Ikechukwu Iloputaife

Antihypertensive Therapy Increases Cerebral Blood Flow and Carotid Distensibility in Hypertensive Elderly Subjects

Many physicians are reluctant to lower blood pressure to recommended levels in elderly hypertensive patients because of concern about producing cerebral hypoperfusion. Because hypertension is associated with potentially reversible structural and functional alterations in the cerebral circulation that may improve with treatment, we investigated whether long-term pharmacological reduction of systolic blood pressure will improve, rather than worsen, cerebral blood flow and its regulation. Three groups of elderly subjects 65 years of age or older were studied prospectively: normotensive subjects (N=19), treated hypertensive subjects with systolic pressure <140 mm Hg (N=18), and uncontrolled hypertensive subjects with systolic pressure >160 mm Hg at entry into the study (N=14). We measured beat-to-beat blood flow velocity in the middle cerebral artery (transcranial Doppler ultrasonography), finger arterial pressure (photoplethysmography), and pulsatile distensibility of the carotid artery (duplex Doppler ultrasonography) at baseline and after 6 months of observation or antihypertensive therapy. After baseline hemodynamic measurements, uncontrolled hypertensive subjects underwent aggressive treatment with lisinopril with or without hydroclorothiazide or, if not tolerated, nifedipine or an angiotensin receptor blocker to bring their systolic pressure <140 mm Hg for 6 months. The other 2 groups were observed for 6 months. After 6 months of successful treatment, uncontrolled hypertensive subjects had significant increases in cerebral blood flow velocity and carotid distensibility that was not seen in the other groups. Treatment reduced cerebrovascular resistance and did not impair cerebral autoregulation. Therefore, judicious long-term treatment of systolic hypertension in otherwise healthy elderly subjects does not cause cerebral hypoperfusion.

Cerebrovascular hemodynamics, gait, and falls in an elderly population: MOBILIZE Boston Study.

Objective: To determine whether alterations in cerebral blood flow regulation are associated with slow gait speed and falls in community-dwelling elderly individuals. Methods: The study sample consisted of 419 individuals from the MOBILIZE Boston Study (MBS) who had transcranial Doppler ultrasound measures of cerebral blood flow velocity. The MBS is a prospective cohort study of a unique set of risk factors for falls in seniors in the Boston area. We measured beat-to-beat blood flow velocity in the middle cerebral artery in response to 1) changes in end-tidal CO2 (cerebral vasoreactivity) and 2) blood pressure changes during a sit-to-stand protocol (cerebral autoregulation). Gait speed was measured during a 4-meter walk. Falls were tracked by monthly calendars, and demographic and clinical characteristics were assessed at baseline. Results: A multivariate linear regression analysis showed that cerebral vasoreactivity was cross-sectionally related to gait speed (p = 0.039). Individuals in the lowest quintile of vasoreactivity had lower gait speeds as compared to those in the highest quintile (p = 0.047). In a negative binomial regression analysis adjusted for relevant covariates, the relationship between cerebral vasoreactivity and fall rate did not reach significance. However, when comparing individuals in the lowest to highest quintile of cerebral vasoreactivity, those in the lowest quintile had a higher fall rate (p = 0.029). Conclusions: Impaired cerebral blood flow regulation, as measured by cerebral vasoreactivity to CO2, is associated with slow gait speed and may lead to the development of falls in elderly people.

