Lp(a): For the Accurate Detection of CVD Risk
Lp(a): For the Accurate Detection of CVD Risk
Lp(a) is an independent risk factor for cardiovascular disease (CVD), even when classical risk factors such as hypertension, elevated cholesterol, and diabetes have been taken into consideration. High levels of Lp(a) is a heredity condition, associated with complex mechanisms involving the proatherogenic and prothrombotic pathways (1).
Traditional CVD testing panel
According to the World Health Organisation (WHO), CVD is the leading cause of death globally, accounting for 31 percent of deaths, totalling 17.7 million deaths per year. 80 percent of all CVD deaths are attributed to heart attacks and strokes, equivalent to 1 in 4. Identifying those who are at a high risk of developing CVD and ensuring that they are receiving the appropriate treatment can prevent premature deaths (2).
The lipid profile is frequently used to assess an individual’s risk of CVD developing later in life. Routine tests to assess CVD risk include: triglycerides, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). LDL-C has been found to strongly correlate with CVD risk (3). NICE recommend measuring total cholesterol, HDL cholesterol, non-HDL cholesterol and triglycerides as the full lipid profile and then review other risk factors, including: age, diet, smoking, QRISK, co-morbidities to view risk and the management of risk (4). However, the current lipid panel needs to be adjusted to ensure that its utilisation is effective in meeting clinician and patient needs.
Lipoprotein(a)
Lipoprotein (a) or Lp(a) consists of two protein molecules, apolipoprotein (a) or apo(a) is covalently linked by a disulphide bond to the apolipoprotein B-100 or apoB-100 of a cholesterol-rich low-density lipoprotein or LDL like particle. Lp(a) is synthesised in the liver and is detectable in the bloodstream (5).
The structure of Lp(a) resembles that of the proteins involved in the breakdown of blood clots, plasminogen and tissue plasminogen activator (TPA). As a result, the biggest concern with Lp(a) is that it prohibits the ability of these proteins to break down blood clots by competing for the ‘binding to fibrin’, boosting the blood’s clotting ability within arteries, thus heightening the risk of heart attacks and strokes. Consequently, high levels of Lp(a) is characterised by atherosclerosis including coronary heart disease, peripheral vascular disease, aortic stenosis, thrombosis and stroke (6).
The Journal of the American Medical Association reviewed 36 studies in 2009 which assessed ‘the role of Lp(a) and vascular disease’ in 126,634 individuals. The study found that a 3.5-fold increase in Lp(a) levels was accompanied with a 13 percent higher risk of coronary heart events and a 10 percent higher risk of stroke (7).
Later, an Italian population study carried out on 826 individuals in 2014 found that elevated levels of Lp(a) is due to two different variations of the apo(a) gene which is determined by the kringle sequence differences at the apo(a) locus. The study found that individuals with one variation had a 50 percent greater risk of CVD, while individuals with both variations had 2.5 times greater risk (7).
According to the Lipoprotein Foundation (2015), based on genetic factors, from birth, one in five or 20% of individuals have high Lp(a) levels greater than 50mg/dL, with most blissfully unaware they have it. Overtime, high levels of Lp(a) gradually narrow the arteries, limiting blood supply to the brain, heart, kidneys and legs, increasing the risk of heart attacks and strokes (5).
Testing for high Lp(a) levels
The Lipoprotein (a) Foundation (2015) recommends that Lp(a) levels should be tested if:
- There is a family history of cardiovascular disease including stroke, heart attack, circulation problems in the legs and/or narrowing of the aorta, at a young age
- Stroke or heart attack if classical risk factors including high LDL-cholesterol, obesity, diabetes and smoking have been eliminated
- High levels of LDL-cholesterol following treatment with statins or other LDL lowering medications(5)
When selecting a Lp(a) assay, the Internal Federation of Clinical Chemistry (IFCC) (2004) Working Group on Lp(a) recommends that laboratories use assays that do not suffer from apo(a) size-related bias to minimise the potential risk of misclassification of patients for coronary heart disease (8).
The Lp(a) Foundation reference Marcovina and Albers (2016) in their recommendations for the best Lp(a) test. The study came to the following conclusions:
- Robust assays based on the Denka method, reportable in nanomoles per litre (nmol/L) are traceable to WHO/IFCC reference material
- Five-point calibrators with accuracy-based assigned target values will minimise the sensitivity of to the size of apo(a)
- Upon request, manufacturers should provide the certificate of evaluation of the calibrator and reagent lots with the relative expiration dates (9)
Benefits of the Randox Lp(a) assay
The Randox Lp(a) assay is one of the only methodologies on the market that detects the non-variable part of the Lp(a) molecule and so suffers minimal size related bias providing more accurate and consistent results. This methodology allows for the detection of Lp(a) in serum and plasma. The Randox Lp(a) kit is standardized to the WHO/IFCC reference material, SRM 2B, and is the closest in terms of agreement to the ELISA reference method.
A five-point calibrator is provided with accuracy-based assigned target values which accurately reflects the heterogeneity of isoforms present in the general population.
Liquid ready-to-use reagents are more convenient as the reagent does not need to be reconstituted, reducing the risk of errors.
Applications are available for a wide range of biochemistry analysers which details instrument-specific settings for the convenient use of the Randox Lp(a) assay on a variety of systems. Measuring units in nmol/L are available upon request.
References
- Li, Yonghong, et al. Genetic Variants in the Apolipoprotein(a) Gene and Coronary Heart Disease. Circulation: Genomic and Precision Medicine. [Online] October 2011. [Cited: April 24, 2018.] http://circgenetics.ahajournals.org/content/4/5/565.
- World Health Organisation. Cardiovascular Disease. [Online] 2017. [Cited: April 30, 2018.] http://www.who.int/cardiovascular_diseases/en/.
- Doc’s Opinion. Lipoprotein (a). [Online] 2013. [Cited: April 30, 2018.] https://www.docsopinion.com/health-and-nutrition/lipids/lipoprotein-a/.
- National Institutional for Health and Care Excellence. Cardiovascular disease: risk assessment and reduction, including lipid modification. [Online] July 2014. [Cited: April 30, 2018.] https://www.nice.org.uk/guidance/cg181/chapter/1-recommendations#lipid-modification-therapy-for-the-primary-and-secondary-prevention-of-cvd-2.
