Age-Related Changes in Clinical and Analytical Variables in Chronic Hemodialyzed Patients.

Worldwide, the number of elderly individuals receiving chronic hemodialysis is rising. The aim of our study was to evaluate several clinical and analytical biomarkers in chronically dialyzed patients and analyze how they change with age. A cross-sectional study was performed by evaluating 289 end-stage renal disease patients undergoing dialysis. We evaluated the hemogram, adipokines, the lipid profile, and several markers related to inflammation, endothelial function/fibrinolysis, nutrition, iron metabolism, and cardiac and renal fibrosis. Clinical data and dialysis efficacy parameters were obtained from all patients. The relationships between studied biomarkers and age were assessed by a statistical comparison between younger (adults with age < 65 years) and older (age ≥ 65 years) patients and by performing regression analysis. Participants presented a mean age of 68.7 years (±13.6), with 66.8% (n = 193) being classified as older. Compared to younger patients, older patients presented the following: (a) significantly lower values of diastolic blood pressure (DBP) and ultrafiltration volume; (b) lower levels of phosphorus, uric acid, creatinine, and albumin; and (c) higher circulating concentrations of tissue-type plasminogen activator (tPA), D-dimer, interleukin-6, leptin, N-terminal pro B-type natriuretic peptide, and tissue inhibitor of metalloproteinase-1. In the multiple linear regression analysis, DBP values, tPA, phosphorus, and D-dimer levels were independently associated with the age of patients (standardized betas: -0.407, 0.272, -0.230, and 0.197, respectively; p < 0.001 for all), demonstrating relevant changes in biomarkers with increasing age at cardiovascular and nutritional levels. These findings seem to result from crosstalk mechanisms between aging and chronic kidney disease.

The Association of Leptin with Left Ventricular Hypertrophy in End-Stage Kidney Disease Patients on Dialysis.

Left ventricular hypertrophy (LVH) is a common cardiovascular complication in end-stage kidney disease (ESKD) patients. We aimed at studying the association of LVH with adiponectin and leptin levels, cardiovascular stress/injury biomarkers and nutritional status in these patients. We evaluated the LV mass (LVM) and calculated the LVM index (LVMI) in 196 ESKD patients on dialysis; the levels of hemoglobin, calcium, phosphorus, parathyroid hormone, albumin, adiponectin, leptin, N-terminal pro B-type natriuretic peptide (NT-proBNP) and growth differentiation factor (GDF)-15 were analyzed. ESKD patients with LVH (n = 131) presented higher NT-proBNP and GDF-15, lower hemoglobin and, after adjustment for gender, lower leptin levels compared with non-LVH patients. LVH females also showed lower leptin than the non-LVH female group. In the LVH group, LVMI presented a negative correlation with leptin and a positive correlation with NT-proBNP. Leptin emerged as an independent determinant of LVMI in both groups, and NT-proBNP in the LVH group. Low hemoglobin and leptin and increased calcium, NT-proBNP and dialysis vintage are associated with an increased risk of developing LVH. In ESKD patients on dialysis, LVH is associated with lower leptin values (especially in women), which are negatively correlated with LVMI, and with higher levels of biomarkers of myocardial stress/injury. Leptin and NT-proBNP appear as independent determinants of LVMI; dialysis vintage, hemoglobin, calcium, NT-proBNP and leptin emerged as predicting markers for LVH development. Further studies are needed to better understand the role of leptin in LVH in ESKD patients.

Nursing Home Residents Hospitalization at the End of Life: Experience and Predictors in Portuguese Nursing Homes.

