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Changes in composition of the intestinal microbiota are linked to the development of obesity and can lead to endothelial cell (EC) dysfunction. It is unknown whether EC can directly influence the microbiota. Insulin-like growth factor-1 (IGF-1) and its receptor (IGF-1R) are critical for coupling nutritional status and cellular growth; IGF-1R is expressed in multiple cell types including EC. The role of ECIGF-1R in the response to nutritional obesity is unexplored. To examine this, we use gene-modified mice with EC-specific overexpression of human IGF-1R (hIGFREO) and their wild-type littermates. After high-fat feeding, hIGFREO weigh less, have reduced adiposity and have improved glucose tolerance. hIGFREO show an altered gene expression and altered microbial diversity in the gut, including a relative increase in the beneficial genus Akkermansia. The depletion of gut microbiota with broad-spectrum antibiotics induces a loss of the favourable metabolic differences seen in hIGFREO mice. We show that IGF-1R facilitates crosstalk between the EC and the gut wall; this crosstalk protects against diet-induced obesity, as a result of an altered gut microbiota.
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Resistencia a la Insulina , Microbiota , Animales , Dieta Alta en Grasa/efectos adversos , Ratones , Ratones Endogámicos C57BL , Obesidad/genética , Receptor IGF Tipo 1/genéticaRESUMEN
BACKGROUND: Many diseases are associated with chronic inflammation, resulting in widening application of anti-inflammatory therapies. Although they are effective as disease-modifying agents, these anti-inflammatory therapies increase the risk of serious infection; however, it remains unknown whether chronic systemic inflammation per se is also associated with fatal infection. METHODS: Using serum C-reactive protein (CRP) data from 461 052 UK Biobank participants, we defined incidence rate ratios (IRRs) for death from infection, cardiovascular disease, or other causes and adjusted for comorbidities and the use of anti-inflammatory therapies. RESULTS: Systemic inflammation, defined as CRP ≥2â mg/L, was common in all comorbidities considered. After adjusting for confounding factors, systemic inflammation was associated with a higher IRR point estimate for infection death (1.70; 95% confidence interval [CI], 1.51-1.92) than cardiovascular (1.48; CI, 1.40-1.57) or other death (1.41; CI, 1.37-1.45), although CIs overlapped. C-reactive protein thresholds of ≥5 and ≥10â mg/L yielded similar findings, as did analyses in people with ≥2, but not <2, comorbidities. CONCLUSIONS: Systemic inflammation per se identifies people at increased risk of infection death, potentially contributing to the observed risks of anti-inflammatory therapies in clinical trials. In future clinical trials of anti-inflammatory therapies, researchers should carefully consider risks and benefits in target populations, guided by research into mechanisms of infection risk.
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Proteína C-Reactiva , Enfermedades Cardiovasculares , Antiinflamatorios , Estudios de Cohortes , Humanos , InflamaciónRESUMEN
Innate immune function is shaped by prior exposures in a phenomenon often referred to as 'memory' or 'training'. Diverse stimuli, ranging from pathogen-associated molecules to atherogenic lipoproteins, induce long-lasting training, impacting on future responses, even to distinct stimuli. It is now recognised that epigenetic modifications in innate immune cells, and their progenitors, underpin these sustained behavioural changes, and that rewired cellular metabolism plays a key role in facilitating such epigenetic marks. Oxygen is central to cellular metabolism, and cells exposed to hypoxia undergo profound metabolic rewiring. A central effector of these responses are the hypoxia inducible factors (or HIFs), which drive transcriptional programmes aiming to adapt cellular homeostasis, such as by increasing glycolysis. These metabolic shifts indirectly promote post-translational modification of the DNA-binding histone proteins, and also of DNA itself, which are retained even after cellular oxygen tension and metabolism normalise, chronically altering DNA accessibility and utilisation. Notably, the activity of HIFs can be induced in some normoxic circumstances, indicating their broad importance to cell biology, irrespective of oxygen tension. Some HIFs are implicated in innate immune training and hypoxia is present in many disease states, yet many questions remain about the association between hypoxia and training, both in health and disease. Moreover, it is now appreciated that cellular responses to hypoxia are mediated by non-HIF pathways, suggesting that other mechanisms of training may be possible. This review sets out to define what is already known about the topic, address gaps in our knowledge, and provide recommendations for future research.