- Lipoprotein(a) Foundation. Understand Inherited Lipoprotein(a). [Online] 2015. [Cited: April 24, 2018.] http://www.lipoproteinafoundation.org/?page=UnderstandLpa.
- Heart UK. Lipoprotein (a). [Online] June 23, 2014. [Cited: April 24, 2018.] https://heartuk.org.uk/files/uploads/huk_fs_mfss_lipoprotein_02.pdf.
- Ashley, Robert. High lipoprotein(a) levels may indicate heart disease in some. The Brunswick News. [Online] March 05, 2018. [Cited: April 24, 2018.] https://thebrunswicknews.com/opinion/advice_columns/high-lipoprotein-a-levels-may-indicate-heart-disease-in-some/article_16ab1049-7a6f-5da0-8966-59e94ae31b6d.html.
- Dati, F; Tate, J R; Marcovina, S M; Steinmetz, A; International Federation of Clinical Chemistry and Laboratory Medicine; IFCC Working Group for Lipoprotein(a) Assay Standardization. First WHO/IFCC International Reference Reagent for Lipoprotein(a) for Immunoassay–Lp(a) SRM 2B. NCBI. [Online] 2004. [Cited: April 30, 2018.] https://www.ncbi.nlm.nih.gov/pubmed/15259385.
- Tsimikas, Sotirios. A Test in Context: Lipoprotein(a) – Diagnosis, Prognosis, Controversies, and Emergining Therapies. 6, s.l. : Elsevier, 2017, Vol. 69. 0735-1097.
If you are a cardiologist or a laboratory who are interested in running cardiology and lipid assays, Randox offer a wide range of high-quality, routine and niche assays including: adiponectin, H-FABP, sLDL, TxBCardio, HDL2/3-C, Homocysteine, Apo C-II, Apo C-III and Apo E. These can be run on most automated biochemistry analysers.
Instrument Specific Applications (ISA’s) are available for a wide range of biochemistry analysers.
For more information, visit: https://www.randox.com/lipoprotein-a or email: reagents@randox.com
Could there be 5 types of diabetes?
A peer-reviewed study, published in The Lancet Medical Journal suggests there are five types of diabetes. Could diabetes be more complex than we once thought? Could diabetes be segmented into five separate diseases?
What is diabetes?
Diabetes is an incurable disease which prohibits the body’s ability to produce and respond to insulin. Currently, diabetes is classified into two main forms, type 1 and type 2.
Type 1 diabetes is an autoimmune disease which manifests in childhood. In type 1 diabetes, the body’s white blood cells attack the insulin-producing cells in the pancreas. As a result, individuals with Type 1 diabetes rely on the injection of insulin for the remainder of their lives.
Type 1 diabetes affects 10 percent of individuals with diabetes. 96 percent of children diagnosed with diabetes have type 1. Type 1 diabetes in children is commonly diagnosed between the ages of 10 and 14. The prevalence of type 1 diabetes in children and young people (under the age of 19) is 1 in every 430-530 and the incidence of type 1 in children under 14 years of age is 24.5/100,000 (Diabetes UK, 2014).
Type 2 diabetes is the result of insulin resistance, meaning that the pancreas does not produce enough insulin or the body’s cells do not respond to the insulin produced. As type 2 diabetes is a mixed condition, with varying degrees of severity, there are a few methods to manage the disease, including dietary control, medication and insulin injections.
Type 2 diabetes is the most common form of diabetes, affecting 90 percent of individuals with diabetes, and has now become a global burden. The global prevalence of diabetes has almost doubled from 4.7 percent in 1980 to 8.5 percent in 2014, with a total of 422 million adults living with diabetes in 2014. It is expected to rise to 592 million by 2035. In 2012, diabetes accounted for 1.5 million deaths globally with hypertension causing a further 2.2 million deaths. 43 percent of these deaths occurred before 70 years of age. Previously type 2 diabetes was commonly seen in young adults but is now commonly seen in children as well. In 2017, 14% more children and teenagers in the UK were treated for diabetes compared to the year before (World Health Organization, 2016).
In both forms of diabetes, hyperglycemia can occur which can lead to number of associated complications including renal disease, cardiovascular disease, nerve damage and retinopathy.
The novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables – peer-review study
This new research studied 13,270 individuals from different demographic cohorts with newly diagnosed diabetes, taking into consideration body weight, blood sugar control and the presence of antibodies, in Sweden and Finland.
This peer-reviewed study identified 5 disease clusters of diabetes, which have significantly different patient characteristics and risk of diabetic complications. The researchers also noted that the genetic associations in the clusters differed from those seen in traditional type 2 diabetes.
Cluster One – Severe autoimmune diabetes (SAID)
SAID is similar to type 1 diabetes. SAID manifests in childhood, in patients with a low BMI, have poor blood sugar and metabolic control due to insulin deficiency and GADA. 6% of individuals studied in the ANDIS study were identified with having SAID.
Cluster Two – Severe insulin-deficient diabetes (SIDD)
SIDD is similar to SAID, however, GADA is negative. This means that the characteristics of SIDD are the same as SAID, young, of a healthy weight and struggled to make insulin, however, SIDD is not the result of an autoimmune disorder as no autoantibodies are present. Patients have a higher risk of diabetic retinopathy. 18% of subjects in the ANDIS study were identified with having SIDD.
Cluster Three – Severe insulin-resistant diabetes (SIRD)
SIRD is similar to that of type 2 diabetes and is characterised by insulin-resistance and a high BMI. Patients with SIRD are the most insulin resistant and have a significantly higher risk of kidney disease, and microalbuminuria, and non-alcoholic fatty liver disease. 15% of subjects in the ANDIS study were identified as having SIRD.
Cluster Four – Mild obesity-related diabetes (MOD)
MOD is a mild form of diabetes which generally affects a younger age group. This is not characterised by insulin resistance but by obesity as their metabolic rates are close to normal. 22% of subjects in the ANDIS study were identified as having MOD.
