One of the most common monogenetic diseases is familial hypercholesterolemia (FH), which is present in approximately 1 in 500 Caucasians. Genetically, FH is an autosomal dominant disease characterized by high low-density lipoprotein (LDL) cholesterol and a high risk of premature coronary heart disease (CHD). Typically, CHD appears in untreated individuals with FH at a mean age of 45 years in men and 55 years in women. 1 When FH is identified, patients without symptoms of CHD, are informed about the genetic predisposition and risk of disease. At-risk family members are counselled to make lifestyle changes. Medical treatment includes plasma cholesterol-reducing agents that have been shown to reduce the risk of atherosclerosis, 2 premature CHD, and death. 3,4
Significant research has been conducted on medical therapies and the underlying genetics, but the psychological consequences of living with FH and the concomitant risk of disease warrant further investigation. 5 Living with a high risk of developing a genetic disease may influence people's lives in different ways. Awareness of one's personal risk may be the factor underlying this influence. If this is true, awareness that one has inherited a familial disease may be an important influence on quality of life.
In a recent study, asymptomatic patients with FH had a quality of life equal to that seen in a reference group, with the exception that 86% of the FH patients were anxious about developing CHD. 6 Quality of life among family members of patients with FH was as good as that seen in reference subjects, although 91% reported feeling anxious that their family member with FH may develop CHD. 7 This anxiety in family members was surprising as patients had at least the same level of quality of life as the reference group. The current study was conducted in order to describe the meaning of quality of life in patients with FH and increased risk of premature CHD. This perspective is needed to better understand why quality of life does not appear to be negatively impacted by awareness that one has FH.
Quality of life is a multidimensional concept defined from different individual perspectives such as happiness, well-being, and satisfaction with life as a whole from an intellectual and emotional perspective. 8,9 Quality of life is also considered to be good if the patients are competent to choose for themselves and it is also related to the person's capabilities to do or be something in order to achieve a certain functioning. 10,11 It is argued that quality of life is influenced by health status but it is also argued that quality of life can be defined as an individual perception of satisfaction with life in different domains of importance, 12,13 maybe apart from health status. 12 In a meta-analysis of quality of life and health status in articles published since 1990, it was concluded that these 2 constructs are delimited from each other and cannot be used interchangeably. 14 According to Hunt, 15 quality of life, if it has any meaning, is rooted in existentialism. The author means that quality of life is an individual domain with only a small impact of health status and is balanced by coping strategies. In opposition to this, Sprangers and Schwartz 16 mean that changes in health status influence the meaning of self-evaluation of health-related quality of life. Health status, personal characteristics, and behavioral, cognitive, and affective processes influence the response shift, which is defined as “a change in the meaning of one's self-evaluation of quality of life as a result of changes in internal standards, values and the conceptualization of quality of life.”(p1509) Quality of life is a variable social process involving the perception of one's position in life, value system, goals, and expectations, which change during one's life span. 17–19
Quality of life can be defined as health-related quality of life or generic quality of life. According to Ferrans, 20 these concepts are distinct. Definitions of health-related quality of life may be categorized into 3 categories. The first focuses on physical function, symptoms, mental health, and work-related ability. The second category focuses on influence of disease and treatment on quality of life. In addition, the third category focuses on the individual and the possibility that disease may also affect positive aspects of life. Positive in this context may include changes in priorities, experience of disease, and existential perspectives. 13,21
Quality of life, according to Ferrans, 13,21 refers to 5 broad aspects of life: social utility, happiness/satisfaction, achievement of personal goals, normal life, and natural capacity. In the current study, Ferrans perspective of quality of life, “a person's sense of well-being that stems from satisfaction or dissatisfaction with the areas of life that are important to him/her” 13(p2) was used, because the patients with FH in this study were without symptoms of CHD.
Grounded theory, based on the work of Glaser, 22–24 was used to understand the underlying meaning of the concept quality of life in patients with FH. Since quality of life is regarded as a social process, grounded theory, with its roots in social processes, was judged to be an appropriate qualitative method. Grounded theory is based on symbolic interactionism: a way of understanding how people perceive, understand, and interpret the world. Through direct interaction with people in open-minded inductive analyses it is possible to understand, the symbolic world of those studied. 25,26
Sample and Subjects
To include individuals with maximum variability, strategic theoretical sampling was used. Each informant was selected after analysis and coding of the previous informant's interview, to find an informant who could widen the categories. Different background characteristics, gender, age, education, and time since diagnosis were part of the selection process used to find similarities and differences in order to ensure discovery of all categories. 22 Individuals with FH and without CHD were recruited from outpatients at a lipid clinic at a university hospital in Sweden. Patients with FH were identified from an earlier study implemented by the research team. 6 Inclusion criteria included subjects 18 years of age or older, Swedish-speaking, absence of acute disease requiring hospital care, and willingness to consent to tape recording of interviews. Six males and 6 females between the ages of 20 and 69 years were interviewed (Table 1).
