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Introduction: A common and severe osteoporotic type fracture in older women is a hip fracture. It is not clear whether bone turnover parameters measured in blood can be a useful tool to predict fracture risk in older persons. The aim of the current study was to assess the association between serum vitamin D (25OHD) levels, parathyroid hormone (PTH), total osteocalcin, carboxy-terminal collagen crosslinks (CTX) and hip fractures in older fallers., Material and Methods: A single centre, prospective cohort study of bone parameters was carried out in 400 female patients aged > 70 years including 200 with a hip fracture and 200 without fractures, admitted after a fall between January 2005 and December 2007., Results: Serum total osteocalcin levels were significantly lower in the fracture group compared to the non-fracture group (20.4 ng/ml vs 26.1 ng/ml, respectively, p = 0.01). This finding remained significant after exclusion of the patients on bisphosphonates (p = 0.003). There were no significant differences in 25OHD, PTH or CTX levels between the two groups., Conclusion: In the current study there was an association between the presence of a hip fracture and lower total serum osteocalcin concentrations. This could be indicative of low bone turnover osteoporosis in these women. An association for other bone turnover markers was lacking.

Aim: Although guidelines regarding falls prevention make a clear distinction between single and recurrent fallers, differences in functional status, physical performance, and quality of life in single and recurrent fallers have not been thoroughly investigated. Therefore, we investigated the differences in functional status, physical performance and health-related quality of life (HRQoL) between single and recurrent fallers., Methods: From October 2008 to October 2011, 616 community-dwelling older adults who visited the emergency department as a result of a fall were enrolled. Physical performance was assessed with the Timed Up & Go (TUG) test, the Five Times Sit to Stand (FTSS) test, handgrip strength and the tandem stand test. Functional status was measured using the activities of daily living and instrumental activities of daily living scales. HRQoL was measured using the European Quality of Life five dimensions (EQ-5D), and the Short Form-12 version 2. A general linear model was used to compare the means of the scores., Results: Recurrent falls in community-dwelling older adults were associated with poorer physical performance as measured by the TUG test (P < 0.001), FTSS test (P = 0.011), handgrip strength (P < 0.001) and tandem stand (P < 0.001), and lower HRQoL scores as measured by the EQ-5D (P = 0.006) and SF-12 (P = 0.006 and P = 0.012)., Conclusion: The present findings provide further evidence that recurrent fallers have poorer physical performance and quality of life than single fallers. Recurrent falls might be a symptom of underlying disease and frailty, and reason for further assessment., (© 2014 Japan Geriatrics Society.)

Background/aims: The diagnosis of delirium is not supported by specific biomarkers. In a previous study, high neopterin levels were found in patients with a postoperative delirium. In the present study, we investigated levels of neopterin, interleukin-6 (IL-6) and insulin-like growth factor-1 (IGF-1) in acutely ill admitted elderly patients with and without a delirium., Methods: Plasma/serum levels of neopterin, IL-6 and IGF-1 were determined in patients aged ≥65 years admitted to the wards of Internal Medicine and Geriatrics. Differences in biomarker levels between patients with and without a delirium were investigated by the analysis of variance in models adjusted for age, gender, comorbidities and eGFR (when appropriate)., Results: Eighty-six patients were included; 23 of them with a delirium. In adjusted models, higher mean levels of neopterin (70.5 vs. 45.9 nmol/l, p = 0.009) and IL-6 (43.1 vs. 18.5 pg/ml, p = 0.034) and lower mean levels of IGF-1 (6.3 vs. 9.3 nmol/l, p = 0.007) were found in patients with a delirium compared to those without., Conclusions: The findings of this study suggest that neopterin might be a potential biomarker for delirium which, through oxidative stress and activation of the immune system, may play a role in the pathophysiology of delirium., (© 2014 S. Karger AG, Basel.)

