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Abdominal fat in association with insulin resistance in men of European and South Asian origin
Abstracts / Atherosclerosis 218 (2011) e1–e12
Changes in function and structure of high-density lipoprotein in obese patients compared with healthy controls Salam Hama ∗ , Handrean Soran, Yifen Liu, Valentine CharltonMenys, Reza Zadeh, Michael France, Rahul Yadav, Maria Jeziorska, Basil Ammori, Paul Durrington Cardiovascular Research Group, University of Manchester, United Kingdom Background: There is an inverse relationship between HDL and cardiovascular disease. We hypothesised that HDL’s anti-oxidant function is altered in obese patients, with or without type 2 diabetes. Methods: 19 obese patients, 8 with type 2 diabetes, and 13 healthy controls were recruited. HDL’s antioxidant ability was tested by measuring lipid peroxide (LPO) formation after incubation of HDL with Cu2+ at baseline and at 3 hours. ApoAI was determined in HDL and its sub-fractions. Serum PON1 activity was measured by a semi-automated method. Results: There was no significant difference in LPO concentration at baseline between controls and obese patients (30 [23–50] vs. 39 [22–94] nmol/ml). LPO formation was, however, significantly greater in obese patients after 3 h (39 [4–93] vs. 67 [10–129] nmol/ml; p < 0.05). PON1 activity tended to be lower in the obese group with (77 [24–271] nmol/ml/min) or without diabetes (142 [26–216] nmol/ml/min) compared with controls (178 [38–457] nmol/ml/min). ApoAI in HDL2 of the obese-diabetic group was significantly lower compared with healthy controls (0.77 [0.69–0.85] vs. 1.01 [0.64–1.74] g/l; p < 0.05). Conclusions: LPO formation in HDL from obese patients was higher than in healthy HDL, suggesting the presence of proinflammatory HDL. Deterioration of HDL’s ability to protect itself against oxidation could indicate deterioration of its protective functions and this could be linked to re-distribution of apoAI in HDL sub-fractions and lower PON1 activity. doi:10.1016/j.atherosclerosis.2011.07.069 Genetic screening for familial hypercholesterolaemia in a cardiothoracic tertiary referral centre J. Breen ∗ , J. Jones, M. Barbir Royal Brompton and Harefield NHS Foundation Trust, United Kingdom Harefield Hospital, Hill End Road, Harefield, Middlesex UB9 6JH, United Kingdom Early identification and treatment of people with Familial Hypercholesterolaemia (FH), is important if we are to reduce their risk of premature cardiovascular disease (CVD). It is estimated that there are approximately 100,000 people in the UK that remain undetected and therefore at higher risk of CVD due to FH. A FH genetic screening clinic (FHGSC) was established in May 2008 at Harefield Hospital a cardiothoracic tertiary referral centre within the North West Thames region, following involvement in The Department of Health Familial Hypercholesterolaemia Cascade Testing Audit Project. The audit project contributed to the development of the National institute for clinical excellence (NICE) published guidelines recommending how people with FH and their families should be diagnosed and treated August 2008. The clinic is part of a comprehensive service for FH at Harefield Hospital that includes detection, genetic screening, follow up and treatment that includes LDL apheresis. The FHGSC is nurse led, with 2 clinic sessions per week. Children are seen separately in a paediatric outpatient department with
e5
access to suitably trained staff. Referrals are from the coronary prevention clinic, cardiology department, cardiac rehabilitation, external consultants and general practioners. Genetic analysis service is provided by Great Ormond Street Hospital and funding is currently met by PCT’s. Results – screened 287 index and 119 relatives. Of the index patients mutations were identified in 72(29%) and in 64(56%) of relatives. Within the 64 positive family members, 23 were aged ≤16 years, 28 were aged ≤20 years and 30 were aged ≤30years, the majority of whom were newly identified. To conclude the FHGSC is part of a comprehensive FH service that has identified a number of people who would have likely remained undetected and therefore would have been at higher risk of developing premature CVD. doi:10.1016/j.atherosclerosis.2011.07.070 Identification of patients with familial hypercholesterolaemia (FH) through the application of genetic testing in young mi patients from the MINAP register M. Futema 1,∗ , R. Whittall 1 , G. Wood 1 , M. Curtis 2 , J. McEwan 2 , S.E. Humphries 1 1 2