(1) Background: Nursing Home (NH) residents are a population with health and social vulnerabilities, for whom emergency department visits or hospitalization near the end of life can be considered a marker of healthcare aggressiveness. With the present study, we intend to identify and characterize acute care transitions in the last year of life in Portuguese NH residents, to characterize care integration between the different care levels, and identify predictors of death at hospital and potentially burdensome transitions; (2) Methods: a retrospective after-death study was performed, covering 18 months prior to the emergence of the COVID-19 pandemic, in a nationwide sample of Portuguese NH with 614 residents; (3) Results: 176 deceased patients were included. More than half of NH residents died at hospital. One-third experienced a potentially burdensome care transition in the last 3 days of life, and 48.3% in the last 90 days. Younger age and higher technical staff support were associated with death at hospital and a higher likelihood of burdensome transitions in the last year of life, and Palliative Care team support with less. Advanced Care planning was almost absent; (4) Conclusions: The studied population was frail and old without advance directives in place, and subject to frequent hospitalization and potentially burdensome transitions near the end of life. Unlike other studies, staff provisioning did not improve the outcomes. The results may be related to a low social and professional awareness of Palliative Care and warrant further study.

Alkaline phosphatase and mortality in stroke patients: a systematic review.

Background: Increased plasma levels of alkaline phosphatase (ALP) have been associated to a worse prognosis in several types of diseases. In the present review, the authors aimed to study the relationship between plasma levels of ALP and overall mortality in patients with stroke. Methods: A systematic review was carried out, searching two databases: Web of Science and Medline/PubMed. Results: A total of nine studies that included data on overall mortality in stroke patients were selected. The selected studies were published between 2010 and 2022 and were predominantly from Asia. The articles reviewed quantified ALP levels through different methods: highest versus lowest quintiles of plasma ALP (three reports); highest versus lowest quartiles of plasma ALP (four reports); and plasma ALP levels in deceased versus in surviving patients (two reports). All selected studies showed an increased mortality associated to elevated ALP levels, irrespective of stroke type and length of follow-up, from a mean of 10 days to 2.5 years. The studies comparing the highest to the lowest ALP quintiles showed an aggregate value of 1.8 times greater risk of mortality for the former, when compared to the latter. Whereas, the studies comparing the highest to the lowest ALP quartiles showed an aggregate value of 2.4 times greater risk of mortality for the former, when compared to the latter. Conclusions: Elevated ALP levels are associated with increased mortality in stroke patients and provide cost effective prognostic indicators of mortality in stroke.

Plasma alkaline phosphatase is associated with mortality risk in patients with aortic valve stenosis.

Background: Aortic valve stenosis is an important clinical condition, with a significant mortality rate in the elderly. Plasma values of alkaline phosphatase (ALP) have been shown to act as a marker of prognosis in different clinical conditions and in the general population. Methods: Plasma levels of ALP were studied in a cohort of patients with aortic valve stenosis, and a 5-year survival evaluation was performed. Results: Twenty-four patients were under study, of whom 12 were dead at the 5-year follow-up. The median age at baseline evaluation was 79 years (interquartile range, 72-85 years), and 11 patients were female (13 were male). The median value of ALP, of 83 IU/L, was used to separate patients into two groups: 2 patients who died in the group with low ALP values versus 10 patients who died in the group with high ALP values. Using ALP with the same cutoff level, the Kaplan-Meier study with log-rank analysis showed a significance level <0.01. Cox regression analysis showed an overall significant result, with a significant level for plasma ALP (significance level 0.03), but not for age, sex, or transvalvular gradient (assessed by echocardiography). Conclusions: Elevated plasma ALP is associated with increased mortality risk in patients with aortic valve stenosis. This finding may merit evaluation in studies with a larger number of patients.

Walking Speed and Mortality: An Updated Systematic Review.

OBJECTIVE: The aim of our systematic review was to update the current evidence on the association between slow walking speed (WS) and mortality, expanding the current knowledge available in the literature. METHODS: A systematic review of the published data on the association of WS and mortality was carried out by searching on PubMed and ISI Web of Knowledge databases. RESULTS: From a title and abstract analysis, 61 articles were included that met the prespecified criteria. After a full-text analysis, 6 articles were excluded and the remaining articles accounted for 120,838 patients and > 25,148 deaths were registered. The duration of follow-ups ranged between 2 and 21 years. In general, studies have shown a consistent association between WS and mortality from all causes. CONCLUSIONS: WS showed continuous and consistent evidence to be a good predictor of mortality. As such, our study supports the use of this tool in clinical practice as a way to improve health care.

