Psychosocial Impact of Screening for Intracranial Aneurysms in Relatives With Familial Subarachnoid Hemorrhage
Background and Purpose— In families with ≥2 relatives with intracranial aneurysms (IAs), screening for IAs in asymptomatic first-degree relatives is often recommended. We assessed the long-term psychosocial impact of such screening.
Methods— We identified all persons with IA (screen-positives) and matched them for age and sex with 2 controls without IA (screen-negatives) from hospital-based registers of familial IA. Persons underwent telephone interviews using questionnaires that covered the areas of psychosocial impact of screening, health-related quality of life (HRQoL), and mood. Data were compared between screen-positives and screen-negatives, and with reference populations.
Results— Overall, 105 persons from 33 families with IA were included, of whom 35 were screen-positive and 70 were screen-negative. Of the screen-positives, 12 (44%) had reduced their work and 23 (66%) had experienced changes in ≥1 area of independence, self-esteem, future outlook, or personal relationships. In contrast, only 1 (2%) screen-negative person had stopped working and 12 (17%) others had experienced changes in their self-esteem, future outlook, or relationships. Screen-positives had lower HRQoL compared with screen-negatives and the reference population, whereas both screen groups had higher mean depression scores than the reference population. Despite these effects, only 3 persons regretted participating in screening.
Conclusion— Although screening for IA is an important preventative strategy in high-risk individuals, it is associated with considerable psychosocial effects, both positive and negative. Greater awareness of such outcomes, and appropriate intervention where necessary, would appear to be a necessary component of IA screening programs.
Persons with ≥2 first-degree family members with a history of intracranial aneurysms (IAs) are at increased risk of subarachnoid hemorrhage (SAH).1 Given that screening of the cerebral circulation may detect asymptomatic IAs in ≈8% of the relatives,2 and the yield of repeated screening 5 years after a negative screen is also high in this group,3 various guidelines such as those of the American Heart Association recommend that screening should be considered in relatives with familial SAH.4
The yield of screening for IAs and the risks associated with diagnostic interventions and preventive treatment are well accepted. However, less well understood are the psychosocial consequences of screening for IA because no formal assessments of such outcomes have been conducted to date. Indirect evidence from screening programs in breast cancer and abdominal aortic aneurysms indicate the potential benefits of a positive result of screening could be offset by depression and reduced quality of life in persons,5 whereas a screen-negative result may be associated with such relief that it can increase the psychosocial well-being of participants.6
We aimed to determine the psychosocial effects of screening for familial IAs by comparing aspects of social well-being and lifestyle, health-related quality of life (HRQoL), and mood symptoms in persons with positive screens with persons with normal screens and with such measures in the general population.
Persons and Methods
We included relatives who had been screened for IAs between 1993 and 2003 because of familial SAH from registers at 2 institutions: the Academic Medical Center Amsterdam and the University Medical Center Utrecht. Familial SAH was defined as ≥2 first-degree family members with SAH or unruptured IAs. We identified all persons with an IA detected on screening (screen-positives) and selected for each person with a positive screen 2 controls from the group of relatives in whom no IAs were detected (screen-negatives). The 2 groups were matched for age (±3 years) and sex. Potential control persons who declined to participate, could not be contacted by telephone after several attempts, or had moved outside the area were replaced by other controls. In all persons, the screening had to be performed ≥1 year previously.
Some of the participants had participated in another study on screening for familial IA and had provided written informed consent for follow-up contact and administration of questionnaires about their health. The others had consented at their last visit to an outpatient clinic for further contact and participation in a research project regarding the outcome from IA screening.
Participants underwent standardized, semistructured, telephone interviews with 1 of 2 researchers (M.J.H.W., P.V.N.), who administered 4 questionnaires: 1 developed specifically for the purposes of the study, 2 questionnaires assessing HRQoL, and the Hospital Anxiety and Depression Scale (HADS). The specifically developed questionnaire contained a series of questions on health and lifestyle covering aspects of behavior, work, health insurance, relationships, reproductive decision-making, self-esteem, and level of independence, all of which may have been affected by the screening. Each question could only be answered by “yes” or “no.” If the answer to the question was yes, the subsequent question was whether the outcome was attributable to screening (again, yes or no). The 2 researchers did 5 of the interviews together at the start and in the middle of the study to avoid possible interobserver variation.