The use of potentially inappropriate medications (PIMs) by older people and potential prescribing omissions (PPOs) represent a serious problem. It increases the risk of adverse drug reactions (ADRs), however it is susceptible to influence in a substantial number of cases. Use of the STOPP/START criteria developed in Ireland to optimise pharmacotherapy of older people reduces the number of ADRs and medication errors. Licensing of new drugs, the increased number of potentially inappropriate drugs, and the availability of new literature were grounds for an update of the first version of the STOPP/START criteria which was published in 2008. In order to develop a screening tool with a broader application, a consensus panel of experts in the field of pharmacotherapy of older people was selected from 14 European countries for the second version of the STOPP/START criteria, including two from the Netherlands. The translation of the second version of the STOPP/START criteria has been adapted to the situation in the Netherlands, partly by omitting drugs that are not licensed in the Netherlands.

Background: Fall-induced injuries in persons aged 65 years and older are a major public health problem. Data regarding circumstances leading to specific injuries, such as traumatic brain injury (TBI) and hip fractures in older adults are scarce., Objective: To investigate the activity distributions leading to indoor and outdoor falls requiring an emergency department (ED) visit, and those resulting in TBIs and hip fractures., Participants: 5880 older adults who visited the ED due to a fall., Methods: Data is descriptive and stratified by age and gender., Results: Two-thirds of all falls occurred indoors. However, there were higher proportions of outdoor falls at ages 65-79 years (48%). Walking up or down stairs (51%) and housekeeping (17%) were the most common indoor activities leading to a TBIs. Walking (42%) and sitting or standing (16%) was the most common indoor activities leading to a hip fracture. The most common outdoor activities were walking (61% for TBIs and 57% for hip fractures) and cycling (10% for TBIs and 24% for hip fractures)., Conclusion: In the present study we found that the indoor activities distribution leading to TBIs and hip fractures differed. Notably, about half of the traumatic brain injuries and hip fractures in men and women aged 65-79 years occurred outdoors. This study provides new insights into patterns leading to injurious falls by age, gender and injury type, and may guide the targeting of falls prevention at specific activities and risk groups, including highly functional older men and women., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: general opinion is growing that drug cessation in complex older patients is warranted in certain situations. From a clinical viewpoint, drug cessation seems most warranted in four situations, i.e., falls, delirium, cognitive impairment and end-of-life situations. To date, little information about the effects of drug cessation in these four situations is available., Objectives: to identify the effects and effectiveness of drug cessation on falls, delirium and cognitive impairment. For end-of-life situations, we reviewed cessation of inappropriate drug use., Methods: electronic databases were searched using MeSH terms and relevant keywords. Studies published in English were included if they evaluated the effects of drug cessation in older persons, aged ≥65 years, with falls, delirium or cognitive impairment; or cessation of inappropriate drug use in end-of-life situations., Results: we selected seven articles for falls, none for delirium, two for cognition and two for end-of-life situations. Withdrawal of psychotropics reduced fall rate; a prescribing modification programme for primary care physicians reduced fall risk. Withdrawal of psychotropics and a systematic reduction of polypharmacy resulted in an improvement of cognition. Very little rigorous research has been conducted on reducing inappropriate medications in patients approaching end of life., Conclusion: little research has focussed on drug cessation. Available studies showed a beneficial impact of cessation of psychotropic drugs on falls and cognitive status. More research in this field is needed. The issue of systematic drug withdrawal in end-of-life cases is controversial, but is increasingly relevant in the face of rising numbers of older people of this clinical status.

Few studies have reported the risk of death related to Alzheimer's disease (AD) in large population-based cohorts. The objective of this study was to analyze the impact of AD on all-cause mortality in a nationwide sample of persons with AD. Community-dwelling persons with AD and an equal number of individually matched (age, gender, and region of residence) control persons without AD were identified from the registers of Social Insurance Institution of Finland at the end of 2005. Deaths in this sample (n = 56,041, mean age 79.7 years, 67.8% women) during a 57-month follow-up period were recorded. Using a nested case-control design, unadjusted and adjusted (cardiovascular disease, cancer, diabetes, and asthma and/or COPD) hazard ratios (HR) with 95% confidence intervals (CI) were computed using proportional hazards regression. The results were categorized according to age at death (<80, 80 to 89, ≥ 90 years) and duration of AD (≤ 3, 4 to 6, ≥ 7 years). The unadjusted HR for death associated with AD was 2.03 (95% CI: 1.97 to 2.09). The HR was highest in the youngest age category [HR = 3.46 (95% CI: 3.18 to 3.77)], and still significantly elevated in the oldest age category [HR = 1.50 (95% CI: 1.41 to 1.60)]. Comorbidity adjustments did not change the HRs, and even a short duration of AD (≤ 3 years) was associated with a significantly increased risk of death. In conclusion, AD was associated with an increased risk of death that was more pronounced at younger ages and existed even after a recent diagnosis of AD.