Cluster Five – Mild age-related diabetes (MARD)
MARD is the most common form of diabetes manifesting later in life compared to the previous four clusters. Patients with MARD have mild problems with glucose regulation, similar to MOD. 39% of subjects in the ANDIS study were identified with having MARD.
This new sub-classification of diabetes could potentially enable doctors to effectively diagnose diabetes earlier, through the characterisation of each cluster, including: BMI measurements, age, presence of autoantibodies, measuring HbA1c levels, ketoacidosis, and measuring fasting blood glucose levels. This will enable a reduction in the incidence of diabetes complications and the early identification of associated complications, and so patient care can be tailored, thus improving healthcare (NHS, 2018) (The Week, 2018) (Ahlqvist, et al., 2018) (Collier, 2018) (Gallagher, 2018).
The Randox diabetes reagents cover the full spectrum of laboratory testing requirements from risk assessment, using our Adiponectin assay, to disease diagnosis and monitoring, using our HbA1c, glucose and fructosamine assays, to the monitoring of associated complications, using our albumin, beta-2 microglobulin, creatinine, cystatin c, d-3-hydroxybutyrate, microalbumin and NEFA assays.
Whilst this study is valuable, alone it is not sufficient for changes in the diabetes treatment guidelines to be implemented, as the study only represents a small proportion of those with diabetes. For this study to lead the way, the clusters and associated complications will need to be verified in ethnicities and geographical locations to determine whether this new sub-stratification is scientifically relevant.
References
Ahlqvist, E. et al., 2018. Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. [Online]
Available at: http://www.thelancet.com/journals/landia/article/PIIS2213-8587(18)30051-2/fulltext?elsca1=tlpr
[Accessed 16 April 2018].
Collier, J., 2018. Diabetes: Study proposes five types, not two. [Online]
Available at: https://www.medicalnewstoday.com/articles/321097.php
[Accessed 16 April 2018].
Diabetes UK, 2014. Diabetes: Facts and Stats. [Online]
Available at: https://www.diabetes.org.uk/resources-s3/2017-11/diabetes-key-stats-guidelines-april2014.pdf
[Accessed 16 April 2018].
Gallagher, J., 2018. Diabetes is actually five seperate diseases, research suggests. [Online]
Available at: http://www.bbc.co.uk/news/health-43246261
[Accessed 16 April 2018].
NHS, 2018. Are there actually 5 types of diabetes?. [Online]
Available at: https://www.nhs.uk/news/diabetes/are-there-actually-5-types-diabetes/
[Accessed 16 April 2018].
The Week, 2018. What are the five types of diabetes?. [Online]
Available at: http://www.theweek.co.uk/health/92048/what-are-the-five-types-of-diabetes
[Accessed 16 April 2018].
World Health Organization, 2016. Global Report on Diabetes, Geneva: World Health Organization.
If you are a clinician, dietitian or laboratory who are interested in running diabetes assays, Randox offer a wide range of high-quality routine and niche assays including: fructosamine, glucose, HbA1c for diagnosing and monitoring diabetes, albumin, beta-2 microglobulin, creatinine, cystatin c, NEFA, microalbumin, and d-3-hydroxybutyrate to monitor associated complications, and adiponectin as a biomarker for diabetes risk assessment. These assays can be run on most automated biochemistry analysers.
Instrument Specific Applications (ISA’s) are available for a wide range of biochemistry analysers. Contact us to enquire about your specific analyser.
For more information, visit: https://www.randox.com/diabetes-reagents or email: reagents@randox.com
The Importance of Equine Health
With the Grand National around the corner, Randox Reagents have investigated the importance of equine health, focusing on racehorses.
Maintaining good health in racehorses is vital as proper management can reduce the incidence of many disease conditions. Racehorses are bred, raised, and trained to perform as athletes. Therefore, it is vital that the performance health of racehorses is continually assessed to ensure that they are physically fit, happy and healthy.
Racehorse’s have a busy life. They are broken in from 18 months of age, usually using traditional methods such as long reining, followed by accepting a rider and training alongside other horses. At 2 years of age, the real training begins which focuses on fitness and speed rather than ‘schooling’ the horse in the conventional way. This training is undertaken alongside another horse to teach the trainee horse how to race but at the same time, it is taught to settle and listen to the jockey.
In peak season, the horse’s weekly exercise regime consists of: two days of fast gallop work with steady trotting or cantering the rest of the week, with a rest day on Sunday’s (depending on races scheduled for the horse).
The most important bodily systems for top athletic performance in racehorses include:
Skeletal system (including bone, tendons and ligaments) problems such as torn or stretched ligaments or tendons or a broken bone will be very painful, inducing lameness and prohibiting performance
Muscles enable the horse to perform. Fatigued or damaged muscles will result in poor performance as the horse cannot generate enough energy and strength to maintain its high performance
Respiratory system (nasal passages, throat and lungs) problems prohibits the normal flow of oxygen through the body, which prohibits the energy required for exercise
Cardiovascular system (heart, blood vessels, volume of blood and red blood cells) problems prohibits the movement of oxygen from the lungs to the muscles, again prohibiting the generation of energy required for exercise.
Central nervous system (CNS) problems can result in the loss of coordination and the fine control that accompanies minor problems to the CNS can significantly prohibit exercise performance
Due to the intense training that racehorses undergo, it is vitally important that their health is continually assessed to diagnose and treat injuries and the jockey allows the horse time to recover from the injury. The most common sites of injury include: forelegs, back and pelvis such as bowed tendon (tendonitis), strained suspensory ligaments, splints, osselets, sesamoid fractures, condylar fractures, knee fractures, bone chips, bucked skins and pin firing. It is vitally important that racehorses are allowed time to rest and heal after an injury. Training or racing a horse whilst injured can be detrimental.
Randox Equine Panel
Randox offer 10 scientifically proven assays for equine health which are made from the same high-quality material as our human assays, providing accurate and precise results. These assays have extensive measuring ranges for the accurate detection of disease or inflammation which are suitable for use with serum, plasma and whole blood. Instrument specific applications (ISA’s) are available for an extensive range of biochemistry analysers suitable for use with manual, semi-automated and fully automated analysers.
