Is neurocardiovascular instability a risk factor for cognitive decline and/or dementia? The science to date

Neurocardiovascular instability (NCVI) is defined as ‘age-related changes in blood pressure and heart-rate behaviour, predominantly resulting in hypotension and bradyarrhythmia’ The four most common presentations of NCVI are orthostatic hypotension (OH), carotid sinus hypersensitivity/syndrome (CSH/CSS), vasovagal syncope (VVS) and post-prandial hypotension (PPH), although there is considerable overlap between these conditions. The criteria for diagnosis of these syndromes are given in Table 1. Clinically, these conditions manifest as dizziness, falls, pre-syncope and syncope. Older people are more susceptible to NCVI because of age-related physiological changes in the cardiovascular system, the autonomic nervous system, and humoral control of blood pressure. These neurocardiovascular changes are further complicated by co-morbidity and polypharmacy in older people.

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Drug metabolism and ageing

Menopause International ◽

10.1258/136218005775544589 ◽

2005 ◽

Vol 11 (2) ◽

pp. 51-56 ◽

Cited By ~ 50

Author(s):

Hilary Wynne

Keyword(s):

Blood Flow ◽

Older People ◽

Liver Blood Flow ◽

Drug Distribution ◽

Drug Clearance ◽

Cytochrome P450 Enzymes ◽

Liver Size ◽

Age Related ◽

Co Morbidity ◽

Age Related Changes

Older people are major consumers of drugs and because of this, as well as co-morbidity and age-related changes in pharmacokinetics and pharmacodynamics, are at risk of associated adverse drug reactions. While age does not alter drug absorption in a clinically significant way, and age-related changes in volume of drug distribution and protein binding are not of concern in chronic therapy, reduction in hepatic drug clearance is clinically important. Liver blood flow falls by about 35% between young adulthood and old age, and liver size by about 24–35% over the same period. First-pass metabolism of oral drugs avidly cleared by the liver and clearance of capacity-limited hepatically metabolized drugs fall in parallel with the fall in liver size, and clearance of drugs with a high hepatic extraction ratio falls in parallel with the fall in hepatic blood flow. In normal ageing, in general, activity of the cytochrome P450 enzymes is preserved, although a decline in frail older people has been noted, as well as in association with liver disease, cancer, trauma, sepsis, critical illness and renal failure. As the contribution of age, co-morbidity and concurrent drug therapy to altered drug clearance is impossible to predict in an individual older patient, it is wise to start any drug at a low dose and increase this slowly, monitoring carefully for beneficial and adverse effects.

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Effect of aging on cerebral tissue oxygenation in relation to reflex syncope

EP Europace ◽

10.1093/europace/euab116.325 ◽

2021 ◽

Vol 23 (Supplement_3) ◽

Author(s):

I Kharraziha ◽

P Torabi ◽

M Johansson ◽

R Sutton ◽

A Fedorowski ◽

...

Keyword(s):