Cardiovascular Genetics BHF Laboratories, UCL, United Kingdom Heart Hospital UCL, United Kingdom
Background: FH is a common co-dominant genetic disease caused by mutations affecting the metabolism of LDL-cholesterol (LDL-C). These result in high levels of LDL-C leading to early coronary heart disease (CHD). Early diagnosis and rapid treatment can significantly reduce the mortality and morbidity associated with FH. The aim of this study is to examine the acceptability and feasibility of using the MINAP register to identify possible cases of FH by DNA testing and to carry out Cascade Testing in their relatives. Methods: Letters were sent to MINAP registrants at UCL who were males under 55 years, and females under 60 years of age. Saliva specimens were collected from those who consented for the study and DNA extracted using an Oragene® DNA purification kit. A commercial Amplification Refractory Mutation System (ARMS) kit was used to screen for the most common FH mutations in the UK population, including 18 mutations in LDLR, 1 in APOB (p.Arg3527Gln) and 1 in PCSK9 (p.Asp374Tyr). High-Resolution Melt (HRM) was examined as an additional possible mutation detection method. Results: Of 430 letters sent, 182 consent forms were returned (42%) and of these 137 saliva samples were returned (overall response rate 32%). There was no difference in response between males and females. In 119 DNA samples examined to date the ARMS test detected one LDLR mutation (c.301G>A) resulting in an amino acid change (p.Glu101Lys). HRM also detected this mutation. Conclusions: Since The ARMS kit detects roughly 50% of all FH mutations present in the UK this suggests an overall prevalence of FH of 2% in subjects surviving an MI at a young age. Additional FH patients may be detectable using HRM of saliva sample DNA. doi:10.1016/j.atherosclerosis.2011.07.071 Abdominal fat in association with insulin resistance in men of European and South Asian origin Reza Hajhosseiny Imperial College London, 69 Deepfield Way, Coulsdon, Surrey CR5 2SR, United Kingdom Background: Type-2 diabetes is one of the biggest killers worldwide, with varying prevalence between ethnic groups. South Asians have a higher risk of diabetes compared to Europeans. There is a
e6
Abstracts / Atherosclerosis 218 (2011) e1–e12
growing consensus that variation in ethnic abdominal fat distribution could explain these disparities. Objectives: To quantify abdominal fat depots in our bi-ethnic population, relating these to metabolic disturbances such as dysglycaemia. Method: 158 participants attended our clinic, where conventional risk factors for insulin resistance were measured. The software imageJ was used to analyse the fat layers from CT scans of the abdomen. Results: Normalising for height, South Asians had significantly more visceral fat (104 cm2 /m, p = 0.0163) versus Europeans 81.1 cm2 /m. Both deep (42.5 cm2 /m vs 29.8 cm2 /m, p = 0.0004) and superficial subcutaneous (62.8 cm2 /m vs 47.3 cm2 /m, p = 0.0012) fats were also higher. Diabetes prevalence was double that of Europeans (p = 0.039), with elevated HBA1c (6.50% vs 5.98%, p = 0.005), fasting glucose (5.3 mmol/l vs 5.1 mmol/l, p = 0.089) and 2 h post load glucose (7.45 mmol/l vs 6.53 mmol/l, p = 0.095). There was a strong correlation between visceral fat and fasting glucose (r = 0.500, p = 0.0002), HBA1c (r = 0.452, p = 0.001) and 2 h post load glucose (r = 0.268, p = 0.104) in South Asians. Relatively weaker correlations were also observed for deep and superficial subcutaneous fat layers. Conclusion: The increased central obesity, in particular visceral obesity of South Asians is associated with their dysglycaemia. Interventions which target truncal and abdominal fat reduction may be the most helpful preventive measures for insulin resistance and diabetes. doi:10.1016/j.atherosclerosis.2011.07.072 Assessment of 2 methods for isolation of high-density lipoprotein Salam Hama ∗ , Handrean Soran, Valentine Charlton-Menys, Yifen Liu, Rahul Yadav, Michael France, Basil Ammori, Paul Durrington Cardiovascular Research Group, University of Manchester, United Kingdom Background: HDL is heterogeneous. It can sub-divided into HDL2 and HDL3. HDL2 is thought to offer more protection than HDL3 against atherosclerosis. Two main techniques are commonly used to separate HDL subfractions, ultracentrifugation and