|Year : 2015 | Volume
| Issue : 3 | Page : 94-98
Cardiovascular disease, pulse pressure and cognitive decline in ambulatory and hospitalized old patients
Elpidio Santillo1, Luciano Marini1, Luca Fallavollita1, Fabrizio Balestrini1, Alberto Castagna2
1 Geriatric Rehabilitative Department for Cardiovascular Disease, Italian National Research Center on Aging, Fermo, Italy
2 Expert Center for Cognitive Disorders at Pavullo nel Frignano, Local health authority, Modena; Regional Center of Neurogenetic, Lamezia Terme, Catanzaro, Italy
|Date of Web Publication||27-Oct-2015|
Contrada Mossa, Dipartimento Geriatrico Riabilitativo ad
Indirizzo Cerebro-Cardiovascolare, Italian National Research Center on Aging, Contrada Mossa, Fermo - 63900
Source of Support: None, Conflict of Interest: None
Context: Correlations between hypertension, dementia, and cardiovascular diseases in elderly subjects are far from having been elucidated and to date, studies involving old patients from different care settings are lacking. Aims: We aimed to investigate the differences regarding clinical blood pressure values in old subjects from diverse settings of care (ambulatory and hospitalized) examining patients with and without cognitive decline. We wanted also to search the associations between cardiovascular disease, pulse pressure (PP), and cognitive decline in hypertensive subjects. Materials and Methods: The study retrospectively analyzed data from 320 patients (155 ambulatory and 165 hospitalized). Patients' data records were evaluated for diagnosis of cardiovascular diseases and cognitive decline. All subjects underwent blood pressure measurement with the calculation of PP. Results: Patients with dementia or mild cognitive impairment (MCI) showed a greater PP than patients without dementia or MCI (69 mmHg vs 58 mmHg, P: 0.000). In hypertensive patients (n: 219), regression analysis showed an increased risk of cognitive impairment in subjects with cardiovascular disease: odds ratio (OR) 3.65 [95% confidence interval (CI), 1.63 to 8.18], in subjects with higher PP: OR 2.34 (95% CI, 1.15 to 4.77) and in older ones OR: 1.06 (95% CI, 1.01 to 1.12). Conclusions: In our study, old subjects with cognitive impairment showed higher PP. Elderly hypertensive patients with cardiovascular disease from various care settings should always be examined to identify the trend in the development or progression of cognitive decline.
Keywords: Aging, cardiovascular diseases, dementia, hypertension, pulse pressure, vascular stiffness
|How to cite this article:|
Santillo E, Marini L, Fallavollita L, Balestrini F, Castagna A. Cardiovascular disease, pulse pressure and cognitive decline in ambulatory and hospitalized old patients. J Health Res Rev 2015;2:94-8
|How to cite this URL:|
Santillo E, Marini L, Fallavollita L, Balestrini F, Castagna A. Cardiovascular disease, pulse pressure and cognitive decline in ambulatory and hospitalized old patients. J Health Res Rev [serial online] 2015 [cited 2021 May 10];2:94-8. Available from: https://www.jhrr.org/text.asp?2015/2/3/94/168369
| Introduction|| |
It is well-known that elderly patients often present several comorbidities due to the high rate of chronic diseases developed during the senescence process. Comorbidities confer a major risk of both disability and mortality in old individuals, also producing a significant burden on health care expenses., Researches and investigations performed in older subjects should take into account the main comorbid illnesses, analyzing the eventual correlations in order to clearly explain the possible common pathological pathways.,
In geriatric age, dementia and cardiovascular diseases are frequent comorbidities.,,
Hypertension is a common risk factor for both cardiovascular disease and dementia., Pulse pressure (PP) is a measure of the pulsatile component of systemic blood pressure. Elderly hypertensives often present high PP that is associated to increased vascular stiffness predisposing to the risk of cardiovascular diseases.,
Cognitive impairment evolves according to heterogeneous trajectories that are evident on comparing old individuals from different care settings. Unfortunately, few studies have analyzed the characteristics of old patients in different settings of care.,,
We reasoned that even in the presence of clinical heterogeneity, cognitive disorders and cardiovascular disease could, however, share common vascular causes. So, the aims of our study were to examine the differences of PP, cognitive decline and cardiovascular disease in elderly patients from different care settings and investigate their correlations in hypertensive subjects.