Blood Pressure ◽

Tissue Oxygenation ◽

Vasovagal Syncope ◽

Age Groups ◽

Cerebral Tissue ◽

Reflex Syncope ◽

Age Related ◽

Head Up Tilt ◽

Cerebral Tissue Oxygenation ◽

Increased Susceptibility

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Swedish Heart and Lung Foundation, The Swedish Heart and Lung Association, ALF funds, Skåne University Hospital Funds, The Crafoord Foundation. Background There is an increased susceptibility to syncope with aging attributed to age-related physiological impairments. Cerebral oximetry non-invasively measures cerebral tissue oxygenation (SctO2) and has been shown to be valuable in syncope evaluation. SctO2 has been found to decrease with aging but it is unknown whether the decrease in SctO2 is related to increased susceptibility to syncope during orthostatic provocation. By measuring SctO2 during head up tilt test (HUT) we can study age-related differences in SctO2 and their impact on developing reflex syncope. Purpose To investigate the effect of age on the cerebral tissue oxygenation threshold for syncope and presyncope among patients with vasovagal syncope. Methods Non-invasive haemodynamic monitoring and near-infrared spectroscopy (NIRS) were applied during head-up tilt (HUT) in 139 vasovagal syncope patients (mean [SD] 45[17] years, 60% female), and 82 control patients with a normal response to HUT (45[18] years, 61% female). Group differences in SctO2 and systolic blood pressure (SBP) during HUT in supine position, after 3 and 10 min of HUT, 30 seconds prior to syncope ("presyncopal phase") and during syncope in different age groups (<30, 30-60 and >60 years) were compared using one-way ANOVA and Tukey"s multiple comparison test. Associations between age and SctO2 were studied using linear regression models adjusted for sex and concurrent SBP. Results Lower SctO2 in supine position was associated with increasing age among controls (B=-0.085, p = 0.010) but not among VVS patients (B=-0.036, p = 0.114). No age-related differences in SctO2 were found after 3 and 10 minutes of HUT and during syncope. Mean SctO2 (%) during the presyncopal phase decreased over the advancing age groups (<30: 66.9 ± 6.2, 30-60: 64.5 ± 6.1, >60: 62.2 ± 5.8; p = 0.009 for inter-group comparison). In contrast, mean SBP during the presyncopal phase did not differ by age groups (<30: 85.6 ± 21.8, 30-60: 77.6 ± 19.7, >60: 77.6 ± 20.8 mmHg, p = 0.133). Age was associated with lower SctO2 during the presyncopal phase after adjusting for sex and SBP (B = 0.096, p = 0.001). Conclusion Older VVS patients have lower cerebral tissue oxygenation in the presyncopal phase compared with younger patients independently of systolic blood pressure. These results suggest either that with imminent reflex syncope cerebral tissue oxygenation diminishes more with advancing age or that cerebral deoxygenation is better tolerated by older reflex syncope patients. Abstract Figure.

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Hypertension in older people

Stroke in the Older Person ◽

10.1093/med/9780198747499.003.0024 ◽

2020 ◽

pp. 365-380

Author(s):

Wayne Sunman

Keyword(s):

Blood Pressure ◽

Older People ◽

Stroke Unit ◽

Pressure Control ◽

Stroke Patients ◽

The United Kingdom ◽

Age Related ◽

Diastolic Hypertension ◽

Pressure Lowering ◽

Age Related Changes

‘Hypertension in older people’ highlights the issues concerning ageism in the diagnosis and management of hypertension, the prevalence, future predictions, and its historical aspects. Stroke is a disease of old age. The average age of stroke patients passing through our stroke unit is 76 years, in common with other units in the United Kingdom. Trials examining only those patients under 80 years old are examining a skewed population, in which around 40% of patients have been excluded. The author examines several trials of blood pressure lowering in older people, age related changes in blood pressure, the importance of systolic versus diastolic hypertension, targets of blood pressure control, impact of frailty, dementia, and cognitive impairment, orthostatic hypotension, and diabetes. Post-stroke blood pressure management is discussed in greater detail along with a review of the important trials in this group of patients.

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Blood pressure in frail older adults: associations with cardiovascular outcomes and all-cause mortality

Age and Ageing ◽

10.1093/ageing/afaa028 ◽

2020 ◽

Vol 49 (5) ◽

pp. 807-813 ◽

Cited By ~ 2

Author(s):

Jane A H Masoli ◽

Joao Delgado ◽

Luke Pilling ◽

David Strain ◽

David Melzer

Keyword(s):

Blood Pressure ◽

Primary Care ◽

Older People ◽

Excess Mortality ◽

Cardiovascular Outcomes ◽

Sensitivity Analyses ◽

Clinical Practice Research Datalink ◽

Frail Older People ◽

Co Morbidity ◽

All Cause Mortality

Abstract Background Blood pressure (BP) management in frail older people is challenging. An randomised controlled trial of largely non-frail older people found cardiovascular and mortality benefit with systolic (S) BP target <120 mmHg. However, all-cause mortality by attained BP in routine care in frail adults aged above 75 is unclear. Objectives To estimate observational associations between baseline BP and mortality/cardiovascular outcomes in a primary-care population aged above 75, stratified by frailty. Methods Prospective observational analysis using electronic health records (clinical practice research datalink, n = 415,980). We tested BP associations with cardiovascular events and mortality using competing and Cox proportional-hazards models respectively (follow-up ≤10 years), stratified by baseline electronic frailty index (eFI: fit (non-frail), mild, moderate, severe frailty), with sensitivity analyses on co-morbidity, cardiovascular risk and BP trajectory. Results Risks of cardiovascular outcomes increased with SBPs >150 mmHg. Associations with mortality varied between non-frail <85 and frail 75–84-year-olds and all above 85 years. SBPs above the 130–139-mmHg reference were associated with lower mortality risk, particularly in moderate to severe frailty or above 85 years (e.g. 75–84 years: 150–159 mmHg Hazard Ratio (HR) mortality compared to 130–139: non-frail HR = 0.94, 0.92–0.97; moderate/severe frailty HR = 0.84, 0.77–0.92). SBP <130 mmHg and Diastolic(D)BP <80 mmHg were consistently associated with excess mortality, independent of BP trajectory toward the end of life. Conclusions In representative primary-care patients aged ≥75, BP <130/80 was associated with excess mortality. Hypertension was not associated with increased mortality at ages above 85 or at ages 75–84 with moderate/severe frailty, perhaps due to complexities of co-existing morbidities. The priority given to aggressive BP reduction in frail older people requires further evaluation.