precipitation. Our literature search revealed that the precipitation methods are reported to give higher results for HDL3 cholesterol (HDL3-C) than ultracentrifuge methods, but there have been few direct comparisons. Methods: Blood was drawn from 12 healthy volunteers after overnight fasting and serum total HDL-cholesterol (HDL-C) was determined by a 3rd generation automated assay. We also used sequential ultracentrifugation to isolate total HDL (density >1.063 g/ml), HDL2 (density 1.063–1.125 g/ml) and HDL3 (density >1.125 g/ml) and assayed cholesterol in these fractions. In another 12 healthy volunteers we used a Dextran/MgCl2 precipitation method to isolate total HDL and HDL3 and HDL2-C was calculated by subtraction. Results: Serum total HDL-C for the two groups was similar (1.76 ± 0.70 mmol/l vs. 1.69 ± 0.30 mmol/l; mean ± SD). Total HDLC at density >1.063 g/ml was 1.65 ± 0.49 mmol/l (94%) compared with 1.48 ± 0.32 mmol/l (88%) by precipitation. HDL3-C by ultracentrifugation was 0.35 ± 0.09 mmol/l (23% of total HDL-C) and much higher by precipitation at 1.24 ± 0.36 mmol/l (84% of total HDL-C) (P < 0.0001). Conclusions: Our study draws attention to widespread disagreement in the literature about the distribution of cholesterol in HDL subfractions, which would appear to be method specific. There is
a need to resolve these differences and to establish a universally agreed reference method. doi:10.1016/j.atherosclerosis.2011.07.073 The general practioners and the challenge of hypertriglyceridaemia: The scorers, the losers and the spectators Background: Increasing referrals from GPs to lipid clinic seeking advice on the management of hypertriglyceridaemia or expressing difficulty in normalising triglyceride level. Method: A questionnaire to 300 GPs evaluating whether they follow a systematic approach, based on pathogenesis, to assess cases of hypertriglyceridaemia and what is the management plan(s). Results: 53.3% define hypertriglyceridaemia “a triglyceride level” 1.5–2.5 mmol/L, 5.8% quoted reference range. Unacceptable 9.2% reported TG above 4 mmol/L. 96% request fasting blood sample and 73% repeat TG testing. 94% and 68% assess eating pattern and physical activity respectively. 90% weigh patients and 20% measure waist circumference. 91% calculate BMI, 66% do not know or use wrong formula for BMI, the rest use computer. 97% assess alcohol intake, 47% ask about alcohol binge. 31% gave wrong answer to safety limit for alcohol drinking. 93% check glucose level. 87% request liver function, 81% arrange liver ultrasound if suspect fatty liver. 52% obtain family history of hypertriglyceridaemia. 16% know TG level associated with risk for pancreatitis. 57% expressed no confidence in treating patients, due to lack of experience 54%, absence of guidelines 34%, combined reasons 42%. 81% of non-confident GP treat patients, 15% refer patients to specialist, 4% take no action, totalling not good practice to 85%. GPs advise more on healthy eating 84% than referring patients to dietician 43%. 54% use statins as first drug therapy [43% simvastatin, 9% atorvastatin and 2% rosuvastatin] rather than fibrates 11%. 21% use combined statins therapy, 18%, 2% and 1% add fibrates, omacor and ezetimibe respectively. Conclusion: Knowledge of pathogenesis of hypertriglyceridaemia is not full, attention to lifestyle and components of lipid profile is not optimal, no systematic/uniform approach to obtain history, assess, and investigate patients, and management varies considerably Guidelines and education tools are needed to optimize/standardize patient care. doi:10.1016/j.atherosclerosis.2011.07.074 Hyperlipidaemia as initial presentation of myeloma Wycliffe Mbagaya ∗ , Julian H. Barth Leeds Teaching Hospitals NHS Trust, United Kingdom We report the case of a 70 year old woman referred by her GP with refractory hypercholesterolaemia. She had initially been diagnosed to have raised cholesterol 18 months earlier. This did not improve on three different statins and continued on simvastatin 80 mg/day. She had no significant medical history, no diabetes, no hypertension or vascular disease. She was an ex-smoker who stopped smoking 15years before and drank 1 unit of alcohol daily. She weighed 59.4 kg with a Body Mass Index of 24; she had no xanthomata or xanthelasma. She had posterior cervical lymphadenopathy and a palpable liver 2 cm below costal margin. Her lipid profiles was as follows
Cholesterol Triglycerides
January 2004