As HRQoL instruments, we used the validated Dutch versions of the Medical Outcome Study 36-item short form questionnaire (SF-36) and the EuroQol.7,8 The SF-36 comprises 36 questions covering 8 domains: physical functioning (PF), role limitations because of physical problems (role-physical [RP]), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role limitations because of emotional problems (role-emotional [RE]), and mental health (MH). An absence of problems in a domain is indicated by a score of 100 for the PF, RP, BP, SF, and RE domains, and of 50 for the GH, VT, and MH domains. For example, a score of 100 in PF indicates an ability to perform all activities without limitations attributable to ill health, whereas a score of 50 in MH indicates an ability to function without personal or emotional problems. To obtain scores of >50 for GH, VT, and MH, a subject must rate his/her health positively; for example, a score of 100 in MH would indicate that the subject feels “peaceful and happy and is calm all the time.” The EuroQol contains 5 questions addressing mobility, daily activities, pain, self-care, and anxiety and depression, with responses converted to an overall score ranging from 0 (worst) to 100 (best), and a visual analog scale (EQ-VAS) in which persons can rate their overall health state by placing a mark on a vertical scale which ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). For the purposes of this study, persons were asked to “rate their overall health on a scale from 0 to 100.” The HADS,9 a simple screening test for symptoms of anxiety and depression, contains 14 questions on mood that provide separate rating scales for anxiety and depressive symptoms ranging from 0 to 21 to allow the classifications of “normal” (scores <8), “possible depression or anxiety” (scores of 8 to 10), and “probable depression or anxiety” (scores >10).10
Data on screen-positives were compared with those of screen-negatives and with reference Dutch populations, which consisted of a representative sample of 199 persons for the HADS,9 4172 persons for the SF-36,7 and 113 persons for the EuroQol (Stolk et al, unpublished data, 2004). Responses to the specially developed health and lifestyle questionnaire were only compared between the groups of persons who had undergone IA screening using the γ2 test statistic. Differences between groups in scores on the HADS, the SF-36, and the EuroQol were assessed using Student’s t test statistic. All data are reported with 95% CIs.
Overall, 39 persons with IAs identified through screening for familial SAH were listed on registries. Three of them had moved since the last screening and their address was unknown, and 1 person declined to participate, leaving 35 persons who were included in this study. Seven of these persons had a small IA and were managed conservatively; the remaining 28 had been treated for the detected IA.
There were 184 screen-negative relatives, from which 70 age- and sex-matched controls were selected. For 5 persons who could not be contacted and 2 others who declined participation, replacement persons of the same sex and comparable age were found.
Thus, a total of 105 persons were included in this study; they came from 33 different families (Table 1).
Lifestyle, Work, Social, and Emotional Outcomes
Of 27 screen-positives who were in full-time employment at the time of screening, 12 (44%) had stopped working or reduced their hours after screening (Table 2). In contrast, only 1 (2%) of 53 employed screen-negatives had stopped working, but this was done voluntarily because the “healthy” outcome had led to a re-evaluation of priorities in life. Three (9%) screen-positives reported an increase in health insurance payments after screening.
Altogether, two thirds of screen-positives reported changes in their social circumstances and emotional well-being, including a decrease in their level of independence, reduced self-esteem, alteration in their ability to cope with stress, or a change in outlook on the future. At least 1 of these changes was negative in nature in 21 (60%) of the respondents. Four subjects reported negative effects on relationships, although another 7 said that their relationships had improved because the bond with a partner had tightened as a consequence of the findings. One person decided not to have a second child because of the detection of an IA. Of the 70 screen-negatives, 12 (17%) reported changes in their social or emotional well-being, but in only 7 (10%) was this negative in nature.
There were 17 (49%) of 35 screen-positives and only 9 (13%) of 70 screen-negatives who said that they had changed to a healthier lifestyle as a consequence of screening.
Nine (26%) of 35 screen-positives reported that they avoided certain daily activities because of concern that they might lead to IA formation or rupture. Despite these changes, only 2 (6%) screen-positives and 1 (1%) screen-negative said that they regretted participating in the screening program. Both screen-positives who regretted screening were relatives in whom the aneurysm was left untreated.
