Non-HDL or LDL cholesterol in heterozygous familial hypercholesterolaemia: findings of the Simon Broome Register (2020)

Type of publication:
Journal article

Author(s):
Soran H.; Durrington P.N.; Cooper J.A.; Humphries S.E.; *Capps N.; McDowell I.F.W.; Neil A.

Citation:
Current Opinion in Lipidology; August 2020, Volume 31, Issue 4, p. 167-175

Abstract:
PURPOSE OF REVIEW: The role of non-HDL-C in the identification and management of lipid disorders is not clearly defined, although UK guidelines recommend its wider use in assessing the need for lipid-lowering therapy and as a treatment target. RECENT FINDINGS: We examined the implications of the use of non-HDL-C as opposed to LDL-C in 253 people with hypercholesterolaemia before treatment and 573 after treatment in whom fasting total serum cholesterol, HDL-C and LDL-C had been recorded and the diagnosis of heterozygous familial hypercholesterolemia (heFH) was investigated by genetic testing. The difference and the limits of agreement between non-HDL-C and LDL-C calculated using the Friedewald formula were assessed in those with and without heFH-causing mutations. SUMMARY: There were 147 mutation-positive and 106 mutation-negative pretreatment participants and 395 mutation-positive and 178 mutation-negative patients receiving treatment. The difference between non-HDL-C and LDL-C pretreatment in mutation-positive people (mean LDL-C 7.73 mmol/l) was 0.67 mmol/l (95% CI 0.62-0.73) and posttreatment (mean LDL-C 4.71 mmol/l) was 0.62 mmol/l (95% CI 0.59-0.65) with wide limits of agreement of -0.02 to 1.37 and 0.07-1.18 mmol/l, respectively. Among patients with heterozygous familial hypercholesterolaemia, use of estimated LDL-C derived from non-HDL-C in place of calculated LDL-C may result in diagnostic misclassification and difficulty in assessing the true reduction in LDL-C with treatment, because of the wide inter-individual limits of agreement around the mean difference between non-HDL-C and LDL-C.

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Categorising sub-massive pulmonary thromboembolism: No isolated role for shock index or its modified form (2019)

Type of publication:
Conference abstract

Author(s):
*Abdulsamad S.P.; *Crawford E.; *Makan A.; *Ahmad N.; *Srinivasan K.; *Moudgil H.

Citation:
European Respiratory Journal; Sep 2019; vol. 54, PA1469

Abstract:
Background and Objectives: Managing sub-massive pulmonary thromboembolism (PTE) remains a therapeutic challenge and efforts have been made to sub-categorise continued risk based on clinical assessment and objective measures such as a raised serum lactate (>4 mmol/l) or abnormal Shock Index (Heart rate/systolic blood pressure, SIndex). The objective here was to investigate the SIndex and its modified form (MSIndex) to (1) report frequency of abnormal results in a population being investigated for PTE and (2) assess potential benefits in avoiding adverse outcome.
Method(s): Retrospective analysis of 1505 CT pulmonary angiograms undertaken over a 12 month period. Abnormal SIndex was taken as outside limits 0.5-0.9. MSindex was calculated conventionally as heart rate divided by (2xdiastolic blood pressure+systolic blood pressure)/3 and considered abnormal if <0.7 or >1.3. Analysis was on Excel.
Result(s): Mean age for the population was 67.7 (range 17-101) years. 337/1505 (22.4%) scans showed PTE and of this population 19 patients had adverse outcome either died within 3 months (7 had malignancy) or requiring Intensive Care during the admission. For patients without PTE (n=1168), the SIndex was abnormal in 334(28.6%) and the MSindex in 293 (25.1%). For patients with PTE (n=337), respectively these figures were 89 (26.4%) and 68 (20.2%). Of those with adverse outcomes, 13/19 Sindex and 17/19 MSIndex values were not abnormal.
Conclusion(s): Neither the SIndex not the MSIndex are discriminatory in helping distinguish the at risk groups with PTE and therefore cannot be used as an isolated criteria.

Global longitudinal strain detects trastuzumab induced cardiotoxicity early in a clinical population (2020)

Type of publication:
Conference abstract

Author(s):
*Grylls, J., *Ellis, C., *Ingram, T., *Lee, E.

