Cardiovascular care

Trial of atorvastatin for the primary prevention of cardiovascular events in patients with rheumatoid arthritis (TRACE RA): A multicenter, randomized, placebo controlled trial (2019)

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Type of publication:
Journal article

Author(s):
Kitas GD, Nightingale P, Armitage J, Sattar N, Belch JJF, Symmons DPM; TRACE RA consortium.

Collaborators (137) Kitas G, Belch J, Symmons D, Williams H, Vasishta S, Storey R, Nightingale P, Bruce I, Durrington P, McInnes I, Nightingale P, Sattar N, Situnayake D, Struthers A, Lowe G, Armitage J, Fox K, Haskard D, Dore C, Bosworth A, Kitas G, Belch J, Symmons D, Williams H, Frenneaux M, Edwards C, Emberson J, Bax D, Cobbe S, Stott D, Sturrock R, Macfarlane P, Klocke R, Pullar T, Knight S, Rowe I, Kumar P, Goodson N, Mulherin D, Brzeski M, Gardiner P, Situnayake D, Walker D, Callaghan R, Allen M, McCarey D, George E, Deighton C, Kirkham B, Teh LS, Luqmani R, Chakravarty K, Nixon J, Richards S, Scott D, Woolf T, Prouse P, Packham J, Davies M, DeLord D, O'Neill T, Pande I, Harvie J, Watts R, Rankin E, Papasavvas G, Emery P, Sinha A, Dasgupta B, Bruce I, Creamer P, Zoma A, Walsh D, Van-Laar J, *Capps N, Cairns A, Marguerie C, Kumar N, Abernethy R, Lillicrap M, Ralston S, Makadsi R, Hopkinson N, Tan S, Akil M, Ahmad Y, Adler M, Bukhari M, Sanders P, Roussou E, Binymin K, Hassan A, Hughes R, O'Reilly D, Sainsbury P, Richmond R, Malgorzata M, Nisar M, McEntergart A, Roy D, Marks J, Batley M, McKenna F, Irani M, Harris H, Smyth A, Tunn E, Young A, Thomas J, Hall F, Marshall T, Rao C, Baburaj K, Dixey J, Gendi N, Birrell F, Chelliah G, Teh LS, Morgan A, Fishman D, Knights S, Coady D, Makadsi R, Smith B, Harrison B, Walker D, Siebert S, Chan A, Putchakayala K, Al-Ansari A, Gough A, Naz S, Kumar N, Pyne D, Mahmud T, Patel Y, Isdale A.

Citation:
Arthritis Rheumatol. 2019 Apr 15. doi: 10.1002/art.40892. [Epub ahead of print]

Abstract:
OBJECTIVE:

Rheumatoid arthritis (RA) is associated with increased cardiovascular event (CVE) risk. The impact of statins in RA is not established. We assessed whether atorvastatin is superior to placebo for the primary prevention of CVE in RA patients.

METHODS:

Randomized, double-blind, placebo-controlled trial designed for 80% power at p<0.05 to detect a 32% CVE risk reduction based on an estimated 1.8% per annum (pa) event rate. Patients aged >50 years or with RA duration >10 years; without clinical atherosclerosis, diabetes, or myopathy; received atorvastatin 40mg daily or matching placebo. Primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, transient ischemic attack, or any arterial revascularization. Secondary/tertiary endpoints included plasma lipids and safety.

RESULTS:

3002 patients (mean age 61 years, 74% female) were followed for a median 2.51 years (IQR 1.90-3.49) [7,827 patient-years] – early termination was due to lower than expected event rate (0.77% pa). Among patients allocated atorvastatin 24/1504 (1.6%) had a primary endpoint, compared with 36/1498 (2.4%) on placebo (hazard ratio 0.66, 95%CI 0.39-1.11, p=0.115); adjusted hazard ratio (0.60, 95%CI 0.32-1.15, p=0.127). At trial end, patients on atorvastatin had 0.77±0.04 mmol/L lower LDL-cholesterol compared to placebo (p<0.0001); CRP (mg/L) was also significantly lower on atorvastatin than placebo (2.59 (0.94-6.08) vs. 3.60 (1.47-7.49) – p<0.0001). CVE risk reduction per mmol/L LDLc reduction was 42% (95%CI -14%-70%). Adverse events in the atorvastatin (298 (19.8%)) and placebo (292 (19.5%)) groups were similar.

