Patient Prefer Adherence. 2010; 4: 335343. PMCID: PMC2943225 Published online 2010 September 7.

Copyright 2010 Tsiantou et al, publisher and licensee Dove Medical Press Ltd. Factors affecting adherence to antihypertensive medication in Greece: results from a qualitative study Vassiliki Tsiantou,1 Polina Pantzou,2 Elpida Pavi,1 George Koulierakis,2 and John Kyriopoulos1 1 Department of Health Economics, National School of Public Health, Athens, Greece; 2 Department of Sociology, National School of Public Health, Athens, Greece Correspondence: Vassiliki Tsiantou, National School of Public Health, Department of Health Economics, Alexandras Ave 196, 11521 Athens, Greece, Tel +30 210 64 35 328, Fax +30 210 64 49 571, Email vtsiantou@esdy.edu.gr Received August 26, 2010 This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.
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Other Sections o Abstract o Introduction o Methods o Results o Patientphysician relationship o Patientpharmacist relationship o Discussion o Conclusion o References

Abstract Introduction: Although hypertension constitutes a major risk factor for cardiovascular morbidity and mortality, research on adherence to antihypertensive treatment has shown that at least 75% of patients are not adherent because of the combined demographic, organizational, psychological, and diseaseand medication-related factors. This study aimed to elicit hypertensive patients beliefs on hypertension and antihypertensive treatment, and their role to adherence. Methods: Transcripts from semistructured interviews and focus groups were content analyzed to extract participants beliefs about hypertension and antihypertensive treatment, and attitudes toward patientphysician and patientpharmacist relationships. Results: Hypertension was considered a very serious disease, responsible for stroke and myocardial infarction. Participants expressed concerns regarding the use of medicines and the adverse drug reactions. Previous experience with hypertension, fear of complications, systematic disease management, acceptance of hypertension as a chronic disease, incorporation of the role of the patient and a more personal relationship with the doctor facilitated adherence to the treatment. On the other hand, some patients discontinued treatment when they believed that they had controlled their blood pressure. Conclusion:

Cognitive and communication factors affect medication adherence. Results could be used to develop intervention techniques to improve medication adherence. Keywords: hypertension, medication adherence, patient compliance, doctorpatient communication, antihypertensive medicine
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Other Sections o Abstract o Introduction o Methods o Results o Patientphysician relationship o Patientpharmacist relationship o Discussion o Conclusion o References

Introduction Nonadherence to treatment medication, especially in chronic diseases, is a complicated issue affecting patients health, health expenditure, and recourses utilization.1,2 A number of studies, both qualitative and quantitative, examine the factors that are believed to explain variations in adherence in other chronic diseases.35 Based on such findings, interventions have been designed to improve patient compliance.6 Research on health behaviors, such as medication adherence, has resulted in the formulation of specific psychological theories addressing patients beliefs and roles. Leventhal and colleagues Self-Regulatory Model (SRM)7 suggests that when individuals face a health threat, they form both cognitive and emotional representations of the disease, which act in parallel to influence associated health behaviors. Cognitive representations comprise of beliefs on illness identity, antecedent causes, consequences, timeline, and cure-control,8 whereas the emotional representations comprise individuals emotional reaction to the disease. Furthermore, individuals beliefs about treatment have been proposed as another determinant to understand the way in which patients make decisions about their treatment.9 Finally, different aspects of doctorpatient communication have been examined as potential predictors of medication adherence.10 Hypertension is the medical condition where the systolic blood pressure is more than 140 mm Hg and the diastolic blood pressure is more than 90 mm Hg.11 It is a chronic disease which is considered to be one of the major public health problems and a significant cardiovascular risk factor. According to the World Health Organization (WHO), each year, at least 7.1 million people die as a result of increased blood pressure.12 For the treatment of hypertension, a broad range of antihypertensive medications are currently available, as well as Therapeutic Lifestyle Changes such as weight reduction, increased physical activity, and reduction of dietary salt intake, which have proven to be important in disease management.13 Although there is evidence that increased blood pressure can actually be controlled with the cardiovascular risk factor being thus reduced,14 75% of patients diagnosed with hypertension cannot achieve full control of their blood pressure.13 Poor blood pressure control is associated with higher healthcare resource utilization and costs15 and increased risk of cardiovascular diseases. Nonadherence to

antihypertensive medication is the main reason for failure to control blood pressure among those under treatment.16 In Greece, although there is no nationwide data available for the prevalence of hypertension, it is estimated that 25% of the adult population are suffering from it.11 Moreover, it is estimated that 40% of hypertensive adults are unaware of their condition, and 25% of those receiving treatment do not succeed in controling their blood pressure.11 Other studies have shown that awareness and control of hypertension and blood pressure is lower in Greece compared with other countries.17,18 In addition, few studies have been conducted in Greece investigating the issue of adherence to treatment. The aim of the present study was to investigate the factors affecting antihypertensive medication adherence in Greece.
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Other Sections o Abstract o Introduction o Methods o Results o Patientphysician relationship o Patientpharmacist relationship o Discussion o Conclusion o References

Methods Study design Semistructured interviews and focus groups were conducted in order to elicit data from people with hypertension. Semistructured interviews were preferred for those attending the Hypertension Centers (HCs) (Group A), allowing the investigators to approach them individually, as HC attendees were of older age. Older age is related to sensory loss that interferes with reception of the spoken message. People with sensory loss thus frequently experience communication problems.19 One-to-one semistructured interviews could overcome this problem, which might otherwise influence older age participants ability to participate effectively in focus groups. Focus groups were preferred for the group of younger participants (Group B), aged between 40 and 50 years, who were not or usually were not attending the HC, suffer from sensory loss. The age criterion was based on the available data regarding hypertension prevalence in Greece.20 According to these data, diagnosed hypertensive patients younger than the age of 40 years represent less than 1.6% of the total number of hypertensive patients. Although it would be really hard for these patients to be identified, we decided to have this age criterion of hypertensive patients older than 30 years in case we could not find anyone between the ages of 3040 years. In the case of focus groups, the lower limit was increased, from 30 to 40 years of age, because it was impossible for us to identify hypertensive patients between the ages of 3040 years among the registered hypertensive patients. Fieldwork was conducted during the period MayJuly 2008. Participants and settings Group A participants were recruited from HC established in hospitals of the greater Athens area. Three HCs were purposively selected in order to reflect different geographic and socioeconomic

regions. Two were established in public hospitals, and the third was established in an insurance fund hospital. In each center, the physician in charge assisted researchers to recruit patients. Participants had to meet the following inclusion criteria in order to participate in the study: (a) being aged above 30 years, (b) receiving antihypertensive treatment for at least 1 year, and (c) speaking the Greek language fluently. When patients who met the inclusion criteria attended the HC, on a specific day, an invitation letter was given to them by their physician explaining the purpose and the methodology of the study. In total, 25 patients accepted to be interviewed. Interviews were conducted, immediately after patients medical examination in a private room in the HC, provided for the purposes of this study. All interviews were facilitated by two researchers (psychologist [PP] and co-moderator [VT]). All interviews were anonymous and were audio taped, after participants consent. For Group B participants, the inclusion criteria were as follows: (a) being aged between 40 and 50 years, (b) receiving antihypertensive treatment for at least 1 year, (c) not consulting an HC, and (d) speaking the Greek language fluently. Recruitment for Group B participants was made with convenience and purposive sampling. A telephone invitation survey among 200 registered hypertensive patients was conducted in order to identify those who met the inclusion criteria and were willing to attend the focus group sessions. In total, 18 patients (50% female) accepted to participate. Similar to semistructured interviews, participants were informed about the aims of the study, the methodology, and were assured of anonymity and confidentiality. Two focus groups were organized, one comprising of 9 males and the other comprising of 9 females, in order to facilitate group dynamics and achieve higher homogeneity.21 Each group was moderated by an experienced psychologist and a co-moderator whose primary responsibility was to take notes during sessions. Both researchers met after each session in order to assess the procedure and identify crucial elements for the interpretation of the data. Focus groups took place at the Department of Health Economics, National School of Public Health in Athens. The first session had a duration of 2 hours 8 minutes and the second 2 hours 22 minutes. Comfortable chairs, beverages, and snacks were offered in order to create a pleasant atmosphere and lighten the burden of the long duration of the focus group. Focus group sessions were tape-recorded, after participants written consent. Content and questions According to standard methodology, open-ended questions and probes were predetermined for use during the semistructured interviews and the focus groups. These were based on the review of the relevant literature, taking into consideration the recommendations of the research team. Questions and probes fell within four research topics (see Table 1): perceptions and beliefs about hypertension, perceptions and beliefs toward antihypertensive treatment, patientphysician relationship, and patientpharmacist relationship. Commencing questions in each research topic were general, capturing participants beliefs in hypertension and treatment. Probes were more specific in order to elicit the opinion, experience, and behavior of the participant. Only demographic information was collected by a purpose-made short questionnaire. Table 1 Topics and subtopics of the qualitative study

