New treatment for familial
hypercholesterolemia: Impact on diet and quality of life
A qualitative interview study on patients on anti-PCSK9 treatment
Jorun Birgitta Bø
Master thesis at the Department of Nutrition Institute of Basic Medical Science
Faculty of Medicine UNIVERSITY OF OSLO
May 2018
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New treatment for familial
hypercholesterolemia: Impact on diet and quality of life
A qualitative interview study on patients on anti-PCSK9 treatment
Master thesis by Jorun Birgitta Bø
Supervisors: Kjetil Retterstøl, Margareta Wandel and Gisle Langslet
Master thesis at the Department of Nutrition Institute of Basic Medical Science
Faculty of Medicine UNIVERSITY OF OSLO
May 2018
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© Jorun Birgitta Bø 2018
New treatment for familial hypercholesterolemia: Impact on diet and quality of life. A qualitative interview study on patients on anti-PCSK9 treatment
Jorun Birgitta Bø http://www.duo.uio.no/
Print: Reprosentralen, University of Oslo
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Abstract
Background: Familial hypercholesterolemia (FH) is a genetically inherited disease
characterized by high levels of low-density lipoprotein cholesterol (LDL-C) in plasma and an increased risk of cardiovascular disease. Treatment of FH involves lipid-lowering medication and diet. Unfortunately, many patients do not reach their required LDL-C treatment goals when using conventional treatment. Decreased quality of life (QOL) has been reported in patients who do not reach their treatment goals. The new lipid-lowering medication, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, successfully reduce cholesterol levels below target goal levels. Yet, there is little available information on how patients experience this new medication and how it affects different aspects of life.
Aim: The aim of this study was to explore how the PCSK9 inhibitors affected the participants’ view of their diagnosis, the dietary treatment and their QOL.
Subjects and methods: Sixteen adults with genetically verified FH, using PCSK9 inhibitors to treat FH, were recruited from the outpatient Lipid Clinic in Oslo. Data was gathered through in-depth interviews that were analyzed qualitatively through a thematic analysis.
Results: Five themes were developed through the analysis: Deep-rooted habits, more relaxed about food, off the sick list, change in concerns and gratitude. Participants did not believe their diets changed after they started using the PCSK9 inhibitors, but they felt more relaxed, less guilty and experienced an increased enjoyment of food when eating high-fat foods, especially in situations that were out of the ordinary. The reduction in cholesterol from the PCSK9 inhibitors gave some participants a feeling of being off the sick list. In addition to this, they experienced a feeling of success and a reduction in concerns regarding CVD. The use of the PCSK9 inhibitors resulted in some new concerns. They worried that adverse effects could occur, but also that the beneficial effects would fade. Still, the participants were very grateful for the PCSK9 inhibitors, and they felt privileged to receive them.
Conclusion: The PCSK9 inhibitors were experienced as positive and the participants did not wish to be without them. The benefits may improve patients’ life satisfaction and wellbeing.
Health care professionals must be aware that the PCSK9 inhibitors have an impact on patients and consider this during consultations. Further research on benefits and disadvantages of the medication should be carried out and the results be disclosed to the patients.
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Acknowledgements
The present study was carried out at the Department of Clinical Nutrition, Faculty of
Medicine, University of Oslo and the Lipid Clinic, Rikshospitalet, Oslo University Hospital from August 2017 to May 2018.
Working on this thesis has been an exciting and educational journey. Many have contributed to making this final result possible. I would like to thank the 16 participants who found the time to contribute to the study. Thank you for sharing your knowledge and experiences on living with FH and the PCSK9 inhibitors.
Thank you to the Lipid Clinic for including me in the environment and teaching me more about FH.
I would especially like to express my gratitude to Kjetil Retterstøl and Margareta Wandel for guiding and supporting me through the year. Your enthusiasm and true interest in the project has been inspiring and motivating. Thank you Kjetil for sharing your knowledge on FH and the PCSK9 inhibitors. Thank you for bringing me to consultations and including me in the research environment. Thank you Margareta for guiding me in the field of qualitative research. Thank you for sharing your knowledge, your thoughts and ideas.
Thank you to Gisle Langslet for help in the planning of the study for reading through this thesis and contributing with feedback. Thank you to Leiv Ose for reading the thesis and giving your comments.
Finally, I would like to thank my support team of parents, siblings and friends who have supported me and cared for me throughout this year. Thank you to my fellow students for creating a good work environment and breaks to look forward too. This year would not have been the same without you.
Jorun Birgitta Bø May 2018
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Table of contents
1 Introduction ... 1
2 Background ... 2
2.1 Familial hypercholesterolemia ... 2
2.1.1 Genetics and pathophysiology ... 2
2.1.2 Clinical features and diagnosis ... 3
2.1.3 Prevalence ... 4
2.1.4 Lifetime risk ... 5
2.2 Treatment of FH ... 6
2.2.1 Treatment goals ... 6
2.2.2 Conventional medical treatment ... 6
2.2.3 Dietary treatment ... 7
2.2.4 Lifestyle treatment ... 7
2.2.5 The Lipid Clinic ... 8
2.3 PCSK9 inhibitors ... 8
2.3.1 Mechanisms and effect ... 8
2.3.2 PCSK9 inhibitors in the Norwegian health care system ... 10
2.3.3 Cost-effectiveness ... 11
2.4 Adherence to treatment ... 11
2.5 Quality of Life in patients with FH ... 12
3 Aim and research questions ... 14
3.1 Aim ... 14
3.2 Research questions ... 14
4 Methods ... 15
4.1 Study design ... 15
4.1.1 Qualitative approach ... 15
4.2 Recruitment and participants ... 15
4.3 Ethical considerations ... 17
4.3.1 Approvals ... 17
4.3.2 Formalities ... 17
4.4 Data collection ... 18
4.4.1 Interview guide ... 18
4.4.2 The in-depth interviews ... 18
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4.4.3 The interviewer ... 19
4.5 Additional information ... 19
4.5.1 Demographic characteristics and medication ... 19
4.5.2 SMART-DietTM ... 19
4.6 Data analysis ... 20
4.6.1 Familiarization ... 20
4.6.2 Generating codes ... 20
4.6.3 Developing themes ... 21
4.6.4 Statistical analysis ... 21
4.7 Presentation of the data ... 21
5 Results ... 22
5.1 Participant characteristics and context ... 22
5.1.1 Participant characteristics ... 22
5.1.2 View on the FH diagnosis ... 24
5.1.3 View of the dietary treatment ... 25
5.1.4 The Lipid Clinic and their role in treatment ... 27
5.1.5 Self-perceived quality of life ... 28
5.2 Five themes ... 29
5.2.1 Deep-rooted habits ... 30
5.2.2 More relaxed about food ... 31
5.2.3 Off the sick list ... 32
5.2.4 Change in concerns ... 34
5.2.5 Gratitude ... 37
6 Discussion ... 40
6.1 Discussion of methodology ... 40
6.1.1 Data collection ... 40
6.1.2 Thematic analysis ... 42
6.1.3 Quality measures in qualitative research ... 43
6.1.4 Ethical considerations ... 46
6.1.5 Benefits of a qualitative approach ... 46
6.2 Discussion of the findings ... 47
6.2.1 Overview of the results ... 47
