All Cholesterol is not the Same

We live in an age of heart disease and strokes where medicine often focuses solely on a patient’s LDL cholesterol number as the most important factor to prevent these deadly diseases. A functional MD like myself hopes to see that perspective shift as more research like this article comes to light. The researchers from Ohio University build upon the work of many others which again indicate that the LDL number in a standard cholesterol panel falls short of predicting who is at risk for cardiovascular disease.

For years, even decades, doctors have targeted the LDL or Low-Density-Lipoprotein number with diet and meds like statins as the primary way to improve heart health. This has not been entirely wrong, but many individuals with “good” LDL still developed heart attacks and strokes. Their hopes of a healthier more abundant life were hindered by chronic illness. Researchers and patients asked “What are we missing?”. It turns out inflammation and the size of the LDL particle play a large role in the disease process.

Other studies (and blogs) have or will focus on the inflammation aspect, but for today we look at this article indicating that higher LDL subclass B levels were better predictors than simple total LDL. This subclass or group of cholesterol particles still belong to the LDL class, but they are denser and smaller than their large subclass A cousins. Other studies have revealed similar correlations, but correlations don’t prove causation. It could be coincidence or another underlying factor causing both.

This paper goes a step further in looking for mechanism through which LDL size could directly cause or contribute to vascular disease. They used nano-detectors (microscopic detectors) to measure levels of nitric oxide (NO) and peroxynitrite (ONOO-) in blood vessel endothelium (cell layer lining blood vessels). The balance between these two molecules has been shown to influence vascular disease. More nitric oxide dilates vessels, lessening blockage while higher levels of peroxynitrite constricts vessels and contributes to inflammation in the vessel wall.
In the study, higher levels of the small, dense subclass B LDL particles lead to lower nitric oxide and higher peroxynitrite. This lead to more inflammatory cells binding the endothelial lining. If the LDL was oxidized by inflammation, the process went even faster towards vascular blockage.
At Sanctuary, we don’t settle for old approaches to heart disease. We read studies like this one, use medical discernment by comparing this study to what other studies and our clinical experience reveal, and apply the best of natural and conventional medicine to our patient’s specific needs. We want them to live healthier, more abundant lives so that a heart attack or stroke does not steal health from them.

Original Article
Jiangzhou Hua, Tadeusz Malinski. Variable Effects Of LDL Subclasses Of Cholesterol On Endothelial Nitric Oxide/Peroxynitrite Balance – The Risks And Clinical Implications For Cardiovascular Disease. International Journal of Nanomedicine, 2019; Volume 14: 8973 DOI: 10.2147/IJN.S223524

Thanks to Science Daily
Ohio University. “‘Bad cholesterol’ is only as unhealthy as its composition: Research demonstrates that current guidelines for diagnosing risk are ‘dangerously misleading’.” ScienceDaily. ScienceDaily, 18 November 2019. <>.

Other articles on the topic.
High percentage of heart attack patients have “low LDL’s”
Sachdeva A, Cannon CP, Deedwania PC, 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;157(1):111–117.
Other articles supporting this article:
Nishikura T, Koba S, Yokota Y, et al. Elevated small dense low-density lipoprotein cholesterol as a predictor for future cardiovascular events in patients with stable coronary artery disease. J Atheroscler Thromb. 2014;21:755–767. doi:10.5551/jat.23465
Hoogeveen RC, Gaubatz JW, Sun W, et al. Small dense low-density lipoprotein-cholesterol concentrations predict risk for coronary heart disease: the atherosclerosis risk in communities (aric) study. Arterioscler Thromb Vasc Biol. 2014;34:1069–1077. doi:10.1161/ATVBAHA.114.303284
Austin MA. Small, dense low-density-lipoprotein as a risk factor for coronary heart-disease. Int J Clin Lab Res. 1994;24:187–192. doi:10.1007/BF02592460
Blake GJ. Low-density lipoprotein particle concentration and size as determined by nuclear magnetic resonance spectroscopy as predictors of cardiovascular disease in women. Circulation. 2002;106:1930–1937. doi:10.1161/01.cir.0000033222.75187.b97
Prado KB, Shugg S, Backstrand JR. Low-density lipoprotein particle number predicts coronary artery calcification in asymptomatic adults at intermediate risk of cardiovascular disease. J Clin Lipidol. 2011;5:408–413. doi:10.1016/j.jacl.2011.07.00124
Sacks FM. Low-density lipoprotein size and cardiovascular disease: a reappraisal. J Clin Endocrinol Metab. 2003;88:4525–4532. doi:10.1210/jc.2003-030636

Small, dense LDL causes more severe cardiovascular damage.
Austin MA, Breslow JL, Hennekens CH, Buring JE, Willett WC, Krauss RM. Low-density lipoprotein subclass patterns and risk of myocardial infarction. JAMA. 1988;260:1917–1921.

Initial discovery of LDL subclasses
Lindgren FT, Elliott HA, Gofman JW. The ultracentrifugal characterization and isolation of human blood lipids and lipoproteins, with applications to the study of atherosclerosis. J Phys Colloid Chem. 1951;55:80–93.
and confirmed by others
Griffin BA, Caslake MJ, Yip B, Tait GW, Packard CJ, Shepherd J. Rapid isolation of low density lipoprotein (ldl) subfractions from plasma by density gradient ultracentrifugation. Atherosclerosis. 1990;83:59–67. doi:10.1016/0021-9150(90)90131-2
MM KR S, Lindgren FT, Forte TM. Heterogeneity of serum low density lipoproteins in normal human. J Lipid Res. 1981;22:236–244.
Davies IG. Rapid separation of LDL subclasses by iodixanol gradient ultracentrifugation. Clin Chem. 2003;49:1865–1872.

Sanctuary Functional Medicine, under the direction of Dr Eric Potter, IFMCP MD, provides functional medicine services to Nashville, Middle Tennessee and beyond. We frequently treat patients from Kentucky, Alabama, Mississippi, Georgia, Ohio, Indiana, and more... offering the hope of healthier more abundant lives to those with chronic illness.

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