The Randox range of assays, suitable for equine use, cover a range of biomarkers:
Adiponectin is used to assess equine metabolic syndrome (EMS) which is characterised by obesity, regional adiposity, insulin resistance, and susceptibility to laminitis. Laminitis is one of the most common causes of lameness in horses. It is a painful and potentially crippling condition, which in severe cases usually results in the horse being humanely euthanised.
Aspartate Aminotransferase (AST) levels directly correlate with the severity of muscle inflammation or damage, or liver damage. The highest levels of AST will be seen around 24hours after muscle injury and persist for 2-3 weeks.
CK-NAC is a sensitive marker for the detection of musculoskeletal diseases; and is useful to assess the extent of severe muscle trauma, crush injuries, and burns and the likelihood of developing rhabdomyolysis.
For health professionals
If you are a veterinarian or laboratory who are interested in running equine assays, Randox offer a wide range of high-quality routine and niche assays including: albumin, alkaline phosphatase, bilirubin, calcium, GLDH, glucose and urea. These can be run on most automated biochemistry analysers.
Instrument Specific Applications (ISA’s) are available for a wide range of biochemistry analysers. Contact us to enquire about your specific analyser.
For more information, email reagents@randox.com
Complement C4 – Biomarker for Systemic Lupus Erythematosus (SLE)
Systemic Lupus Erythematosus (SLE) is an autoimmune disorder associated with a deficiency in complement C4. Complement C4 is one of nine components of the complement system which is an integral part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from the host, promote inflammation, and attack the cell membrane of pathogens.
Complement C4 is a vital component of two immunology pathways: Classical pathway and Mannrose Binding Lectin (MBL) pathway.
The classical pathway is triggered by antibody-antigen complexes which induces a conformational change in the C1 complex. The activated C1 complex cleaves the C4 component, resulting in a reactive C4b which covalently binds to proteins or polysaccharides at the surface in close proximity of the C1 component. The bound C4b complexes binds to the C2 component rendering C2 for proteolysis by C1.
The MBL pathway is activated through the binding of MBL to mannose residues on the pathogen surface. This in turn activates the MBL-associated serine proteases, MASP-1 and MASP-2, which activates the C4 and C2 components, to form the C3 convertase, C4b2a. The C4b2a complex splits C3 into two fragments which causes the release of vasoactive mediators such as histamine.
Complement C4 deficiency is commonly associated with systemic lupus erythematosus (SLE).
According to lupus.org, 16,000 new cases of lupus are reported each year. Approximately 1 in 250 people may end up developing SLE at some point with 90% of SLE patients being female aged between 15-44 years. The causes of SLE are unknown, but are believed to be linked to environmental, genetic, and hormonal factors. 1.5 million Americans are living with diagnosed lupus.
There are four forms of lupus:
- Systemic – accounts for approximately 70% of all lupus cases. In half of these cases, a major organ or tissue in the body, such as the heart, lungs, kidneys, or brain will be affected.
- Cutaneous lupus – accounts for approximately 10% of all lupus cases and only affects the skin.
- Drug-induced lupus accounts for approximately 10% of all lupus cases and is caused by high doses of certain medications.
- Neonatal lupus is a rare condition in which the mother’s antibodies affect the fetus. At birth, the baby may have a skin rash, liver problems, or low blood cell counts, but these symptoms typically disappear completely after six months with no lasting effects.
The Randox Complement C4 assay
The Randox Complement C4 assay is used for the quantitative in vitro determination of complement C4 concentration in serum. The Randox Complement C4 assay can be used as a biomarker in the diagnosis and monitoring of SLE. It is the cell-bound levels of processed complement activation products, especially E-C4d (erythrocyte-bound C4) that makes the complement C4 assay a biomarker for SLE.
Key Features of the Randox Complement C4 assay
Liquid ready-to-use reagents – The Randox reagent comes in a convenient liquid format requiring minimal preparation thus reducing the risk of errors.
Exceptional correlation with standard methods – The Randox methodology was compared against other commercially available methods and the Randox Complement C4 assay showed a correlation coefficient of r=0.98.
Wide measuring range – The healthy range for Complement C4 is 7 -49 mg/dl. The Randox Complement C4 assay can comfortably detect levels outside of the healthy range measuring between 2.90 – 152 mg/dl.
Excellent stability – Stable until expiry date when stored at +2 to +8°C.
For health professionals
If you are a clinician or laboratory who are interested in running specific protein assays, Randox offer a wide range of high-quality routine and niche assays including: Cystatin C, Complement C3, CRP, Lipoprotein (a), Apolipoprotein C-II, Apolipoprotein C-III and Apolipoprotein E. These can be run on most automated biochemistry analysers.
Instrument Specific Application (ISA’s) are available for a wide range of biochemistry analysers. Contact us to enquire about your specific analyser.
For more information, download our Specific Proteins Brochure email reagents@randox.com
Rare inherited diseases of copper metabolism
This year, Randox Reagents are supporting Rare Disease Day on 28th February. Randox offer a test that aids in the diagnosis and monitoring of Wilson Disease and Menkes Disease which are rare inherited disorders of copper metabolism.
What is a rare disease?
According to the European Union, a rare disease is defined as a disease that affects less than 5 in 10,000 of the general population. 7% of the population will be affected by a rare disease at some point in their life. This equates to 30 million people in Europe.
Wilson Disease
Wilson Disease is a rare inherited autosomal recessive disorder of copper metabolism, characterised by excessive deposition of copper in various bodily tissues, particularly the liver, brain, and corneas of the eyes. This is due to mutations of the ATP7B gene which is responsible for encoding specific proteins that are responsible for the transportation of copper from the liver around the body, which is prohibited due to the mutations. If left untreated, Wilson Disease can cause hepatic disease, central nervous system dysfunction, or death. Approximately 1 in 30,000 people are affected by Wilson Disease worldwide (WDA, 2018). The first sign of Wilson Disease is liver dysfunction in more than half of patients, beginning at six years of age, however, it usually presents clinically in teenage years or early twenties manifesting as acute hepatitis. Some individuals with Wilson Disease have been thought to have infectious hepatitis or infectious mononucleosis and so it is vital that those with unexplained, abnormal liver tests are tested for Wilson Disease.