Background: Falls are a common mechanism of injury in the older population, putting an increasing demand on scarce healthcare resources. The objective of this study was to determine healthcare costs due to falls in the older population., Methods: An incidence-based cost model was used to estimate the annual healthcare costs and costs per case spent on fall-related injuries in patients ≥ 65 years, The Netherlands (2007-2009). Costs were subdivided by age, gender, nature of injury, and type of resource use., Results: In the period 2007-2009, each year 3% of all persons aged ≥ 65 years visited the Emergency Department due to a fall incident. Related medical costs were estimated at €675.4 million annually. Fractures led to 80% (€540 million) of the fall-related healthcare costs. The mean costs per fall were €9370, and were higher for women (€9990) than men (€7510) and increased with age (from €3900 at ages 65-69 years to €14,600 at ages ≥ 85 year). Persons ≥ 80 years accounted for 47% of all fall-related Emergency Department visits, and 66% of total costs. The costs of long-term care at home and in nursing homes showed the largest age-related increases and accounted together for 54% of the fall-related costs in older people., Discussion: Fall-related injuries are leading to a high healthcare consumption and related healthcare costs, which increases with age. Programmes to prevent falls and fractures should be further implemented in order to reduce costs due to falls in the older population and to avoid that healthcare systems become overburdened., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objectives: To evaluate the feasibility and validity of gait parameters measured with an electronic walkway system in predicting short-term fall risk in nursing home residents with dementia., Methods: 57 ambulatory nursing home residents with moderate to severe dementia participated in this prospective cohort study. We used the GAITRite(®) 732 walkway system to assess gait parameters. Measurements were collected every 3 months over a 15 month period, with each measurement being a baseline for the subsequent measurement. Falls were retrieved from incident reports. The predictive validity of the GAITRite(®) parameters was expressed in terms of sensitivity and specificity. Logistic regression analysis was conducted to examine the association between these parameters and falls occurrence within three months., Results: Reduced velocity (OR=1.22; 95% CI 1.04-1.43) and reduced mean stride length (OR=1.19; 95% CI 1.03-1.40) were the best significant gait predictors of a fall within three months, with a sensitivity of 82% for velocity and 86% for mean stride length, and a specificity of 52% for velocity and for mean stride length. The test procedure took an average of 5 min per participant. Some verbal persuasion or physical cueing was necessary in 142 measurements (80.7%)., Conclusion: Gait parameters as measured with an electronic walkway system can be used for the prediction of short-term fall risk in nursing home residents with moderate to severe dementia. However some form of persuasion might be needed to perform the task. To refine our findings, large prospective studies on the predictive validity of gait parameters in this type of population are needed., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Vertebral fractures are a common consequence of osteoporosis in older persons. With the ageing of the population, numbers are expected to rise., Objective: To determine trends in health care demand due to vertebral fracture related emergency department (ED) visits and hospitalizations in the older Dutch population., Design and Setting: Secular trend analysis of vertebral fracture related ED visits between 1986 and 2008, using the Dutch Injury Surveillance System. All ED visits with a primary diagnosis of a vertebral fracture in persons aged ≥65 years were extracted from this database., Main Outcome Measure: Numbers, age-specific and age-adjusted incidence rates (per 100,000 population) of ED visits and hospitalization rates due to vertebral fractures in the older Dutch population were calculated for each year of the study., Results: The total number of ED visits due to a vertebral fracture increased from 913 in 1986 to 2502 in 2008 (174% increase). The majority of fractures were caused by a low-energetic fall incident (83%). The overall age-adjusted incidence rate increased from 51.6 per 100,000 population in 1986 to 103.6 in 2008. Incidence rates increased with age and were higher in females than in males. The hospitalization rate remained stable at about 50-55%, in both females and males., Conclusion: Vertebral fracture related ED visits and hospitalizations are increasing rapidly in the older Dutch population, especially in the oldest-old. Most vertebral fractures were associated with falls. These findings indicate that a pro-active approach in the diagnosis and treatment of osteoporosis and in the prevention of falls in both men and women is warranted., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background/objectives: Falls are a major public health problem. Older persons are frequently underrepresented in trials, including falls prevention trials. Insight into possible reasons for non-participation could help to improve trial designs and participation rates among this age-group. The aim of this study was to explore reasons why older people refuse to participate in falls prevention trials., Setting: A qualitative study., Participants: Community-dwelling adults aged ≥65 years who attended the Emergency Department due to a fall and refused to participate in a falls prevention trial (IMPROveFALL-study)., Measurements: A structured interview guide was used, and interview transcripts were subjected to an independent content analysis by two researchers., Results: 15 interviews were conducted. A main reason to refuse trial participation was mobility impairment. In contrast, younger and more "active" and mobile seniors considered themselves "too healthy" to participate. Persons with multiple comorbidities mentioned that they attended a hospital too often, or experienced adequate follow-up by their own physicians already. Transport problems, including distance to the hospital, parking facilities, and travel expenses were another issue. During the interviews it was emphasized by the patients, that they knew the reason for their fall. However, they were not familiar with the positive effects of falls prevention programmes., Conclusions: Older persons reported multiple reasons to refuse participation in a falls prevention study, such as health-related factors, several practical problems, and personal beliefs about the causes and preventability of falls. Anticipation of those issues might contribute to an improvement in participation rates of older fallers, shorter study duration, and a better generalizability of research findings., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Although memory complaints are one of the first clinical symptoms in patients with Alzheimer's disease (AD), damage to the parietal lobe, a key structure in the visuomotor coordination network, was recently identified in early-stage AD. The aim of this study was to quantify visuomotor coordination in patients with probable AD and to compare their visuomotor performance with controls using five eye-hand coordination tasks of variable complexity. Eye and hand movements were measured in 16 AD patients and 18 controls. The measurement setup consisted of a touch screen, an eye-tracking device, and a motion capturing system. We investigated eye-hand coordination by quantifying absolute and relative latencies of eye and hand movements and by analyzing eye and hand kinematics. We found that AD patients need significantly more time to initiate and execute goal-directed hand movements. AD patients are also unable to suppress reflexive eye and, to a lesser extent, hand movements. Furthermore, AD patients use a stepwise approach of eye and hand movements to touch a sequence of stimuli, whereas controls more often show an anticipatory approach. The impairments in reflex suppression of eye and hand movements, and changes in relative timing of eye-hand coordination, in AD patients support the notion that cortical networks involving the posterior parietal cortex are affected at an early disease-stage. It also suggests that the problems of AD patients to perform daily activities that require eye-hand coordination are not only caused by cognitive decline, but also by degeneration of neural networks involved in visuomotor coordination.