Cardiac rehabilitation in elderly myocardial infarction survivors: focus on circulatory power.

Exercise-based cardiac rehabilitation (EBCR) is paramount after an acute myocardial infarction (AMI). Older individuals have been reported as having a worse prognosis after an AMI, and some series have reported differences in the functional response to EBCR. The peak circulatory power (CP), a non-invasive parameter, has been described as a surrogate for the cardiac power, showing promising results as a comprehensive measure of the cardiovascular response. Whilst this, data concerning the impact of EBCR on CP, particularly among elderly individuals, remains elusive. To address this issue, an observational, retrospective study including all patients admitted due to an AMI who completed a phase II EBCR programme between 11/2012 and 4/2017, was conducted, with CP being analysed by a symptom-limited cardiopulmonary exercise test. A total of 379 patients, 30% aged ≥65 years-old, were included. CP significantly improved after the EBCR programme (in all patients, as well as in both subgroups). Older patients presented lower CP than their younger counterparts at the beginning and the end of the programme, while presenting smaller improvements (122 ± 540 vs 293 ± 638 mmHg mL/kg/min, p = 0.013). This was maintained after adjusting for several potential confounding factors. A contemporary ECBR programme was associated with significant improvements in CP among AMI patients. Though those aged ≥65 years-old presented smaller improvements in CP than younger individuals, these still presented significant increases in this parameter. These results highlight the importance of EBCR in this challenging higher risk group of patients.

Syncope and COVID-19 disease - A systematic review.

BACKGROUND: Syncope is not a common manifestation of COVID-19, but it may occur in this context and it can be the presenting symptom in some cases. Different mechanisms may explain the pathophysiology behind COVID-19 related syncope. In this report, we aimed to examine the current frequency and etiology of syncope in COVID-19. METHODS: A systematic review across PubMed, ISI Web of Knowledge and SCOPUS was performed, according to PRISMA guidelines, in order to identify all relevant articles regarding both COVID-19 and syncope. RESULTS: We identified 136 publications, of which 99 were excluded. The frequency of syncope and pre-syncope across the selected studies was 4.2% (604/14,437). Unexplained syncope was the most common type (87.9% of the episodes), followed by reflex syncope (7.8% of the cases). Orthostatic hypotension was responsible for 2.2% of the cases and syncope of presumable cardiac cause also accounted for 2.2% of cases. Arterial hypertension was present in 52.0% of syncope patients. The use of angiotensin receptor blockers or angiotensin converting enzyme inhibitors were not associated with an increased incidence of syncope (chi-square test 1.07, p 0.30), unlike the use of beta-blockers (chi-square test 12.48, p < 0.01). CONCLUSION: Syncope, although not considered a typical symptom of COVID-19, can be associated with it, particularly in early stages. Different causes of syncope were seen in this context. A reevaluation of blood pressure in patients with COVID-19 is suggested, including reassessment of antihypertensive therapy, especially in the case of beta-blockers.

Risk factors among stroke subtypes and its impact on the clinical outcome of patients of Northern Portugal under previous aspirin therapy.