Patients were contacted by telephone, asked to participate, and scheduled for an interview. Written information regarding the time and place was mailed to patients who agreed to participate. The interview was performed in patients' homes (6 interviews) or in a small conference room at the university (6 interviews) according to the patients' wishes. The strategic theoretical sampling continued throughout the data collection until saturation was reached after 10 interviews. Two more interviews were conducted for thoroughness and no new dimensions emerged. Permission to carry out the study was granted by the Research Ethics Committee, Faculty of Health Science, Linköping University.
An interview guide was developed by the principal investigators. 27 The guiding questions were as follows: (a) explain what quality of life means to you, (b) describe your quality of life in relation to your situation of having FH, and (c) has your quality of life changed since being told you have FH, and if yes, how? All interviews began with the first question and the following questions were used if the information was not obtained spontaneously. Follow-up questions were used for confirmation. Codes from analysed data guided subsequent interviews. 23 The interviewer was not involved in the medical care of the patients with FH. Interviews lasted 30 to 60 minutes. All interviews were transcribed verbatim.
Data were analysed using constant comparative analysis, a fundamental element of grounded theory analyses. Data were analysed line by line through open coding to generate substantive codes. Substantive codes were compared to find similarities and differences and to generate categories identifying the underlying meaning of quality of life. Categories were then related to each other (collapsed) and data were reviewed repeatedly to verify fitness and relevance. The categories were selectively coded focusing on identification of a core category. The core category is a theoretical construct with relevance and explanatory function, which emerges from the data.
Data were systematically gathered and analysed, with a continuous interplay between analysis and data collection. Two of the authors analysed all the interviews independently. When coding was compared, the two agreed concerning codes and categories. The analysis, the categories, and the core variable became a foundation for further data collection. During data collection, the categories were constantly refitted to be sure they represented the data.
To address rigor, the four components of trustworthiness in qualitative data identified by Lincoln and Guba 28 were met. Credibility was achieved when two of the authors reviewed the data and reached consensus about the analysis. Transferability of the findings to other populations must be carefully evaluated by users in light of the biographical and disease characteristics of the sample. Dependability, which builds on the credibility established, was addressed through the use of an additional researcher (C.B.) who worked as a collaborating analyst during the data collection and analysis. Conformability relates to the ability of an auditor to follow the researcher's decisions as documented in memos. The additional researcher (C.B.) served in this capacity. Together these techniques support the trustworthiness of this qualitative study.
Harmony in Life
Analysis of the interviews revealed that the meaning of quality of life for patients living with FH and at risk of CHD involved finding harmony in life—the core category. Everyone must live with what life gives him or her; quality of life involves balancing one's life situation to find harmony. Individuals make autonomous choices reflecting their own perspective and resources about how to manage life in order to attain harmony. Harmony may have different meanings to different individuals.
The foundation of harmony is living with the ambition of balancing life stressors, the environment, and the positive parts of life. Individuals were cognizant of the burden of genetic disease and the lifelong threat of losing a family member, as the experience of CHD or death of family members has an enduring impact on life. Emotional well-being was influenced by such difficult psychological experiences. On the other hand, being in a family provided a sense of belonging that was supportive. They had family members with whom they could share the burdens and experiences of life. This sharing improved their ability to balance life and find harmony. The threat of premature death caused thoughts of existentialism, which induced personal development. This personal development evolved into support of the next generation to which FH will be left as a legacy.
Existential thoughts focused on transmission of the trait to the next generation. A sense of the threat was always there, as a part of life and a part of the whole family's life. In some way, this awareness provided security, support, and acceptance of the situation. One way to manage life with a family history of disease and death was acceptance and living life in the present instead of focusing on the future. Another way was to have a healthy lifestyle in order to prolong life.
Four categories emerged during the comparative analysis. The categories of harmony in life were satisfaction, togetherness, cognizance, and impending mortality. In order to attain harmony in life, satisfaction was related to the possibilities of togetherness and handling the cognizance of FH and impending mortality. Togetherness was related to shared cognizance and thoughts of impending mortality, as well as satisfaction with life. Cognizance influenced satisfaction and togetherness positively and negatively. The experience of impending mortality was dependent on cognizance and togetherness, which influenced satisfaction (Fig 1).
Satisfaction with life is one category of harmony in life. In order to attain satisfaction with life, an internal strength such as that achieved through personal development and activity was important. Personal development is the sense of maturing through the general experience of life. Personal development refers to maturing into adulthood and acquiring the ability to live a full life with all the associated experiences. Motivation to mature individually was based on a sense of liberty and creative ability.
