High Throughput Plasma Proteomics and Risk of Heart Failure and Frailty in Late Life.

Importance: Heart failure (HF) and frailty frequently coexist and may share a common pathobiology, although the underlying mechanisms remain unclear. Understanding these mechanisms may provide guidance for preventing and treating both conditions. Objective: To identify shared pathways between incident HF and frailty in late life using large-scale proteomics. Design, Setting, and Participants: In this cohort study, 4877 aptamers (Somascan v4) were measured among participants in the community-based longitudinal Atherosclerosis Risk In Communities (ARIC) cohort study at visit 3 (V3; 1993-1995; n = 10 638) and at visit 5 (V5; 2011-2013; n = 3908). Analyses were externally replicated among 3189 participants in the Cardiovascular Health Study (CHS). Data analysis was conducted from February 2022 to June 2023. Exposures: Protein aptamers, measured at study V3 and V5. Main Outcomes and Measures: Outcomes assessed included incident HF hospitalization after V3 and after V5, prevalent frailty at V5, and incident frailty between V5 and visit 6 (V6; 2016-2017; n = 4131). Frailty was assessed using the Fried criteria. Analyses were adjusted for age, gender, race, field center, hypertension, diabetes, smoking status, body mass index, estimated glomerular filtration rate, prevalent coronary heart disease, prevalent atrial fibrillation, and history of myocardial infarction. Mendelian randomization (MR) analysis was performed to assess potential causal effects of candidate proteins on HF and frailty. Results: A total of 4877 protein aptamers were measured among 10 638 participants at V3 (mean [SD] age, 60 [6] years; 4886 [46%] men). Overall, 286 proteins were associated with incident HF after V3 (822 events; P < 1.0 × 10-5), 83 of which were also associated with incident after V5 (336 events; P < 1.7 × 10-4). Among HF-free participants at V5 (n = 3908; mean [SD] age, 75 [5] years; 1861 [42%] men), 48 of 83 HF-associated proteins were associated with prevalent frailty (223 cases; P < 6.0 × 10-4), 18 of which were also associated with incident frailty at V6 (152 cases; P < 1.0 × 10-3). These proteins enriched fibrosis and inflammation pathways and demonstrated stronger associations with incident HF with preserved ejection fraction (HFpEF) than HF with reduced ejection fraction. All 18 proteins were associated with both prevalent frailty and incident HF in CHS. MR identified potential causal effects of several proteins on frailty and HF. Conclusions and Relevance: In this study, the proteins associated with risk of HF and frailty enrich for pathways related to inflammation and fibrosis as well as risk of HFpEF. Several of these proteins could potentially contribute to the shared pathophysiology of frailty and HF.

The global clinical studies of long COVID.

Long COVID are those who still have symptoms, signs, and conditions after the initial phase of infection of SARS-CoV-2. The incidence of long COVID varies among regions - 31% in North America, 44% in Europe, and 51% in Asia, which is challenging the healthcare system, but there is limited guideline for its treatment. With more and more nation-wide projects funded by the government such as RECOVER initiative in US and NIHR funding in UK, an increasing number of ongoing clinical trials are investigating the efficacy of diverse therapies on reversing long COVID. After searching the WHO International Clinical Trial Registry Platform, 587 clinical studies are identified as long COVID studies. Among these, 312 studies (53.2%) are testing potential therapies. Most of the long COVID trials were conducted in the United States (58 trials [18.6%]), followed by India (55 trials [17.6%]), and Spain (20 trials [6.4%]). Interventions in these clinical trials include physical exercise, rehabilitation therapy, behavioral therapy, and pharmacological therapies including herbs, paxlovid, and fluvoxamine. These trials are aiming to deal with these long COVID symptoms and signs including fatigue, decreased pulmonary function, reduce cognitive function, and others. To date, only 11 of these 312 studies have published their results that were not confirmative unfortunately. Future studies should be designed to address sleep disorders which were seldomly included in registered clinical studies. Moreover, interventions aimed at treating the underlying pathophysiology of long COVID are also necessary but currently lacking.

