Patients Cardiometabolic Assessment
Cardiovascular disease (CVD) is still the leading cause of death globally, accounting for 1 in 3 deaths in the United States.1,2 While 50% of adult Americans have at least one of the commonly known risk factors—high blood pressure, high low-density lipoprotein (LDL) cholesterol, and smoking—many more are equally at risk from diabetes, obesity, sedentary lifestyle, poor diet, and/or excess alcohol intake.3
It’s not just about cholesterol!
Traditional methods used to lower risk of heart disease and diabetes focus on fasting blood lipids (cholesterol, triglycerides) and glucose. However, cholesterol levels can be normal in patients hospitalized with coronary artery disease, and by the time blood glucose is high enough to be diagnostic of prediabetes (let alone diabetes), the body’s ability to normalize it may be only 20% what it should be.4,5 In fact, other risk factors are now known to play a major role in CVD-related disease and death.6
Scientific research is proving that INFLAMMATION and INSULIN RESISTANCE are intimate precursors to cardiometabolic diseases and huge risk factors for heart disease.7-9
Inflammation can be triggered by gut problems (e.g., imbalances in gut flora, infections, food sensitivities) often stemming from factors such as a poor diet, stress, excess weight, sleep deficits, and hormonal imbalances.10 If detected early using simple blood tests and addressed with diet/lifestyle changes and sometimes supplements/medicines, many chronic diseases can be prevented or erased.11-15
The comprehensive biomarker tests offered by Salveo Diagnostics are effective tools to help uncover and treat the root causes of cardiometabolic disease, using validated blood biomarkers of hidden risk factors such as insulin resistance, inflammation, cardiac stress, and thrombosis.
Cholesterol is a type of fatty substance or lipid that is a key component of cell membranes in the body. Your body can make its own cholesterol, but it is also found in many foods. It is used to make important hormones and vitamins. Cholesterol travels through your bloodstream packaged inside proteins called lipoproteins. Total cholesterol reflects the amount of cholesterol carried by all the different types of lipoproteins, including low-density lipoproteins (LDL), high-density lipoproteins (HDL), very-low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), and lipoprotein(a) [Lp(a)] particles.
Low-density lipoprotein cholesterol (LDL-C), the type of cholesterol transported within the LDL particles, is considered “bad” because it can contribute to the fatty buildup in the blood vessels known as “plaque.” As the LDL-C accumulates and the fatty plaques grow, the arteries narrow, which restricts blood flow to the heart and vital organs, increasing your risk for cardiovascular disease and stroke.
High-density lipoprotein cholesterol (HDL-C) is considered “good” as it is carried by HDL particles that act as scavengers, removing excess LDL cholesterol from the arteries and carrying it back to the liver. Here, it can be broken down and excreted from the body or recycled into other lipoproteins (e.g., VLDL, IDL, or LDL). HDL particles also help prevent blood clotting and have beneficial anti-inflammatory properties that are considered protective against heart disease.
Non-HDL-cholesterol (non-HDL-C) describes the cholesterol contained within all the “high-risk” (atherogenic) apoB-containing lipoproteins including VLDL, IDL, LDL, and Lp(a), and is calculated by subtracting the HDL-C value from the total cholesterol value. Knowing your non-HDL-C level can help in predicting cardiovascular risk.
Triglycerides are storage molecules for dietary fats that the body uses for energy. They are carried in the bloodstream (along with cholesterol) inside lipoproteins. Most of the fats we consume from food are in the form of triglycerides. Excess calories, alcohol, or sugars in the diet are also turned into triglycerides. Having a high level of triglycerides in your blood may be a sign of insulin resistance, metabolic syndrome, or diabetes, all risk factors for heart disease.
The triglycerides /HDL-C ratio gives an indication of risk for heart disease due to insulin resistance. As insulin resistance increases risk of heart disease, a high trigelycerides/HDL-C ratio supports more intensive efforts to improve the body’s handling of blood sugar (e.g., by improved diet and lifestyle).
