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) 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.
- 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.
“CVDs are the number 1 cause of death globally: more people die annually from CVDs than from any other cause”. In 2015, roughly 17.7 million people died from CVD, representing 31% of all global deaths: 7.4 million were due to coronary heart disease and 6.7 million were due to stroke. (WHO, 2017)
Cardiac health and regular cardiovascular screening is important to enable risk factors to be detected in their earliest stages. There are a few factors which contribute to CVD. These include: smoking, unhealthy diet, excessive alcohol consumption, low physical activity levels. Whilst there are only a few factors contributing to CVD, these can be maintained by the patient through living a healthy lifestyle including: quitting smoking, consuming no more than the recommended allowance of alcohol, cutting out junk food, and exercising for 30 minutes a day, 3 – 5 days a week. In a perfect world, this would be easy and CVD would not be a global problem. However, due to busy lifestyles, cravings, reduced willpower, and convenience, not all individuals in today’s world will be able to avoid CVDs. Therefore, it is vitally important that individuals are tested for CVDs to detect them in the earliest stages to reduce damage, prevent further damage, or even death. Furthermore, many individuals suffer from inherited cardiac risk factors, which stresses the need for accurate testing of both traditional and novel cardiac risk biomarkers.
Randox offer the complete solution to cardiac risk assessment including: RX analysers, traditional and novel reagents, internal quality control (Acusera), and external quality control (RIQAS).
Randox has developed the RX series range of clinical chemistry analysers for high-quality semi-automated and fully automated testing. Choose between the RX misano, RX monaco, RX daytona+, RX imola, and the RX modena depending on the throughput of your laboratory. The RX series offers a suitable analyser for your laboratory’s needs. For more information on the Randox RX series, please click here or email firstname.lastname@example.org
As previously mentioned, early assessment of cardiac risk is vital. Randox offer a range of novel risk biomarkers for both very early and the genetic assessment of cardiac risk.
The niche Adiponectin assay allows for the early assessment of CVD. Adiponectin levels are inversely correlated with abdominal visceral fat which has proven to be a strong predictor of T2DM. Body-Mass Index (BMI) is a common method for determining which patients are classified as underweight, healthy, overweight or obese, however, BMI does not take into account gender, ethnicity or activity levels. For example, measuring the BMI of athletes who have a high BMI due to muscle weighing heavier than fat would classify them as obese which is inaccurate. Measuring adiponectin levels is therefore a much more reliable indicator of at-risk patients compared to BMI.
LDL cholesterol is often referred to as the ‘bad cholesterol’. High concentrations of LDL-cholesterol is considered to be the most important clinical predictor, of all single parameters, with respect to coronary atherosclerosis. However, sLDL is a smaller, more dense subfraction of LDL-cholesterol. sLDL particles more readily permeate the inner arterial wall and are more susceptible to oxidation. Individuals with a predominance of sLDL have a 3-fold increased risk of myocardial infarction. Measurement of sLDL allows the clinician to get a more comprehensive picture of lipid risk factors and tailor treatment accordingly.
Elevated levels of Lp(a) are considered to be both a casual risk factor and independent genetic marker of atherosclerotic disorders. The major challenge associated with Lp(a) measurement is the size variation of apo(a) within Lp(a). Dependent upon the size of apo(a) in the assay calibrator, many assays under or overestimate apo(a) size in the patient sample. Numerous commercially available products suffer apo(a) size related bias, resulting in an over estimation of Lp(a) in samples with large apo(a)molecules and an under estimation in samples with small apo(a) molecules. The antibody used in the Randox method detects the complete Lp(a) molecule providing accurate and consistent results. This was proven by the IFCC who developed a gold standard ELISA reference assay and compared 22 commercially available tests. The Randox Lp(a) method displayed the least (minimal) amount of apo(a) size related bias, proving it be a superior offering.
HDL3 Cholesterol is a smaller and more dense subfraction of the HDL particle. HDL is the scavenger of cholesterol within arterial walls and the levels of HDL3 is too low, the ability to remove this cholesterol is reduced. Therefore, it is widely accepted that there is an inverse correlation between HDL3 and CVD risk.
Instrument Specific Applications (ISA’s) are available for a wide range of biochemistry analysers. Contact us to enquire about your specific analyser.