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Hipoxia , Transducción de Señal , Hipoxia de la Célula , Proteínas de Unión al ADN/metabolismo , Humanos , Hipoxia/genética , Inmunidad Innata , Oxígeno/metabolismoRESUMEN
BACKGROUND: Observational studies investigating risk factors in coronavirus disease 2019 (COVID-19) have not considered the confounding effects of advanced care planning, such that a valid picture of risk for elderly, frail and multi-morbid patients is unknown. We aimed to report ceiling of care and cardiopulmonary resuscitation (CPR) decisions and their association with demographic and clinical characteristics as well as outcomes during the COVID-19 pandemic. METHODS: Retrospective, observational study conducted between 5th March and 7th May 2020 of all hospitalised patients with COVID-19. Ceiling of care and CPR decisions were documented using the Recommended Summary Plan for Emergency Care and Treatment (ReSPECT) process. Unadjusted and multivariable regression analyses were used to determine factors associated with ceiling of care decisions and death during hospitalisation. RESULTS: A total of 485 patients were included, of whom 409 (84·3%) had a documented ceiling of care; level one for 208 (50·9%), level two for 75 (18·3%) and level three for 126 (30·8%). CPR decisions were documented for 451 (93·0%) of whom 336 (74·5%) were 'not for resuscitation'. Advanced age, frailty, White-European ethnicity, a diagnosis of any co-morbidity and receipt of cardiovascular medications were associated with ceiling of care decisions. In a multivariable model only advanced age (odds 0·89, 0·86-0·93 p < 0·001), frailty (odds 0·48, 0·38-0·60, p < 0·001) and the cumulative number of co-morbidities (odds 0·72, 0·52-1·0, p = 0·048) were independently associated. Death during hospitalisation was independently associated with age, frailty and requirement for level two or three care. CONCLUSION: Ceiling of care decisions were made for the majority of patients during the COVID-19 pandemic, broadly in line with known predictors of poor outcomes in COVID-19, but with a focus on co-morbidities suggesting ICU admission might not be a reliable end-point for observational studies where advanced care planning is routine.
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Planificación Anticipada de Atención , COVID-19/terapia , Toma de Decisiones Clínicas , Adulto , Anciano , Anciano de 80 o más Años , Reanimación Cardiopulmonar , Femenino , Humanos , Cuidados para Prolongación de la Vida , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
INTRODUCTION: The adult congenital heart disease (ACHD) population is rapidly expanding. However, a significant proportion of these patients suffer sudden cardiac death. Recommending implantable cardioverter-defibrillator (ICD) insertion requires balancing the need for appropriate therapy in malignant arrhythmia against the consequences of inappropriate therapy and procedural complications. Here we present long-term follow-up data for ICD insertion in patients with ACHD from a large Level 1 congenital cardiac center. METHODS AND RESULTS: All patients with ACHD undergoing ICD insertion over an 18-year period were identified. Data were extracted for baseline characteristics including demographics, initial diagnosis, ventricular function, relevant medication, and indication for ICD insertion. Details regarding device insertion were gathered along with follow-up data including appropriate and inappropriate therapy and complications. A total of 136 ICDs were implanted during this period: 79 for primary and 57 for secondary prevention. The most common congenital cardiac conditions in both groups were tetralogy of Fallot and transposition of the great arteries. Twenty-two individuals in the primary prevention group received appropriate antitachycardia pacing (ATP), 14 underwent appropriate cardioversion, 17 received inappropriate ATP, and 15 received inappropriate cardioversion. In the secondary prevention group, 18 individuals received appropriate ATP, 8 underwent appropriate cardioversion, 8 received inappropriate ATP, and 7 were inappropriately cardioverted. Our data demonstrate low complication rates, particularly with leads without advisories. CONCLUSION: ICD insertion in the ACHD population involves a careful balance of the risks and benefits. Our data show a significant proportion of patients receiving appropriate therapy indicating that ICDs were inserted appropriately.