Reexamining the Effect of Antihypertensive Medications On Falls in Old Age

Conflicting data on the relationship between antihypertensive medications and falls in elderly people may lead to inappropriate undertreatment of hypertension in an effort to prevent falls. We aimed to clarify the relationships between the chronic use of different classes of antihypertensive medications and different types of falls, to determine the effect of medication dose, and to assess whether the risk of falls is associated with differences in cerebral blood flow. We assessed demographics, clinical characteristics, and chronic antihypertensive medication use in 598 community-dwelling people with hypertension, aged 70 to 97 years, then followed them prospectively for self-reported falls using monthly calendar postcards and telephone interviews. Antihypertensive medication use was not associated with an increased risk of falls. Participants reporting use of angiotensin-converting enzyme inhibitors had a significantly decreased 1-year risk of injurious falls (odds ratio, 0.62; 95% confidence interval, 0.39–0.96), whereas those using calcium channel blockers had a decreased risk of all falls (odds ratio, 0.62; 95% confidence interval, 0.42–0.91) and indoor falls (odds ratio, 0.57; 95% confidence interval, 0.36–0.91), compared with participants not taking these drugs. Larger doses of these classes were associated with a lower fall risk. Participants taking calcium channel blockers had higher cerebral blood flow than those not taking these medications. In relatively healthy community-dwelling elderly people, high doses of antihypertensive agents are not associated with an increased risk of falls.

Enhanced Vasoreactivity and Its Response to Antihypertensive Therapy in Hypertensive Elderly Women

Several previous studies have demonstrated sex differences in cardiovascular autonomic control in healthy young women, but little is known about the regulation of blood pressure in hypertensive elderly women, who have the greatest risk of adverse cardiovascular events. Therefore, we examined sex differences in physiological responses to upright tilt in 21 healthy (13 men and 8 women), 22 controlled hypertensive (10 men and 12 women), and 18 uncontrolled hypertensive (9 men and 9 women) elderly men and women. Of these, 19 normotensives, 18 controlled hypertensives, and 14 uncontrolled hypertensives completed 6 months of observation or pharmacological therapy for uncontrolled hypertension. All of the subjects underwent continuous monitoring of cardiac (RR) interval (ECG), finger arterial pressure (photoplethysmography), and stroke volume (transthoracic impedance) and periodic measurements of forearm blood flow (venous occlusion plethysmography) while resting supine and during a graded head-up tilt. Blood pressure and RR-interval power spectra were computed. Baroreflex gain was estimated by the cross-spectral and sequence methods. In contrast to other groups, elderly hypertensive women increased systemic vascular resistance during tilt. This response was associated with greater low-frequency systolic pressure variability, a presumed marker of sympathetic vascular control. After 6 months of successful antihypertensive therapy, women showed attenuation of the systemic vascular resistance response and a reduction in low-frequency systolic blood pressure variability to levels similar to men and normotensive controls. These results highlight the beneficial effects of antihypertensive therapy on the systemic vasculature, particularly for elderly women in whom enhanced vasoreactivity may contribute to excessive cardiovascular morbidity and mortality.

Patterns, Predictors, and Outcomes of Falls Trajectories in Older Adults: The MOBILIZE Boston Study with 5 Years of Follow-Up

Background Falls may occur as unpredictable events or in patterns indicative of potentially modifiable risks and predictive of adverse outcomes. Knowing the patterns, risks, and outcomes of falls trajectories may help clinicians plan appropriate preventive measures. We hypothesized that clinically distinct trajectories of falls progression, baseline predictors and their coincident clinical outcomes could be identified. Methods We studied 765 community-dwelling participants in the MOBILIZE Boston Study, who were aged 70 and older and followed prospectively for falls over 5 years. Baseline demographic and clinical data were collected by questionnaire and a comprehensive clinic examination. Falls, injuries, and hospitalizations were recorded prospectively on daily calendars. Group-Based Trajectory Modeling (GBTM) was used to identify trajectories. Results We identified 4 distinct trajectories: No Falls (30.1%), Cluster Falls (46.1%), Increasing Falls (5.8%) and Chronic Recurring Falls (18.0%). Predictors of Cluster Falls were faster gait speed (OR 1.69 (95CI, 1.50–2.56)) and fall in the past year (OR 3.52 (95CI, 2.16–6.34)). Predictors of Increasing Falls were Diabetes Mellitus (OR 4.3 (95CI, 1.4–13.3)) and Cognitive Impairment (OR 2.82 (95CI, 1.34–5.82)). Predictors of Chronic Recurring Falls were multi-morbidity (OR 2.24 (95CI, 1.60–3.16)) and fall in the past year (OR 3.82 (95CI, 2.34–6.23)). Symptoms of depression were predictive of all falls trajectories. In the Chronic Recurring Falls trajectory group the incidence rate of Hospital visits was 121 (95% CI 63–169) per 1,000 person-years; Injurious falls 172 (95% CI 111–237) per 1,000 person-years and Fractures 41 (95% CI 9–78) per 1,000 person-years. Conclusions Falls may occur in clusters over discrete intervals in time, or as chronically increasing or recurring events that have a relatively greater risk of adverse outcomes. Patients with multiple falls, multimorbidity, and depressive symptoms should be targeted for preventive measures.

