Margaret Gagnon

Dynamic Regulation of Middle Cerebral Artery Blood Flow Velocity in Aging and Hypertension

BACKGROUND AND PURPOSE Although aging and hypertension may predispose hypertensive elderly subjects to cerebral hypoperfusion during orthostatic stress, their effects on the acute cerebral autoregulatory response to hypotension are not known. METHODS Continuous middle cerebral artery blood flow velocity (BFV) (transcranial Doppler ultrasound) and mean arterial pressure (MAP, Finapres) were measured in response to (1) acute hypotension during standing, (2) steady-state sitting and standing, and (3) hypercarbia during CO(2) rebreathing in 10 healthy young subjects (age 24+/-1 years), 10 healthy elderly subjects (age 72+/-3 years), and 10 previously treated hypertensive elderly (age 72+/-2 years) subjects. CO(2) reactivity was computed as the slope of cerebrovascular conductance (CVC=BFV/MAP) versus end-expiratory CO(2). Coherence, transfer magnitudes, and phases between low-frequency MAP and BFV signals were computed from their autospectra during 5 minutes of sitting and standing. RESULTS MAP fell to a similar extent in all groups by an average of 21 to 26 mm Hg (22% to 26%) within 30 seconds of standing. Mean BFV also fell in all subjects but significantly less in the older subjects (-4.7+/-0. 7 cm/s in hypertensives and -5.3+/-1.2 cm/s in normotensives, P=NS) compared with younger subjects (-10.1+/-1.1 cm/s, P<0.05). CO(2) reactivity was greater in the young subjects (0.19+/-0.01) compared with normotensive (0.14+/-0.01, P<0.05) and hypertensive elderly subjects (0.11+/-0.02, P<0.05) (P=NS between elderly groups). Fewer hypertensive subjects had coherence between MAP and BFV signals; for subjects with coherence, there were no significant group differences in phase or transfer magnitudes in either sitting or standing positions. CONCLUSIONS Despite reduced CO(2) reactivity, elderly normotensive and previously treated hypertensive subjects retain cerebral autoregulatory capacity in response to acute orthostatic hypotension.

Effects of Age and Gender on Autonomic Control of Blood Pressure Dynamics

Both age and gender influence cardiovascular autonomic control, which in turn may influence the ability to withstand adverse cardiac events and respond to orthostatic stress. The purpose of this study was (1) to quantify age- and gender- related alterations in autonomic control of blood pressure (BP) and (2) to examine the impact of these autonomic alterations on BP response to orthostatic stress. We measured continuous BP and R-R intervals and vasoactive peptide levels in the supine and 60 degrees head-up tilt positions during paced respiration (0.25 Hz) in 89 carefully screened healthy subjects (41 men, 48 women, aged 20 to 83 years). Data were analyzed by gender (age adjusted) and by age group (gender adjusted). During tilt, women had greater decreases in systolic BP than men (-10.2+/-2 versus -1.2+/-3 mm Hg; P=0.02) and smaller increases in low-frequency (sympathetically mediated) BP power (P=0.02). Upright plasma norepinephrine was lower in women (P=0.02). Women had greater supine high-frequency R-R interval power than men (P=0.0001). In elderly subjects, the tilt-induced increase in low-frequency BP power was also diminished (P=0.01), despite higher supine (P=0.02) and similar upright norepinephrine levels compared with younger subjects. Thus, healthy women have less sympathetic influence on BP and greater parasympathetic influence on R-R interval than men. Elderly subjects also have reduced sympathetic influence on BP, but this appears to be more consistent with a reduction in vasomotor sympathetic responsiveness.

The MOBILIZE Boston Study: Design and methods of a prospective cohort study of novel risk factors for falls in an older population

BackgroundFalls are the sixth leading cause of death in elderly people in the U.S. Despite progress in understanding risk factors for falls, many suspected risk factors have not been adequately studied. Putative risk factors for falls such as pain, reductions in cerebral blood flow, somatosensory deficits, and foot disorders are poorly understood, in part because they pose measurement challenges, particularly for large observational studies.MethodsThe MOBILIZE Boston Study (MBS), an NIA-funded Program Project, is a prospective cohort study of a unique set of risk factors for falls in seniors in the Boston area. Using a door-to-door population-based recruitment, we have enrolled 765 persons aged 70 and older. The baseline assessment was conducted in 2 segments: a 3-hour home interview followed within 4 weeks by a 3-hour clinic examination. Measures included pain, cerebral hemodynamics, and foot disorders as well as established fall risk factors. For the falls follow-up, participants return fall calendar postcards to the research center at the end of each month. Reports of falls are followed-up with a telephone interview to assess circumstances and consequences of each fall. A second assessment is performed 18 months following baseline.ResultsOf the 2382 who met all eligibility criteria at the door, 1616 (67.8%) agreed to participate and were referred to the research center for further screening. The primary reason for ineligibility was inability to communicate in English. Results from the first 600 participants showed that participants are largely representative of seniors in the Boston area in terms of age, sex, race and Hispanic ethnicity. The average age of study participants was 77.9 years (s.d. 5.5) and nearly two-thirds were women. The study cohort was 78% white and 17% black. Many participants (39%) reported having fallen at least once in the year before baseline.ConclusionOur results demonstrate the feasibility of conducting comprehensive assessments, including rigorous physiologic measurements, in a diverse population of older adults to study non-traditional risk factors for falls and disability. The MBS will provide an important new data resource for examining novel risk factors for falls and mobility problems in the older population.