6.2.2 Attitude towards the FH diagnosis ... 47
6.2.3 Experience of the dietary treatment ... 50
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6.2.4 Effects on self-perceived quality of life ... 52
6.2.5 Practical implications and need for further research ... 55
7 Conclusion ... 56
References ... 57
Appendices ... 65
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List of figures
Figure 1: Clinical features of familial hypercholesterolemia (FH)
Figure 2: Low-density lipoprotein cholesterol (LDL-C) burden in individuals with or without familial hypercholesterolemia (FH) as a function of the age of initiation of statin therapy Figure 3: Normal low-density lipoprotein (LDL) uptake and LDL receptor (LDL-R) degradation by proprotein convertase subtilisin/kexin type 9 (PCSK9)
Figure 4: Flow chart of the recruitment process Figure 5: Overview of the five themes
Figure 6: Summary of the positive aspects related to the use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors that could have an impact on wellbeing and life satisfaction
List of tables
Table 1: Participant characteristics
Table 2: Total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and SMART- DietTM scores before and after the use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors
List of appendices Appendix 1: Invitation letter
Appendix 2: Respond from the Regional Committee for Medical and Health Research Ethics Appendix 3: Respond from the Data Protection Official at Oslo University hospital
Appendix 4: Consent form Appendix 5: Interview Guide
Appendix 6: Demographics and use of medication form Appendix 7: SMART-DietTM questionnaire
XIII Abbreviations
APOB Apolipoprotein B100 BMI Body mass index CHD Coronary heart disease CVD Cardiovascular disease E% Percent of total energy intake
FH Familial hypercholesterolemia, heterozygous HoFH Familial hypercholesterolemia, homozygous
LC Lipid Clinic
LDL Low-density lipoprotein LDL-C LDL cholesterol
LDL-R LDL receptor
NKT for FH the Norwegian National Advisory Unit on Familial Hypercholesterolemia PCSK9 Proprotein convertase subtilisin/kexin type 9
QOL Quality of life TA Thematic analysis TC Total cholesterol
WHO World Health Organization
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1 Introduction
Heterozygous familial hypercholesterolemia (FH) is a genetic disease that is inherited through an autosomal dominant trait (1). FH is characterized by a high level of low-density lipoprotein cholesterol (LDL-C) in plasma. This increase in LDL-C results in an increased risk of
cardiovascular disease (CVD) and especially coronary heart disease (CHD). In untreated individuals, CHD typically appears at a mean age of 55 years in women and 45 years in men (2).
Once diagnosed, patients with FH are treated with medication and diet. The first choice of treatment is statins, often with ezetimibe ad on, (3) in combination with a healthy diet with a reduced intake of dietary trans-fat and saturated fat (4). Unfortunately, not all patients reach their target goals using only statins and diet. These patients require additional medication such as bile acid sequestrants and/or proprotein convertase subtilisin/kexin type 9 (PCSK9)
inhibitors (3).
PCSK9 inhibitors are the newest available treatment for patients with FH and results from several large studies show that PCSK9 inhibitors effectively reduce LDL-C and reduce the risk of cardiovascular events (5-9). The PCSK9 inhibitors represent a new and promising option for additional treatment; yet, currently there is little information available on how the patients experience the PCSK9 inhibitors and what effect they have on patients’ quality of life (QOL) or their view of the dietary treatment. A reduced QOL was reported in patients with FH who had not reached their treatment goals (10). In addition, patients with FH may experience guilt and shame when they do not comply with the dietary treatment (11) and the dietary treatment is experienced as a greater concern than the medical treatment (12).
In the present study, patients’ experience of the PCSK9 inhibitors and the impact of this new type of medication on diet and QOL, will be studied through a qualitative approach.
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2 Background
2.1 Familial hypercholesterolemia
2.1.1 Genetics and pathophysiology
In the early 20th century, scientists showed an interest in the relations between certain clinical traits such as xanthomasis (cholesterol deposits on the body) and cardiovascular symptoms.
One of them, the Norwegian pathologist Francis Harbitz observed that xanthomasis was linked to early death (13). Following the work done by Harbitz, the Norwegian internist Carl Müller discovered that xanthomasis could be connected to hypercholesterolemia and the development of CVD, and that this followed a dominant hereditary trait (14). The disease was named Müller-Harbitz disease, later known as Familial hypercholesterolemia (FH) (13).
Today, FH is known as a genetic disease characterized by high levels of LDL-C in the plasma. Cholesterol is a small lipid molecule that is present in, and important for, all cell membranes of the body. Furthermore, it is an important precursor for steroid hormones, vitamin D and bile acids. It is present in small amounts in food, but it is not essential because it can be synthesized by the body. When cholesterol is transported in the circulation to its destination cells, it is packaged in cholesterol carrying lipoproteins. The most important lipoproteins for cholesterol transportation are low-density lipoprotein (LDL) and high-density lipoprotein (HDL) (15).
Already in the 1950s, scientists observed that patients who had suffered myocardial
infarctions had increased levels of LDL-C (16). High levels of LDL-C in plasma increase the risk of cholesterol retention in the arterial walls and the risk of development of
atherosclerosis. Circulating LDL-C, detained in the walls of the vessels, leads to the formation of atherosclerotic plaques. The most common cause of myocardial infarctions is the rupture of these atherosclerotic plaques (15).
People with FH have mutations in genes that are important for regulation and uptake of LDL- C from plasma. Most common are mutations in the genes for the LDL receptor (LDL-R), apolipoprotein B100 (APOB) and PCSK9. Over 2000 different mutations have been associated with increased LDL-C levels and FH (17).
3 People with FH are either heterozygous for mutations in the mentioned genes meaning that one allele is affected, or they are very rarely affected in both alleles resulting in the more severe homozygous FH (HoFH). Individuals with HoFH typically develop clinical signs of hypercholesterolemia in early childhood and if untreated, few survive past the age of 30 (2).
In this thesis, the term FH refers to people with heterozygous FH.
2.1.2 Clinical features and diagnosis
Normally individuals with undiscovered FH are asymptomatic, and Norwegian FH patients are diagnosed due to either family history (cascade screening) or as index patients typically due to opportunistic testing, e.g. after a cardiovascular event. Clinical signs or symptoms of FH are rare but can occur in some individuals. Signs of FH may be visible in form of
cholesterol deposits on the body (Figure 1). These include tendon xanthomas at any age (most commonly found in the finger extensor tendons or the Achilles tendons), arcus cornea in patients under the age of 45, and tuberous xanthomas or xanthelasmas in patients younger than 25 (18). Cardinal features of untreated FH are early myocardial infarction, stroke and increased risk of mortality (17).