| Materials and Methods|| |
The present study retrospectively analyzed data from 320 elderly patients: 155 ambulatory patients from the Expert Center for Cognitive Disorders of Pavullo in Frignano, Province of Modena, Italy (accessed in the period from December 2011 to June 2012) and 165 consecutively hospitalized patients from the Cardiology Unit of the Italian National Research Center on Aging of Fermo, Province of Fermo, Italy (admitted from October 2010 to May 2012). The study subjects had all retired from work. Marital status data were available for the group of hospitalized individuals comprising 53% married, 37% widowed, 8% unmarried, 2% divorced individuals. Each patient included in the study had given informed consent to the processing of personal data for the purposes of scientific research and statistical analysis.
Definitions for diagnosis
Two expert clinicians revised the clinical, psychometric, laboratory, and instrumental documentation of all patients, searched for evidences of previous diagnoses of cardiovascular diseases, dementia, and mild cognitive impairment (MCI). Furthermore, the history of diabetes mellitus and hypertension was researched among the comorbidities.
History of cardiovascular disease was confirmed in the presence of the following one or more documented diagnosis: Ischemic heart disease, stroke, heart failure, peripheral arterial obliterative disease, and arterial revascularization procedures.
Previous diagnosis of dementia was confirmed in accordance with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM IV-TR) criteria. MCI diagnosis needed accordance with the Petersen criteria. In case of disagreement of the two experts, the opinion of a third expert clinician was required.
For the diagnosis of hypertension, a finding of systolic blood pressure (SBP) ≥140 mmHg or diastolic blood pressure (DBP) ≥90 mmHg or antihypertensive therapy or a history of documented diagnosis of high blood pressure was required.
Patients were identified as diabetic if they had two serum glucose values ≥126 mg/dL after fasting (at least for 8 h) or a random blood glucose ≥200 mg/dL or glycated hemoglobin ≥6.5% or glucose ≥200 mg/dL after 2 h of oral glucose load of 75 g or antidiabetic therapy or a history of documented diagnosis of diabetes mellitus.
Blood pressure measurement
Measurement of blood pressure was performed in all subjects with conventional auscultatory method as recommended by the guidelines of the European Society of Cardiology (ESC)/European Society of Hypertension (ESH) 2007. The measurements took place with the patient lying down for at least 10 min by using a sphygmomanometer cuff appropriate for the arm of the subject. SBP and DBP were detected in the appearance of the I and V Korotkoff sounds. The values used for analysis were obtained from the average of three measurements taken at a distance of 5 min.
The PP was calculated as:
PP = (SBP-DBP)
The mean arterial pressure (MAP) was calculated as:
MAP = PAD +(PP/3)
The heart rate (HR) was measured by electrocardiogram and was expressed in number of beats per minute (beats/min).
The patients were initially divided into two groups according to the clinical setting of origin (ambulatory and hospitalized) and then based on the presence/absence of dementia or MCI. The values were expressed as mean ± standard deviation (SD) or as percentage (%). Comparisons between the groups of subjects were performed using the Student's t-test for continuous variables. The Chi-square test with two tails was used to test the null hypothesis for categorical variables. For hypertensive patients (n: 219), the existence of significant associations between dementia or MCI and other covariates was examined using the Chi-square test with two tails. In the analysis, association values of PP were stratified according to whether they were above or below the fiftieth percentile of the distribution of the respective population (ambulatory or hospitalized). A multivariate model (stepwise forward conditional logistic regression) was built to test the possible independent relationship between cognitive impairment and other variables in hypertensive subjects in the study. The following covariates were included in the model: Age, sex, PP, antihypertensive therapy, and history of cardiovascular disease and diabetes mellitus. Data were expressed as odds ratios (ORs) with 95% confidence interval (CI). A P < 0.05 was considered statistically significant. Calculations were made with statistical software (OpenStat 17.0 by W. Miller, Iowa State University, USA).
| Results|| |
Characteristics of the patients in the study divided according to setting of origin
The characteristics of patients divided according to the setting of origin (ambulatory or hospitalized) are shown in [Table 1]. The outpatients when compared to inpatients exhibited a significantly higher age (82 years vs 80 years, P: 0.020 by Student's t-test), significantly higher values of SBP and PP, and a higher frequency of dementia or MCI. Hospitalized patients, however, exhibited a significantly higher rate of hypertension and antihypertensive treatment and a greater HR. There were no significant differences between the two groups in the distribution of gender and the presence of diabetes or history of cardiovascular disease.
|Table 1: Data of patients divided according to care settings (Student's t-test for continuous variables, Chi-square for categorical variables)|
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Characteristics of the patients in the study were divided according to the diagnosis of dementia or MCI.