BACKGROUND: In Western European countries, acute ischemic stroke (AIS) remains the third leading cause of death. Among the risk factors for cerebrovascular disease, some have more influence than others in certain stroke subtypes. The aim of this study was to evaluate the impact of risk factors among Stroke Subtypes on the clinical outcome of Portuguese patients under previous aspirin therapy. MATERIALS AND METHODS: We studied a cohort of 371 patients diagnosed with AIS and a clinical follow-up protocol was set up.The patients were admitted in a Department of Internal Medicine of a major hospital. Standardized data assessment and stroke subtype classification (Oxfordshire Community Stroke Project) were used. RESULTS: Arterial hypertension (80.4 %), overweight (72.6 %) and dyslipidemia (62.0 %) were the most prevalent risk factors with no statistical differences among the group's subtypes. Current smoking was more prevalent in POCI(62.9 %) with differences among subtypes (p = 0.002). Atrial fibrillation was more commonly reported in TACI (39.3 %) and less common in POCI (8.1 %) (p < 0.001).Comparing TACI vs Non TACI Stroke Subtypes demonstrated major differences in cumulative survival,among the cases with no previous aspirin treatment, after 3 years (51.9 % vs 88.8 %).The increased risk of mortality at 12 months is consistently observed for the presence of a previous atrial fibrillation (OR 3.01 95 %CI 1.69-5.39), TACI subtype (OR 10.4 95 %CI 4.83-22.6) and NIHSS over 10 (OR 9.33 95 % CI 4,49-19.4). When we analyze the impact of previous aspirin treatment in the risk for a new stroke event, it seems to have a protective effect in a time frame of 12 months, but this protection is lost extending at 24 months (p = 0.094 vs p = 0.005). DISCUSSION: Our results indicate that smoking, atrial fibrillation and age have different relevance in their distribution among ischemic stroke subtypes at the time of diagnosis. Concerning the influence of the main stroke risk factors on the clinical outcome, our results present a strong influence of atrial fibrillation and of age. Severity of disease at diagnosis, represented by TACI subtype is clearly associated to decreased survival among patients with no record of previous aspirin therapy. Our results reinforce the relevance cohort studies of different populations, to achieve a more comprehensive knowledge of the impact of risk factors on stroke subtypes and on its clinical outcome.

Identifiable relatives in the family history: not without individual consent.

The family history is a traditional section of the clinical record. Data on family members in the clinical record may be anonymous but yet these may be easily identifiable; therefore, exposing the relatives of the patient to the fact that a written record is produced, mentioning them, without their consent. This is in direct contradiction with European data protection and other regulations and in contradiction with a reasonable ethical perspective. For the purpose of obtaining an image of the present state of affairs, we used as a convenience sample, the series of Case Records published in 2019 in The New England Journal of Medicine (January to December). From a total number of 40 reports, identifiable relatives were present in 30. The number of identifiable relatives varied between none and 6. It is not the right of each individual to disclose sensitive clinical information regarding other persons, without consent from these latter. Family history should no longer include identifiable relatives, unless consent is obtained from each identifiable person. The authors offer the following guidelines on this topic: (1) Do not mention any identifiable relative of the patient in the medical history without consent from the said relative; (2) Do not mention in the family history clinical conditions seemingly unrelated to the present clinical situation; (3) Do not mention in the family history clinical conditions that the patient does not (him/) herself have and that may be seen as social stigmata; (4) Consult the institutional Ethics committee in case of reasonable doubt.

Differential impact of a cardiac rehabilitation program in functional parameters according to patient gender.

INTRODUCTION: Exercise-based cardiac rehabilitation (EBCR) programs are of paramount importance in the management of acute myocardial infarction (AMI) survivors. Albeit this, female patients tend to be less referred for these programs, while also having a poorer prognosis. We aimed at assessing the impact of a contemporary EBCR program on functional parameters after an AMI, and specifically the impact of gender on its potential benefits. METHODS: Observational, retrospective cohort study including all patients admitted to a tertiary center due to an AMI who completed a phase II EBCR program after discharge, between November 2012 and April 2017. Functional parameters were assessed by a symptom-limited cardiopulmonary exercise test (CPET). Patients were dichotomized according to gender. RESULTS: A total of 379 patients were included, 19% of whom were women. After the program, peak oxygen uptake (pVO2) and exercise duration increased significantly (P<0.001). Though female patients presented a lower pVO2 and completed a shorter CPET at both the beginning and end of the study, there were no differences in the magnitude of improvement in these parameters between both groups [pVO2 delta 1.37 ± 3.08 vs 1.31 ± 2.62 mL/kg/min, P=0.876; CPET duration delta 120 (60-167) vs 85 (60-146), P=0.176]. CONCLUSIONS: A contemporary EBCR program was associated with significant improvements in functional parameters, as assessed by CPET. Though female patients had lower levels of pVO2, the benefits of this program were similar among groups. These results highlight the importance of EBCR among this higher risk subset of patients.

