme-linked immunosorbent assay. The metabolic syndrome was defined according to the Adult Treatment Panel III of the National Cholesterol Education Program.

Results Incident metabolic syndrome was diagnosed at the year 20 follow-up in 12.9% (243 of 1889) of participants who did not have metabolic syndrome at the 15-year follow-up. The odds ratios (ORs) for incident metabolic syndrome after 5 years’ follow-up and adjusted for age, sex, race, study center, cigarette smoking, body mass index, physical activity, and LDL cholesterol levels by quintiles of oxidized LDL were 2.1 (95% confidence interval [CI], 1.1-3.8) for the second quintile (55.4-69.1 U/L); 2.4 (95% CI, 1.3-4.3) for the third quintile (69.2-81.2 U/L); 2.8 (95% CI, 1.5-5.1) for the fourth quintile (81.3-97.3 U/L); and 3.5 (95% CI, 1.9-6.6) for the fifth quintile (≥97.4 U/L). The adjusted ORs for incidence of dichotomous components of metabolic syndrome in the highest vs the lowest quintile of oxidized LDL were 2.1 (95% CI, 1.2-3.6) for abdominal obesity, 2.4 (95% CI, 1.5-3.8) for high fasting glucose, and 2.1 (95% CI, 1.1-4.0) for high triglycerides. Low-density lipoprotein cholesterol was not associated with incident metabolic syndrome or with any of its components in the fully adjusted model containing oxidized LDL.

Conclusion Higher concentration of oxidized LDL was associated with increased incidence of metabolic syndrome overall, as well as its components of abdominal obesity, hyperglycemia, and hypertriglyceridemia.

Persons with the metabolic syndrome are at increased risk of developing type 2 diabetes and coronary heart disease (CHD) as well as increased mortality from CHD and other causes.1,2 Findings from the Third National Health and Nutrition Examination Survey showed that prevalence of metabolic syndrome increased with age from 6.7% among participants aged 20 to 29 years, to 43.5% for participants aged 60 to 69 years, and 42.0% for those aged 70 years or older.3

Several groups developed assays for oxidation-specific epitopes on plasma low-density lipoprotein (LDL). Two assays use antibodies against oxidized phospholipids4,5; our assay uses the monoclonal antibody (mAb) 4E6 directed against an oxidation-dependent epitope in the apolipoprotein B-100 moiety of LDL.6,7It is generally believed that “fully oxidized LDL” does not exist in the circulation. Blood is rich in antioxidants. In addition, such highly oxidized particles would be rapidly cleared in the liver via scavenger receptors.8 In contrast, circulating minimally oxidized LDL in which oxidative modification has not been sufficient to cause changes recognized by scavenger receptors was demonstrated.9 Therefore, all assays for oxidized LDL presumably detect minimally oxidized LDL. This oxidized LDL is only a minor fraction of LDL ranging from 0.001% in healthy controls10 to approximately 5% in patients with acute coronary events.6 Because LDL is the substrate for oxidation, concentrations of oxidized LDL correlate with LDL concentrations, and in turn with the cholesterol within LDL. In addition, concentrations of oxidized LDL depend on the sensitivity of LDL particles to oxidation; small dense LDL contains smaller amounts of antioxidants and are therefore more prone to oxidation. Previously, metabolic syndrome was shown to be associated with a higher prevalence of small dense LDL.11

Using the mAb-4E6–based enzyme-linked immunosorbent assay (ELISA), we have shown that in the Health, Aging, and Body Composition cohort, a high coronary heart disease risk status (based on the Framingham score) before coronary heart disease events is associated with high concentrations of circulating oxidized LDL, even after adjustment for LDL cholesterol.12 Because individuals with the metabolic syndrome are at increased risk of macrovascular disease, death, or both,2,13 it was no surprise that metabolic syndrome was associated with high concentrations of oxidized LDL.14– 17

No study, however, has examined the relation between oxidized LDL and the development of the metabolic syndrome. Because biological studies in cellular and animal models do suggest that oxidized LDL contributes to processes that lead to the incidence of metabolic syndrome,18,19 we hypothesized that oxidized LDL is associated with the incidence of metabolic syndrome. We tested this hypothesis by determining the association between the concentration of oxidized LDL and the incidence 5 years later of metabolic syndrome and its components.

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Dr. Weeks’ Comment:   HDL is called “good” and LDL is called  “bad” but that is too simplistic and obfuscates the fact that both have a beneficial role and that heart disease itself is driven primarily by inflammation. For example, the well-known and oft ignored Cholesterol Paradox suggests that after a certain age, the lower…
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