Acusera – Internal Quality Control
The Acusera cardiac controls have been designed to cover a wide range of cardiac markers at clinical decision levels, eliminating the extra expense of an additional low level control. The controls are available in a both liquid ready-to-use and lyophilized formats making them ideal for all situations and manufactured from 100% human serum a matrix similar to that of the patient is guaranteed. For more information on the Randox Acusera internal quality control, please click here or email email@example.com
RIQAS – External Quality Control
The RIQAS Liquid Cardiac EQA programme is designed to monitor the performance of up to 9clinically significant cardiac markers including: CK-MB mass, D-dimer, Digoxin, homocysteine, hsCRP, myoglobin, NT proBNP, troponin I, and troponin T. RIQAS is ISO/IEC 17043 accredited and allows the registration of up to five instruments at no extra cost. All samples are 100% human serum and provided in a liquid ready-to-use format for enhanced convenience. Submit your results bi-weekly and view reports online via RIQAS.Net. For more information on RIQAS, the world’s largest international EQA scheme, please click here or email firstname.lastname@example.org
For further information, please contact the Randox PR team via email: email@example.com or phone 028 9442 2413
It was Friday Fun Day (or should we say Bun Day?) for everyone at Randox headquarters today!
In aid of the Stroke Association NI, talented bakers from across the company brought in their cakes, biscuits, buns and sweet treats to enter in to the Great Randox Bake Off 2017.
With an impressive line-up of chocolate brownies, Victoria sponges, rainbow cakes and more, the competition was fierce for the fifteen Randox bakers who offered up their home-baked goods to the strict judging panel.
Randox Health Director, Nuailin FitzGerald; Nuailin’s daughter Angharad; Randox Receptionist and Administrator Teresa McCloskey, and Stroke Association representative Paul Montgomery, made up the team of judges who rated each bake out of 10 for both appearance and taste (it’s a tough job but someone’s got to do it, right?)
While the judges made their notes, a large group of Randox employees waited eagerly to hear who would be crowned Randox Star Baker.
Would it be Rachel Walls’ Biochip Cake?
Michael Mulligan’s Swampy Magenta Banoffee Pie?
Or would Grace Catney win with her We Are Randox cupcakes?
The judges then took themselves off to the private judging room where they deliberated on who would receive the coveted prize, while everyone else was able to finally taste all the wonderful treats on display!
To sample the goodies everyone gave generously to the Stroke Association donation bucket and while doing so made their own predictions as to who would win.
But only the judges had the deciding vote…
In third place, was Rachel Withers’ Make May Purple themed meringue cake.
In joint second place – Nicola McHugh’s Rainbow Cake and Clare McKibben’s beautifully iced Randox cake!
The winner of the Great Randox Bake Off 2017 was…Michelle Bradley!
Michelle’s perfectly smooth icing and ornate flower decorations really wowed the judges, and they were equally impressed when they tasted the light and delicious sponge inside.
A big thank you to everyone who donated today at our Great Randox Bake Off, and for taking the time to sample the entrants’ baked goods. Weren’t they tasty?
Of course a huge thank you also goes to the judges of our Great Randox Bake Off, and in particular to Paul Montgomery for taking the time to visit Randox and speak to our team about the importance of stroke awareness.
We all learnt a lot and had fun while doing so!
For more information on the Great Randox Bake Off email the Randox PR team: firstname.lastname@example.org or phone 028 9442 2413
With the January blues in full force we decided to have a look back over all the wonderful events that Randox staff took part in during 2016. Together Randox staff rallied together to raise money for numerous events and charities making a huge difference to the lives of others.
Back in April Rachel Walls, our technical support specialist in Ardmore initiated a bake sale on behalf of her sister, Ursula McKenna who ran both the Dublin Marathon and Manchester half Marathon in aid of Cystic Fibrosis Trust. The bake sale was a roaring success and Randox staff enjoyed a selection of scrumptious buns raising a total of £308 that went towards Ursula’s total fundraising amount of £3000.
“Our cousin suffers from Cystic Fibrosis, and running a few marathons is easy compared to what he has to deal with on a daily basis.”
Cystic Fibrosis is a genetic condition caused by a faulty gene that controls the movement of salt and water across the cell wall. This causes mucus to build up in the lungs and digestive tract, causing problems with breathing and digestion. An estimated 1 in 2,500 babies born in the UK have Cystic Fibrosis, with more than 2.5 million people in the UK carrying the faulty gene. Currently there is no cure for Cystic Fibrosis, however there are treatments to help manage the symptoms. The Cystic Fibrosis Trust helps suffers by funding cutting-edge research, driving up standards of care and supporting people with the condition and their loved ones every step of the way.