Aortic valve fenestrations: a review.

BACKGROUND: Aortic valve fenestrations (AVFs) seem to be relatively common; however, their impact in human heart disease is not entirely clear. METHODS: A review was carried out to assess all scientific literature on human patients related to AVFs, as described in the published literature. The search was conducted on 2 different databases, Medline (PubMed), and ISI Web of Knowledge. RESULTS: Fifty-five reports were under analysis. Autopsy studies showed AVFs to be present in 55.9% of individuals studied in such studies. They occur more frequently in men and, in general, their frequency increases with age. Although common, fenestrations rarely cause regurgitation; however, they may play an important role in the pathophysiology of some cases of severe aortic regurgitation. AVFs have been described in patients with Down syndrome and Marfan syndrome, in patients with bicuspid or quadricuspid valves, and in patients with myxomatous valvular degeneration. Echocardiographic assessment of aortic regurgitation seems to have limitations in the diagnosis of valvular fenestrations. CONCLUSIONS: Fenestrations of the aortic valve are very common and are associated with certain clinical conditions. It is unknown if AVFs play any role in the current epidemic of aortic valve disease. Future studies should aim to better define the role of AVFs in aortic valve disease, to further understand its etiology and to develop diagnostic criteria.

Mortality and use of angiotensin-converting enzyme inhibitors in COVID 19 disease: a systematic review.

BACKGROUND: Interest exists concerning the use of angiotensin-converting enzyme inhibitors (ACEis) in patients with COVID-19 disease. OBJECTIVES: The aim of the study was to perform a systematic review on mortality associated to the use of ACEi in patients with COVID-19 disease. METHODS: Search in Medline (PubMed), in ISI Web of Knowledge and in medRxiv database; use of other sources. RESULTS: A total of 33 articles were evaluated. Concerning the papers used to produce the meta-analyses, 7 studies were selected, 5 of which were used. These 5 studies involved a total number of 944 patients treated with ACEi and 5173 not treated with ACEi. Increased mortality was seen in association to the use of ACEi in the context of COVID-19 disease (ACEi users vs nonusers; odds ratio, 1.48; 95% confidence interval, 1.02-2.15; P = .04). When compared to mortality in patients treated with angiotensin receptor blockers, mortality of patients treated with ACEi was not significantly different (odds ratio, 0.96; 95% confidence interval, 0.76-1.21; P = .74). Concerning the remaining reports, different types of data adjustments were used by several authors, after which increased mortality was not seen in association to the use of ACEi in this context. CONCLUSIONS: ACEi use could act as a marker of increased mortality risk in some but not all COVID-19 disease settings. The data now presented do not prove a causal relation but argue in favor of carrying out clinical trials studying ACEi in COVID-19 patients, to establish the safety of ACEi use in this context.

Low density lipoprotein cholesterol values and outcome of stroke patients: influence of previous aspirin therapy.

Background: The link between low-density lipoprotein cholesterol (LDL-C) and stroke risk remains controversial and few studies have evaluated the effect of LDL-C after stroke survival.Aims: We assessed the hypothesis proposing the effect of LDL-C on the outcome of stroke patients under the influence of previous Aspirin Therapy.Methods: Associations between LDL-C and outcomes. The effect of LDL cholesterol on stoke outcome was evaluated using Kaplan-Meier methodology, log-rank test, Cox proportional hazard models and Bootstrap Analysis.Results: In a cohort of 342 cases, we observed that among stroke patients with no record of previous aspirin therapy LDL-C levels within recommended range (nLDL-C) are associated to a poor overall survival on (p < 0.001, log-rank test) leading to a 4-fold increased mortality risk in both timeframes of 12 (HR 4.45, 95% CI 1.55-12.71; p = 0.004) or 24 months (HR 4.13, 95%CI 1.62-10.50;p = 0.003) after the first event of stroke. Moreover, modelling the risk of a second event after the first stroke in the timeframe of 24 months demonstrated a predictive capacity for nLDL-C plasmatic levels (HR 3.94, 95%CI 1.55-10.05; p = 0.004) confirmed by Bootstrap analysis (p = 0.003; 1000 replications). In a further step, the inclusion of LDL-C in simulating models equations to predict the risk of a second event in the timeframe of 12 months increased nearly 20% the predictive ability (c-index from 0.763 to 0.956).Conclusion: A worse outcome was seen in stroke patients with normal levels of LDLC, but this finding was restricted to patients not under previous aspirin therapy.