COVID-19 vaccine hesitancy prevalence in Mexico: A systematic review and metanalysis.

Background: Vaccine hesitancy (VH) is a recognized threat to public health that undermines efforts to mitigate disease burden. This study aims to gather available evidence regarding COVID-19 VH in Mexico, estimate the prevalence of VH, and its determinants to inform policymaking in this country. Methods: Following PRISMA guidelines, a systematic review of the MEDLINE literature, articles that estimated the prevalence of COVID-19 VH in Mexico were included in the analysis to obtain a pooled estimate. We used a binomial-normal model for meta-analysis of proportions (i.e., generalized linear mixed model) to perform the metanalysis. We then performed a narrative review of COVID-19 VH in Mexican subpopulations. Results: Seven studies met inclusion criteria. We estimated a pooled prevalence of COVID-19 VH of 16 % (95 % CI: 11-23 %) in Mexico. We found an association between VH and demographic characteristics, intrinsic vaccine factors, and beliefs. Subgroup analyses from specific studies suggested that patients with clinical conditions such as breast cancer or rheumatologic diseases had a higher prevalence of VH. Conclusions: VH is a highly complex and dynamic phenomenon in Mexico. Characterizing and understanding COVID-19 vaccine hesitancy in the Mexican population helps target future policy interventions to mitigate the spread and impact of infectious diseases. The implications of VH differ among groups that may be at higher risk of severe disease, underscoring the importance of prompt research among these groups as well as targeted interventions to address VH.

Late-life plasma proteins associated with prevalent and incident frailty: A proteomic analysis.

Proteomic approaches have unique advantages in the identification of biological pathways that influence physical frailty, a multifactorial geriatric syndrome predictive of adverse health outcomes in older adults. To date, proteomic studies of frailty are scarce, and few evaluated prefrailty as a separate state or examined predictors of incident frailty. Using plasma proteins measured by 4955 SOMAmers in the Atherosclerosis Risk in Community study, we identified 134 and 179 proteins cross-sectionally associated with prefrailty and frailty, respectively, after Bonferroni correction (p < 1 × 10-5 ) among 3838 older adults aged ≥65 years, adjusting for demographic and physiologic factors and chronic diseases. Among them, 23 (17%) and 82 (46%) were replicated in the Cardiovascular Health Study using the same models (FDR p < 0.05). Notably, higher odds of prefrailty and frailty were observed with higher levels of growth differentiation factor 15 (GDF15; pprefrailty = 1 × 10-15 , pfrailty = 2 × 10-19 ), transgelin (TAGLN; pprefrailty = 2 × 10-12 , pfrailty = 6 × 10-22 ), and insulin-like growth factor-binding protein 2 (IGFBP2; pprefrailty = 5 × 10-15 , pfrailty = 1 × 10-15 ) and with a lower level of growth hormone receptor (GHR, pprefrailty = 3 × 10-16 , pfrailty = 2 × 10-18 ). Longitudinally, we identified 4 proteins associated with incident frailty (p < 1 × 10-5 ). Higher levels of triggering receptor expressed on myeloid cells 1 (TREM1), TAGLN, and heart and adipocyte fatty-acid binding proteins predicted incident frailty. Differentially regulated proteins were enriched in pathways and upstream regulators related to lipid metabolism, angiogenesis, inflammation, and cell senescence. Our findings provide a set of plasma proteins and biological mechanisms that were dysregulated in both the prodromal and the clinical stage of frailty, offering new insights into frailty etiology and targets for intervention.

Bidirectional Association Between Frailty and Cardiac Structure and Function: The Atherosclerosis Risk in Communities Study.

