- Email: [email protected]
Establishing a familial hypercholesterolaemia register - The first year
Atherosclerosis Supplements 36 (2019) 24e27
Contents lists available at ScienceDirect
Atherosclerosis Supplements journal homepage: www.elsevier.com/locate/atherosclerosis
Establishing a familial hypercholesterolaemia register - The first year Myra Tilney a, b, * a
Department of Medicine, Faculty of Medicine and Surgery, Mater Dei Hospital, University of Malta, B'kara Bypass, Malta Dept of Primary Care & Public Health, School of Public Health, 319, Global eHealth Unit, Imperial College London, Reynolds Bldg, St Dunstan's Rd, London, W6 8RP, UK b
a b s t r a c t Background and aims: Familial hypercholesterolemia (FH) is an autosomal dominant condition raising the risk of premature cardiovascular disease up to twentyfold.[1] [2] It is under-diagnosed and undertreated, in spite of availability of effective treatment. Registers are recommended to assist in the recognition and improvement of the condition since treatment reduces morbidity and mortality. Disease registers enable longitudinal review and the application of continuous quality improvement methodology. The aims of this paper are to describe the process of setting up a new FH register in Malta based on phenotype, the preliminary results achieved, the barriers encountered, how these were overcome, and future plans for development. Methods: The registry was established as an observational clinical study designed for a small healthcare system with limited resources. Effective process design requires attention to standards, capacity, outcome measurement and feedback, which have been incorporated. Results: 43 individuals have been registered applying Dutch Lipid Clinic Network standards, including 9 Definite, 16 Probable and 18 Possible FH. Cascade testing has identified three younger, and one older FH individuals; amenable risk factors and target outcomes are available for feedback and action. Barriers included insufficient infrastructure, limited stakeholder involvement, time limitations impacting clinical care and data collection, poor recognition, awareness and referral, and limited cascade testing. Overcoming these required persistence, reorganizing clinical work, with some assistance from clinic nurses, forward planning to involve patients and raising FH awareness through presentations to various audiences. Conclusions: During this year the register was established and is functional: awareness is being raised. Future steps will target process improvement for effectiveness and sustainability. © 2019 Elsevier B.V. All rights reserved.
1. Introduction The stimulus to set up an FH Register was triggered by the FH Global Collaboration [3]. I provide a Lipid Clinic service, together with a colleague; referrals include both primary and secondary dyslipidaemias, for primary, secondary and tertiary prevention and management-but the clinic did not register or list specific causation or management. A number of patients' dylipidaemia was less responsive, and had been identified as Familial Hypercholesterolemia on clinical grounds using international criteria. Process design combined with a continuous quality improvement
* Department of Medicine, Faculty of Medicine and Surgery, Mater Dei Hospital, University of Malta, B'kara Bypass, Malta. E-mail addresses: [email protected], [email protected]. https://doi.org/10.1016/j.atherosclerosissup.2019.01.005 1567-5688/© 2019 Elsevier B.V. All rights reserved.
approaches have been applied in industry [4,5] and healthcare [6], to improve outcomes in various areas, and are now advocated for the management of FH [7]. The logical approach appealed and it was natural to try to change ‘routine work’ and collect ‘data for feedback’ using continuous quality improvement methodology [8] to improve patient care. 1.1. The context Cardiovascular diseases are an important cause of premature mortality in Malta, accounting for 17.1% of Premature Years of Life Lost under 65 years (PYLL-65) in 2013 [9]; FH is likely to be a contributor to this statistic. The population of Malta is 460,297 [10]; with an estimated prevalence of FH ranging from 920 to 1841 (based on prevalence of 1:500 to 1:250). The Lipid Clinic is based at Mater Dei Hospital, the only acute general hospital and is provided
M. Tilney / Atherosclerosis Supplements 36 (2019) 24e27
25
by two consultant physicians supported by nursing, dietetics and lifestyle clinics. Genetic tests for FH are not yet available on the health service and there is a dearth of information as to what genotypes or mutations are to be found in the Maltese population. This situation is not unique, and may be of interest to clinicians in similar settings.
phenotypes; initially first degree relatives are identified and invited to clinic for screening, alternatively, if deferred, a note is provided for the patient to give to relatives to show to their general practitioner.
