Lipid clinic experience with bempedoic acid in three UK centres.

OBJECTIVE: Novel lipid-lowering therapies are being introduced. Few studies exist of the real-world effectiveness of adenosine-tri-phosphate citrate lyase inhibition with bempedoic acid. METHODS: This study audited bempedoic acid therapy in 216 consecutive patients from three hospital centres - a university hospital (n = 77) and two district general hospitals (n = 106 and 33). Cardiovascular disease (CVD) risk factors, prescription qualification criteria, efficacy and adverse effects were assessed. RESULTS: The population was aged 65.9 ± 11.0 years, 42% were male, 25% had type 2 diabetes, and 31% had familial hypercholesterolaemia. CVD was present in 19% and multibed vascular disease in 8%. Statin intolerance was reported in 92%. Bempedoic acid reduced total cholesterol by 1.58 ± 1.44 mmol/L (20%), LDL-C by 1.37 ± 1.31 mmol/L (27%), triglycerides by 0.22 mmol/L (2%) with an 0.06 mmol/L (1%) increase in HDL-C after 22 ± 9 months follow-up. An LDL-C <2.5 mmol/L was achieved in 40% and <2 mmol/L in 20%. Efficacy (r2 = .33) was predicted by baseline LDL-C (ß = .54; p <.001). No significant changes were seen in transaminases, creatinine, creatine kinase, urate or HbA1c. Treatment was discontinued by 33% of patients and occurred due to myalgia (43%), lack of efficacy (16%) and gastrointestinal adverse effects (15%). No cases of gout were observed. In a logistic regression only the number of previous drug classes not tolerated (ß = 1.60; p = .009) was a contributing factor to discontinuation. CONCLUSION: This audit suggests that bempedoic acid therapy is effective but that adverse effects and discontinuation are common. This suggests nocebo effects might be generalizable to all lipid-lowering drug therapies in susceptible individuals.

The Association between Metabolic Syndrome and Multiple Myeloma.

Multiple myeloma (MM) is a haematological malignancy arising from monoclonal proliferation of plasma cells in the bone marrow, resulting in the presence of paraproteins or M-protein in serum. The involvement of paraproteins produced by malignant plasma cells in the development of hyperlipidaemia and low-HDL cholesterol has been described, as has an association with MM and obesity, hypertension, and type 2 diabetes mellitus, and insulin resistance, that is, features of the metabolic syndrome (MS). There is an association between MS components, inflammatory cytokines, and the development of MM, and some drugs used in the treatment of MS such as statins and metformin may improve outcomes in MM.

Review of referral criteria to lipid clinics and outcomes of treatment in four UK centres.

BACKGROUND: Little data exist on the referral patterns and effectiveness of lipid clinics. METHODS: An audit was conducted in four clinics of 100 consecutive referrals each. Data were recorded on referral criteria, cardiovascular disease (CVD) risk factors, drug history, investigations, diagnoses, therapies, results and referrals. RESULTS: Patients were aged 56 ± 14 years, 47% were male and 87% were primary prevention. Risk factors included smoking (16%), type 2 diabetes (13%) and hypertension (13%). Referrals were made for hypercholesterolaemia (68%), diagnosis of FH (31%), statin intolerance (23%) and hypertriglyceridaemia (23%). Initial total cholesterol (TC) was 7.65 ± 2.64 mmol/L, triglycerides (TG) 2.17 (0.41-76.9 mmol/L) mmol/L, HDL-C 1.53 ± 0.71 mmol/L, LDL-C 4.57 ± 1.66 mmol/L with non-HDL-C 5.90 ± 2.09 mmol/L. Criteria for FH were met in 21% with genetic testing in 13% and lipid cascade testing in 30% of index cases. Triglycerides >20 mmol/L were present in 4%. The diagnosis was changed in 21%: hypercholesterolaemia (7%), mixed hyperlipidaemia (7%) and hypertriglyceridaemia (7%). Hepatic steatosis was identified in 14.5%. Lipoprotein(a) levels >125 nmol/L occurred in 41% in one clinic. Therapy changes included altered statins (40%), addition of a fibrate (11%) or ezetimibe (8%). These reduced TC by 1.92 mmol/L (19%; P = 0.0001), LDL-C 1.07 mmol/L (15%; P = 0.02), non-HDL-C 1.50 mmol/L (16%; P < 0.001), and TG 2.3 (-4 to 38) mmol/L (16%; P < 0.001) with 11% extra achieving TG <5 mmol/L while HDL-C increased by 7% (P = 0.37). CONCLUSIONS: Lipid clinics have diverse functions including diagnosis of FH, managing severe hypercholesterolaemia, mixed hyperlipidaemia and statin intolerance. Effectiveness criteria of average reductions of 1.5 mmol/L in TC or non-HDL-C, 1 mmol/L in LDL-C and 2 mmol/L in TG would be reasonable for newly referred patients.

