icon_cardiac

Cardiac Function

Cardiac Function markers may be used to assess injury, stress and stretch of the heart muscle.

SMC™ cTnI*

Cardiac troponin-I is a contractile protein found in cardiomyocytes. In the primary prevention setting, even slight elevations indicate risk for incident heart failure (HF), and cardiovascular (CV) death.1,2,3 In secondary prevention, patients with elevations are at risk for future myocardial infarction, HF, or CV death.4,5

In the Minnesota Heart Survey, Singulex hs-cTnI levels > 10 pg/mL were associated with an 8.5x increase in CV death compared to levels ≤ 10 pg/mL in an asymptomatic population.3

In Merlin TIMI 36, patients with non-ST elevation ACS and Singulex SMC hs-cTnI levels between 4.84-10.05 pg/mL, were associated with 2.19x increase in CV death or myocardial infarction (MI) by one year, as compared to those with cTnI levels < 4.84 pg/mL.10

NT-proBNP

Peptide released in response to cardiac wall stress or stretch. Elevations in NT-proBNP may indicate risk for developing atherosclerosis, cardiac dysfunction and heart failure, and are independently associated with cardiac events in both primary and secondary prevention patient populations.1,2,3

In a general population, high NT pro-BNP indicated up to 4.1 times increased risk for heart failure, CV events and all-cause mortality.3

In the PROTECT study with heart failure patients, increasing NT-proBNP concentrations over time, were associated with 2x increased occurrence of CV events, compared to stable or decreasing NT-proBNP concentrations below 1000 pg/mL.4

icon_inflammation

Inflammation

Chronic inflammatory activity underlies many disease states such as cardiovascular disease, diabetes and sleep disordered breathing.1 The ability to measure and monitor inflammation may aid in the proactive management of patients.

SMC™ Endothelin*

Endothelin is a pro-inflammatory peptide, secreted by vascular endothelial cells and vascular smooth muscle cells, that regulates arterial vasomotor tone and thus blood pressure.1 In addition, it is secreted by and exerts its effects on renal, pulmonary, cardiac, hepatic, and adipose cells.1 ET promotes the development of atherosclerotic vascular disease by stimulating inflammatory cytokine release, platelet aggregation, cell adhesion molecule expression, and vascular smooth muscle cell proliferation.2

In a study including patients with chronic stable angina, only endothelin was found to be an independent predictor of rapid disease progression (OR 6.6).3

SMC™ IL-6*

Pro-inflammatory cytokine that may increase platelet aggregation and synthesis of C-reactive protein (CRP), and is associated with increased severity of cardiovascular disease (CVD).1 IL-6 is involved in the pathogenesis of atherosclerosis, as elevated IL-6 concentrations are found in atheromatous arterial plaques.2,3 There is a strong independent association between elevated IL-6 levels and the presence of clinical and subclinical CVD, including heart failure and mortality in the elderly.4,6

In the EPIC-Potsdam study, an adjusted OR of 2.6 for developing type 2 diabetes was found in those with elevated IL-6.7

Severe sleep apnea associated with elevated IL-6 after sleep (OR=3.82).5

SMC™ IL-17A*

IL-17A is a T-cell derived cytokine that stimulates stromal cells and macrophages to secrete proinflammatory cytokines.1 It is responsible for inducing and mediating immune and inflammatory responses.2

Elevations are seen in cardiovascular disease and it has been shown that IL-17A plays a role in atherosclerosis and plaque instability.2,3

SMC™ TNF-α*

TNF-α is a pro-inflammatory cytokine secreted by macrophages. Elevated levels may contribute to insulin resistance and endothelial dysfunction.1,2 There is a strong independent association between elevated TNF-α levels and the presence of clinical and subclinical cardiovascular disease, and heart failure (HF).3,4,5

In the Health Aging and Body Composition study, IL-6 and TNF-α were independently associated with incident heart failure, in a multivariable adjusted model.4

Increased TNF-α concentration is associated with peripheral insulin resistance and increased plasma glucose and insulin levels prior to onset of type 2 diabetes.6

Ferritin

Ferritin is an iron-containing protein produced in the liver. Elevated iron stores may enhance the oxidation of lipids through the production of free radicals via the Fenton Reaction.1 Additionally, iron deposits in the liver, beta cells, and peripheral muscle tissue may contribute to insulin resistance by interfering with the ability of insulin to suppress hepatic glucose production, and disrupting glucose metabolism in muscle.2

In the EPIC-Norfolk study, elevated ferritin was found to have an OR of 3.2 for incident type 2 diabetes.3

Homocysteine

Homocysteine is the by-product of methionine metabolism, a process that requires vitamin B6, vitamin B9 (folic acid), and vitamin B12. Elevated levels are an independent cardiovascular risk factor, and may contribute to cardiovascular disease by damaging endothelial cells, altering platelet aggregation, inhibiting vasodilation, and increasing oxidation of low-density lipoprotein (LDL) cholesterol.1,2

Each increase of 5 umol/L in homocysteine level increases the CHD events by 20%, independently of traditional risk factors.3

hs-CRP

Primarily an acute phase reactant produced in the liver that is associated with generalized inflammatory response and atherogenesis. Elevated concentrations are predictive of recurrent ischemia, myocardial infarction, and stroke.1

In high-functioning older persons, a measure of inflammation can identify those at risk of mortality and functional decline. OR up to 6.6 with elevations of IL-6 > 3.8pg/mL, hs-CRP > 2.65 mg/l, low albumin 2

Lp-PLA2

Vascular specific inflammatory enzyme that is associated with the formation of rupture-prone plaque.1

Lp-PLA2 activity is an independent predictor of coronary heart disease and stroke in the general population.2,3,4

In the REGARDS study, Lp-PLA2 Activity levels above 225 nmol/min/ml activity units, showed a significant increase in CHD events in patients without known CHD (HR 1.54).5

Uric Acid

Uric acid is a product of purine metabolism.

