Tischa J. M. van der Cammen

Arterial Stiffness and Risk of Coronary Heart Disease and Stroke The Rotterdam Study

Background— Arterial stiffness has been associated with the risk of cardiovascular disease in selected groups of patients. We evaluated whether arterial stiffness is a predictor of coronary heart disease and stroke in a population-based study among apparently healthy subjects. Methods and Results— The present study included 2835 subjects participating in the third examination phase of the Rotterdam Study. Arterial stiffness was measured as aortic pulse wave velocity and carotid distensibility. Cox proportional hazards regression analysis was performed to compute hazard ratios. During follow-up, 101 subjects developed coronary heart disease (mean follow-up period, 4.1 years), and 63 subjects developed a stroke (mean follow-up period, 3.2 years). The risk of cardiovascular disease increased with increasing aortic pulse wave velocity index. Hazard ratios and corresponding 95% CIs of coronary heart disease for subjects in the second and third tertiles of the aortic pulse wave velocity index compared with subjects in the reference category were 1.72 (0.91 to 3.24) and 2.45 (1.29 to 4.66), respectively, after adjustment for age, gender, mean arterial pressure, and heart rate. Corresponding estimates for stroke were 1.22 (0.55 to 2.70) and 2.28 (1.05 to 4.96). Estimates decreased only slightly after adjustment for cardiovascular risk factors, carotid intima-media thickness, the ankle-arm index, and pulse pressure. The aortic pulse wave velocity index provided additional predictive value above cardiovascular risk factors, measures of atherosclerosis, and pulse pressure. Carotid distensibility as measured in this study was not independently associated with cardiovascular disease. Conclusions— Aortic pulse wave velocity is an independent predictor of coronary heart disease and stroke in apparently healthy subjects.

Searching for an Operational Definition of Frailty: A Delphi Method Based Consensus Statement. The Frailty Operative Definition-Consensus Conference Project

BACKGROUND There is no consensus regarding the definition of frailty for clinical uses. METHODS A modified Delphi process was used to attempt to achieve consensus definition. Experts were selected from different fields and organized into five Focus Groups. A questionnaire was developed and sent to experts in the area of frailty. Responses and comments were analyzed using a pre-established strategy. Statements with an agreement more than or equal to 80% were accepted. RESULTS Overall, 44% of the statements regarding the concept of frailty and 18% of the statements regarding diagnostic criteria were accepted. There was consensus on the value of screening for frailty and about the identification of six domains of frailty for inclusion in a clinical definition, but no agreement was reached concerning a specific set of clinical/laboratory biomarkers useful for diagnosis. CONCLUSIONS There is agreement on the usefulness of defining frailty in clinical settings as well as on its main dimensions. However, additional research is needed before an operative definition of frailty can be established.

Societal consequences of falls in the older population: injuries, healthcare costs, and long-term reduced quality of life.

BACKGROUND Fall incidents are a major cause of morbidity and mortality in older adults. The aim of this cohort study was to determine the incidence, costs, and quality of life for fall-related injuries in the older Dutch population presenting at the emergency department. METHODS Data on fall-related injuries in persons aged 65 years or older were retrieved from the Dutch Injury Surveillance System, which records injuries treated at the emergency department, and a patient follow-up survey conducted between 2003 and 2007. Injury incidence, discharge rates, healthcare costs, and quality of life measures were calculated. RESULTS Fall-related injuries were to the upper or lower limb in 70% of cases and consisted mainly of fractures (60%), superficial injuries (21%), and open wounds (8%). Falls led to a total healthcare cost of €474.4 million, which represents 21% of total healthcare expenses due to injuries. Both admitted and nonadmitted patients reported a reduced quality of life up to 9 months after the injury. CONCLUSIONS Fall-related injuries in older adults are age and gender related, leading to high healthcare consumption, costs, and long-term reduced quality of life. Further implementation of falls prevention strategies is needed to control the burden of fall-related injuries in the aging population.

Selective Serotonin Reuptake Inhibiting Antidepressants Are Associated With an Increased Risk of Nonvertebral Fractures

Background: Fractures related to osteoporosis and falling constitute a major health problem in the elderly population. Exposure to antidepressants is associated with an increased risk of falls and fractures, but most previous studies incriminate tricyclic antidepressants (TCAs) rather than selective serotonin reuptake inhibitors (SSRIs). Objective: To examine the association between antidepressants, including TCAs, SSRIs, and other antidepressants and the risk of nonvertebral fractures in elderly. Design: Prospective population-based cohort study. Setting: The Rotterdam Study, consisting of 7983 individuals aged 55 years and older. Participants: All persons from the Rotterdam Study. Results: One thousand two hundred nineteen persons experienced a nonvertebral fracture, 25 during TCA use and 18 during SSRI use. After adjustment for age, sex, lower-limb disability, and depression, the risk of nonvertebral fracture was 2.35 (95% confidence interval, 1.32-4.18) for current users of SSRIs compared with nonusers of antidepressants. Multiple adjusting for many possible risk factors did not affect the association. To deal with potential confounding by indication, we subsequently restricted the analysis to antidepressant users (n = 1217). Compared with past users of TCAs or SSRIs, current users of SSRIs had a 2.07-fold (95% confidence interval, 1.23-3.50) increased risk of fracture, which further increased with prolonged use. In this analysis, depressive state at baseline and during follow-up did not play a role, suggesting absence of confounding by indication. The use of TCAs was associated with an increased fracture risk that decreased with prolonged use. Conclusions: Not only users of TCAs but also of SSRIs have a significantly increased risk of nonvertebral fractures, in SSRI users especially after prolonged use. Despite fewer early adverse effects of SSRIs, physicians treating elderly depressive patients should be aware of the unfavorable long-term consequence of SSRIs on fracture risk.

