Blood pressure variability and cognitive decline in older people: a 5-year longitudinal study.

BACKGROUND: Cognitive impairment is common in later life. Identifying potential modifiable risk factors for cognitive decline may ameliorate the burden of disease. Cross-sectional studies show an association between blood pressure (BP) variability and impaired cognitive function in patients with hypertension and/or dementia. However, research examining the association between BP variability and cognitive function in the general older population is scarce. OBJECTIVE: In this study, we examined the association between BP variability and cognitive function over 5-year follow-up in an unselected community-dwelling cohort. METHODS: Ambulatory BP monitoring was performed in 353 community-dwelling people aged at least 65 years. Cognitive assessment, using the Mini Mental State Examination (MMSE) and Cambridge Cognitive Examination (CAMCOG), was performed at baseline and at 5-year follow-up. BP variability was calculated using the coefficient of variation. Cognitive change over 5 years was defined as baseline score minus follow-up score. RESULTS: Increased daytime systolic variability was associated with poorer performance on the CAMCOG total score and subscores. Daytime diastolic variability was associated with poorer performance on total CAMCOG, CAMCOG executive score, and MMSE. These findings were independent of demographic and cardiovascular risk factors. Daytime systolic variability was also independently associated with greater decline in total CAMCOG and MMSE scores over 5-year follow-up. CONCLUSION: Increased BP variability is associated with poorer cognitive function in older people and may represent a novel modifiable risk factor for cognitive decline.

Modified criteria for carotid sinus hypersensitivity are associated with increased mortality in a population-based study.

AIMS: Carotid sinus hypersensitivity (CSH) is arbitrarily defined as ≥3 s asystole or vasodepression of ≥50 mmHg in response to carotid sinus massage (CSM). Using this definition, 39% of older people meet the criteria for CSH. It has been suggested that current criteria are too sensitive. Krediet et al. [The history of diagnosing carotid sinus hypersensitivity: why are the current criteria too sensitive? Europace 2011;13:14-22] and Kerr et al. [Carotid sinus hypersensitivity in asymptomatic older persons: implications for diagnosis of syncope and falls. Arch Intern Med 2006;166:515-20] have proposed modified criteria. This population-based study aimed to compare the prevalence of CSH defined according to standard, Krediet and Kerr criteria, and to establish if CSH defined according these criteria is associated with all-cause mortality. METHODS AND RESULTS: A total of 272 community-dwelling people aged ≥65 were recruited at random. Carotid sinus massage was performed for 5 s in supine and head-up positions. Heart rate and blood pressure response were recorded using an electrocardiogram and photoplethysmography. Cox regression analysis was used to examine the association between each definition of CSH and all-cause mortality. The prevalence of CSH defined according to standard, Krediet, and Kerr criteria was 39, 52, and 10%, respectively. Seventy-one participants died over a mean follow-up of 8.6 years (SD 2.1). Carotid sinus hypersensitivity defined according to standard and Krediet criteria was not associated with survival. Carotid sinus hypersensitivity defined according to Kerr criteria was associated with all-cause mortality independent of age and sex [hazard ratio (HR) 2.023 (95% confidence interval (95% CI) 1.131-3.618) P = 0.018)]. This remained significant after adjusting for cardiovascular risk factors [HR 2.174 (1.075-3.900) P = 0.009]. CONCLUSION: Carotid sinus hypersensitivity defined according to Kerr criteria is associated with increased mortality. This raises an interesting question as to the suitability of the current criteria used to define CSH.

Ambulatory Blood Pressure Variability Increases Over a 10-Year Follow-Up in Community-Dwelling Older People.

BACKGROUND: Greater ambulatory blood pressure variability (ABPV) is associated with end-organ damage and increased mortality. Age-related changes in the cardiovascular and autonomic nervous systems make age-associated increases in ABPV likely. Cross-sectional studies support this hypothesis, showing greater ABPV among older compared to younger adults. The only longitudinal study to examine changes in ABPV, however, found ABPV decreased over 5 years follow-up. This unexpected observation probably reflected the highly selected nature of the study participants. METHODS: In this longitudinal study, we assessed changes in ABPV over 10 years in a community-cohort of older people. In addition, we examined the extent to which ABPV was predicted by demographics, cardiovascular risk factors, and medication. Clinical examination and 24-hour ambulatory blood pressure monitoring were carried out at baseline and at 10 years follow-up in 83 people, median age 70 years. ABPV was calculated using SD and coefficient of variation (Cv). Three time periods were examined: daytime, nighttime, and 24 hours. RESULTS: Daytime and 24-hour, systolic and diastolic, SD, and Cv were significantly greater at follow-up than at baseline (P < 0.001 in all cases). Mean BP did not change. CONCLUSIONS: Multilevel modeling showed follow-up interval had a significant, positive effect on SD and Cv (P < 0.004), independent of age, sex, and medication.ABPV increased over a 10-year follow-up despite stable mean BP. ABPV may therefore be an additional target for treatment in older people. Future studies should examine what degree of ABPV is harmful and if control of ABPV reduces adverse outcome.