Figure 1: Clinical signs of familial hypercholesterolemia (FH). (A) Extensor tendon xanthoma (B) Achilles tendon xanthoma (C) Pattelar tendon xanthoma (D) Xanthelasma (Photos A-C by Kjetil Retterstøl and D by Leiv Ose)
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In Norway it is recommended (19) that individuals should be tested genetically for FH if total cholesterol (TC) levels are higher than:
- Children: 6.0 mmol/L
- Adults age 20-40: 7.0 mmol/L - Adults over 40: 8.0 mmol/L
FH can be diagnosed both clinically and genetically. Several diagnostic criteria have been developed to clinically evaluate patients with suspected FH, and the most commonly used are the Simon Broome Criteria from the United Kingdom, the U.S Make Early Diagnosis
(MEDPED) criteria and the Dutch Lipid Clinic Network (DLCN) criteria. Several have
recommended the DLCN criteria (20, 21). The diagnosis of FH by the DLCN criteria relies on five factors: family history, clinical history of premature CHD, physical examination for corneal arcus and tendon xanthoma, biochemical results (LDL-C), and DNA analysis to search for a causative mutation in the genes for LDL-R, APOB or PCSK9 (20).
The golden standard for a FH diagnosis is a genetic diagnosis and a detected mutation results in an almost 100 % certain diagnosis. Patients in Norway with suspected FH are offered a genetic test which is performed after a written consent (3). Unfortunately, not all individuals with clinical FH have a detectable mutation (20).
2.1.3 Prevalence
The prevalence of FH is widely discussed. Determining the prevalence of FH is difficult due to the use of different diagnostic tools. Previous assumptions were that FH occurred in 1 in 500 individuals globally (2) but several studies have reported that the prevalence may be higher. Results from a recent Cochrane report state that the prevalence of FH is roughly 1 in 250 (22) and in Norway the prevalence of clinically defined FH was found to be 1 in 300 (23). In the general population, FH is one of the most common monogenic hereditary
diseases. HoFH occurs in about 1 in every 1 million people (18). In Norway, no more than 12 people are currently diagnosed with HoFH (24).
Although the prevalence is difficult to determine, researchers agree that FH is underdiagnosed in all populations and it is assumed that less than 1% of patients with FH are diagnosed in most populations (20). The Norwegian National Advisory Unit on Familial
Hypercholesterolemia (NKT for FH) has estimated that 17 000 - 25 000 Norwegians have FH
5 (25) but currently only 7893 individuals in Norway have been genetically diagnosed with FH (February 2018) (26), indicating that 32% - 46% of FH cases in Norway are genetically diagnosed.
2.1.4 Lifetime risk
Patients with FH differ from patients who have acquired high cholesterol through an
unhealthy lifestyle. Due to the increased cholesterol levels these patients have had throughout their lives, they have acquired an increased burden of cholesterol (Figure 2) (20). In untreated patients with FH, the risk of premature CHD is elevated 20 fold (18). Among FH patients who have been treated with cholesterol lowering medication and diet, CVD mortality is higher compared to the general public (27, 28). The increased LDL-C burden and the increased risk of mortality in patients with FH underlines the importance of early diagnosis and treatment (20)
Figure 2: Low-density lipoprotein cholesterol (LDL-C) burden in individuals with or without familial hypercholesterolemia (FH) as a function of the age of initiation of statin therapy.
(Reproduced from Nordestgaard et al. European Heart Journal. 2013) (20)
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2.2 Treatment of FH
The aim of all treatment for patients with FH is to reduce the LDL-C levels and the risk of CVD. The treatment of FH consists of medical treatment, dietary treatment and lifestyle treatment (3, 20).
2.2.1 Treatment goals
Treatment of FH aims to reduce LDL-C levels below a set treatment goal. The treatment goal for patients with a normal risk of developing CVD is LDL-C <2.5 mmol/L, while patients with high risk of CVD have the treatment goal LDL-C <1.8 mmol/L. High-risk patients are those with diabetes (Type 1 or 2), previous CHD, or those who started treatment late (after 40 years of age) (20, 29). These treatment goals bring the LDL-C levels lower than “normal” due to the increased LDL-C burden the patients have (3).
2.2.2 Conventional medical treatment
Statins are recommended as the first-line of treatment for patients with FH (1, 3) because they are considered to be cheap and cost-effective, and the risk of serious adverse effects is low (30). Statins inhibit the rate limiting enzyme in the livers own cholesterol synthesis thereby upregulating LDL-R on the cell surface causing an increased uptake of LDL-C (1). The first statin for humans, lovastatin, was available in 1987 and this was a revolution for the treatment of FH (31). Large studies on the use of statins concluded that long-term use of statins were safe and could improve survival among patients with CHD (32) and that they efficiently reduced LDL-C (1, 33).
However, a challenge with statins is that some patients do not tolerate high-dose statin therapy and they are not able to take the dosage required to reduce their LDL-C to adequate levels. Muscle symptoms such as weakness and stiffness are especially experienced (34). In clinical studies 1 - 8 % of the participants report muscle symptoms from statins (35).
Many patients with FH do not reach their treatment goals when using only statins and they are required to use additional medication such as ezetimibe, bile acid sequestrants and/or PCSK9 inhibitors (1, 3).
7 2.2.3 Dietary treatment
Müller wrote in his paper in 1939 that as treatment for FH he recommended a diet low in cholesterol. Therefore, he recommended that patients reduce their intake of animal fat, such as egg yolk, butter, high-fat milk and heavy cream (14). He had little scientific research to support his assumptions, but dietary recommendations today still resemble Müllers advice.
Today we know that the fat composition in the diet, the amount of fat, dietary cholesterol, fiber and unfiltered coffee affect serum cholesterol levels. An increased intake of trans fat and saturated fat, increases the concentrations of TC and LDL-C in plasma (15). A lipid-lowering diet with increased intake of unsaturated fats and a reduced intake of saturated fats may reduce LDL-C levels up to 30 % (36).
The main components in the dietary advice given to patients with FH in Norway is similar to the advice given to the public (37). It is recommended that patients with FH have an intake of trans fat <1 % of total energy intake (E%) and an intake of saturated fat <7 E%. Total fat intake should not exceed 35 E%. Carbohydrate intake should be between 45 and 55 E% and the intake of white sugar should not exceed 10 E%. Patients are recommended to eat 25-40 g of dietary fiber each day (29). Patients are also recommended to eat plant sterols daily (4) since an intake of 2 g of plant sterols may reduce TC and LDL-C up to 7-10 % (29). In addition to this, patients are advised to avoid unfiltered coffee (4).
