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OBJECTIVE: The impact of comprehensive risk factor control on heart failure (HF) risk and HF-free survival time in individuals with type 2 diabetes (T2D) was evaluated in this study. RESEARCH DESIGN AND METHODS: This prospective study included 11,949 individuals diagnosed with T2D, matched with 47,796 non-T2D control study participants from the UK Biobank cohort. The degree of comprehensive risk factor control was assessed on the basis of the major cardiovascular risk factors, including blood pressure, BMI, LDL cholesterol, hemoglobin A1c, renal function, smoking, diet, and physical activity. Cox proportional hazards models were used to measure the associations between the degree of risk factor control and HF risk. Irwin's restricted mean was used to evaluate HF-free survival time. RESULTS: During a median follow-up of 12.3 years, 702 individuals (5.87%) with T2D and 1,402 matched control participants (2.93%) developed HF. Each additional risk factor controlled was associated with an average 19% lower risk of HF. Optimal control of at least six risk factors was associated with a 67% lower HF risk (hazard ratio [HR] 0.33; 95% CI 0.20, 0.54). BMI was the primary attributable risk factor for HF. Notably, the excess risk of HF associated with T2D could be attenuated to levels comparable to those of non-T2D control participants when individuals had a high degree of risk factor control (HR 0.66; 95% CI 0.40, 1.07), and they exhibited a longer HF-free survival time. CONCLUSIONS: Comprehensive management of risk factors is inversely associated with HF risk, and optimal risk factor control may prolong HF-free survival time among individuals with T2D.
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BACKGROUND: Ideal cardiovascular health (CVH) has been associated with reduced cardiovascular disease risk and mortality, but its association with cardiac arrhythmias were still unsettled. In this prospective cohort study, we investigated the relationship between CVH and subsequent arrhythmias risk, including atrial fibrillation/flutter (AF), ventricular arrhythmias, and bradyarrhythmias. METHODS: Data from 287,264 participants initially free of arrhythmias in the UK Biobank were included in the analysis. Cox regression models were used to examine the relationship between CVH levels calculated by the American Heart Association's Life's Essential 8 (LE8) metrics, with cardiac arrhythmias risk. RESULTS: During a median follow-up period of 12.8 years, 16,802 incident AF, 2186 incident ventricular arrhythmias, and 4128 incident bradyarrhythmias were identified. After adjustment for confounding factors, participants with high initial CVH levels had a significantly lower risk for AF (HR 0.63, 95% CI 0.59-0.68), ventricular arrhythmias (HR 0.48, 95% CI 0.40-0.59), and bradyarrhythmias (HR 0.64, 95% CI 0.55-0.74) compared to those with low CVH levels. Furthermore, each SD increase in LE8 scores was associated with a 15% lower risk of AF, 21% for ventricular arrhythmias, and 13% for bradyarrhythmias, respectively. Additionally, a significant interaction was observed between CVH levels and the genetic risk of AF (P for interaction, 0.021). The reverse correlation seemed to be more noticeable in individuals with a lower genetic susceptibility to AF. CONCLUSIONS: We concluded that higher levels of CVH, estimated by the LE8 metrics, were associated with significantly reduced risks of AF, ventricular arrhythmias, and bradyarrhythmias.