Liberty is grounded in choices and priorities from spiritual, emotional, and economical perspectives. To live in the present instead of the future, enjoying even small parts of life at the time translates into happiness and appreciation of life. A quality life with closeness to people provided enjoyment of life emotionally and spiritually leading to peace and satisfaction. Satisfaction with life was closely related to a sense of togetherness and a capacity to be cognizant of the negative influences in life.
A sense of closeness and love in a relationship, with someone near to long for, is a dimension of togetherness. Sharing life with someone close gives a feeling of satisfaction, the sense of being needed by another human being. A healthy life together is a great gift, which enhances harmony in life. Togetherness was also improved by a sense of belonging to a family with children and grandchildren. Spending time together with family promoted happiness. Emotional involvement with grandchildren implied a new and deeper meaning of life, as grandchildren are a part of one's life. Likewise, a conscious choice of close friends was important in enjoying life both emotionally and spiritually. Togetherness gave a sense of freedom and satisfaction and thus balance.
One thinks of what is important in life. I socialize with people that I really like.
Security and trust in close friends provided support and satisfaction that facilitated harmony in life. Togetherness improved satisfaction and made it easier to live and share cognizance and threat.
Cognizance of a threat is experienced with awareness and by choosing a strategy to balance life. Being aware of one's life situation, including the threat of disease, can motivate a healthy lifestyle. Cognizance can facilitate living normally with confidence that modern medicine will prevent the disease. Alternately, being cognizant of something threatening to life can be suppressed and balanced by living from day to day without facing the threat. Ignoring cognizance and not letting it influence one's life may cause one to be less aware.
I think I am a bit afraid so I prefer to disappear into my own world of imagination.
A sense of threat that something that may happen anytime gave some a feeling of uncertainty. Lack of knowledge about what the threat and disease mean caused anxiety. Anxiety was also due to lack of knowledge concerning prevention of the disease. Feeling threatened by something that may occur any time together with lack of knowledge gave a sense of uncertainty about the future.
Cognizance and impending mortality are dimensions that influence life when living with a genetic predisposition for disease. Consciousness could decrease the risk of impending mortality by motivating a healthy lifestyle that consequently would decrease worries about health. Alternately, without compliance to a healthy lifestyle, consciously or unconsciously, anxiety increased as the threat of disease increased. Anxiety about family members influenced life more than anxiety about one's own disease. Experience of disease and death in the family may be worse when an individual recognizes that they may be in similar circumstances. The disease experience is connected with the fear of life ending too early.
And one week later my other sister had a heart attack and died, so they were both very sick, and then I thought if it can happen to two, it can happen to me too.
Preventive medical treatment built confidence in the potential for living a long life. Some critical reflections on using medical treatment throughout life were connected with cost, thoughts of side effects and, accordingly, noncompliance.
Disease is not supposed to happen to someone near, but when it does it causes existential reflections about one's life situation. Impending mortality may influence appreciation of life. Cognizance and impending mortality may be supported by togetherness with those around us, which led to life satisfaction, an outcome that harmonized life.
These findings broaden the knowledge regarding what quality of life means when living with a genetic predisposition for disease. The findings provide evidence that patients with FH have generalized thoughts about quality of life and have applied these reflections to their life situations. General thoughts such as satisfaction and togetherness are common dimensions in quality-of-life outcomes 29,30 while cognizance and impending mortality are related to the genetic predisposition for disease. This study suggests that patients living with a genetic predisposition for CHD are constantly balancing life situations to attain harmony.
Satisfaction with life was an important dimension in this study in terms of its influence on the ability to achieve harmony in life, consistent with previous findings. Both patients with FH and their family members reported a good quality of life, as did the control subjects in quantitative studies of quality of life. 6,7 In patients living with chronic leukemia, satisfaction was also found to be the foundation for quality of life. 29
Togetherness was the essential category identified for pair relationships, family, and friends. Together-ness was expressed as a very important dimension supporting harmony in life. A similar result was shown in another sample of persons with FH who reported valuing family life significantly higher than a comparison control group. 6 Togetherness with family members was expressed as important among patients with acute leukemia, as well as among patients with chronic leukemia. Both groups likewise considered friends to be of great importance in their lives. 29,31 Malm et al 32 found cohabiting patients with a pacemaker assessed their quality of life as being higher than single patients did. Patients at risk for medullary thyroid carcinoma also indicated their family to be the most important part of their quality of life. 33 In women at risk for breast cancer, the risk was viewed as a family affair, affecting everybody around them; both family and friends provided emotional support. 34 Living in a family facilitates harmony in life and the possibility of sharing the burden of awareness of genetic disease.