August 2005
October 2005
6.8 mmol/L 2.9 mmol/L
10.4 mmol/L 7.5 mmol/L
23.2 mmol/L 17.7 mmol/L
Changes in function and structure of high-density lipoprotein in obese patients compared with healthy controls Salam Hama ∗ , Handrean Soran, Yifen Liu, Valentine CharltonMenys, Reza Zadeh, Michael France, Rahul Yadav, Maria Jeziorska, Basil Ammori, Paul Durrington Cardiovascular Research Group, University of Manchester, United Kingdom Background: There is an inverse relationship between HDL and cardiovascular disease. We hypothesised that HDL’s anti-oxidant function is altered in obese patients, with or without type 2 diabetes. Methods: 19 obese patients, 8 with type 2 diabetes, and 13 healthy controls were recruited. HDL’s antioxidant ability was tested by measuring lipid peroxide (LPO) formation after incubation of HDL with Cu2+ at baseline and at 3 hours. ApoAI was determined in HDL and its sub-fractions. Serum PON1 activity was measured by a semi-automated method. Results: There was no significant difference in LPO concentration at baseline between controls and obese patients (30 [23–50] vs. 39 [22–94] nmol/ml). LPO formation was, however, significantly greater in obese patients after 3 h (39 [4–93] vs. 67 [10–129] nmol/ml; p < 0.05). PON1 activity tended to be lower in the obese group with (77 [24–271] nmol/ml/min) or without diabetes (142 [26–216] nmol/ml/min) compared with controls (178 [38–457] nmol/ml/min). ApoAI in HDL2 of the obese-diabetic group was significantly lower compared with healthy controls (0.77 [0.69–0.85] vs. 1.01 [0.64–1.74] g/l; p < 0.05). Conclusions: LPO formation in HDL from obese patients was higher than in healthy HDL, suggesting the presence of proinflammatory HDL. Deterioration of HDL’s ability to protect itself against oxidation could indicate deterioration of its protective functions and this could be linked to re-distribution of apoAI in HDL sub-fractions and lower PON1 activity. doi:10.1016/j.atherosclerosis.2011.07.069 Genetic screening for familial hypercholesterolaemia in a cardiothoracic tertiary referral centre J. Breen ∗ , J. Jones, M. Barbir Royal Brompton and Harefield NHS Foundation Trust, United Kingdom Harefield Hospital, Hill End Road, Harefield, Middlesex UB9 6JH, United Kingdom Early identification and treatment of people with Familial Hypercholesterolaemia (FH), is important if we are to reduce their risk of premature cardiovascular disease (CVD). It is estimated that there are approximately 100,000 people in the UK that remain undetected and therefore at higher risk of CVD due to FH. A FH genetic screening clinic (FHGSC) was established in May 2008 at Harefield Hospital a cardiothoracic tertiary referral centre within the North West Thames region, following involvement in The Department of Health Familial Hypercholesterolaemia Cascade Testing Audit Project. The audit project contributed to the development of the National institute for clinical excellence (NICE) published guidelines recommending how people with FH and their families should be diagnosed and treated August 2008. The clinic is part of a comprehensive service for FH at Harefield Hospital that includes detection, genetic screening, follow up and treatment that includes LDL apheresis. The FHGSC is nurse led, with 2 clinic sessions per week. Children are seen separately in a paediatric outpatient department with
e5
access to suitably trained staff. Referrals are from the coronary prevention clinic, cardiology department, cardiac rehabilitation, external consultants and general practioners. Genetic analysis service is provided by Great Ormond Street Hospital and funding is currently met by PCT’s. Results – screened 287 index and 119 relatives. Of the index patients mutations were identified in 72(29%) and in 64(56%) of relatives. Within the 64 positive family members, 23 were aged ≤16 years, 28 were aged ≤20 years and 30 were aged ≤30years, the majority of whom were newly identified. To conclude the FHGSC is part of a comprehensive FH service that has identified a number of people who would have likely remained undetected and therefore would have been at higher risk of developing premature CVD. doi:10.1016/j.atherosclerosis.2011.07.070 Identification of patients with familial hypercholesterolaemia (FH) through the application of genetic testing in young mi patients from the MINAP register M. Futema 1,∗ , R. Whittall 1 , G. Wood 1 , M. Curtis 2 , J. McEwan 2 , S.E. Humphries 1 1 2