May was the month that Randox staff and the Randox Biosciences department joined together to help raise awareness of stroke by wearing purple clothes to work.
Stoke is a brain attack that occurs when the blood supply to part of the brain is cut off. Blood carries essential nutrients and oxygen to the brain so without blood your brain cells can be damaged or die.
This damage can have different effects, depending on where it happens in your brain. A stroke can affect the way your body works as well as how you think, feel and communicate. The Stroke Association have dedicated the month of May to raising awareness and increasing the public’s knowledge of this condition.
In July Gary Laverty, one of our software developers who works in our Laurelbank site took a beating when he allowed Randox staff to throw water balloons at him in order to raise money for Macmillan Cancer Support. This charity aims to improve the lives of everyone who is diagnosed with cancer. Their aim is to make life a little brighter and ensure that no one faces this horrible disease alone. They are on hand to offer assistance right from the beginning of a diagnosis, through treatment and beyond, including support to the wider family circle.
Gary raised a total of £409.38 on the day which was presented to Margaret Young from Macmillan Cancer Support at Randox headquarters in Crumlin.
Gary Laverty said,
“When my father was ill last year, Macmillan offered tremendous support to both him and my family. Their commitment to helping cancer patients is incredible, really life-changing. I debated a few fundraising ideas but thought that the water balloon idea was something unusual so I hoped people would see it as a really fun event. The fundraiser went really well and I am delighted at the amount we raised for such an amazing charity! My colleagues got really involved and it was a really fun event, thankfully it wasn’t too cold on the day!”
In the months leading up to Christmas Randox Teoranta in Dungloe our team of scientists engineers and software developers organised a Christmas shoebox appeal in conjunction with Team Hope, a charity based in Ireland, who for the past 18 years have delivered Christmas shoebox gifts to over three million children in some of the remotest and poorest parts of the world. Randox Teoranta filled a total of 54 boxes with items ranging from school essentials, clothes, hats, scarves gloves and socks and of course extra special gifts for Christmas including games toys, sweets and even musical instruments.
Claire Newbon, Manufacturing Operative said,
“Within the team here at Randox Teoranta we are all very fortunate to have great jobs, loving families and a roof over our heads. But we are very aware that there are adults and children in other parts of the world who aren’t so lucky, through no fault of their own.
“At the most joyful time of the year, the Teoranta team wanted to be able to share the magic of Christmas with those children who would otherwise not get any presents.”
In the week leading up to Christmas Randox staff organised a Christmas jumper day with donations going towards Save the Children and a Christmas raffle on behalf of Hope 365. £640.25 was raised for Save the Children, and £4464.00 was raised for Hope 365, which would go towards furnishing “Hope Homes” in Ethiopia so that the children will have somewhere peaceful to sleep at night.
The Christmas raffle took place on 23rd December during which all staff from each site came together to see if they were lucky enough to win any of the prizes that were on offer. Prizes included a 55inch TV, M&S and Amazon vouchers, Christmas hampers, an IPad Air 2 and an extra day’s annual leave.
Randox Teoranta in Donegal also held their own Christmas Raffle and Coffee Morning with all proceeds going towards the local hospital in Dungloe. A total of €740 was raised for the hospital which was greatly appreciated.
Thank you for your generous donations throughout the year, we hope that we can continue to support charities and events throughout 2017.
If you would like to further support Hope 365 they are actively seeking 52 people to take part in a marathon or part of a marathon this year, to compliment a person who is running 52 marathons in one year for the charity. There is also a football academy, endorsed by Paddy McNair, which is taking place in July in Ethopia if you would like to get involved with this. For further information, please contact Internal Communications.
If you would like to get involved with charity fundraising in 2017, please share your ideas with us by emailing email@example.com.
“If you experience any neurological symptom that comes on suddenly and is unfamiliar (eg not like your normal migraine) then you should seek urgent medical advice. And take an Aspirin (unless you’re allergic to it).” That’s the advice today from Dr Mark Porter, writing in The Times about what to do in the event you think you’re suffering a stroke.
It’s good advice to keep a packet in your medicine cabinet, but did you know that it’s thought 91% of strokes are avoidable?
What is a stroke?