[Table 2] shows the characteristics of patients divided according to the presence/absence of cognitive impairment. Persons suffering from cognitive impairment were characterized for presenting higher age, higher values of PP (69 mmHg vs 58 mmHg; P: 0.000 by Student's t-test; [Figure 1] and higher SBP. There were no significant differences in the proportion of patients with hypertension, diabetes mellitus, and history of cardiovascular disease between the two groups. However, patients suffering from dementia or MCI were characterized by a lower intake of antihypertensive therapy (47% vs 60% P: 0.023 by chi square).
|Table 2: Characteristics of patients divided according to cognitive impairment (Student's t-test for continuous variables, Chi-square for categorical variables)|
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|Figure 1: Mean pulse pressure values in old patients (ambulatory and hospitalized) with and without cognitive impairment|
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Association analysis in hypertensive patients
As shown in [Table 3], the presence of cognitive impairment among patients with hypertension (n: 219) was significantly associated with history of cardiovascular disease, with higher PP and with the absence of antihypertensive therapy. No significant associations between dementia or MCI and diabetes mellitus and sex were found.
|Table 3: Associations (chi.square) between cognitive impairment (dementia or MCI) and covariates in hypertensive patients (n:219)|
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Logistic regression analysis was performed in hypertensive patients in the study in order to estimate the risk of cognitive impairment (dementia or MCI)-associated with history of cardiovascular disease and higher values of PP independently from the effect of other covariates. As shown in [Table 4], in this model the history of cardiovascular disease conferred a risk that was more than triple to present cognitive impairment [OR3.65 (95% CI, 1.63 to 8.18)]. Also, higher PP was associated with a risk of cognitive impairment that was more than double [OR 2.34 (95% CI, 1.15 to 4.77)]. As expected, even higher age was associated with an increased risk of cognitive impairment [OR: 1.06 (95% CI, 1.01 to 1.12)] independently from other covariates included in the model (sex, history of diabetes mellitus, and antihypertensive therapy).
|Table 4: Multivariate logistic regression analysis (stepwise forward conditional: last step). Dependent variable: Dementia or MCI|
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| Discussion|| |
Interestingly, our study found an independent association between the history of cardiovascular disease and cognitive impairment in elderly hypertensive patients from the two examined care settings.
A positive independent correlation between PP and cognitive impairment has been also observed in hypertensive patients. The described associations appear more robust because they are evident on observing old hypertensive patients in a different clinical context.
These findings confirm that in elderly patients with hypertension, higher PP reflecting vascular remodeling might be involved in the development of cognitive decline. In fact, atherosclerosis seems to play an important role not only in the development of vascular dementia but also in the pathogenesis of degenerative forms. Several mechanisms underlying this relationship have been proposed such as ischemia triggering an inflammatory response that can lead to neurodegeneration or ischemic lesions affecting specific neuronal networks. Furthermore, previous studies have shown that cardiovascular disease and dementia may be associated based on the sharing of common pathogenetic factors.,,,, Consequently, the treatment of some cardiovascular risk factors such as hypertension might have a beneficial impact on the development or progression of cognitive impairment and dementia. Information on the efficacy of antihypertensive therapy in the prevention of cognitive impairment has been provided by several randomized double-blind, placebo-controlled longitudinal studies.,,,,,, In particular, the Systolic Hypertension in Europe (Syst-Eur) study furnished evidence on the efficacy of antihypertensive therapy in preventing Alzheimer's disease. In the Perindopril Protection Against Recurrent Stroke Study (PROGRESS), the development of dementia associated with recurrent cerebrovascular events was investigated with the result of a significant risk reduction in subjects treated with the angiotensin-converting-enzyme (ACE) inhibitor perindopril  Overall, the evidence provided by the trials suggest that antihypertensive therapy may be effective both in the prevention of Alzheimer's disease and in vascular forms. It is hypothesized that the underlying mechanisms of the protection deriving from antihypertensive treatment are various and include a reduction in the incidence of cerebrovascular disease, inhibition of amyloidogenesis secondary to hypoxia, and a potential neuroprotective effect of some antihypertensive drugs.