2. Aims
The taxation-based healthcare system provides coverage with free at point of care services and medication; however, preventive services are not yet fully developed [19]. Patients are advised regarding dietary and lifestyle changes-which although insufficient, are an important part of their management. Nurses trained in lifestyle management and dieticians are available for support. Intermediate and high intensity statins are available at no charge, as are fibrates and colestyramine, however ezetimibe and PCSK9 inhibitors are only available out of pocket. Lipid apheresis is not available.
In setting up a registry, a number of aims are being addressed: To establish a standardized clinical register of FH patients in Malta To facilitate cascade testing To facilitate overall review, enabling feedback and improving quality of care To enable longitudinal outcomes review
2.2. Availability of therapies
2.3. Preliminary results 2.1. Patients and methods After reviewing the evidence and recommendations for registries [11], and specifically FH registers [7,12e14], a clinical observational study [11] was designed, justified by the dearth of information on the condition both nationally and internationally. A protocol was prepared, identifying the diagnostic criteria for inclusion and the data to be collected (Table 1). The Dutch Lipid Clinic Network (DLCN) criteria [1,15,16] were formally listed as the diagnostic standard, with recruitment planned from Lipid Clinic and those referred to outpatients for specialist assessment for dyslipidaemias. The data to be collected was drawn up from the literature and an exhaustive list of potential data (including outcomes of interest) from the collaborative registry [3]. Patient Information sheets and consent forms were prepared in English and Maltese, with paediatric age-appropriate versions also. The other clinician providing the Lipid Clinic service was invited and accepted to participate. Approval was requested and obtained for data processing and protection, and managerial approval in both primary and secondary care, since patients could be seen in both areas. The study protocol conforms with the Declaration of Helsinki (1975) edition [17]; it was reviewed and approved by the University Research Ethics committee. Data generated will be retained under the standards established by the Declaration of Taipei (2016) [18], and all results will be anonymised. Once the necessary ethical and regulatory authorisations were obtained from the competent authorities, the register commenced in January 2017. After full written informed consent is obtained, data is inserted into Excel (Microsoft) spreadsheets which are stored securely with real-time back up. The data entered reflects routine clinical practice and does not require any additional investigations to be carried out over and above standard care. Cascade testing is based on
From January 2017 to January 2018, data was collected from 43 patients ranging from 24 to 70 years of age; all those invited for inclusion accepted, bar one. Nine satisfy the DLCN criteria for Definite FH, sixteen satisfy the DLCN criteria for Probable FH, and eighteen for Possible FH. Those classifying as Definite FH are all Caucasian, and include four men and five women; their characteristics are listed in Table 2. Although the numbers are small, they give a clear indication as to the detail that will be collected. Four out of nine patients had overt cardiovascular disease-one of these is a current smoker, with another smoker who is asymptomatic. All are on high intensity statins-bar one woman who refuses any treatment after developing statin-related myopathy, and another who is on a lower dose of rosuvastatin due to adverse effects. Only three out of the nine ‘Definite FH’ patients are at target. Cascade testing is ongoing and has resulted in the identification of four new patientsthree younger and one older individual. 3. Discussion The establishment of this register has resulted in the formal listing of FH patients; these are still less than 5% of the estimated prevalence in the country. Many patients are most likely under the care of cardiologists and other disciplines. Improving detection is a priority, requiring raising awareness and involving patients more closely. The lack of identification of children is of concern, since early treatment is recommended to reduce the risk of cardiovascular events [20]. However, current guidelines recommend that paediatric assessment be carried out after confirming the presence of a genetic mutation in an index case [21,22]. The high prevalence of coronary artery disease is in keeping with the literaturealthough it seems higher [2], but the numbers are small. The register will facilitate better care by enabling better targeting of
Table 1 Data components being collected. Demography Family history Personal medical history Genetic data (only if available: this is not collected routinely) Physical Examination Laboratory results including highest lipid profile/current results Current treatment-Lipid Lowering/other treatment Investigations targeting the cardiovascular system (ECG, Echocardiogram, Ultrasound/ABI, Coronary Calcium score/Coronary angiography Subsequent updates Outcomes
26
M. Tilney / Atherosclerosis Supplements 36 (2019) 24e27 Table 2 Baseline characteristics of Definite FH (DLCN above 9)a Period: January 2017eJanuary 2018 N ¼ 9, (4 M/5F). Age Range
24e70
Caucasian Formal Diagnosis DLCN Family history of dyslipidaemia Active smoker Coronary artery disease Myocardial infarction CABG PCI Peripheral vascular disease Hypertension Diabetes Mellitus Highest LDL (mmol/Li) (Median)(Interquartile ranges) Current LDL (mmol/Li) (Median)(Interquartile ranges) On statins currently At LDL target (as per ESC/EAS guidelines [20])
100% 100% 9e19 100% 22% 44% 11% 11% 11% 22% 33% 11% 8.74, (8.45e9.44) 3.61 (2.91e4.54) 89% 33% overall(43% of those on statins)
a In the absence of genetic testing, the data for ‘Definite FH’ are presented as are they are most likely to be truly representative of FH.