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Desfibriladores Implantables , Cardiopatías Congénitas , Transposición de los Grandes Vasos , Adulto , Muerte Súbita Cardíaca/epidemiología , Muerte Súbita Cardíaca/prevención & control , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/terapia , Humanos , Sistema de RegistrosRESUMEN
PURPOSE: Low 25-hydroxyvitamin D (25[OH]D) concentrations have been associated with adverse outcomes in selected populations with established chronic heart failure (CHF). However, it remains unclear whether 25[OH]D deficiency is associated with mortality and hospitalisation in unselected patients receiving contemporary medical and device therapy for CHF. METHODS: We prospectively examined the prevalence and correlates of 25[OH]D deficiency in 1802 ambulatory patients with CHF due to left ventricular systolic dysfunction (left ventricular ejection fraction ≤ 45%) attending heart failure clinics in the north of England. RESULTS: 73% of patients were deficient in 25[OH]D (< 50 nmol/L). 25[OH]D deficiency was associated with male sex, diabetes, lower serum sodium, higher heart rate, and greater diuretic requirement. During a mean follow-up period of 4 years, each 2.72-fold increment in 25[OH]D concentration (for example from 32 to 87 nmol/L) is associated with 14% lower all-cause mortality (95% confidence interval (CI) 1, 26%; p = 0.04), after accounting for potential confounding factors. CONCLUSIONS: Low 25-hydroxyvitamin D deficiency is associated with increased mortality in patients with chronic heart failure due to left ventricular systolic dysfunction. Whether vitamin D supplementation will improve outcomes is, as yet, unproven.
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Insuficiencia Cardíaca/mortalidad , Deficiencia de Vitamina D/mortalidad , Anciano , Enfermedad Crónica , Estudios de Cohortes , Comorbilidad , Inglaterra/epidemiología , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/sangre , Humanos , Masculino , Prevalencia , Estudios Prospectivos , Factores Sexuales , Vitamina D/análogos & derivados , Vitamina D/sangre , Deficiencia de Vitamina D/sangreRESUMEN
BACKGROUND: The Surprise Question, 'Would you be surprised if this person died within the next year?' is a simple tool that can be used by clinicians to identify people within the last year of life. This review aimed to determine the accuracy of this assessment, across different healthcare settings, specialties, follow-up periods and respondents. METHODS: Searches were conducted of Medline, Embase, AMED, PubMed and the Cochrane Central Register of Controlled Trials, from inception until 01 January 2024. Studies were included if they reported original data on the ability of the Surprise Question to predict survival. For each study (including subgroups), sensitivity, specificity, positive and negative predictive values and accuracy were determined. RESULTS: Our dataset comprised 56 distinct cohorts, including 68 829 patients. In a pooled analysis, the sensitivity of the Surprise Question was 0.69 ((0.64 to 0.74) I2=97.2%), specificity 0.69 ((0.63 to 0.74) I2=99.7%), positive predictive value 0.40 ((0.35 to 0.45) I2=99.4%), negative predictive value 0.89 ((0.87 to 0.91) I2=99.7%) and accuracy 0.71 ((0.68 to 0.75) I2=99.3%). The prompt performed best in populations with high event rates, shorter timeframes and when posed to more experienced respondents. CONCLUSIONS: The Surprise Question demonstrated modest accuracy with considerable heterogeneity across the population to which it was applied and to whom it was posed. Prospective studies should test whether the prompt can facilitate timely access to palliative care services, as originally envisioned. PROSPERO REGISTRATION NUMBER: CRD32022298236.
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INTRODUCTION: Type 2 diabetes is a common and adverse prognostic co-morbidity for patients with heart failure with reduced ejection fraction (HFrEF). The effect of diabetes on long-term outcomes for heart failure with preserved ejection fraction (HFpEF) is less established. METHODS: Prospective cohort study of patients referred to a regional HF clinic with newly diagnosed with HFrEF and HFpEF according to the 2016 European Society of Cardiology guidelines. The association between diabetes, all-cause mortality and hospitalisation was quantified using Kaplan-Meier or Cox regression analysis. RESULTS: Between 1st May 2012 and 1st May 2013, of 960 unselected consecutive patients referred with suspected HF, 464 and 314 patients met the criteria for HFpEF and HFrEF respectively. Within HFpEF and HFrEF groups, patients with diabetes were more frequently male and in both groups patients with diabetes were more likely to be treated with ß-adrenoceptor antagonists and angiotensin converting enzyme inhibitors. After adjustment for age, sex, medical therapy and co-morbidities, diabetes was associated with increased mortality in individuals with HFrEF (HR 1.46 95% CI: 1.05-2.02; p = .023), but not in those with HFpEF (HR 1.26 95% CI 0.92-1.72; p = .146). CONCLUSION: In unselected patients with newly diagnosed HF, diabetes is not an adverse prognostic marker in patients with HFpEF, but is in HFrEF.