Background Frailty and heart failure frequently coexist in late life. Limited data exist regarding the longitudinal associations of frailty and subclinical cardiac dysfunction. We aim to quantify the association of frailty with longitudinal changes in cardiac function and of cardiac function with progression in frailty status in older adults. Methods and Results Participants in the Atherosclerosis Risk in Communities cohort underwent frailty assessments at Visit 5 (V5; 2011-2013), V6 (2016-2017), and V7 (2018-2019), and echocardiographic assessments at V5 and V7. We assessed the association between frailty status at V5 and changes in frailty status from V5 to V7 and changes in cardiac function over 6 years. We then evaluated the association of cardiac function measured at Visit 5 with progression in frailty status over 4 years. Multivariable regression models adjusted for demographics and comorbidities. Among 2574 participants free of heart failure at V5 and V7 (age 74±4 years at V5 and 81±4 years at V7), 3% (n=83) were frail. Frailty at V5 was associated with greater left atrial volume index and E/e' ratio at V5 and 7. Participants who transitioned from robust at V5 to frail at V7 demonstrated greater increases in left ventricular mass index, left atrial volume index, and E/e' over the same period. Among 1648 robust participants at Visit 5, greater left ventricular mass index and mean wall thickness, lower tissue Doppler imaging e', and higher E/e' ratio at Visit 5 were associated with progression in frailty status. Conclusions Among robust, older adults free of heart failure, progression in frailty and subclinical left ventricular remodeling and diastolic dysfunction are interrelated.

Determinants of COVID-19 vaccine hesitancy among pregnant persons.

BACKGROUND: Vaccines reduce the risk of contracting and developing complications from coronavirus disease 2019 (COVID-19). Pregnant people are at increased risk of disease-related complications but have a higher prevalence of vaccine hesitancy (VH) than their nonpregnant counterparts. OBJECTIVE: This study aimed to describe risk factors and COVID-19- and vaccine-related perspectives that lead to VH among pregnant people in Mexico to target strategies to increase vaccine acceptance in this population. METHODS: A cross-sectional survey-based study to evaluate risk factors and COVID-19- and vaccine-related perspectives associated with VH among pregnant people was conducted. Respondents were pregnant people of all ages attending a regular follow-up visit or admitted to labor and delivery in a third-level maternity hospital in Mexico. VH was defined as not having received a COVID-19 vaccine and either declining or being undecided to accept a vaccine during their pregnancy. We used bivariate and multivariable logistic regression models to estimate assess the relationship among demographic factors, COVID-19- and vaccine-related perspectives, and VH. RESULTS: A total of 1475 respondents completed the questionnaire; 216 (18%) were under the age of 18 years, and 860 (58%) had received at least one dose of a COVID-19 vaccine. In this sample, 264 (18%) were classified as vaccine hesitant. Key factors associated with VH were adolescence, having family as a primary source of information, first pregnancy, and history of vaccines in previous pregnancies. COVID-19 perspectives were also strongly associated with VH. CONCLUSIONS: Among pregnant people in Mexico, VH is associated with demographic factors, vaccination history, sources of information, and perceived risks to the fetus. This information is relevant to policy makers and health care professionals to identify those more likely to be hesitant and to inform strategies to increase vaccine uptake among pregnant people.

Relationship of age at menarche, coitarche and first gestation: A retrospective cohort analysis.

Introduction: Teenage pregnancy is defined as a pregnancy occurring between ages 10 and 19 (Loredo-Abdlá et al., 2017; Belitzky, 1985; Kaplanoglu et al., 2015), and is associated with increased morbidity and mortality for both mother and child. Several factors have been identified with increased risk of a teenage pregnancy, including incomplete sexual education awareness and increased exposure at a young age. In addition, an earlier onset of sexual intercourse, or coitarche, has been linked to a higher risk of teenage pregnancy. Early menarche, defined as first menstruation before the age of 12 has been previously identified as a risk factor for an earlier coitarche, possibly linking an early menarche with a higher incidence of teenage pregnancy. This study aims to compare and determine the relationship between the incidence of teenage pregnancy with early menarche and coitarche in a low income setting. Design Setting Participants Interventions Main Outcome Measures: A cross sectional review of electronic records of women admitted for delivery in a second level center in northeastern Mexico, being a low-income setting, where 814 teenage and 1474 adult mothers were included. Results: Primigravid teenagers had earlier menarche and coitarche than adult counterparts and opted for postpartum contraception more frequently. Linear regression analysis revealed significant unadjusted beta coefficients between age at first pregnancy and coitarche (0.839) and menarche (0.362). Menarche and coitarche had a significant linear regression association of 0.395. Conclusion: We found amongst primigravid patients that teenagers had earlier menarche and coitarche than adults, which in turn correlated to their age at their first pregnancy.

