Dement Geriatr Cogn Disord 2014;37:357–365 DOI: 10.1159/000357701 Accepted: December 3, 2013 Published online: February 8, 2014
© 2014 S. Karger AG, Basel 1420–8008/14/0376–0357$39.50/0 www.karger.com/dem
Original Research Article
Risk of Subsequent Dementia in Patients with Hypertensive Encephalopathy: A Nationwide Population-Based Study in Taiwan Wei-Shih Huang a, e Chun-Hung Tseng a, e Fung-Chang Sung b, d Chia-Hung Kao c, e
Cheng-Li Lin b, d
Chi-Yu Lin f
a Department
of Neurology, b Management Office for Health Data, and c Department of Nuclear Medicine and PET Center, China Medical University Hospital, d Department of Public Health and e Graduate Institute of Clinical Medical Science, School of Medicine, College of Medicine, China Medical University, Taichung, and f Department of Neurology, Changhua Christian Hospital, Changhua, Taiwan
Key Words Hypertensive encephalopathy · Dementia · Reversible posterior leukoencephalopathy syndrome · Posterior reversible encephalopathy syndrome Abstract Background/Aims: We investigated the association of hypertensive encephalopathy (HE) with subsequent dementia. Methods: Using universal insurance claims data, we identified a study cohort of 5,504 participants with HE newly diagnosed between 1997 and 2010 and a comparison cohort of 22,016 healthy participants. Incidence and risks of dementia were estimated for both cohorts until the end of 2010. Results: The dementia incidence was 1.45-fold [95% confidence interval (CI) = 1.27–1.66] higher in the study cohort than in the comparison cohort, with an adjusted hazard ratio (HR) of 1.38 (95% CI = 1.19–1.59) for the study cohort. The risk was higher for males than for females and elderly patients. With an incidence of 13.4 per 1,000 person-years, the HR of dementia increased to 2.09 (95% CI = 1.18–3.71) for the HE patients with the comorbidities of head injury and diabetes compared to those without HE and comorbidities. The risk of developing dementia declined with the follow-up time. Conclusion: Hypertensive patients with HE displayed a significantly higher risk for dementia than those without HE. The risk increased further in those with the comorbidities of head injury and diabetes. Physicians should be aware of the link between HE and dementia when assessing patients with HE. © 2014 S. Karger AG, Basel
C.-H.T. and W.-S.H. contributed equally to this work. Dr. Chia-Hung Kao Graduate Institute of Clinical Medical Science, School of Medicine College of Medicine, China Medical University 2, Yuh-Der Road, Taichung 404 (Taiwan) E-Mail d10040 @ mail.cmuh.org.tw
358
Dement Geriatr Cogn Disord 2014;37:357–365 DOI: 10.1159/000357701
© 2014 S. Karger AG, Basel www.karger.com/dem
Huang et al.: Risk of Subsequent Dementia in Patients with Hypertensive Encephalopathy: A Nationwide Population-Based Study in Taiwan
Introduction
The term ‘hypertensive encephalopathy’ (HE) was first used in 1928 by Oppenheimer and Fishberg [1] to describe episodes of acute organic brain syndrome correlated with hypertension, which is characterized by unspecific neurological symptoms including headaches, visual disturbances, altered mental statuses, and seizures [2]. The term ‘reversible posterior leukoencephalopathy syndrome’ (RPLS), first used by Hinchey et al. [3] in 1996, has also been used to refer to similar cases because of their indistinguishable reversible clinical pictures with elevated mean arterial pressure and the same radiological feature in computed tomography or magnetic resonance images as edema involving white matter in the parietooccipital areas [2–4]. Meanwhile, the association of hypertension with RPLS is well documented but hypertension is not always present in such cases; particularly in patients treated with immunosuppressant, hypertension may be absent [3]. Therefore, the older term ‘HE’ seems indeed too restrictive for an appropriate naming, and the term ‘RPLS’ was considered misleading by other authors because the involvement of gray matter was also observed. Thus, the term ‘posterior reversible encephalopathy syndrome’ was introduced [5]. The mechanism of these possible brain-capillary leak syndromes is suggested to be extreme elevation of systemic blood pressure, which causes the breakdown of the autoregulatory vascular endothelium of the brain [3]. Although HE is typically reversible, failure to treat the dramatic rise in blood pressure may promptly lead to fatal consequences. This emerging syndrome requires accurate diagnosis and early management. The precise incidence of HE is unknown. However, hypertensive crises (76% urgencies, 24% emergencies) were reported to be more than one fourth of all medical emergencies in Athens in 2010 and can result in acute end-organ injuries such as cerebral infarction, acute myocardial infarction (AMI), heart failure, acute renal failure, and HE [6]. Dementia is an emerging health problem for elderly people in Taiwan. Several risk factors are associated with dementia, including