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Diabetes Mellitus Tipo 2 , Insuficiencia Cardíaca , Humanos , Masculino , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Estudios Prospectivos , Volumen Sistólico/fisiología , Progresión de la Enfermedad , Pronóstico , HospitalizaciónRESUMEN
AIMS: Diabetes mellitus (DM) increases heart failure incidence and worsens prognosis, but its molecular basis is poorly defined in humans. We aimed to define the diabetic myocardial transcriptome and validate hits in their circulating protein form to define disease mechanisms and biomarkers. METHODS AND RESULTS: RNA-sequencing data from the Genotype-Tissue Expression (GTEx) project was used to define differentially expressed genes (DEGs) in right atrial (RA) and left ventricular (LV) myocardium from people with versus without DM (type 1 or 2). DEGs were validated as plasma proteins in the UK Biobank cohort, searching for directionally concordant differential expression. Validated plasma proteins were characterized in UK Biobank participants, irrespective of diabetes status, using cardiac magnetic resonance imaging, incident heart failure and cardiovascular mortality.We found 32 and 32 DEGs associated with DM in the RA and LV, respectively, with no overlap between these. Plasma proteomic data was available for 12, with ERBB3, NRXN3 and HSPA2 (all LV hits) exhibiting directional concordance. Irrespective of DM status, lower circulating ERBB3 and higher HSPA2 were associated with impaired left ventricular contractility and higher LV mass. Participants in the lowest quartile of circulating ERBB3 or highest quartile of circulating HSPA2 had increased incident heart failure and cardiovascular death vs. all other quartiles. CONCLUSIONS: DM is characterized by lower Erbb3 and higher Hspa2 expression in the myocardium, with directionally concordant differences in their plasma protein concentration. These are associated with left ventricular dysfunction, incident heart failure and cardiovascular mortality.
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AIMS: Current guidelines recommend that disease-modifying pharmacological therapies may be considered for patients who have heart failure with mildly reduced ejection fraction (HFmrEF). We aimed to describe the characteristics, outcomes, provision of pharmacological therapies and dose-related associations with mortality risk in HFmrEF. METHODS AND RESULTS: We explored data from two prospective observational studies, which permitted the examination of the effects of pharmacological therapies across a broad spectrum of left ventricular ejection fraction (LVEF). The combined dataset consisted of 2388 unique patients, with a mean age of 73.7 ± 13.2 years of whom 1525 (63.9%) were male. LVEF ranged from 5 to 71% (mean 37.2 ± 12.8%) and 1504 (63.0%) were categorised as having reduced ejection fraction (HFrEF), 421 (17.6%) as HFmrEF and 463 (19.4%) as preserved ejection fraction (HFpEF). Patients with HFmrEF more closely resembled HFrEF than HFpEF. Adjusted all-cause mortality risk was lower in HFmrEF (hazard ratio [HR] 0.86 (95% confidence interval [CI] 0.74-0.99); p = 0.040) and in HFpEF (HR 0.61 (95% CI 0.52-0.71); p < 0.001) compared to HFrEF. Adjusted all-cause mortality risk was lower in patients with HFrEF and HFmrEF who received the highest doses of beta-blockers or renin-angiotensin inhibitors. These associations were not evident in HFpEF. Once adjusted for relevant confounders, each mg equivalent of bisoprolol (HR 0.95 [95% CI 0.91-1.00]; p = 0.047) and ramipril (HR 0.95 [95%CI 0.90-1.00]; p = 0.044) was associated with incremental reductions in mortality risk in patients with HFmrEF. CONCLUSIONS: Pharmacological therapies were associated with lower mortality risk in HFmrEF, supporting guideline recommendations which extend the indications of these agents to all patients with LVEF < 50%. HFmrEF more closely resembles HFrEF in terms of clinical characteristics and outcomes. Pharmacological therapies are associated with lower mortality risk in HFmrEF and HFrEF, but not in HFpEF.
