TMAO

TMAO

Gut microbes live symbiotically within the human digestive tract and play important roles in host defense, immunity, and nutrient processing and absorption. This diverse community is unique to each person and influenced by both acute and chronic dietary exposures to various food sources. Nutrients such as phosphatidylcholine (also known as lecithin), choline, and L-carnitine are abundant in animal-derived products such as red meat, egg yolk and full-fat dairy products. When consumed, these nutrients are processed by gut bacteria resulting in the release of various metabolites including TMA (trimethylamine) into the blood. TMA is then transported to the liver where it is converted into TMAO (trimethylamine N-oxide) which has been shown to regulate various physiological processes involved in the development of atherosclerosis.

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ADMA/SDMA

ADMA-SDMAADMA and SDMA may identify endothelial dysfunction due to nitric oxide deficiency. ADMA directly inhibits nitric oxide production and identifies increased risk of cardiovascular disease and adverse events. SDMA indirectly inhibits nitric oxide production and identifies endothelial dysfunction and/or renal insufficiency due to its preferential clearance by the kidneys.

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Myeloperoxidase

MPOMPO is a white blood cell-derived inflammatory enzyme that measures disease activity from the luminal aspect of the arterial wall. Briefly, when the artery wall is damaged, or inflamed, MPO is released by invading white blood cells where it accumulates. MPO mediates the vascular inflammation that propagates plaque formation and activates protease cascades that are linked to plaque vulnerability. White blood cell activation in the bloodstream, in response to luminal injury of the artery wall including fissures, erosions or a degrading collagen cap, leads to MPO release in the bloodstream. This combination of detrimental effects demonstrates that MPO is actively involved in the progression of atherosclerosis.

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F2-Isoprostanes (F2-IsoPs)

F2-IsopsF2-IsoPs, prostaglandin-like compounds formed from the free radical-mediated oxidation of arachidonic acid, are the ‘gold standard’ for measuring oxidative stress in the body. F2-IsoPs also have potent biological effects associated with inflammation and therefore may mediate chronic disease initiation and progression. Additionally, F2-IsoPs may also act as potent vasoconstrictors via thromboxane formation in the endothelium, and promote platelet activation resulting in thrombus formation.

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OxLDL

OxLDLOxLDL measures protein damage due to the oxidative modification of the ApoB subunit on LDL cholesterol. The oxidation of LDL cholesterol is one of the first steps in the development of atherosclerosis. Briefly, LDL-C enters the artery wall where it becomes oxidized. OxLDL is then recognized by scavenger receptors on the macrophages which engulf OxLDL, resulting in foam cell formation, vascular inflammation and the initiation of atherosclerosis.

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Microalbumin

MACRMicroalbumin is the quantification of small amounts of albumin, a serum protein, in urine that can be used to identify microvascular endothelial dysfunction. The presence of small amounts of albumin in the urine may suggest the presence of systemic endothelial dysfunction – an early indicator of heart disease. This test is more sensitive than a standard dipstick test routinely performed in an office setting.

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Lp-PLA2 Activity

Lp-PLA2

Lp-PLA2, or lipoprotein-associated phospholipase-A2, measures disease activity within the artery wall below the collagen or calcified cap due to the activation of macrophages. Lp-PLA2 is not an acute phase reactant. When disease is active in the artery, increased levels of Lp-PLA2 are produced by macrophages and foam cells within the intima of the artery. Lp-PLA2 also interacts with oxidized LDL, which increases inflammation and enhances a proatherogenic state, as well as plaque vulnerability. Research suggests that it plays a direct role in the atherosclerotic disease process.

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CoQ10

CoQ10Coenzyme Q10 (CoQ10) is a fat-soluble, vitamin-like substance present in most cells, primarily in mitochondria. CoQ10 has two major roles within the human body: it participates in aerobic cellular respiration generating energy (i.e., ATP) and is a powerful antioxidant. CoQ10 exists as two forms in the body: ubiquinone and ubiquinol (the active form of CoQ10, which is made from ubiquinone).

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MTHFR

MTHFRMTHFR (5,10-methylenetetrahydrofolate reductase) is an enzyme involved in the metabolism of folate. MTHFR catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, the major circulating form of folate. In turn, 5-methyltetrahydrofolate is involved in the conversion of homocysteine to methionine. MTHFR has an important role in maintaining folate and methionine levels, as well as helping to keep circulating homocysteine levels low. MTHFR is also involved in the methylation pathway, which has multiple, wide-ranging roles in the body, including regulation of gene expression and enzymatic activities.