Falls occur frequently in older adults. With ageing populations worldwide, an increase in fall-related traumatic head injuries can be expected. The aim of our study was to determine trends in traumatic head-injury-related hospitalizations among older adults. Therefore, a secular trend analysis of fall-related traumatic head injuries in the older Dutch population between 1986 and 2008 was performed, using the National Hospital Discharge Registry. All significant fall-related traumatic head injury hospitalizations in persons aged ≥65 years were extracted from this database. During the study period, traumatic head-injury-related hospitalizations increased by 213% to 3,010 in 2008. The incidence rate increased annually by 1.2% (95% CI: 0.6; 1.9) between 1986 and 2000. Since 2001, the increase has accelerated up to 11.6% (95% CI: 9.5; 13.8) per year. Overall, the age-adjusted incidence rate increased from 53.1 in 1986 to 119.1 per 100,000 older persons in 2008. Age-specific incidence rates increased in all age groups, especially in persons aged ≥85 years. Despite an overall reduction in the length of hospital stay per admission, the total number of hospital-bed-days increased with 31.5% to 20,250 between 1991 and 2008. In conclusion, numbers and incidence rates of significant traumatic head-injury-related hospitalization after a fall are increasing rapidly in the older Dutch population, especially in the oldest old, resulting in an increased health care demand. The recent increase might be explained by the ageing population, but also other factors may have contributed to the increase, such as an increased awareness of traumatic head injuries, the implementation of renewed guidelines for traumatic head injuries, and improved radiographic tools.