Hypoplastic Left Heart Syndrome: A Review.

Hypoplastic left heart syndrome is a rare and poorly understood congenital disorder featuring a univentricular myocardium, invariably resulting in early childhood death if left untreated. The process to palliate this congenital cardiomyopathy is of high complexity and may include invasive interventions in the first week of life. The preferred treatment strategy involves a staged correction with 3 surgical procedures at different points in time. The Norwood procedure is usually performed within the first weeks of life and aims to increase systemic circulation and relieve pulmonary vascular pressure. This procedure is followed by the bidirectional Glenn and the Fontan procedures in later life, which offer to decrease stress in the ventricular chamber. The prognosis of children with this disease has greatly improved in the past decades; however, it is still largely driven by multiple modifiable and nonmodifiable variables. Novel and clever alternatives have been proposed to improve the survival and neurodevelopment of these patients, although they are not used as standard of care in all centers. The neurodevelopmental outcomes among these patients have received particular attention in the last decade in light to improve this very limiting associated comorbidity that compromises quality of life.

Killip-Kimball classification in octogenarians with acute coronary syndrome: an 11-year experience / Clasificación de Killip-Kimball en octogenarios con síndrome coronario agudo: 11 años de experiencia

Abstract Objective: The objective of the study is to validate the use of the Killip-Kimball classification (KC) as a predictor of outcomes in an octogenarian cohort with acute coronary syndrome. Methods: A retrospective analysis of patients who underwent a catheterization procedure for acute coronary syndrome (ACS) was performed. ACS was defined as per the American Heart Association guidelines, and included ST-elevation myocardial infarction (STEMI), non-STEMI and Unstable Angina. We determined factors associated with the KC upon admission to the emergency room. Likewise, we compared in-hospital mortality, length of stay, and other outcomes dividing the patients by KC. Results: A total of 133 patients with a mean age of 83 years were analyzed and assigned a KC from 1 to 4 according to clinical presentation. Each group included 86, 9, 23, and 15 patients, respectively. In-hospital mortality was 12%, 5% in KC-I, 11% in KC-II, 22% in KC-III, and 40% in KC-IV with a significant difference between classes (p = 0.002). In addition, we found higher KC groups to be associated with acute kidney injury during the hospitalization (p < 0.01). Conclusion: Despite a strong reduction in mortality for elderly patients with ACS in recent decades, patients presenting with ACS and higher KC have a high mortality rate, as described in younger cohorts. KC remains a reliable prognostic tool, with applicability in octogenarian patients.

Resumen Objetivo: Validar el uso de la clasificación de Killip- Kimball como predictor de desenlaces en una cohorte de pacientes octogenarios con síndrome coronario agudo. Métodos: Se realizó un análisis retrospectivo de pacientes sometidos a cateterismo por síndrome coronario agudo (ACS). Se incluyeron infarto al miocardio con y sin elevación del segment ST, así como angina inestable, utilizando las definiciones de la American Heart Association (AHA). Se determinaron los factores que influyeron en la clasificación de Killip-Kimball (KC) al momento de ingreso al hospital. Se comparó la mortalidad, la estancia intrahospitalaria y otros desenlaces, dividiendo a los pacientes por su KC. Resultados: Un total de 133 pacientes se incluyeron en el análisis y se clasificaron dependiendo de su KC (I-IV). Cada grupo incluyó 86, 9, 23 y 15 pacientes, respectivamente. La edad media fue de 83 años. La mortalidad intrahospitalaria fue de 5, 11, 22 y 40%, respectivamente para cada KC, y 12% global. Hubo una diferencia significativa en la mortalidad por clase (p = 0.002). Adicionalmente, se encontró que a mayor KC, mayor riesgo de lesión renal aguda durante la hospitalización (p < 0.01). Conclusión: A pesar de una reducción en la mortalidad de adultos mayores con ACS en décadas recients, pacientes con ACS y mayor KC tienen riesgo aumentado de morir, igual que pacientes en grupos de edad menores. La KC continñua siendo una herramienta confiable para la clasificación y con utilidad pronóstica, con aplicabilidad en pacientes mayores de 80 años.