Pro-protein subtilisin kexin-9 (PCSK9) inhibition in practice: lipid clinic experience in 2 contrasting UK centres.

BACKGROUND: Prescribing criteria have been suggested for proprotein convertase subtilisin kexin-9 (PCSK-9) inhibitors but few studies exist of their real-world effectiveness. METHODS: This study audited PCSK-9 inhibitor therapy in 105 consecutive patients from two hospital centres-a university hospital (UH; n = 70) and a district general hospital (DGH; n = 35). Baseline characteristics including cardiovascular disease risk factors, NICE qualification criteria, efficacy and side effects were assessed. RESULTS: Baseline LDL-C levels were similar in both centres. NICE criteria were met for 2.05 items in the whole study (UH patients 1.7 and DGH patients 2.7). District general hospital patients were more likely to have familial hypercholesterolaemia (89 vs 69%; P = .02); intolerance to statins (94 vs 52%; P < .001) and polyvascular disease (42% vs 17%; P = .005). Prescriptions (evolocumab 73%; alirocumab 23%) were collected by 76% of patients (UH 64% vs DGH 100%). Therapy was discontinued by time of review in 15% of patients (UH 7% vs DGH 25%; P = .02). In adherent patients PCSK-9 inhibitor treatment reduced TC by 28% (2.24 ± 2.39 mmol/L; P < .001) and LDL-C by 49% (2.10 ± 1.33 mmol/L; P < .001). A LDL-C < 2.5 mmol/L was achieved in 30% of patients and <2.0 mmol/L in 20%. PCSK-9 therapy was effective and safe in patients with increased lipoprotein (a), diagnosed muscle diseases (including myopathies and muscular dystrophy) or poststatin rhabdomyolysis, nephrotic syndrome or HIV disease. Mixed results were obtained in patients with significant mixed hyperlipidaemia. CONCLUSIONS: This study suggests that PCSK-9 inhibitors are effective but that prescriptions should not be changed to long-term delivery until patients have been reviewed and shown to be adherent.

Metabolic Syndrome in Long-Term Survivors of Hematopoietic Stem-Cell Transplantation.

Since its introduction more than 50 years ago, hematopoietic stem-cell transplantation (HSCT) has transformed from an inescapably fatal procedure to one where cure from malignant and other nonmalignant hematologic diseases is becoming increasingly common. Nevertheless, longevity is not entirely restored. New causes of mortality have emerged; of particular importance is that of increased cardiovascular disease (CVD), related to metabolic syndrome and its components. Controversy exists over whether the metabolic abnormalities induced are a direct effect of HSCT itself or a consequence of other therapies involved. Analysis of the mechanisms that promote the changes in metabolic components will give insight into future HSCT therapy as well as CVD pathogenesis and prevention.

Acute pancreatitis associated with severe hypertriglyceridaemia; A retrospective cohort study.