CONCLUSION:

Atorvastatin 40mg daily was safe and resulted in significantly greater reduction of LDLc than placebo in patients with RA. The 40% (adjusted) CVE risk reduction is consistent with the Cholesterol Treatment Trialists' Collaboration meta-analysis of statin effects in other populations.

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Coronary heart disease mortality in severe vs. non-severe familial hypercholesterolaemia in the Simon Broome Register (2019)

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Type of publication:
Journal article

Author(s):
Humphries, Steve E; Cooper, Jackie A; *Capps, Nigel; Durrington, Paul N; Jones, Ben; McDowell, Ian F W; Soran, Handrean; Neil, Andrew H W; Simon Broome Familial Hyperlipidaemia Register Group

Citation:
Atherosclerosis. 2019 Feb;281:207-212

Abstract:
BACKGROUND AND AIMS The International Atherosclerosis Society (IAS) has proposed that patients with "severe" FH (SFH) would warrant early and more aggressive cholesterol-lowering treatment such as with PCSK9 inhibitors. SFH is diagnosed if LDL-cholesterol (LDLC)>10mmol/L, or LDLC >8.0mmol/L plus one highrisk feature, or LDLC >5mmol/L plus two high-risk features. Here we compare CHD mortality in SFH and nonSFH (NSFH) patients in the UK prospective Simon Broome Register since 1991, when statin use became routine.METHODS 2929 definite or possible PFH patients (51% women) aged 20-79 years were recruited from 21 UK lipid clinics and followed prospectively between 1992 and 2016. The excess CHD standardised mortality ratio (SMR) compared to the England and Wales population was calculated (with 95% confidence intervals).RESULTS1982 (67.7%) patients met the SFH definition. Compared to the non-SFH, significantly (p < 0.001) more SFH patients had diagnosed CHD at baseline (24.6% vs. 17.5%), were current smokers (21.9% vs 10.2%) and had a BMI>30kg/m2 (14.9% vs. 7.8%). 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 NSFH 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. NSFH was 1.22 (0.80-1.87) p=0.36, indicating that the excess risk was largely accounted for by these factors.CONCLUSIONS CHD mortality remains elevated in treated FH, especially for SFH, emphasising the importance of optimal lipid-lowering and management of other risk factors.

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Patient experience within the adult congenital heart disease outreach network: A questionnaire-based study (2018)

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Type of publication:
Journal article

Author(s):

Georgina Ooues, Paul Clift, Sarah Bowater, Sayqa Arif, Andrew Epstein, Neeraj Prasad, Dawn Adamson, Mandy Cummings, Charles Spencer, Paul Woodmansey, Jenny Borley, *Thomas Ingram, Adrian Morley-Davies, William Roberts, Najmi Qureshi, Susan Hawkesford, Nichola Pope, James Anthony, Thomas Gaffey, Sara Thorne, Lucy Hudsmith and On behalf of The West Midlands ACHD Network, UK

Citation:
Journal of Congenital Cardiology; Sep 2018; vol. 2 (no. 1)

