Dr Shawn M. Carney
Heart Disease Risk? The Lipid Panel does not 'measure up'
Updated: Oct 26, 2022
There are cardiovascular tests far beyond the standard lipid panel which can provide more insight into one's risk of heart attack or stroke, yet with over ten years of clinical practice, I've scarcely heard of a cardiologist ordering these for their patients.
There are rare exceptions to this, however, usually they are particularly well-informed patients who have appealed to their medical doctor that these tests be ordered, and not the doctor's suggestion. ... ... This is the part where, if we were in my clinic now, I would tell you that: 'If I move that diploma to the side, you can see where I bang my head against the wall'.
Prevalence of Cardiovascular Disease
Heart disease remains the leading cause of death for men, women, and people of most racial and ethnic groups in the United States.1 One person dies every 36 seconds in the United States from cardiovascular disease.1 There was even a study back in 2009 which reviewed over 100,000 hospitalized cases and found nearly half of all heart attack patients did not demonstrate prior risk which would indicate they were heading toward an attack.2 Some risk factors for heart disease are more obvious than others. Things that increase one's risk include smoking, having high blood pressure or diabetes, having a family history, being overweight or over 45 years of age if a male and over 50 years of age if female, as well as being under significant stress. But these are not the only risk factors.
Years ago researchers learned that people with elevated levels of blood lipids had an increased risk of cardiovascular disease. Lipids are water insoluble, organic molecules that serve as the most important storage form of chemical energy in the body and are commonly referred to as 'fats'. There are six types of lipids including fatty acids, triglycerides, phospholipids, cholesterol, lipoproteins, and eicosanoids.
The 'Classic' Lipid Panel
A 'lipid panel' is used to identify the amounts of certain types of these fat molecules circulating in a person's bloodstream, namely, some key lipoproteins and triglycerides. Lipoproteins are the way in which lipids get transported around and they have a core of cholesterol esters and triglycerides, as well as phospholipids and free cholesterol. Since there is such a heavy cholesterol composition to lipoproteins, they are generally measured and interpreted as 'cholesterol', which includes the term 'total cholesterol', a standard component on lipid panels.
A lipid panel measures five different types of lipids from a blood sample, including:
Total cholesterol: This is your overall cholesterol level — the combination of LDL-C, VLDL-C and HDL-C.
Low-density lipoprotein (LDL) cholesterol [LDL-C]: This is a calculation of the type of cholesterol that is considered 'bad cholesterol'. Remember it by thinking: 'L-for low-life'. It is often not done as a direct measurement and can collect in your blood vessels as it is deposited coming from production in the liver. LDL-C increases your risk of cardiovascular disease and atherosclerosis.
Very low-density lipoprotein (VLDL) cholesterol [VLDL-C]: This is a type of cholesterol that’s usually present in very low amounts when the blood sample is a fasting sample since it mostly comes from food you’ve recently eaten. An increase in this type of cholesterol in a fasting sample may be a sign of abnormal lipid metabolism.
High-density lipoprotein (HDL) cholesterol [HDL-C]: This is the type of cholesterol that’s known as 'good cholesterol' and it moves cholesterol in the opposite direction from LDL-C. Remember it by thinking: 'H-for heavenly'. It helps decrease the buildup of LDL-C in your blood vessels and returns cholesterol to the liver for processing.
Triglycerides: Triglycerides are the major storage form of fatty acids, which are burned for energy. They are formed after we eat from unused calories and stored in your fat cells. Excess amounts of triglycerides in your blood are associated with cardiovascular disease, diabetes, prediabetes, hypothyroidism and pancreatic inflammation. If these levels are too high, it will interfere with the calculated LDL-C test which is routinely ordered; at these times, laboratories will almost invariably perform an additional 'direct-LDL' test to better measure the LDL-C itself.
Blood tests commonly report LDL-C, the amount of cholesterol which is estimated to be contained with LDL particles, using a formula called the Friedewald equation. But reviews as to the limitations with this method have been published for years in the peer review literature.3,4 For LDL-C, this is 'strike-1'.