interventions e.g. for smokers and lower LDL levels. Finally, one patent refused inclusion within the register citing privacy concerns.
entertaining the diagnosis of FH is lower [27]-so in the absence of nationally validated data, the relevant data tables [27] are consulted.
3.1. Barriers to establishing an effective and sustainable register 3.2. Next steps 3.1.1. Inadequate resourcing-both local and national The lack of infrastructural support is the major long-term challenge to maintaining the register. During the initial stage, relevant stakeholders were approached (including health information, hospital authorities, genetics, amongst others) to identify whether any support could be provided, however, resource constraints did not permit. Little support was available for the time and effort required for registry design and preparation of the relevant documentation, and necessary authorisations. More consultation time is required with patients, obtaining written informed consent, collating and entering data in real time. Effective data capture is time consuming and is not yet adequately geared to assist analysis; using the spreadsheet as part of the record can partly offset this, but is not ideal. In addition, cascade testing has become more frequent and formalized; the clinic nurses organise the logistics, and adequate time is allocated for clinical review. Finally, data curation, analysis, and process improvement are all time consuming-generally post-clinic. The optimal long term solution would be to incorporate the register into an electronic medical record. 3.1.2. Poor recognition and referral Low awareness and patient identification provide another barrier; various initiatives aiming to raise awareness include approaching the laboratory to flag lipid profiles suggestive of FH (as suggested in the literature [21]), as well as presenting to various audiences including the Maltese Cardiac Society [23], to general practitioners and primary care nurses and professions allied to medicine [24], and to public health physicians [25]. Cascade testing is initiated for those patients identified phenotypically as definite or probable FH, once they give consent-starting with their offspring, which is usually quite straightforward. Since practice is based on phenotype, there is less concern-or awareness regarding insurance and other related implications [26]. Inviting siblings can be sensitive, for a variety of reasons-ranging from a reluctance by the patient to inform siblings, to ‘difficult’ relationships, and also because relatives may already be under the care of another clinician. This is an unresolved area requiring refinement. In cascade testing first degree relatives the LDL threshold for
The registration process was designed to enable data collection to start in our context. The aims and outcome measures were selected to facilitate improvement -and are being used as a basis for iterative development using quality improvement methodology [8]. By adopting a Plan-Do-Study-Act (PDSA) approach, the register will incrementally help to address the steps needed to improve awareness and patient identification. A website could raise awareness by targeting patients, general practitioners and the public via a secure online presence, initially providing information. Other possible interventions targeting referral include financial reward-this could be important for private practitioners considering that 60% of primary care is provided by the private sector [19]; alternatively designing a shared care type of system might address the inherent perverse incentive and inadequate resourcing concurrently. Stakeholder involvement is key to the long term success of the registry and will be pursued by setting up an advisory board (including patient and other representatives e.g. cardiology, general practice, genetics, paediatrics, lipid clinic, health information, IT) with external expert input. Patient representation (which is not well developed in Maltese healthcare) will be encouraged. Pharma could possibly assist the process-although it cannot dictate the agenda. Cascade testing can be improved through the introduction of genetic testing, and involvement of geneticists. Improving liaison with general practitioners would facilitate the process, as would family tree software. To date forward cascade testing has been practiced-but in future, reverse cascade testing [28] (although unproven), has promise, especially if combined with routine paediatric review incorporating a family history of premature cardiovascular disease. 