Other Lipoprotein Markers
As part of an expanded lipid profile, the concentration of low-density lipoprotein particles (LDL-P) is measured to better assess your risk for cardiovascular disease, heart attacks, and strokes. LDL particles carry cholesterol around the body for use in various tissues. Elevated LDL-P has been linked to heart disease even when LDL cholesterol levels are normal, and it is often seen in patients who have insulin resistance and type 2 diabetes.
Lipoprotein(a) [Lp(a)] is an LDL particle with a protein attached to it [called apo(a)] that is used to carry cholesterol, fats, and proteins in your bloodstream. Having high levels of Lp(a) can increase the build-up of fatty deposits in your blood vessels (atherosclerosis) and increase your risk of forming blood clots that could potentially lead to a heart attack or stroke. The amount of Lp(a) in your blood is largely genetic and inherited from one or both of your parents. If you have a family history of heart disease, this is an important lab value to check.
Very-low-density lipoprotein particles (VLDL-P) are rich with triglycerides and are made in the liver for release into the bloodstream in response to the body’s energy needs. After the triglycerides are broken down into fatty acids, the VLDL particles are rapidly converted to intermediate-density lipoprotein (IDL) particles that are cleared from the blood or made into LDL particles.
Intermediate-density lipoprotein particles (IDL-P) are leftovers from the breakdown of VLDL particles and although they contain less triglycerides than VLDL, they are still a risk factor for heart disease. Many of them are converted to LDL particles that contribute to atherogenesis, or fatty buildup in your blood vessels. IDL particles may be seen in patients with diabetes, metabolic syndrome, underactive thyroid, and fatty liver disease.
The apolipoprotein B (apoB) test measures the concentration of all lipoproteins that could cause plaque buildup in the blood vessels [VLDL, IDL, Lp(a), and LDL]. Most of these are LDL particles that deposit cholesterol into the artery wall. Even if your LDL cholesterol is normal, a high apoB value can mean high risk for cardiovascular disease, heart attacks, or strokes.
Apolipoprotein A-I (apoA-I) is the main protein of high-density lipoprotein (HDL) particles and is measured to assess the concentration of HDL particles (HDL-P). ApoA-I also helps lower inflammation in the blood vessels. Low apoA-I levels are linked to diabetes, cardiovascular disease, heart attacks, and strokes, meaning that the “good” cholesterol may not be protecting your heart like it should.
A high ratio of apoB to apoA-I increases your risk of heart attacks and strokes and has been linked to insulin resistance (where the body is struggling to keep blood sugar levels normal) as well as severe heart blockages (called coronary stenosis) in patients with chronic heart disease.
High-density lipoprotein particles can be separated into two major subspecies – HDL2 are the larger, less dense particles, HDL3 the small, denser ones. HDL2-C reflects the cholesterol contained within the HDL2 particles, which have the most heart-protective antioxidant and anti-atherogenic properties. When adjusted for age, the risk for coronary heart disease and associated mortality associated is significantly greater for patients with low HDL2-C than for those with high HDL2-C.
Small dense LDL cholesterol (sdLDL-C) measures the cholesterol that is carried inside the smaller LDL particles. As sdLDL particles contain less cholesterol than large buoyant ones, an increased sdLDL-C level indicates there are more atherogenic particles (the ones likely to cause fatty build up in your blood vessels) than may be indicated by the LDL-C value.
Apolipoprotein E genotype testing is used to assess cardiovascular risk and to help individualize your plan of care. ApoE is one of the main regulators of blood lipid level (e.g., cholesterol, triglycerides). The apoE protein exists in three genetic isoforms (ApoE2, ApoE3, and ApoE4) that determine how people respond to fat in their diet and differentially affect risk of heart disease and Alzheimer’s disease. Which isoforms you have can be determined by testing for certain DNA variants in the APOE gene (inherited from your parents).