Menkes Disease
Menkes Disease is more likely to affect premature babies and is a rare inherited x-link recessive disorder of copper metabolism, characterised by sparse, kinky hair; failure to gain weight and grow at the expected rate (failure to thrive); and deterioration of the nervous system. This is due to mutations of the ATP7A gene which is responsible for the absorption of copper from food in the small intestines and supplying copper to certain enzymes that are critical for the structure of bone, skin, hair, blood vessels, and the nervous system. Approximately 1 in 100,000 people are affected by Menkes disease worldwide (USA National Library of Medicine, 2018). The first sign of Menkes Disease develops at 2-3 months of age and includes curly, sparse, coarse, dull, and discoloured haired.
As there are no cures for Wilson Disease or Menkes Disease, treatment aids to reduce/replace copper within the body. The Randox Copper assay can comfortably detect copper levels outside of the healthy range to aid in the diagnosis and monitoring of treatment of Wilson Disease and Menkes Disease.
Randox Copper Assay
The Randox Copper assay is used to measure the amount of copper in the blood; to help with the diagnosis and monitoring of rare inherited diseases related to copper toxicity (Wilson Disease) and copper deficiency (Menkes Disease). Copper deficiency is less likely because a normal diet contains plenty of copper including organ meats, beans, and wholegrains, however, copper deficiency is more likely to occur in those who are malnourished, more likely children.
For more information visit: https://www.randox.com/copper
To request an application for your specific analyser, contact reagents@randox.com
Acetaminophen-Induced Acute Kidney Failure
Acetaminophen is a commonly used medicine for pain-relief. During cold and flu season, it is common to resort to pain-relief medicines to relieve headaches, and ache and pain symptoms associated with a cold or flu as there is no cure. However, the therapeutic range for acetaminophen is 10-30 mg/l, which is small and very easy to go over. During cold and flu season, it is important to monitor the amount of paracetamol entering your body as acetaminophen is more dangerous than suspected. At therapeutic levels, acetaminophen does not produce any adverse effects, however, long-term treatment, prolonged use, and taking a few more than the recommended dose can be severely damaging and fatal. Accidental acetaminophen overdose took the lives of 1,500 people in the U.S between 2001 and 2010. The Randox Acetaminophen assay is used to determine the concentration levels of acetaminophen in the blood to determine if an overdose has taken place.
It is commonly recognised that acetaminophen overdose causes hepatotoxicity, but it is less commonly recognised that it can also cause nephrotoxicity in less than 2% of patients. Nephrotoxicity is toxicity of the kidneys and is often associated with a reduced amount of glutathione which is important for normal cellular metabolism in the kidneys. The Randox Glutathione Reductase assay is required for the regeneration of reduced glutathione. Glutathione is often discussed in association with the Randox Glutathione Peroxidase, which requires reduced glutathione for activation. Both Glutathione reagents are unique to Randox.
Acute renal failure due to acetaminophen manifests as acute tubular necrosis, which can occur alone or in combination with hepatic necrosis. Nephrotoxicity can also occur when the therapeutic levels of acetaminophen are not exceeded. This most commonly occurs when acetaminophen is taken in combination with alcohol. Upon testing acetaminophen levels and the results fall within the therapeutic range, the Randox Ethanol assay can test alcohol levels to determine if a combination of alcohol and acetaminophen caused nephrotoxicity. Renal impairment may be more common than previously suspected as acute renal failure occurs in 10-40% of patients with severe hepatic necrosis. Upon testing acetaminophen to determine toxicity, Randox also offer the following renal tests to test for nephrotoxicity:
- Creatinine (Enzymatic and JAFFE)
- Cystatin C
- IgG
For more information visit: https://www.randox.com/acetaminophen
To request an application for your specific analyser, contact reagents@randox.com
Liver Cirrhosis is a Global Health Burden
#LoveYourLiver this January. This month, we are taking a closer look at Liver Cirrhosis.
Liver cirrhosis occurs when the healthy tissue of the liver is replaced with scar tissue (fibrosis) due to long-term liver damage. Liver cirrhosis can result in liver failure which can be fatal.
Liver complications such as liver disease and cirrhosis can be detrimental if it is not treated or monitored. Liver disease is the only major cause of death still increasing year-on-year. Globally, deaths due to liver cirrhosis have increased from 676,000 in 1980 to over 1 million in 2010 (NCBI, 2014). Cirrhosis and other chronic liver diseases have increased by 12.4% from 2006-2016 and was the cause of 1,256,900 deaths in 2016 (Global Burden of Disease, 2016).
There are a few factors that increase the risk of liver cirrhosis. The three main factors are heavy alcohol consumption, an undiagnosed hepatitis infection, particularly hepatitis C, and non-alcoholic steatohepatitis (a more severe form of non-alcoholic fatty liver disease) due to obesity.
There are numerous symptoms associated with liver cirrhosis. Some of the more severe symptoms include:
- Jaundice – yellowing of the skin and whites of the eyes
- Personality changes, confusion, difficulty concentrating, memory loss, or hallucinations
- A tendency to bleed or bruise easily
- In women, abnormal periods
- In men, enlarged breasts, a swollen scrotum (the loose sac of skin that contains the testicles) or shrunken testicles
- Vomiting
- Diarrhea
- Stomach pain – swollen or bloated stomach
Liver cirrhosis cannot be cured, but the aim of treatment is to manage the symptoms and complications, and to stop the condition getting worse.
#LoveYourLiver and prevent or reduce the symptoms of liver cirrhosis through: moderating alcohol consumption, not sharing needles to inject drugs, using a condom during sex, taking medications as prescribed, and maintaining a healthy weight.
The early stages of liver cirrhosis usually does not present any symptoms and is often first detected using routine blood tests. Liver cirrhosis can be diagnosed and monitored through the following routine blood tests:
Alanine Aminotransferase (ALT)
ALT is one of the enzymes within the aminotransferases group and are among the most sensitive liver enzymes. The normal concentration levels of ALT in the blood are low, however, when the liver is damaged, such as liver cirrhosis, the levels of ALT increase. During the diagnosis of liver cirrhosis, the root cause of the damage can be established, such as disease, drug or injury. ALT is commonly measured alongside AST as part of the hepatic panel.