4. Conclusion During this first year, the register has facilitated better recognition and management of FH patients- and will hopefully impact on long term cardiovascular outcomes. However, it is clear that it will require better recognition and referral to provide a complete
M. Tilney / Atherosclerosis Supplements 36 (2019) 24e27
picture of FH in Malta. Conflicts of interest I have received consultation fees from Sanofi. Author contribution The article was designed, and written by the author. Funding This research was not directly funded by any sponsors. There was no input by any sponsors in terms of the research conduct, study design, data collection, analysis or interpretation. Acknowledgement The contribution of Dr Conrad Azzopardi, Consultant Physician, for his patient data is gratefully acknowledged. References [1] Nordestgaard BG, et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J 2013;34(45). 3478-90a. [2] Mundal L, et al. Cardiovascular disease mortality in patients with genetically verified familial hypercholesterolemia in Norway during 1992e2013. European Journal of Preventive Cardiology 2016;24(2):137e44. [3] Familial Hypercholesterolaemia Studies Collaboration EAS, et al. Pooling and expanding registries of familial hypercholesterolaemia to assess gaps in care and improve disease management and outcomes: rationale and design of the global EAS Familial Hypercholesterolaemia Studies Collaboration. Atherosclerosis Suppl 2016;22:1e32. [4] Deming W. Out of the crisis. Cambridge: Cambridge University Press; 1986. [5] Juran JM, FM G. Quality planning and analysis. New York: McGraw-Hill; 1980. [6] Batalden PB. Building knowledge for quality improvement in healthcare: an introductory glossary. J Qual Assur 1991;13(5):8e12. [7] Genest, J., et al., Canadian cardiovascular society position statement on familial hypercholesterolemia. Can J Cardiol. 30(12): p. 1471e1481. [8] Rubenstein L, et al. How can we recognize continuous quality improvement? Int J Qual Health Care 2014;26(1):6e15. [9] Directorate for Health Information and Research. Annual mortality report. 2013. [10] National Statistics Office Malta. Economic and financial data for Malta. 2018 [cited 2018 29th March 2018]; Available from: https://nso.gov.mt/en/nso/
27
National_Summary_Data_Page/Pages/NSDP.aspx. [11] Gliklich R, Dreyer N, Leavy M. Registries for evaluating patient registries: a user's guide. In: AHRQ methods for effective health care. Rockville, MD: Agency for Healthcare Research and Quality (US); 2014. €rz, and T. Grammer, Establishment of a nationwide cascade [12] Schmidt, N., W. Ma screening program and register for familial hypercholestrolemia in Germanycare high. Atherosclerosis. 252: p. e31-e32. [13] Ellis KL, Pang J, Watts GF. Registries, codifications and cardiovascular outcomes in familial hypercholesterolaemia. Eur J Prev Cardiol 2017;24(2): 133e6. [14] Watts GF, et al. Integrated guidance on the care of familial hypercholesterolaemia from the International FH Foundation. Eur J Prev Cardiol 2015;22(7):849e54. [15] Austin MA, et al. Genetic causes of monogenic heterozygous familial hypercholesterolemia: a HuGE prevalence review. Am J Epidemiol 2004;160(5): 407e20. [16] Haase A, Goldberg AC. Identification of people with heterozygous familial hypercholesterolemia. Curr Opin Lipidol 2012;23(4):282e9. [17] World Medical Association. Declaration of Helsinki. 1975. [18] World Medical Association. WMA Declaration of Taiepei on ethical considerations regarding health databases and biobanks. 2016. Available from: https://www.wma.net/policies-post/wma-declaration-of-taipei-on-ethicalconsiderations-regarding-health-databases-and-biobanks/. [19] Azzopardi Muscat N, et al. Malta: health system review. In: Health systems in transition; 2014. p. 1e97. [20] Catapano AL, et al. ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J 2016;37(39):2999e3058. 2016. [21] Watts GF, et al. A model of care for familial hypercholesterolaemia: key role for clinical biochemistry. Clin Biochem Rev 2012;33(1):25e31. [22] NICE. People at risk of familial hypercholesterolaemia should have DNA test, says NICE. BMJ 2017;359:j5112. [23] Maltese cardiac society. In: Maltese cardiac society meeting 2017 (programme); 2017 [cited 2018 21st March 2018]; Available from: https://www. mcardios.org/conference-2017-programme. [24] Primary Care Department. In: 9th biennial primary health care department conference 2017; 2017 [cited 2018 21st March 2018]; webpage]. Available from: https://www.um.edu.mt/newspoint/events/happeninginmalta/2017/ 10/9thbiennialprimaryhealthcaredepartmentconference2017. [25] Malta Association of Public Health Medicine. In: National public health symposium 2017; 2017 [cited 2018 21st March 2018]; Symposium programme]. Available from: https://maphm.files.wordpress.com/2017/10/maphmsymposium-2017-detailed-programme.pdf. [26] Will CM, Armstrong D, Marteau TM. Genetic unexceptionalism: clinician accounts of genetic testing for familial hypercholesterolaemia. Soc Sci Med 2010;71(5):910e7. [27] Starr B, et al. Development of sensitive and specific age- and gender-specific low-density lipoprotein cholesterol cutoffs for diagnosis of first-degree relatives with familial hypercholesterolaemia in cascade testing. In: Clinical chemistry and laboratory medicine; 2008. p. 791. [28] Martin AC, et al. Beyond cascade screening: detection of familial hypercholesterolaemia at childhood immunization and other strategies. Curr Opin Lipidol 2017;28(4):321e7.
Contents lists available at ScienceDirect
Atherosclerosis Supplements journal homepage: www.elsevier.com/locate/atherosclerosis
Establishing a familial hypercholesterolaemia register - The first year Myra Tilney a, b, * a
Department of Medicine, Faculty of Medicine and Surgery, Mater Dei Hospital, University of Malta, B'kara Bypass, Malta Dept of Primary Care & Public Health, School of Public Health, 319, Global eHealth Unit, Imperial College London, Reynolds Bldg, St Dunstan's Rd, London, W6 8RP, UK b
a b s t r a c t Background and aims: Familial hypercholesterolemia (FH) is an autosomal dominant condition raising the risk of premature cardiovascular disease up to twentyfold.[1] [2] It is under-diagnosed and undertreated, in spite of availability of effective treatment. Registers are recommended to assist in the recognition and improvement of the condition since treatment reduces morbidity and mortality. Disease registers enable longitudinal review and the application of continuous quality improvement methodology. The aims of this paper are to describe the process of setting up a new FH register in Malta based on phenotype, the preliminary results achieved, the barriers encountered, how these were overcome, and future plans for development. Methods: The registry was established as an observational clinical study designed for a small healthcare system with limited resources. Effective process design requires attention to standards, capacity, outcome measurement and feedback, which have been incorporated. Results: 43 individuals have been registered applying Dutch Lipid Clinic Network standards, including 9 Definite, 16 Probable and 18 Possible FH. Cascade testing has identified three younger, and one older FH individuals; amenable risk factors and target outcomes are available for feedback and action. Barriers included insufficient infrastructure, limited stakeholder involvement, time limitations impacting clinical care and data collection, poor recognition, awareness and referral, and limited cascade testing. Overcoming these required persistence, reorganizing clinical work, with some assistance from clinic nurses, forward planning to involve patients and raising FH awareness through presentations to various audiences. Conclusions: During this year the register was established and is functional: awareness is being raised. Future steps will target process improvement for effectiveness and sustainability. © 2019 Elsevier B.V. All rights reserved.