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Insuficiencia Cardíaca , Disfunción Ventricular Izquierda , Humanos , Masculino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Femenino , Volumen Sistólico , Función Ventricular Izquierda , PronósticoRESUMEN
OBJECTIVE: Obesity and diabetes frequently coexist, yet their individual contributions to cardiovascular risk remain debated. We explored cardiovascular disease biomarkers, events, and mortality in the UK Biobank stratified by BMI and diabetes. RESEARCH DESIGN AND METHODS: A total of 451,355 participants were stratified by ethnicity-specific BMI categories (normal, overweight, obese) and diabetes status. We examined cardiovascular biomarkers including carotid intima-media thickness (CIMT), arterial stiffness, left ventricular ejection fraction (LVEF), and cardiac contractility index (CCI). Poisson regression models estimated adjusted incidence rate ratios (IRRs) for myocardial infarction, ischemic stroke, and cardiovascular death, with normal-weight nondiabetes as comparator. RESULTS: Five percent of participants had diabetes (10% normal weight, 34% overweight, and 55% obese vs. 34%, 43%, and 23%, respectively, without diabetes). In the nondiabetes group, overweight/obesity was associated with higher CIMT, arterial stiffness, and CCI and lower LVEF (P < 0.005); these relationships were diminished in the diabetes group. Within BMI classes, diabetes was associated with adverse cardiovascular biomarker phenotype (P < 0.005), particularly in the normal-weight group. After 5,323,190 person-years follow-up, incident myocardial infarction, ischemic stroke, and cardiovascular mortality rose across increasing BMI categories without diabetes (P < 0.005); this was comparable in the diabetes groups (P-interaction > 0.05). Normal-weight diabetes had comparable adjusted cardiovascular mortality to obese nondiabetes (IRR 1.22 [95% CI 0.96-1.56]; P = 0.1). CONCLUSIONS: Obesity and diabetes are additively associated with adverse cardiovascular biomarkers and mortality risk. While adiposity metrics are more strongly correlated with cardiovascular biomarkers than diabetes-oriented metrics, both correlate weakly, suggesting that other factors underpin the high cardiovascular risk of normal-weight diabetes.
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Enfermedades Cardiovasculares , Diabetes Mellitus , Accidente Cerebrovascular Isquémico , Infarto del Miocardio , Humanos , Enfermedades Cardiovasculares/etiología , Sobrepeso/complicaciones , Estudios de Cohortes , Grosor Intima-Media Carotídeo , Bancos de Muestras Biológicas , Volumen Sistólico , Factores de Riesgo , Índice de Masa Corporal , Función Ventricular Izquierda , Obesidad/epidemiología , Infarto del Miocardio/complicaciones , Fenotipo , Biomarcadores , Accidente Cerebrovascular Isquémico/complicaciones , Reino Unido/epidemiologíaRESUMEN
AIMS: Optimal management of heart failure with reduced ejection fraction (HFrEF) includes titration of guideline-directed medical therapy (GDMT) to the highest tolerated dose within the licensed range. During hospitalization, GDMT doses are often significantly altered, although it is unknown whether the cause of hospitalization influences this. METHODS AND RESULTS: We recruited 711 people with stable HFrEF from specialist heart failure clinics and prospectively assessed events occurring during first unplanned hospitalization. Dose changes of ACE inhibitors or angiotensin receptor blockers (ACEi/ARB), beta-blockers, mineralocorticoid receptor antagonists, and loop diuretics were recorded during 414 hospitalizations, categorized as due to decompensated heart failure, other cardiovascular causes, infection, or other non-cardiovascular causes. Most hospitalizations resulted in no change to GDMT. ACEi/ARB dose was reduced in 21% of hospitalizations and was more common during non-cardiovascular hospitalization (25.4% vs. 13.9%; P = 0.005). ACEi/ARB dose reduction was associated with older age and lower left ventricular ejection fraction at study recruitment, and poorer renal function, lower systolic blood pressure, higher serum potassium, and less frequent care from a cardiologist during admission. People experiencing ACEi/ARB reduction had worse age-adjusted survival after discharge, without differences in heart failure re-hospitalization. De-escalation of beta-blockers occurred in 8% of hospitalizations, most often due to other non-cardiovascular causes; this was not associated with post-discharge survival or re-hospitalization with heart failure. CONCLUSIONS: De-escalation of HFrEF GDMT is more common during non-cardiovascular hospitalization and for ACEi/ARB is associated with reduced survival. Post-discharge care plans should include robust plans to consider re-escalation of GDMT in these cases.