Abstract:
Background: Specialist multi-disciplinary care improves outcomes of Adult Congenital Heart Disease (ACHD) patients. Following the NHS England Congenital Heart Disease standards review, the aim is to deliver high quality, patient-centred, care closer to patients' homes. Cardiac investigations performed on the same day of outpatient appointments reduce the non-attendance rates. This young cohort of patients, benefits from comprehensive multi-disciplinary management. We developed a Patient Questionnaire across our West Midlands ACHD network to measure patient experience. Methods: Patient questionnaires were distributed to patients attending outpatient clinics in all 8 Outreach Centres and the Level 1 ACHD Centre (University Hospitals Birmingham). Results: 71 males (55%) and 59 females (45%), median age range 25-34years old (range between 16 and 75years old), returned the questionnaires (n=130). Most patients travelled less than one hour to hospital (93%, n=120) and less than 20miles (86%, n=99). The mean travel distance was 14+/-12.3miles (range 1 to 160miles), with Level 1 ACHD Centre patients travelling a significantly longer distance (mean 29.6+/-44miles) compared to the local Outreach Centres (mean 11.3+/-9miles, p=0.0037). There was a wide variability in the provision of parking, although most patients found the appointment time and location convenient (91%, n=117 and 95%, n=121 respectively). There was also marked variation in the number of electrocardiograms (19-100%) and echocardiograms (0-60%) performed on the same day as their clinic appointment. Most patients felt they were given enough information regarding their condition (85%, n=98), with no significant differences between the centres (p=0.24). Conclusion: To our knowledge, this is the first questionnaire-based study assessing patient experience within the NHS ACHD Outreach network with significantly reduced travel times and maintained high patient satisfaction. There was a wide variation ininvestigations performed and patient information leaflets provided. Standardisation of services is required at allcentres to ensure equity of care, with Specialist Nurses' input and more availability of tests on the day of clinicappointments in all centres.

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Assessment of chronic obstructive airways disease in heart failure : An analysis of current practice (2018)

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Type of publication:
Conference abstract

Author(s):
*Muthusami R.; *Mahmoud M.; *Crawford E.; *Makan A.; *Ahmad N.; *Srinivasan K.S.; *Moudgil H.; *Candassamy N.

Citation:
American Journal of Respiratory and Critical Care Medicine; May 2018; vol. 197

Abstract:
RATIONALE Heart Failure (HF) and Chronic Obstructive Pulmonary Disease (COPD) are global epidemics incurring significant morbidity and mortality with overlapping symptoms & risk factors. Whereas with other coexisting co-morbidities such as with Diabetes Mellitus and Ischaemic Heart Disease, much work has been done to concurrently improve outcomes from both pathologies, whether anything is uniformly undertaken in practice to firstly recognize and secondly improve outcomes from HF and COPD is less understood. The objective here was to establish our current pattern of assessment to identify potential areas of improvement that would enable us to better manage the modern multi-morbid patient. METHODS Electronic medical records of all patients admitted to our District General Hospital (serving fairly static population 250,000) over a 6 month period to end December 2016 and referred internally to our Heart Failure Specialist Team were assessed. Data for all admitted cases were cross-referenced to Electrocardiography (ECHO) and Pulmonary Function Lab Databases. RESULTS 116 patients (63% male) with mean (SD, range) age 74.9 (11.7, 32-100) years had been admitted and of these 37% had died over the subsequent 12 months follow up period. Of the total, 113 (97%) had prior transthoracic cardiac ECHO (updated within a two year window); Mean estimated Left Ventricular Ejection Fraction (LVEF) was 41%. Comparatively, only 31 (27%) patients had undergone Spirometry testing at our centre over the preceding 10 year period and of these approximately half (51%) had shown obstructive spirometry. Collectively, 44 (38%) were known to have any Obstructive Airways Disease with 32 (28%) being COPD but a slightly higher figure at 50 (43%) were on inhaler treatment. . Sub-analysing, the 59 (51%) specifically with Ischaemic Heart Disease as opposed to other causes for Heart Failure (Valvular Heart Disease, Cardiomyopathy etc.) had a higher 12 month mortality rate (49%) as well as higher prevalence of known COPD (32%), higher proportion of patients with obstructive spirometry (65%) and patients on inhaler therapy (45%). Only 2 of the 7 patients on Amiodarone had Spirometry. CONCLUSION The basic provision of spirometry to Heart Failure patients, and in particular those with Ischaemic Heart Disease, needs to be improved with our findings probably consistent with others providing the same models of diagnosis driven care. Our findings are in a population with established Heart Failure and potentially in their final years of life but there may be improved quality of life and care planning, if assessing those presenting earlier.