In many populations, both SBP and PP tend to increase with advancing years while DBP tends to be reduced. The increase in PP in the elderly is considered due to a higher arterial stiffness. Since PP is an indicator of arterial stiffness, reflecting on the structural and functional age-related changes of the arterial system, it is conceivable that high PP may contribute to the pathogenesis of dementia as proposed by the paradigm of the "vascular cognitive impairment." The correlation between increased PP and cognitive decline could be explained by the common pathologic substrate of a more diffuse atherosclerosis capable of altering the vascular elasticity. It is also known that increase of PP may alter the diastolic coronary perfusion, determine left ventricular hypertrophy and dysfunction, and increase the myocardial oxygen consumption, thus predisposing to development of ischemic heart disease. The age-related increase in PP itself also exerts significant direct and indirect effects on both the cerebrovascular system and the brain despite the ability of autoregulation and the fact that the distance from the aorta could render the brain vascular bed less vulnerable to central pulsatile stress., Numerous studies, in fact, confirmed that high blood pressure was strongly associated with white matter lesions, the extent of which in the brain seemed to correlate significantly with SBP and cognitive impairment.,,,,
Finally, our study found some significant differences concerning blood pressure on comparing outpatients with those who had recovered, probably attributable to the criteria of admission of patients in the two centers. In particular, with regard to the hemodynamic profile, the finding of a lower PP and a higher HR in hospitalized subjects may be consequent to acute illness requiring hospitalization. However, the lower PP of inpatients may be partly attributed to their lower age when compared to that of outpatients. Conversely, no significant difference was found in the average values of MAP, a measure that integrates both systolic and DBP, and this has been proposed to be strictly associated with brain perfusion pressure.
Limitations of the study
First, our study is retrospective so we cannot prove causation. Also, as all the patients were elderly, the results may not be applicable to other age groups. Moreover, depression was not evaluated in our study and so, the diagnosis of prevalent cognitive impairment could be confounded. The study shows, however, the strengths to be conducted in a group of patients of advanced age in two different settings of care and have provided a statistical analysis that takes into account potential confounders (age, sex, diabetes mellitus, and antihypertensive therapy) in assessing the association between cognitive impairment, PP, and cardiovascular disease history.
| Conclusions|| |
In the present study, a higher PP resulted independently associated with the presence of cognitive impairment. The simple calculation of the differential pressure in elderly patients in various clinical settings of care could provide an idea of the risk of development or progression of cognitive impairment, guiding clinicians toward appropriate choices in diagnostic and therapeutic management.
Similarly, a history of cardiovascular disease in old hypertensive patients should suggest investigation of the individual cognitive status by virtue of the relationship with cognitive impairment, as was also evident in our study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest
| References|| |
Fried LP, Ferrucci L, Darer J, Williamson JD, Anderson G. Untangling the concepts of disability, frailty, and comorbidity: Implications for improved targeting and care. J Gerontol A Biol Sci Med Sci 2004;59:255-63.
Hoffman C, Rice D, Sung HY. Persons with chronic conditions: Their prevalence and costs. JAMA 1996;276:1473-9.
Fuchs Z, Blumstein T, Novikov I, Walter-Ginzburg A, Lyanders M, Gindin J, et al
. Morbidity, comorbidity, and their association with disability among the community-dwelling oldest-old in Israel. J Gerontol A Biol Sci Med Sci 1998;53:M447-55.
Kishimoto M, Ojima T, Nakamura Y, Yanagawa H, Fujita Y, Kasagi F, et al
. Relationship between the level of activities of daily living and chronic medical conditions among the elderly. J Epidemiol 1998;8:272-7.
Wimo A, Winblad B, Aguero-Torres H, von Strauss E. The magnitude of dementia occurrence in the world. Alzheimer Dis Assoc Disord 2003;17:63-7.