The terms 'LDL' and 'LDL-C' have come to be used interchangeably by much of the medical community, but that is misleading as they are not the same thing. Indeed, the cholesterol content of LDL particles varies more than 2-fold among individuals.,5,6,7 "One person may have large, more cholesterol-rich LDL while a second may have smaller cholesterol-poor LDL particles. At the same LDL-C concentration, the second person will have higher numbers of LDL particles".5
'Why does this matter?' you may ask.
The answer is that research has increasingly found the clinical risk of disease to more tightly follow the number of LDL particles, not just a calculation for how much cholesterol they have.5 This has been substantiated so well that in 2008, the American Diabetes Association (ADA) and American College of Cardiology (ACC) issued a joint statement suggesting direct LDL particle number (LDL-P) measurement by nuclear magnetic resonance (NMR) as a superior method for assessing individual risk of cardiovascular events.8,9 For LDL-C, this is 'strike-2'.
Another type of marker which has been found to have better clinical correlation than LDL-C is apolipoprotein-B 100 (apo-B). Apo-B is found in many types of lipid particles, including most of those mentioned above. Since these each only carry one apo-B molecule, this becomes a fruitful way to assess true particle number for particles most likely to contribute to cardiovascular disease. Elevated apo-B is also associated with a 2.0-2.5x increased risk of cardiovascular disease. "As with ... NMR-based measurements of LDL particle number, in several epidemiological studies and in post hoc analyses of clinical trials, apo-B has been found to be a better predictor of CVD risk than LDL cholesterol, particularly the on-treatment LDL cholesterol level".9
"[In conclusion], ...analysis demonstrated that ... apo-B and LDL-P were ... unequivocally superior to LDL-C, ...these data add to the evidence that LDL-C should no longer be accepted as the most accurate measure of the LDL-related risk of cardiovascular disease".10
Centers for Disease Control and Prevention. Underlying Cause of Death, 1999–2018. CDC WONDER Online Database. Atlanta, GA: Centers for Disease Control and Prevention; 2018. Accessed March 12, 2020.
Sachdeva, A. et al. 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.
Martin, S. et al. Comparison of a novel method vs the Friedewald equation for estimating low-density lipoprotein cholesterol levels from the standard lipid profile. JAMA. 2013. Nov.
Maki, K. et al. LDL-C Estimation: The Perils of Living With Imperfection. J Am Coll Cardiol. 2022. Feb.
Otvos, JD, et al. Clinical Implications of Discordance Between LDL Cholesterol and LDL Particle Number. J Clin Lipidol. 2011. Mar-Apr.
Otvos JD, et al. Measurement issues related to lipoprotein heterogeneity. Amer J Cardiol. 2002. Oct.
Cromwell WC, et al. LDL particle number and risk for future cardiovascular disease in the Framingham Offspring Study – Implications for LDL management. J Clin Lipidol. 2007. Dec.
Sniderman, A., et al. Discordance analysis and the Gordian Knot of LDL and non-HDL cholesterol versus apoB. Curr Opin Lipidol. 2014. Dec.
Brunzell, J. et al. Lipoprotein Management in Patients With Cardiometabolic Risk. J Am Coll Cardiol. 2008. April.
Moria, S. et al. Discordance of low-density lipoprotein (LDL) cholesterol with alternative LDL-related measures and future coronary events. Circulation. 2014. February
*image credits: //www.123rf.com/photo_40576178_red-puzzle-heart-with-stethoscope-on-brown-wooden-background.html
The content and any recommendations in this article are for informational purposes only. They are not intended to replace the advice of the reader's own licensed healthcare professional or physician and are not intended to be taken as direct diagnostic or treatment directives. Any treatments described in this article may have known and unknown side effects and/or health hazards. Each reader is solely responsible for his or her own healthcare choices and decisions. The author advises the reader to discuss these ideas with a licensed naturopathic physician.