Iron deficiency in heart failure: A retrospective review of current practice and patient outcomes in a district general hospital (2018)

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Type of publication:
Conference abstract

Author(s):
*Chatrath N.; *Kundu S.; *Makan J.

Citation:
Heart; Jun 2018; vol. 104, Supp 6

Abstract:
Iron deficiency (ID) affects up to 50% of patients with heart failure (HF) with higher rates in decompensated, hospitalised patients.1 ID is associated with poor functional capacity and recurrent hospital admissions. The 2016 European Society of Cardiology (ESC) guidelines for management of HF advocate measurement of ferritin and Transferrin Saturations (TSAT) in all HF patients. ID is defined by serum ferritin <100 mg/L or 100-299 mg/ L and TSAT <20%0.2 Intravenous Iron therapy is recommended for any patient meeting these parameters. This retrospective study looked at the diagnosis and management of ID in HF patients in a district general hospital. All 111 (n=111) inpatients with a diagnosis of HF with reduced ejection fraction (HFrEF), admitted between April-October 2016 were included. The mean age of the population was 75 (30100), 37% female and 63% male. 64% (n=71) were anaemic (Male n=46, Female n=25) as defined by our laboratory haemoglobin reference ranges for gender. Only 51% (n=57) of all patients had Ferritin checked during admission or within 3 months of discharge with an average Ferritin of 161 mg/L (11-1432). 30.6% (n=34) of all patients had absolute iron deficiency (Ferritin <100 mg/L) and 14.4% (n=11) had ferritin in the range 100300 mg/L, in which further TSAT testing to confirm functional iron deficiency is recommended but is not performed locally unless specifically requested by the clinician. Only 4.5% (n=5) of all patients had further investigations looking into causes of ID, including gastro-intestinal work-up. 47.8% (n=53) died in the 1 year follow-up period with 9% (n=10) not surviving past the initial admission. Of the 101 patients surviving the initial admission, there was a total of 135 hospital admissions within the follow-up period, 58% (n=78) of which were directly related to HF. 11.7% of all patients (n=13) were prescribed oral iron therapy on discharge and only 2 out of all patients had intravenous iron therapy during admission or within 6 months of discharge. This study highlights the high readmission and mortality rates of hospitalised HF patients and that ID is an underdiagnosed comorbidity in this population. A new protocol has been proposed which involves mandatory testing of ferritin, and TSAT if required, at the time of diagnosis and during regular follow-up. Local research is underway to further evaluate the benefits of iron replacement in HF and the effects of the proposed protocol on this population.

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Coronary heart disease mortality in treated familial hypercholesterolaemia: Update of the UK Simon Broome FH register (2018)

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Type of publication:
Journal article

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

Citation:
Atherosclerosis; Jul 2018; vol. 274 ; p. 41-46

Abstract:
 Background and aims: Patients with familial hypercholesterolaemia (FH) have an elevated risk of coronary heart disease (CHD). Here we compare changes in CHD mortality in patients with heterozygous (FH) pre 1992, before lipid-lowering therapy with statins was used routinely, and in the periods 1992-2008 and 2008-2016. Methods: 1903 Definite (DFH) and 1650 Possible (PFH) patients (51% women) aged 20-79 years, recruited from 21 lipid clinics in the United Kingdom and followed prospectively between 1980 and 2016 for 67,060 person-years. The CHD standardised mortality ratio (SMR) compared to the population in England and Wales was calculated (with 95% Confidence intervals). Results: There were 585 deaths, including 252 from CHD. Overall, the observed 2.4-fold excess coronary mortality for treated DFH post-1991 was significantly higher than the 1.78 excess for PFH (35% 95% CI 3%-76%). In patients with DFH and established coronary disease, there was a significant excess coronary mortality in all time periods, but in men it was reduced from a 4.83-fold excess (2.32-8.89) pre-1992 to 4.66 (3.46-6.14) in 1992-2008 and 2.51 (1.01-5.17) post-2008, while in women the corresponding values were 7.23 (2.65-15.73), 4.42 (2.70-6.82) and 6.34 (2.06-14.81). Primary prevention in men with DFH resulted in a progressive reduction in coronary mortality over the three time-periods, with no excess mortality evident post-2008 (0.89 (0.29-2.08)), although in women the excess persisted (post-2008 3.65 (1.75-6.72)). Conclusions: The results confirm the benefit of statin treatment in reducing CHD mortality, but suggest that FH patients with pre-existing CHD and women with FH may not be treated adequately.