Risk factors associated with elevated UA include hypertension, metabolic syndrome, obstructive sleep apnea, vascular disease, endothelial dysfunction, and stroke. Elevated UA is a negative prognostic marker for stroke, and is associated with inflammatory markers such as CRP, IL-6 and TNF-α.1,2,3

In the NHANES-III study the prevalence of metabolic syndrome was very high among individuals with gout. Age and sex adjusted OR 3.05.4

Vitamin D

The primary function of vitamin D is the regulation of intestinal calcium absorption and the maintenance of serum calcium concentration via the stimulation of bone resorption.1 Most Americans do not achieve adequate vitamin D levels.2 An estimated 90% of adults between 51 and 70 years of age do not obtain adequate vitamin D from their diet.3 Low levels of vitamin D are associated with endothelial dysfunction, inflammation, hypertension and left ventricular hypertrophy, elevated parathyroid hormone (PTH), osteoporosis, cancer, insulin resistance and type 2 diabetes, and risk for cardiovascular events.4,5,6

For every 10 ng/mL decline in vitamin D, there is a 9% greater relative hazard of mortality, and a 25% greater relative hazard of myocardial infarction.7

  • Folate
  • Vitamin B12

icon_lipid

Lipid Management

The Lipid Management menu of tests provide greater detail by identifying the quantity and quality of cholesterol particles. National organizations such as the AACE and ACE, as well as the ADA and ACC Foundation recommend the routine measurement of lipid particle number.1,2

Apo A-1

Apo A-1 is the major protein of high density lipoprotein (HDL). Apo A-1 containing particles mediate reverse cholesterol transport by returning excess cholesterol from peripheral tissues to the liver. Low levels indicate suboptimal reverse cholesterol transport.1

In a meta-analysis, a RR of 1.62 for incident CHD was found with low apo A-1.2

Apo B

Apo B is the primary protein component in very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), lipoprotein(a) [Lp(a)], chylomicrons and chylomicron remnants. Apo B is associated with each particle in a 1:1 ratio; it is considered a direct measure of atherogenic lipoproteins.1

Elevated apo B is associated with the presence of carotid atherosclerosis, cardiovascular events, the metabolic syndrome and type 2 diabetes.1

In a meta-analysis, a 1.99 RR for CHD was found in individuals in the top third versus those in the bottom third tertile.2

HDL-C

HDL particles contain close to equal amounts of lipid and protein. The function of HDL is to mediate reverse cholesterol transport, in which cholesterol from the peripheral tissues is returned to the liver for excretion as bile.1

HDL is additionally cardioprotective, due to its anti-inflammatory, anti-oxidative, and anti-thrombotic characteristics.1,2

Low HDL is an independent risk factor for cardiovascular disease, while high HDL has been shown to be protective against the development of cardiovascular disease.1,2

In a meta-analysis, CHD risk decreases by 2-3% for every 1-mg/dL increase in HDL-C level.3

HDL-2b*

The cardioprotective function and inverse relationship with cardiovascular disease seen in HDL comes mostly from the subclass HDL-2b.1

Low HDL-2b is associated with adverse cardiovascular events.1,2

Lp(a)

Lp(a) is the most powerful genetic risk factor for cardiovascular disease.1 Structurally similar to plasminogen, it competes for plasminogen receptor sites, which results in increased coagulability and reduced fibrinolysis.2 Lp(a) is a stable risk factor for coronary artery disease, peripheral vascular disease, ischemic stroke and abdominal aortic aneuryism.3

For each 10 mg/dL increase in Lp(a), there was a significant 6%-9% increase in relative risk of CHD.4

LDL-C (direct)

LDL-C is a measure of the cholesterol content of LDL particles. Elevated LDL-C may promote atherosclerosis, particularly when the LDL is oxidized.1

LDL-C was associated with an overall incident cardiovascular disease HR of 1.20.2

sdLDL*

The atherogenicity of sdLDL is related to its extended time in circulation, ability to more easily enter the arterial wall, and susceptibility to oxidation. Elevated sdLDL is independently associated with incident cardiovascular disease (CV), as well as disease progression and severity.1

Elevations show up to 3.6x increased risk of incident ischemic heart disease in men.2,3

In the ARIC study, a HR of 1.61 was found with elevated sdLDL even in individuals considered to be at low CV risk based on LDL-C levels.4

Triglycerides

Triglycerides are an important biological marker of cardiovascular disease risk, due to their association with remnant particles (such as very low-density lipoprotein (VLDL) and intermediatedensity lipoprotein (IDL)) and impaired reverse cholesterol transport. Elevated triglycerides are an independent cardiovascular risk, especially in those at risk for or diagnosed with type 2 diabetes.1

In a meta-analysis, an OR of 1.72 was found for incident coronary heart disease.2

  • Total Cholesterol
  • Total CK

icon_diabete

Diabetes & Weight Management

Nearly 30% of people with diabetes are undiagnosed.1 The Diabetes & Weight Management menu of tests may help risk stratify patients for diabetes and heart disease and may be used to monitor therapy effectiveness.

