153 research outputs found

    HEALTH OUTCOMES IN OLDER ADULTS WITH CARDIOVASCULAR DISEASE

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    In the United States, longevity is increasing, and more adults are living into old age, a stage of life when age-related biologic and physiologic mechanisms predispose individuals to cardiovascular disease (CVD) in a context of complexity related to their age.1 Two thirds of all patients with CVD are older than 60 years of age, and more than 85% of patients over age 85 years live with some form of CVD.2 Although acute CVD is a leading cause of morbidity and mortality for adults of any age, older patients are at higher risk for adverse outcomes2, 3 including mortality, re-hospitalizations, diminished quality-of-life, and functional decline. Many older adults with acute CVD are managed based on evidence derived from cohorts of younger patients with the goal of achieving optimal cardiovascular care. Yet broader contextual health challenges exit in older populations.4 For example, multimorbidity, polypharmacy, cognitive decline, sarcopenia, and frailty are among the geriatric syndromes common in this population that can be exacerbated during their acute cardiovascular illness. Because these geriatric conditions frequently coexist with acute cardiovascular disease, the care for older patients is complex and can have a major impact on the healthcare system as a whole. In this thesis, I attempted to study older population in two domains. First, I evaluated the influence of two geriatric syndromes, frailty and sarcopenia, on health outcomes among older adults with acute cardiovascular illness from patient perspective. Second, I evaluated the impact of acute cardiovascular illness on healthcare utilization and cost among older patients from epidemiologic perspective. Seven manuscripts are included in this dissertation. Domain 1: Assessment of geriatric syndromes in older adults with cardiovascular disease. Domain 2: Healthcare utilization and cost among older adults with cardiovascular disease

    Differences in treatment and clinical outcomes in patients aged ≥75 years compared with those aged ≤74 years following acute coronary syndromes: a prospective multicentre study

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    \ua9 Author(s) (or their employer(s)) 2023.Objective This study describes the differences in treatment and clinical outcomes in patients aged ≥75 years compared with those aged ≤74 years presenting with acute coronary syndrome (ACS) and undergoing invasive management. Methods A large-scale cohort study of patients with ST-elevation/non-ST-elevation myocardial infarction (MI)/unstable angina underwent coronary angiography (January 2015-December 2019). Patients were classified as older (≥75 years) and younger (≤74 years). Regression analysis was used to yield adjusted risks of mortality for older versus younger patients (adjusted for history of heart failure, hypercholesterolaemia, peripheral vascular disease, chronic obstructive pulmonary disease, ischaemic heart disease, presence of ST-elevation MI on presenting ECG, female sex and cardiogenic shock at presentation). Results In total, 11 763 patients were diagnosed with ACS, of which 39% were aged ≥75 years. Percutaneous coronary intervention was performed in fewer older patients than younger patients (81.2% vs 86.2%, p<0.001). At discharge, older patients were prescribed less secondary-prevention medications than younger patients. Median follow-up was 4.57 years. Older patients had a greater risk of in-hospital mortality than younger patients (adjusted OR (aOR) 2.12, 95% CI 1.62 to 2.78, p<0.001). Older patients diagnosed with ST-elevation MI had greater adjusted odds of dying in-hospital (aOR 2.47, 95% CI 1.79 to 3.41, p<0.001). Older age was not an independent prognostic factor of mortality at 1 year (adjusted HR (aHR) 0.95, 95% CI 0.82 to 1.09, p=0.460) and at longer term (aHR 0.98, 95% CI 0.87 to 1.10, p=0.684). Conclusions Older patients are discharged with less secondary prevention. Patients aged ≥75 years are more likely to die in-hospital than younger patients

    DETERMINATION OF DEPTH OF PLACEMENT OF TUNNELS AND CAVITIES BY THE BOUNDARY ELEMENT METHOD

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    A boundary element numerical algorithm has been developed for the determination of stresses and deformations around cavities and tunnels. A study of the influence of depth below the ground surface on the distribution of stresses and deformations around cavities and tunnels is presented in this paper. The soil is assumed to behave linearly elastic. A computer program has been built to perform the numerical computations. The results show that with increasing the depth of placement of tunnel or opening below the ground surface, the settlements decrease. The maximum stresses occur at the haunches of the tunnel rather than at the crown. For the circular cavity that is considered in this paper, it was found that with increasing the depth below the ground surface (depth/tunnel diameter > 3), the surface settlements do not exceed 6 % from those obtained for the case of no-cavity condition