Optimising patient experience within the ACHD outreach network: A questionnaire based study (2018)

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Type of publication:
Conference abstract

Author(s):
Ooues G.; Clift P.; Bowater S.; Arif S.; Hawkesford S.; Pope N.; Anthony J.; Gaffey T.; Thorne S.; Hudsmith L.; Epstein A.; Prasad N.; Adamson D.; Cummings M.; Spencer C.; Woodmansey P.; *Ingram T.; Morley-Davies A.; Roberts W.; Qureshi N.

Citation:
Heart; Feb 2018; vol. 104, Suppl 2, A12

Abstract:
Purpose The NHS England Congenital Heart Disease standards review is based on a network model to deliver high quality, safe and effective services as locally as possible. We developed a Patient Questionnaire across our Adult Congenital Heart Disease (ACHD) West Midlands network to measure patient experience, satisfaction and to improve services across the network. Methods Patient questionnaires were distributed to patients in all 8 Outreach and the Level 1 ACHD Centre (University Hospital Birmingham). Data was analysed including patients' replies on travel to outpatient clinic, satisfaction on location and timing of their appointment, review by ACHD Specialist Nurse and tests performed, information on their condition and leaflets provided and patients' demographics. Results 130 questionnaires were returned. The majority of patients (67%, n=87) travelled to their appointment with their own car, either alone (36%, n=46) or with a member of their family (44%, n=56). Most patients (93%, n=120) travelled less than one hour to hospital and less than 20 miles (86%, n=99). Patients attending Level 1 Centre appointments travelled a longer distance (mean 29.6+/-44 miles) compared to the Outreach Centres (mean 9.9+/-2.8 miles). Almost all patients found the appointment time and location convenient for them (91%, n=117% and 95%, n=121), and were given enough information regarding their condition (85%, n=98). Conclusion With the development of ACHD Network Outreach clinics to facilitate services and appointments closer to patients' homes, travel times are reduced and high patient satisfaction is maintained.

Link to full-text [NHS OpenAthens account required]

Coronary heart disease mortality in treated Familial Hypercholesterolaemia: Update of the UK Simon Broome FH Register (2017)

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Type of publication:
Conference abstract

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

Citation:
Atherosclerosis Supplements; 2017; vol. 28, Pages 41-46

Abstract:
Background: Guidelines for the management of patients with Familial Hypercholesterolaemia (FH) recommend the use of high intensity statin therapy to reduce subsequent risk of Coronary Heart Disease (CHD). Here we compare changes in CHD mortality in patients with heterozygous (FH) pre 1992 before lipid-lowering therapy with statins was used routinely, and in the periods 1992-2008 and 2008 till the present. Methods: Analysis used 1903 Definite (DFH) and 1650 Possible (PFH) patients (51% women) aged 20-79 years, recruited from 21 lipid clinics in the United Kingdom and followed prospectively between 1980-1991 (6627 personyears) 1992-2008 (43117 person-years) and 2009-2016 (17317 person-years). The excess CHD standardised mortality ratio (SMR) compared to the population in England and Wales was calculated (with 95% Confidence intervals). Results: There were 252 deaths from CHD. Overall, treated DFH patients had a higher CHD SMR than PFH patients (post 1991 35% higher 2.40 (2.00-2.86) vs 1.78 (1.44-2.19) p = 0.03). In treated DFH patients with previous CHD the CHD SMR was significantly elevated at all time periods but in men fell from a 4.83-fold excess (2.32-8.89) pre-1992 to 4.66 (3.46-6.14) in 1992-2008 and 2.51 (1.01-5.17) post 2008, while in women these values were 7.23 (2.65-15.73), 4.42 (2.70-6.82) and 6.34 (2.06-14.81)). In treated DFH men with no previous CHD the CHD SMR fell over the three time periods, and was not significantly elevated post 2008 (0.89 (0.29-2.08), but in women the SMR remained significantly elevated (post 2008 3.65 (1.75-6.72)). Conclusions: The data confirm the major benefit in CHD mortality associated with statin treatment, but suggest that FH patients with pre-existing disease, and women with FH may not be being treated adequately.