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RATIONALE: The disruption of the balance between fatty acid (FA) uptake and oxidation (FAO) leads to cardiac lipotoxicity, serving as the driving force behind diabetic cardiomyopathy (DbCM). Sirtuin 5 (Sirt5), a lysine de-succinylase, could impact diverse metabolic pathways, including FA metabolism. Nevertheless, the precise roles of Sirt5 in cardiac lipotoxicity and DbCM remain unknown. OBJECTIVE: This study aims to elucidate the role and underlying mechanism of Sirt5 in the context of cardiac lipotoxicity and DbCM. METHODS AND RESULTS: The expression of myocardial Sirt5 was found to be modestly elevated in diabetic heart failure patients and mice. Cardiac dysfunction, hypertrophy and lipotoxicity were exacerbated by ablation of Sirt5 but improved by forced expression of Sirt5 in diabetic mice. Notably, Sirt5 deficiency impaired FAO without affecting the capacity of FA uptake in the diabetic heart, leading to accumulation of FA intermediate metabolites, which mainly included medium- and long-chain fatty acyl-carnitines. Mechanistically, succinylomics analyses identified carnitine palmitoyltransferase 2 (CPT2), a crucial enzyme involved in the reconversion of fatty acyl-carnitines to fatty acyl-CoA and facilitating FAO, as the functional succinylated substrate mediator of Sirt5. Succinylation of Lys424 in CPT2 was significantly increased by Sirt5 deficiency, leading to the inactivation of its enzymatic activity and the subsequent accumulation of fatty acyl-carnitines. CPT2 K424R mutation, which mitigated succinylation modification, counteracted the reduction of enzymatic activity in CPT2 mediated by Sirt5 deficiency, thereby attenuating Sirt5 knockout-induced FAO impairment and lipid deposition. CONCLUSIONS: Sirt5 deficiency impairs FAO, leading to cardiac lipotoxicity in the diabetic heart through the succinylation of Lys424 in CPT2. This underscores the potential roles of Sirt5 and CPT2 as therapeutic targets for addressing DbCM.
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Carnitina O-Palmitoiltransferasa , Cardiomiopatías Diabéticas , Ácidos Grasos , Metabolismo de los Lípidos , Miocitos Cardíacos , Sirtuinas , Animales , Cardiomiopatías Diabéticas/metabolismo , Cardiomiopatías Diabéticas/genética , Cardiomiopatías Diabéticas/patología , Carnitina O-Palmitoiltransferasa/metabolismo , Carnitina O-Palmitoiltransferasa/genética , Sirtuinas/metabolismo , Sirtuinas/genética , Ratones , Ácidos Grasos/metabolismo , Miocitos Cardíacos/metabolismo , Humanos , Masculino , Oxidación-Reducción , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/complicacionesRESUMEN
BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia with high morbidity and mortality implications. Several studies have described a paradoxical inverse relationship between serum cholesterol and the risk of AF, but it remains unknown whether remnant cholesterol (RC) is associated with AF incidence. OBJECTIVE: This study aims to prospectively investigate the association between RC and AF. METHODS: A total of 392,783 participants free of AF at baseline from the UK Biobank were included for the analysis. Cox proportional hazards model, subgroup analysis, and sensitivity analyses were used to evaluate the independent association between RC levels and the risk of new-onset AF. Furthermore, we performed a discordance analysis by using the median cutoff points of low-density lipoprotein cholesterol (LDL-C) and RC. RESULTS: After a median follow-up of 12.8 years (interquartile range 12.0-13.6 years), a total of 23,558 participants experienced incident AF. Compared with the highest RC level, the lower RC level was associated with an increased risk of AF incidence (quartile 1 vs quartile 4: hazard ratio 1.396; 95% confidence interval [CI] 1.343-1.452). The results remained robust across a series of sensitivity analyses. In the discordance analyses, a significantly higher risk of AF was observed in participants with discordant low RC/high LDL-C levels than in those with concordant high RC/LDL-C levels. In the low LDL-C group, RC reduction even contributed to an additional 15.8% increased rate of incident AF (low RC/low LDL-C: hazard ratio 1.303; 95% CI 1.260-1.348 vs high RC/low LDL-C: hazard ratio 1.125; 95% CI 1.079-1.172). CONCLUSION: Low RC levels were associated with an increased risk of incident AF independent of traditional cardiovascular risk factors.
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Fibrilación Atrial , Colesterol , Humanos , Fibrilación Atrial/epidemiología , Fibrilación Atrial/sangre , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Incidencia , Colesterol/sangre , Factores de Riesgo , Reino Unido/epidemiología , Estudios de Seguimiento , LDL-Colesterol/sangre , Anciano , Medición de Riesgo/métodos , Biomarcadores/sangreRESUMEN
The original version of this article (Liu et al., 2021) unfortunately contained a mistake: statement of equal contribution is missing. This correction article shows that Chiyu LIU and Sixu CHEN contributed equally to this work. The original article has been corrected.
