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 Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 2  |  Issue : 3  |  Page : 94-98

Cardiovascular disease, pulse pressure and cognitive decline in ambulatory and hospitalized old patients


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 Publication27-Oct-2015

Correspondence Address:
Elpidio Santillo
Contrada Mossa, Dipartimento Geriatrico Riabilitativo ad Indirizzo Cerebro-Cardiovascolare, Italian National Research Center on Aging, Contrada Mossa, Fermo - 63900
Italy
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2394-2010.168369

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  Abstract 

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 2019 Dec 8];2:94-8. Available from: http://www.jhrr.org/text.asp?2015/2/3/94/168369


  Introduction Top


It is well-known that elderly patients often present several comorbidities due to the high rate of chronic diseases developed during the senescence process.[1] Comorbidities confer a major risk of both disability and mortality in old individuals, also producing a significant burden on health care expenses.[1],[2] 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.[3],[4]

In geriatric age, dementia and cardiovascular diseases are frequent comorbidities.[5],[6],[7]

Hypertension is a common risk factor for both cardiovascular disease and dementia.[8],[9] 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.[10],[11]

Cognitive impairment evolves according to heterogeneous trajectories that are evident on comparing old individuals from different care settings.[12] Unfortunately, few studies have analyzed the characteristics of old patients in different settings of care.[12],[13],[14]

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 Top


Subjects

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.[15] MCI diagnosis needed accordance with the Petersen criteria.[16] 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.[17] 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).

Statistical analysis

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 Top


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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Multivariate analysis

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 Top


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.[18] 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.[18] Furthermore, previous studies have shown that cardiovascular disease and dementia may be associated based on the sharing of common pathogenetic factors.[19],[20],[21],[22],[23] 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.[24],[25],[26],[27],[28],[29],[30] In particular, the Systolic Hypertension in Europe (Syst-Eur) study furnished evidence on the efficacy of antihypertensive therapy in preventing Alzheimer's disease.[24] 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 [27] 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.[31]

In many populations, both SBP and PP tend to increase with advancing years while DBP tends to be reduced.[32] 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."[33] 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.[34] 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.[35] 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.[36],[37] 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.[38],[39],[40],[41],[42]

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.[43]

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 Top


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

Nil.

Conflicts of interest

There are no conflicts of interest

 
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