Association of bradykinin receptor 2 (BDKRB2) variants with physical performance and muscle mass: Findings from the LACE sarcopenia trial.

Introduction: Understanding genetic contributors to sarcopenia (age-related loss of muscle strength and mass) is key to finding effective therapies. Variants of the bradykinin receptor 2 (BDKRB2) have been linked to athletic and muscle performance. The rs1799722-9 and rs5810761 T alleles have been shown to be overrepresented in endurance athletes, possibly due to increased transcriptional rates of the receptor.

Activin type I receptor polymorphisms and body composition in older individuals with sarcopenia-Analyses from the LACE randomised controlled trial.

Background: Ageing is associated with changes in body composition including an overall reduction in muscle mass and a proportionate increase in fat mass. Sarcopenia is characterised by losses in both muscle mass and strength. Body composition and muscle strength are at least in part genetically determined, consequently polymorphisms in pathways important in muscle biology (e.

ACE I/D genotype associates with strength in sarcopenic men but not with response to ACE inhibitor therapy in older adults with sarcopenia: Results from the LACE trial.

Background: Angiotensin II (AII), has been suggested to promote muscle loss. Reducing AII synthesis, by inhibiting angiotensin converting enzyme (ACE) activity has been proposed as a method to inhibit muscle loss. The LACE clinical trial was designed to determine whether ACE inhibition would reduce further muscle loss in individuals with sarcopenia but suffered from low recruitment and returned a negative result.

Effect of perindopril or leucine on physical performance in older people with sarcopenia: the LACE randomized controlled trial.

Background: This trial aimed to determine the efficacy of leucine and/or perindopril in improving physical function in older people with sarcopenia.

Methods: Placebo-controlled, parallel group, double-blind, randomized two-by-two factorial trial. We recruited adults aged ≥ 70 years with sarcopenia, defined as low gait speed (<0.

A prospective study of the association between orthostatic hypotension and falls: definition matters.

Background: falls are a common cause of morbidity and mortality in older people. Orthostatic hypotension (OH) is considered an important risk factor for falls, but longitudinal studies have failed to show a clear association. This disparity may be because conventional methods of measuring blood pressure (BP) changes are too imprecise and/or the diagnostic criteria for OH are inappropriate.

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.

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.

Brain oxygenation responses to an autonomic challenge: a quantitative fMRI investigation of the Valsalva manoeuvre.

In late age, the autonomic nervous system (ANS) has diminished ability to maintain physiological homeostasis in the brain in response to challenges such as to systemic blood pressure changes caused by standing. We devised an fMRI experiment aiming to map the cerebral effects of an ANS challenge (Valsalva manoeuvre (VM)). We used dual-echo fMRI to measure the effective transverse relaxation rate (R2*, which is inversely proportional to brain tissue oxygenation levels) in 45 elderly subjects (median age 80 years old, total range 75-89) during performance of the VM.

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.

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.

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.

Falls and fall-related injury are common in older people with chronic liver disease.

Background: Improved survival with chronic liver disease (CLD) and increased incidence in the older has led to a rapidly expanding population which faces similar "geriatric syndromes" as the general population. With risk factors such as autonomic dysfunction, cognitive impairment, and muscle abnormalities in CLD it is expected that falls and injury will be common.

Aim: To determine prevalence of falls and injury in chronic liver disease and to identify potential modifiable fall associations.

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.

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.

Autonomic dysfunction in primary biliary cirrhosis correlates with fatigue severity.

Background And Aims: Autonomic dysfunction has previously been described in primary biliary cirrhosis patients. In nonhepatic diseases, fatigue is associated with autonomic dysfunction and impaired baroreflex sensitivity. Here, we investigate the prevalence of autonomic dysfunction using highly sensitive detection modalities and its relationship with fatigue in both noncirrhotic and cirrhotic primary biliary cirrhosis patients.

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.

Reduced heart rate variability and baroreflex sensitivity in primary biliary cirrhosis.

Background: Standardized mortality ratio for primary biliary cirrhosis (PBC) is 2.87. Even after accounting for liver and cancer-related deaths there is an unexplained excess mortality associated with PBC.

Autonomic function is impaired in elderly stroke survivors.

Background And Purpose: Impaired autonomic function is common in the acute poststroke phase but little is known about the longer term effects, particularly in older people. We sought to determine if autonomic function is impaired after stroke recovery in older patients.

Methods: A cross-sectional case-control study comparing autonomic function in 76 nondemented stroke patients with 70 community-living controls aged older than 75 years.

Familial neurocardiogenic (vasovagal) syncope.

Vasovagal syncope (VSS) is an exaggerated tendency towards the common faint caused by a sudden and profound hypotension with or without bradycardia. The etiology of VVS is unknown though several lines of evidence indicate central and peripheral abnormalities of sympathetic function. Studies however indicate a strong heritable component to the etiology of VVS in over 20% of cases.