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Osteoporosis is a significant health concern. While multiple techniques have been utilized to diagnose this condition, certain limitations still persist. Raman spectroscopy has shown promise in predicting bone strength in animal models, but its application to humans requires further investigation. In this study, we present an in vitro approach for predicting osteoporosis in 10 patients with hip fractures using Raman spectroscopy. Raman spectra were acquired from exposed femoral heads collected during surgery. Employing a leave-one-out cross-validated linear discriminant analysis (LOOCV-LDA), we achieved accurate classification (90 %) between osteoporotic and osteopenia groups. Additionally, a LOOCV partial least squares regression (PLSR) analysis based on the complete Raman spectra demonstrated a significant prediction (r2 = 0.84, p < 0.05) of bone mineral density as measured by dual X-ray absorptiometry (DXA). To the best of our knowledge, this study represents the first successful demonstration of Raman spectroscopy correlating with osteoporotic status in humans.
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Fracturas de Cadera , Osteoporosis , Animales , Humanos , Espectrometría Raman , Osteoporosis/diagnóstico , Densidad Ósea , Absorciometría de Fotón/métodosRESUMEN
BACKGROUND AND AIMS: The associations between dietary vitamin C (VC), vitamin E (VE) intake and aortic aneurysm and dissection (AAD) remain unclear. This study aimed to prospectively investigate the associations between dietary VC and VE with the incident risk of AAD. METHODS AND RESULTS: A total of 139 477 participants of UK Biobank cohort were included in the analysis. Dietary VC and VE consumptions were acquired through a 24-h recall questionnaire. Cox proportional regression models were used to examine the associations between VC, VE intake and the risk of AAD. Incident AAD was ascertained through hospital inpatient records and death registers. During a median follow-up of 12.5 years, 962 incident AAD events were documented. Both dietary VC [adjusted hazard ratio (HR), 0.77; 95 % confidence intervals (CI), 0.63-0.93; P-trend = 0.008] and VE (adjusted HR, 0.70; 95 % CI, 0.57-0.87; P-trend = 0.002) were inversely associated with incident AAD when comparing the participants in the highest quartile with those in the lowest. In subgroup analyses, the associations were more pronounced in participants who were over 60 years old, participants with smoking history, hypertension or hyperlipidemia, who were under the high risk of AAD. CONCLUSION: Higher dietary VC and VE intakes are associated with reduced risk of AAD. Our study emphasizes the importance of diet adjustment strategies targeted on VC and VE to lower the incidence rate of AAD especially in the high-risk population.
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Aneurisma de la Aorta , Disección Aórtica , Ácido Ascórbico , Factores Protectores , Vitamina E , Humanos , Masculino , Estudios Prospectivos , Persona de Mediana Edad , Femenino , Ácido Ascórbico/administración & dosificación , Ácido Ascórbico/efectos adversos , Vitamina E/administración & dosificación , Factores de Riesgo , Anciano , Incidencia , Disección Aórtica/epidemiología , Disección Aórtica/prevención & control , Aneurisma de la Aorta/epidemiología , Aneurisma de la Aorta/prevención & control , Medición de Riesgo , Reino Unido/epidemiología , Factores de Tiempo , Dieta/efectos adversos , AdultoRESUMEN
AIM: To investigate the association between cardiovascular health metrics defined by Life's Essential 8 (LE8) scores and vascular complications among individuals with type 2 diabetes (T2D). MATERIALS AND METHODS: This prospective study included 11 033 participants with T2D, all devoid of macrovascular diseases (including cardiovascular and peripheral artery disease) and microvascular complications (e.g. diabetic retinopathy, neuropathy and nephropathy) at baseline from the UK Biobank. The LE8 score comprised eight metrics: smoking, body mass index, physical activity, non-high-density lipoprotein cholesterol, blood pressure, glycated haemoglobin, diet and sleep duration. Cox proportional hazards models were established to assess the associations of LE8 scores with incident macrovascular and microvascular complications. RESULTS: During a median follow-up of 12.1 years, we identified 1975 cases of incident macrovascular diseases and 1797 cases of incident microvascular complications. After adjusting for potential confounders, each 10-point increase in the LE8 score was associated with an 18% lower risk of macrovascular diseases and a 15% lower risk of microvascular complications. Comparing individuals in the highest and lowest quartiles of LE8 scores revealed hazard ratios of 0.55 (95% confidence interval 0.47-0.62) for incident macrovascular diseases, and 0.61 (95% confidence interval 0.53-0.70) for incident microvascular complications. This association remained robust across a series of sensitivity analyses and nearly all subgroups. CONCLUSION: Higher LE8 scores were associated with a lower risk of incident macrovascular and microvascular complications among individuals with T2D. These findings underscore the significance of adopting fundamental strategies to maintain optimal cardiovascular health and curtail the risk of developing diabetic vascular complications.