Aspartate Aminotransferase (AST)
AST is an enzyme found throughout the body. Elevated concentration levels of AST in the blood is directly correlated to the severity of the tissue damage. AST also allows for the root cause of the damage to be diagnosed. Excessive levels are indicative of damage due to acetaminophen overdose or acute viral hepatitis. Moderately high levels are indicative of alcohol abuse. Slightly high levels are indicative of cirrhosis.
AST is commonly measured alongside ALT as part of the hepatic panel, although ALT levels are higher in most types of liver damage.
Albumin
Albumin is a special protein made in the liver and provides the body with the proteins it requires to grow and repair tissue. The body requires a proper balance of albumin to prevent fluid from seeping out of blood vessels. Decreased concentrations levels of this protein in the blood is an indicator of liver cirrhosis.
Randox supply a range of third party clinical diagnostic hepatic reagents to aid in the diagnosis and managing the complications of liver cirrhosis. All reagents are available for use on a range of third party biochemistry analysers. Randox offer the following hepatic reagents to diagnose liver cirrhosis:
Alanine Aminotransferase (ALT)
Aspartate Aminotransferase (AST)
Randox also offer the following high performance and unique tests to diagnose liver cirrhosis:
Why choose Randox reagents?
- Randox offers the largest range of chemistries
- Liquid ready-to-use reagents available
- Automated applications for a wide range of clinical analysers
- Excellent correlation to reference methods
- Wide measuring ranges
- Flexible pack sizes
- Official accreditation to national and international standards including UKAS, ISO 13485:2003, and FDA.
- Easy fit reagents
- Easy read reagents
To request an application for your specific analyser, contact reagents@randox.com
For more information on liver function or to view our hepatic panel, visit https://www.randox.com/liverfunction/
The Global Burden of Obesity
Obesity is a condition where a person has abnormal or excessive fat accumulation that presents a serious risk to health. This December, Randox are highlighting the health implications of this potentially deadly condition, especially throughout the midst of this festive season when it is all too easy to overindulge in fatty foods and sugary treats!
Worldwide obesity has almost tripled between 1975 and 2016, with over 650 million adults and 340 million children being recorded as obese in 2016 alone, highlighting that the prevalence of the condition is rapidly rising. Randox are dedicated to improving health and increasing the awareness and prevention of obesity and its consequences.
What are the causes and consequences of obesity?
With more people around the world adopting sedentary lifestyles and the increasing consumption of foods high in sugar and fat, there is a higher risk of an energy imbalance between calories consumed and calories expended, which is the fundamental cause of obesity. This increases the risk of a number of diseases such as cardiovascular disease, diabetes, musculoskeletal disease and some forms of cancer, with each condition having detrimental effects to your health.
One of the more serious consequences of obesity is type 2 diabetes mellitus (T2DM), where a resistance to insulin is developed causing blood sugar to rise higher than normal. This can lead to serious, long-term problems such as kidney damage, cardiovascular disease and blindness.
How are Randox supporting the battle against the world’s obesity crisis?
Through extensive investment in R&D, we are able to offer cutting-edge diagnostic tests to assess the risk of obesity-related diseases before they occur!
Randox offers the unique adiponectin test to assess the risk of developing T2DM. Low adiponectin levels have also been linked with the risk of developing other pathologies including metabolic syndrome and cardiovascular diseases. The adiponectin test is applicable to both patients with diagnosed clinical obesity, and those deemed to have a ‘healthy’ BMI through a condition known as ‘abdominal obesity’.
This is because while it is widely recognised that people who are overweight or obese are at higher risk of developing T2DM, you don’t have to be overweight to be at risk of developing diabetes. When abdominal visceral fat is stored further underneath the skin and accumulates around major organs, a condition known as abdominal obesity, it greatly increases the risk of developing T2DM. When abdominal visceral fat levels become increased, adipocytes which secrete the protein hormone adiponectin become reduced; this reduces the anti-inflammatory and insulin-sensitising properties of this powerful hormone.
The adiponectin test is available for use on hundreds of clinical biochemistry analysers, and can also be run on our world leading RX series range of clinical chemistry analysers. Find out more here: www.randox.com/obesity/
Our world-renowned quality control products help ensure the accuracy of obesity-related testing!
When diagnosing and monitoring obesity-related complications such as cardiovascular disease (CVD) and T2DM, it is vital that laboratories have a robust quality control system in place to ensure the accuracy and reliability of the results produced. This is especially true considering, 70% of medical decisions are based on a laboratory test result.
It is estimated that over 90% of T2DM is related to obesity. When monitoring diabetes, glycated haemoglobin (HbA1c) levels in the blood provide an indication of average blood glucose levels for the previous 3 months. It is therefore important that the chosen quality control will effectively challenge the test system across the patient reportable range, as an inaccurate result at the cut-off could mean a patient does not receive appropriate diabetes treatment. Our Acusera Liquid HbA1c control provides clinically relevant levels, not only helping to ensure accurate instrument performance but maximising laboratory efficiency. Find out more here: www.randox.com/obesity/
Obesity prevention
Thankfully, for those deemed to be at risk, obesity and related illnesses are largely preventable through engaging in regular physical activity (60 minutes daily recommended for adults), limiting energy intake from total fats and sugars and increasing the consumption of fruit and veg, whole grains and nuts. Knowing your risk allows you to stay in control of your health throughout this festive season!
Further to our clinical lab tests, our Randox Health clinics offer heart health, metabolic health and diabetes health testing as part of our Everyman, Everywoman and Signature packages to identify and assess risk of developing obesity-related diseases. Our clinics utilise the same cutting-edge tests and quality control that we have available to clinical laboratories globally, as well as our patented Biochip Array Technology (BAT).
For more information about our clinical diagnostic range of obesity-related products, visit www.randox.com/obesity/
The Risk of Gestational Diabetes to Women – World Diabetes Day
Every year, Randox Reagents support World Diabetes Day on the 14th November. This year, the theme is ‘Women and diabetes – our right to a healthy future’ with the International Diabetes Federation running a campaign aiming to provide all women with diabetes with affordable and equitable access to care and education to better manage their diabetes and improve their health outcomes. A type of diabetes that affects women is gestational diabetes.