    EFFECT OF TRANSVERSE BASE RESTRAINT ON THE CRACKING BEHAVIOR OF MASSIVE CONCRETE

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    The effect of considering the third dimension in mass concrete members on its cracking behavior is investigated in this study. The investigation includes thermal and structural analyses of mass concrete structures. From thermal analysis, the actual temperature distribution throughout the mass concrete body was obtained due to the generation of heat as a result of cement hydration in addition to the ambient circumstances. This was performed via solving the differential equations of heat conduction and convection using the finite element method. The finite element method was also implemented in the structural analysis adopting the concept of initial strain problem. Drying shrinkage volume changes were calculated using the procedure suggested by ACI Committee 209 and inverted to equivalent temperature differences to be added algebraically to the temperature differences obtained from thermal analysis. Willam-Warnke model with five strength parameters is used in modeling of concrete material in which cracking and crushing behavior of concrete can be included. The ANSYS program was employed in a modified manner to perform the above analyses. A thick concrete slab of 1.5m in thickness and 10m in length was analyzed for different widths 2, 4, 8, and 10m to produce different aspect ratios (B/L) of 0.2, 0.4, 0.8, and 1.0 respectively. The results of the analyses show an increase in cracking tendency of mass concrete member as the aspect ratio of the same member is increased due to the effect of transverse base restraint. Accordingly, such effect cannot be ignored in the analysis of base restrained mass concrete structures subjected to temperature and drying shrinkage volume changes

    The Association of Intensive Blood Pressure Treatment and Non-Fatal Cardiovascular or Serious Adverse Events in Older Adults With Mortality: Mediation Analysis in Sprint

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    AIMS: Randomized clinical trials of hypertension treatment intensity evaluate the effects on incident major adverse cardiovascular events (MACEs) and serious adverse events (SAEs). Occurrences after a non-fatal index event have not been rigorously evaluated. The aim of this study was to evaluate the association of intensive (\u3c120 \u3emmHg) to standard (\u3c140 \u3emmHg) blood pressure (BP) treatment with mortality mediated through a non-fatal MACE or non-fatal SAE in 9361 participants in the Systolic Blood Pressure Intervention Trial. METHODS AND RESULTS: Logistic regression and causal mediation modelling to obtain direct and mediated effects of intensive BP treatment. Primary outcome was all-cause mortality (ACM). Secondary outcomes were cardiovascular (CVM) and non-CV mortality (non-CVM). The direct effect of intensive treatment was a lowering of ACM [odds ratio (OR) 0.75, 95% confidence interval (CI): 0.60-0.94]. The MACE-mediated effect substantially attenuated (OR 0.96, 95% CI: 0.92-0.99) ACM, while the SAE-mediated effect was associated with increased (OR 1.03, 95% CI: 1.01-1.05) ACM. Similar patterns were noted for intensive BP treatment on CVM and non-CVM. We also noted that SAE incidence was 3.9-fold higher than MACE incidence (13.7 vs. 3.5%), and there were a total of 365 (3.9%) ACM cases, with non-CVM being 2.6-fold higher than CVM [2.81% (263/9361) vs. 1.09% (102/9361)]. The SAE to MACE and non-CVM to CVM preponderance was found across all age groups, with the ≥80-year age group having the highest differences. CONCLUSION: The current analytic techniques demonstrated that intensive BP treatment was associated with an attenuated mortality benefit when it was MACE-mediated and possibly harmful when it was SAE-mediated. Current cardiovascular trial reporting of treatment effects does not allow expansion of the lens to focus on important occurrences after the index event

    Impact of multimorbidity on long-term outcomes in older adults with non-ST elevation acute coronary syndrome in the North East of England : a multi-centre cohort study of patients undergoing invasive care

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    OBJECTIVES: Older adults have a higher degree of multimorbidity, which may adversely affect longer term outcomes from non-ST elevation acute coronary syndrome (NSTE-ACS). We investigated the impact of multimorbidity on cardiovascular outcomes 5 years after invasive management of NSTE-ACS. DESIGN: Prospective cohort study. SETTING: Multicentre study conducted in the north of England. PARTICIPANTS: 298 patients aged ≥75 years with NSTE-ACS and referred for coronary angiography, with 264 (88.0%) completing 5-year follow-up. MAIN OUTCOME MEASURES: Multimorbidity was evaluated at baseline with the Charlson comorbidity index (CCI). The primary composite outcome was all-cause mortality, myocardial infarction, stroke, urgent repeat revascularisation or significant bleeding. RESULTS: Mean age was 80.9 (±6.1) years. The cohort median CCI score was 5 (IQR 4-7). The primary composite outcome occurred in 48.1% at 5 years, at which time 31.0% of the cohort had died. Compared with those with few comorbidities (CCI score 3-5), a higher CCI score (≥6) was positively associated with the primary composite outcome (adjusted HR (aHR) 1.64 (95% CI 1.14 to 2.35), p=0.008 adjusted for age and sex), driven by an increased risk of death (aHR 2.20 (1.38 to 3.49), p=0.001). For each additional CCI comorbidity, on average, there was a 20% increased risk of the primary composite endpoint at 5 years (aHR 1.20 (1.09 to 1.33), p<0.001). CONCLUSIONS: In older adults with NSTE-ACS referred for coronary angiography, the presence of multimorbidity is associated with an increased risk of long-term adverse cardiovascular events, driven by a higher risk of all-cause mortality. TRIAL REGISTRATION NUMBER: NCT01933581; ClinicalTrials.gov