Cardiovascular Genetics BHF Laboratories, UCL, United Kingdom Heart Hospital UCL, United Kingdom
Background: FH is a common co-dominant genetic disease caused by mutations affecting the metabolism of LDL-cholesterol (LDL-C). These result in high levels of LDL-C leading to early coronary heart disease (CHD). Early diagnosis and rapid treatment can significantly reduce the mortality and morbidity associated with FH. The aim of this study is to examine the acceptability and feasibility of using the MINAP register to identify possible cases of FH by DNA testing and to carry out Cascade Testing in their relatives. Methods: Letters were sent to MINAP registrants at UCL who were males under 55 years, and females under 60 years of age. Saliva specimens were collected from those who consented for the study and DNA extracted using an Oragene® DNA purification kit. A commercial Amplification Refractory Mutation System (ARMS) kit was used to screen for the most common FH mutations in the UK population, including 18 mutations in LDLR, 1 in APOB (p.Arg3527Gln) and 1 in PCSK9 (p.Asp374Tyr). High-Resolution Melt (HRM) was examined as an additional possible mutation detection method. Results: Of 430 letters sent, 182 consent forms were returned (42%) and of these 137 saliva samples were returned (overall response rate 32%). There was no difference in response between males and females. In 119 DNA samples examined to date the ARMS test detected one LDLR mutation (c.301G>A) resulting in an amino acid change (p.Glu101Lys). HRM also detected this mutation. Conclusions: Since The ARMS kit detects roughly 50% of all FH mutations present in the UK this suggests an overall prevalence of FH of 2% in subjects surviving an MI at a young age. Additional FH patients may be detectable using HRM of saliva sample DNA. doi:10.1016/j.atherosclerosis.2011.07.071 Abdominal fat in association with insulin resistance in men of European and South Asian origin Reza Hajhosseiny Imperial College London, 69 Deepfield Way, Coulsdon, Surrey CR5 2SR, United Kingdom Background: Type-2 diabetes is one of the biggest killers worldwide, with varying prevalence between ethnic groups. South Asians have a higher risk of diabetes compared to Europeans. There is a
e6
Abstracts / Atherosclerosis 218 (2011) e1–e12
growing consensus that variation in ethnic abdominal fat distribution could explain these disparities. Objectives: To quantify abdominal fat depots in our bi-ethnic population, relating these to metabolic disturbances such as dysglycaemia. Method: 158 participants attended our clinic, where conventional risk factors for insulin resistance were measured. The software imageJ was used to analyse the fat layers from CT scans of the abdomen. Results: Normalising for height, South Asians had significantly more visceral fat (104 cm2 /m, p = 0.0163) versus Europeans 81.1 cm2 /m. Both deep (42.5 cm2 /m vs 29.8 cm2 /m, p = 0.0004) and superficial subcutaneous (62.8 cm2 /m vs 47.3 cm2 /m, p = 0.0012) fats were also higher. Diabetes prevalence was double that of Europeans (p = 0.039), with elevated HBA1c (6.50% vs 5.98%, p = 0.005), fasting glucose (5.3 mmol/l vs 5.1 mmol/l, p = 0.089) and 2 h post load glucose (7.45 mmol/l vs 6.53 mmol/l, p = 0.095). There was a strong correlation between visceral fat and fasting glucose (r = 0.500, p = 0.0002), HBA1c (r = 0.452, p = 0.001) and 2 h post load glucose (r = 0.268, p = 0.104) in South Asians. Relatively weaker correlations were also observed for deep and superficial subcutaneous fat layers. Conclusion: The increased central obesity, in particular visceral obesity of South Asians is associated with their dysglycaemia. Interventions which target truncal and abdominal fat reduction may be the most helpful preventive measures for insulin resistance and diabetes. doi:10.1016/j.atherosclerosis.2011.07.072 Assessment of 2 methods for isolation of high-density lipoprotein Salam Hama ∗ , Handrean Soran, Valentine Charlton-Menys, Yifen Liu, Rahul Yadav, Michael France, Basil Ammori, Paul Durrington Cardiovascular Research Group, University of Manchester, United Kingdom Background: HDL is heterogeneous. It can sub-divided into HDL2 and HDL3. HDL2 is thought to offer more protection than HDL3 against atherosclerosis. Two main techniques are commonly used to separate HDL subfractions, ultracentrifugation and precipitation. Our literature search revealed that the precipitation methods are reported to give higher