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CYP2C19

CYP2C19CYP2C19 is a member of the cytochrome P450 family of enzymes involved in the metabolism and bioactivation of drugs. In particular, CYP2C19 is integral for the generation of the active form of clopidogrel (Plavix®), which is prescribed in a prodrug form. This prodrug is converted by CYP2C19 to the active form in the liver. Several variants of CYP2C19 have been identified which have an impact on its ability to metabolize drugs. The main CYP2C19 alleles include the non-functional alleles *2 and *3, as well as the hyperactive *17 allele.

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ApoE

ApoEApoE is an apolipoprotein found in blood that, in association with lipids, forms lipoproteins including very low-density lipoproteins (VLDL). ApoE plays multiple roles in the regulation of lipid and lipoprotein levels in the blood. ApoE serves as a ligand for members of the low-density lipoprotein (LDL) receptor family, and is involved in the removal of lipoproteins from the circulation for excretion in the liver. ApoE is also involved in the formation of chylomicrons and VLDL, and affects the activity of other proteins and enzymes that are involved in lipid metabolism, such as hepatic lipase and lipoprotein lipase.

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Adiponectin

AdiponectinAdiponectin is an abundant hormone released by adipocytes (or fat cells), commonly referred to as an adipokine. Adiponectin plays a large metabolic role in the body, participating in the regulation of glucose levels, insulin sensitivity and lipid catabolism. Adiponectin also helps support proper endothelial functioning and has multiple anti-inflammatory properties, including inhibiting the transformation of macrophages to foam cells, one of the first steps of atherosclerosis.

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OmegaCheck

OmegaCheckOmega-3 and omega-6 fatty acids are polyunsaturated long chain fatty acids (PUFA) required by the body for proper functioning, normal growth and the formation of neural synapses and cellular membranes. Omega-3 and -6 fatty acids are considered “essential” and obtained primarily from dietary sources.

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HDL2b

HDL2bHDL cholesterol, like LDL cholesterol, can be divided into several subfractions, based on density, size and protein composition. The HDL2 subfraction (HDL2a, HDL2b) consists of larger, more buoyant particles while particles in the HDL3 subfraction (HDL3a, HDL3b, HDL3c) are smaller and denser. The largest and most buoyant HDL particle is HDL2b.

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Vitamin D, 25OH

VitaminDVitamin D is a fat-soluble vitamin naturally present in some foods, but the main source is synthesis within the body after exposure to sunlight. Vitamin D has various roles within the body, but primarily regulates the absorption of calcium in the gut, maintaining adequate serum calcium and phosphate concentrations that contribute to mineralization of bone.

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Galectin-3

Galectin-3Galectin-3 is one of the most widely studied galectins, a family of soluble β-galactoside-binding lectins that play regulatory role in inflammation. Galectin-3 affects the synthesis of matrix compounds, such as type I collagen. When cardiac tissue is injured, macrophages infiltrate the tissue and secrete galectin-3, which promotes collagen synthesis and ultimately leads to cardiac fibrosis and adverse cardiac remodeling.

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GlycoMark®

GlycoMarkThe GlycoMark® test is a surrogate marker to detect frequent and high glycemic excursions in diabetic patients and measures blood levels of 1,5-anhydroglucitol (1,5-AG), a glucose-like sugar found in food. When blood glucose levels are well controlled, most circulating 1,5-AG is reabsorbed in the kidneys instead of being excreted in the urine. In healthy individuals, circulating levels of 1,5-AG are high, with median values exceeding 20 μg/mL. However, when blood glucose levels are high, 1,5-AG reabsorption is blocked and a majority is excreted in the urine.

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Thyroid Stimulating Hormone (TSH)

TSHTSH is a hormone synthesized and secreted by the pituitary gland. It stimulates the thyroid gland to secrete the hormones thyroxine (T4) and triiodothyronine (T3) which in turn regulate the release of TSH from the pituitary in a negative feedback loop. TSH is not tightly regulated as it is under control of thyroid releasing hormone (TRH) and feedback from fluctuating systemic thyroid hormones which are subject to binding issues, iodine effects, and many other factors.

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