Some respondents faced the threat and others ignored it. Managing life cognizant of a genetic threat was easier for some when facing the facts. For others, ignoring the genetic threat made life easier because they did not know about the disease. In a study of parents' perceptions of their children with FH, 11% of the parents thought that their quality of life would have been better without awareness of the disease. 35 Because of an uncertain future, Appleton et al 34 reported women with an increased risk of breast cancer as “taking one day at a time,” which may be one way of putting the threat aside. Living with a threat may strengthen one's coping capacity while the threat may cause existential thoughts and possibly bring family members nearer to each other because of the fear of losing a family member. Hyland 36 notes that symptoms do not necessarily cause problems in patients with effective coping strategies.
Personal experience of premature CHD and losing a family member through CHD may cause anxiety but one coping strategy is to balance life by acceptance of the disease threat. Anxiety that family members will develop CHD may be expressed rather than face the fear of one's own death. This focus on the family instead of oneself was noted by Tatarkiewicz 8 who asserts that one's own death usually seems to be distant and unreal. From an emotional perspective, feelings of suffering due to uncertainty about the future can be hard to bear, while the possibility of seeing into the future is likewise unbearable. Great suffering is usually identified as unhappiness but Tatarkiewicz 8 implies that it is its effect on our attitude that can be called unhappiness. Intellectually, the individual can change the internal balance in order to adapt to the environment and what is dealt with, in order to facilitate the attainment of happiness. The meaning of quality of life, as rooted in existentialism and argued by Hunt, 15 seems to be supported by these findings where cognizance and impending mortality were categories of harmony in life.
Acceptance or ignoring could be due to a response shift after an experience of CHD in the family. 16 According to Schönnesson 37 existential responsibility, a sense of coherence, and meaningfulness are also aspects of quality of life. Thoughts of transmitting the genetic predisposition to the next generation may be part of existential responsibility, while creating a family, for many people, provides a sense of coherence and meaningfulness in life. According to Tatarkiewicz, 8 awareness of genetic disease is not less painful despite being general and unavoidable. Awareness of having been able to change things or take a different turn would be even more distressing than death.
The meaning of genetically mediated impending mortality and how it may appear is especially hard to bear when reaching the age at which a family member developed CHD. Similar thoughts were experienced by daughters of women with a family history of breast cancer, as well as by women informed about an increased genetic risk of breast cancer, when they reached the same age as their mothers were when diagnosed with breast cancer. 34,38 Anxiety about loss of health, loss of life, and loss of position in life is something that can haunt the individual for years and affect harmony. These thoughts about effects on harmony in life and happiness are in agreement with Tatarkiewicz. 8
From a general human perspective, everyone has some strategies for attaining harmony in life. With thoughts of impending mortality, there is perhaps even more intensive striving towards harmony, as the threat can reduce lifespan. Living with threat has to be balanced with an emphasis on the good parts of life to attain harmony. Living a normal family life and having close friends seems to be an important aspect of attaining harmony in life.
Grounded theory was an appropriate method for a study of this type, as it facilitated understanding of the human and social processes surrounding awareness of FH. As grounded theory is grounded empirically, through conceptualization and descriptive fitting of examples from the data, there is the possibility of transferability of the findings. 24 Living with other kind of threats, genetic or otherwise may be an experience similar to the threat of CHD.
This study was limited by failure to include patients from other cultures with FH, although 10% of Swedish inhabitants are immigrants. People from different cultures may experience their quality of life and awareness of disease in different ways, which is why cultural differences in this context would be interesting to study separately. The sampling method of strategic theoretic selection from a list of patients diagnosed with FH can be seen as a selection bias, although this list represented the total population of patients diagnosed with FH.
Patients with FH have an increased risk of developing CHD. This study gives new perspectives of the meaning of living with genetic disease where threat is expressed as something that gives a feeling of uncertainty. From an ethical perspective it could be argued that cognizance contributes to a better quality of life. Some patients live a life in harmony without cognizance of the genetic predisposition for disease and some are fully aware of FH as a genetic trait and seek to prevent premature disease.
When caring for these patients, it is important to meet each individual patient on his or her own level and to support the strategies chosen by that patient to balance life towards harmony. There is no standardized care advice that can be recommended as every patient experiences his or her situation individually. It is important to provide patients with information and support according to their lifestyle and their desires and to provide medical treatment according to individual needs. Patients whose coping strategy is to put aside the cognizance must be respected for their chosen strategy, although they need to receive answers to their questions. Awareness of patients' suffering from anxiety and uncertainty of the future demonstrates sensitivity and respect and supports patients in their goal of reaching harmony. Healthcare professionals need to be aware of changes in response due to cognizance of impending mortality, as living with such a threat is transferable to individuals with other genetic traits that may cause future disease.
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