Cardiac Iodine-123-Meta-Iodo-Benzylguanidine Uptake in Carotid Sinus Hypersensitivity.

BACKGROUND: Carotid sinus syndrome is the association of carotid sinus hypersensitivity with syncope, unexplained falls and drop attacks in generally older people. We evaluated cardiac sympathetic innervation in this disorder in individuals with carotid sinus syndrome, asymptomatic carotid sinus hypersensitivity and controls without carotid sinus hypersensitivity. METHODS: Consecutive patients diagnosed with carotid sinus syndrome at a specialist falls and syncope unit were recruited. Asymptomatic carotid sinus hypersensitivity and non-carotid sinus hypersensitivity control participants recruited from a community-dwelling cohort. Cardiac sympathetic innervation was determined using Iodine-123-metaiodobenzylguanidine (123-I-MIBG) scanning. Heart to mediastinal uptake ratio (H:M) were determined for early and late uptake on planar scintigraphy at 20 minutes and 3 hours following intravenous injection of 123-I-MIBG. RESULTS: Forty-two subjects: carotid sinus syndrome (n = 21), asymptomatic carotid sinus hypersensitivity (n = 12) and no carotid sinus hypersensitivity (n = 9) were included. Compared to the non- carotid sinus hypersensitivity control group, the carotid sinus syndrome group had significantly higher early H:M (estimated mean difference, B = 0.40; 95% confidence interval, CI = 0.13 to 0.67, p = 0.005) and late H:M (B = 0.32; 95%CI = 0.03 to 0.62, p = 0.032). There was, however, no significant difference in early H:M (p = 0.326) or late H:M (p = 0.351) between the asymptomatic carotid sinus hypersensitivity group and non- carotid sinus hypersensitivity controls. CONCLUSIONS: Cardiac sympathetic neuronal activity is increased relative to age-matched controls in individuals with carotid sinus syndrome but not those with asymptomatic carotid sinus hypersensitivity. Blood pressure and heart rate measurements alone may therefore represent an over simplification in the assessment for carotid sinus syndrome and the relative increase in cardiac sympathetic innervation provides additional clues to understanding the mechanisms behind the symptomatic presentation of carotid sinus hypersensitivity.

Symptomatic presentation of carotid sinus hypersensitivity is associated with impaired cerebral autoregulation.

BACKGROUND: Carotid sinus hypersensitivity (CSH) is associated with syncope, unexplained falls, and drop attacks in older people but occurs asymptomatically in 35% of community-dwelling elders. We hypothesized that impaired cerebral autoregulation is associated with the conversion of asymptomatic CSH to symptomatic CSH. We therefore conducted a case-control study evaluating individuals with CSH with and without the symptoms of syncope or unexplained falls, as well as non-CSH controls, to determine whether the blood pressure and heart rate changes associated with CSH are associated with symptoms only when cerebral autoregulation is altered. METHODS AND RESULTS: Bilateral middle cerebral artery blood flow velocities (BFV) were measured in consecutive patients with symptomatic CSH (n=22) and asymptomatic controls with (n=18) and without CSH (n=14) using transcranial Doppler ultrasonography during lower body negative pressure-induced systemic hypotension. Within-group comparisons revealed significantly lower cerebrovascular resistance index (CVRi) at nadir for the asymptomatic CSH group (right, mean [95% CI]: 2.2 [1.8, 2.8] versus 2.6 [2.2, 3.0]; P=0.005; left: 2.8 [2.4, 3.3] versus 3.1 [2.7, 3.8]; P=0.016). Between-group comparisons showed higher mean BFV (right: estimated mean difference, B=5.49 [1.98, 8.80], P=0.003; left: 4.82 [1.52, 8.11], P=0.005) and lower CVRi (right: B=0.08 [0.03, 0.12], P=0.003, left: B=0.07 [0.02, 0.12], P=0.006) in asymptomatic CSH versus symptomatic CSH groups. There were no significant differences in bilateral mean BFV or right CVRi between the non-CSH and symptomatic CSH groups but differences were present for left CVRi (B=0.07 [0.02, 0.013], P=0.015). CONCLUSION: Cerebral autoregulation is altered in symptomatic CSH and therefore appears to be associated with the development of hypotension-related symptoms in individuals with CSH.

Carotid sinus hypersensitivity: disease state or clinical sign of ageing? Insights from a controlled study of autonomic function in symptomatic and asymptomatic subjects.