CVD Metabolism, Inflammation, Oxidative Stress, and Nutrition
Myeloperoxidase (MPO) is an antimicrobial enzyme made by white blood cells that helps defend the body against harmful bacteria, viruses. When inflammation occurs in the body due to stress, infection, or trauma, white blood cells called neutrophils rush to the scene and release MPO to form reactive compounds that destroy any invading pathogens. Chronic inflammation, however, may lead to elevated MPO levels in the blood and “oxidative stress” that promotes formation of plaque in the arteries and increases risk for heart attack or stroke.
The high-sensitivity C-reactive protein (CRP) test measures levels of a protein made in the liver in response to an immune reaction. CRP is a marker of hidden inflammation in the body. Elevated CRP can be caused by acute processes (e.g., infections, trauma, surgery) or by chronic inflammatory conditions (e.g., arthritis, obesity) and can be a strong predictor of cardiovascular disease and stroke.
Fibrinogen is a protein made in the liver that is needed for blood clotting. It is involved in the early stages of plaque build-up in the arteries and is measured to determine the amount of inflammation that is present. High fibrinogen levels are a risk factor for peripheral artery disease, heart attack, and stroke.
Lp-PLA2 is a biomarker of vascular inflammation associated with the presence of unstable plaque in the arteries. Lp-PLA2 activity is an FDA-cleared test for identifying individuals at higher risk of atherosclerosis, coronary heart disease, and stroke. Lp-PLA2 activity and markers of systemic inflammation (e.g., hs-CRP, fibrinogen) are synergistically associated with the likelihood of major cardiovascular events such as heart attack and stroke.
Vitamin D is a fat-soluble vitamin used to make the steroid hormone calcitriol (vitamin D3) that is most known for its role in strengthening teeth and bones and boosting the immune system. Vitamin D is made by the skin when exposed to sunlight and occurs naturally in foods such as egg yolks, soy, and oily fish such as salmon and sardines. It is important for a healthy gut lining and to control inflammation in the body. Deficiency of this important vitamin has also been linked to cardiovascular disease and a higher risk for heart attacks and strokes.
Homocysteine is an intermediate amino acid that is formed during the metabolism of amino acid methionine to another amino acid, cysteine. As this process requires vitamin B12 and folic acid, an elevated homocysteine level can be an indication of deficiencies in these vitamins. High homocysteine levels are also related to inflammation, oxidative stress (involved with cell aging), and conditions such as heart disease, kidney disease (in patients with high blood pressure), osteoporosis, depression, memory loss, and neurological decline. A poor diet, thyroid disorders, genetic factors, and certain drugs can cause mild-to-moderately elevated homocysteine levels. Homocysteine also rises significantly as we age.
Vitamin B12 plays an important role in many vital processes in the body. It is essential for the “methylation cycle,” a complex biochemical pathway that contributes to key functions such as detoxification, immunity, DNA synthesis, and energy production. Vitamin B12 also plays an important role in synthesis and breakdown of proteins, and in the formation of red blood cells and neurotransmitters. Because the liver holds a reserve of vitamin B12, its deficiency can go unnoticed for several years, but may be seen with high homocysteine (marker of inflammation), neurologic conditions, or megaloblastic anemia. B12 deficiencies have also been linked to strokes and brittle bones.
Folate (vitamin B9) helps the body make new proteins, blood cells, and DNA, which carries the genetic information in our cells. It is important in the conversion of amino acid homocysteine to cysteine in the methylation cycle. The body cannot make folate, so if you are not eating enough folate-rich foods, homocysteine can build up, causing inflammation and increased risk for heart disease and stroke. Folate deficiency has also been linked to nervous system disorders such as depression, memory/attention deficits, and dementia.