Early increase of serum ferritin among COVID-19 patients is associated with need of invasive mechanical ventilation and with in-hospital death.

BACKGROUND: COVID-19 may trigger an acute hyperinflammatory syndrome characterised by heightened levels of acute phase reactants and is associated with adverse outcomes among hospitalised individuals. The relationship between 48-hour changes in acute phase reactants and adverse outcomes is unclear. This study evaluated the relationship between change in four acute phase reactants (interleukin-6, procalcitonin, ferritin, and C-reactive protein), and the risk for in-hospital death and invasive mechanical ventilation. METHODS: A retrospective cohort among 2,523 adult patients hospitalised with COVID-19 pneumonia was conducted. Changes in IL-6, procalcitonin, ferritin, and CRP from admission to 48 h after admission were recorded. Delta was calculated using the difference in each acute phase reactant at admission and at 48-hours. Delta in acute phase reactants and the risk for in-hospital death and invasive mechanical ventilation was assessed using logistic regression models adjusting for demographics and comorbidities. RESULTS: Patients with both admission and 48-hour measurement for interleukin-6 (IL-6) (n = 541), procalcitonin (n = 828), ferritin (n = 1022), and C-reactive protein (CRP) (n = 1919) were included. Baseline characteristics were similar across all four populations. Increases in ferritin associated with a heightened risk of in-hospital death (OR 1.00032; 95%CI 1.00007- 1.00056; p < .001) and invasive mechanical ventilation (OR 1.00035; 95%CI 1.00014- 1.00055; p = .001). Therefore, for every 100 ng/mL increase in ferritin, the odds for in-hospital death and invasive mechanical ventilation increase by 3.2% and 3.5%, respectively. CONCLUSIONS: Delta in ferritin is associated with in-hospital death and invasive mechanical ventilation. Other acute phase reactants were not associated with these outcomes among COVID-19 inpatients.

Hybrid revascularization vs. coronary bypass for coronary artery disease: a systematic review and meta-analysis.

INTRODUCTION: Coronary artery bypass graft is the mainstay of treatment for multivessel coronary artery disease and is superior to percutaneous coronary intervention. Combined approaches such as hybrid coronary revascularization integrate coronary artery bypass grafting with percutaneous coronary intervention during the same procedure or weeks apart. These attempt to improve surgical morbidity and long-term outcomes. EVIDENCE ACQUISITION: Per PRISMA criteria, a systematic review of keywords "Hybrid Revascularization," "Hybrid Coronary Revascularization," "Surgical," "Surgery," "Treatment," "CABG," "HCR" and "PCI" was conducted in PubMed, EMBASE and SCOPUS. Studies comparing this technique's performance on either single or two-stage approach against traditional multiple vessel coronary artery bypass grafting were screened and analyzed for our review. EVIDENCE SYNTHESIS: Twenty-two studies totaling 6981 participants were ultimately included for analysis. Mean differences in operative time, bleeding, ventilator time and length of stay were significantly lower in the hybrid coronary revascularization group. Odds ratios in transfusions and in-hospital myocardial infarction were also lower in the hybrid coronary revascularization group. Results for in-hospital and all-cause mortality, major adverse cardiac events (MACE), stroke, reintervention, and complete revascularization were not significantly different. CONCLUSIONS: Our analysis shows hybrid coronary revascularization is a feasible alternative to traditional coronary artery bypass grafting. Short-and long-term outcomes including mortality, MACE, and postoperative morbidity are similar between both groups, while hybrid approaches are associated with decreased perioperative morbidity.

Killip-Kimball classification in octogenarians with acute coronary syndrome: An 11-year experience.