2.2.4 Lifestyle treatment
In addition to medical treatment and dietary treatment, it is crucial that patients receive guidance on lifestyle. High body mass index (BMI), high blood pressure, smoking, diabetes and physical inactivity increase the risk of CVD in patients with FH (20, 29). Adults should be physically active, with the recommendations of 150 minutes per week with activity of moderate intensity or 75 minutes per week with activity of high intensity (38). Patients with excessive weight (BMI >25) and/or abdominal adiposity (waist circumference >94 cm for men, >80 cm for women) should reduce their caloric intake and increase their energy expenditure in order to reduce their body weight (29). Patients who smoke should receive advice and guidance on smoking cessation (38).
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2.2.5 The Lipid Clinic
The pediatrician Leiv Ose established the Lipid Clinic (LC) at Oslo University Hospital in 1983/1984. This is the largest LC in Norway. The LC is specialized within the field of dyslipidemias.
The LC has two important tasks. The first is to serve as an outpatient clinic for patients with FH and other dyslipidemias (39). Patients are referred to the LC by their general practitioner, occupational health systems or hospitals. Clinical suspicion of FH is a common cause of referral. At the LC, a specialized physician will follow up patients with FH. In addition, all patients receive dietary counselling by a specialized dietitian. Patients are followed up differently depending on age. Children and adolescents receive yearly follow-ups whereas adults receive follow-up consultations every year or every three years depending on treatment results and risk of CVD. In addition, the LC refers its patients to cardiac specialists for risk assessments such as electro- or echocardiography or ultrasound of the arteries.
The second task is that it is an important institution for research on FH and other dyslipidemias. Research done at the LC involves testing of new lipid-lowering drugs, studying diet, dietary patterns and dietary changes (39).
2.3 PCSK9 inhibitors
It was estimated that treatment goals were reached in no more than roughly 50 % of patients with FH using conventional treatment with diet, statins and ezetimibe (10). The need for a more efficient medication has been obvious.
2.3.1 Mechanisms and effect
In 2003, a gain-of-function mutation in the gene for the enzyme PCSK9 was discovered.
People with the mutation had elevated LDL-C levels in plasma and were diagnosed with FH (40). PCSK9 is present mainly in the liver, intestines and kidneys and is important in the recycling process of the LDL-R (Figure 3). The LDL-R is located on the cell surface and is responsible for uptake of LDL from plasma. When PCSK9 binds to the LDL-R, it is marked for degradation. The LDL-R is transferred into the cell and degraded by the lysosomes. An increase in PCSK9 leads to an increased degradation of LDL-R (34). Inversely, a loss-of-
9 function mutation in PCSK9 will lead to an increased recycling of LDL-R and an increased uptake of LDL-C in the hepatocytes (34). Loss-of-function mutations have been associated with a 15 % reduction in LDL-C and a 46 % reduction in early CHD (41).
Figure 3: Normal low-density lipoprotein (LDL) uptake and degradation of LDL receptor (LDL-R) by proprotein convertase subtilisin/kexin type 9 (PCSK9)
Similar to many other discoveries in medicine, these findings led to the development of a new medication, in this case the PCSK9 inhibitors. Inhibition of PCSK9 simulated what was seen in loss-of-function individuals. This led to a reduced degradation of LDL-R, leading to an increased number of LDL-R’s on the cell surface, and an increased uptake of LDL-C from plasma (34).
Several large studies have evaluated the effects of the PCSK9 inhibitors on patients with FH.
When added to statin therapy, PCSK9 inhibitors may reduce LDL-C approximately 60 % (5- 9). Studies also report fewer cardiac events in the PCSK9 inhibitor groups compared to the placebo groups (5, 7, 9) In the Fourier trail median LDL-C was reduced from 2.4 mmol/L to 0.78 mmol/L (5). The GLAGOV-study reported that coronary artery plaque volume decreased in the PCSK9 inhibitor group compared to a slight increase in plaque volume in the placebo
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group (42). The final outcomes from the ODYSSEY trial found a significant difference in all- cause mortality when comparing PCSK9 inhibitors and placebo (9).
Patients using PCSK9-inhibitors have reported few side effects. Most commonly experienced are injection site reactions. The long-term studies have not found significant differences regarding adverse effects such as neurocognitive events and newly-onset diabetes (5, 9).
2.3.2 PCSK9 inhibitors in the Norwegian health care system Two PCSK9 inhibitors are available for use in Norway, evolocumab (Repatha) and alirocumab (Praluent). They are bought at the pharmacy and resemble insulin pens for diabetics. They are injected subcutaneously into stomach, thighs or upper arm by the patients themselves every second week.
In Norway, the PCSK9 inhibitors are reimbursed for patients who meet certain criteria. The reimbursement policy for the PCSK9 inhibitors has changed several times since they became available in Norway in autumn 2015. In the beginning, PCSK9 inhibitors were reimbursed to patients with a genetically verified FH diagnosis, a LDL-C >1.8 mmol/L with maximum tolerated dosage of statin and/or Ezetimibe, and a high risk of CVD. Statin intolerant patients needed to have tried at least three approved statins and ezetimibe (43).
In June 2016, it was decided that the PCSK9 inhibitors should only be reimbursed for patients with HoFH. Patients who had been granted reimbursement before this would continue to have their medication reimbursed, but no new patients would be granted reimbursement (44). In May 2017, the rules for reimbursement were again changed. Up to this date, these rules still apply and patients in primary prevention now receive reimbursement if they have a
genetically verified FH diagnosis and LDL-C higher than 5 mmol/L despite maximal tolerated lipid-lowering treatment. Patients in secondary prevention receive PCSK9 inhibitors with a LDL-C higher than 4 mmol/L despite maximal tolerated lipid-lowering treatment (45).
For patients who meet the criteria for reimbursement, an application must be sent from specialists in cardiology, internal medicine or pediatrics explaining the patients need for PCSK9 inhibitors. Applications are handled by The Norwegian Health Economics Administration (HELFO) (45).
11 2.3.3 Cost-effectiveness
The PCSK9 inhibitors are expensive and it is estimated that the use of PCSK9 inhibitors for one person will cost roughly 70 000 NOK per year for evolocumab and 60 000 NOK per year for alirocumab (46, 47), although the actual price in Norway is presently a business secret between the health authorities and the companies.
The PCSK9-inhibitors are effective on LDL-C levels, but the cost is much higher than for other lipid-lowering medications. A Norwegian study concluded that the PCSK9 inhibitors were only cost-effective in secondary prevention for older patients with high absolute risk, but not in primary prevention (48). Using the secret price, the Norwegian Medicines Agency have decided that it is cost-effective in FH when following the criteria for reimbursement
mentioned above (45).
2.4 Adherence to treatment
Adherence to the treatment of FH is crucial for the best prevention of CVD. World Health Organization (WHO) estimates that in developed countries the adherence to treatment in patients suffering from chronic diseases is about 50 % (49).
Among patients with FH, the adherence to medical treatment is good, but the adherence to dietary and lifestyle treatment is lower. In one study 99 % of the participants reported optimal medical adherence, but only 49 % followed the recommendations for diet and lifestyle (50).