age, sex, inflammation, genetic factors, comorbidity, environmental factors, and lifestyle [7]. The association of HE with risk of dementia has rarely been evaluated. In this study, we investigated whether the diagnosis of HE is linked to an increased risk of developing subsequent dementia by using the Taiwanese National Health Insurance Research Database (NHIRD). The database is available to researchers in Taiwan and has been extensively used in epidemiologic studies [8]. The wide coverage of this large, nationwide database allowed us to examine the relationship between HE and the subsequent development of dementia. Materials and Methods Data Sources The National Health Insurance system is a government-operated, single-payer health insurance program, which was launched in 1995 and covered approximately 99% of the 23.74 million people in Taiwan by 2009 [9]. With authorization from the Department of Health, the National Health Research Institutes (NHRI) is responsible for managing the claims data from all health providers and available information on all insurants. The NHRI established several databases for academic and administrative uses, providing information on the basic patient demographic status, diagnostic codes, medical institutions, outpatient and inpatient orders, prescriptions, and expenditures for care. Data files are linked with scrambled patient identification numbers to protect the privacy of the patients. We used the nationwide population-based data for the period from 1996 to 2010 released by the NHRI. The International Classifications of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) codes were used to define diseases in the claims data. We confirm that all data were de-identified and analyzed anonymously. In addition, this study was approved by the Ethics Review Board at China Medical University (CMU-REC-101–012). Several Taiwanese studies had demonstrated the high accuracy and validity of ICD-9 diagnosis in NHIRD [10, 11].
359
Dement Geriatr Cogn Disord 2014;37:357–365 © 2014 S. Karger AG, Basel www.karger.com/dem
DOI: 10.1159/000357701
Huang et al.: Risk of Subsequent Dementia in Patients with Hypertensive Encephalopathy: A Nationwide Population-Based Study in Taiwan
1,974,009 patients with newly diagnosed hypertension (ICD-9-CM codes 401–405) from the National Health Insurance Program (n = 23,740,000)
Hypertension patients without HE between 1997 and 2010
Hypertension patients with HE between 1997 and 2010 (n = 10,784)
Stroke, dementia before the index date (n = 5,725), age
© 2014 S. Karger AG, Basel 1420–8008/14/0376–0357$39.50/0 www.karger.com/dem
Original Research Article
Risk of Subsequent Dementia in Patients with Hypertensive Encephalopathy: A Nationwide Population-Based Study in Taiwan Wei-Shih Huang a, e Chun-Hung Tseng a, e Fung-Chang Sung b, d Chia-Hung Kao c, e
Cheng-Li Lin b, d
Chi-Yu Lin f
a Department
of Neurology, b Management Office for Health Data, and c Department of Nuclear Medicine and PET Center, China Medical University Hospital, d Department of Public Health and e Graduate Institute of Clinical Medical Science, School of Medicine, College of Medicine, China Medical University, Taichung, and f Department of Neurology, Changhua Christian Hospital, Changhua, Taiwan
Key Words Hypertensive encephalopathy · Dementia · Reversible posterior leukoencephalopathy syndrome · Posterior reversible encephalopathy syndrome Abstract Background/Aims: We investigated the association of hypertensive encephalopathy (HE) with subsequent dementia. Methods: Using universal insurance claims data, we identified a study cohort of 5,504 participants with HE newly diagnosed between 1997 and 2010 and a comparison cohort of 22,016 healthy participants. Incidence and risks of dementia were estimated for both cohorts until the end of 2010. Results: The dementia incidence was 1.45-fold [95% confidence interval (CI) = 1.27–1.66] higher in the study cohort than in the comparison cohort, with an adjusted hazard ratio (HR) of 1.38 (95% CI = 1.19–1.59) for the study cohort. The risk was higher for males than for females and elderly patients. With an incidence of 13.4 per 1,000 person-years, the HR of dementia increased to 2.09 (95% CI = 1.18–3.71) for the HE patients with the comorbidities of head injury and diabetes compared to those without HE and comorbidities. The risk of developing dementia declined with the follow-up time. Conclusion: Hypertensive patients with HE displayed a significantly higher risk for dementia than those without HE. The risk increased further in those with the comorbidities of head injury and diabetes. Physicians should be aware of the link between HE and dementia when assessing patients with HE. © 2014 S. Karger AG, Basel
C.-H.T. and W.-S.H. contributed equally to this work. Dr. Chia-Hung Kao Graduate Institute of Clinical Medical Science, School of Medicine College of Medicine, China Medical University 2, Yuh-Der Road, Taichung 404 (Taiwan) E-Mail d10040 @ mail.cmuh.org.tw