Two patients, a 96-year-old woman and a 94-year-old man, were diagnosed with metastatic cutaneous melanoma. The first patient had undergone radical excision of the primary tumour 18 months before. The second patient presented with neurological symptoms caused by a metastatic melanoma; the primary tumour had recently been resected. Both patients died within three weeks of the diagnosis. Cutaneous melanomas have a high metastatic rate. Treatment options are limited for metastatic disease. The incidence of melanoma increases with age. Old age is an independent risk factor, which is also associated with a poor prognosis. Older patients more often present with more serious histological characteristics and more aggressive types of melanoma. The Breslow thickness is also higher in patients aged 65 or over. Nodular melanoma, lentigo maligna or acral lentiginous melanoma are observed more frequently in this group of patients. Moreover, elderly people more frequently present with liver or cerebral metastases. Early diagnosis improves the prognosis, also in the elderly.

Background: The prevalence of cardiovascular disease and Alzheimer's disease (AD) increases with age. A number of studies have demonstrated an association between AD and cardiovascular risk factors and disease. However, data are inconsistent., Methods: Cross-sectional observational study in a geriatric outpatient population. Analysis of data from 327 patients diagnosed with probable AD in a geriatric outpatient clinic. Comparison of blood pressure levels, cardiovascular diagnoses, and Mini-Mental State Examination (MMSE) score between the patients., Results: MMSE score decreased with age (beta = -0.25; 95% CI: -0.35 to 0.15), and a positive correlation was found with systolic blood pressure (beta = 0.03; 95% CI: 0.003-0.06), pulse pressure (beta = 0.05; 95% CI: 0.01-0.08) and hypertension (beta = 1.56; 95% CI: 0.05-3.07). An increase in cardiovascular disease load had a negative effect on cognitive performance. After adjustment for duration of dementia (data present for 216 patients), results were slightly changed., Conclusions: Higher systolic blood pressure and pulse pressure were associated with a better cognitive test performance. Patients with probable AD and 2 or more cardiovascular diagnoses had lower MMSE scores., (2009 S. Karger AG, Basel.)

Identification of patients with cardiac dysfunction can be difficult in the geriatric population. Recently, different subtypes of the natriuretic peptide family have been advocated as biomarker for the diagnosis of heart failure in the emergency department setting. In this study we looked at associations between natriuretic peptide plasma levels and echocardiographic abnormalities in geriatric outpatients. Two-dimensional transthoracic echocardiography was performed in 209 community-dwelling subjects, visiting the geriatric outpatient clinic of our university hospital. Subjects were 65 years or older and had no markedly impaired cognitive function. Mean atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) plasma levels were respectively 11.0 and 10.8 pmol/l. BNP, but not ANP correlated with left ventricular dysfunction and left ventricular mass, whereas both peptides correlated with left atrial dimension and valvular lesions. A natriuretic peptide level in the highest tertile was associated with a higher risk of any echocardiographic abnormality, with odds ratios for BNP of 7.15 (range 2.15-23.71), and for ANP of 3.07 (range 1.15-8.16). In conclusion, elevated BNP and ANP plasma levels are closely related to cardiac abnormalities in elderly subjects. The association between cardiac abnormalities and natriuretic peptides is stronger for BNP than for ANP, hence for detection of cardiac abnormalities measurement of BNP plasma values are preferred over ANP plasma values.

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.

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 [beta = -0.029; 95% confidence interval (CI): -0.040, -0.019] and the carotid distensibility coefficient positively associated with BRS (beta = 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.

Objective: The role of orthostatic hypotension in falls in older people is generally accepted. Because of the high degree of intra- and interobserver variability in conventional measurements of orthostatic hypotension, application of continuous measurement systems has been proposed. The clinical relevance of a blood pressure drop lasting one heartbeat, however, is unknown. We therefore investigated which time average of continuous-finger-blood-pressure measurement (Finometer) showed the best association between orthostatic hypotension and falls. This was also compared with conventional sphygmomanometer measurements., Methods: In 217 geriatric outpatients supine and standing (finger) blood pressure to diagnose orthostatic hypotension was monitored with Finometry (beat-to-beat and 1, 5, 10, 15, 20 and 30 s averages) and sphygmomanometry. History of fall incidents (previous year) was registered., Results: The best association (C=0.22, P=0.003) with falls history was found for the 5-s average of Finometry, whereas falls and orthostatic hypotension assessed by sphygmomanometry did not correlate. The odds ratio of a fall according to orthostatic hypotension using the 5-s average was 2.54 (95% CI: 1.37 to 4.71)., Conclusions: Orthostatic hypotension and falls are correlated when using Finometry, with the best association found when using 5-s averages. As the etiology of falls is often multifactorial, orthostatic hypotension and falls are poorly correlated, irrespective of the method or time average that is applied.