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Angiopatías Diabéticas , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Angiopatías Diabéticas/epidemiología , Angiopatías Diabéticas/etiología , Reino Unido/epidemiología , Anciano , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Adulto , Factores de Riesgo , Índice de Masa Corporal , Fumar/efectos adversos , Fumar/epidemiología , Hemoglobina Glucada/análisis , Hemoglobina Glucada/metabolismo , Ejercicio Físico , Estudios de Seguimiento , Presión Sanguínea , IncidenciaRESUMEN
BACKGROUND: This study examines the association between traditional cardiovascular health (CVH) metrics and major adverse cardiovascular events (MACE) incidence in individuals with diverse sleep patterns. METHODS AND RESULTS: We analyzed data from 208 621 participants initially free of cardiovascular disease (CVD) in the UK Biobank study. Sleep patterns were assessed using scores for chronotype, duration, insomnia, snoring, and daytime dozing. Traditional CVH scores were derived from the Life's Simple 7 metrics. Cox proportional hazards multivariate regression assessed associations between distinct combinations of CVH and sleep scores and MACE, including nonfatal myocardial infarction, nonfatal stroke, and CVD mortality. Over a mean follow-up of 12.73 years, 9253 participants experienced incident MACE. Individuals with both a healthy sleep pattern and ideal CVH levels had the lowest MACE risk compared with those with a poor sleep pattern and poor CVH levels (hazard ratio, 0.306 [95% CI, 0.257-0.365]; P<0.001). Elevated CVH scores were associated with a reduced risk of MACE across different sleep patterns. Similar trends were observed for individual MACE components, heart failure, and all-cause mortality. These findings remained robust in sensitivity analyses and across various subgroups. CONCLUSIONS: In individuals without known CVD, maintaining a favorable sleep pattern and achieving optimal CVH levels, as measured by traditional metrics, were associated with the lowest MACE risk. Enhanced CVH significantly reduced CVD risk, even in individuals with a poor sleep pattern. These results emphasize the importance of considering multiple dimensions of sleep health alongside CVH to mitigate CVD risk. REGISTRATION: URL: https://www.ukbiobank.ac.uk; Unique identifier: 91090.
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Enfermedades Cardiovasculares , Sueño , Humanos , Masculino , Femenino , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/mortalidad , Estudios Prospectivos , Persona de Mediana Edad , Reino Unido/epidemiología , Anciano , Incidencia , Factores de Riesgo , Medición de Riesgo/métodos , Adulto , Factores de Riesgo de Enfermedad Cardiaca , Calidad del Sueño , Estado de Salud , Factores de TiempoRESUMEN
BACKGROUND International studies have shown that use of a subcutaneous implantable cardioverter defibrillator (S-ICD) could reduce lead-related complications while maintaining adequate defibrillation performance; however, data from the Chinese population or other Asian groups are limited. MATERIAL AND METHODS SCOPE is a prospective, multicenter, observational cohort study. Two hundred patients with primary prevention indication for sudden cardiac death (SCD), who are candidates for S-ICD, will be enrolled. From the same population, another 200 patients who are candidates for transvenous implantable cardioverter defibrillator (TV-ICD) will be enrolled after being matched for age, sex, SCD high-risk etiology (ischemic cardiomyopathy, and non-ischemic cardiomyopathy, ion channel disease, and other) and atrial fibrillation in a 1: 1 ratio with enrolled S-ICD patients. All the patients will be followed for 18 months under standard of care. RESULTS The primary endpoint is proportion of patients free from inappropriate shock (IAS) at 18 months in the S-ICD group. The lower 95% confidence bound of the proportion will be compared with a performance goal of 90.3%, which was derived from the previous meta-analysis. The comparisons between S-ICD and TV-ICD on IAS, appropriate shock, and complications will be used as secondary endpoints without formal assumptions. CONCLUSIONS This is the first prospective multicenter study focusing on the long-term performance of S-ICD in a Chinese population. By comparing with the data derived from international historical studies and a matched TV-ICD group, data from SCOPE will allow for the assessment of S-ICD in the Chinese population in a contemporary real-world implantation level and programming techniques, which will help us to further modify the device implantation and programming protocol in this specific population in the future.
