Horizon Scanning Reports

Advantages over Existing Technology:

Tests for cholesterol and triglycerides can be performed during consultation, as they require less than 5 minutes to perform. Patients can be informed of their results immediately, providing more accurate categorisation in the QRISK (1) or Framingham Risk Scores (2) and appropriate action, such as starting cholesterol lowering therapy, can be taken.

Details of Technology:

Plasma lipids are comprised of triglycerides and cholesterols (high density lipoprotein [HDL], low density lipoprotein [LDL] and very low density lipoprotein [VLDL]) and levels of these lipids in serum are highly correlated with risk of vascular and cardiac events. Framingham and QRISK calculators require both total and HDL cholesterol measurements. Two small point-of-care CRMLN (Cholesterol Reference Method Laboratory Network) (3) certified devices are on the UK market to measure total and HDL cholesterol:
1. Cholestech LDX® System (Inverness Medical, UK). The device measures a range of values from a fingerstick blood sample. Several test cassettes are available, measuring the following: total cholesterol; total cholesterol and glucose; total cholesterol and HDL; total cholesterol, HDL, and glucose; A lipid panel consisting of total cholesterol (2.6-12.9 mmol/l), HDL (0.4-2.6 mmol/l), triglycerides (0.5-7.3 mmol/l), total cholesterol/HDL ratio, estimate of LDL and VLDL, and an all-inclusive panel consisting of total cholesterol, HDL, triglycerides, glucose, total cholesterol/HDL ratio, estimate of LDL and VLDL.
2. Professional CardioChek P.A. (Polymer Technology Systems, Inc., Indiana, USA). Handheld device using test strips which perform a range of tests from a fingerstick blood sample, depending on the test trip selected: lipid panel and single testing for glucose, ketone, total cholesterol (2.6-10.3 mmol/l), HDL cholesterol (0.6-2.2 mmol/l), triglycerides (1.3-12.8 mmol/l) and calculated LDL cholesterol.

Patient Group and Use:

• Patients requiring primary prevention of cardiovascular disease.
• Management of patients diagnosed with cardiovascular disease.
• NHS Health Check for adults aged 40 to 74.

Importance:

Cardiovascular disease (CVD) is the main cause of death in the UK, accounting for almost 198 000 deaths per year (9). One in three deaths is caused by CVD. Estimates on the prevalence of all coronary heart disease in the UK report 970 000 men and 439 000 women aged 35 and over have had a heart attack and just over 1.1 million men and 850 000 women have had angina. An estimated 1.5 million men and 1 million women aged 35 and over are living in the UK with coronary heart disease. Lipid lowering therapy (usually a statin) is used in all patients with a history of cardiovascular disease. Lipid tests are monitored on a regular (yearly) basis in such patients. Assessment of cardiovascular risk for primary prevention is recommended by NICE for all patients over the age of 40 and includes body mass index, blood pressure, screening for diabetes mellitus and lipid measurement.

Previous Research:

Accuracy compared to existing technology

An evaluation was carried out by the UK NHS Purchasing and Supply Agency in 2005 on 106 samples comparing the Cardiochek device with laboratory results (13). Correlations between the laboratory and CardioChek were 0.86 (total cholesterol), 0.74 (HDL cholesterol) and 0.98 (triglyceride). Imprecision was approximately 12% (total cholesterol), 22% (HDL cholesterol) and 14% (triglyceride). Overall the study showed that sensitivity and specificity for detection of risk of coronary heart disease were 85% and 80%, respectively, using total cholesterol results; and 75% and 79%, respectively, using HDL cholesterol. Another study comparing the accuracy of CardioCheck PA with reference methods in 109 patient samples showed that CardioChek classified 48% of patients with normal lipids as having hypercholesterolemia (10).

The accuracy of Cholestech LDX measurements of abnormal blood levels of total cholesterol (TC), calculated low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) was compared to laboratory analyses (7). The reported correlations for TC, LDL-C, HDL-C and TG were 0.91, 0.88, 0.77 and 0.93, respectively (all p< 0.01) and the sensitivity and specificity of the fingerstick method to identify abnormal lipids and hsCRP was > or = 75%. Fingerstick screening was therefore accurate and showed good clinical utility. A study of point-of-care testing (POCT) in Ireland using Cholestech LDX validated the use of this device (6). However one study of the accuracy of Cholestech in hyperlipidemic individuals over the age of 70 showed that the portable measurements systematically overestimated triglycerides and HDL-C, while LDL-C concentrations were underestimated (12). An evaluation report carried was out by the UK Medical Devices Agency in 1995 comparing 119 samples using the Cholestech with laboratory results. The correlation was 0.97 for total cholesterol and 0.95 for HDL cholesterol. Imprecision was therefore ~5% for total cholesterol and 5-10% for HDL cholesterol (14).

A study comparing CardioChek PA and Cholestech LDX) with a standard venous blood sample tested in a laboratory, showed that the Cholestech LDX analyser demonstrated better reproducibility than the CardioChek PA analyser when compared with laboratory gold standard analysis (4). A second study comparing the accuracy of these two devices also concluded that the Cholestech LDX device is the better POCT device for cardiovascular risk assessment in the primary care setting, as it showed higher accuracy and correlation to laboratory analyses than the CardioChek PA device (5).