Fratiglioni L, Grut M, Forsell Y, Viitanen M, Grafström M, Holmén K, et al
. Prevalence of Alzheimer's disease and other dementias in an elderly urban population: Relationship with age, sex, and education. Neurology 1991;41:1886-92.
Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM, et al
.; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics-2011 update: A report from the American Heart Association. Circulation 2011;123:e18-209.
MacMahon S, Peto R, Cutler J, Collins R, Sorlie P, Neaton J, et al
. Blood pressure, stroke, and coronary heart disease. Part 1, Prolonged differences in blood pressure: Prospective observational studies corrected for the regression dilution bias. Lancet 1990;335:765-74.
Gąsecki D, Kwarciany M, Nyka W, Narkiewicz K. Hypertension, brain damage and cognitive decline. Curr Hypertens Rep 2013;15:547-58.
Domanski M, Norman J, Wolz M, Mitchell G, Pfeffer M. Cardiovascular risk assessment using pulse pressure in the first national health and nutrition examination survey (NHANES I). Hypertension 2001;38:793-7.
Gasowski J, Fagard RH, Staessen JA, Grodzicki T, Pockock S, Boutitie F, et al
.; INDANA Project Collaborators. Pulsatile blood pressure component as predictor of mortality in hypertension: A meta-analysis of clinical trial control groups. J Hypertens 2002;20:145-51.
Hayden KM, Reed BR, Manly JJ, Tommet D, Pietrzak RH, Chelune GJ, et al
. Cognitive decline in the elderly: An analysis of population heterogeneity. Age Ageing 2011;40:684-9.
Kume Y, Sugita T, Oga K, Kagami K, Igarashi H. A pilot study: Comparative research of social functioning, circadian rhythm parameters, and cognitive function among institutional inpatients, and outpatients with chronic schizophrenia and healthy elderly people. Int Psychogeriatr 2015;27:135-43.
Cohen HJ, Feussner JR, Weinberger M, Carnes M, Hamdy RC, Hsieh F, et al
. A controlled trial of inpatient and outpatient geriatric evaluation and management. N Engl J Med 2002;346:905-12.
American Psychiatric Association. Diagnostic criteria from DSM-IV-TR. American Psychiatric Pub, 2000.
Petersen RC, Doody R, Kurz A, Mohs RC, Morris JC, Rabins PV, et al
. Current concepts in mild cognitive impairment. Arch Neurol 2001;58:1985-92.
Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, et al
. Management of Arterial Hypertension of the European Society of Hypertension; European Society of Cardiology. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 2007;25:1105-87.
de la Torre JC. Is Alzheimer's disease a neurodegenerative or a vascular disorder? Data, dogma, and dialectics. Lancet Neurol 2004;3:184-90.
Haring B, Leng X, Robinson J, Johnson KC, Jackson RD, Beyth R, et al
. Cardiovascular disease and cognitive decline in postmenopausal women: Results from the Women's Health Initiative Memory Study. J Am Heart Assoc 2013;2:e000369.
Kuller LH, Lopez OL, Jagust WJ, Becker JT, DeKosky ST, Lyketsos C, et al
. Determinants of vascular dementia in the Cardiovascular Health Cognitive Study. Neurology 2005;64:1548-52.
Rosano C, Naydeck B, Kuller LH, Longstreth WT Jr, Newman AB. Coronary artery calcium: Association with brain magnetic resonance imaging abnormalities and cognitive status. J Am Geriatr Soc 2005;53:609-15.
Zhong W, Cruickshanks KJ, Schubert CR, Acher CW, Carlsson CM, Klein BE, et al
. Carotid atherosclerosis and 10-year changes in cognitive function. Atherosclerosis 2012;224:506-10.
Newman AB, Fitzpatrick AL, Lopez O, Jackson S, Lyketsos C, Jagust W, et al
. Dementia and Alzheimer's disease incidence in relationship to cardiovascular disease in the cardiovascular health study cohort. J Am Geriatr Soc 2005;53:1101-7.
Forette F, Seux ML, Staessen JA, Thijs L, Birkenhäger WH, Babarskiene MR, et al
. Prevention of dementia in randomised double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial. Lancet 1998;352:1347-51.