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Insuficiencia Cardíaca , Humanos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/epidemiología , Antagonistas de Receptores de Angiotensina/uso terapéutico , Volumen Sistólico/fisiología , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Cuidados Posteriores , Prevalencia , Función Ventricular Izquierda , Alta del Paciente , Hospitalización , Antagonistas Adrenérgicos beta/uso terapéutico , Factores de RiesgoRESUMEN
INTRODUCTION: Diabetes mellitus (DM) is associated with increased risk of hospitalisation in people with heart failure and reduced ejection fraction (HFrEF). However, little is known about the causes of these events. METHODS: Prospective cohort study of 711 people with stable HFrEF. Hospitalisations were categorised by cause as: decompensated heart failure; other cardiovascular; infection or other non-cardiovascular. Rates of hospitalisation and burden of hospitalisation (percentage of follow-up time in hospital) were compared in people with and without DM. RESULTS: After a mean follow-up of 4.0 years, 1568 hospitalisations occurred in the entire cohort. DM (present in 32% [n=224]) was associated with a higher rate (mean 1.07 vs 0.78 per 100 patient-years; p<0.001) and burden (3.4 vs 2.2% of follow-up time; p<0.001) of hospitalisation. Cause-specific analyses revealed increased rate and burden of hospitalisation due to decompensated heart failure, other cardiovascular causes and infection in people with DM, whereas other non-cardiovascular causes were comparable. Infection made the largest contribution to the burden of hospitalisation in people with and without DM. CONCLUSIONS: In people with HFrEF, DM is associated with a greater burden of hospitalisation due to decompensated heart failure, other cardiovascular events and infection, with infection making the largest contribution.
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Diabetes Mellitus , Insuficiencia Cardíaca , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiología , Diabetes Mellitus/terapia , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/terapia , Hospitalización , Humanos , Estudios Prospectivos , Volumen SistólicoRESUMEN
AIMS: Understanding of the pathophysiology of progressive heart failure (HF) in patients with heart failure with preserved ejection fraction (HFpEF) is incomplete. We sought to identify factors differentially associated with risk of progressive HF death and hospitalization in patients with HFpEF compared with patients with HF and reduced ejection fraction (HFrEF). METHODS AND RESULTS: Prospective cohort study of patients newly referred to secondary care with suspicion of HF, based on symptoms and signs of HF and elevated natriuretic peptides (NP), followed up for a minimum of 6 years. HFpEF and HFrEF were diagnosed according to the 2016 European Society of Cardiology guidelines. Of 960 patients referred, 467 had HFpEF (49%), 311 had HFrEF (32%), and 182 (19%) had neither. Atrial fibrillation (AF) was found in 37% of patients with HFpEF and 34% with HFrEF. During 6 years follow-up, 19% of HFrEF and 14% of HFpEF patients were hospitalized or died due to progressive HF, hazard ratio (HR) 0.67 (95% CI: 0.47-0.96; P = 0.028). AF was the only marker that was differentially associated with progressive HF death or hospitalization in patients with HFpEF HR 2.58 (95% CI: 1.59-4.21; P < 0.001) versus HFrEF HR 1.11 (95% CI: 0.65-1.89; P = 0.7). CONCLUSIONS: De novo patients diagnosed with HFrEF have greater risk of death or hospitalization due to progressive HF than patients with HFpEF. AF is associated with increased risk of progressive HF death or hospitalization in HFpEF but not HFrEF, raising the intriguing possibility that this may be a novel therapeutic target in this growing population.