Impact compared to existing technology

A multi-centre cluster randomised controlled trial of point-of-care testing in GP practices of patients with established hyperlipidaemia, established type 1 or type 2 diabetes, or taking anticoagulant therapy was recently conducted in Australia. The study showed that for all tests except INR and HDL cholesterol, the POCT approach demonstrated the same clinical effectiveness as pathology laboratory testing (8). A descriptive survey of general practioners and patients showed that cholesterol POCT was strongly supported by both, citing factors such as convenience, issues of patient care and efficiency (11).

Guidelines:

1. The NHS Health Check: Vascular Risk Assessment and Management Best Practice Guidance recommends the use of Framingham and QRISK calculators to ascertain the individual’s 10-year risk of developing cardiovascular disease (15).
2. Lipid modification: Cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease. NICE clinical guideline 67 (16).

Research Questions:

1. Has the device accuracy been sufficiently tested in practice?
2. In the UK Primary Health Care setting, what is the acceptability of and satisfaction with POC cholesterol testing?
3. Is the use of point of care lipid testing cost effective?
4. What is the impact of POCT on clinical decision making?
5. POCT versus laboratory testing for the NHS Health Check
6. POCT versus laboratory testing for treatment compliance

Suggested next step:

Systematic review of point-of-care cholesterol testing in primary care.

References:

1. The QRISK cardiovascular disease calculator. http://www.qrisk.org/. Accessed on 28 October 2009
2. The Framingham Heart Study risk calculator. http://www.framinghamheartstudy.org/risk/index.html. Accessed on 28 October 2009.
3. National Reference System for Cholesterol, Cholesterol Reference Method Laboratory Network. Total Cholesterol. Certification Protocol for Manufacturers. October 2004. http://www.cdc.gov/labstandards/pdf/crmln/RevisedTCprotocolOct04.pdf
4. Dale RA, Jensen LH, Krantz MJ. 2008. Comparison of Two Point-of-Care Lipid Analyzers for Use in Global Cardiovascular Risk Assessments.The Annals of Pharmacotherapy: 42: 633-639.
5. Shephard MD, Mazzachi BC, Shephard AK. 2007. Comparative performance of two point-of-care analysers for lipid testing. Clin Lab.;53(9-12):561-6.
6. Carey M, Markham C, Gaffney P, Boran C, Maher V. 2006. Validation of a point of care lipid analyser using a hospital based reference laboratory.Ir J Med Sci.;175(4):30-5.
7. Parikh P, Mochari H, Mosca L. 2009. Clinical utility of a fingerstick technology to identify individuals with abnormal blood lipids and high-sensitivity C-reactive protein levels. Am J Health Promot.;23(4):279-82.
8. Bubner TK, Laurence CO, Gialamas A, Yelland LN, Ryan P, Willson KJ, Tideman P, Worley P, Beilby JJ. 2009. Effectiveness of point-of-care testing for therapeutic control of chronic conditions: results from the PoCT in General Practice Trial. Med J Aust.;190(11):624-6.
9. Allender S, Peto V, Scarborough P, Kaur A, Rayner M. 2008. Coronary heart disease statistics. BHF: London. http://www.heartstats.org/datapage.asp?id=7998. Accessed on 28 October 2009.
10. Mendez-Gonzalez J, Bonet-Marques R, Ordonez-Llanos J. 2009. Lipid Profile in Ambulatory Patients Using 3 Point-of-Care Devices and Comparison With Reference Methods. Point of Care, 8(3):110-116 110.1097/POC.1090b1013e3181b31692.
11. Cohen J, Piterman L, McCall LM, Segal L. 1998. Near-patient testing for serum cholesterol: attitudes of general practitioners and patients, appropriateness, and costs. Med J Aust. 168(12):605-9.
12. Stein JH, Carlsson CM, Papcke-Benson K, Einerson JA, McBride PE, Wiebe DA. 2002. Inaccuracy of lipid measurements with the portable Cholestech L.D.X analyzer in patients with hypercholesterolemia. Clin Chem. 48(2):284-90.
13. Batki AD, Holder R, Hughes L, Nayyar P, Thorpe GHG. 2005. Polymer Technology Systems CardioChek PA lipid monitoring system. NHS Purchasing and Supply Agency, Centre for Evidence-based Purchasing evaluation report no. 05051.
14. Batki AD, Thimason HL, Holder, R, Thorpe GHG. 1995. Cholestech LDX lipid analyser. Medical Devices Agency evaluation report no. MDS/95/23.
15. Putting Prevention First. NHS Health Check: Vascular Risk Assessment and Management. Best Practice Guidance. UK Department of Health. April 2009.
16. Lipid modification: Cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease. NICE clinical guidance 76. May 2008.

This report was prepared by the Primary Care Diagnostic Horizon Scanning Centre Oxford