1. Introduction The stimulus to set up an FH Register was triggered by the FH Global Collaboration [3]. I provide a Lipid Clinic service, together with a colleague; referrals include both primary and secondary dyslipidaemias, for primary, secondary and tertiary prevention and management-but the clinic did not register or list specific causation or management. A number of patients' dylipidaemia was less responsive, and had been identified as Familial Hypercholesterolemia on clinical grounds using international criteria. Process design combined with a continuous quality improvement
* Department of Medicine, Faculty of Medicine and Surgery, Mater Dei Hospital, University of Malta, B'kara Bypass, Malta. E-mail addresses: [email protected], [email protected]. https://doi.org/10.1016/j.atherosclerosissup.2019.01.005 1567-5688/© 2019 Elsevier B.V. All rights reserved.
approaches have been applied in industry [4,5] and healthcare [6], to improve outcomes in various areas, and are now advocated for the management of FH [7]. The logical approach appealed and it was natural to try to change ‘routine work’ and collect ‘data for feedback’ using continuous quality improvement methodology [8] to improve patient care. 1.1. The context Cardiovascular diseases are an important cause of premature mortality in Malta, accounting for 17.1% of Premature Years of Life Lost under 65 years (PYLL-65) in 2013 [9]; FH is likely to be a contributor to this statistic. The population of Malta is 460,297 [10]; with an estimated prevalence of FH ranging from 920 to 1841 (based on prevalence of 1:500 to 1:250). The Lipid Clinic is based at Mater Dei Hospital, the only acute general hospital and is provided
M. Tilney / Atherosclerosis Supplements 36 (2019) 24e27
25
by two consultant physicians supported by nursing, dietetics and lifestyle clinics. Genetic tests for FH are not yet available on the health service and there is a dearth of information as to what genotypes or mutations are to be found in the Maltese population. This situation is not unique, and may be of interest to clinicians in similar settings.
phenotypes; initially first degree relatives are identified and invited to clinic for screening, alternatively, if deferred, a note is provided for the patient to give to relatives to show to their general practitioner.
2. Aims
The taxation-based healthcare system provides coverage with free at point of care services and medication; however, preventive services are not yet fully developed [19]. Patients are advised regarding dietary and lifestyle changes-which although insufficient, are an important part of their management. Nurses trained in lifestyle management and dieticians are available for support. Intermediate and high intensity statins are available at no charge, as are fibrates and colestyramine, however ezetimibe and PCSK9 inhibitors are only available out of pocket. Lipid apheresis is not available.
In setting up a registry, a number of aims are being addressed: To establish a standardized clinical register of FH patients in Malta To facilitate cascade testing To facilitate overall review, enabling feedback and improving quality of care To enable longitudinal outcomes review
2.2. Availability of therapies
2.3. Preliminary results 2.1. Patients and methods After reviewing the evidence and recommendations for registries [11], and specifically FH registers [7,12e14], a clinical observational study [11] was designed, justified by the dearth of information on the condition both nationally and internationally. A protocol was prepared, identifying the diagnostic criteria for inclusion and the data to be collected (Table 1). The Dutch Lipid Clinic Network (DLCN) criteria [1,15,16] were formally listed as the diagnostic standard, with recruitment planned from Lipid Clinic and those referred to outpatients for specialist assessment for dyslipidaemias. The data to be collected was drawn up from the literature and an exhaustive list of potential data (including outcomes of interest) from the collaborative registry [3]. Patient Information sheets and consent forms were prepared in English and Maltese, with paediatric age-appropriate versions also. The other clinician providing the Lipid Clinic service was invited and accepted to participate. Approval was requested and obtained for data processing and