Analysis

All interviews and focus group recordings, as well as notes kept by the focus group comoderator, during the sessions were fully transcribed. Transcriptions were analyzed using content analysis,22 without using any qualitative data software. Each researcher (PP and VT) separately studied the transcriptions and the notes kept by the co-moderator, identified the emergent themes and keywords, and categorized the findings according to the four research topics. Then, the research team met in order to compare the findings, interpret results, and formulate conclusions. Demographic data were analyzed using MS Excel 2007.
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Other Sections o Abstract o Introduction o Methods o Results o Patientphysician relationship o Patientpharmacist relationship o Discussion o Conclusion o References

Results Group A comprised of 25 participants aged between 47 and 79 years (mean age, 63.7 years), whereas the 18 participants in Group B were aged between 40 and 50 years (mean age, 44.6 years; Table 2). Participants did not differ significantly in relation to gender. Group A participants were more likely (84%) to be under medication treatment for co-morbidities than their Group B counterparts (66.7%); however, this difference did not reach statistical significance. Table 2 Demographic characteristics of the participants

Perceptions and beliefs about hypertension Hypertension was considered a very serious disease responsible for even more dangerous medical conditions such as stroke and myocardial infarction. Stress, anxiety, limited physical activity, and unhealthy diet emerged as the perceived most important risk factors of hypertension.
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Hypertension has very serious consequences, you can have a stroke it is very bad. (Group A, female) Cardiovascular diseases and death. This is what I am thinking when I hear hypertension. If you dont control it you will die. (Group B, female) I believe that stress is the major factor that makes all of us or at least most of us suffering from hypertension (Group B, male) It is not only stress, but the way of life in general. (Group B, male)

Sources of information

The main sources of information were the physician or the pharmacist, the media, the Internet, and people who suffered from hypertension. However, participants admitted that their physician was the most trusted source. Participants were interested in further information for two reasons: to achieve a better understanding of their doctors advice and to check the validity of this advice.
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My doctor gave me some information, but I search information through Internet too, so I can cross-check what he says. (Group A, male) mainly my doctor and some books. But usually I talk with people who also suffer from hypertension, I feel more comfortable discussing with them (Group A, female) There are TV programs about health, but I always discuss everything I hear with my doctor (Group B, male)

Symptoms and disease diagnosis Although hypertension was associated with well-recognized symptoms, such as headaches and dizziness, participants often did not seek health care, at least until those symptoms became unbearable.
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I knew that I had high blood pressure but I had never gone to a doctor, until I couldnt bear the pain of the headaches (Group A, male) I was feeling a constant pressure in my head, so I decided to consult a doctor (Group B, female)

When symptoms were mild, participants were usually referring to a pharmacist. If symptoms were more intense, they were looking for a specialist mainly an internist or a cardiologist.
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I was not feeling well, so I went to a pharmacist to measure my blood pressure (Group B, female) One day, I felt very strange, like having a heart attack or stroke; I was so scared that I went to the hospital (Group B, male) I had strong headaches and because my father had also hypertension, I went to a cardiologist (Group A, female)

Participants perceptions and beliefs toward antihypertensive treatment Attitudes and beliefs towards drugs Concerns and fear were expressed by the majority of participants regarding the use of medicines. Some of them expressed the opinion that the long-term use of medicines will have an impact on their immune system.
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In general, I avoid taking medicines. If the decision is on me I will not take any drugs (Group A, male) Some years ago I was suffering from spondylolisthesis and my doctor prescribed anti-inflammatory, and then my blood pressure was 18 to 19. (Group A, female) I have taken so many drugs that I have destroyed my immune system (Group A, female) I dont like it (taking drugs) at all, because you try to fix one thing and something else goes wrong (Group A, female)

Yes, but so many drugs? Dont all of these end up in the liver? For how long can it (the liver) bear all these? and it is only one. I dont know, I am a little afraid. (Group B, female)

Adverse drug reactions Adverse drug reactions were an issue of great concern for the majority of study participants. Some of them had stopped their treatment because they were afraid of the possible side effects. Avoidance of getting to know the possible side effects was also one of the reasons given for not reading the information leaflet of the drug.
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If I read (in the leaflet) that the drug has adverse drug reactions and this or that can happen to me, I stop the treatment (Group A, male) If you read about side effects you should not take any medicine. However, I have prevented some reactions because I had read the information leaflet (Group A, male) I dont read the side effects, because then I think that I suffer from all these reactions (Group B, female) I usually read the side effects, but I cant understand everything I trust my doctor who prescribes it. If something goes wrong I believe that I will understand it (Group B, male)

Factors influencing adherence to antihypertensive treatment The level of adherence among participants ranged. Previous experiences regarding hypertension and the fear or knowledge that they could suffer from a complication if they did not control their blood pressure were important reasons for medication adherence.
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I didnt know what it means to have high blood pressure for years and what this can cause to you (Group A, male) because I have read and I know what can happen to me if I do not follow the treatment (Group A, female) I take the pill every day, because I am afraid (Group B, female) my neighbor had a stroke 5 years ago and he hasnt recovered yet. I see all these and I follow my treatment because I am afraid that this will happen to me too. (Group B, male) I am afraid of what will happen to me because of the hypertension, there is also the heredity. (Group B, male)

In addition, systematic disease management, especially in HC, was a significant factor influencing treatment adherence.
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Here (in the HC) I have a program and I come regularly for my blood pressure (Group A, male) First of all, it is very important that I come here regularly and I have a program, an antihypertensive program, and since Ive started taken my pills nothing has gone wrong (Group A, male)

Another important factor affecting adherence was the acceptance of the disease and the adoption of the patients role. Most of the participants, especially the younger ones who participated in focus groups, were hesitant and negative to the idea of taking a medicine for their whole life. The sooner they perceived hypertension as a chronic disease, the more adherent they became.
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at first I was really stressed. I didnt want to believe that I will receive an antihypertensive treatment, why me? I was feeling really sad, it was like killing me (Group B, male) I believe that it is tragic to take a medication for the whole of your life, I cant stand it. I believe that it is the beginning of the end, the beginning of taking more drugs (Group B, male)

Sometimes, acceptance of the disease led to the change of patients lifestyle.

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after this (the diagnosis of hypertension) the whole perspective about my diet changed (Group B, male)

Adherence characteristics Adherence to treatment was easier if the medication were received in the morning. In this case, the majority of participants had associated their medication with their breakfast or had invented different tricks in order to remember it.
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I take it during breakfast, I am used to it now (Group A, female) I take it every morning, I set the alarm clock in order to remember it, you have to associate it with something, otherwise you forget it (Group B, male)

Most of the participants admitted during weekends they received their medication some hours later than the appropriate, believing that this was an innocent tactic, although their doctor had warned them for the opposite.
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At the weekends I take my pill 3 hours later I dont believe it does any harm. On the contrary, three hours more sleep is good because our organism is calm when we are sleeping. When we wake up we need the pill (Group B, female)

The drug substance also seemed to be an important factor affecting adherence when its effects interferes with patients activities.
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I take one pill every morning. But, because it is diuretic, when I go out I do not take it (Group A, male)

Finally, some of the participants mentioned that they stopped the treatment from time-to-time when they no longer suffered from symptoms or when they believed that they had controlled their blood pressure.
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If my blood pressure is at good levels, I cant see the reason to take it (the pill). I am afraid to take it because it might cause hypotension to me. (Group A, female)

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When I have symptoms I follow my treatment, when I feel good I dont . (Group B, female) I stopped the treatment for a period, just to see what will happen, if I will get better but it didnt work (Group B, male) Other Sections o Abstract o Introduction o Methods o Results o Patientphysician relationship o Patientpharmacist relationship o Discussion o Conclusion o References