    Uncoupling of ATP-Mediated Calcium Signaling and Dysregulated Interleukin-6 Secretion in Dendritic Cells by Nanomolar Thimerosal

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    Dendritic cells (DCs), a rare cell type widely distributed in the soma, are potent antigen-presenting cells that initiate primary immune responses. DCs rely on intracellular redox state and calcium (Ca(2+)) signals for proper development and function, but the relationship between these two signaling systems is unclear. Thimerosal (THI) is a mercurial used to preserve vaccines and consumer products, and is used experimentally to induce Ca(2+) release from microsomal stores. We tested adenosine triphosphate (ATP)-mediated Ca(2+) responses of DCs transiently exposed to nanomolar THI. Transcriptional and immunocytochemical analyses show that murine myeloid immature DCs (IDCs) and mature DCs (MDCs) express inositol 1,4,5-trisphosphate receptor (IP(3)R) and ryanodine receptor (RyR) Ca(2+) channels, known targets of THI. IDCs express the RyR1 isoform in a punctate distribution that is densest near plasma membranes and within dendritic processes, whereas IP(3)Rs are more generally distributed. RyR1 positively and negatively regulates purinergic signaling because ryanodine (Ry) blockade a) recruited 80% more ATP responders, b) shortened ATP-mediated Ca(2+) transients > 2-fold, and c) produced a delayed and persistent rise (≥ 2-fold) in baseline Ca(2+). THI (100 nM, 5 min) recruited more ATP responders, shortened the ATP-mediated Ca(2+) transient (≥ 1.4-fold), and produced a delayed rise (≥ 3-fold) in the Ca(2+) baseline, mimicking Ry. THI and Ry, in combination, produced additive effects leading to uncoupling of IP(3)R and RyR1 signals. THI altered ATP-mediated interleukin-6 secretion, initially enhancing the rate of cytokine secretion but suppressing cytokine secretion overall in DCs. DCs are exquisitely sensitive to THI, with one mechanism involving the uncoupling of positive and negative regulation of Ca(2+) signals contributed by RyR1

    TAVR in Older Adults: Moving Toward a Comprehensive Geriatric Assessment and Away From Chronological Age

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    Calcific aortic stenosis can be considered a model for geriatric cardiovascular conditions due to a confluence of factors. The remarkable technological development of transcatheter aortic valve replacement was studied initially on older adult populations with prohibitive or high-risk for surgical valve replacement. Through these trials, the cardiovascular community has recognized that stratification of these chronologically older adults can be improved incrementally by invoking the concept of frailty and other geriatric risks. Given the complexity of the aging process, stratification by chronological age should only be the initial step but is no longer sufficient to optimally quantify cardiovascular and noncardiovascular risk. In this review, we employ a geriatric cardiology lens to focus on the diagnosis and the comprehensive management of aortic stenosis in older adults to enhance shared decision-making with patients and their families and optimize patient-centered outcomes. Finally, we highlight knowledge gaps that are critical for future areas of study

    Life\u27s Essential 8: Optimizing Health in Older Adults

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    The population worldwide is getting older as a result of advances in public health, medicine, and technology. Older individuals are living longer with a higher prevalence of subclinical and clinical cardiovascular disease (CVD). In 2010, the American Heart Association introduced a list of key prevention targets, known as Life\u27s Simple 7 to increase CVD-free survival, longevity, and quality of life. In 2022, sleep health was added to expand the recommendations to Life\u27s Essential 8 (eat better, be more active, stop smoking, get adequate sleep, manage weight, manage cholesterol, manage blood pressure, and manage diabetes). These prevention targets are intended to apply regardless of chronologic age. During this same time, the understanding of aging biology and goals of care for older adults further enhanced the relevance of prevention across the range of functions. From a biological perspective, aging is a complex cellular process characterized by genomic instability, telomere attrition, loss of proteostasis, inflammation, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. These aging hallmarks are triggered by and enhanced by traditional CVD risk factors leading to geriatric syndromes (eg, frailty, sarcopenia, functional limitation, and cognitive impairment) which complicate efforts toward prevention. Therefore, we review Life\u27s Essential 8 through the lens of aging biology, geroscience, and geriatric precepts to guide clinicians taking care of older adults

    Baghdad’s thirdspace: Between liminality, anti-structures and territorial mappings

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    Wedged in-between the dense urban grain of Baghdad, blast walls of t-shaped concrete have littered the streets and neighbourhoods since 2003, after the US led invasion. The idiosyncrasy of these walls lies in their exaggerated spatial liminality. They appear, change location and disappear overnight, and on a daily basis, leaving Iraqis to navigate through labyrinths of in-between spaces. This article critically reveals the new social and power structures that have emerged in the context of the city in response to the condition resulting from this unique urban intervention. This uncanny spatial and social condition of permanent liminality will be analysed through Victor Turner’s critical theories of liminality and anti-structure coupled with Edward Soja’s theory of Thirdspace, interpreting, through a series of territorial mappings, a complex liminal condition in a contested and disrupted city
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