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Fibrilación Atrial , Cardiomiopatías , Desfibriladores Implantables , Humanos , Estudios Prospectivos , Resultado del Tratamiento , Muerte Súbita Cardíaca/prevención & control , Muerte Súbita Cardíaca/epidemiología , Prevención Primaria , ChinaRESUMEN
BACKGROUND: Emerging evidence has linked daytime napping with the risk of cardiovascular events. Cardiac arrhythmias are considered an early clinical stage for cardiovascular diseases. However, whether napping frequency is associated with incident arrhythmias remains unknown. OBJECTIVE: This study aimed to prospectively investigate the association between napping frequency and cardiac arrhythmias. METHODS: Daytime napping frequency was self-reported in response to touchscreen questionnaires. The primary outcomes were incident arrhythmias including atrial fibrillation/flutter (AF/Af), ventricular arrhythmia, and bradyarrhythmia. Cox regression analysis was conducted on the basis of 491,117 participants free of cardiac arrhythmias from the UK Biobank. The 2-sample mendelian randomization (MR) and 1-sample MR were used to ensure a causal effect of genetically predicted daytime napping on the risk of arrhythmias. RESULTS: During a median follow-up of 11.91 years, 28,801 incident AF/Af cases, 4132 incident ventricular arrhythmias, and 11,616 incident bradyarrhythmias were documented. Compared with never/rarely napping, usually napping was significantly associated with higher risks of AF/Af (hazard ratio, 1.141; 95% CI, 1.083-1.203) and bradyarrhythmia (hazard ratio, 1.138; 95% CI, 1.049-1.235) but not ventricular arrhythmia after adjustment for various covariates. The 2-sample MR and 1-sample MR analysis showed that increased daytime napping frequency was likely to be a potential causal risk factor for AF/Af in FinnGen (odds ratio, 1.626; 95% CI, 1.061-2.943) and bradyarrhythmia in the UK Biobank (odds ratio, 1.005; 95% CI, 1.002-1.008). CONCLUSION: The results of this study add to the burgeoning evidence of an association between daytime napping frequency and an increased risk of cardiac arrhythmias including AF/Af, ventricular arrhythmia, and bradyarrhythmia.
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Arritmias Cardíacas , Análisis de la Aleatorización Mendeliana , Sueño , Humanos , Análisis de la Aleatorización Mendeliana/métodos , Femenino , Masculino , Estudios Prospectivos , Arritmias Cardíacas/epidemiología , Arritmias Cardíacas/genética , Arritmias Cardíacas/fisiopatología , Incidencia , Persona de Mediana Edad , Sueño/fisiología , Reino Unido/epidemiología , Factores de Riesgo , Estudios de Seguimiento , AncianoRESUMEN
Remnant cholesterol (RC) has been associated with atherosclerotic cardiovascular disease, but its relationship with hypertension remains unclear. This prospective cohort study aimed to investigate the association between RC and subsequent hypertension risk. Data from the UK Biobank, comprising 295,062 participants initially free of hypertension, were analyzed. Cox proportional hazards regression assessed the association between RC quartiles and hypertension risk. Discordance analysis evaluated the risk of hypertension in discordant/concordant groups of RC and low-density lipoprotein cholesterol (LDL-C) using the difference in percentile units (>10 units). Restricted cubic spline curves were used to model the relationship between RC and hypertension risk. The mean ± SD age of participants was 55.1 ± 8.1 years, with 40.6% being men and 94.7% White. During a median follow-up of 12.8 years, 39,038 participants developed hypertension. Comparing extreme quartiles of RC, the hazard ratio (HR) for incident hypertension was 1.20 (95% CI: 1.17-1.24). After adjusting for traditional risk factors, each 1 mmol/L increase in RC levels was associated with a 27% higher risk of incident hypertension (HR: 1.27; 95% CI: 1.23-1.31). The discordant group with high RC/low LDL-C exhibited a higher risk of incident hypertension compared to the concordant group (HR: 1.06; 95% CI: 1.03-1.09). Spline curves further demonstrated a positive association between RC and the risk of incident hypertension. We concluded that elevated RC emerged as an independent risk factor of incident hypertension, extending beyond traditional risk factors. Monitoring RC levels and implementing interventions to lower RC may have potential benefits in preventing hypertension.