AIM: Acute Pancreatitis (AP) secondary to hypertriglyceridaemia (HTG) is a rare association of which little is known in the literature. This study investigates patient characteristics and outcomes (reoccurrence and mortality) in those presenting with AP secondary to HTG in one of the largest reported British cohorts. METHODS: A retrospective observational case note review of all patients treated at our institution between 2004 and 2012. Data are expressed as mean and standard deviation if parametric and as median and range if non-parametric. Full fasting lipid profiles and patient demographics were recorded to elucidate further the cause of the severe hypertriglyceridaemia (>10 mmol/L fasting). RESULTS: There were 784 patients admitted with AP admitted to our institution within the study period. APHTG was present in 18 patients (2.3%). Peak serum triglyceride concentration was 43.9 mmol/L, SD 18.9 mmol/L. Serum amylase activity was 'falsely' low (with raised urine amylase) in about 10% of the patients with acute pancreatitis and hypertriglyceridaemia. 67% of our patients had type 2 diabetes mellitus or impaired glucose tolerance, 28% had a fatty liver and 50% displayed alcohol excess all these conditions are known to be associated with HTG There was a 94.5% reduction in serum triglyceride between presentation and last follow-up visit. There were also no deaths or recurrent episodes of AP during the study period. CONCLUSIONS: APHTG was present in 2.3% of patients presenting with AP. The reoccurrence and mortality rates were zero in this cohort. This may in part be due to aggressive serum triglyceride lowering by a multi-disciplinary team. Early clinical recognition is vital to provide targeted treatment and to try and reduce further episodes of AP.

Causes of hypoamylasaemia in a hospital population.

AIMS: We noted serum amylase activity results in our laboratory that fell below the lower reference limit, although there was no obvious explanation for this and the literature on this topic is relatively sparse. METHODS: We studied hospital laboratory requests and reports of individuals showing hypoamylasaemia over a one-year period. RESULTS: We report one of the few studies to look at hypoamylasaemia in a hospital population. We found that 5.4% of the hospital serum amylase activity results were below the reference range quoted by our laboratory. CONCLUSIONS: Some of the associations we observed with hypoamylasaemia were diabetes mellitus, cystic fibrosis, hypertriglyceridaemia and use of the antibiotic gentamicin. We suggest that clinicians and laboratories should be aware of the causes of hypoamylasaemia to aid interpretation of abnormally low amylase activity in their patients.

Use of lipid-lowering medications in myasthenia gravis: a case report and literature review.

We present a patient with myasthenia gravis (MG) who developed worsening of his condition after starting ezetimibe. We review the literature concerning lipid-modifying medications and MG. The use of bile acid sequestrant agents may have a place in the lipid management of MG patients because they did not seem to cause muscle-related side effects or worsening of MG.

Refeeding syndrome: problems with definition and management.

Refeeding syndrome (RFS) broadly encompasses a severe electrolyte disturbance (principally low serum concentrations of intracellular ions such as phosphate, magnesium, and potassium) and metabolic abnormalities in undernourished patients undergoing refeeding whether orally, enterally, or parenterally. RFS reflects the change from catabolic to anabolic metabolism. RFS sometimes is undiagnosed and unfortunately some clinicians remain oblivious to its presence. This is particularly concerning as RFS is a life-threatening condition, although it need not be so and early recognition reduces morbidity and mortality. Careful patient monitoring and multidiscipline nutrition team management may help to achieve this goal. The diagnosis of RFS is not facilitated by the fact that there is no universal agreement as to its definition. The presence of hypophosphatemia alone does not necessarily mean that RFS is present as there are many other causes for this, as discussed later in this article. RFS is increasingly being recognized in neonates and children. An optimal refeeding regimen for RFS is not universally agreed on due to the paucity of randomized controlled trials in the field.

Seasonal factitious increase in serum potassium: still a problem and should be recognised.

AIM: Spurious serum elevation of potassium concentration can occur in the presence of cold ambient temperatures and the aim of this study was to assess the effect of changes in temperature on the average serum potassium concentration in our population. METHOD: We conducted a retrospective review of all serum potassium samples received to the laboratory between January 2009 and September 2012 from accident & emergency (AE), general practice (GP), in-patient (IP) and out-patient (OP) departments and compared these with the mean ambient temperatures for these months supplied by the Met Office for South East and Central England. RESULTS: We have identified that in a relatively condensed south London region seasonal factitious serum potassium elevation occurs in primary care samples but also somewhat surprisingly also in hospital in-patient and out-patient samples although apparently less so in AE samples. We found an inverse correlation between ambient temperature and serum potassium in GP blood samples (Pearson correlation coefficient=-0.83, P<0.001), there were weaker correlations with inpatient (-0.41, P=0.005) and outpatient samples (-0.28, P=0.06) but not in AE samples. CONCLUSION: Factitious seasonal potassium increase can occur in patient blood samples particularly those from primary health care.