In addition, patients with FH experience the dietary treatment as more challenging to follow than the medical treatment (12). Patients also perceive the medical treatment to be more effective and therefore devalue the effect of the dietary treatment (51). Lack of adherence to treatment could be due to little knowledge about the risk of CVD (52) or a low perceived vulnerability to CVD (51).
Frich et.al (11) reported that patients with FH could experience guilt and shame related to self-management of their condition, especially related to the dietary management. Similar experiences of guilt were expressed in a Swedish study (53). Guilt and shame could also be experienced if the results from cholesterol tests were not favorable or if health professionals commented on the patients unfavorable cholesterol results, weight or diet (11).
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Two previous master theses have explored patients’ views on dietary treatment (54, 55) but to the author’s knowledge, no previous studies have studied how the reduction of cholesterol levels due to PCSK9 inhibitors affects the diet of patients with FH and their attitude towards the dietary treatment. The dietary treatment may be a source of guilt and shame for patients with FH and adherence to the dietary recommendations appears to be difficult. It is likely that the reduction of cholesterol levels by the PCSK9 inhibitors could positively affect the
negative emotions related to the dietary treatment. On the other hand, a reduction of cholesterol levels may lead to less adherence to the dietary treatment.
2.5 Quality of Life in patients with FH
Many different definitions exist for QOL, and they include different aspects. Some separate health related QOL and non-health related QOL, while others mention QOL as a whole, including all aspects of life. Common for many of the definitions are that wellbeing and satisfaction are important aspects (56). WHO defines QOL as:
Individuals’ perception of their position in life in the context of the culture and value system in which they live and in relation to their goals, expectations, standards and concerns.
It is a broad ranging concept affected in a complex way by the persons’ physical health, psychological state, level of independence, social relationships and their relationship to salient features of their environment (57).
QOL could be affected in patients with FH by factors such as the fear of developing CVD, adverse effects, the cost of a lifelong treatment, or the awareness that they have a genetic disease (17). In a Swedish study among patients with FH, the meaning of QOL was explored.
They found that QOL relied on finding harmony in life something that was found by balancing the stressors with the positive aspects in life (58). A study on a FH population in southern Europe, reported that factors that contributed to a reduced QOL in patients with FH were the presence of CVD, female gender, older age, xanthomas, depression, obesity, a lower level of physical activity and a lower level of education (59).
Several studies have assessed the issue of QOL in patients with FH. A study in Norway found that patients with FH had QOL scores similar to those of a Norwegian reference population (12). Similar findings were reported in studies from other countries (59-61). Although these studies did not find differences in QOL between FH patients and a reference group in the
13 general public, the studies report that the patients expressed more concerns about the risk of CVD and early death (12, 61), in one study 86 % of the participants were anxious they would develop CVD (61).
A Danish study reported that “the QOL impact of FH is related to treatment efficacy” (10).
This study interviewed two focus groups. The first group consisted of people with FH who had met their treatment goals, the other with people who had not yet met their treatment goals.
The group who had not reached their treatment goals had a markedly lower QOL. This also affected their perceived severity of FH. The study concluded that to maintain QOL in people with FH, treatment must be improved (10).
Several large studies have seen the effects of PCSK9 inhibitors on cholesterol levels and cardiovascular endpoints. The PCSK9 inhibitors show slightly greater results on cholesterol levels than statins. However, on top of statins it can lead to exceptionally low cholesterol levels but little is known on how the patients experience the PCSK9 inhibitors. To the authors knowledge there are no qualitative studies on QOL in patients using PCSK9 inhibitors. Those who receive PCSK9 inhibitors in Norway are the patients who have not met their treatment goals using conventional treatment. The PCSK9 inhibitors contribute to a better medical management of cholesterol levels and the use of this medication could possibly affect QOL in patients.
Knowledge on the patients’ experience of the PCSK9 inhibitors and how this affects their view on diagnosis, dietary treatment and QOL is important for the future treatment of this group of patients.
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3 Aim and research questions
3.1 Aim
The aim of this study was to explore if the use of the new cholesterol lowering medicine, known as PCSK9 inhibitors, had an effect on patients’ attitude towards their diet and the dietary treatment, and explore if the use of PCSK9 inhibitors affected their self-perceived QOL.
3.2 Research questions
1. Does the new treatment and the following reduction in cholesterol levels affect the patients’ attitude towards their FH diagnosis?
2. How do patients experience the dietary treatment now, compared to earlier, when they did not use PCSK9 inhibitors?
3. Does the new treatment affect patients’ self-perceived QOL?
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4 Methods
4.1 Study design
This study used an inductive qualitative research method to explore the research questions.
The qualitative approach chosen for this study was thematic analysis (TA). Data came from sixteen in-depth interviews carried out with the help of a semi structured interview guide. The interviews were held between August 2017 and November 2017.
4.1.1 Qualitative approach
TA is described as “a method for identifying, analyzing and reporting patterns (themes) within data” (62). TA is a descriptive method aiming to describe what is found in the data.
The method does not aim to generate a theory (63). This is a widely used method among qualitative researchers. It was described already in the 1970s but the method was rarely acknowledged before Braun and Clarke published the paper “Using thematic analysis in psychology” in 2006 (62). When first presented, it was as a method well designed for research within psychology, but it has later been recognized as a well-designed method in other fields, such as health and wellbeing research (64).
TA is a flexible method and it is not bound to any theoretical framework. It can be used on most types of data, as it is a method for the data analysis only (65). The findings are easily understood by researchers, the general public and policy makers (63). For researchers with little or no experience within the field of qualitative research, TA is considered a good method because it is easy to learn and perform. Braun and Clarke wrote in their paper “It is the first qualitative method of analysis that researchers should learn, as it provides core skills that will be useful for conducting many other forms of qualitative analysis” (62). The master student had no previous experience with qualitative research and TA was therefore considered a good and effective method for the project.
4.2 Recruitment and participants
Participants were recruited based on purposive sampling. The following inclusion criteria were set before the start of the study:
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- Current patient at the outpatient LC - Diagnosed with FH
- Currently using PCSK9 inhibitors for the treatment of FH - Not suffering from a serious diagnosis (e.g. cancer or dementia)
A list including most patients (n=223) approved for the use of PCSK9 inhibitors in Norway medio 2017 was presented to the master student by the LC in august 2017. Due to financial limitations and convenience, it was desirable to include patients residing in the Oslo area.
After inviting all eligible participants in the city of Oslo, four people residing near Oslo city were also invited to join the study. The recruitment process is illustrated in figure 4.
Six people did not meet the inclusion criteria. Of these, two people were pregnant and had stopped using PCSK9 inhibitors before pregnancy; two had stopped using PCSK9 inhibitors due to experienced side effects and two suffered from serious diagnoses.
Figure 4: Flow chart of the recruitment process
Patients who met the inclusion criteria received a letter in the mail (appendix 1). The letter informed eligible participants of the study’s intentions and that the master student would
17 contact them. One week after sending the letters, the master student contacted the eligible participants by phone. The master student gave information about the study and asked if they wished to participate. If the participant accepted the invitation, the master student and the participant agreed on a time and date for the interview, according to a time convenient for the participant.