protection, and managerial approval in both primary and secondary care, since patients could be seen in both areas. The study protocol conforms with the Declaration of Helsinki (1975) edition [17]; it was reviewed and approved by the University Research Ethics committee. Data generated will be retained under the standards established by the Declaration of Taipei (2016) [18], and all results will be anonymised. Once the necessary ethical and regulatory authorisations were obtained from the competent authorities, the register commenced in January 2017. After full written informed consent is obtained, data is inserted into Excel (Microsoft) spreadsheets which are stored securely with real-time back up. The data entered reflects routine clinical practice and does not require any additional investigations to be carried out over and above standard care. Cascade testing is based on
From January 2017 to January 2018, data was collected from 43 patients ranging from 24 to 70 years of age; all those invited for inclusion accepted, bar one. Nine satisfy the DLCN criteria for Definite FH, sixteen satisfy the DLCN criteria for Probable FH, and eighteen for Possible FH. Those classifying as Definite FH are all Caucasian, and include four men and five women; their characteristics are listed in Table 2. Although the numbers are small, they give a clear indication as to the detail that will be collected. Four out of nine patients had overt cardiovascular disease-one of these is a current smoker, with another smoker who is asymptomatic. All are on high intensity statins-bar one woman who refuses any treatment after developing statin-related myopathy, and another who is on a lower dose of rosuvastatin due to adverse effects. Only three out of the nine ‘Definite FH’ patients are at target. Cascade testing is ongoing and has resulted in the identification of four new patientsthree younger and one older individual. 3. Discussion The establishment of this register has resulted in the formal listing of FH patients; these are still less than 5% of the estimated prevalence in the country. Many patients are most likely under the care of cardiologists and other disciplines. Improving detection is a priority, requiring raising awareness and involving patients more closely. The lack of identification of children is of concern, since early treatment is recommended to reduce the risk of cardiovascular events [20]. However, current guidelines recommend that paediatric assessment be carried out after confirming the presence of a genetic mutation in an index case [21,22]. The high prevalence of coronary artery disease is in keeping with the literaturealthough it seems higher [2], but the numbers are small. The register will facilitate better care by enabling better targeting of
Table 1 Data components being collected. Demography Family history Personal medical history Genetic data (only if available: this is not collected routinely) Physical Examination Laboratory results including highest lipid profile/current results Current treatment-Lipid Lowering/other treatment Investigations targeting the cardiovascular system (ECG, Echocardiogram, Ultrasound/ABI, Coronary Calcium score/Coronary angiography Subsequent updates Outcomes
26
M. Tilney / Atherosclerosis Supplements 36 (2019) 24e27 Table 2 Baseline characteristics of Definite FH (DLCN above 9)a Period: January 2017eJanuary 2018 N ¼ 9, (4 M/5F). Age Range
24e70
Caucasian Formal Diagnosis DLCN Family history of dyslipidaemia Active smoker Coronary artery disease Myocardial infarction CABG PCI Peripheral vascular disease Hypertension Diabetes Mellitus Highest LDL (mmol/Li) (Median)(Interquartile ranges) Current LDL (mmol/Li) (Median)(Interquartile ranges) On statins currently At LDL target (as per ESC/EAS guidelines [20])
100% 100% 9e19 100% 22% 44% 11% 11% 11% 22% 33% 11% 8.74, (8.45e9.44) 3.61 (2.91e4.54) 89% 33% overall(43% of those on statins)
a In the absence of genetic testing, the data for ‘Definite FH’ are presented as are they are most likely to be truly representative of FH.
interventions e.g. for smokers and lower LDL levels. Finally, one patent refused inclusion within the register citing privacy concerns.
entertaining the diagnosis of FH is lower [27]-so in the absence of nationally validated data, the relevant data tables [27] are consulted.