Adiponectin*

Adiponectin is a protein hormone secreted primarily by adipocytes. It has anti-inflammatory, anti- antiatherogenic, and insulin- sensitizing effects on the heart and blood vessels. Serum levels of adiponectin are reduced in patients with type 2 diabetes, insulin resistance, obesity, and coronary artery disease.1

Paradoxically, elevated levels may be seen in post acute coronary syndrome and chronic heart failure patients, and are predictive for mortality.2

Longitudinal studies have shown that circulating levels of adiponectin are a marker for all-cause mortality, heart failure, CAD and type 2 diabetes.3

In a meta-analysis, higher levels of adiponectin were associated with lower risk of type 2 diabetes across diverse populations, consistent with a dose-response relationship.4

Cortisol

Cortisol is a hormone responsible for regulating blood sugar, energy production, inflammation, and immune response. Cortisol levels may elevate in a response to physical, mental, or environmental stress.1

Cortisol directly affects the heart and blood vessels, influencing vascular function, atherogenesis, and vascular remodeling.1,2 Elevations may also affect glucose and lipid metabolism, as well as blood pressure.1

5x increased risk of cardiovascular death.3

Cystatin C

Cystatin C is a serum protein produced at a steady rate by all nucleated cells. It is cleared only via glomerular filtration and is less influenced by age, gender, race, and muscle mass than creatinine, making it an ideal marker for assessing kidney function.1,2 Studies have shown cystatin C to be a marker for early detection of kidney disease, and a superior risk marker to creatinine-based eGFR for cardiovascular morbidity and mortality.1,3

A combined creatinine -cystatin C equation is superior to equations based on either marker alone and may be useful for detecting and confirming chronic kidney disease.2 In addition cystatin C distinguishes between “higher risk” and “lower risk” individuals for CKD complications with creatinine-based eGFR <60 ml/min.4

HR 3.87 for cardiovascular mortality in a secondary prevention population with elevated cystatin C.5

Ferritin

Ferritin is an iron-containing protein produced in the liver. Elevated iron stores may enhance the oxidation of lipids through the production of free radicals via the Fenton Reaction.1 Additionally, iron deposits in the liver, beta cells, and peripheral muscle tissue may contribute to insulin resistance by interfering with the ability of insulin to suppress hepatic glucose production, and disrupting glucose metabolism in muscle.2

In the EPIC-Norfolk study, elevated ferritin was found to have an OR of 3.2 for incident type 2 diabetes.3

GGT

GGT is an enzyme primarily produced by the liver. It is associated with diseases that cause damage to the liver or bile ducts, such as cancer and viral hepatitis.1

An increased GGT level over time may predict onset of metabolic syndrome, incident CVD and death and is associated with insulin resistance and incident type 2 diabetes in both men and women.2,3

OR 2.49 and 2.53 in middle aged men and women, respectively, for type 2 diabetes.2

HR up to 1.67 for incident CVD in the Framingham Heart Study.3

Glucose

Elevated glucose is a risk for both microvascular and macrovascular disease, and contributes to endothelial dysfunction and cardiovascular disease (CVD). Elevated fasting levels above 100 mg/dL are associated with an increased risk of developing type 2 diabetes and future CVD.1

Impaired fasting glucose is associated with obesity (especially abdominal or visceral obesity), dyslipidemia with high triglycerides and/or low HDL cholesterol, and hypertension.2

Impaired fasting glucose carried a 6.02 RR for the development of diabetes mellitus.3

HbA1c

HbA1c represents the average level of blood glucose over the previous 3 months, and demonstrates the degree of glucose control.1

A 1% increase in HbA1c concentrations is associated with a 20–30% increase in cardiovascular events and all-cause mortality.2

Insulin

Elevated fasting insulin levels are associated with pre-diabetes, type 2 diabetes, and future cardiovascular events.1 Generally, elevated insulin levels are detected before changes in glucose levels.1

Elevations in both insulin and apo B were found to have an OR of 11.0 for ischemic heart disease risk.1

Leptin*

Leptin is an adipokine that helps regulate appetite by signaling satiety to receptors in the hypothalamus. It also has peripheral actions that stimulate vascular inflammation, oxidative stress, and vascular smooth muscle hypertrophy.1 These actions may contribute to the pathogenesis of type 2 diabetes, hypertension, and cardiovascular disease (CVD).1

Elevated leptin and high blood pressure is associated with OR 4.89 in men and OR 4.10 in women for ischemic stroke.2

Higher levels of leptin have been associated with increased risk of breast cancer in postmenopausal women (OR 1.94).3,4

Vitamin D

The primary function of vitamin D is the regulation of intestinal calcium absorption and the maintenance of serum calcium concentration via the stimulation of bone resorption.1 Most Americans do not achieve adequate vitamin D levels.2 An estimated 90% of adults between 51 and 70 years of age do not obtain adequate vitamin D from their diet.3 Low levels of vitamin D are associated with endothelial dysfunction, inflammation, hypertension and left ventricular hypertrophy, elevated parathyroid hormone (PTH), osteoporosis, cancer, insulin resistance and type 2 diabetes, and risk for cardiovascular events.4,5,6

For every 10 ng/mL decline in vitamin D, there is a 9% greater relative hazard of mortality, and a 25% greater relative hazard of myocardial infarction.7

  • Calcium
  • Magnesium
  • Phosphorus

icon_bone

Calcium, Bone & Mineral Health

PTH, calcium, magnesium, phosphorus, and vitamin D function together to maintain a homeostatic state; imbalances may adversely affect cardiovascular and bone health.