Patientphysician relationship The majority of participants considered the relationship with their physician of great importance. Good atmosphere during consultation and physicians time spent on giving advice and answering questions were mentioned as the most important characteristics of a good doctor. Distant and formal behavior of physician could be a reason for changing the doctor for some participants.
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I appreciate my doctor very much, he explains everything to me. He doesnt care only about prescribing. He practices real medicine. (Group A, male) First of all they really seem to care about me. They listen to my questions and wishes and I understand it (Group A, male) I stopped consulting my first doctor because of his behavior. I dont know, this was probably because of his age, he was old, but the distance between me and the physician was big. I wanted to ask something and I hesitated, and when I did so his answers were yes or no, nothing more . (Group B, female)

Good communication and a rewarding behavior of the physician as well as a high level of confidence also seemed to facilitate adherence.
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If I have good results, then my doctor congratulates me (Group A, female) I believe that the doctor should inspire you confidence, then you will follow the treatment and if the doctor is strict you will comply . (Group A, female) I feel gratitude; the whole team here works for me. (Group A, male) Other Sections o Abstract o Introduction o Methods o Results o Patientphysician relationship o Patientpharmacist relationship

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Discussion Conclusion References

Patientpharmacist relationship Regarding patientpharmacist relationship, participants trusted their pharmacists advice on taking the appropriate medication when they concerned a minor health condition such as a sore throat or a cold. For more serious conditions such as hypertension, they trusted only their physician for prescribing a drug. Still, participants consult their pharmacist for additional information on treatment, such as whether they should take the drug before or after dinner.
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I dont want to take medicines if my doctor hasnt prescribed them (Group A, female) (I trust the pharmacist) for simple things like throat, nose and things like these. For more serious conditions I consult the doctor (Group A, male) I could trust my pharmacist for something simple like a sore throat. In that case I could consult the pharmacist instead of the physician (Group B, male) I will ask the pharmacist for additional information, for example if I should take my medication before or after dinner, things like that (Group A, male) the pharmacist is not a doctor. The pharmacist sells drugs (Group B, female)

Participants from the insurance fund HC referred to drug cost as another reason for not seeking pharmacists advice on taking the appropriate medication.
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These are expensive (the antihypertensive drugs). How can I pay for these without a prescription? I am a pensioner and my pension is low (Group A, female) my doctor has prescribed all the drugs I take I cant take it without a prescription, I am a pensioner and you understand (Group A, female) Other Sections o Abstract o Introduction o Methods o Results o Patientphysician relationship o Patientpharmacist relationship o Discussion o Conclusion o References

Discussion Research on the adherence of antihypertensive treatment has shown that patients nonadherence to medication is related with a mix of demographic, organizational, psychological, and diseaseand medication-related variables.23,24 Thus, investigating patients beliefs regarding hypertension itself and antihypertensive treatment, as well as communication factors that affect

adherence, can have a great impact on designing effective interventions in order to improve treatment adherence. The present study is the first in Greece, which examined hypertensive patients beliefs about hypertension and antihypertensive medicines, as well as patients behaviors concerning treatment adherence. It also examined patientdoctor relationship and its impact on adherence. Finally, the study examined patients beliefs about the role of pharmacists. In general, results are consistent with findings from other qualitative studies on antihypertensive medication adherence.25,26 The majority of participants considered hypertension as a very serious disease and were afraid and anxious about potential serious consequences on their health in case of failure to manage the disease. These negative feelings toward hypertension represent a finding that differs from those of other studies, where hypertension was found to be considered a less important disease with well-recognized symptoms.23 Further research based on theoretical models like SRM is required so that Greek patients beliefs about hypertension is further explored. Stress emerged as one of the main risk factors of hypertension. Even though participants acknowledged the importance of this factor, stress was believed to be inevitable, and this situation was attributed to the modern way of living. Participants were being informed about hypertension from a plethora of sources, but they trusted mainly their physician. Furthermore, they were feeling comfortable to discuss about hypertension with other hypertensive patients. This finding was also confirmed during the focus group sessions where participants were interested in sharing their experiences and discussing their health problem with each other. Participants reported that they attend different health care facilities depending on the severity of symptoms. This behavior reflects the characteristics of the health care system in Greece and the way it is organized. In the absence of integrated primary care with a gate-keeping system, patients seek care and advice of the pharmacists when it concerns minor health conditions while they face limited or no barriers at all in accessing and choosing health care providers. This enables them to visit a specialist as often as they wish without referral from a general practitioner. Based on the results of our study, the factors that influence medication adherence concern the management of the disease, the treatment characteristics, and the patientphysician relationship. The systematic disease management includes regular appointments with the physician and intense counseling in order for the patient to be aware of the complications of uncontrolled blood pressure. Treatment characteristics, such as the time of receiving the medicine, the number of doses, and the drug substance, were reported as influential factors. These characteristics, which may be considered minor, are really important for patient compliance and have been identified in other studies as well.23,2527 Although an association between adherence and demographic characteristics such as age and gender could not be established due to the nature of the study, it seems that younger adults in Greece face greater difficulty in the acceptance of the disease and consequently in adhering to treatment. Age-related illness perception, with the elderly being more adherent, has also been reported in other studies.27 Building on the results of the present study, a longitudinal quantitative survey would be useful in order to further explore confirm or reject the aforementioned finding. Results suggest that the major factor affecting positive medication adherence is a good doctor patient relationship. A physician who encourages and rewards patients, and most importantly, spends quality time with them in giving information and providing explanations about the

disease and treatment contributes significantly in patients compliance. This finding is consistent with a number of previous studies that have established the importance of this relationship.23,25,26 In contrast, pharmacistpatient relationship seems that it did not affect medication adherence among study participants. However, a finding worthwhile to be further researched is the role of cost of drugs in adherence because this was a matter of great concern for a number of participants, especially those attending insurance funds HC. Cost and particularly level of copayment has been identified as an important factor associated with adherence to pharmaceutical treatment.28 Perceptions of personal risk and outcome expectancies, as well as redefinition of self concept or social role, have been proven to create a teachable moment for risk-reducing health behaviors.29,30 In our study, participants do create a teachable moment about hypertension, by cognitively escalating the severity of their symptoms. Previous experiences regarding hypertension, either personal or those of friends and family, and knowledge about the complications of the disease were major determinants of a teachable moment. Nevertheless, due to organizational factors, participants seem to adopt a risk-reducing health behavior (ie, visit an HC) only at a very late stage. A primary intervention stage should be identified, and early prevention strategies should be adopted so that hypertensive patients benefit at an earlier prohypertension stage rather than waiting until they are diagnosed with hypertension. Limitations All participants of the present study reported adherence to treatment at the time of the study, a finding initially indicating high levels of adherence in Greek hypertensive patients compared with previous studies conducted in Greece.20 Nevertheless, participants mentioned that they did not take medication at the right time, or skipped if they felt well, indicating a rather nonadherent than adherent pattern of behavior. This inconsistency perhaps shows a cognitive bias, which underline causes worth further investigation. Psychological factors like patients frustration due to inefficient antihypertensive treatment or the meaning of monitoring blood pressure at home or telemonitoring might have some effects on adherence. Furthermore, the detected inconsistency could represent a time-related reference: participants referred to all these behaviors regarding their pharmaceutical treatment, considering them as past behaviors and not things that they usually do in the present. In addition, this result may only be due to a volunteer effect and can be considered a methodological limitation given that, according to literature, adherence to antihypertensive treatment ranges between 50% and 70%.13 Unanimous adherence allowed the identification of the factors contributing to adherence but prevented us from exploring the factors that inhibit it (although it could well be assumed that the opposite factors can be responsible for nonadherence). From a methodological point of view, the smaller number of participants interviewed in HC, three compared to the number of participants in the other two HCs, could be considered another limitation of the study. However, due to the qualitative methodology adopted and the fact that direct comparisons among HCs were not an objective of the study, this sample difference has a limited effect on results. Finally, the long duration of the focus groups may be considered another limitation of the study. Although we took care to achieve a comfortable environment for participants, it is not quite sure whether they were fully engaging in the end of the discussion. Conclusion

In conclusion, the present study confirmed that cognitive and communication factorspatients who were better informed, had previous experiences of the disease, and a good relationship and communication with their physicianwere important determinants for adherence. These results could form the basis for designing effective interventions adjusted to the Greek reality aiming at both enhancing doctorpatient communication and empowering the patient himself. Such interventions have the potential to improve the adherence of hypertensive patients medication and can consequently reduce hypertension-related costs. Acknowledgments This study was supported by NOVARTIS Hellas S.A.C.I. We are also grateful to the physicians and all the patients who participated in the study. Footnotes Disclosure The authors report no conflicts of interest in this work.
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8. Leventhal H, Diefenbach M, Leventhal EA. Illness cognition: using common sense to understand treatment adherence and affect cognition interactions. Cognit Ther Res. 1992;16:143163. 9. Horne R. Patients beliefs about treatment: the hidden determinant of treatment outcome? J Psychosom Res. 1999;47(6):491495. [PubMed] 10. Berry D, Michas IC, Bersellini E. Communicating information about medication: the benefits of making it personal. Psychol Health. 2003;18(1):127139. 11. Hellenic Society for the study of Hypertension Guidelines for the management of hypertension [in Greek] 2008. Athens; Available from: http://www.hypertension.gr/pdf/guidelines-2008.pdf. Accessed Apr 15, 2010. 12. World Health Organization Preventing Chronic Diseases: A Vital Investment. Geneva, Switzerland: WHO; 2005. 13. World Health Organization Adherence to Long Term Therapies: Evidence for Action. Geneva, Switzerland: WHO; 2003. 14. McInnes GT. How important is optimal blood pressure? Clin Ther. 2004;26(Suppl A):S3 S11. 15. Paramore LC, Halpern MT, Lapuerta P, et al. Impact of poorly controlled hypertension on healthcare resource utilization and cost. Am J Manag Care. 2001;7(4):389398. [PubMed] 16. Neutel JM, Smith D. Improving patient compliance: a major goal in the management of Hypertension. J Clin Hypertens. 2003;5(2):127132. 17. Efstratopoulos A, Voyaki S, Baltas A, et al. Prevalence, awareness, treatment and control of hypertension in Hellas, Greece. The Hypertension Study in General Practice in Hellas. Am J Hypertens. 2006;19(1):5360. [PubMed] 18. Psaltopoulou T, Orfanos P, Naska A, Lenas D, Trichopoulos D, Trichopoulou A. Prevalence, awareness, treatment and control of hypertension in a general population sample 26913 adults in the Greek EPIC study. Int J Epidemiol. 2004;33(6):13451352. [PubMed] 19. Heine C, Browning CJ. Communication and psychosocial consequences of sensory loss in older adults: overview and rehabilitation directions. Disabil Rehabil. 2002;4(15):763773. [PubMed] 20. Yiannakopoulou ECh, Papadopoulos JS, Cokkinos DV, Mountokalakis TD. Adherence to antihypertensive treatment: a critical factor for blood pressure control. Eur J Cardiovasc prev Rehabil. 2005;12(3):243249. [PubMed] 21. Gibbs A Focus Groups Guildford, United Kingdom: University of Survey; 1997. Available from: http://sru.soc.surrey.ac.uk/SRU19.html. Accessed Jun 5, 2010. 22. Bowling A. Research methods in Health: Investigating Health and Health Services. 2nd ed. Berkshire, UK: Open University Press; 2002. 23. Gascon J, Sanchez-Ortuno M, Llor B, et al. Why hypertensive patients do not comply with the treatment. Results from a qualitative study. Fam Pract. 2003;21(2):125130. [PubMed] 24. Chapman RH, Benner JS, Petrilla AA, et al. Predictors of adherence with antihypertensive and lipid-lowering therapy. Arch Intern Med. 2005;165(10):11471152. [PubMed] 25. Benson J, Britten N. Patients decision about whether or not to take antihypertensive drugs: qualitative study. BMJ. 2002;325:873. [PMC free article] [PubMed] 26. Bane C, Hughes C, Cupples M, McElnay J. The journey to concordance for patients with hypertension: a qualitative study in primary care. Pharm World Sci. 2007;29(5):534540. [PubMed]

27. Jin J, Sklar G, Oh V, Li S. Factors affecting therapeutic compliance: a review from the patients perspective. Ther Clin Risk Manag. 2008;4(1):269286. [PMC free article] [PubMed] 28. Taira DA, Wong KS, Frech-Tamas F, Chung RS. Copayment level and compliance with antihypertensive medication: analysis and policy implications for managed care. Am J Manag Care. 2006;12(11):678683. [PubMed] 29. McBride C, Emmons K, Lipkus I. Understanding the potential of teachable moments: the case of smoking cessation. Health Educ Res. 2003;18(2):156170. [PubMed] 30. Rohrer J, Anderson G, Furst J. Obesity and pre-hypertesion in family medicine: implications for quality improvement. BMC Health Serv Res. 2007;7:212. [PMC free article] [PubMed]
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2943225/

Predisposing Factors for Severe, Uncontrolled Hypertension in an Inner-City Minority Population

Steven Shea, M.D., Dawn Misra, Martin H. Ehrlich, M.D., M.P.H., Leslie Field, R.N., and Charles K. Francis, M.D. N Engl J Med 1992; 327:776-781September 10, 1992 Abstract Article References Citing Articles (40) HYPERTENSION is one of the most common medical conditions in the United States, with a prevalence of about 22 percent among adults 18 to 74 years of age, according to the second National Health and Nutrition Examination Survey.1 The results of at least 15 randomized controlled clinical trials of drug treatment for hypertension2 , 3 support the current consensus recommendations for treatment.4 The development of a broad pharmacologic armamentarium and the dissemination of information to both physicians and the general public through the National High Blood Pressure Education Program5 have led to improvements in blood-pressure control6 7 8 and have contributed to reductions in the incidence of stroke and ischemic heart disease.9 10 11 Despite these gains, poorly controlled hypertension remains a major health problem, particularly among minority populations, the poor, those with lower educational levels, and those with limited access to medical care.12 13 14 Increasing the rate of blood-pressure control among patients with hypertension to at least 50 percent is one of the national health promotion and disease prevention objectives for the year 2000.15 Hypertensive emergencies and urgent hypertension are the most extreme forms of poorly controlled hypertension4 , 16 and thus can be used as indicator conditions for poorly controlled hypertension. Hypertensive emergencies, which include malignant hypertension, are evidenced by acute end-organ damage and require blood-pressure reduction within one hour.4 , 16 Urgent hypertension, characterized by a severe or accelerated elevation in blood pressure that should be treated within several hours,4 may often be treated in the emergency room with fast-acting drugs, without hospital admission.17 18 19 20 An earlier retrospective study of patients with hypertensive emergencies found that hypertension had previously been diagnosed in more than 90 percent,21 suggesting that hypertensive emergency is almost entirely preventable and that correctable barriers to its prevention may exist. Specific hypotheses suggested in that study were that the lack of medical insurance, the lack of a primary care physician, noncompliance with an antihypertensive drug regimen, and alcohol abuse or the use of illicit drugs may be predisposing factors for hypertensive emergencies and urgent

hypertension. We report here the results of a casecontrol study conducted to test these hypotheses.

Methods Setting and Subjects

The study was conducted between October 1989 and June 1991 at the Presbyterian Hospital and Harlem Hospital Center in New York. The case patients presented to or were admitted from the emergency room at one of these two hospitals with malignant hypertension (codes 401.0, 402.00, 402.01, 403.0, 404.0, 405.0, and 405.01 of the International Classification of Diseases, 9th revision [ICD-9]22), hypertensive encephalopathy (ICD-9 code 437.2), hypertensive emergency, or severe, uncontrolled hypertension. The control patients had hypertension as indicated by current drug treatment for hypertension or a history of hypertension; these patients presented to or were admitted from the emergency room at Presbyterian Hospital or Harlem Hospital with acute conditions not known to be related to the hypothesized risk factors for severe, uncontrolled hypertension. Examples of such conditions were gastroenteritis, muscle spasm, allergy, backache, hernia, and otitis media. Patients were excluded from the control group if they had previously been admitted for hypertensive emergency, malignant hypertension, or severe, uncontrolled hypertension. Patients were excluded from both the case and control groups if they were admitted for acute myocardial infarction, acute pulmonary edema, aortic dissection, stroke, or renal failure, if they were under 21 years of age, or if they were pregnant. Eligible subjects were identified each day from admission logs in the emergency rooms and the medical and surgical services at the two hospitals. Five eligible case patients and six eligible control patients declined to participate in the study. There were no patients whose physicians refused permission for the research assistants to screen and attempt to enroll the patient. Altogether, 94 potential case patients and 116 potential controls were interviewed. We excluded three subjects who were not black or Hispanic from the analysis (one white case patient, one white control patient, and one Native American control patient). One French-speaking Haitian black case patient was not excluded, since the research assistant spoke fluent French. Thus, data on 93 case patients and 114 controls were analyzed. A computerized search of all discharges from the Presbyterian Hospital during the study period, using the ICD-9 codes used to define cases, showed that all eligible case patients had been identified and enrolled.

Data Collection
Data were collected by trained research assistants in structured interviews with patients and with use of chart-abstraction forms. Interview forms were available in Spanish and English; the research assistant at the Presbyterian Hospital, where all the Hispanic patients were seen, was bilingual. All interview data were obtained in the patient's preferred language at the time of the visit to the emergency room or during the hospital admission. This study was approved by the institutional review boards of Columbia

Presbyterian Medical Center and the Harlem Hospital Center, and informed consent was obtained from all patients.

Measurements
The blood pressure on admission was defined as the first blood pressure recorded on the emergency room chart. The KeithWagenerBarker grade of hypertensive retinopathy,23 the presence of new microscopic hematuria (three or more red cells per high-power field), the presence of encephalopathy attributed to hypertension (indicated by an altered level of consciousness or clouding of the sensorium), and the presence or absence of exclusionary criteria were ascertained by review of the patients' charts. For control patients, the diagnoses recorded in the emergency room or on admission and the presence or absence of hypertension were ascertained by review of the charts. Information on demographic variables, educational level, employment, marital status, use of health services, cigarette-smoking habits, previous diagnosis and treatment of hypertension, and use or abuse of alcohol and illicit drugs was obtained in the interview. For the 81 patients who reported consuming any alcohol in the previous year, the number of alcohol-related problems during that period was ascertained with use of 41 questions from the 1988 Health Interview Survey. Complete data were obtained from 78 patients. Acceptable detection rates for these questions have been reported.24 We assumed that patients who reported no alcohol consumption during the previous year had no problems related to alcohol. The interview also included questions on the use of several categories of illicit drugs (marijuana, cocaine, "crack" cocaine, heroin, methadone, and "other drugs") during the previous year. Adherence to the prescribed regimen of blood-pressure medication was assessed with a five-item compliance scale derived from the four-item scale developed by Morisky et al.25 On the basis of preliminary studies in the population we were studying, we made minor changes in the wording of the four yesno questions in the scale of Morisky et al. The revised versions read as follows: Do you ever forget to take your high-bloodpressure pills? Are you ever careless in taking your pills? Do you ever miss taking your pills when you are feeling better? Do you ever miss taking any of your pills because you are feeling sick? We also added a fifth question: Do you ever miss taking your highblood-pressure medication for any reason? This scale was scored by assigning one point to each positive response, so that a higher score indicated a lower level of compliance. Cronbach's coefficient alpha,26 a measure of the internal consistency of the scale, was 0.71 for the 202 patients who provided complete data for all five items. Morisky et al. reported that Cronbach's alpha was 0.61 for their four-item scale.25

Statistical Analysis
Bivariate associations were tested with use of the chi-square statistic for categorical data and the t-test for continuous data. The use of a continuity correction for tables with fewer than five subjects in the smallest cell did not materially affect the odds ratio or the test statistic, and the results are reported without this correction. Multiple logistic-regression

models were used to calculate adjusted regression coefficients. In these models, age was coded as a continuous variable, and sex, race or ethnic group (black or Hispanic), educational level (less than high-school graduation vs. high-school graduation or equivalency or more), current smoking, one or more alcohol-related problems, and use of illicit drugs in the past year were coded as dichotomous variables. Odds ratios and confidence intervals were calculated from these adjusted regression coefficients.27 In order to simplify the interpretation of the results, all these control variables were retained in all the multiple logistic-regression models, even though in some models the coefficients were not materially affected by the removal of one or more of the control variables. Adjustment for additional variables, including employment, marital status, and site of data collection (Presbyterian Hospital vs. Harlem Hospital) did not materially affect the odds ratios in any model we examined, and these variables were not included in the final models. Additional multiple logistic-regression analyses were performed to test the independence of the three main independent variables examined namely, whether the patient had any medical insurance, whether the patient had a primary care physician, and the score for compliance with the antihypertensive drug regimen on the five-point scale by adjusting each for the other two. Logistic-regression analyses were performed with SAS/PC software.28 Other analyses were performed with SPSS/PC +.29 All reported P values are two-tailed.

Results
At the time of the visit to the emergency room, the 93 case patients had severely elevated

Clinical blood pressure (mean, 222/141 mm Hg) (Table 1Table 1 Characteristics of 93 Case Patients with Severe, Uncontrolled Hypertension.), and 30 case patients (32 percent) had clinical evidence of acute end-organ damage manifested by hypertensive encephalopathy, grade III or grade IV retinopathy, or new microscopic hematuria. Ninety-one of the case patients (98 percent) reported that they had previously been given a diagnosis of hypertension and had previously been treated for this condition. Case patients who were admitted to the hospital did not differ from those who were treated in the emergency room and released in terms of mean systolic blood pressure, mean age, or the proportion who were male. The mean diastolic blood pressure was somewhat higher among the case patients who were admitted than among those who were treated and released (144 mm Hg vs. 137 mm Hg), and the case patients who were admitted were more likely to be black, reflecting the higher proportion of patients admitted at Harlem Hospital Center, where the patient population was predominantly black, than at Presbyterian Hospital, where the patient population included more Hispanics. The case and control patients were similar with regard to education and place of interview; case patients were younger and were more likely to be male, black, employed,

and married (Table 2Table 2 Selected Characteristics of Case Patients and Controls.). In bivariate analyses, the lack of a primary care physician, the lack of medical insurance, the presence of one or more alcohol-related problems, and illicit drug use were

Bivariate associated with severe, uncontrolled hypertension (Table 3Table 3 Odds Ratios for Severe, Uncontrolled Hypertension among Case Patients and Controls, According to Various Characteristics.*). The mean score on the compliance scale was 2.3 1.3 for case patients, as compared with 1.1 1.2 for controls (t = 6.78, 200 df; P<0.001). In multivariate analyses, the lack of a primary care physician, the lack of medical insurance, and noncompliance with the antihypertensive regimen were significantly associated with severe, uncontrolled hypertension after adjustment for age, sex, race or

ethnic group, educational level, and current smoking (Table 4Table 4 Adjusted Odds Ratios for Severe, Uncontrolled Hypertension According to Various Risk Factors.*). The occurrence of one or more alcohol-related problems and illicit drug use in the previous year was no longer significant after adjustment for these covariates, although the adjusted odds ratio for one or more alcohol-related problems was of the same order of magnitude as that for noncompliance with the drug regimen. The magnitude of the odds ratios for the lack of a primary care physician, the lack of medical insurance, and noncompliance with the drug regimen remained approximately the same after further adjustment for one or more alcohol-related problems and illicit drug use in the previous year. Additional adjustment of each of these three variables for the other two showed significant independent associations between severe, uncontrolled hypertension and both lack of a primary care physician and noncompliance with the

Adjusted Odds Ratios for antihypertensive regimen (Table 5Table 5 Severe, Uncontrolled Hypertension According to Various Risk Factors.*). Lack of

medical insurance was marginally associated with severe hypertension. The magnitude of the odds ratios was minimally changed by this additional adjustment. Analyses were also conducted in which patients with Medicaid insurance only (n = 56) were classified as uninsured, to test whether such patients were effectively uninsured because of physicians' reluctance to treat patients covered by Medicaid, but the odds ratios for lack of medical insurance combined with Medicaid coverage, as compared with all other insurance, were smaller than when the original classification scheme was used, indicating that Medicaid patients were best classified as insured. The results of subgroup analyses in which the case patients who were admitted and those who were treated in the emergency room and released were compared separately with the whole control group were consistent with the findings of the main analyses. The lack of a primary care physician was associated with a greater likelihood that a patient would usually have blood-pressure checks performed in an emergency room (odds ratio, 10.5; 95 percent confidence interval, 3.7 to 29.4), that he or she would not have regular blood-pressure checks (odds ratio, 12.1; 95 percent confidence interval, 6.1 to 24.1), and that he or she would not have had a blood-pressure check within six months of admission or the index visit to the emergency room (odds ratio, 9.1; 95 percent confidence interval, 3.5 to 24.0). No patient who had a primary care physician reported receiving prescriptions for antihypertensive medications in the emergency room, whereas 20 of the 70 patients without a primary care physician (29 percent) did receive such medication there. The lack of medical insurance was associated with not having a primary care physician (odds ratio, 2.7; 95 percent confidence interval, 1.4 to 5.1), not having regular blood-pressure checks (odds ratio, 2.9; 95 percent confidence interval, 1.5 to 5.6), and not having had a blood-pressure check within six months of admission or the index visit to the emergency room (odds ratio, 2.7; 95 percent confidence interval, 1.2 to 6.1).

Discussion
During the 21 months of data collection at two hospitals, all but 1 of the 93 case patients with severe, uncontrolled hypertension, as defined in this study, were either black or Hispanic. At Harlem Hospital Center, this racial and ethnic distribution is explained by the fact that the population served by the hospital is almost entirely black. A different explanation is required for the case patients enrolled at the Presbyterian Hospital, where the population served includes a large number of white and privately insured referral patients. No cases of severe, uncontrolled hypertension were identified among these patients. A similar observation was made in an earlier study of hypertensive emergencies at the Presbyterian Hospital during the 1980s.21 The overcrowding of inner-city emergency rooms30 31 32 has led many physicians to avoid or bypass the emergency room in caring for their privately insured patients. Thus, we could not estimate the magnitude of the effects of race and socioeconomic status as risk factors from our data, which were obtained by enrolling patients either seen in the emergency room and released or admitted from the emergency room. Nonetheless, the racial and ethnic composition of the group of case patients in this study and in our earlier study21 indicates

that severe, uncontrolled hypertension occurs more frequently among blacks and Hispanics than among non-Hispanic whites and that severe, uncontrolled hypertension is strongly linked to socioeconomic status. This study confirms our earlier finding21 that almost all cases of hypertension had previously been diagnosed and treated. Thus, the failure to detect hypertension, to make patients aware that they have hypertension, or to initiate treatment does not seem to have been a major contributor to the occurrence of severe, uncontrolled hypertension in this population. The lack of a primary care physician was the strongest predictor of severe hypertension. The lack of health care insurance was also a risk factor, suggesting that financial barriers to care contribute to the poor control of hypertension. This finding is consistent with data from the Rand Health Insurance Experiment, which showed that hypertensive patients randomly assigned to free care had lower mean blood pressures than those randomly assigned to health care plans that entailed cost sharing, a difference that was greatest among low-income persons with hypertension.14 Compliance with treatment has been widely recognized as a key issue in achieving bloodpressure control.33 We found that noncompliance with an antihypertensive regimen was strongly associated with severe, uncontrolled hypertension. Several factors have been identified as obstacles to compliance with antihypertensive treatment, including the cost of medications34 , 35 and dosing frequency.36 Another factor contributing to noncompliance and the resulting poorly controlled hypertension may be a lack of knowledge about blood pressure. Data from a 1989 survey indicate that higher educational attainment is associated with knowing one's own blood pressure and with knowing that a "good" blood pressure is 140/90 mm Hg or less.37 That study also found that blacks and Hispanics were less likely than whites to know their own blood pressures or to know what constitutes a "good" blood pressure, even after adjustment for educational attainment. It is possible that our findings may not pertain to persons with hypertension who live under different circumstances. In particular, rural populations may face different barriers to blood-pressure control than the urban population we studied. However, large numbers of blacks and Hispanics with hypertension live in inner cities in the United States, and our findings are likely to apply to them. The hypertension-control strategy followed by the U.S. Public Health Service in concert with state and local health agencies focuses on increasing knowledge of high blood pressure and its consequences, encouraging the adoption of behavior conducive to bloodpressure control, and implementing systems to improve surveillance and control.38 Our data support the recognition that a key variable is compliance with antihypertensive treatment. Our findings also emphasize the potential importance of changes in the health care system to address the inadequacy of emergency rooms for the treatment of chronic conditions and to increase access to physicians who provide primary or long-term care for hypertension.39 Our findings also point to the importance of health insurance as a

means of providing such access to health care, especially for poor and minority population groups. Supported by a grant (RO1-HL38260) from the National Heart. Lung, and Blood Institute (to Dr. Shea). Steven Shea, M.D. Dawn Misra Martin H. Ehrlich, M.D., M.P.H. Leslie Field, R.N. Charles K. Francis, M.D. From the Department of Medicine, Division of General Medicine. Columbia University College of Physicians and Surgeons (S.S.), the Division of Epidemiology. Columbia University School of Public Health (S.S., D.M.), and the Department of Medicine, Harlem Hospital Center (M.H.E., L.F., C.K.F.), all in New York. Address reprint requests to Dr. Shea at Atchley Pavilion 1310, 161 Fort Washington Ave., New York, NY 10032. We are indebted to Dr. Deborah Hasin for her assistance in designing the sections of the interview dealing with alcohol and illicit drug abuse, to Dr. Bruce Levin for statistical advice, to Drs. Benjamin Okonta and Haydee Rondon for their assistance in data collection, and to Drs. Nancy M. Bennett, Lee Goldman, Jennifer L. Kelsey, and Katherine G. Nickerson for their comments on the manuscript.
http://www.nejm.org/doi/full/10.1056/NEJM199209103271107#t=article+Methods

Journal of Human Hypertension (2004) 18, 207213. doi:10.1038/sj.jhh.1001656

Risk factors for uncontrolled hypertension in Italy

This work was carried out by CliCon Srl. E Degli Esposti1, M Di Martino2, A Sturani3, P Russo4, C Dradi5, S Falcinelli5 and S Buda2
1. 2. 3. 4. 5.
1 2

Clinical Effectiveness Unit, AUSL Ravenna, Italy CliCon Srl, Health Economics and Outcomes Research, Ravenna, Italy 3 Hypertension Unit, AUSL, Ravenna, Italy 4 Department of Human Physiology and Pharmacology, University of Rome "La Sapienza", Italy 5 General Practitioner, Ravenna, Italy

Correspondence: M Di Martino, CliCon Srl, Via San Vitale, 5, 48100 Ravenna, Italy. E-mail: mailbox@clicon.it Received 26 June 2003; Revised 18 September 2003; Accepted 29 September 2003.
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Abstract
To identify factors related to poor control of blood pressure in primary care, we designed a retrospective casecontrol analysis of clinical and demographic data recorded in the General Practitioners (GP) database. Study data were provided on a voluntary basis by 21 GPs from a practice-based network in primary care. The study included 2519 hypertensive patients enrolled between January 1 and December 31, 2000. The interventions were antihypertensive medication, and the main outcome measures were control of systolic and diastolic blood pressure (BP). The independent variables considered were: age of patient and GP; patient gender, body mass index, history of smoking, diabetes mellitus, or cholesterol tests; family history of hypertension; previous visits for cardiologic, nephrologic, or vascular surgery evaluation; prior hospitalizations for myocardial infarction or heart failure, and number of admissions for surgery; length of patient follow-up, type of antihypertensive medication, mean daily dosage, adherence to the drug regimen, and number of other medications currently being taken by the patient. Blood pressure was uncontrolled (>140/90 mmHg) in 1525 (60%) of the 2519 hypertensive patients enrolled. The presence of diabetes mellitus, increasing patient age, and increasing GP age significantly increased the risk of uncontrolled BP. Factors significantly associated with a reduced risk of uncontrolled BP were the number of other medications currently being taken by the patient and a prior history of MI. We conclude that the failure of antihypertensive medication to adequately control BP is determined by both the patient's characteristics and factors related to the patient doctor relationship. Successful treatment of hypertension requires patient adherence to the regimen that has been agreed on by the patient and the physician.

Keywords:

uncontrolled blood pressure, antihypertensive drugs, General Practitioner

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Introduction
In Italy, hypertension is a common medical disorder affecting more than 8 million people.1 In the Ravenna (Italy) area, antihypertensive drugs are prescribed for an estimated 19% of the population of 355 000.2 Despite significant efforts to diagnose and treat hypertension, approximately two out of three people with hypertension have not achieved the generally recommended target blood pressure (BP) of less than 140/90 mmHg,3,4 thus remaining at a higher risk for heart attack, stroke, heart failure, and kidney disease. Failure to achieve the targeted BP control is a global problem. In the United States, fewer than 30% of hypertensive patients have BP values lower than 140/90 mmHg,5 while, in the United Kingdom, only 6% of hypertensive patients have attained these target BP levels.6 Even with less stringent levels of BP control of 160/95 mmHg, data from Australia, Canada, Finland, India, Scotland, and Spain suggest that no more than 20% of the population would achieve this goal.7 The identification of factors related to poor control of BP can help to target populations in need of medical attention, and to aid in the development of effective treatment strategies for specific subpopulations.7 The objective of the present casecontrol study was to identify risk factors for uncontrolled BP among those patients enrolled in the Pandora project, a prospective ongoing global outcomes study begun in 1996 to organize a database for epidemiological assessments and to improve the management of hypertension in primary care.
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Methods
Data collection and patients

Of 330 general practitioners (GPs) in the Ravenna, Italy area, 21 voluntarily participated in the PANDORA project. In Italy, the GP is the doctor working outside the hospital, who is delegated by the National Health System to provide care for a known number of subjects. Each GP was asked to enrol two hypertensive patients per week in the study, starting on 01/01/1996. When this study was carried out, the GPs participating in the Pandora project had a cohort of about 33 000 beneficiary subjects representing 9.3% of persons living in the Ravenna area. The Pandora project was approved by the Local Ethics Committee, and informed consent was obtained from each patient enrolled. All GPs were supplied with a personal computer that was connected to a remote server via a modem, a printer, an automatic BP device (Dinamap 1846SX, Critikon, Tampa, FL, USA), and a dedicated software package dubbed So.Ge.Pa. The remote server is also linked to the Local Health Unit database (patient, GP, prescription, hospital, and death records) and to the

hypertension unit. At the remote station, a team of different specialists (computer scientist, economist, statist, epidemiologist, pharmacologist) produces a variety of reports which are regularly returned to the various operators. The So.Ge.Pa. software controlled the operation of the BP device, which was connected to the computer. The BP value recorded and entered into the database at each visit represented the average of three consecutive readings obtained at 1-min intervals after the patient had remained seated for 5 min. BP was measured in the dominant upper arm during the daytime, morning or afternoon, in accordance with conventional clinical practice. A tube 3.6 m in length and a cuff of 2333 cm for normal subjects or 3140 cm for obese subjects were used. Clinical and laboratory data were gathered and stored either by the GPs themselves or through links with Health Service databases, as already documented.8 At the enrolment visit, the GP recorded the patient's currently prescribed antihypertensive regimen, defining the drug(s), active ingredient(s), and the number of tablets the patient was instructed to take daily. At the end of each visit, the antihypertensive treatment was again prescribed by the GP, who had complete discretion to decide the type of drug and the dosage for an individual patient, and the frequency with which BP would be measured. The antihypertensive drugs purchased by each patient were identified from the pharmaceutical database kept by the Local Health Unit of Ravenna, which logs each prescription, records the code number of the prescribing physician, the national health number of the patient, the date dispensed, the AnatomicalTherapeuticChemical classification (ATC), the number of packs, and the number of tablets per pack. All drug prescriptions considered in this study are fully reimbursed by the National Health System. The completeness and coherence of the information recorded for each patient were periodically checked at the remote station and only those patients whose recorded data which satisfied the inclusion criteria of the study were considered in the analysis.
Patient characteristics and outcome measures

The main outcome measure for this casecontrol study was BP control (yes/no). Adequate control was defined as a representative SBP of less than 140 mmHg and a DBP of less than 90 mmHg; for patients with diabetes, BP control was defined as a representative SBP of <130 mmHg and a DBP of <85 mmHg.4 Eligible patients were at least 18 years of age, and had been enrolled in the Pandora project for at least 1 year prior to the BP measurement period from 1 January to 31 December 2000. Patients were excluded if they had end-stage renal disease or malignant systemic disease (ie lupus erythematosus). The representative BP was the BP reading from the most recent visit during the measurement period. Only those patients whose records included at least one BP value measured at least 365 days before the representative value were included in the study. The control group consisted of those patients with diagnosed hypertension whose BP was adequately controlled at the end of the measurement period. Cases were those patients with diagnosed hypertension whose BP was not adequately controlled at the end of the follow-up measurement period. A

patient follow-up period was defined retrospectively as the interval, in days, between the representative BP and the earliest BP value present in the patient's record. The independent variables considered in this study included the age of the patient and GP; patient gender, body mass index (BMI); history of smoking, diabetes mellitus, or cholesterol tests; family history of hypertension; previous visits for cardiologic, nephrologic, or vascular surgery evaluation; prior hospitalizations for myocardial infarction (MI) or heart failure; number of admissions for surgery; and length of patient follow-up, type of antihypertensive medication, mean daily dosage (MDD), utilization of antihypertensive drugs and number of other medications currently being taken by the patient (antiaggregants, anti-inflammatories, anithypolipaemia drugs, antiasthmatics, and drugs for the treatment of heart diseases).
Utilization of antihypertensive drugs

Utilization of antihypertensive agents was defined for the purpose of this study as the MDD of the drugs purchased during the follow-up period, expressed as the number of tablets per day. The formula utilized was: number of tablets prescribed from the first to the penultimate prescription, divided by the number of days from the first to the last prescription. The duration (expressed in days) of the antihypertensive treatment (DT) was then calculated as the number of days from the first to the last prescription plus the number obtained by dividing the number of tablets indicated in the final prescription by the MDD. The calculations were based on the total number of tablets purchased by each patient, regardless of the active principle that each contained. Three categories for use of antihypertensive medication were defined, regardless of the type and number of active ingredients taken: patients were defined as (1) occasional users if they received only one prescription of antihypertensive medication during the study period; (2) interrupted users if, during the study period, they interrupted the use of any antihypertensive drug; (3) continuous users if, during the study period, they continuously took antihypertensive drugs (by maintaining, combining or switching the active ingredient) without interrupting the pharmacological therapy. In the case of nonoccasional users, four types of antihypertensive treatment were identified on the basis of MDD: patients with MDD <0.5 tablets/day; patients with MDD 0.5 tablets/day and <1 tablet/day; patients with MDD 1 tablet/day and <2 tablets/day; patients with MDD 2 tablets/day.
Statistical analysis

Continuous variables are presented as mean values plus or minus the standard deviation. Statistical significance between means was calculated by independent-samples t-test or, alternatively, by paired-samples t-test. Association between categorical variables and BP control was tested using the Pearson's 2 test.9 For all analyses, P-values of less than 0.05 were considered significant. Unadjusted odds ratios were obtained to identify factors predictive of not achieving adequate control of BP, the outcome variable. A multivariable logistic regression model10 was then developed, identifying factors predictive of not achieving adequate BP control while simutaneously adjusting for potential confounders. A forward stepwise approach was undertaken

setting entry/removal criteria for each independent variable at (P-value(in)=0.05, Pvalue(out)=0.10) using the Wald test statistic. The fit of the model was assessed with the Hosmer Lemeshow goodness-of-fit test statistic,10 with P <0.05 taken to be evidence of a statistically significant difference between observed and predicted values. All statistical analysis were performed with the SPSS statistical package.11
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Results
Patient characteristics

There were 6392 hypertensive patients in the Pandora project population from 1 January to 31 December 2000, representing 19.4% of the total beneficiaries in the care of the 21 GPs. Of these, 2519 met the inclusion criteria for the present study, including 1525 cases (60.5%) and 994 controls (39.5%). All the subjects included in the study were white. The characteristics of the patients enrolled are shown in Table 1. Compared with controls, cases were significantly older and less likely to smoke. The percentage of patients who had diabetes mellitus was significantly greater among cases than controls. The percentage of patients with previous hospital admissions for cardiovascular reasons and the percentage of patients taking two or more co-medications were higher in the controls than in the cases. Compared with controls, cases also had a slightly higher BMI, which was statistically significant, and a significantly shorter duration of follow-up.
Table 1 - Characteristics of case and control patients at enrolment.

Full table

Utilization of antihypertensive drugs

Cases and controls differed significantly in their use of antihypertensive medications (Table 2). Adherence to the antihypertensive regimen was significantly higher among cases compared with controls (83.4 vs 77.7%, P<0.001). Although by definition, cases were those patients with uncontrolled BP, the MDD and number of classes of antihypertensive agents purchased in the pharmacy were significantly greater than those of the control group. With regard to the type of antihypertensive drugs used, approximately 50% of cases and controls received angiotensinconverting-enzyme (ACE) inhibitors. The use of diuretics and -blockers was greater among controls, whereas the use of calcium channel blockers was greater among cases.

Table 2 - Utilization of antihypertensive drugs in the two groups of patients.

Full table

The MDD value increased significantly (P<0.001) when passing from patients currently taking no other medications to patients taking one co-medication and to patients taking two or more comedications (0.84, 0.98, and 1.27 tablets/day, respectively).
Control of blood pressure

The percentage of normotensive patients increased from 32% at enrolment to 39.5%. at the end of the follow-up period. At the end of the follow-up period, 22.3% (222 patients) of the control group had a representative BP of <140/90 mmHg even if they had suspended antihypertensive treatment. Antihypertensive treatment was suspended by 16.6% (253 patients) in the case group, even if their BP remained within the hypertensive range. Overall, 45.3% (1141 patients) of the cases had residual systolic hypertension, 2.4% (60 patients) had residual diastolic hypertension, and 12.8% (324 patients) had systolicdiastolic hypertension. The mean SBP of cases vs controls at enrolment (153 20 vs 140 21 mmHg, respectively) and at the end of follow-up (153 13 vs 126 10 mmHg, respectively) was significantly higher (P<0.001). Cases also had a higher mean DBP than controls at enrolment (82 11 vs 80 11 mmHg, respectively) and at the end of followup (81 12 vs 74 8 mmHg, respectively) (Figure 1). Among cases, there was a significant decrease in DBP from enrolment to the end of follow-up (82 11 vs 81 12 mmHg, respectively, P<0.005) without any variation in SBP (153 20 vs 153 13 mmHg, respectively). By contrast, the controls showed a significant decrease from enrolment to the end of follow-up in both SBP (140 21 vs 126 10 mmHg, respectively) and DBP (80 11 vs 74 8 mmHg) (P<0.001 for both comparisons). Using Joint National Committee VI guidelines,4 at the end of follow-up, 71.9% (1096 patients) cases had stage I hypertension, 23.1% (352 patients) had stage II hypertension, and 5.0% (77 patients) had stage III hypertension.
Figure 1.

Blood pressure in control and case patients.

Full figure and legend (63K)

Risk factors

On enrolment in the study, there were significant differences in the risk factors present in cases and controls (Table 3). Several factors were significantly associated with the persistence of elevated BP, especially patient age of 50 years or more, the presence of diabetes mellitus, and the absence of a prior admission for MI. The risk of persistence of elevated BP, moreover, decreased with the increase in the number of other medications currently being taken by the patient. With regard to the characteristics of antihypertensive therapy, the risk of persistent elevated BP was higher in patients who used medication continuously, and in those receiving the highest MDD (Table 4).
Table 3 - Bivariate odds ratios about patients' characteristics.

Full table

Table 4 - Bivariate odds ratios about utilization of antihypertensive drugs.

Full table

The results of the multivariate logistic regression model (Table 5) indicate that the presence of diabetes mellitus, increasing patient age, and increasing age of the GP significantly increased the risk of uncontrolled BP. Hypertensive patients with diabetes were almost six times more likely to have uncontrolled BP compared to those without diabetes. Significant factors that reduced the risk of uncontrolled BP were an increasing number of other medications currently being taken by the patient and a prior MI. The HosmerLemeshow goodness-of-fit test (P=0.900) indicated a good fit of the model.

Table 5 - Logistic regression model: predictors of not achieving adequate blood pressure control.

Full table

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Discussion
Poor control of BP appears to be determined by both the patient's characteristics and factors related to the patientdoctor relationship. Randomized controlled trials (RCT) generally conducted at tertiary-care centres in highly selected patient populations have demonstrated that any reduction of elevated BP either to levels within the normal range12,13 or to those above 140/90 mmHg lowers the likelihood of morbidity and mortality due to cardiovascular or renal events, as well as premature death.14,15,16,17 However, the lack of applicability of these findings to the community-based practice setting is demonstrated by the finding that normal BP levels are achieved in more than 50% of patients treated in RCTs13,14,15,16 and only in less than 30% of those treated in actual clinical practice.4,5,6,7 In this observational, practice-based study, the majority (60%) of hypertensive patients failed to reach the targeted goal BP. A possible bias could have been introduced by the patient selection process, because the GPs might have selected those patients who were generally more compliant than the general patient population. If true, such a bias could contribute to further support present findings since the general population of hypertensive patients in Ravenna could be expected to have even poorer BP control. The use of clinic BP measurements might have substantially overestimated the proportion of patients with uncontrolled hypertension as a result of the 'white coat' component.18,19 However, most of the patients had been treated with antihypertensive drugs for an average of 2.5 years prior to study enrolment, suggesting that the BP values recorded were representative. Lastly, pretreatment BPs could not be reliably ascertained for most of the patients, and they were included because they had established hypertension and were taking antihypertensive drugs. The purpose of this study was to identify factors contributing to poor control of BP in patients receiving long-term antihypertensive therapy. Other studies have evaluated barriers and facilitators to the management of hypertension in primary care, including physician-related factors, ethnicity of the patients, co-morbidity, and continuity of care.20,21,22,23,24 In this study, several factors appear to affect the risk of uncontrolled BP in the primary care setting: the patient's age, the presence of comorbidities such as diabetes mellitus and/or target organ damage (ie previous MI), the number of other medications currently being taken by the patient, and the GP's age. How these factors affect BP control is not known. However, the medical status of the patient is known to be an important determinant. In the present study, confirming the results of

other papers,22,23 a prior MI enhanced the probability of achieving goal BP, possibly because GPs and patients may be more motivated to treat a symptomatic disease than asymptomatic conditions, or because patients with a prior MI were seen by hospital physicians and had their treatment regimen prescribed by specialists rather than by their primary-care physician. Moreover, our physicians have little training and experience in treating to target, as we have observed in patients with diabetes. According to the results of this study, an increase in the number of other medications currently being taken by the patient decreases the probability of poor control of BP. A possible explanation for this phenomenon is that, although the patients taking other medications present a more complex clinical situation, they are more accustomed to and careful about their treatment, they take higher doses of the drugs and thus control their BP in a better way. An unexpected finding was that the dosing regimen of antihypertensive drugs and utilization of antihypertensive drugs did not influence BP. A study at a hypertension hospital clinic found that the intensity of antihypertensive therapy was not associated with the degree of BP control, and that older patients needed more than one drug to reduce their BP.25 Others have found that the BP in adult hypertensive patients gradually increases over time,26 which may have contributed to the findings in the present study. An additional factor may have been the fact that fewer than 10% of cases received diuretics, the use of which often results in BP control in patients with resistant hypertension.27 The recent findings of Berlowitz et al28 strongly support a substantial physician component to poor BP control, for reasons that are not entirely clear. Other studies have indicated the doctor patient relationship as an important factor affecting the control of hypertension.20,21 In the present study, the likelihood of poor BP control was increased when the GP was aged 50 years and older. Moreover, in a previous study, we found that adherence to antihypertensive treatment was lower in newly treated patients who were followed by older physicians.29 This study provides a framework for identifying hypertensive patients who are at a high risk of poor control, and many of the factors identified may be amenable to improvement. Older patients and diabetics can be targeted for greater attention to BP control, particularly in view of the evidence for improvement in clinical outcomes with hypertension therapy in these populations.17,16 In conclusion, the failure of antihypertensive medication to adequately control BP is determined by both the patient's characteristics and factors related to the patientdoctor relationship. Successful treatment of hypertension, also in asymptomatic conditions, requires patient adherence to the regimen that has been agreed on with the physician.
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References
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