358
Dement Geriatr Cogn Disord 2014;37:357–365 DOI: 10.1159/000357701
© 2014 S. Karger AG, Basel www.karger.com/dem
Huang et al.: Risk of Subsequent Dementia in Patients with Hypertensive Encephalopathy: A Nationwide Population-Based Study in Taiwan
Introduction
The term ‘hypertensive encephalopathy’ (HE) was first used in 1928 by Oppenheimer and Fishberg [1] to describe episodes of acute organic brain syndrome correlated with hypertension, which is characterized by unspecific neurological symptoms including headaches, visual disturbances, altered mental statuses, and seizures [2]. The term ‘reversible posterior leukoencephalopathy syndrome’ (RPLS), first used by Hinchey et al. [3] in 1996, has also been used to refer to similar cases because of their indistinguishable reversible clinical pictures with elevated mean arterial pressure and the same radiological feature in computed tomography or magnetic resonance images as edema involving white matter in the parietooccipital areas [2–4]. Meanwhile, the association of hypertension with RPLS is well documented but hypertension is not always present in such cases; particularly in patients treated with immunosuppressant, hypertension may be absent [3]. Therefore, the older term ‘HE’ seems indeed too restrictive for an appropriate naming, and the term ‘RPLS’ was considered misleading by other authors because the involvement of gray matter was also observed. Thus, the term ‘posterior reversible encephalopathy syndrome’ was introduced [5]. The mechanism of these possible brain-capillary leak syndromes is suggested to be extreme elevation of systemic blood pressure, which causes the breakdown of the autoregulatory vascular endothelium of the brain [3]. Although HE is typically reversible, failure to treat the dramatic rise in blood pressure may promptly lead to fatal consequences. This emerging syndrome requires accurate diagnosis and early management. The precise incidence of HE is unknown. However, hypertensive crises (76% urgencies, 24% emergencies) were reported to be more than one fourth of all medical emergencies in Athens in 2010 and can result in acute end-organ injuries such as cerebral infarction, acute myocardial infarction (AMI), heart failure, acute renal failure, and HE [6]. Dementia is an emerging health problem for elderly people in Taiwan. Several risk factors are associated with dementia, including age, sex, inflammation, genetic factors, comorbidity, environmental factors, and lifestyle [7]. The association of HE with risk of dementia has rarely been evaluated. In this study, we investigated whether the diagnosis of HE is linked to an increased risk of developing subsequent dementia by using the Taiwanese National Health Insurance Research Database (NHIRD). The database is available to researchers in Taiwan and has been extensively used in epidemiologic studies [8]. The wide coverage of this large, nationwide database allowed us to examine the relationship between HE and the subsequent development of dementia. Materials and Methods Data Sources The National Health Insurance system is a government-operated, single-payer health insurance program, which was launched in 1995 and covered approximately 99% of the 23.74 million people in Taiwan by 2009 [9]. With authorization from the Department of Health, the National Health Research Institutes (NHRI) is responsible for managing the claims data from all health providers and available information on all insurants. The NHRI established several databases for academic and administrative uses, providing information on the basic patient demographic status, diagnostic codes, medical institutions, outpatient and inpatient orders, prescriptions, and expenditures for care. Data files are linked with scrambled patient identification numbers to protect the privacy of the patients. We used the nationwide population-based data for the period from 1996 to 2010 released by the NHRI. The International Classifications of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) codes were used to define diseases in the claims data. We confirm that all data were de-identified and analyzed anonymously. In addition, this study was approved by the Ethics Review Board at China Medical University (CMU-REC-101–012). Several Taiwanese studies had demonstrated the high accuracy and validity of ICD-9 diagnosis in NHIRD [10, 11].
359
Dement Geriatr Cogn Disord 2014;37:357–365 © 2014 S. Karger AG, Basel www.karger.com/dem
DOI: 10.1159/000357701
Huang et al.: Risk of Subsequent Dementia in Patients with Hypertensive Encephalopathy: A Nationwide Population-Based Study in Taiwan
1,974,009 patients with newly diagnosed hypertension (ICD-9-CM codes 401–405) from the National Health Insurance Program (n = 23,740,000)
Hypertension patients without HE between 1997 and 2010
Hypertension patients with HE between 1997 and 2010 (n = 10,784)
Stroke, dementia before the index date (n = 5,725), age