Health-Related Quality of Life
Screen-positives were similar to the reference population with regard to overall scores on the EuroQol (difference of means 5.7; 95% CI, −3.1 to 14.5), but different from screen-negatives (difference of means 13.9; 95% CI, 3.5 to 24.3; Table 3). Screen-negatives had significantly better overall HRQoL than the reference population (difference of means 8.2; 95% CI, 1.6 to 14.8).
On the EQ-VAS, screen-positives evaluated their overall health state as lower than that of screen-negatives (difference of means 5.6; 95% CI, −2.1 to 13.3) and of the reference population (difference of means 8.3; 95% CI, 1.7 to 14.8). Screen-negatives also tended to evaluate their overall health lower than the reference population (difference of means 2.7; 95% CI, −1.9 to 7.2).
Compared with the reference population, screen-positives performed significantly worse on the SF-36 domains of BP (difference of means 14.5; 95% CI, 6.3 to 22.6) and VT (difference of means 6.5; 95% CI, 0.1 to 12.9), whereas screen-negatives performed significantly better on VT (difference of means 6.4; 95% CI, 1.8 to 10.9), SF (difference of means 7.4; 95% CI, 2.3 to 12.5), RE (difference of means 10.2; 95% CI, 2.5 to 17.9), and MH (difference of means 9.9; 95% CI, 3.7 to 14.0; Figure 1). There were no differences in quality of life between the 7 untreated screen-positives and the 28 treated screen-positives.
Anxiety and Depression
Mean HADS scores for depression (Figure 2A) were similar for screen-positives and screen-negatives (5.6±2.7 versus 5.6±2.2), but they were statistically significantly higher than in the reference population (3.4±3.3; difference of means 2.2; 95% CI, 1.1 to 3.4). However, the mean scores for depression in both IA subject groups were below the threshold for “possible depression,” and only 2 (5.7%) screen-positives and 3 (4.3%) screen-negatives had scores in the range of “probable depression” (Figure 2B).
The mean HADS score for anxiety (Figure 2A) was lower in the screen-negatives (4.2±3.3) than in the screen-positives (5.0±4.1) and in the reference population (5.1±3.6), although the mean difference of 0.9 (95% CI, −0.1 to 1.82) between screen-negatives and the reference population was not statistically significant. Only 3 screen-negatives (4.3%) had a score in the range of “probable” anxiety compared with 5 (14.3%) screen-positives (Figure 2B).
The 7 untreated screen-positives had comparable depression subscores but slightly higher anxiety subscores (mean 6.1) than the treated screen-positives, but this difference was not statistically significant.
Screening for IAs can have a significant impact on lifestyle and psychosocial well-being of persons long after the results are known. The most pronounced effects were seen in those persons who screened positive for IA, with many reporting adverse outcomes in aspects of lifestyle, behavior, work, and social and emotional functioning. Even so, up to half of these persons also reported changing their behavior toward healthier living. Similar effects were reported in <1 in 10 of the screen-negatives. The HRQol in screen-positive persons was lower than the HRQol in screen-negatives and the reference population.
There are no previous published data on the psychosocial effects of screening for IAs. Indirect evidence from other screening programs indicate that a normal result may be reassuring and be associated with an increase the health and well-being of participants.6 The higher scores in certain aspects of HRQoL and lower anxiety levels in screen-negatives compared with a reference population are consistent with findings in other patient groups. With regard to our assessment of work, lifestyle, and social and emotional functioning, we often found negative effects on self-esteem, coping with stress, and future outlook among screen-positives, whereas these areas of life were frequently viewed more favorably for screen-negatives. These results are comparable with the psychosocial impact of genetic screening in other neurological diseases such as Huntington disease, ataxias, and neuromuscular disorders.11,12
The psychosocial impact of screening in relatives with a detected but untreated aneurysm may also vary according to the information given about the rupture risk of the aneurysm. However, all relatives, including the 7 untreated ones, were seen by 1 of 2 neurologists who gave all information on screening and aneurysms as neutrally as possible.
The results of the questionnaires did not differ significantly between the untreated and treated screen-positives, except that both screen-positives who regretted screening had an untreated aneurysm.
The strengths of this study lie in a large and representative sample of persons, with only a few persons lost to follow-up and a high level of participation. Because the baseline characteristics of nonparticipants were comparable to that of participants, selection bias is likely to be low. Most of the data were obtained using simple and direct questions and with well-validated and reliable instruments.