HEART UK statement on the management of homozygous familialhypercholesterolaemia in the United Kingdom (2016)

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Type of publication:
Journal article

Author(s):
France M., Rees A., Datta D., Thompson G., *Capps N., Ferns G., Ramaswami U., Seed M., Neely D., Cramb R., Shoulders C., Barbir M., Pottle A., Eatough R., Martin S., Bayly G., Simpson B., Halcox J., Edwards R., Main L., Payne J., Soran H.

Citation:
Atherosclerosis, December 2016, vol./is. 255/(128-139)

Abstract:
This consensus statement addresses the current three main modalities of treatment of homozygous familial hypercholesterolaemia (HoFH): pharmacotherapy, lipoprotein (Lp) apheresis and liver transplantation. HoFH may cause very premature atheromatous arterial disease and death, despite treatment with Lp apheresis combined with statin, ezetimibe and bile acid sequestrants. Two new classes of drug, effective in lowering cholesterol in HoFH, are now licensed in the United Kingdom. Lomitapide is restricted to use in HoFH but, may cause fatty liver and is very expensive. PCSK9 inhibitors are quite effective in receptor defective HoFH, are safe and are less expensive. Lower treatment targets for lipid lowering in HoFH, in line with those for the general FH population, have been proposed to improve cardiovascular outcomes. HEART UK presents a strategy combining Lp apheresis with pharmacological treatment to achieve these targets in the United Kingdom (UK). Improved provision of Lp apheresis by use of existing infrastructure for extracorporeal treatments such as renal dialysis is promoted. The clinical management of adults and children with HoFH including advice on pregnancy and contraception are addressed. A premise of the HEART UK strategy is that the risk of early use of drug treatments beyond their licensed age restriction may be balanced against risks of liver transplantation or ineffective treatment in severely affected patients. This may be of interest beyond the UK.

Comparison of the size of persistent foramen ovale and atrial septal defects in divers with shunt-related decompression illness and in the general population (2015)

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Type of publication:
Journal article

Author(s):
Wilmshurst P.T., Morrison W.L., Walsh K.P., Pearson M.J., Nightingale S.

Citation:
Diving and Hyperbaric Medicine, June 2015, vol./is. 45/2(89-93)

Abstract:
Introduction: Decompression illness (DCI) is associated with a right-to-left shunt, such as persistent foramen ovale (PFO), atrial septal defect (ASD) and pulmonary arteriovenous malformations. About one-quarter of the population have a PFO, but considerably less than one-quarter of divers suffer DCI. Our aim was to determine whether shunt-related DCI occurs mainly or entirely in divers with the largest diameter atrial defects. Methods: Case control comparison of diameters of atrial defects (PFO and ASD) in 200 consecutive divers who had transcatheter closure of an atrial defect following shunt-related DCI and in an historic group of 263 individuals in whom PFO diameter was measured at post-mortem examination. Results: In the divers who had experienced DCI, the median atrial defect diameter was 10 mm and the mean (standard deviation) was 9.9 (3.6) mm. Among those in the general population who had a PFO, the median diameter was 5 mm and mean was 4.9 (2.6) mm. The difference between the two groups was highly significant (P < 0.0001). Of divers with shuntrelated DCI, 101 (50.5%) had an atrial defect 10 mm diameter or larger, but only 1.3% of the general population studied had a PFO that was 10 mm diameter of larger. Conclusions: The risk of a diver suffering DCI is related to the size of the atrial defect rather than just the presence of a defect.

Link to more details or full-text: