Will new tests reveal truth about cholesterol?

Have you heard about the latest in cholesterol testing? It is called LDL particle number (LDL-P) and size. And it’s about time mainstream medicine inched closer to our relationship with cholesterol…

Until this revelation, cholesterol testing has focused unnecessarily on LDL cholesterol.  Now let’s look at these newer blood tests for heart disease risk profiling. I am still convinced that there are more important risks to look at than even lipoproteins.

LDL Cholesterol versus other lipoproteins and heart disease risk

You may have been very surprised to learn in a previous article about cholesterol that measuring your LDL-Cholesterol gives you very little information regarding your risk for a heart attack. While elevated LDL-C levels are blamed as the villain behind heart disease, it is only an association, but not the cause…

Remember that in 2009 it was revealed by the American Heart Journal that nearly 75% of patients who are hospitalized for a heart attack have LDL cholesterol levels within the recommended target for LDL cholesterol.

And researcher from the Framingham Heart Study tells us that “Total cholesterol was not associated with the risk of coronary heart disease”. Moreover, a 1994 JAMA article reported that hypercholesterolemia or low HDL-C are not important risk factors for deaths by heart attack in persons over age 70 years.

However, we do know that for men over age 65, the HDL-C is an important measurement.

More important than measuring cholesterol, is to eliminate these risk factors: smoking, hypertension, diabetes, elevated waist/hip ratio (abdominal obesity), unhealthy dietary patterns, unhealthy psychosocial factors, and maximize your daily consumption of fruits and vegetables, and get regular physical activity.

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Yet, in the wake of discovering that elevated LDL-cholesterol really has little to do with the cause of heart attacks as we age, a newer set of lipoprotein testing has become available. Because you will likely be urged to get these tests by your doctor, you should know what they are and what they are measuring. Therefore, let me share more detail about these and why even these tests fall short of expectations.

• Oxidized LDL measures the amount of your sticky or “oxidized” LDL cholesterol. Oxidized LDL seems to help predict progression towards arteriosclerosis (“hardening of the arteries”).
• LDL particle number (LDL-P) and size: the more particles of LDL you have, the higher your risk for arteriosclerotic plaque to build up inside your heart arteries. Also, smaller LDL-P size can more easily enter the blood vessel wall and help to develop arteriosclerosis if you have inflammation present (not caused by cholesterol itself, but by the other risk factors mentioned above). Nuclear magnetic resonance (NMR) spectroscopy is the preferred way to measure LDL-P.
• Lipoprotein (a) or Lp(a): elevated Lp(a) levels are a “very strong risk factor” for heart disease…and we know that this level is not significantly lowered with cholesterol-lowering medications. So, the Lp(a) test could add some information if you have a family history of heart disease (and a normal LDL-C level).
• Apolipoprotein B is another way to estimate LDL particle concentration. Low levels correspond with increased risk of plaque build-up, or arteriosclerosis. Reducing the other causes of inflammation mentioned above improves these measurements.

While your level of LDL-C cholesterol has little to do with your risk of heart attack, I read labs online saying that measuring the number of LDL particles and/or their size “might be an additional factor to consider when determining CVD risk.” One reputable lab company now states on their website that by testing those with normal LDL-cholesterol levels, their test for LDL-P “provides physicians with the actual LDL particle count, allowing healthcare providers to accurately determine and diagnose cardiovascular risk in their practice.”

But how much more helpful is it really? Some physicians write that people with predominantly small and dense LDL particles have a “three-fold greater risk” of coronary artery disease. I have not seen anything even close to that in the scientific studies. I am still looking for some science to substantiate that but have been unsuccessful to date.

And regarding LDL-P, in the first I study found on Pubmed.com, researchers reported that “LDL-P was a more sensitive indicator of CVD (cardiovascular disease) in both sexes than LDL-C.” First off, from the studies I have presented so far, LDL-C has been shown not to be significantly related to heart disease over age 65 years. And secondly, this study found that those with the lowest levels of LDL-P had 59 [heart attack] events per 1000 person-years compared to 81 events per 1000 person-years in those with the lowest levels of LDL-C.  That’s only about 28% less—  a far cry from the 3-fold increased risk we see in diabetics, for example.