Eighteen participants wished to participate in the study after the phone conversations. Two participants withdrew from the study before their interviews. One withdrew due to sickness and the other due to lack of time.
4.3 Ethical considerations
4.3.1 Approvals
The Regional Committee for Medical and Health Research Ethics (REC) reviewed the project application and determined that the project did not need their approval, according to the Health Research Act § 4 (appendix 2). The project was reported to the Data Protection Official at Oslo University hospital (appendix 3). The study followed the recommendations given by the Data Protection Official and the declaration of Helsinki (66).
4.3.2 Formalities
Before the interviews, the master student explained the purpose of the study to the
participants. The participants were informed that the interviews were anonymous and that they could withdraw from the study at any time if they wished. Before the recording of the interviews began, the study’s consent form (appendix 4) was presented to the participants for them to read and sign.
Each participant received an ID-number on the day of his or her interview. All further information related to the participant, forms, audio files, and transcripts, were marked with the ID-number. A list containing the participants’ full name and their ID-number was stored in a locked area at the Department of Nutrition, University of Oslo.
To ensure anonymity, it was decided to present the participant characteristics in a collected table and not link certain descriptive traits to each participant. Giving too much information
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on the individual participants, could make them easier to identify, due to a small number of patients using this medication in the Oslo area.
4.4 Data collection
4.4.1 Interview guide
The semi structured interview guide was developed by the master student in collaboration with the supervisors (appendix 5). The interview guide contained a list of questions that were relevant for the research questions. Using a semi structured interview guide ensured that the same topics were covered in all interviews but at the same time it opened for follow-up of interesting aspects. An extensive interview guide was made, as the master student had no previous experience with qualitative interviews. The majority of the questions were open- ended to encourage free speech. The master student asked follow-up questions beyond the interview guide when the participants replied with short answers or when they mentioned interesting aspects. Interesting aspects that emerged in early interviews were followed up in later interviews.
The interview guide was tested in two pilot interviews with a 25-year old woman and a 57- year old man. The participants were not relevant for the study. These interviews were used as practice situations for the master student and the two participants gave feedback on the interview guide. Some changes were made to the interview guide after the pilot interviews.
4.4.2 The in-depth interviews
All sixteen interviews were held face-to-face by the master student. Twelve interviews were held in a conference room at Domus Medica at the University of Oslo. Four participants requested that the master student came to their location. One interview was held in a participant’s home and three interviews were held at participants’ offices.
The interviews were recorded with an Olympus digital voice recorder (VN-741PC). The same recorder was used for all interviews. After each interview, the master student wrote field notes, including information on the interview and interesting thoughts.
19 The interviews lasted from around 40 minutes to 90 minutes, with an average time of about one hour.
The master student prepared a selection of coffee, tea and water at every interview to create a more casual environment with the intention to encourage the participant to speak freely.
4.4.3 The interviewer
The master student carried out the interviews in this study. She was a 24-year-old woman studying Clinical Nutrition at the University of Oslo. She had no prior connection to the LC or any patients with FH. The master student had experience with following a diet. Due to a chronic disease, the master student had followed a strict diet since she was a teenager.
4.5 Additional information
4.5.1 Demographic characteristics and medication
The participants filled out a form on demographics and use of medication (appendix 6). The form was marked with the participants ID-number. The data received from the form were sorted in Microsoft Excel and used to describe the participants in the results chapter.
4.5.2 SMART-DietTM
After the interview, the participants filled out a food frequency questionnaire, SMART- DietTM (appendix 7). This is a questionnaire developed by the LC. Physicians and dietitians at the LC use SMART-DietTM during their consultations to evaluate the patients’ diet and give dietary advice. The questionnaire contains 26 questions on diet and lifestyle and after
answering the questions on diet, the patients receive a score. This score gives an indication on adherence to the dietary treatment recommended by the LC. The maximum possible score is 41 points. The score is rated in one of three groups: 27 points or less Your diet should be improved in many areas, 28-35 points Your diet can be improved in some areas, and 36 points or more You have a healthy diet. Patients normally fill out SMART-DietTM before each
consultation at the LC and the SMART-DietTM scores are recorded in the patient journal.
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The SMART-DietTM forms gave information on participants smoking habits, exercise, weight as well as adherence to dietary treatment. SMART-DietTM scores from before the participants used PCSK9-inhibitors were retrieved from the patient journals.
4.6 Data analysis
Braun and Clarke (62) provided a detailed description on how to carry out a TA, including a six-phase approach for the analysis. The six phases were: familiarizing yourself with the data, generating initial codes, searching for themes, reviewing themes, defining and naming
themes, and producing the report. Braun and Clarke also present a “15 point checklist of criteria for good thematic analysis” (62). The analysis in this study followed the six phases and the 15-point checklist.
4.6.1 Familiarization
The audio records from the interviews were transferred to the computer and transcribed verbatim by the master student. To ensure that the interviews were correctly transcribed, they were re-listened to and the transcripts were corrected if necessary. The transcripts consisted of in total 282 pages, ranging from 12 to 24 pages for each interview.
The master student read and re-read the transcripts for familiarization before the coding process began. During transcription and read-throughs, the master student noted interesting aspects, thoughts and potential codes.
4.6.2 Generating codes
TA includes complete coding of the entire data set. Complete coding involves searching across the entire data set to identify anything and everything that might be of interest or relevance to the research questions (65). Throughout the coding process, equal amount of attention was given to each data item. The interviews were coded manually and using the computer software NVivo 11 Pro.
In the first round of coding, the master student used manual coding. The interviews were coded using highlighting pens, post-it notes and colored pens. The interviews were then coded in NVivo 11 Pro. The codes from the first round were added to the software and more codes
21 were generated. The complete coding resulted in a long list of codes. These codes were sorted into groups, which were again sorted into broader groups.
4.6.3 Developing themes
Groups of codes created the basis for the development of themes. The master student discussed the codes and the grouping with the supervisors in search of themes. Ideas for themes were developed. Themes were changed during the analysis process and after discussions between the master student and the supervisors; five themes remained as important themes, relevant for the research questions.
4.6.4 Statistical analysis
Statistical analysis was used to compare values for TC, LDL-C and SMART-DietTM scores before and after the use of PCSK9 inhibitors. Tests for normality showed that many of the values were not normally distributed. Median values were therefore presented. Statistical analysis was performed using the software IBM SPSS Statistics 25. A non-parametric Wilcoxon Signed Ranks test was used to compare the values.
4.7 Presentation of the data
The findings in the study were based on the entire data material. The presented findings were supported by quotes, used to illustrate the findings. The participants were presented with a letter and a number where W indicated that the participant was a woman, and M indicated a man.
The interviews were held in Norwegian and all quotes used in the results chapter were
translated from Norwegian to English. Some quotes were shortened to make the text easier to read. Segments that were taken away were replaced with (…). In some quotes, the master student added words in brackets […] to help the reader understand the context of the quote or to replace words that were taken out due to anonymity.