Factors associated with hallux valgus in a population-based study of older women and men: the MOBILIZE Boston Study.

OBJECTIVE To examine potential risk factors for hallux valgus in community-dwelling elders. METHOD Data from 600 MOBILIZE Boston Study participants (386 women and 214 men) were analyzed. Hallux valgus was defined as >15 degrees angular deviation of the hallux with respect to the first metatarsal bone toward the lesser toes. Associations of hallux valgus with age, body mass index (BMI), race, education, pes planus, foot pain, and in women, history of high heel shoe use, were assessed using sex-specific Poisson regression with robust variance estimation for risk ratios (RR) and 95% confidence intervals (CI). RESULTS Hallux valgus was present in 58% of women and 25% of men. Higher BMI was inversely associated with presence of hallux valgus in women (P trend=0.001), with the strongest inverse association observed in those with BMI of 30.0 or more compared to those with normal BMI (RR=0.7, 95% CI: 0.5, 0.9). Women, who usually wore high-heeled shoes during ages 20-64 years compared to those who did not, had increased likelihood of hallux valgus (RR=1.2, 95% CI: 1.0, 1.5). Among men, those with BMI between 25.0 and 29.9 had increased likelihood of hallux valgus compared to those with normal BMI (RR=1.9, 95% CI: 1.0, 3.5). Men with pes planus were more likely to have hallux valgus (RR=2.1, 95% CI: 1.3, 3.3) compared to men without pes planus. CONCLUSION In women, hallux valgus was associated with lower BMI and high heel use during ages 20-64, while in men, associations were observed with higher BMI and pes planus. Our results suggest that the etiologic mechanisms for hallux valgus may differ between men and women.

Muscle Strength and Fall Rates Among Residents of Japanese and American Nursing Homes: An International Cross-Cultural Study

OBJECTIVE: In Western society, aging is often associated with adoption of a sedentary lifestyle and associated disuse muscle atrophy and weakness. Recent studies suggest a relationship between quadriceps muscle weakness and falls in elderly residents of US nursing homes (NHs). We hypothesized that fall rates would be lower in Japanese NHs, where lifestyle differences such as squatting to toilet or sleeping on the floor may maintain quadriceps strength and result in fewer falls. Therefore, we examined the relationships between falls, muscle strength, lifestyle, and other clinical characteristics in residents of a Japanese and an American NH.

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.

Estrogen Replacement Therapy Improves Baroreflex Regulation of Vascular Sympathetic Outflow in Postmenopausal Women

Background—Menopausal estrogen loss has been associated with increased cardiovascular disease in postmenopausal women. However, the link between estrogen and cardiovascular disease remains unclear. Some data suggest estrogen mediates its effect through changes in arterial pressure and its regulation. However, the data available in older women are equivocal regarding estrogen’s ability to reduce resting arterial pressure or to improve its regulation. Methods and Results—We studied 11 healthy, postmenopausal women before and after 6 months of estrogen administration. Arterial pressure was measured by brachial auscultation and finger photoplethysmography. Vascular sympathetic nerve activity was measured in the peroneal nerve by microneurography, and the slope of the relations between changes in heart period, sympathetic activity, and arterial pressure caused by bolus infusions of nitroprusside and phenylephrine were used as an index of baroreflex gain. Estrogen therapy did not change systolic pressure (128±2 versus 123±2 mm Hg) or cardiac-vagal baroreflex gain (6.6±0.9 versus 6.7±0.7 ms/mm Hg). However, vascular sympathetic baroreflex gain was increased (−4.6±0.6 versus −7.4±1.0 arbitrary integrated units/mm Hg;P =0.02). Conclusion—These findings suggest long-term estrogen replacement therapy has effects on cardiovascular regulation that may not be reflected in resting arterial pressures.

Issues in Conducting Epidemiologic Research Among Elders: Lessons From The MOBILIZE Boston Study

Conducting research in elderly populations is important, but challenging. In this paper, the authors describe specific challenges that have arisen and solutions that have been used in carrying out The MOBILIZE Boston Study, a community-based, prospective cohort study in Massachusetts focusing on falls among 765 participants aged 70 years or older enrolled during 2005-2007. To recruit older individuals, face-to-face interactions are more effective than less personal approaches. Use of a board of community leaders facilitated community acceptance of the research. Establishing eligibility for potential participants required several interactions, so resources must be anticipated in advance. Assuring a safe and warm environment for elderly participants and offering a positive experience are a vital priority. Adequate funding, planning, and monitoring are required to provide transportation and a fully accessible environment in which to conduct study procedures as well as to select personnel highly skilled in interacting with elders. It is hoped that this paper will encourage and inform future epidemiologic research in this important segment of the population.

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.

Effects of postprandial walking exercise on meal-related hypotension in frail elderly patients.

The purpose of this study was to assess the hemodynamic effects of a postmeal walk in frail elderly patients with postprandial hypotension. We demonstrated that frail elderly patients with postprandial hypotension are able to increase their blood pressure and heart rate in response to a postmeal walking exercise, but this effect is limited to the exercise period only and is not sustained during subsequent rest.