Objective: The objective of the study is to validate the use of the Killip-Kimball classification (KC) as a predictor of outcomes in an octogenarian cohort with acute coronary syndrome. Methods: A retrospective analysis of patients who underwent a catheterization procedure for acute coronary syndrome (ACS) was performed. ACS was defined as per the American Heart Association guidelines, and included ST-elevation myocardial infarction (STEMI), non-STEMI and Unstable Angina. We determined factors associated with the KC upon admission to the emergency room. Likewise, we compared in-hospital mortality, length of stay, and other outcomes dividing the patients by KC. Results: A total of 133 patients with a mean age of 83 years were analyzed and assigned a KC from 1 to 4 according to clinical presentation. Each group included 86, 9, 23, and 15 patients, respectively. In-hospital mortality was 12%, 5% in KC-I, 11% in KC-II, 22% in KC-III, and 40% in KC-IV with a significant difference between classes (p = 0.002). In addition, we found higher KC groups to be associated with acute kidney injury during the hospitalization (p < 0.01). Conclusion: Despite a strong reduction in mortality for elderly patients with ACS in recent decades, patients presenting with ACS and higher KC have a high mortality rate, as described in younger cohorts. KC remains a reliable prognostic tool, with applicability in octogenarian patients.

Objetivo: Validar el uso de la clasificación de Killip- Kimball como predictor de desenlaces en una cohorte de pacientes octogenarios con síndrome coronario agudo. Métodos: Se realizó un análisis retrospectivo de pacientes sometidos a cateterismo por síndrome coronario agudo (ACS). Se incluyeron infarto al miocardio con y sin elevación del segment ST, así como angina inestable, utilizando las definiciones de la American Heart Association (AHA). Se determinaron los factores que influyeron en la clasificación de Killip-Kimball (KC) al momento de ingreso al hospital. Se comparó la mortalidad, la estancia intrahospitalaria y otros desenlaces, dividiendo a los pacientes por su KC. Resultados: Un total de 133 pacientes se incluyeron en el análisis y se clasificaron dependiendo de su KC (I-IV). Cada grupo incluyó 86, 9, 23 y 15 pacientes, respectivamente. La edad media fue de 83 años. La mortalidad intrahospitalaria fue de 5, 11, 22 y 40%, respectivamente para cada KC, y 12% global. Hubo una diferencia significativa en la mortalidad por clase (p = 0.002). Adicionalmente, se encontró que a mayor KC, mayor riesgo de lesión renal aguda durante la hospitalización (p < 0.01). Conclusión: A pesar de una reducción en la mortalidad de adultos mayores con ACS en décadas recients, pacientes con ACS y mayor KC tienen riesgo aumentado de morir, igual que pacientes en grupos de edad menores. La KC continñua siendo una herramienta confiable para la clasificación y con utilidad pronóstica, con aplicabilidad en pacientes mayores de 80 años.

COVID-19 vaccine hesitancy and acceptance in Mexico: a web-based nationwide survey.

OBJECTIVE: To identify factors associated with COVID-19 vaccine hesitancy and acceptance among the Mexican population. METHODS: In a web-based nationwide survey in early December 2020, respondents were inquired about their sociodemographic characteristics and their willingness to accept a hypothetical COVID-19 vaccine given a 50% or 90% effectiveness. A logistic regression model was used to identify the factors associated with hesitancy and acceptance. RESULTS: A total 3 768 responses were analyzed. A 90% effective vaccine was accepted by 85% of respondents, while only 46% would accept being vaccinated with a 50% effective vaccine. In univariate analysis, each age group (40-49, 50-59, and ≥60) was strongly associated with vaccine hesitancy for a 90% effective vaccine (OR 0.48, 95% CI 0.38, 0.63; OR 0.33, 95 CI 0.26, 0.41; and OR 0.28, 95 CI 0.21, 0.38, respectively) compared to the 18-39 age group. After multivariable adjustment, similar magnitudes of association were observed. Being female and higher socioeconomic status were also associated with higher vaccine hesitancy. CONCLUSIONS: Vaccine hesitancy represents a major public health problem in Mexico and is driven by multiple factors. Our study provides relevant insights for the development of effective policies and strategies to ensure widespread vaccination in Mexico.