MTHFR C677T and A1298C Genotypes
Methyltetrahydrofolate reductase (MTHFR) is an enzyme that works together with the folate vitamins in the “methylation cycle,” a complex biochemical pathway that contributes to key processes such as detoxification, immunity, DNA synthesis, and energy production in the body. It helps to recycle the amino acid homocysteine to another (essential) amino acid, methionine. When the MTHFR gene has a mutation or single nucleotide polymorphism (SNP), at nucleotide position C677T and/or A1298C, it produces a less effective MTHFR enzyme that disrupts the process of methylation. This hinders the breakdown of folate and has cascade effects in the body including inflammation, impaired production of neurotransmitters, build-up of toxins and heavy metals, pregnancy complications/birth defects, susceptibility to stress and depression, and increased risk of cardiovascular disease.
Gamma-Glutamyltransferase (GGT) is present in the cell membranes of many tissues (e.g., liver, kidney, pancreas), although the main source of blood GGT is the liver. Circulating GGT is a sensitive indicator of liver inflammation and can be increased in conditions such as diabetes, fatty liver disease, overactive thyroid, chronic obstructive pulmonary disease, and kidney failure. This marker is an indirect measure of the body’s exposure to environmental toxins including certain drugs, infectious agents, and other chemicals that accumulate in the liver. A high GGT level may also be seen with regular alcohol use and has been linked to ongoing oxidative stress and risk for cardiovascular disease.
Uric acid is produced from the natural breakdown and turnover of body cells and from certain foods (especially meats and meat products). It is a normal constituent of urine. High levels of uric acid (hyperuricemia) may be caused by increased production or decreased elimination of uric acid in the kidneys, and can lead to the formation and accumulation of crystals in the joints and other tissues. This condition is called gout and can be very painful. High uric acid levels are also a risk factor for high blood pressure, metabolic syndrome, heart attacks, kidney disease, heart failure, and strokes.
Creatine kinase (CK) is an enzyme that is found in the muscles, heart, and brain. This test is often used to detect inflammation or serious injury to the muscles, and to diagnose rhabdomyolysis (rapid muscle breakdown) in persons experiencing weakness, muscle aches, and dark urine. The urine may be dark because of the presence of myoglobin, a substance that is released by the damaged muscle tissue that can be harmful to the kidneys. Elevated CK levels may also signal muscle damage due to certain medications or exposure to a toxin. Serum CK may also be used to monitor the effectiveness of blood pressure therapy, and in patients experiencing chest pain, to detect cardiac muscle damage that could be related to a heart attack.
Fasting blood glucose is a strong predictor of risk for diabetes and is often used to diagnose type 2 diabetes and prediabetes. If left untreated, high blood glucose causes inflammation of the blood vessels, making them weaker and more liable to narrowing because of plaque build-up, increasing your risk for coronary artery disease.
Hemoglobin A1c (HbA1c) is formed by the slow attachment of glucose to hemoglobin, the oxygen-carrying protein in the red blood cells. Unlike fasting glucose which gives your blood sugar level at one point in time, measuring HbA1c reflects the percentage of red blood cells with glucose attached to them over their lifespan (2-3 months). This shows how well your blood sugar has been controlled over that extended period of time. HbA1c is helpful in monitoring the effectiveness of blood glucose management and predicting risk of complications (e.g., nerve damage). Chronically high HbA1c has been associated with premature aging and risk of age-related diseases such as heart disease.
Insulin is a hormone secreted by the pancreatic beta cells in response to increases in blood glucose after a meal. It regulates blood glucose by causing glucose uptake in organs and tissues (where it is used for energy), and by blocking the production of more glucose by the liver. Elevated fasting insulin may be a sign of “insulin resistance,” one of the first warning signs of prediabetes which can lead to diabetes if left unchecked.