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Fibrilación Atrial , Insuficiencia Cardíaca Diastólica , Insuficiencia Cardíaca , Humanos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/epidemiología , Volumen Sistólico/fisiología , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/diagnóstico , Estudios Prospectivos , Pronóstico , Insuficiencia Cardíaca Diastólica/complicacionesRESUMEN
Background Therapeutic advances have reduced cardiovascular death rates in people with cardiovascular diseases (CVD). We aimed to define the rates of cardiovascular and noncardiovascular death in people with specified CVDs or accruing cardiovascular multimorbidity. Methods and Results We studied 493 280 UK residents enrolled in the UK Biobank cohort study. The proportion of deaths attributed to cardiovascular, cancer, infection, or other causes were calculated in groups defined by 9 distinct self-reported CVDs at baseline, or by the number of these CVDs at baseline. Poisson regression analyses were then used to define adjusted incidence rate ratios for these causes of death, accounting for sociodemographic factors and comorbidity. Of 27 729 deaths, 20.4% were primarily attributed to CVD, 53.6% to cancer, 5.0% to infection, and 21.0% to other causes. As cardiovascular multimorbidity increased, the proportion of cardiovascular and infection-related deaths was greater, contrasting with cancer and other deaths. Compared with people without CVD, those with 3 or more CVDs experienced adjusted incidence rate ratios of 7.0 (6.2-7.8) for cardiovascular death, 4.4 (3.4-5.6) for infection death, 1.5 (1.4-1.7) for cancer death, and 2.0 (1.7-2.4) for other causes of death. There was substantial heterogeneity in causes of death, both in terms of crude proportions and adjusted incidence rate ratios, among the 9 studied baseline CVDs. Conclusions Noncardiovascular death is common in people with CVD, although its contribution varies widely between people with different CVDs. Holistic and personalized care are likely to be important tools for continuing to improve outcomes in people with CVD.
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Enfermedades Cardiovasculares , Bancos de Muestras Biológicas , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/mortalidad , Causas de Muerte , Estudios de Cohortes , Humanos , Factores de Riesgo , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Non-communicable diseases (NCDs) have been highlighted as important risk factors for COVID-19 mortality. However, insufficient data exist on the wider context of infectious diseases in people with NCDs. We aimed to investigate the association between NCDs and the risk of death from any infection before the COVID-19 pandemic (up to Dec 31, 2019). METHODS: For this observational study, we used data from the UK Biobank observational cohort study to explore factors associated with infection death. We excluded participants if data were missing for comorbidities, body-mass index, smoking status, ethnicity, and socioeconomic deprivation, and if they were lost to follow-up or withdrew consent. Deaths were censored up to Dec 31, 2019. We used Poisson regression models including NCDs present at recruitment to the UK Biobank (obesity [defined by use of body-mass index] and self-reported hypertension, chronic heart disease, chronic respiratory disease, diabetes, cancer, chronic liver disease, chronic kidney disease, previous stroke or transient ischaemic attack, other neurological disease, psychiatric disorder, and chronic inflammatory and autoimmune rheumatological disease), age, sex, ethnicity, smoking status, and socioeconomic deprivation. Separate models were constructed with individual NCDs replaced by the total number of prevalent NCDs to define associations with multimorbidity. All analyses were repeated with non-infection-related death as an alternate outcome measure to establish differential associations of infection death and non-infection death. Associations are reported as incidence rate ratios (IRR) accompanied by 95% CIs. FINDINGS: After exclusion of 9210 (1·8%) of the 502â505 participants in the UK Biobank cohort, our study sample comprised 493â295 individuals. During 5â273â731 person-years of follow-up (median 10·9 years [IQR 10·1-11·6] per participant), 27â729 deaths occurred, of which 1385 (5%) were related to infection. Advancing age, male sex, smoking, socioeconomic deprivation, and all studied NCDs were independently associated with the rate of both infection death and non-infection death. Compared with White ethnicity, a pooled Black, Asian, and minority ethnicity group was associated with a reduced risk of infection death (IRR 0·64, 95% CI 0·46-0·87) and non-infection death (0·80, 0·75-0·86). Stronger associations with infection death than with non-infection death were observed for advancing age (age 65 years vs 45 years: 7·59, 95% CI 5·92-9·73, for infection death vs 5·21, 4·97-5·48, for non-infection death), current smoking (vs never smoking: 3·69, 3·19-4·26, vs 2·52, 2·44-2·61), socioeconomic deprivation (most vs least deprived quintile: 2·13, 1·78-2·56, vs 1·38, 1·33-1·43), class 3 obesity (vs non-obese: 2·21, 1·74-2·82, vs 1·55, 1·44-1·66), hypertension (1·36, 1·22-1·53, vs 1·15, 1·12-1·18), respiratory disease (2·21, 1·96-2·50, vs 1·28, 1·24-1·32), chronic kidney disease (5·04, 4·28-7·31, vs 2·50, 2·20-2·84), psychiatric disease (1·56, 1·30-1·86, vs 1·23, 1·18-1·29), and chronic inflammatory and autoimmune rheumatological disease (2·45, 1·99-3·02, vs 1·41, 1·32-1·51). Accrual of multimorbidity was also more strongly associated with risk of infection death (five or more comorbidities vs none: 9·53, 6·97-13·03) than of non-infection death (5·26, 4·84-5·72). INTERPRETATION: Several NCDs are associated with an increased risk of infection death, suggesting that some of the reported associations with COVID-19 mortality might be non-specific. Only a subset of NCDs, together with the accrual of multimorbidity, advancing age, smoking, and socioeconomic deprivation, were associated with a greater IRR for infection death than for other causes of death. Further research is needed to define why these risk factors are more strongly associated with infection death, so that more effective preventive strategies can be targeted to high-risk groups. FUNDING: British Heart Foundation.