results for HDL3 cholesterol (HDL3-C) than ultracentrifuge methods, but there have been few direct comparisons. Methods: Blood was drawn from 12 healthy volunteers after overnight fasting and serum total HDL-cholesterol (HDL-C) was determined by a 3rd generation automated assay. We also used sequential ultracentrifugation to isolate total HDL (density >1.063 g/ml), HDL2 (density 1.063–1.125 g/ml) and HDL3 (density >1.125 g/ml) and assayed cholesterol in these fractions. In another 12 healthy volunteers we used a Dextran/MgCl2 precipitation method to isolate total HDL and HDL3 and HDL2-C was calculated by subtraction. Results: Serum total HDL-C for the two groups was similar (1.76 ± 0.70 mmol/l vs. 1.69 ± 0.30 mmol/l; mean ± SD). Total HDLC at density >1.063 g/ml was 1.65 ± 0.49 mmol/l (94%) compared with 1.48 ± 0.32 mmol/l (88%) by precipitation. HDL3-C by ultracentrifugation was 0.35 ± 0.09 mmol/l (23% of total HDL-C) and much higher by precipitation at 1.24 ± 0.36 mmol/l (84% of total HDL-C) (P < 0.0001). Conclusions: Our study draws attention to widespread disagreement in the literature about the distribution of cholesterol in HDL subfractions, which would appear to be method specific. There is
a need to resolve these differences and to establish a universally agreed reference method. doi:10.1016/j.atherosclerosis.2011.07.073 The general practioners and the challenge of hypertriglyceridaemia: The scorers, the losers and the spectators Background: Increasing referrals from GPs to lipid clinic seeking advice on the management of hypertriglyceridaemia or expressing difficulty in normalising triglyceride level. Method: A questionnaire to 300 GPs evaluating whether they follow a systematic approach, based on pathogenesis, to assess cases of hypertriglyceridaemia and what is the management plan(s). Results: 53.3% define hypertriglyceridaemia “a triglyceride level” 1.5–2.5 mmol/L, 5.8% quoted reference range. Unacceptable 9.2% reported TG above 4 mmol/L. 96% request fasting blood sample and 73% repeat TG testing. 94% and 68% assess eating pattern and physical activity respectively. 90% weigh patients and 20% measure waist circumference. 91% calculate BMI, 66% do not know or use wrong formula for BMI, the rest use computer. 97% assess alcohol intake, 47% ask about alcohol binge. 31% gave wrong answer to safety limit for alcohol drinking. 93% check glucose level. 87% request liver function, 81% arrange liver ultrasound if suspect fatty liver. 52% obtain family history of hypertriglyceridaemia. 16% know TG level associated with risk for pancreatitis. 57% expressed no confidence in treating patients, due to lack of experience 54%, absence of guidelines 34%, combined reasons 42%. 81% of non-confident GP treat patients, 15% refer patients to specialist, 4% take no action, totalling not good practice to 85%. GPs advise more on healthy eating 84% than referring patients to dietician 43%. 54% use statins as first drug therapy [43% simvastatin, 9% atorvastatin and 2% rosuvastatin] rather than fibrates 11%. 21% use combined statins therapy, 18%, 2% and 1% add fibrates, omacor and ezetimibe respectively. Conclusion: Knowledge of pathogenesis of hypertriglyceridaemia is not full, attention to lifestyle and components of lipid profile is not optimal, no systematic/uniform approach to obtain history, assess, and investigate patients, and management varies considerably Guidelines and education tools are needed to optimize/standardize patient care. doi:10.1016/j.atherosclerosis.2011.07.074 Hyperlipidaemia as initial presentation of myeloma Wycliffe Mbagaya ∗ , Julian H. Barth Leeds Teaching Hospitals NHS Trust, United Kingdom We report the case of a 70 year old woman referred by her GP with refractory hypercholesterolaemia. She had initially been diagnosed to have raised cholesterol 18 months earlier. This did not improve on three different statins and continued on simvastatin 80 mg/day. She had no significant medical history, no diabetes, no hypertension or vascular disease. She was an ex-smoker who stopped smoking 15years before and drank 1 unit of alcohol daily. She weighed 59.4 kg with a Body Mass Index of 24; she had no xanthomata or xanthelasma. She had posterior cervical lymphadenopathy and a palpable liver 2 cm below costal margin. Her lipid profiles was as follows
Cholesterol Triglycerides
January 2004
August 2005
October 2005
6.8 mmol/L 2.9 mmol/L
10.4 mmol/L 7.5 mmol/L
23.2 mmol/L 17.7 mmol/L