Bottom line: science has not established a definitive causal relationship here. In fact, one group of researchers reported on their study of 100 healthy subjects (control group) compared to 100 patients with heart disease aged 43 to 77 years. They found the mean LDL particle size (nm) was not really significantly smaller in heart disease patients (24.5 ± 1.1) compared to people without heart disease (26.1 ± 0.9) — only a 6% difference.

In my view and from what I have presented here, these tests have been over-promoted—hyped up by laboratories to bring in more business for them. All the while the focus should not be on testing your blood, but changing behavior.

Sources:

1. Sachdeva A, Cannon CP, Deedwania PC, Labresh KA, Smith SC Jr, Dai D, Hernandez A, Fonarow GC. Lipid levels in patients hospitalized with coronary artery disease: an analysis of 136,905 hospitalizations in Get With The Guidelines. Am Heart J. 2009 Jan;157(1):111-117.e2. Online at: https://www.ncbi.nlm.nih.gov/pubmed/?term=136%2C905+patients%2C+2000+and+2006

2. Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR. High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med. 1977 May;62(5):707-14. PubMed PMID: 193398. Find online at: https://www.ncbi.nlm.nih.gov/pubmed/193398/

3. Krumholz HM, Seeman TE, Merrill SS, Mendes de Leon CF, Vaccarino V, Silverman DI, Tsukahara R, Ostfeld AM, Berkman LF. Lack of association between cholesterol and coronary heart disease mortality and morbidity and all-cause mortality in persons older than 70 years. JAMA. 1994 Nov 2;272(17):1335-40. Find online at: https://www.ncbi.nlm.nih.gov/pubmed/?term=Lack+of+Association+Between+Cholesterol+and+Coronary+Heart+Disease+Mortality+and+Morbidity+and+All-cause+Mortality+in+Persons+Older+Than+70+Years

4. William P. Castelli, MD, Keaven Anderson, PhD, Peter W. F. Wilson, MD, and Daniel Levy, MD. Lipids and Risk of Coronary Heart Disease The Framingham Study. AEP Vol. 2, No. l/2 January/March 1992: 23-28. Find online at: https://eurekamag.com/pdf.php?pdf=002424191

5. Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, McQueen M, Budaj A, Pais P, Varigos J, Lisheng L; INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004 Sep 11-17;364(9438):937-52. PubMed PMID: 15364185. Found online at: https://www.ncbi.nlm.nih.gov/pubmed/15364185

6. https://www.ncbi.nlm.nih.gov/pubmed/22650003

7. http://www.truehealthdiag.com/wp-content/uploads/2015/09/Diabetes-2004-Holvoet-1068-73-oxLDL-mets.pdf

8. Jeyarajah EJ, Cromwell WC, Otvos JD. Lipoprotein particle analysis by nuclear magnetic resonance spectroscopy. Clin Lab Med. 2006;26:847–70. [PubMed]

9. Sniderman A, Vu H, Cianflone K. Effect of moderate hypertriglyceridemia on the relation of plasma total and LDL apoB levels. Atherosclerosis. 1991;89:109–16. [PubMed]

10. https://labtestsonline.org/understanding/analytes/lipoprotein-subfractions/tab/test/

11. https://www.spectracell.com/media/uploaded/l/0e2061095_lpp-product-guide.pdf

12. http://www.docsopinion.com/2012/11/21/the-difference-between-ldl-c-and-ldl-p/

13. Cromwell WC, Otvos JD, Keyes MJ, Pencina MJ, Sullivan L, Vasan RS, Wilson PW, D’Agostino RB. LDL Particle Number and Risk of Future Cardiovascular Disease in the Framingham Offspring Study – Implications for LDL Management. J Clin Lipidol. 2007 Dec;1(6):583-92. Online: https://www.ncbi.nlm.nih.gov/pubmed/19657464

14. https://www.ncbi.nlm.nih.gov/pubmed/17150019

15. Tosheska K, Labudovic D, Jovanova S, Jaglikovski B, Alabakovska S. Cholesteryl ester transfer protein, low density lipoprotein particle size and intima media thickness in patients with coronary heart disease. Bosn J Basic Med Sci. 2011 Aug;11(3):169-73. https://www.ncbi.nlm.nih.gov/pubmed/21875419