The fructosamine test measures the amount of “glycated” proteins in the blood (proteins like hemoglobin or albumin that have a sugar molecule bound to them). This indicates how well your blood sugar has been controlled over the past 2-3 weeks, in comparison to a fasting glucose (immediate) or HbA1c (past 2-3 months). High fructosamine levels can indicate a higher risk of cardiovascular disease and have been associated with diabetic complications such as kidney disease and vision loss, even when HbA1c is normal.
The Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) Index is a mathematical equation that uses your fasting glucose and insulin levels to estimate your body’s ability to regulate blood glucose. It takes into account glucose output from the liver, insulin secretion from the pancreas, and the uptake of glucose into cells and tissues to be used for energy. HOMA-IR generally increases if your body is becoming “insulin resistant” and helps to track the function of your pancreas over time. It is a better predictor of risk for diabetes and cardiovascular disease than fasting glucose or fasting insulin alone.
C-peptide is a protein fragment that is produced, along with insulin, from the precursor proinsulin in the beta cells of the pancreas. The amount of C-peptide that is circulating in your bloodstream can be used as a gauge of insulin secretion, as it stays in the blood circulation longer than insulin. A high C-peptide level is an early indicator of insulin resistance and is associated with increased risk of diabetes and cardiovascular disease. C-peptide can also help in differentiating between type 1 and type 2 diabetes.
Adiponectin is an anti-inflammatory hormone produced by fat tissue in the body that helps to protect the heart from disease. It supports blood vessel function, inhibits plaque build-up in the blood vessels, and improves the body’s handling of blood glucose. Low levels of adiponectin may increase risk of type 2 diabetes.
Leptin is a fat-secreted hormone that signals the brain to suppress your appetite when you are full after eating a meal. It also helps regulate blood sugar and lipids. Because leptin comes from fat, overweight people tend to have higher leptin levels, and leptin levels that stay high over time can increase risk of developing diabetes. This “leptin resistance” may also contribute to age-related cognitive issues and dementia.
Insulin-like growth factor 1 is a hormone made mainly in the liver that is important for maintaining muscle mass and strength, for preventing “apoptosis” (programmed cell death), and protecting against oxidative stress, which can cause inflammation and aging. It is also a helpful marker of overall nutrient status. In adults, IGF-1 deficiency is linked to metabolic syndrome, osteoporosis, and increased risk for cardiovascular disease. Too much IGF-1 is considered a risk for some cancers.
Free Fatty Acids
Free fatty acids (FFA) result from the breakdown of triglycerides and are released from body fat into the bloodstream as a source of energy, under the control of insulin and hormones called catecholamines (epinephrine, norepinephrine, and dopamine). The level of FFA in the blood depends on their rate of release from body fat and recent dietary fat intake. High FFA levels can impair the body’s response to insulin and cause blood glucose levels to rise, raising risk for insulin resistance and diabetes. Increased delivery of FFA to the liver also causes a shift toward an unhealthy blood lipid profile, promoting the formation of fatty deposits in the blood vessels.
Proinsulin is the major storage form of insulin and is an accurate marker of pancreatic beta cell function and insulin resistance. High proinsulin levels have been seen in patients with impaired glucose tolerance and are a risk factor for the development of type 2 diabetes.
The ratio of proinsulin to C-peptide measures how well the beta cells convert proinsulin to insulin and C-peptide in the pancreas. When the pancreas is under stress, usually due to chronically high blood sugar levels, the beta cells may lose their processing abilities, and this causes a disproportionate elevation in proinsulin. The proinsulin/C-peptide ratio is a strong predictor of type 2 diabetes.
The anti-GAD IgG test can detect specific antibodies in the blood showing that the body is being tricked into attacking its own beta cells (called an autoimmune attack). Low (but positive) levels of anti-GAD antibodies in the blood are a strong predictor of type 1 diabetes (i.e., juvenile diabetes) and of future onset of diabetes in otherwise healthy individuals. Anti-GAD levels may also rise in association with other seemingly non-related autoimmune diseases or age-related neurodegenerative disorders.