Circulating Vascular Cell Adhesion Molecule-1 Is Associated With Cerebral Blood Flow Dysregulation, Mobility Impairment, and Falls in Older Adults

Soluble vascular cell adhesion molecule-1 (sVCAM-1) is associated with hypertension, vascular inflammation, and systemic endothelial dysfunction. We evaluated whether elevated plasma sVCAM-1 is associated with impaired cerebrovascular function and mobility impairments in elderly people. We studied the cross-sectional relationships between plasma sVCAM-1 level, gait speed, and cerebrovascular hemodynamics, and its longitudinal relationship with falls in 680 community-dwelling participants aged ≥65 years in the Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly (MOBILIZE) Boston Study. Falls were recorded prospectively for 1 year on daily calendars. sVCAM-1 was measured by ELISA assay and beat-to-beat blood flow velocity in the middle cerebral artery during rest and in response to changes in end-tidal CO2 was measured by transcranial Doppler ultrasound. sVCAM-1 concentration was 1094±340 ng/mL in normotensives, 1195±438 ng/mL in controlled hypertensives, and 1250±445 ng/mL in uncontrolled hypertensives (P=0.008). The mean resting blood flow velocity and cerebral vasomotor range were, respectively, 41.0±10.3 cm/s and 1.3±0.4 cm/s per millimeter of mercury. Elevated sVCAM-1 levels indicative of endothelial dysfunction were associated with reduced resting blood flow velocity (P=0.017) and cerebral vasomotor range (P=0.0048). Elevated sVCAM-1 levels were associated with slower gait speed (<0.8 m/s; odds ratio, 3.01; 95% confidence interval, 1.56–5.83; P=0.0011) and an increased odds of injurious falls (odds ratio, 2.4; 95% confidence interval, 1.4–4.2; P=0.0028). An elevated sVCAM-1 level may be a marker of cerebral blood flow dysregulation because of endothelial damage from hypertension. It may also signal the presence of cerebral microvascular disease and its clinical consequences, including slow gait speed and falls.

The Complexity of Standing Postural Sway Associates with Future Falls in Community-Dwelling Older Adults: The MOBILIZE Boston Study

Standing postural control is complex, meaning that it is dependent upon numerous inputs interacting across multiple temporal-spatial scales. Diminished physiologic complexity of postural sway has been linked to reduced ability to adapt to stressors. We hypothesized that older adults with lower postural sway complexity would experience more falls in the future. 738 adults aged ≥70 years completed the Short Physical Performance Battery test (SPPB) test and assessments of single and dual-task standing postural control. Postural sway complexity was quantified using multiscale entropy. Falls were subsequently tracked for 48 months. Negative binomial regression demonstrated that older adults with lower postural sway complexity in both single and dual-task conditions had higher future fall rate (incident rate ratio (IRR) = 0.98, p = 0.02, 95% Confidence Limits (CL) = 0.96–0.99). Notably, participants in the lowest quintile of complexity during dual-task standing suffered 48% more falls during the four-year follow-up as compared to those in the highest quintile (IRR = 1.48, p = 0.01, 95% CL = 1.09–1.99). Conversely, traditional postural sway metrics or SPPB performance did not associate with future falls. As compared to traditional metrics, the degree of multi-scale complexity contained within standing postural sway-particularly during dual task conditions- appears to be a better predictor of future falls in older adults.