PTH

Primary hyperparathyroidism is the unregulated overproduction of PTH associated with abnormal parathyroid function, resulting in abnormal calcium homeostasis. The catabolic effect of primary hyperparathyroidism promotes osteoclast activity and bone resorption and is considered a cause of secondary osteoporosis.1 In secondary hyperparathyroidism, chronic vitamin D deficiency leads to a decrease in blood calcium, which stimulates increased PTH secretion. Excessive PTH levels have a pro-inflammatory effect, stimulating the release of cytokines by vascular smooth muscle cells, promoting cardiomyocyte hypertrophy and vascular remodeling.2,3

Elevations showed a HR of 1.47 for increased risk of death, coronary artery disease, myocardial infarction and stroke, independent of vitamin D levels.4

Vitamin D

The primary function of vitamin D is the regulation of intestinal calcium absorption and the maintenance of serum calcium concentration via the stimulation of bone resorption.1 Most Americans do not achieve adequate vitamin D levels.2 An estimated 90% of adults between 51 and 70 years of age do not obtain adequate vitamin D from their diet.3 Low levels of vitamin D are associated with endothelial dysfunction, inflammation, hypertension and left ventricular hypertrophy, elevated parathyroid hormone (PTH), osteoporosis, cancer, insulin resistance and type 2 diabetes, and risk for cardiovascular events.4,5,6

For every 10 ng/mL decline in vitamin D, there is a 9% greater relative hazard of mortality, and a 25% greater relative hazard of myocardial infarction.7

  • Calcium
  • Magnesium
  • Phosphorus

icon_renalhepatic

Renal & Hepatic

The Renal & Hepatic menu of tests may be used to detect, evaluate and monitor disease and/or damage.

Cystatin C (Renal)

Cystatin C is a serum protein produced at a steady rate by all nucleated cells. It is cleared only via glomerular filtration and is less influenced by age, gender, race, and muscle mass than creatinine, making it an ideal marker for assessing kidney function.1,2 Studies have shown cystatin C to be a marker for early detection of kidney disease, and a superior risk marker to creatinine-based eGFR for cardiovascular morbidity and mortality.1,3

A combined creatinine -cystatin C equation is superior to equations based on either marker alone and may be useful for detecting and confirming chronic kidney disease.2 In addition cystatin C distinguishes between “higher risk” and “lower risk” individuals for CKD complications with creatinine-based eGFR <60 ml/min.4

HR 3.87 for cardiovascular mortality in a secondary prevention population with elevated cystatin C.5

GGT (Hepatic)

GGT is an enzyme primarily produced by the liver. It is associated with diseases that cause damage to the liver or bile ducts, such as cancer and viral hepatitis.1

An increased GGT level over time may predict onset of metabolic syndrome, incident CVD and death and is associated with insulin resistance and incident type 2 diabetes in both men and women.2,3

OR 2.49 and 2.53 in middle aged men and women, respectively, for type 2 diabetes.2

HR up to 1.67 for incident CVD in the Framingham Heart Study.3

  • BUN (Renal)
  • Calcium (Renal)
  • Chloride (Renal)
  • CO2 (Renal)
  • Creatinine (Renal)
  • Phosphorus (Renal)
  • Potassium (Renal)
  • Sodium (Renal)
  • Albumin (Hepatic)
  • Alkaline Phosphatase (Hepatic)
  • ALT (Hepatic)
  • AST (Hepatic)
  • Bilirubin – Direct (Hepatic)
  • Bilirubin – Total (Hepatic)
  • Protein – Total (Hepatic)

icon_thyroid

Thyroid

Most thyroid diseases are life-long conditions that can be managed with medical attention.

Free T3

Free T3 is the physiologically active form of T3.

Free T4

Lower free thyroxine (T4) levels have been associated with increased cardiovascular risk, insulin resistance, hyperlipidemia, and metabolic syndrome.1,2,3

T3

T3 concentration in serum is more a reflection of the functional state of the peripheral tissue than the secretory performance of the thyroid gland. T3 works directly on the cardiomyocyte and systemic vasculature, affecting systemic vasculature resistance, blood volume, cardiac contractility, heart rate, and cardiac output.1

~30% of patients with congestive heart failure have low T3.1

Reduced T3 is a predictor of all-cause and cardiovascular mortality.1

T4

Lower free thyroxine (T4) levels have been associated with increased cardiovascular risk, insulin resistance, hyperlipidemia, and metabolic syndrome.1,2,3

TgAb

This antibody targets thyroglobulin, the storage form of thyroid hormones. Thyroglobulin (Tg) may leak into the bloodstream when there is follicular destruction through inflammation (i.e. Hashimoto’s thyroiditis) or rapid disordered growth of thyroid tissue (i.e. Graves’ disease). This may result in the development of autoantibodies to Tg (+TgAb) in some individuals.1

TPOAb

Thyroid antibodies develop when the immune system mistakenly targets components of the thyroid gland or thyroid proteins leading to chronic inflammation of the thyroid (thyroiditis), tissue damage and/or disruption of thyroid function. TPOAb is the most common test for autoimmune thyroiditis disease (sensitive and specific); it can be detected in both Hashimoto’s thyroiditis and Graves’ disease.1,2

TSH

Both hyperthyroidism and hypothyroidism produce changes in cardiac contractility, myocardial oxygen consumption, cardiac output, blood pressure, and vascular resistance.1

Hyperthyroidism and hypothyroidism may lead to cardiac arrhythmias, and hypothyroidism may contribute to hypercholesterolemia.1

The risk of CHF was higher among those with high TSH of 7.0-9.9 mIU/L (HR 2.58) and those with TSH of 10.0 mIU/L (HR 3.26).2

icon_hormones

Hormones

The Hormone menu of tests may be used to evaluate hormone balance and detect and manage disease.

Cortisol

Cortisol is a hormone responsible for regulating blood sugar, energy production, inflammation, and immune response. Cortisol levels may elevate in a response to physical, mental, or environmental stress.1

Cortisol directly affects the heart and blood vessels, influencing vascular function, atherogenesis, and vascular remodeling.1,2 Elevations may also affect glucose and lipid metabolism, as well as blood pressure.1

5x increased risk of cardiovascular death.3

DHEA-S

DHEAS is an adrenal androgen with weak intrinsic effect and a precursor to testosterone and dihydrotestosterone as well as estrogen. DHEAS is used to help evaluate adrenal function, detect adrenal tumors or cancers and determine the cause of virilization in girls and women and early puberty in boys.1 In women, DHEAS is associated with polycystic ovarian syndrome (PCOS), hirsutism, acne, amenorrhea and/or infertility.1

Estradiol

Primarily produced in the ovaries in pre-menopausal women and in the testicles in men. It is used to evaluate ovarian function.1 In women, estradiol is associated with assessing hormonal imbalances such as infertility, menopause, and abnormal menstrual periods but also monitor pregnancy, bone metabolism and metabolic conditions.1

Abnormal estradiol levels are associated with increased risk of developing atherosclerosis in premenopausal women.2

Abnormal estradiol levels are associated with increased risk for CVD, atherosclerosis, ischemic heart disease and bone loss in menopausal women.3

FSH

FSH is a hormone associated with reproduction and the stimulation of the release of an egg from the ovary (ovulation) in women and testosterone production in men. It is used to evaluate the function of ovaries or testicles. It is associated with pituitary disorder or hypothalamic disorder.1

In women, abnormal levels are associated with infertility, abnormal menstrual cycles and menopause.1

In men, abnormal levels are associated with testosterone production, infertility, low sperm count, low muscle mass and decreased sex drive.1

LH

LH is a hormone associated with reproduction and the stimulation of the release of an egg from the ovary (ovulation) in women and testosterone production in men. It is used to evaluate the function of ovaries or testicles. It is associated with pituitary disorders or hypothalamic disorders.1

In women abnormal levels are associated with infertility, abnormal menstrual cycles and menopause.1

In men, abnormal levels are associated with testosterone production, infertility, low sperm count, low muscle mass and decreased sex drive.1

Progesterone

Progesterone is a hormone used to help determine the causes of infertility, track ovulation, help diagnose an ectopic or failing pregnancy, monitor the health of a pregnancy, monitor progesterone replacement therapy, or help diagnose the cause of abnormal uterine bleeding in women.1 In men, progesterone is associated with development of sperm.1

Prolactin

Prolactin is a hormone responsible for the production of breast milk, galactorrhea and prolactinoma.1 Hyperprolactinemia is associated with an increased risk of overall cancer.2 Prolactinomas are associated with optic nerve disorders, headaches and visual disturbances.1

In women, abnormal levels are associated with infertility and absence of menstrual periods.1

In men, abnormal levels are associated with erectile dysfunction, reduced libido, nipple discharge, infertility and low testosterone. Severe hyperprolactinemia is associated with sexual dysfunction in men.2

Elevated prolactin was associated with hypoactive sexual desire (HR 8.60) in men.2

SHBG

Testosterone and estradiol circulate in the bloodstream, bound mostly to SHBG. SHBG is a sex hormone transport protein that affects the circulating levels of bioavailable testosterone, and has emerged as one of many factors associated with type 2 diabetes, metabolic syndrome, sleep apnea, and cardiovascular disease (especially in women).1,2,3,4,5,6,7,8

Total testosterone and SHBG tests are ordered to evaluate free androgens by calculating the Free Testosterone Index (FTI), a method of quantifying the amount of testosterone, not bound to SHBG.

Testosterone

Low testosterone in men is frequently accompanied by adverse health consequences, including decreased muscle mass, increased abdominal fat, insulin resistance, dyslipidemia, and hypertension.1,2 Studies in men have also shown that low testosterone levels are associated with increased risk of mortality, cardiovascular events and future type 2 diabetes.3,4,5

Elevated testosterone levels in women are associated with adverse metabolic features, including insulin resistance and type 2 diabetes, abdominal obesity, dyslipidemia, chronic inflammation, cardiovascular disease, and polycystic ovary syndrome (PCOS).6,7

icon_oncology

Oncology

The Oncology menu of tests may be used as an aid in the detection and management of prostate cancer.

Total PSA

Prostate Specific Antigen (PSA) is a glycoprotein produced by cells of the prostate gland and absorbed into the bloodstream. Increases in glandular size and tissue damage may increase circulating PSA levels. PSA, in combination with the digital rectal examination (DRE) substantially enhances prostate cancer detection rate.1 Prostate cancer screening is controversial; any man who is considering getting tested should first be informed in detail about the potential harms and benefits.2

Free PSA

Most PSA in the blood is bound to serum proteins. Free PSA is not protein bound. The risk of cancer increases if the free to total ratio is less than 25%.3

* Information herein pertains to testing performed by or for the Singulex Clinical Laboratory. Singulex proprietary lab developed tests (SMC™ tests, sd-LDL, HDL2b, Adiponectin, and Leptin) were developed and performance characteristics were determined by Singulex. These tests have not been cleared or approved by the U.S. Food and Drug Administration.

References

Cardiac Function

cTnI

1. Sundstrom J, et al. Eur Heart J. 2009; 30: 773-781.
2. Wang T, et al. Circulation. 2012; 126: 1596-604.
3. Apple F, et al. Clin Chem. 2012; 58: 930-935.
4. Omland T, et al. J Am Coll Cardiol. 2013; 61: 1240-9.
5. White H, et al. J Am Coll Cardiol. 2014; 63: 345-54.
10. Bonaca M, et al. Eur Heart J Acute Cardiovasc Care. 2015; 4: 431 -40.

NT-proBNP

1. Rosenberg J, et al. Euro Heart J. 2009; 30: 66-73.
2. Tsai S, et al. Yonsei Med J. 2010; 51: 151-163.
3. Don-Wauchope A, et al. Heart Fail Rev. 2014; 19: 541-51.
4. Gaggin H, et al. Cong Heart Fail. 2013; 19: 135-42.

Inflammation

1. Kalogeropoulos A, et al. Heart Failure Clin. 2012; 8: 113–123.

Endothelin

1. Bohm F, et al. Cardiovasc. Res. 2007; 76: 8-18.
2. Weil B, et al. Can J Cardiol. 2012; 28: 347-53.
3. Zouridakis E, et al. E Heart J. 2001; 22:1578-84.

TNF-α

1. Winkler G, et al. Diabet Med. 1999; 16: 207-11.
2. Zhang H, et al. Clin Sci. 2009; 116: 219-230.
3. Dunlay S, et al. Circulation. 2008; 118: 625-631.
4. Kalogeropoulos A, et al. J Am Coll Cardiol. 2010; 55: 2129-37.
5. Cesari M, et al. Am J Cardiol. 2003; 92: 522-8.
6. Miyazaki Y, et al. Intern J of Obesity. 2003; 27:88-94

Homocysteine

1. Lipi G, et al. Clin Chem Lab. 2012; 50: 2075-2080.
2. Varga E, et al. Circulation. 2005; 111: e289-e293.
3. Humphrey L, et al. Mayo Clin Proc. 2008; 83: 1203-12.

IL-6

1. Luc G, et al. Arterioscler Thromb Vasc Biol. 2003; 23: 1255-1261.
2. Raaz-Schrauder D, et al. Cytokine. 2012; 57: 251-257.
3. Fisman E, et al. Adv Cardiol. 2008; 45: 44-64.
4. Kalogeropoulos A, et al. J Am Coll Cardiol. 2010; 55: 2129-37.
5. Maeder M, et al. Clin Biochem. 2015; 48: 340 -6.
6. Harris T, et al. Am J Med. 1999; 106: 506-512.
7. Spranger J, et al. Diabetes. 2003; 52: 812-817.

Lp-PLA2

1. Ballantyne C, et al. Circulation. 2004; 109: 837-42.
2. Lp-PLA2 Studies Collaboration, et al. Lancet. 2010; 375: 1536-1544.
3. Persson M, et al. Arterioscler Throm Vasc Biol. 2007; 27:1411-1416.
4. O’Donoghue M, et al. Circulation. 2006; 113:1745-1752.
5. Package Insert: Lp-PLA2 activity assay, diaDexus, Inc.

Uric Acid

1. Ruggiero C, et al. Eur Heart J. 2006; 27: 1174–1181.
2. Fang J, Alderman M. JAMA. 2000; 283: 2404-2410.
3. Feig D, et al. N Engl J Med. 2008; 359: 1811-21.
4. Choi H, et al. Arthritis and Rheumatism. 2007; 109-115.

IL-17A

1. Fisman E, et al. Adv Cardiol. 2008; 45: 44-64.
2. Erbel C, et al. Basic Res Cardiol. 2011; 106: 125-134.
3. Zhu F, et al. Clin Immunol. 2011; 141: 152-60.

hs-CRP

1. The Emerging Risk Factors Collaboration. Lancet. 2010; 375: 132-40.
2. Reuben D, et al. J Am Geriatr Soc. 2002; 50: 638-644.

Lipid Management

1. Garber A, et al. Endocrine Practice. 2016; 22:84–113.
2. Brunzell J, et al. Diabetes Care. 2008; 31:811–822.

Triglycerides

1. Miller M, et al. Circulation. 2011; 123: 2292-333.
2. Sarwar N, et al. Circulation. 2007; 115: 450-458.

LDL-C

1. Medline Plus. “What is Cholesterol.” Available at http://www.nhlbi.nih.gov/health/health-topics/topics/hbc. Accessibility verified October 23, 2014.
2. Otvos J, et al. J Clin Lipidol. 2011 ; 5: 105–113.

Apo B

1. Cole T, et al. Clinical Chemistry. 2013; 59: 752-770.
2. Thompson A et al. J. Intern Med. 2006; 259: 481-92.

HDL-C

1. Assman G, Gotto A. Circulation. 2004; 109: III8-14.
2. Toth P. Circulation. 2004; 109: 1809-1812.
3. Gordon D, et al. Circulation. 1989;79:8-15.

sdLDL

1. Kwon S, et al. Yonsei Med J. 2006; 47: 405-14.
2. Lamarche B, et al. Circulation. 1997; 95: 69-75.
3. St-Pierre A, et al. Arterioscler Thromb Vasc Biol. 2005; 25: 553-559.
4. Hoogeveen R, et al. Arterioscler Thromb Vasc Biol. 2014; 34: 1069-1077.

ApoB/ApoA1 Ratio

1. Walldius G, et al. J Intern Med. 2006; 259: 493-519.
2. Yusuf S et al. Lancet. 2004; 364: 937-952.
3. Kastelein JJ, et al. Circulation. 2008;117:3002-3009.

HDL-2b

1. Zeljkovic A, et al. Atherosclerosis. 2010; 210: 548-54.
2. Jia L, et al. Int J Cardiol. 2007; 120: 331-7.

Apo A1

1. Barter P, Rye K. J Intern Med. 2006; 259: 447-54.
2. Thompson A et al. J. Intern Med. 2006; 259: 481-92.

Lp(a)

1. Nordestgaard B, et al. Eur Heart J. 2010; 31: 2844–53.
2. Kamstrup P, et al. J Am Coll Cardiol. 2013; 61: 1146-1156.
3. Jones G, et al. Clin Chem. 2007; 53: 679-685.
4. Jacobson T. Mayo Clin Proc. 2013; 88: 1294-1311.

Diabetes & Weight Management

1. CDC. National Diabetes Statistics Report, 2014. Available at http://www.cdc.gov/diabetes/pubs/statsreport14/national-diabetes-re¬port-web.pdf. Accessibility verified December 22, 2015.

Glucose

1. American Diabetes Association. Diabetes Care. 2014; 37: Supplement 1 S14-S80.
2. Position Statement ADA. Diabetes Care. 2014; 37: Supplement 1 S14 -S80.
3. Santaguida P, et al. AHRQ Study. 2006; 128: 1–12.

Cortisol

1. Walker B. Eur J Endocrinol. 2007; 157: 545-559.
2. Hamer M, et al. PLoS One. 2012; 7: e31356.
3. Vogelzangs N, et al. J Clin Endocrinol Metab. 2010; 95: 4959-4964.

Ferritin

1. Basuli D, et al. Front Pharmacol. 2014; 5: 117.
2. Fernandez-Real J, et al. Diabetes Care. 1998; 21: 62-68.
3. Forouhi N, et al. Diabetologia. 2007; 50: 949-956.

Insulin

1. Despres J, et al. NEJM. 1996; 334: 952-957.

Adiponectin

1. Szmitko P, et al. Am J Physiol Heart Circ Physiol. 2007; 292: H1655-H1663.
2. Wilson S, et al. Am Heart J. 2011; 161: 1147-1155.
3. Bluher M et al. Metabolism J. 2015; 64:131-145.
4. Li S, et al. JAMA. 2009; 302:179-188.

HbA1c

1. MedlinePlus. “A1c Test.” Available at http://www.nlm.nih.gov/medlineplus/ency/article/003640.htm. Accessibility verified October 23, 2014.
2. Khaw K, et al. Ann Intern Med. 2004; 141: 413-420.

Leptin

1. Koh K, et al. Circulation. 2008; 117: 3238-3249.
2. Soderberg S, et al. Cerbrovasc Dis. 2001; 15:63-69.
3. Ollberding N, et al. Cancer Prev Research. 2013; 6: 188-195.
4. Niu J, et al. PLOS ONE. 2013; 8: 1-8.

Calcium, Bone & Mineral Health

PTH

1. Mazzuoli G. Aging Clinical and Experimental Research. 1998; 3: 225-231.
2. Hagstrom E, et al. Circulation. 2009; 119: 2765-2771.
3. Deo R, et al. Hypertension. 2011; 58: 1021-1028.
4. Anderson J, et al. Am Heart J. 2011; 162: 331-339.e2.

Vitamin D

1. Reid IR. Clinical aspects of the use of vitamin D and its metabolites. In: Orwoll ES, Bliziotes M, editors. Osteoporosis: Pathophysiology and Clinical Management. Totowa, NJ: Humana Press; 2003. pp. 293 -307.
2. Moore C., et al. Journal of the American Dietetic Association. 2004; 104: 980-983.
3. Sunyecz, J. A. Therapeutics and Clinical Risk Management. 2008; 4: 827 -836.
4. Wang T, et al. Circulation. 2008; 117: 503-511.
5. Lee J, et al. J Am Coll Cardiol. 2008; 52: 1949-56.
6. Cosman F, et al. Osteoporosis International. 2014; 25: 2359-2381.
7. Kestenbaum B, et al. J Am Coll Cardiol. 2011; 58: 1433-41.

Renal & Hepatic

Cystatin C

1. Koenig W, et al. Clinical Chemistry. 2005; 51:321-327.
2. Inker L, et al. N Engl J Med. 2012; 367:20-29.
3. Svensson-Färbom P, et al. J Intern Med. 2014; 275: 506-21.
4. Peralta C et al. Am Soc Nephrol. 2011;22:147-155.
5. Keller T, et al. Eur Heart J. 2009; 30: 314-320.

GGT

1. American Association for Clinical Chemistry. “GGT”. https://labtestsonline.org/understanding/analytes/ggt/tab/test. Accessibility verified April 5, 2016.
2. Andre P, et al. Diabetologia. 2006; 49: 2599-603.
3. Lee S, et al. Arterioscler Thromb Vasc Biol. 2007; 27: 127-133.

Thyroid

TSH

1. Klein I, et al. Circulation. 2007; 116: 1725-1735.
2. Rodondi N, et al. Arch Intern Med. 2005; 165: 2460-2466.

T4 Total

1. Klein I, et al. Circulation. 2007; 116: 1725-1735.
2. Fischbach F and Dunning M. Nurses’ Quick Reference to Common Laboratory & Diagnostic Tests, 4th ed. (PA : Lippincott Williams & Wilkins, 2006).
3. Duntas L, et al. Thyroid. 2007; 17: 1075-84.

TgAb

1. Mayo Clinic. “Thyroglobulin Antibody, Serum”. Available at http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/84382. Accessibility verified April 5, 2016.

T3 Total

1. Klein I, et al. Circulation. 2007; 116: 1725-1735.

Free T4

1. Klein I, et al. Circulation. 2007; 116: 1725-1735.
2. Fischbach F and Dunning M. Nurses’ Quick Reference to Common Laboratory & Diagnostic Tests, 4th ed. (PA : Lippincott Williams & Wilkins, 2006).
3. Duntas L, et al. Thyroid. 2007; 17: 1075-84.

TPOAb

1. American Association for Clinical Chemistry. “Thyroid Antibodies”. Available at https://labtestsonline.org/understanding/analytes/thyroid-antibodies/tab/test.
2. Huang HL et al. Annals Thyroid Res.2014; 1: 17-22.

Hormones

DHEAS

1. American Association for Clinical Chemistry. ”DHEAS”. Available at https://labtestsonline.org/understanding/analytes/dheas/tab/test.
Accessibility verified March 30, 2016.

Abnormal Estradiol

1. American Association for Clinical Chemistry. “Estrogens”. Available at https://labtestsonline.org/understanding/analytes/estrogen/tab/test/. Accessibility verified April 5, 2016.
2. The ESHRE Capri Workshop Group. Human Reproduction Update. 2006; 12: 483–497.
3. Mosca L, et al. Circulation. 2001; 104: 499-503.

Prolactin

1. American Association for Clinical Chemistry. “Prolactin”. https://labtestsonline.org/understanding/analytes/prolactin/tab/test. Accessibility verified April 5, 2016.
2. Corona G, et al. J Sex Med. 2007; 4:1485-93.

Testosterone

1. Laaksonen D, et al. Eur J Endocrinol. 2003; 149: 601-608.
2. Salenave S, et al. Ann Endocrinol (Paris). 2012; 73: 141-6.
3. Araujo A, et al. J Clin Endocrin Metab. 2011; 96: 3007-3019.
4. Khaw K, et al. Circulation. 2007; 116: 2694-2701.
5. Allan C, et al. Asian J Andrology. 2014; 16: 232-238.
6. Ding E, et al. JAMA. 2006; 295: 1288-1299.
7. Patel S, et al. J Clin EndocrinMetab. 2009; 94: 4776-4784.

Abnormal Luteinizing Hormone (LH)

1. American Association for Clinical Chemistry. “LH”. Available at https://labtestsonline.org/understanding/analytes/lh/tab/test. Accessibility verified April 5, 2016.

Progesterone

1. American Association for Clinical Chemistry. “Progesterone”. https://labtestsonline.org/understanding/analytes/progesterone/tab/test. Accessibility verified April 5, 2016.

SHBG

1. Selby, C. Ann Clin Biochem. 1990; 27 (Pt 6): 532-41.
2. Li C, et al. Diabetes Care. 2010; 33: 1618-24.
3. Maggio M, et al. J Clin Endocrinol Metab. 2011; 96: 1053-9.
4. Grunstein R, et al. J Clin Endocrinol Metab. 1989; 68: 352-8.
5. Michos E, et al. Atherosclerosis. 2008; 200: 432-8.
6. Joffe H, et al. Ann Epidemiol. 2006; 16: 105-12.
7. Le T, et al. Trends in Endocrinology and Metabolism: TEM. 2012; 23: 32-40.
8. El Khoudary S, et al. Atherosclerosis. 2012; 225: 180-186.

Abnormal Follicle Stimulating Hormone (FSH)

1. American Association for Clinical Chemistry. “FSH”. https://labtestsonline.org/understanding/analytes/fsh/tab/test. Accessibility verified April 5, 2016

Oncology

Total PSA, Free PSA

1. Catalona W, et al. J Urol. 1994; 151: 1283–1290.
2. Prostate-Specific Antigen Best Practice Statement Update Panel. 2013 Update. American Urological Association. Available at http://www.auanet.org/education/guidelines/prostate-specific-antigen.cfm. Accessibility verified April 5, 2016.
3. Catalona, W.J., et al. JAMA. 1995; 274 (15):1214-20.