Gestational diabetes – what is it?
Gestational Diabetes Mellitus (GDM) is a form of diabetes which appears in pregnancy, characterised by high blood sugar due to the hormones produced in pregnancy, usually developing in the second or third trimester and disappearing after giving birth. This is a serious condition which can lead to the baby growing larger than usual and can coincide with premature birth, stillbirth and pre-eclampsia, which are detrimental to a mother’s health.
According to the International Diabetes Federation, 1 in 7 births is affected by gestational diabetes. In addition, approximately half of women with a history of GDM go on to develop type 2 diabetes within five to ten years after delivery.
Diagnosis and Monitoring of Gestational Diabetes
Due to the severe complications that can occur with gestational diabetes, it is extremely important to accurately diagnose and monitor the condition. Tests which are commonly used to diagnose diabetes include HbA1c and glucose, including fructosamine, which due to the shorter time span, is particularly useful to evaluate the effectiveness of medication changes and to monitor the treatment of gestational diabetes.
Complications associated with gestational diabetes include diabetic ketoacidosis, a serious complication of diabetes which occurs when blood sugar levels are consistently high and insulin levels are severely low, making it essential to measure D-3-Hydroxybutyrate levels. This is a niche test which is available from Randox Reagents – find out more here.
Preventing Gestational Diabetes
As well as diagnosing and monitoring gestational diabetes, it is important that women get tested early in order to put in place measures to help avoid developing diabetes, improving quality of life for themselves and their baby. Ways in which they can do this is through adopting a healthier lifestyle in terms of monitoring diet and getting regular exercise.
Randox offer an automated adiponectin test which predicts the risk of patients developing both gestational and Type 2 Diabetes Mellitus (T2DM). Therefore, it is important to measure adiponectin before pregnancy as low concentrations are associated with reduced glucose tolerance during pregnancy and can identify women at high risk for gestational diabetes.1
Innovations in diabetes testing has led to the ability to more accurately detect risk, diagnose and manage the complications of diabetes. Randox offer a wide range of diabetes reagents in an automated biochemistry format, allowing rapid and accurate assessment for both laboratory professionals and clinicians.
Join Randox Reagents on World Diabetes Day 2017 to help spread awareness and prevent gestational diabetes in women by providing them with access to education and improve their health outcomes!
Randox are dedicated to providing the highest quality tests for diabetes diagnosis, complications monitoring and risk assessment – download our diabetes brochure to find out more about what we have to offer!
For more information, please contact us at reagents@randox.com
Lipoprotein(a) Foundation commend celebrity personal trainer, Bob Harper, as he speaks out about the risk of Lp(a)
The Lipoprotein(a) Foundation have commended health and fitness expert Bob Harper for speaking out after recently suffering a heart attack. The celebrity personal trainer and host of the US television series ‘The Biggest Loser’, has revealed that high levels of Lp(a) were responsible for the heart attack he suffered at the age of 51 at the beginning of this year.1
Harper had been completing a normal workout at his gym when he suffered full cardiac arrest. Luckily, two doctors were in the vicinity who saved his life by performing CPR and using an Automated External Defibrillator (AED). In an interview following his heart attack, Harper has said,
“I’ve learned a lot about the fact genetics does play a part in this, it is so important to know your health… I’m a guy that lives a very healthy lifestyle, very regimented, I work out all the time, but there were things going on inside of my body that I needed to be more aware of and I strongly encourage anyone that’s listening right now to go to their doctor, get their cholesterol checked, see what’s going on on the inside”.
Scroll down to watch the interview in full.
What is Lp(a)?
Lp(a) is a particle which is produced in the liver and found in the blood which carries cholesterol, fats and proteins. Levels of Lp(a) in individuals are genetically determined, and are not affected by diet, exercise or lifestyle changes.2
So how does a seemingly fit and healthy person have a heart attack at the age of 51?
Lp(a) is currently the strongest inherited risk factor for heart attack and stroke, with one in five people globally inheriting high Lp(a).1 Levels of Lp(a) are not routinely tested in standard cardiovascular assessments, and despite the particle itself being an altered form of LDL cholesterol, standard cholesterol tests do not reveal inherited Lp(a) levels as it is independent from total cholesterol and LDL levels.3
High Lp(a) can also be unrelated to other common risks factors of cardiovascular diseases for example, smoking, diet, diabetes, high blood pressure and lack of exercise. This is why seemingly healthy individuals can have high Lp(a) in their genes and still be at high risk of cardiovascular diseases.
Why is Lp(a) not routinely measured if high levels pose such a risk?
The widespread use of Lp(a) as an independent risk factor for cardiovascular disease risk has, until recently, been hindered by the lack of internationally accepted standardisation and the fact that many commercial Lp(a) methods suffer from apo(a) size related bias, potentially leading to patient misclassification.
The size of the apo(a) protein is genetically determined and varies widely hence, levels of Lp(a) can vary up to 1000-fold between individuals.4 To find out more about the clinical significance of Lp(a), please refer to the section below entitled ‘For Health Professionals’.
What can you do if you have high Lp(a)?
Research has shown that lowering Lp(a) could significantly reduce the impact of cardiovascular diseases. A recent study published in the American Heart Association journal, Arteriosclerosis, Thrombosis and Vascular Biology, found that reducing high Lp(a) could potentially prevent up to 1 in 14 cases of myocardial infarction (heart attack) and 1 in 7 cases of aortic valve stenosis.5 Of those studied, nearly one third of heart attacks and half of all cases of aortic stenosis were attributed to high Lp(a).6 This study demonstrates the clinical significance of measuring Lp(a), making it a major independent genetic risk factor for cardiovascular diseases.
Why test Lp(a)?
Lp(a) will be tested as part of a lipid profile if: there is a strong family history of CVD, a patient has existing heart or vascular diseases, a patient has an inherited predisposition for high cholesterol or if a person has had a stroke or heart attack but has normal lipid levels.7
Dr Christie Ballantyne, Chief of Cardiology at Baylor College of Medicine, has said “the most important part of knowing your Lp(a) level is understanding your overall risk and finding the right lifestyle modifications or medications to target all the other traditional risk factors. Those risk factors become even more important to monitor when your Lp(a) levels are high”.8
For patients
If you are concerned that you may be at risk of having elevated levels of Lp(a) due to your family history, ask your doctor or medical provider to test lipoprotein (a), along with other lipid tests, to clinically evaluate your risk of developing cardiovascular diseases.