Executive Network Activation is Linked to Walking Speed in Older Adults: Functional MRI and TCD Ultrasound Evidence From the MOBILIZE Boston Study

Background Changes in cerebral blood flow velocity (CBF) in response to a cognitive task (task-related ΔCBF) have been shown by Transcranial Doppler ultrasonography (TCD) to be reduced in slow walkers. However, it is unknown whether reduced task-related ΔCBF is associated with reduced neural activity in specific brain regions, as measured by blood-oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI). Methods We assessed the regional changes in neural activity associated with reduced middle cerebral artery (MCA) task-related ΔCBF to an executive task and slow walking speed in 67 community-dwelling older adults from the MOBILIZE Boston Study. Participants underwent walking assessments and TCD ultrasonography measures of MCA ΔCBF during the n-back task of executive function. A subset of participants (n = 27) completed the same task during fMRI. Individual BOLD activation maps for the n-back task were correlated with TCD measures and network-level averages were associated with TCD and preferred walking speed. Results Participants with diminished task-related ΔCBF walked more slowly (β = .39, p = .001). fMRI revealed significant associations between task-related ΔCBF and regional BOLD activation in several brain regions/networks supplied by the MCA. Of these regions and networks, those within the executive network were most strongly associated with walking speed (β = .36, p = .01). Conclusions Task-related ΔCBF during an executive function task is related to activation in several neural networks and impairment in the ability to recruit the executive network in particular is associated with slow walking speed in older adults.

Evaluation of an automated falls detection device in nursing home residents

To determine the concordance between falls recorded using an investigational fall detection device and falls reported by nursing staff in a nursing home.

Elevated Soluble Vascular Cell Adhesion Molecule-1 Is Associated With Cerebrovascular Resistance and Cognitive Function.

Background Elevated plasma soluble vascular cell adhesion molecule-1 (sVCAM-1) is a presumed marker of endothelial dysfunction, both in the brain and systemic circulation. Impairments in memory and cognition have been associated with cardiovascular diseases, but little is known about their relationships to abnormal cerebral endothelial function. Methods We studied the cross-sectional association between sVCAM-1 and markers of cerebrovascular hemodynamics and cognitive function in 680 community-dwelling participants in the MOBILIZE Boston Study, aged 65 years and older. Cognitive function was assessed using the Hopkins Verbal Learning Memory Test and Trail Making Tests (TMTs) A and B. Global cognitive impairment was defined as Mini-Mental State Examination (MMSE) score less than 24. sVCAM-1 was measured by ELISA assay. Beat-to-beat blood flow velocity (BFV) and cerebrovascular resistance (CVR = mean arterial pressure / BFV) in the middle cerebral artery were assessed at rest by transcranial Doppler ultrasound. Results sVCAM-1 concentrations were higher among participants with an MMSE score <24 versus ≥24 (1,201±417 vs 1,122±494ng/mL). In regression models adjusted for sociodemographic characteristics and health conditions, increasing levels of sVCAM-1 were linearly associated with higher resting CVR (p = .006) and lower performance on the Hopkins Verbal Learning Memory (immediate recall and delayed recall) and adjusted TMT B tests (p < .05). Higher levels of sVCAM-1 were also associated with global cognitive impairment on the MMSE (odds ratio = 3.9; 95% confidence interval: 1.4-10.9; p = .011). Conclusions In this cohort of elderly participants, we observed a cross-sectional association between elevated sVCAM-1 levels and both cognitive impairment and increased cerebrovascular resistance. Longitudinal studies are needed to determine whether elevated sVCAM-1 is a cause or consequence of cerebrovascular damage.