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.

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.

Arterial stiffness is one of the characteristics of vascular aging. Increases in pulse pressure, which reflect an increase in the stiffness of the large arteries, are associated with elevated C-reactive protein (CRP) levels. This may suggest a role of inflammation in the development of arterial stiffness. We investigated the relation between measures of arterial stiffness and CRP within the framework of the Rotterdam Study, a population-based cohort study including subjects aged 55 years and older. The carotid-femoral pulse wave velocity and the distensibility coefficient of the carotid artery were used as measures of arterial stiffness. Data on both arterial stiffness and CRP were available for 866 participants. In adjusted models, levels of CRP were linearly associated with pulse wave velocity (regression coefficient 0.088, 95% CI 0.006-0.170). Adjusted mean values of pulse wave velocity were significantly different across tertiles of CRP, being higher in the highest tertile of CRP. However, no significant association between CRP and carotid distensibility was observed.

The insertion/deletion (I/D) polymorphism of the ACE gene may be involved in structural arterial changes. Aim of the present study was to assess the relationship between the ACE I/D gene and vessel wall stiffness among older adults. The study was conducted within the Rotterdam study, a population-based cohort study including subjects aged 55 years and older. The II, ID and DD genotypes of the ACE gene were determined in all subjects. The distensibility coefficient (10(-3)/kPa) of the carotid artery and the carotid-femoral pulse wave velocity were measured during the third phase of the Rotterdam study (1997-1999) and were used as measure of arterial stiffness. Data on both carotid stiffness and the ACE genotype were available for 3001 participants. After adjustment for age and gender, subjects with the ID and DD genotype had higher carotid stiffness compared to subjects with II genotype (distensibility coefficient (10(-3)/kPa) 10.24 (95% CI, 10.06-10.43), 10.27 (95% CI, 10.02-10.52), 10.65 (95% CI, 10.37-10.93), respectively (ID versus II genotype, P = 0.017), (DD versus II genotype, P = 0.037)). In stratified analyses, the association was strongest in subjects younger than 70 years. No difference was seen for pulse wave velocity among genotypes. In conclusion, the results of this population-based study show that the ACE ID/DD genotypes are associated with higher common carotid stiffness.

Increased intima-media thickness (IMT) of the common carotid arteries is related to generalized atherosclerosis and increased risk of future myocardial infarction and cerebrovascular disease. An association between IMT and the presence of coronary artery disease (CAD) has been documented, but controversial data have been found about the relation between increased IMT and the extent of CAD. An association between carotid atherosclerosis and cardiac remodeling has also been reported. It is still unclear whether increased IMT of the common carotid arteries might be associated with prevalent cardiovascular disease in older adults. This study included 70 patients, 37 with CAD and 33 matched for age and gender without CAD. All patients underwent a baseline clinical examination, B-mode ultrasound of the carotid arteries, and echocardiography. The authors evaluated the possible association between increased IMT with the presence and extent of CAD and the presence of left ventricular hypertrophy (LVH). The patients with CAD had significantly increased IMT compared to patients without CAD. IMT was found to increase with the number of coronary vessels affected, after adjustment for age, gender, hypertension, hypercholesterolemia, diabetes mellitus, and smoking habits. The test for trend was highly significant (p<0.001). Patients with LVH had significantly increased IMT as compared with patients without LVH. IMT of the common carotid arteries was increased in the presence of CAD and increased with the number of coronary vessels diseased. Second, the authors found that IMT of the common carotid arteries was significantly increased in patients with LVH. Increased IMT, as an indicator of subclinical cardiovascular disease, may help to identify patients who would benefit from aggressive therapeutic measures.