For health professionals
Click below for information regarding the challenges associated with the measurement of Lp(a) and the clinical significance it holds.
The widespread use of Lp(a) as an independent risk factor for cardiovascular disease risk has, until recently, been impeded by the lack of internationally accepted standardisation and the fact that many commercial Lp(a) methods suffer from apo(a) size related bias, potentially leading to patient misclassification. The size of the apo(a) protein is genetically determined and varies widely hence, levels of Lp(a) can vary up to 1000-fold between individuals.4
As a result, international criteria has been set to overcome these challenges. The International Federation of Clinical Chemistry (IFCC) Working Group on Lp(a) recommends that laboratories use assays which do not suffer from apo(a) size-related bias, in order to minimise the potential risk of misclassification of patients for coronary heart disease. The Lipoprotein(a) Foundation has referenced Marcovina and Albers (2016) as their recommendation for the best Lp(a) test.9 This recommendation is a result of the following conclusions:
- Robust assays based on the Denka method are available, which are reported in nanomoles per litre (nmol/L) and are traceable to WHO/IFCC reference material
- Five point calibrators with accuracy assigned target values will minimise the sensitivity to apo(a) size
A number of guidelines are in place for the testing of Lp(a) in patients.
-The European Guidelines for Management of Dyslipidaemia state that Lp(a) should be measured in individuals considered at high risk of CVD or with a strong family history of premature CVD.
-The European Atherosclerotic Society suggest that Lp(a) should be measured once in all subjects at intermediate or high risk of CVD/CHD who present with10 :
1. Premature CVD
2. Family hypercholesterolaemia
3. A family history of premature CVD and/or elevated Lp(a)
4. Recurrent CVD despite statin treatment
5. ≥3% 10-year risk of fatal CVD according to the European guidelines
6. ≥10% 10-year risk of fatal and/or non-fatal CHD according to the US guidelines
-EAS Consensus Panel states the evidence clearly supports Lp(a) as a priority for reducing cardiovascular risk, beyond that associated with LDL cholesterol. Clinicians should consider screening statin-treated patients with recurrent heart disease, in addition to those considered at moderate to high risk of heart disease.
- The Randox Lp(a) assay is one of the only methodologies on the market that detects the non-variable part of the Lp(a) molecule and therefore suffers minimal size related bias – providing more accurate and consistent results. The Randox Lp(a) kit is standardised to the WHO/ IFCC reference material SRM 2B and is closest in terms of agreement to the ELISA reference method.
- Five calibrators with accuracy-based assigned target values are provided – which accurately reflect the heterogeneity of isoforms present in the general population
- Measuring units available in nmol/L upon request
- Highly sensitive and specific – method for Lp(a) detection in serum and plasma
- Applications are available for a wide range of biochemistry analysers – which detail instrument-specific settings for the convenient use of Randox Lp(a) on a variety of systems
- Liquid ready-to-use reagents – for convenience and ease-of-use
For further information on Lp(a), click here or email: reagents@randox.com
1. Lipoprotein(a) Foundation, Lipoprotein(a) Foundation Thanks Bob Harper for Revealing High Lp(a) Levels Led to His Recent Heart Attack on The Dr Oz Show, 2017 Available from: http://www.businesswire.com/news/home/20170425006724/en/ [Accessed: 16 March 2017]
2. Lipoprotein Foundation, Understand Inherited Lipoprotein (a), Available from: https://goo.gl/bH5A8R [Accessed: 16 March 2017]
3. Kumar, V., Abbas, A. K. and Aster, J. C., Robbins and Cotran Pathologic Basic of Disease, (Philadelphia: Elsevier Saunders, 2015), p. 494 in Google books, https://goo.gl/VEnVX9 [Accessed 27th April 2017]
4. Kamstrup P.R., Tybjaerg-Hansen A., Steffensen R., Nordestgaard B.G. Genetically elevated lipoprotein (a) and increased risk of myocardial infarction. JAMA. Vol. 301, p. 2331-2339 (2009).
5. Afshar, M. Kamstrup, P.R., Williams, K., Snidermann, A. D., Nordestgaard, B.G., Thanassoulis, G., Estimating the Population Impact of Lp(a) Lowering on the Incidence of Myocardial Infarction and Aortic Stenosis – Brief Report., Ateriosclerosis, Thrombosis, and Vascular Biology, 2016;36:2421-2423, Available from: http://doi.org/10.1161/ATVBAHA.116.308271
6. The Lipoprotein(a) Foundation, Lipoprotein(a) Foundation Supports National Heart Valve Disease Month, Highlights Genetic Link between Lp(a) and Aortic Valve Disease, Business Wire. (2017), Available from: https://goo.gl/LhQFGj [Accessed: 16 March 2017]
7. Lab Tests Online, Lp(a), 2014, Available from: https://goo.gl/W2PWSN [Accessed: 16 March 2017]
8.Gutierrez, G., The heart attack risk factor you haven’t heard of, Baylor College of Medicine, 2017, Available from: https://goo.gl/9X4Xko [Accessed: 16 March 2017]
9. Marcovina, S.M. and Albers, J.J. Lipoprotein (a) measurements for clinical application. Lipid Res. Vol. 57, p. 526-37 (2016).
10. Nordestgaard, B. G., Chapman, M. J., Ray, K., Bore´n, J., Andreotti, F., Watts, G. F., Ginsberg, H., Amarenco, P., Catapano, A., Descamps, O. S., Fisher, E., Kovanen, P. T., Kuivenhoven, J. A., Lesnik, P., Masana, L., Reiner, Z., Taskinen, M. R., Tokgozoglu, L., and Tybjærg-Hansen, A., for the European Atherosclerosis Society Consensus Panel. Lipoprotein(a) as a cardiovascular risk factor: current status. European Heart Journal. Vol. 23, p. 2844-2853 (2010).