AIMS: This study sought to improve the currently limited understanding of the pathophysiology of carotid sinus hypersensitivity (CSH) by comparing autonomic function measured by heart rate variability (HRV) and baroreflex sensitivity inpatients with symptomatic CSH and asymptomatic individuals with and without CSH. METHODS AND RESULTS: Twenty-two patients with symptomatic CSH, 18 individuals with asymptomatic CSH, and 14 asymptomatic older individuals without CSH were recruited to our study. Non-invasive measurements of heart rate and blood pressure were obtained during 10 min of supine rest. Low frequency (LF), high frequency (HF), and total power spectral density (PSD) for HRV were determined using the autoregressive method. The baroreflex slope (BRS) and baroreflex effectiveness index (BEI) were determined using the sequence method for baroreflex sensitivity. There were significant increases in the LF-HRV (P = 0.014), total PSD (P = 0.031), LF:HF (P = 0.047), normalized (nu) LF-HRV (0.049), down ramp BEI (P = 0.017), and total BEI (P = 0.038) in the symptomatic CSH group compared with non-CSH controls. The asymptomatic CSH group had significantly higher LF-HRV (P = 0.001), total PSD (P = 0.002), nuLF-HRV (P = 0.026), and LF:HF (P = 0.030), as well as up, down, and total BRS (P = 0.012, P = 0.015, and P = 0.011, respectively) and BEI (P = 0.049, P = 0.001, and P = 0.006, respectively) than non-CSH control participants. CONCLUSION: This study has demonstrated an association between CSH with increased resting sympathetic activity and baroreflex sensitivity regardless of the presence of symptoms, indicating the presence of autonomic dysregulation in individuals with CSH. Our findings therefore suggest that CSH is part of a generalized autonomic disorder but do not differentiate between asymptomatic and symptomatic individuals.

A study of orthostatic hypotension in late-life depression.

OBJECTIVE: Studies examining vascular risk factors in depression report conflicting evidence but have not assessed orthostatic hypotension, a recently recognized risk factor for white matter hyperintensities. METHOD: The authors used noninvasive phasic orthostatic blood pressure monitoring to assess orthostatic hypotension in 17 subjects with late-life major depression and 17 comparison subjects. All received a neuropsychiatric assessment and standardized cardiovascular assessment. RESULTS: The authors found a higher proportion of subjects met standard criteria for orthostatic hypotension in the depressed group (94% versus 65%, X = 4.5, df = 1, p = 0.034), and the degree of systolic blood pressure drop on standing was highly significantly greater in this group (t = 4.02, df = 32, p <0.001; mean drop of 46 mm Hg). Depressed subjects also experienced more clinical symptoms consistent with orthostatic hypotension. CONCLUSIONS: Our findings suggest orthostatic hypotension may be an important factor in explaining the absence of an excess of clinically determined vascular risk factors in late-life depression.

Carotid sinus hypersensitivity in asymptomatic older persons: implications for diagnosis of syncope and falls.

BACKGROUND: Carotid sinus hypersensitivity is the most commonly reported cause of falls and syncope in older persons. Recent guidelines recommend 5 to 10 seconds of carotid sinus massage in supine and upright positions with beat-to-beat monitoring. The aim of this study was to determine the prevalence of carotid sinus hypersensitivity in (1) an unselected community sample of older people and (2) a subsample with no history of syncope, dizziness, or falls using recently standardized diagnostic criteria. METHODS: One thousand individuals older than 65 years were randomly sampled from a single general practice register; 272 participants underwent supine and upright carotid sinus massage with continuous heart rate and phasic blood pressure monitoring. Carotid sinus hypersensitivity was defined as asystole of 3 seconds or greater and/or a drop in systolic blood pressure of 50 mm Hg or greater. RESULTS: Carotid sinus hypersensitivity was present in 107 individuals (39%); 24% had asystole of 3 seconds or greater during carotid sinus massage; and 16% had symptoms (including syncope) with carotid sinus hypersensitivity. Age (odds ratio, 1.05; 95% confidence interval, 1.00-1.09) and male sex (odds ratio, 1.71; 95% confidence intervals, 1.04-2.82) were the only predictors of carotid sinus hypersensitivity. In 80 previously asymptomatic individuals, carotid sinus hypersensitivity was present in 28 (35%) and accompanied by symptoms in 10. The 95th percentile for carotid sinus massage response was 7.3 seconds' asystole and a 77-mm Hg drop in systolic blood pressure. CONCLUSIONS: Carotid sinus hypersensitivity is common in older persons, even those with no history of syncope, dizziness, or falls. The finding of a hypersensitive response should not necessarily preclude further investigation for other causes of syncope.