Differential Impact of a Cardiac Rehabilitation Program on Functional Parameters in Elderly versus Non-Elderly Myocardial Infarction Survivors.

BACKGROUND: Exercise-based cardiac rehabilitation (EBCR) plays a pivotal role in the management of acute myocardial infarction (AMI). Studies have shown that older individuals have a worse prognosis after an AMI, attesting to the importance of risk reduction strategies. We aimed at assessing the impact of age (patients dichotomized as ≥65 years old or <65 years old) on the functional benefits of an EBCR program among AMI survivors. DESIGN: Observational, retrospective cohort study. PARTICIPANTS: All patients admitted due to an AMI who completed a phase II EBCR program after discharge, between November 2012 and April 2017. INTERVENTION: EBCR program. MEASUREMENTS: Functional parameters were assessed by a symptom-limited cardiopulmonary exercise test. RESULTS: A total of 379 patients were included (30% aged ≥65 years). After the EBCR program, peak oxygen uptake (pVO2) and exercise duration increased significantly. Patients aged ≥65 years presented with more comorbidities and a lower functional capacity. Those aged ≥65 years presented significantly smaller improvements in pVO2 (0.79 ± 2.61 vs. 1.60 ± 3.11 mL/kg/min, p = 0.016) and exercise duration [75 (59-120) vs. 120 s (60-180), p = 0.002]. This was maintained after adjusting for several potential confounders. CONCLUSION: Older patients have a worse functional capacity than their younger counterparts. Still, a contemporary EBCR program was associated with significant functional improvements among those aged ≥65 years. The smaller improvements even after adjustments for potential confounders suggest that physiological differences may contribute to this finding. These results highlight the relevance of EBCR among this higher-risk subgroup.

Medical therapeutics: mortality effects, uncertainty, and informed consent.

Many drugs used in medical therapeutics are able to save human lives. Unfortunately, many such drugs have also led to the death of patients. This fact raises important issues discussed in light of a number of cases taken from cardiovascular therapeutics. Medical therapeutics currently includes a vast number of different types of interventions, including drugs, devices, surgery, and diets. In what regards drugs, we currently use molecules with profound influences on the human body-some of which leading occasionally to negative outcomes or even to patient death. A reasonable degree of statistical certainty goes along with a large degree of individual uncertainty-a phenomenon is seen in a group of patients but a quite different phenomenon may be seen in a particular case. When treating an individual patient, it is his/her interest and personal preferences that must be taken into consideration, not the interests of society or of science. The choice of medical therapy with a definite intrinsic mortality risk must imply strict accordance from the part of the patient. Since many therapeutic modalities do carry a definite mortality risk, an overall change in medical practice is necessary. Informed consent should be the rule, and should be the starting point for medical therapeutics.

GWAS contribution to atrial fibrillation and atrial fibrillation-related stroke: pathophysiological implications.

Atrial fibrillation (AF) and stroke are included in a group of complex traits that have been approached regarding of their study by susceptibility genetic determinants. Since 2007, several genome-wide association studies (GWAS) aiming to identify genetic variants modulating AF risk have been conducted. Thus, 11 GWAS have identified 26 SNPs (p < 5 × 10-2), of which 19 reached genome-wide significance (p < 5 × 10-8). From those variants, seven were also associated with cardioembolic stroke and three reached genome-wide significance in stroke GWAS. These associations may shed a light on putative shared etiologic mechanisms between AF and cardioembolic stroke. Additionally, some of these identified variants have been incorporated in genetic risk scores in order to elucidate new approaches of stroke prediction, prevention and treatment.