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Colesterol , Hipertensión , Humanos , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Femenino , Estudios Prospectivos , Colesterol/sangre , Adulto , Factores de Riesgo , Incidencia , LDL-Colesterol/sangre , Anciano , Reino Unido/epidemiología , Estudios de CohortesRESUMEN
BACKGROUND: Mitral annular disjunction (MAD) is an under-recognised phenotype associated with severe ventricular arrhythmias. Limited knowledge has been gained on its molecular genesis. METHODS: A total of 150 unrelated deceased Chinese were collected for whole-exome sequencing, with analysis focusing on a panel of 118 genes associated with 'abnormal mitral valve morphology'. Cases were prespecified as 'longitudinally extensive MAD (LE-MAD)' or 'longitudinally less-extensive MAD (LLE-MAD)' according to the gross disjunctional length with a cut-off of 4.0 mm. The pedigree investigation was conducted on a case carrying an ultra-rare (minor allele frequency <0.1%) deleterious variant in DCHS1. RESULTS: Seventy-seven ultra-rare deleterious variants were finally identified. Exclusively, 12 ultra-rare deleterious variants distributed in nine genes occurred in LE-MAD, which were ANK1, COL3A1, DCHS1, FBN2, GNPTAB, LZTR1, PLD1, RYR1 and VPS13B. Ultra-rare deleterious variants in those nine genes were predominantly distributed in LE-MAD compared with LLE-MAD (28% vs 5%, OR 7.30, 95% CI 2.33 to 23.38; p<0.001), and the only gene related to LE-MAD with borderline significance was DCHS1. LE-MAD was consistently observed in a sizeable Chinese family, in which LE-MAD independently co-segregated with an ultra-rare deleterious variant in DCHS1, rs145429962. CONCLUSION: This study initially proposed that isolated LE-MAD might be a particular phenotype of MAD with a complex genetic predisposition. Deleterious variants in DCHS1 might be associated with the morphogenesis of LE-MAD.
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Enfermedades de las Válvulas Cardíacas , Prolapso de la Válvula Mitral , Humanos , Prolapso de la Válvula Mitral/genética , Válvula Mitral , Mutación/genética , Arritmias Cardíacas , Susceptibilidad a Enfermedades , Factores de Transcripción/genética , Transferasas (Grupos de Otros Fosfatos Sustitutos)/genéticaRESUMEN
BACKGROUND: The AHA has recently introduced a novel metric, Life's Essential 8, to assess cardiovascular health (CVH). Nevertheless, the association between varying levels of LE8 and the propensity for CKD is still unclear from a large prospective cohort. Our objective is to meticulously examine the relationship between LE8 and its associated susceptibilities to CKD. METHODS: A total of 251,825 participants free of CKD from the UK Biobank were included. Cardiovascular health was scored using LE8 and categorized as low, moderate, and high. Cox proportional hazard models were employed to evaluate the associations of LE8 scores with new-onset CKD. The genetic risk score for CKD was calculated by a weighted method. RESULTS: Over a median follow-up of 12.8 years, we meticulously documented 10,124 incident cases of CKD. Remarkably, an increased LE8 score correlated with a significant reduction of risk in new-onset CKD (high LE8 score vs. low LE8 score: HR = 0.300, 95% CI 0.270-0.330, p < 0.001; median LE8 score vs. low LE8 score: HR = 0.531, 95% CI 0.487-0.580, p < 0.001). This strong LE8-CKD association remained robust in extensive subgroup assessments and sensitivity analysis. Additionally, these noteworthy associations between LE8 scores and CKD remained unaffected by genetic predispositions to CKD. CONCLUSIONS: An elevated degree of CVH, as delineated by the discerning metric LE8, exhibited a pronounced and statistically significant correlation with a marked reduction in the likelihood of CKD occurrence.