Di Bari M, Pahor M, Franse LV, Shorr RI, Wan JY, Ferrucci L, et al
. Dementia and disability outcomes in large hypertension trials: Lessons learned from the systolic hypertension in the elderly program (SHEP) trial. Am J Epidemiol 2001;153:72-8.
Prince MJ, Bird AS, Blizard RA, Mann AH. Is the cognitive function of older patients affected by antihypertensive treatment? Results from 54 months of the Medical Research Council's trial of hypertension in older adults. BMJ 1996;312:801-5.
van Gijn J. The PROGRESS Trial: Preventing strokes by lowering blood pressure in patients with cerebral ischemia. Emerging therapies: Critique of an important advance. Stroke 2002;33:319-20.
Arnold JM, Yusuf S, Young J, Mathew J, Johnstone D, Avezum A, et al
. Prevention of Heart Failure in Patients in the Heart Outcomes Prevention Evaluation (HOPE) Study. Circulation 2003;107:1284-90.
Beckett NS, Peters R, Fletcher AE, Staessen JA, Liu L, Dumitrascu D, et al
. HYVET Study Group. Treatment of hypertension in patients 80 years of age or older. N Engl J Med 2008;358:1887-98.
Peters R, Beckett N, Forette F, Tuomilehto J, Clarke R, Ritchie C, et al
. HYVET investigators. Incident dementia and blood pressure lowering in the Hypertension in the Very Elderly Trial cognitive function assessment (HYVET-COG): A double-blind, placebo controlled trial. Lancet Neurol 2008;7:683-9.
Valenzuela M, Esler M, Ritchie K, Brodaty H. Antihypertensives for combating dementia? A perspective on candidate molecular mechanisms and population-based prevention. Transl Psychiatry 2012;2:e107.
Franklin SS, Gustin W 4th
, Wong ND, Larson MG, Weber MA, Kannel WB, et al
. Hemodynamic patterns of age-related changes in blood pressure. The Framingham Heart Study. Circulation 1997;96:308-15.
Moorhouse P, Rockwood K. Vascular cognitive impairment: Current concepts and clinical developments. Lancet Neurol 2008;7:246-55.
Waldstein SR, Carrington Rice S, Thayer JF, Najjar SS, Scuteri A, Zonderman AB. Pulse pressure and pulse wave velocity are related to cognitive decline in the Baltimore Longitudinal Study of Aging. Hypertension 2008;51:99-104.
Benetos A, Rudnichi A, Safar M, Guize L. Pulse pressure and cardiovascular mortality in normotensive and hypertensive subjects. Hypertension 1998;32:560-4.
van der Flier WM, van Straaten EC, Barkhof F, Verdelho A, Madureia S, Pantoni L, et al
. Small vessel disease and general cognitive function in nondisabled elderly: The LADIS study. Stroke 2005;36:2116-20.
Birns J, Markus H, Kalra L. Blood pressure reduction for vascular risk: Is there a price to be paid? Stroke 2005;36:1308-13.
Guo Z, Fratiglioni L, Winblad B, Viitanen M. Blood pressure and performance on the Mini-Mental State Examination in the very old. Cross-sectional and longitudinal data from the Kungsholmen Project. Am J Epidemiol 1997;145:1106-13.
Kuusisto J, Koivisto K, Mykkänen L, Helkala EL, Vanhanen M, Hänninen T, et al
. Essential hypertension and cognitive function. The role of hyperinsulinemia. Hypertension 1993;22:771-9.
Scherr PA, Hebert LE, Smith IA, Evans DA. Relation of blood pressure to cognitive functions in the elderly. Am J Epidemiol 1991;134:1303-15.
Kilander L, Nyman H, Boberg M, Hansson L, Lithell H. Hypertension is related to cognitive impairment: A 20-year follow-up of 999 men. Hypertension 1998;31:780-6.
Parati G, Pomidossi G, Albini F, Malaspina D, Mancia G. Relationship of 24-hour blood pressure mean and variability to severity of target-organ damage in hypertension. J Hypertens 1987;5:93-8.
Steiner LA, Andrews PJ. Monitoring the injured brain: ICP and CBF. Br J Anaesth 2006;97:26-38.
[Table 1], [Table 2], [Table 3], [Table 4]