3.1. Barriers to establishing an effective and sustainable register 3.2. Next steps 3.1.1. Inadequate resourcing-both local and national The lack of infrastructural support is the major long-term challenge to maintaining the register. During the initial stage, relevant stakeholders were approached (including health information, hospital authorities, genetics, amongst others) to identify whether any support could be provided, however, resource constraints did not permit. Little support was available for the time and effort required for registry design and preparation of the relevant documentation, and necessary authorisations. More consultation time is required with patients, obtaining written informed consent, collating and entering data in real time. Effective data capture is time consuming and is not yet adequately geared to assist analysis; using the spreadsheet as part of the record can partly offset this, but is not ideal. In addition, cascade testing has become more frequent and formalized; the clinic nurses organise the logistics, and adequate time is allocated for clinical review. Finally, data curation, analysis, and process improvement are all time consuming-generally post-clinic. The optimal long term solution would be to incorporate the register into an electronic medical record. 3.1.2. Poor recognition and referral Low awareness and patient identification provide another barrier; various initiatives aiming to raise awareness include approaching the laboratory to flag lipid profiles suggestive of FH (as suggested in the literature [21]), as well as presenting to various audiences including the Maltese Cardiac Society [23], to general practitioners and primary care nurses and professions allied to medicine [24], and to public health physicians [25]. Cascade testing is initiated for those patients identified phenotypically as definite or probable FH, once they give consent-starting with their offspring, which is usually quite straightforward. Since practice is based on phenotype, there is less concern-or awareness regarding insurance and other related implications [26]. Inviting siblings can be sensitive, for a variety of reasons-ranging from a reluctance by the patient to inform siblings, to ‘difficult’ relationships, and also because relatives may already be under the care of another clinician. This is an unresolved area requiring refinement. In cascade testing first degree relatives the LDL threshold for
The registration process was designed to enable data collection to start in our context. The aims and outcome measures were selected to facilitate improvement -and are being used as a basis for iterative development using quality improvement methodology [8]. By adopting a Plan-Do-Study-Act (PDSA) approach, the register will incrementally help to address the steps needed to improve awareness and patient identification. A website could raise awareness by targeting patients, general practitioners and the public via a secure online presence, initially providing information. Other possible interventions targeting referral include financial reward-this could be important for private practitioners considering that 60% of primary care is provided by the private sector [19]; alternatively designing a shared care type of system might address the inherent perverse incentive and inadequate resourcing concurrently. Stakeholder involvement is key to the long term success of the registry and will be pursued by setting up an advisory board (including patient and other representatives e.g. cardiology, general practice, genetics, paediatrics, lipid clinic, health information, IT) with external expert input. Patient representation (which is not well developed in Maltese healthcare) will be encouraged. Pharma could possibly assist the process-although it cannot dictate the agenda. Cascade testing can be improved through the introduction of genetic testing, and involvement of geneticists. Improving liaison with general practitioners would facilitate the process, as would family tree software. To date forward cascade testing has been practiced-but in future, reverse cascade testing [28] (although unproven), has promise, especially if combined with routine paediatric review incorporating a family history of premature cardiovascular disease. 4. Conclusion During this first year, the register has facilitated better recognition and management of FH patients- and will hopefully impact on long term cardiovascular outcomes. However, it is clear that it will require better recognition and referral to provide a complete
M. Tilney / Atherosclerosis Supplements 36 (2019) 24e27
picture of FH in Malta. Conflicts of interest I have received consultation fees from Sanofi. Author contribution The article was designed, and written by the author. Funding This research was not directly funded by any sponsors. There was no input by any sponsors in terms of the research conduct, study design, data collection, analysis or interpretation. Acknowledgement The contribution of Dr Conrad Azzopardi, Consultant Physician, for his patient data is gratefully acknowledged. References [1] Nordestgaard BG, et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J 2013;34(45). 3478-90a. [2] Mundal L, et al. Cardiovascular disease mortality in patients with genetically verified familial hypercholesterolemia in Norway during 1992e2013. European Journal of Preventive Cardiology 2016;24(2):137e44. [3] Familial Hypercholesterolaemia Studies Collaboration EAS, et al. Pooling and expanding registries of familial hypercholesterolaemia to assess gaps in care and improve disease management and outcomes: rationale and design of the global EAS Familial Hypercholesterolaemia Studies Collaboration. Atherosclerosis Suppl 2016;22:1e32. [4] Deming W. Out of the crisis. Cambridge: Cambridge University Press; 1986. [5] Juran JM, FM G. Quality planning and analysis. New York: McGraw-Hill; 1980. [6] Batalden PB. Building knowledge for quality improvement in healthcare: an introductory glossary. J Qual Assur 1991;13(5):8e12. [7] Genest, J., et al., Canadian cardiovascular society position statement on familial hypercholesterolemia. Can J Cardiol. 30(12): p. 1471e1481. [8] Rubenstein L, et al. How can we recognize continuous quality improvement? Int J Qual Health Care 2014;26(1):6e15. [9] Directorate for Health Information and Research. Annual mortality report. 2013. [10] National Statistics Office Malta. Economic and financial data for Malta. 2018 [cited 2018 29th March 2018]; Available from: https://nso.gov.mt/en/nso/
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