Arterial stiffness, cardiovagal baroreflex sensitivity and postural blood pressure changes in older adults: the Rotterdam Study

Objective Arterial stiffness may be involved in the impairment of the arterial baroreflex. In the present study the associations between arterial stiffness and cardiovagal baroreflex sensitivity (BRS) and between BRS and postural blood pressure (BP) changes were investigated within the framework of the Rotterdam Study. Methods Arterial stiffness was determined by aortic pulse wave velocity and the carotid distensibility coefficient. Continuous recording of the R–R interval and finger BP was performed with the subject resting supine, and BRS was estimated from the spontaneous changes in systolic BP and corresponding interbeat intervals. Measures of aortic stiffness or carotid distensibility and BRS were available in 2490 and 2083 subjects, respectively. The association between arterial stiffness and ln BRS was investigated by multivariate linear regression analysis and then by analysis of covariance, comparing BRS by quartiles of arterial stiffness. Results The mean age of the subjects was 71.7 ± 6.6 (41.7% men). Aortic stiffness was negatively associated [β = −0.029; 95% confidence interval (CI): −0.040, −0.019] and the carotid distensibility coefficient positively associated with BRS (β = 0.017; 95% CI: 0.010, 0.024). An orthostatic decrease in systolic BP was absent in 1609 subjects, between 1 and 10 mmHg in 502 and >10 mmHg in 269 subjects, with corresponding mean values (95% CI) of ln BRS of 1.47 (1.44–1.51), 1.43 (1.37–1.49) and 1.36 (1.28–1.44) ms/mmHg (test for trend P < 0.019). An orthostatic decrease in diastolic BP was absent in 1123 subjects, 1–10 mmHg in 1057 and >10 mmHg in 209 subjects, with corresponding mean values of ln BRS of 1.49 (1.45–1.53), 1.41 (1.37–1.45) and 1.45 (1.36–1.54) ms/mmHg (P < 0.04). Conclusion In a large population of older subjects, arterial stiffness appears to be an independent determinant of impaired BRS. Within the same population, impaired BRS was associated with orthostatic BP changes.

Trends in Fall-Related Hospital Admissions in Older Persons in the Netherlands

BACKGROUND Fall-related injuries, hospitalizations, and mortality among older persons represent a major public health problem. Owing to aging societies worldwide, a major impact on fall-related health care demand can be expected. We determined time trends in numbers and incidence of fall-related hospital admissions and in admission duration in older adults. METHODS Secular trend analysis of fall-related hospital admissions in the older Dutch population from 1981 through 2008, using the National Hospital Discharge Registry. All fall-related hospital admissions in persons 65 years or older were extracted from this database. Outcome measures were the numbers, and the age-specific and age-adjusted incidence rates (per 10,000 persons) of fall-related hospital admissions in each year of the study. RESULTS From 1981 through 2008, fall-related hospital admissions increased by 137%. The annual age-adjusted incidence growth was 1.3% for men vs 0.7% for women (P < .001). The overall incidence rate increased from 87.7 to 141.2 per 10,000 persons (an increase of 61%). Age-specific incidence increased in all age groups, in both men and women, especially in the oldest old (>75 years). Although the incidence of fall-related hospital admissions increased, the total number of fall-related hospital days was reduced by 20% owing to a reduction in admission duration. CONCLUSIONS In the Netherlands, numbers of fall-related hospital admissions among older persons increased drastically from 1981 through 2008. The increasing fall-related health care demand has been compensated for by a reduced admission duration. These figures demonstrate the need for implementation of falls prevention programs to control for increases of fall-related health care consumption.

Arterial stiffness as the candidate underlying mechanism for postural blood pressure changes and orthostatic hypotension in older adults: the Rotterdam Study.