Citation:
European Heart Journal – Cardiovascular Imaging 2020; Volume 21, Issue Supplement 1

Abstract:
Background: Trastuzumab is highly effective in the treatment of breast cancer, and is often used as an adjuvant therapy. Due to its potential cardiotoxicity, serial monitoring of cardiac function is vital. Ejection fraction (EF) by two-dimensional echocardiography is routinely used but has limitations in measurement variability. Myocardial deformation imaging, in particular Global Longitudinal Strain (GLS), can detect pre-clinical myocardial dysfunction. However, its use is not yet adopted into routine clinical practice.
Aims: Our aim was to ascertain if a clinically significant reduction in GLS (≥11% from baseline) occurred before the onset of EF reduction, in patients who developed cardiotoxicity whilst receiving trastuzumab.
Methods: Between January 2014 and January 2019, 235 consecutive patients received trastuzumab and underwent serial echocardiography at 3 monthly intervals at our institute. Cardiotoxicity is defined as a ≥10% EF reduction from baseline or an EF <50%. Women who developed cardiotoxicity as defined by this change in EF were retrospectively studied.Two-dimensional speckle tracking was used to derive peak longitudinal strain in each myocardial segment from the apical four-, three- and two-chamber view images. GLS was taken as the average value of all these segments. The median time to ≥11% GLS reduction and ≥10% EF reduction or EF <50% was compared.
Results: Thirteen women (mean age 53 ± 9.5 years) developed cardiotoxicity. EF was 61.8 ± 4.4% at baseline and 45.7 ± 7.5% following therapy (p = 0.00). A ≥11% reduction in GLS from baseline was observed in all patients: GLS -20.2 ± 1.5% and -15.6 ± 2.1%, p = 0.00. The median time to cardiotoxicity as defined by EF and GLS was 6 months and 3 months, respectively (p = 0.031), as shown in Table 1. Repeatability analysis showed both EF and GLS measurements in our cohort have good measurement reproducibility. Inter-observer intraclass correlation (ICC) for EF and GLS were 0.912 and 0.913, respectively. Intra-observer ICC for EF and GLS were 0.925 and 0.900, respectively.
Conclusion: Cardiotoxicity developed in a significant portion (6%) of our patients receiving trastuzumab. As a reduction in GLS was detectable early and preceded that of EF by 3 months, this may represent a therapeutic window for initiation of cardio-protective medication, if and when the use of GLS is incorporated into routine practice for cardiotoxicity surveillance.

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CT Calcium Score In The Elderly With Aortic Stenosis (2020)

Type of publication:
Conference abstract

Author(s):
*Pastfield E.; *Botley S.; *Pakala V.; *Ingram T.; *Lee E.

Citation:
Journal of Cardiovascular Computed Tomography; 2020; vol. 14 (no. 1)

Abstract:
Introduction: Degenerative aortic stenosis is a common condition. Many elderly frail patients with multiple comorbidities now have an alternative to conventional surgery since the availability of transcutaneous aortic valve implantation (TAVI). Echocardiography (echo) remains the key tool for the diagnosis of aortic stenosis. CT calcium scoring, has proven a useful adjunct to diagnosis, when there are discordant echo measurements. The current societies’ consensus propose a cut-off score (>2000 for men and >1200 for women) above which ‘severe aortic stenosis is likely’. However, many elderly patients have discordant echo measurements, low calcium score despite having severe aortic stenosis. We propose that the adverse event rates in elderly patients, regardless of calcium score category, are not significantly different. Method(s): We retrospectively examined the records of consecutive patients undergoing CT calcium score between Jan 2017 and Sep 2019. These investigations were done, either for TAVI procedure planning or as an adjunct to assessing the severity of aortic stenosis (in the case of discordant echo measurements). All these patients were followed up for adverse events, defined as a composite of heart failure, chest pain or death. Statistical analysis was performed using SPSS 25 (IBM). Result(s): 88 patients, age 82+/-6 years, 55% men, underwent CT aortic valve calcium scoring and echo. Peak aortic velocity 3.9 +/- 0.8 m/s, mean gradient 35 +/- 13 mmHg, aortic valve area 0.8 +/- 0.2cm2, stroke volume index (SVI) 38 +/- 11 ml/m2. 52.4% of the study population had discordant echo measurements and 43.6% had SVI<35ml/m2. The calcium score for women and men were 2230 +/- 1250 and 3866 +/- 1997 respectively. 24% of these patients had calcium score below the cut-off value for ‘likely severe aortic stenosis’. Median follow up was 382 days (range 66-1381 days) from the initial echo. Adverse events occurred in 20+/-4% and 29+/-5% in the ‘high’ and ‘low’ calcium score groups, independent t-test, p=0.40. Using Kaplan-Meier survival curve, there is no difference in the event free survival days between the two groups, 888 days for the ‘low’ and 702 days for the ‘high’ calcium score groups, Log rank Chi-square=0.26, p=0.61. Conclusion(s): In an elderly population with aortic stenosis, there is no difference in short term adverse event rates (composite of heart failure/death/chest pain) as categorised by their calcium scores. Therefore, the current diagnostic approach may under estimate the severity of aortic stenosis in some patients. [Formula presented]