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Enfermedades Cardiovasculares , Insuficiencia Renal Crónica , Humanos , Estados Unidos , Biobanco del Reino Unido , Bancos de Muestras Biológicas , Estudios Prospectivos , Predisposición Genética a la Enfermedad , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/genética , Factores de RiesgoRESUMEN
BACKGROUND: Commencing work at an early age has been linked to various risk factors for coronary heart disease (CHD), such as shift work and intensive job strain. However, the relationship between starting work too early and CHD risk remains largely unclear. We examined the association between age at job initiation and the risk of CHD. METHODS: UK Biobank participants aged 38 to 70 years without cardiovascular disease who provided data on their age at job initiation were included. The primary outcome was CHD, which was ascertained using hospital and death records. The hazard ratios (HRs) and 95% confidence interval (CIs) for the association between age at job initiation and CHD were calculated using multivariable Cox regression. RESULTS: Of the 501,971 participants, 114,418 eligible participants were included in the final analysis. The median age at job initiation was 19.0 years. During the mean follow-up of 12.6 years, 6,130 (5.4%) first CHD events occurred. We observed that age at job initiation was inversely associated with CHD (HR 0.98, 95% CI 0.97-0.99), and the association was potentially J-shaped. The HRs for the < 17-year, 17-18-year, and 19-21-year age groups were 1.29 (95%CI 1.18-1.41), 1.12 (95% CI 1.03-1.22) and 1.05 (95% CI 0.97-1.14), respectively, compared with those of the ≥ 22-year group. CONCLUSIONS: Age at job initiation was associated with incident CHD, which was independent of socioeconomic status. Participants who commenced employment before the age of 19 years exhibited a higher risk of developing CHD later in adulthood.
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Bancos de Muestras Biológicas , Enfermedad Coronaria , Humanos , Adulto Joven , Adulto , Estudios de Cohortes , Enfermedad Coronaria/epidemiología , Factores de Riesgo , Reino Unido/epidemiologíaRESUMEN
AIM: To examine the associations between serum albumin and the incidences of diabetes and diabetic microvascular complications in participants of the UK Biobank cohort. METHODS: There were 398,146 participants without diabetes and 30,952 patients with diabetes from the UK Biobank cohort included in this study. Multivariate-adjusted Cox proportional hazard models were used to analyze the association of albumin with the incidences of diabetes and diabetic microvascular complications. Mendelian randomization (MR) analysis was used to determine the genetic relationships between serum albumin and diabetes. RESULTS: After a median 12.90 years follow-up, 14,710 participants developed incident diabetes (58.83 ± 7.52 years, 56.10% male). After multivariate adjustment, serum albumin was inversely associated with incident diabetes: hazard ratio (HR) [95% confidence interval] per 10 g/l increase 0.88 [0.82;0.94]. MR analyses suggested a potential genetic influence of serum albumin on diabetes in both the UK Biobank and the FinnGen consortium: odds ratios (ORs) [95% confidence interval per 1 g/l increase 0.99 [0.98;1.00] and 0.78 [0.67;0.92], respectively. In patients with diabetes, higher serum albumin levels were significantly associated with lower risk for diabetic microvascular complications. Specifically, per 10 g/l increase in serum albumin, the HRs for diabetic nephropathy, ophthalmopathy, and neuropathy were 0.42 [0.30;0.58], 0.61 [0.52;0.72], and 0.67 [0.51;0.88], respectively. CONCLUSION: In this large prospective study, serum levels of albumin were inversely associated with the incidences of diabetes and diabetic microvascular complications. These findings underscore the importance of maintaining optimal nutrient status in reducing the risk of diabetes and its complications.