Objective To investigate whether arterial stiffening, one of the characteristics of the aging vascular system, is associated with orthostatic hypotension. Design Cross-sectional data of a cohort study in elderly men and women. Participants We investigated the relationship between arterial stiffness and orthostatic hypotension within the framework of the Rotterdam Study, a population-based study in individuals aged 55 and older. The present study included 3362 subjects participating in the third examination phase. The carotid—femoral pulse wave velocity was used as measure of arterial stiffness. Orthostatic hypotension was assessed with blood pressure measurements in supine and standing position. Results Odds ratios for orthostatic hypotension increased through quartiles of pulse wave velocity; the age, gender and mean arterial pressure adjusted odds ratio in the last quartile of pulse wave velocity was 1.45 (95% confidence interval, 1.09–1.93) when compared with the first quartile (reference). In fully adjusted models estimates remained statistically significant. In subjects with higher stiffness we observed a higher drop in blood pressure but no significant change of heart rate. Conclusions Arterial stiffness is independently associated with orthostatic hypotension. The drop in blood pressure levels and the contemporary attenuated response of heart rate to orthostatic challenge in subjects with stiffer arteries support the hypothesis that arterial stiffness may explain, at least in part, the reduced baroreflex observed in older adults.

The influence of drug use on fall incidents among nursing home residents: a systematic review

BACKGROUND Falls are a major health problem among the elderly, particularly in nursing homes. Abnormalities of balance and gait, psychoactive drug use, and dementia have been shown to contribute to fall risk. METHODS We conducted a systematic review of the literature to investigate which psychoactive drugs increase fall risk and what is known about the influence of these drugs on gait in nursing home residents with dementia. We included studies with a prospective cohort design on psychoactive drug use in nursing homes with dementia residents and with falls as an outcome measure. RESULTS Seventeen studies were included in the review. Pooled risk estimates were not calculated because there was no homogeneity across studies. We assessed the strength of evidence for psychoactive drugs as a prognostic factor for falls by defining four levels of evidence: strong, moderate, limited or inconclusive. Strong evidence was defined as consistent findings (> or =80%) in at least two high quality cohorts. We found strong evidence that the use of multiple drugs (3/3 cohorts, effect sizes 1.30-1 xs 0.30), antidepressants (10/12 cohorts, effect sizes 1.10-7.60), and anti-anxiety drugs (2/2 cohorts, effect sizes 1.22-1.32) is associated with increased fall risk. The evidence for the association of other psychoactive drug classes with fall risk was limited or inconclusive. CONCLUSIONS Research on the contribution of psychoactive drugs to fall risk in nursing home residents with dementia is limited. The scarce evidence shows, however, that multiple drugs, antidepressants and anti-anxiety drugs increase fall risk in nursing home populations with residents with dementia.

Increase in Fall-Related Hospitalizations in the United States, 2001-2008

BACKGROUND The objective was to determine secular trends in unintentional fall-related hospitalizations in people aged 65 years and older in the United States. MATERIALS Data were obtained from a nationally representative sample of emergency department visits from January 1, 2001, to December 31, 2008, available through the National Electronic Injury Surveillance System-All Injury Program. These data were weighted to estimate the number, incidence rates, and the annual percent change of fall-related hospitalizations. RESULTS From 2001 to 2008, the estimated number of fall-related hospitalizations in older adults increased 50%, from 373,128 to 559,355 cases. During the same time period, the age-adjusted incidence rate, expressed per 100,000 population, increased from 1,046 to 1,368. Rates were higher in women compared with men throughout the study period. The age-adjusted incidence rate showed an average annual increase of 3.3% (95% CI, 1.66-4.95). DISCUSSION Both the number and rate of fall-related hospitalizations in the United States increased significantly over the 8-year study period. Unless preventive action is taken, rising hospitalization rates in combination with the aging US population over the next decades will exacerbate the already stressed healthcare system and may result in poorer health outcomes for older adults in the future. Further research is needed to determine the underlying causes for this rising trend.

New Insights: Dose‐Response Relationship Between Psychotropic Drugs and Falls: A Study in Nursing Home Residents With Dementia

The contribution of specific psychotropic drugs to fall risk in patients with dementia has not been quantified precisely until now. The authors evaluated the dose‐response relationship between psychotropic drugs and falls in nursing home residents with dementia. Daily drug use and daily falls were recorded in 248 nursing home residents with dementia from January 1, 2006, to January 1, 2008. For each day of the study period, data on drug use were abstracted from the prescription database, and falls were retrieved from a standardized incident report system, resulting in a data set of 85 074 person‐days. The authors found significant dose‐response relationships for the use of antipsychotics (hazard ratio [HR], 2.78; 95% confidence interval [CI], 1.49–5.17), anxiolytics (1.60; 1.20–2.14), hypnotics and sedatives (2.58; 1.42–4.68), and antidepressants (2.84; 1.93–4.16). Fall risk increased significantly with 28% at 0.25 of the defined daily dose (DDD) of an antipsychotic or antidepressant, with 8% at 0.2 of the DDD of an anxiolytic, and with 56% at 0.5 of the DDD of a hypnotic or sedative; it increased further with dose increments and with combinations of psychotropics. Even at low dosages, psychotropic drugs are associated with increased fall risk in nursing home residents with dementia.