HEART UK consensus statement on Lipoprotein(a): A call to action (2019)

Type of publication:
Journal article

Author(s):
Cegla J.; Neely R.D.G.; France M.; Ferns G.; Byrne C.D.; Halcox J.; Datta D.; *Capps N.; Shoulders C.; Qureshi N.; Rees A.; Main L.; Payne J.; Cramb R.; Viljoen A.; Soran H.

Citation:
Atherosclerosis; Dec 2019; vol. 291 ; p. 62-70

Abstract:
Lipoprotein(a), Lp(a), is a modified atherogenic low-density lipoprotein particle that contains apolipoprotein(a). Its levels are highly heritable and variable in the population. This consensus statement by HEART UK is based on the evidence that Lp(a) is an independent cardiovascular disease (CVD) risk factor, provides recommendations for its measurement in clinical practice and reviews current and emerging therapeutic strategies to reduce CVD risk. Ten statements summarise the most salient points for practitioners and patients with high Lp(a). HEART UK recommends that Lp(a) is measured in adults as follows: 1) those with a personal or family history of premature atherosclerotic CVD; 2) those with first-degree relatives who have Lp(a) levels >200 nmol/l; 3) patients with familial hypercholesterolemia; 4) patients with calcific aortic valve stenosis and 5) those with borderline (but <15%) 10-year risk of a cardiovascular event. The management of patients with raised Lp(a) levels should include: 1) reducing overall atherosclerotic risk; 2) controlling dyslipidemia with a desirable non-HDL-cholesterol level of <100 mg/dl (2.5 mmol/l) and 3) consideration of lipoprotein apheresis.

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Corrigendum: It has been brought to our attention that the wording of the German reimbursement criteria for apheresis is not clear in the above paper (Section 7. Management of patients with raised Lipoprotein(a), Subheading: Apheresis). This should read: “In Germany, Lp(a) levels exceeding 60 mg/dl and LDL-cholesterol in normal range along with progressive CVD has been approved as an indication for regular lipoprotein apheresis since 2008.”

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Current management of children and young people with heterozygous familial hypercholesterolaemia – HEART UK statement of care (2019)

Type of publication:
Journal article

Author(s):
Ramaswami U.; Humphries S.E.; Priestley-Barnham L.; Green P.; Wald D.S.; *Capps N.; Anderson M.; Dale P.; Morris A.A.

Citation:
Atherosclerosis; Nov 2019; vol. 290 ; p. 1-8 [epub ahead of print]

Abstract:
This consensus statement on the management of children and young people with heterozygous familial hypercholesterolaemia (FH) addresses management of paediatric FH in the UK, identified by cascade testing when a parent is diagnosed with FH and for those diagnosed following incidental lipid tests. Lifestyle and dietary advice appropriate for children with FH; suggested low density lipoprotein cholesterol (LDL-C) targets and the most appropriate lipid-lowering therapies to achieve these are discussed in this statement of care. Based on the population prevalence of FH as ~1/250 and the UK paediatric population, there are approximately 50,000 FH children under 18 years. Currently only about 550 of these children and young people have been identified and are under paediatric care.

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Targeting dyslipidaemia to prevent cardiovascular disease (2019)

Type of publication:
Journal article

Author(s):
Viljoen A.; Fuat A.; Takhar A.; Williams S.; *Capps N.