NT-proBNP is secreted from heart muscle cells (called myocytes) in response to cardiac stress or tension, such as volume overload or heart attack/ischemia. It causes the blood vessels to widen or dilate and increases urine excretion from the body to lower circulating fluid volume and lessen stress on the heart. NT-proBNP is a highly effective marker for detecting heart problems and diagnosing heart failure. Mildly elevated levels may predict the risk of future cardiovascular events such as heart attacks or strokes, and are also linked to high blood pressure, sleep apnea, attention/memory problems, and dementia.
Omega-3 Fatty Acids
RBC Omega-3 Index
Omega-3 fatty acids are important parts of cell membranes in the body, where the correct fatty acid composition is vital to your heart and overall health. Omega-3 fatty acids are essential fatty acids, which means that they are essential for your health, but your body cannot make them. If you do not consume enough omega-3 fatty acids from foods or supplements, you may be at higher risk for cardiovascular disease and stroke. An ideal omega-3 index is 8% or greater; at this level you will benefit from positive effects on your blood vessels, heart rate, blood lipids, inflammatory responses, and brain function.
Factor V Leiden Genotype
Factor V Leiden (FVL) is a mutation in the gene for a protein called Factor V that causes your blood to clot more easily. This is the most common inherited risk factor for blood clots occurring in the deep veins, called venous thromboembolism (VTE). Such clots can be serious and even life-threatening, but simple lifestyle modifications can reduce your risk (e.g., avoiding long periods of sitting, staying well hydrated, exercising regularly).
Factor II (Prothrombin) Genotype
The prothrombin (coagulation factor II) G20210A gene mutation leads to increased levels of prothrombin in the blood, making your blood more likely to clot. This genetic variant is the second most common inherited risk factor for venous thromboembolism (VTE).
For Both Genotypes:
VTE occurs in the veins, normally called deep vein thrombosis (DVT). These clots can migrate through the bloodstream to your vital organs and cause pulmonary embolism (lungs), myocardial infarction (heart attack), or stroke (brain). Both FVL and prothrombin (whether you carry one or both altered genes) are predictive of recurring blood clots.
Anticardiolipin (IgG, IgA, IgM) and Anti-beta2 Glycoprotein I (IgG, IgA, IgM)
Antibodies to Anticardiolipin (ACA) and Anti-β2 Glycoprotein I (GPI) have been strongly linked to blood clots in the veins and arteries. These antibodies are often found in people with antiphospholipid syndrome (APS), a condition mainly affecting women that is characterized by abnormal blood clotting together with certain neurological conditions (e.g., migraines), obstetrical complications (e.g., miscarriages), pain and stiffness in the joints, and autoimmune diseases (e.g., systemic lupus erythematosus). APS antibody testing can be used to help determine the cause of unexplained blood clots, low platelet count, or recurrent miscarriages, and may be especially important in women who have a strong family history of stroke, especially prior to pregnancy. APS Antibodies can cause inflammation in the body leading to development of vascular disease in the heart and brain.
Sitosterol, Campesterol, Cholestanol, Desmosterol
Maintaining cholesterol balance within the body is a tightly regulated system that involves using the cholesterol your body already makes, absorbing the cholesterol that you consume, and excreting excess cholesterol through bile from your gallbladder. Measuring blood cholesterol levels directly cannot tell us whether that cholesterol was made in the body or absorbed from food through your intestines, so we measure non-cholesterol sterols (NCS) to help determine whether blood LDL cholesterol levels are high because your body is producing too much or absorbing too much. The NCS levels can also help indicate what type of cholesterol-lowering medicines would be most effective.
Cystatin C is used to assess kidney function. It is more reliable than creatinine, especially in people who are obese, elderly, or malnourished. Cystatin C can detect more subtle changes in kidney filtering capacity earlier than creatine kinase. High cystatin C suggests poor glomerular filtration and declining kidney function, which increases risk of heart disease, heart failure, and stroke.
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