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5 Results
5.1 Participant characteristics and context
5.1.1 Participant characteristics
The group of participants consisted of six women and ten men between the age of 44 and 71 (Table 1). Thirteen participants resided in Oslo city, while three participants lived outside Oslo. Among the participants, there was a diversity in occupations and degree of education.
All participants were genetically diagnosed with FH at the time of the interview. The
participants had known about their increased cholesterol levels for a median time of 29 years, with a range between 12 and 46 years.
Table 1: Participant characteristics
Characteristics N
Gender Male
Female
10 6
Age Median (min , max) 56 (44 , 71)
Marital status Married
Cohabitant Single/Unmarried
10 2 4 Participants with children
Children with FH No children with FH Children not tested
15 9 3 3 Body mass index (kg/m2) Normal weight (20-24,9)
Overweight (25-29,9) Obese (30-)
9 2 5
Smoking Yes
No
2 14
Physical activity Less than one time per week
1-2 times per week 3 or more times per week
1 7 8
23 All participants used other cholesterol-lowering medication in addition to the PCSK9
inhibitors. Most commonly used was a combination of Crestor 40 mg (statin) and Ezetrol 10 mg (ezetimibe). Most of the participants had started using lipid-lowering medication shortly after they were diagnosed with FH. When first diagnosed, many participants had attempted to reduce their cholesterol with diet only, and no medication but this was unsuccessful, and they started using medication, in addition to diet, after about 6-12 months.
Eight participants had experienced side effects of statins; three of these participants no longer used statins to treat their FH due to the side effects they had experienced. The most
commonly experienced side effects were aching, weakness and stiffness in muscles and joints.
Furthermore, some had experienced flushing, headaches, difficulty sleeping, and tiredness.
Half of the participants had experienced CHD and a following need for coronary
interventions. In four participants, CHD in form of clogged arteries was discovered during an examination of the heart and arteries. Four participants had experienced myocardial
infarctions.
At the time of their interview, the participants had used PCSK9 inhibitors for a median time of 20 months, with a range between 8 and 24 months. All participants experienced a reduction in TC and LDL-C after the use of PCSK9 inhibitors. The median reduction in TC was 2.1 mmol/L and 2.3 mmol/L for LDL-C (Table 2).
None of the participants had reached their treatment goals before the use of PCSK9 inhibitors.
Four participants had the treatment goal LDL-C <2.5 mmol/L. Twelve participants had the treatment goal LDL-C <1.8 mmol/L. After the use of PCSK9 inhibitors, ten participants reached their treatment goals. Two participants were 0.2 mmol/L away from their treatment goals. Three participants did not use statins, and although their cholesterol levels were reduced when using PCSK9 inhibitors, they did not reach their treatment goals.
The difference in the median SMART-DietTM score from before and after the PCSK9 inhibitors was small and insignificant (Table 2). The median SMART-DietTM score for the group was evaluated as: Your diet can be improved in some areas both before and after treatment with PCSK9 inhibitors.
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Table 2: Total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and SMART- DietTM scores before and after the use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors
Before PCSK9 inhibitors
Median (min , max)
After PCSK9 inhibitors
Median (min , max)
p-value
TC (mmol/L) 5.6 (3.9 , 9.2) 3.5 (2.5 , 7.5) p<0.001 LDL-C (mmol/L) 3.9 (2.3 , 6.7) 1.6 (0.5 , 4.8) p<0.001 SMART-DietTM Score 35 (29 , 40) 34.5 (28 , 41) p = 0.361
5.1.2 View on the FH diagnosis
The participants had lived with their diagnosis for many years, accepted their diagnosis and did not perceive it as traumatic. The participants discovered their increased cholesterol levels at a median age of 26 years, with a range from 11 to 48 years. All participants had other family members diagnosed with FH, like parents, siblings or children. The participants viewed FH as a genetic disease inherited from their parents and something they would bear with them throughout life. For the participants the important thing was to take their
medication and try to keep their diet. Many said they were glad to have inherited a treatable disease. Some had experienced the early loss of a parent or a sibling due to CVD. They were therefore glad to have been diagnosed since this gave them the opportunity to prevent CVD.
The level of concern regarding the risk of CVD varied from participant to participant. Early in the interviews, most participants said they did not have major concerns about their increased risk of CVD. The participants trusted that their medication prevented CVD. Follow-up appointments with physicians were experienced as reassuring.
“So I know I have FH. I know that I’ve got it. I’m lucky that I was diagnosed that early. I know I have good contact with specialists. Eehm. So I’ve never been worried really” M8 Throughout the interviews, some participants revealed that they might have had some concerns regarding the risk of CVD. For some, growing older, maturing into adulthood, and
25 having children had made them more aware of their risk of CVD. Many said that they were not very concerned, but they also told that the risk of CVD had been on their mind.
“I can worry that my arteries will clog up (…) what would happen if I just collapsed here?
What would happen to my little child if I wasn’t here anymore? Right? All those thoughts that I would not have thought when I was very young, and that you don’t understand until you grow older” W4
Some compared their diagnosis to other diseases such as epilepsy or diabetes. They perceived these conditions more serious than FH because they could give acute severe reactions. FH was perceived as more manageable than these diseases.
“And for us, particularly, we don’t get seizures or anything, so I mean. If you have diabetes or epilepsy then you kind of notice, because it’s sort of unstable. But we never notice” W3 For some, the FH diagnosis was something they shared with other people while others saw the diagnosis as a hidden identity and did not wish to talk about it with friends. Still, common for all participants was the desire to be perceived as normal, and not a person with a disability, by other people.
“I’ll call it a kind of hidden identity, It’s not something I talk about (…) I live with it
consciously and I think about it almost every day, But it’s not like it’s bothering me because I do have such acceptance that this is how it is” M4
“I don’t talk about it much. It’s more like I am aware of it myself. Because, you might be perceived as a bit weird really” W6
5.1.3 View of the dietary treatment
Although all participants had received dietary counseling at the LC, the participants had different perceptions of the importance of the diet for their cholesterol levels. Some had the impression that the diet did not affect their cholesterol levels; others believed there was a small effect, while some experienced the diet as incredibly important for their cholesterol levels.
“I think that what I eat doesn’t matter much for my cholesterol levels, or matter a lot, that the medication is what takes it” M1
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“There’s really nobody who is not convinced that diet is important for cholesterol, and it feels so unproblematic to live a little healthier” M4
Many participants believed that their diet was beneficial for other things, such as weight, surplus energy or a healthy body, and this motivated them to have a healthy diet.