For the brain to function properly, it needs the oxygen and nutrients provided by the blood. Stroke occurs when a blood vessel in the brain bursts or, more commonly, when a blockage develops which leaves the supply of the blood to the brain limited or completely obstructed and without treatment, cells in the brain quickly begin to die.
There are 3 different types of stroke:
- Ischaemic Stroke
- Haemorrhagic Stroke
- Transient Ischaemic Attack (TIA)
Avoidable risk factors
Research was carried out by McMaster University Canada – it compared the lifestyles of people who had a stroke with those who had not, involving nearly 27,000 participants from 32 countries. It found that 9 out of 10 strokes worldwide could be caused by risk factors – many of which can be avoided:
- Lowering blood pressure
- Eating healthily
- Maintaining a healthy weight
- Preventing diabetes
- Lowering cholesterol
- Cutting down on alcohol
- Stopping smoking
- Lowering stress
- Taking preventive medication for any heart arrhythmia
The most important modifiable risk is high blood pressure, increasing the risk by 47.9%, which is why it’s the key target across the world for reducing strokes.
Randox Health can help
Randox Health clinics offer you personalised preventive health programmes that provide a full profile of your entire body’s health, including diabetes health, lung health, liver health, heart health and many more areas. Upon receiving your results, you are given a programme to follow to help improve any areas of your health which are not ‘in the green’ on our scale. This helps you to prevent future illnesses and any unwanted surprises such as a stroke. We’ve helped over 3000 people in our clinics to date – book your test today.
The Stroke Association works to improve stroke prevention, treatment and care with a vision for a world where there are fewer strokes. They host Stroke Awareness Month every year and “Make May Purple” to raise awareness of the ways to lower the risks of taking a stroke and to help those affected by it.
What is a stroke?
For the brain to function properly, it needs the oxygen and nutrients provided by the blood. Stroke occurs when a blood vessel in the brain bursts or, more commonly, when a blockage develops which leaves the supply of the blood to the brain limited or completely obstructed and without treatment; cells in the brain quickly begin to die.
If an individual is at risk or has suffered from a stroke before, medication is often recommended by doctors to lower the risk. Anti-platelet drugs, including Aspirin, keep platelets in the blood from sticking together and forming clots possibly preventing another stroke.
However, there are risks to taking Aspirin every day…
There can be risks of taking Aspirin and some experts do not recommend it if the individual hasn’t already had a stroke. The benefits of taking daily Aspirin therapy don’t outweigh the risk of bleeding in people with a low risk of strokes; although the higher the risk of stroke, the more likely it is that the benefits of daily Aspirin outweigh the risk of bleeding.
Taking daily Aspirin may help to reduce clot-related stroke but it also may increase the risk of a bleeding stroke known as haemorrhagic stroke. Daily Aspirin may also increase the risk of gastrointestinal bleeding, if an individual has a bleeding ulcer or if they are bleeding anywhere else in the gastrointestinal tract, taking Aspirin will cause it to bleed more. Also some individuals can be allergic to Aspirin and if they take any it can trigger a serious allergic reaction.
Not everyone responds in the same way to Aspirin!
For a number of reasons including genetic factors; other medications; dosage problems; diabetes; and elevated cholesterol, not all patients respond in the same way to Aspirin therapy. Aspirin resistance is a serious clinical problem and is estimated to affect up to 30% of patients on a low dosage. It is vital that Aspirin resistance is recognised as these patients may need their treatment altered to prevent dangerous clotting.
The TxBCardio™ test helps to identify patients who have a sub-optimum response to their Aspirin therapy. Patients who have a sub-optimum response to their Aspirin therapy are three times more likely to die from a stroke than those who respond positively to such therapy.
This Stroke Awareness Month, we are encouraging the testing of at-risk individuals to ensure that they are responding in the correct way to Aspirin therapy, by taking the TxBCardio™ test! This will not only help the tailoring of treatment to reduce the risk of stroke, but it will also ensure that patients are not exposed to any unnecessary risk of side-effects associated with daily Aspirin consumption.
For health professionals
The primary action of Aspirin is to inhibit the production of thromboxane in the blood, a chemical which helps to cause blood clotting. However, methods of directly measuring the level of thromboxane in blood are unreliable, and so not widely used. Randox TxBCardio™ measures a direct urinary metabolite of thromboxane, 11dhTxB, therefore providing a reliable and stable measure of a patient’s response to their daily Aspirin therapy. This test is available on most automated biochemistry analysers.
Contact us now to request a brochure or kit insert.