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Cardiovascular Reflex Responses in Patients with Unexplained Syncope

Clinical Science ◽

10.1042/cs0770547 ◽

1989 ◽

Vol 77 (5) ◽

pp. 547-553 ◽

Cited By ~ 43

Author(s):

M. M. A. E. Wahbha ◽

C. A. Morley ◽

Y. M. H. Al-Shamma ◽

R. Hainsworth

Keyword(s):

Blood Pressure ◽

Cardiac Output ◽

Postural Hypotension ◽

Vasovagal Syncope ◽

Pulse Interval ◽

Reflex Responses ◽

Non Invasive ◽

Control Subjects ◽

Cardiovascular Reflex ◽

Age Related

1. This study was undertaken to determine whether, in a group of patients complaining of recurrent syncopal attacks but with no apparent cause, there was evidence of abnormal cardiovascular reflex control. 2. The steady-state responses of blood pressure, heart rate and cardiac output to head-up tilting were determined in 67 patients using entirely ‘non-invasive’ methods. In some patients we also studied the immediate response of pulse interval to carotid baroreceptor stimulation by neck suction. 3. Two of the patients developed vasovagal attacks during the 20 min test period of head-up tilting. Eighteen others showed postural hypotension, defined as a fall in blood pressure to outside the limits of two sds from the mean values of age-related control subjects. 4. Patients who showed postural hypotension had a mean fall in cardiac output significantly larger than that in age-related control subjects. Responses in the non-hypotensive patients did not differ significantly from controls. 5. Stimulation of carotid baroreceptors resulted in significantly smaller responses of pulse interval in the patients defined as having postural hypotension compared with the non-hypotensive patients and with the age-related control subjects. 6. In some of the patients who did not show postural hypotension during the standard test, the duration of tilt was prolonged for up to 1 h. Five out of 26 patients developed vasovagal attacks. All the vasovagal patients showed an initial tachycardia and the response of pulse interval to neck suction was significantly larger than in the controls. 7. This study has shown that simple non-invasive tests of cardiovascular reflex function can divide patients with poor orthostatic tolerance into two groups: those with evidence of small reflex responses, associated with abnormally large falls in cardiac output during tilting, and those with evidence of overactive reflexes associated with the tendency to develop vasovagal syncope.

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Device therapy of resistant hypertension

Orvosi Hetilap ◽

10.1556/oh.2013.29543 ◽

2013 ◽

Vol 154 (6) ◽

pp. 203-208 ◽

Cited By ~ 1

Author(s):

Gábor Simonyi ◽

J. Róbert Bedros ◽

Mihály Medvegy

Keyword(s):

Blood Pressure ◽

Cardiovascular Risk ◽

Resistant Hypertension ◽

Carotid Sinus ◽

Maximum Tolerated Dose ◽

Reduce Blood Pressure ◽

Nerve Fibers ◽

Uncontrolled Hypertension ◽

Sympathetic Nerve Fibers ◽

Treatment Of Hypertension

It is well known that hypertension is an independent cardiovascular risk factor. Treatment of hypertension frequently includes administration of three or more drugs. Resistant hypertension is defined when blood pressure remains above target value despite full doses (the patient’s maximum tolerated dose) of antihypertensive medication consisting of at least three different classes of drugs including a diuretic. Pharmacological treatment of hypertension is often unsuccessful despite the increasing number of drug combinations. Uncontrolled hypertension, however, increases the cardiovascular risk. Device treatment of resistant hypertension is currently testing two major fields. One of them the stimulation of baroreceptors in the carotid sinus and the other is radiofrequency ablation of sympathetic nerve fibers around renal arteries to reduce blood pressure in drug resistant hypertension. Orv. Hetil., 2013, 154, 203–208.

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