“I do notice though, that if I eat leaner things and such and more salads and so, it’s easier to keep my weight, really. You notice that (…) you feel more comfortable when you eat healthier really. More energy” W6
Most of the participants said their diet was influenced by their FH diagnosis. They were aware of what was considered a healthy diet for a patient with FH and they did not experience a need for more dietary counselling. Some participants felt they had a diet consistent with the recommended diet from the LC. Other participants admitted that they had not made great changes to their diet after being diagnosed with FH. Some said that they were able to change some things in their diet, but other foods were too hard to give up. Several participants mentioned that cheese was difficult to give up.
“In the beginning (…) then I counted the eggs and bought low-fat cheese, but then I thought,
“You know what? I can’t take this!” because I like cheese in all shapes and it is fat. Cheese is fat, really, and low-fat products are tasteless and dry” W2
Many participants felt that habits they acquired in their childhood still followed them as grown-ups. Those who brought healthy habits from home experienced that it was easier to follow the diet of FH compared to those who did not have FH friendly habits in their childhood.
“But, like I said, I’m lucky that it was discovered that early. That it has been such a family matter and really, that makes it a kind of lifestyle, a habit. It’s as easy as that” M3
“You’re kind of used to eating hot dogs on a Friday, so, like that. It’s kind of hard to let go of things” M6
Becoming parents motivated many participants to have a healthier diet. Two factors motivated this. The first was the desire to live a long and healthy life together with their children. The second was the hereditary trait of FH and the fact that their children had
27 inherited FH or might have FH. Being a role model for their children was also important for some of the participants.
“Out of four children I have three who of course have this gene. So clearly, we try to be a bit more conscious about it at home too. Try to be better at this. Because we know, we know that most likely it will clog up for them too” M5
“To be a kind of role model even though my kids are grown up now. Like, that I still might in a way show them that I still take this seriously, and I hope they do too” M1
The men especially mentioned the importance of support from their spouse/partner. If the participants experienced support and interest from the other person, it was easier to maintain a healthy diet. The women did not experience the same need for support and talked more about making separate food and having different spreads in the refrigerator.
“I’ve taken a lot of courses and counselling, like what makes, where my wife has attended also, because you need to be two about this. You have to, otherwise you won’t make it” M7
“Me and my partner, we often eat, we often eat a little differently. I make sort of, well, this is kind of my thing and then he has sort of his thing” W5
5.1.4 The Lipid Clinic and their role in treatment
The relationship between the physician and the patient was important for the participants and many spoke warmly of their physician at the LC. Furthermore, the participants had great confidence in their physicians and they felt taken care of by the LC.
“If I had not seen them then I don’t know whether I would have had an infarction now or (…) It’s kind of a feeling of safety (…) I recommend others, if they have high cholesterol to contact them” M6
The physicians’ opinion of the participants’ cholesterol levels was important for the
participants view on their cholesterol levels. If the physician was satisfied with the cholesterol levels, so was the patient.
“And if he [physician] is satisfied, then I am satisfied. That’s what counts” M9
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The physicians at the LC frequently sent the participants for examinations of the heart and arteries. Being sent to these examinations contributed to a feeling of safety in the participants because CVD could be discovered before it became dramatic.
“I’ve done that ultrasound down at [clinic] so that I kind of have a picture that I’m ok, internally. So that’s kind of a safety I think, really think so” W2
The fact that the physicians gave the participants new medication, sent them to examinations and encouraged them, gave a feeling of security. Several also appreciated being seen and respected by the physicians at the LC.
5.1.5 Self-perceived quality of life
Most participants experienced that their current QOL was good. The participants were asked about factors that were important for a good QOL. An important factor mentioned by the majority of the participants, was the importance of a well-functioning home environment and good relationships with spouses, partners or children. Work was another factor mentioned. To succeed in the challenges presented to them at work, and to be liked and respected by
colleagues, were identified as important factors to maintain a good QOL.
“That you have a good relationship at home. That you have a good relationship to also close family, eeh, also that you have a work that’s interesting and that you may also have interests”
M8
Some participants mentioned how coronary interventions, such as stenting, had a positive effect on their QOL, by contributing to better health and often a physical improvement.
Having the opportunity to be physically active, improved QOL for many and they appreciated spending time in the nature, running, skiing, fishing and other outdoor activities. Some also mentioned the importance of feeling useful and contributing in their community.
“The most important thing is to be healthy and that you function, and that you can contribute in every possible way” M4
The participants experienced limitations in mobility as a negative influence on QOL. This was related to CVD, injuries (e.g. knee injuries), tiredness or side effects of their medication, especially statins. Half of the participants had experienced side effects from statins, and
29 several had used statins over many years, even though they caused discomfort. W6 explains that this had previously affected her QOL.
“Because, I’ve experienced a lot of side effects from statins over the years, right. It’s not very comfortable and positive. It decreases your quality of life a lot” W6
FH was not mentioned by any of the participants when they were first asked about QOL.
When asked specifically about the impact FH had on QOL, some, like W6, mentioned that FH had a negative effect on QOL due to side effects of the medication, while others experienced a positive effect of the FH diagnosis because it motivated them to have a healthy lifestyle.
5.2 Five themes
A TA of the sixteen interviews in this study resulted in five main themes
(Figure 5) that were relevant for the research questions. The five themes were: Deep rooted habits, more relaxed about food, off the sick list, change in concerns, and gratitude
Figure 5: Overview of the five themes
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5.2.1 Deep-rooted habits
Most of the participants did not believe that any recent changes in their diets were due to the use of PCSK9 inhibitors or low cholesterol levels. Many participants experienced that the dietary recommendations given to them by the LC, had become a habit after many years.
These habits had become the normality and the participants said that the lack of change in their diet was due to their deep-rooted habits.
“It’s so deep-rooted what I eat or what I choose when I’m out, with milk and type of minced meat and things like that, so, I don’t start eating normal minced meat for that reason or start to drink whole-fat milk for that reason, really (…) It’s just because it’s so deep-rooted, plain and easy” M3
“I think that I am so used to that kind of food. And the rest of my family is too, so if we had eaten fat rich minced meat [medisterdeig] I think they would have asked “what is that?”” W1 Some participants admitted that they had not completely converted to a cholesterol friendly diet before the PCSK9 inhibitors. One of these participants now questioned the need for a special diet.
“When you take the medicine that I take then all of a sudden my cholesterol is good, so I don’t know how important it is. So I think like if you don’t take the medicine, then you’d kind of have to eat a lot of that type of food, but when I take the medicine that I do and I look at the results that I have, then they are good, right?” M6
One participant admitted to changing his diet when his cholesterol levels were reduced.
“But, I am a little nervous about the next time I am going to check it [cholesterol levels]. I actually thought about it earlier this fall “I wonder what my cholesterol is now?” I have been slacking off on my diet” M10
The participants had a desire to be perceived as normal by other people and several of them used the term “normal people” to describe people without FH. The participants did not wish to be of inconvenience to anyone and when eating at other people’s homes they ate what was served. As some participants said, they did not become acutely ill or die when eating high-fat food, and therefore there was no need to make a fuss about food. Many were worried that if they made much trouble regarding food, friends and family would think of them as fanatical.
