Search

Background: We aimed to summarize the published evidence on the fall risk reducing potential of cardiovascular diagnostics and treatments in older adults. Methods: Design:scoping review and evidence map. Data sources:Medline and Embase. Eligibility criteria:all available published evidence; Key search concepts: “older adults,” “cardiovascular evaluation,” “cardiovascular intervention,” and “falls.” Studies reporting on fall risk reducing effect of the diagnostic/treatment were included in the evidence map. Studies that investigated cardiovascular diagnostics or treatments within the context of falls, but without reporting a fall-related outcome, were included in the scoping review for qualitative synthesis. Results: Two articles on cardiovascular diagnostics and eight articles on cardiovascular treatments were included in the evidence map. Six out of ten studies concerned pacemaker intervention of which one meta-analyses that included randomized controlled trials with contradictory results. A combined cardiovascular assessment/evaluation (one study) and pharmacotherapy in orthostatic hypotension (one study) showed fall reducing potential. The scoping review contained 40 articles on cardiovascular diagnostics and one on cardiovascular treatments. It provides an extensive overview of several diagnostics (e.g., orthostatic blood pressure measurements, heart rhythm assessment) useful in fall prevention. Also, diagnostics were identified, that could potentially provide added value in fall prevention (e.g., blood pressure variability and head turning). Conclusion: Although the majority of studies showed a reduction in falls after the intervention, the total amount of evidence regarding the effect of cardiovascular diagnostics/treatments on falls is small. Our findings can be used to optimize fall prevention strategies and develop an evidence-based fall prevention care pathway. Adhering to the World guidelines on fall prevention recommendations, it is crucial to undertake a standardized assessment of cardiovascular risk factors, followed by supplementary testing and corresponding interventions, as effective components of fall prevention strategies. In addition, accompanying diagnostics such as blood pressure variability and head turning can be of added value.

Orthostatic hypotension (OH) is an established and common cardiovascular risk factor for falls. An in-depth understanding of the various interacting pathophysiological pathways contributing to OH-related falls is essential to guide improvements in diagnostic and treatment opportunities. We applied systems thinking to multidisciplinary map out causal mechanisms and risk factors. For this, we used group model building (GMB) to develop a causal loop diagram (CLD). The GMB was based on the input of experts from multiple domains related to OH and falls and all proposed mechanisms were supported by scientific literature. Our CLD is a conceptual representation of factors involved in OH-related falls, and their interrelatedness. Network analysis and feedback loops were applied to analyze and interpret the CLD, and quantitatively summarize the function and relative importance of the variables. Our CLD contains 50 variables distributed over three intrinsic domains (cerebral, cardiovascular, and musculoskeletal), and an extrinsic domain (e.g., medications). Between the variables, 181 connections and 65 feedback loops were identified. Decreased cerebral blood flow, low blood pressure, impaired baroreflex activity, and physical inactivity were identified as key factors involved in OH-related falls, based on their high centralities. Our CLD reflects the multifactorial pathophysiology of OH-related falls. It enables us to identify key elements, suggesting their potential for new diagnostic and treatment approaches in fall prevention. The interactive online CLD renders it suitable for both research and educational purposes and this CLD is the first step in the development of a computational model for simulating the effects of risk factors on falls.

The number of people living with dementia, such as Alzheimer's disease, is increasing worldwide. Persons with dementia often have a high risk of atherosclerotic cardiovascular disease and they are therefore theoretically eligible for treatment of hypertension and hyperlipidemia. However, in this population, beneficial and harmful effects of cardiovascular risk management (CVRM) may be different compared to older persons without cognitive impairment. Current CVRM guidelines are based on trials from which persons with dementia were excluded. In this narrative review, we will discuss how current guidelines can be translated to persons with dementia and which aspects should be taken into account when treating hypertension and hyperlipidemia to prevent major adverse cardiovascular events (MACE). Survival time is significantly shorter in persons with dementia. We therefore suggest that since the main goal of CVRM is prevention of MACE, first of all, the patient's life expectancy and treatment wishes should be evaluated. Risk assessment tools are to be used with care, as they tend to overestimate the 5- and 10-year risk of MACE and benefit from CVRM in the prevention of MACE in persons with dementia. When the clinician and patient have decided that treatment is initiated or intensified, patients should be closely monitored since they are at high risk for adverse drugs events and overtreatment due to the natural course of blood pressure in persons with dementia. In the event of intolerance or side effects, medication should be switched or withdrawn. For persons with dementia and limited life expectancy, deprescribing should be part of usual care.

Antisense oligonucleotides have been explored widely in clinical trials and generally are considered to be nontoxic for the kidney, even at high concentrations. We report a case of toxic acute tubular injury in a healthy 56-year-old female volunteer after a pharmacologically active dose of a locked nucleic acid antisense oligonucleotide was administered. The patient received 3 weekly subcutaneous doses of experimental drug SPC5001, an antisense oligonucleotide directed against PCSK9 (proprotein convertase subtilisin/kexin type 9) that is under investigation as an agent to reduce low-density lipoprotein cholesterol levels. Five days after the last dose, the patient's serum creatinine level increased from 0.81 mg/dL at baseline (corresponding to an estimated glomerular filtration rate [eGFR] of 78 mL/min/1.73 m2) to 2.67 mg/dL (eGFR, 20 mL/min/1.73 m2), and this increase coincided with the presence of white blood cells, granular casts, and minimal hematuria on urine microscopy. The patient's serum creatinine level peaked at 3.81 mg/dL (eGFR, 13 mL/min/1.73 m2) 1 week after the last oligonucleotide dose. Kidney biopsy showed multifocal tubular necrosis and signs of oligonucleotide accumulation. Upon conservative treatment, the patient's serum creatinine level gradually decreased and reached her baseline level 44 days after the last oligonucleotide was administered. The patient recovered fully and kidney function was normal at every follow-up visit.