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Diabetes Mellitus Tipo 2 , Angiopatías Diabéticas , Nefropatías Diabéticas , Humanos , Masculino , Femenino , Estudios Prospectivos , Albúmina Sérica , Bancos de Muestras Biológicas , Nefropatías Diabéticas/epidemiología , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/complicaciones , Angiopatías Diabéticas/epidemiología , Angiopatías Diabéticas/genética , Angiopatías Diabéticas/complicaciones , Reino Unido/epidemiología , Factores de Riesgo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/genéticaRESUMEN
INTRODUCTION: The association between obesity and atrial fibrillation (AF) incidence in heart failure with preserved ejection fraction (HFpEF) patients is currently unclear. Our analyses and results are based on the whole Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial (placebo and spironolactone). METHOD: A total of 2138 subjects without baseline AF were included in the trial. Kaplan-Meier (K-M) curves and Cox regression with hazard ratios (HRs) and confidence intervals (CIs) were used to assess the incidence of AF with obesity. Of 2138 HFpEF patients without baseline AF, 1165 were obese (body mass index [BMI]≥30 kg/m2). RESULT: The K-M curve showed obese patients developed AF more than overweight (25≤ BMI ≤29.9 kg/m2) patients (p=0.013), confirmed by multivariable analysis, while there's no statistical difference between overweight and normal weight (18.5≤ BMI ≤24.9 kg/m2) patients. The occurrence of AF increased by 3% for every kg/m2 increase in BMI (adjusted HR, aHR: 1.03; 95% CI: 1.00-1.06), with a positive linear association (p for nonlinear: 0.145). Obesity was associated with AF incidence (aHR: 1.62; 95% CI: 1.05-2.50) compared with non-obesity (including overweight and normal-weight patients). CONCLUSION: Abdominal obesity was associated with increased AF incidence (aHR: 1.70; 95% CI: 1.04-2.77), and AF incidence rose by 18% per centimeter in circumference (aHR: 1.18; 95% CI: 1.04-1.34). Obesity and abdominal obesity increase the incidence of AF in HFpEF patients. Further studies need to determine whether there is a difference in AF in response to spironolactone across obese HFpEF pheno groups.
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OBJECTIVE: The triglyceride-glucose (TyG) index has been shown to be a new alternative measure for insulin resistance. However, no study has attempted to investigate the association of the TyG index with incident atrial fibrillation (AF) in the general population without known cardiovascular diseases. METHODS: Individuals without known cardiovascular diseases (heart failure, coronary heart disease, or stroke) from the Atherosclerosis Risk in Communities (ARIC) cohort were recruited. The baseline TyG index was calculated as the Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. The association between the baseline TyG index and incident AF was examined using Cox regression. RESULTS: Of 11,851 participants, the mean age was 54.0 years; 6586 (55.6%) were female. During a median follow-up of 24.26 years, 1925 incidents of AF cases (0.78/per 100 person-years) occurred. An increased AF incidence with a graded TyG index was found by KaplanâMeier curves (P < 0.001). In multivariable-adjusted analysis, both < 8.80 (adjusted hazard ratio [aHR] = 1.15, 95% confidence interval [CI] 1.02, 1.29) and > 9.20 levels (aHR 1.18, 95% CI 1.03, 1.37) of the TyG index were associated with an increased risk of AF compared with the middle TyG index category (8.80-9.20). The exposure-effect analysis confirmed the U-shaped association between the TyG index and AF incidence (P = 0.041). Further sex-specific analysis showed that a U-shaped association between the TyG index and incident AF still existed in females but not in males. CONCLUSIONS: A U-shaped association between the TyG index and AF incidence is observed in Americans without known cardiovascular diseases. Female sex may be a modifier in the association between the TyG index and AF incidence.
Asunto(s)
Fibrilación Atrial , Enfermedades Cardiovasculares , Masculino , Humanos , Femenino , Persona de Mediana Edad , Incidencia , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Glucosa , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/epidemiología , Factores de Riesgo , Triglicéridos , Medición de Riesgo , Glucemia/análisis , BiomarcadoresRESUMEN
Phylogenetic tools are fundamental to the studies of evolutionary relationships. In this paper, we present Ksak, a novel high-throughput tool for alignment-free phylogenetic analysis. Ksak computes the pairwise distance matrix between molecular sequences, using seven widely accepted k-mer based distance measures. Based on the distance matrix, Ksak constructs the phylogenetic tree with standard algorithms. When benchmarked with a golden standard 16S rRNA dataset, Ksak was found to be the most accurate tool among all five tools compared and was 19% more accurate than ClustalW2, a high-accuracy multiple sequence aligner. Above all, Ksak was tens to hundreds of times faster than ClustalW2, which helps eliminate the computation limit currently encountered in large-scale multiple sequence alignment. Ksak is freely available at https://github.com/labxscut/ksak.