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Bancos de Muestras Biológicas , COVID-19/etiología , Enfermedades no Transmisibles , SARS-CoV-2 , Adulto , Anciano , COVID-19/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Factores SocioeconómicosRESUMEN
AIMS: In patients with chronic heart failure, QRS duration is a consistent predictor of poor outcomes. It has been suggested that for indicated patients, cardiac resynchronization therapy (CRT) could come sooner in the treatment algorithm, perhaps in parallel with the attainment of optimal guideline-directed medical therapy (GDMT). We aimed to investigate differences in left ventricular (LV) remodelling in those with narrow QRS (NQRS) compared with wide QRS (WQRS) in the absence of CRT, whether an early CRT strategy resulted in unnecessary implants and the effect of early CRT on outcomes. METHODS: Our cohort consisted of 214 consecutive patients with LV ejection fraction (LVEF) of 35% or less who underwent repeat echocardiography 1 year after enrolment. Of these, 116 patients had NQRS, and 98 had WQRS of whom 40 received CRT within 1 year and 58 did not. RESULTS: In the absence of CRT, patients with WQRS had less LV reverse remodelling compared with those with NQRS, with differences in ΔLVEF (+2 vs. +9%, Pâ<â0.001) ΔLV end-diastolic diameter (-1 vs. -2âmm, Pâ=â0.095), ΔLV end-systolic diameter (-2 vs. -4.5âmm, Pâ=â0.038), LV end-systolic volume (-12.6 vs. -25.0âml, Pâ=â0.054) and LV end-diastolic volume (-7.3 vs. -12.2âml, Pâ=â0.071). LVEF was more likely to improve by at least 10% if patients had NQRS or received CRT (Pâ=â0.08). Thirteen (24%) patients with WQRS achieved an LVEF greater than 35% in the absence of CRT; however, none achieved greater than 50%. CONCLUSION: A strictly linear approach to heart failure therapy might lead to delays to optimal treatment in those patients with the most to gain from CRT and the least to gain from GDMT.
Asunto(s)
Electrocardiografía/métodos , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/terapia , Remodelación Ventricular/fisiología , Anciano , Terapia de Resincronización Cardíaca/métodos , Ecocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Volumen Sistólico/fisiología , Resultado del Tratamiento , Función Ventricular Izquierda/fisiologíaRESUMEN
INTRODUCTION: We aimed to evaluate the relationship between temporal changes in renal function and long-term mortality in patients with heart failure with reduced ejection fraction (HFrEF) and identify correlates of deteriorating renal function. METHODS: A total of 381 patients with HFrEF enrolled in a prospective cohort study between 2006-2014 had eGFR measured at initial visit and at 1 year. Baseline characteristics were used in a multivariate analysis to establish variables that predict deterioration in eGFR. Follow-up data were used to assess whether declining eGFR was related to outcomes. RESULTS: Patients were grouped into tertiles based on percentage change in eGFR. In a multivariate logistic regression analysis, male sex was associated with a 1.77-fold ([95% CI 1.01-2.89]; p = 0.045) and diabetes a 1.66-fold ([95% CI 1.02-2.70]; p = 0.041) greater risk of a decline in eGFR compared to those with stable/improving eGFR. Declining eGFR was associated with a 1.4-fold greater risk of death over 10 years ([95% CI 1.08-1.86]; p = 0.01) and a 3.12-fold ([1.44-6.75]; p = 0.004) greater risk of death at 1 year from second eGFR measurement. CONCLUSIONS: In patients with HFrEF diabetes and male sex are independent predictors of a decline in eGFR at 1 year. A decline eGFR over 1 year is associated with higher long-term all-cause mortality.