Citation:
Prescriber; Jul 2019; vol. 30 (no. 7); p. 23-26

Abstract:
Dyslipidaemia is a key risk factor for cardiovascular disease, and its identification and treatment is important for both primary and secondary prevention. This article discusses how to screen for dyslipidaemia and optimise lipid-lowering therapy to improve cardiovascular outcomes.

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Coronary heart disease mortality in severe and non-severe familial hyper-cholesterolaemia : data from the UK Simon Broome FH register (2019)

Type of publication:
Conference abstract

Author(s):
Humphries S.; Cooper J.; *Capps N.; Durrington P.; Jones B.; McDowell I.; Soran H.; Neil A.

Citation:
Atherosclerosis; Aug 2019; vol. 287

Abstract:
Background and Aims: Background: In 2016 the International Atherosclerosis Society (IAS) proposed that patients with “severe” FH (SFH) should be identified since they might warrant early and more aggressive cholesterol-lowering treatment such as with PCSK9 inhibitors. SFH is diagnosed if LDL-cholesterol (LDLC) >10 mmol/L, or LDLC >8.0 mmol/L plus one high-risk feature, or LDLC >5 mmol/L plus two high-risk features. Here we compare CHD mortality in SFH and non-SFH patients in the UK Simon Broome Register since 1991, when
statin use became routine.
Method(s): 2929 Definite or Possible patients (51% women) aged 20-79 years recruited from 21 UK lipid clinics were followed between 1992-2016. The excess CHD standardised mortality ratio (SMR) compared to the population in England and Wales was calculated (95% Confidence intervals).
Result(s): (67.7%) patients met the SFH definition. Post 1991, the SMR for CHD mortality was significantly (p=0.007) higher for SFH (220(184-261) (34,134 person years, 129 deaths observed, vs 59 expected) compared to non-SFH of 144(98-203) (15,432 person years, 32 observed vs 22 expected). After adjustment for traditional risk factors, the Hazard Ratio for CHD mortality in SFH vs non-SFH was 122 (80-187) p=0.36. Applying UK guidelines for the use of PCSK9i agents, overall ~24% of those in the register are likely to be eligible, but if this were restricted to those with SFH, overall ~16% would qualify.
Conclusion(s): CHD mortality remains elevated in treated FH, especially for SFH, emphasising the importance of optimal lipid-lowering, including the use of novel agents, and management of other risk factors

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Preoperative anemia and outcomes in cardiovascular surgery: systematic review and meta-analysis (2019)

Type of publication:
Systematic Review

Author(s):
*Padmanabhan, Hari; Siau, Keith; *Curtis, Jason; Ng, Alex; Menon, Shyam; Luckraz, Heyman; Brookes, Matthew J

Citation:
The Annals of Thoracic Surgery. Dec 2019; vol. 108 (no. 6); p. 1840-1848

Abstract:
BACKGROUND Pre-operative anemia is common in patients scheduled for cardiac surgery. However, its effect on postoperative outcomes remains controversial. This meta-analysis aimed to clarify the impact of anemia on outcomes following cardiac surgery.METHODS A literature search was conducted on MEDLINE, Embase, Cochrane, and Web of Science databases. The primary outcome was 30-day postoperative or in-hospital mortality. Secondary outcomes included acute kidney injury (AKI), stroke, blood transfusion, and infection. A meta-analytic model was used to determine the differences in the above postoperative outcomes between anemic and non-anemic patients. RESULTS Out of 1103 studies screened, 22 met the inclusion criteria. A total of 23624 (20.6%) out of 114277 patients were anemic. Anemia was associated with increased mortality (odds ratio [OR] 2.74, 95% confidence interval [CI] 2.32-3.24; I2=69.6%; p<0?001), AKI (OR 3.13, 95% CI 2.37-4.12; I2=71.1%; p<0?001), stroke (OR 1.46, 95% CI 1.24-1.72; I2=21.6%; p<0?001), and infection (OR 2.65, 95% CI 1.98-3.55; I2=46.7%; p<0?001). More anemic patients were transfused than non-anemic (33.3 versus 11.9%). No statistically significant association was found between mortality and blood transfusion (OR 1.35, 95% CI 0.92-1.98; I2=83.7%; p=0.12) but we were not able to compare mortality with or without transfusion in those who were or were not anemic. CONCLUSIONS Preoperative anemia is associated with adverse outcomes following cardiac surgery. These findings support the addition of preoperative anemia to future risk prediction models, and as a target for risk modification.

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