Several limitations must be acknowledged. This was a cross-sectional study undertaken long after the results of screening were known to persons. Therefore, we were unable to assess the early effects of IA screening, when anxiety and depressive symptoms are more likely to occur. In addition, because of the cross-sectional design, we did not have assessments of HRQol and HADS scores from before screening was performed.
Another limitation was that the reference population for SF-36 measures was slightly younger (±8 years) and contained fewer women (54% versus 66%) than our IA screen persons, and we did not have age- and sex-specific data from the reference population to make adjustments. The validation study of this reference population showed only modest differences between men and women and between the age categories 41 to 60 and 61 to 70 years.12 Therefore, it seems unlikely that comparisons of the crude SF-36 data would have had a major impact on the results.
Finally, the reference population did not consist of persons with familial SAH who had not participated in an IA screening program. It is possible that asymptomatic persons with familial IA who do not participate in screening have a lower HRQol than a reference population without familial SAH. Knowledge of the presence of an unruptured IA is associated with a decrease in quality of life.13 Although nonparticipants have no such knowledge, they probably realize that they are at increased risk of harboring an aneurysm. Furthermore, the experience of SAH-related death or disability in close relatives might have an impact on the quality of life of asymptomatic relatives. Therefore, we recognize that we might have underestimated the positive HRQoL difference for screen-negatives and overestimated the negative HRQoL difference for screen-positives, against the reference population.
The psychosocial impact of IA detection among those who participate in a screening program appears wide-ranging and considerable. Given the major consequences of ruptured IAs, including death in half and disability and reduced HRQoL in many,14 there is no denying the importance of screening to reduce the mortality and morbidity associated with SAH. Yet it needs to be recognized that screening can have a considerable impact on the health and psychological well-being of persons. Appropriate support and professional counseling, where appropriate, may be important components of a screening program. The psychosocial consequences of a positive screening should be discussed with asymptomatic relatives before the decision is made about whether or not to proceed to screening.
This study was supported in part by an established clinical investigator grant from the Netherlands Heart Foundation to G.J.E.R. (D98.014) and a grant from the Netherlands Organization for Scientific Research/ZonMw (945-02-007).
- Received October 12, 2004.
- Revision received December 10, 2004.
- Accepted January 4, 2005.
Bromberg JE, Rinkel GJ, Algra A, Greebe P, van Duyn CM, Hasan D, Limburg M, ter Berg HW, Wijdicks EF, van Gijn J. Subarachnoid haemorrhage in first and second degree relatives of patients with subarachnoid haemorrhage. BMJ. 1995; 311: 288–289.
Raaymakers TW, Rinkel GJ, Ramos LM. Initial and follow-up screening for aneurysms in families with familial subarachnoid hemorrhage. Neurology. 1998; 51: 1125–1130.
Wermer MJ, Rinkel GJ, van Gijn J. Repeated screening for intracranial aneurysms in familial subarachnoid hemorrhage. Stroke. 2003; 34: 2788–2791.
Bederson JB, Awad IA, Wiebers DO, Piepgras D, Haley EC Jr, Brott T, Hademenos G, Chyatte D, Rosenwasser R, Caroselli C. Recommendations for the management of patients with unruptured intracranial aneurysms: a statement for healthcare professionals from the Stroke Council of the American Heart Association. Stroke. 2000; 31: 2742–2750.
Scaf-Klomp W, Sanderman R, van de Wiel HB, Otter R, van den Heuvel WJ. Distressed or relieved? Psychological side effects of breast cancer screening in The Netherlands. J Epidemiol Community Health. 1997; 51: 705–710.
Aaronson NK, Muller M, Cohen PD, Essink-Bot ML, Fekkes M, Sanderman R, Sprangers MA, te Velde A, Verrips E. Translation, validation, and norming of the Dutch language version of the SF-36 Health Survey in community and chronic disease populations. J Clin Epidemiol. 1998; 51: 1055–1068.
van der Schaaf IC, Brilstra EH, Rinkel GJ, Bossuyt PM, van Gijn J. Quality of life, anxiety, and depression in patients with an untreated intracranial aneurysm or arteriovenous malformation. Stroke. 2002; 33: 440–443.
Hop JW, Rinkel GJ, Algra A, van Gijn J. Quality of life in patients and partners after aneurysmal subarachnoid hemorrhage. Stroke. 1998; 29: 798–804.