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BACKGROUND: It is unknown whether dietary intake of polyunsaturated fatty acids (PUFA) modifies the cardiovascular disease (CVD) risk associated with a family history of CVD. We assessed interactions between biomarkers of low PUFA intake and a family history in relation to long-term CVD risk in a large consortium. METHODS: Blood and tissue PUFA data from 40â 885 CVD-free adults were assessed. PUFA levels ≤25th percentile were considered to reflect low intake of linoleic, alpha-linolenic, and eicosapentaenoic/docosahexaenoic acids (EPA/DHA). Family history was defined as having ≥1 first-degree relative who experienced a CVD event. Relative risks with 95% CI of CVD were estimated using Cox regression and meta-analyzed. Interactions were assessed by analyzing product terms and calculating relative excess risk due to interaction. RESULTS: After multivariable adjustments, a significant interaction between low EPA/DHA and family history was observed (product term pooled RR, 1.09 [95% CI, 1.02-1.16]; P=0.01). The pooled relative risk of CVD associated with the combined exposure to low EPA/DHA, and family history was 1.41 (95% CI, 1.30-1.54), whereas it was 1.25 (95% CI, 1.16-1.33) for family history alone and 1.06 (95% CI, 0.98-1.14) for EPA/DHA alone, compared with those with neither exposure. The relative excess risk due to interaction results indicated no interactions. CONCLUSIONS: A significant interaction between biomarkers of low EPA/DHA intake, but not the other PUFA, and a family history was observed. This novel finding might suggest a need to emphasize the benefit of consuming oily fish for individuals with a family history of CVD.
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Enfermedades Cardiovasculares , Ácidos Grasos Omega-3 , Animales , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/genética , Factores de Riesgo , Ácidos Docosahexaenoicos , BiomarcadoresRESUMEN
BACKGROUND: The effect of marine omega-3 PUFAs on risk of stroke remains unclear. METHODS: We investigated the associations between circulating and tissue omega-3 PUFA levels and incident stroke (total, ischemic, and hemorrhagic) in 29 international prospective cohorts. Each site conducted a de novo individual-level analysis using a prespecified analytical protocol with defined exposures, covariates, analytical methods, and outcomes; the harmonized data from the studies were then centrally pooled. Multivariable-adjusted HRs and 95% CIs across omega-3 PUFA quintiles were computed for each stroke outcome. RESULTS: Among 183â 291 study participants, there were 10â 561 total strokes, 8220 ischemic strokes, and 1142 hemorrhagic strokes recorded over a median of 14.3 years follow-up. For eicosapentaenoic acid, comparing quintile 5 (Q5, highest) with quintile 1 (Q1, lowest), total stroke incidence was 17% lower (HR, 0.83 [CI, 0.76-0.91]; P<0.0001), and ischemic stroke was 18% lower (HR, 0.82 [CI, 0.74-0.91]; P<0.0001). For docosahexaenoic acid, comparing Q5 with Q1, there was a 12% lower incidence of total stroke (HR, 0.88 [CI, 0.81-0.96]; P=0.0001) and a 14% lower incidence of ischemic stroke (HR, 0.86 [CI, 0.78-0.95]; P=0.0001). Neither eicosapentaenoic acid nor docosahexaenoic acid was associated with a risk for hemorrhagic stroke. These associations were not modified by either baseline history of AF or prevalent CVD. CONCLUSIONS: Higher omega-3 PUFA levels are associated with lower risks of total and ischemic stroke but have no association with hemorrhagic stroke.
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Ácidos Grasos Omega-3 , Accidente Cerebrovascular Hemorrágico , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Estudios Prospectivos , Ácido Eicosapentaenoico , Ácidos Docosahexaenoicos , Accidente Cerebrovascular Hemorrágico/epidemiología , Accidente Cerebrovascular/epidemiología , Factores de RiesgoRESUMEN
Pulsed field ablation with irreversible electroporation for the treatment of atrial fibrillation involves tissue-specific and non-thermal energy-induced cell necrosis, which helps avoid complications, such as pulmonary vein stenosis, atrial collateral tissue damage, and extensive atrial structural damage, often encountered with traditional thermal ablation. In existing clinical trials, pulsed field ablation has shown excellent effects on pulmonary vein isolation in patients with paroxysmal and persistent atrial fibrillation. Pulsed field ablation is easy, simple, and quick and can reduce iatrogenic injury. Therefore, the application of pulsed field ablation technology in the treatment of atrial fibrillation has a promising future. Notably, the adjustment of parameters in pulsed field ablation with different ablation catheter systems can strongly affect the area and depth of the necrotic myocardium, which greatly affects the likelihood of atrial fibrillation recurrence and incidence of adverse complications after ablation. In this paper, we review the mechanisms, advantages, and limitations of pulsed field ablation based on the results of a series of previous studies and provide ideas and directions for future research.
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BACKGROUND: The relationship between multimorbidity (i.e. ≥ 2 chronic conditions) and incontinence (i.e. urinary and/or faecal incontinence) is underexplored. This study investigated the association between multimorbidity and incident incontinence in Chinese adults aged ≥50 years. METHODS: Data from the 2011 and 2015 waves of the China Health and Retirement Longitudinal Study were used. The association between 12 chronic conditions, multimorbidity and new-onset incontinence was analysed using weighted logistic regression models. Mediation analysis was conducted to explore the potential mediators (self-reported health, subjective memory, depressive symptoms, disability, cognitive function, handgrip strength, mobility limitations, medications and frailty status) between multimorbidity and incontinence. FINDINGS: Among 9,986 individuals aged ≥50 years who were continent at baseline, 5.3% (n = 521) were newly incontinent 4 years later (incident cases). The risk of incident incontinence increased with physical multimorbidity (OR 2.04, 95% CI 1.62-2.57). Compared to no chronic condition, having 1, 2, 3 and ≥ 4 chronic conditions were associated with incident incontinence with OR (95% CI): 1.41 (1.01-1.97), 1.74 (1.24-2.44), 2.82 (1.93-4.12) and 3.99 (2.29-6.95), respectively. The association between multimorbidity and incontinence was mediated by self-reported health (41.2%), medications (26.6%), mobility limitations (20.9%), depressive symptoms (12.8%), disability (11.6%), subjective memory (8.7%) and frailty status (8.3%). CONCLUSION: This longitudinal study found that physical multimorbidity and specific chronic conditions may increase the risk of new-onset incontinence among Chinese adults aged ≥50 years. Self-reported health, medications and mobility limitations seemed to be important intermediate conditions between multimorbidity and incident incontinence.
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Fragilidad , Humanos , Anciano , Fuerza de la Mano , Estudios Longitudinales , Limitación de la Movilidad , Multimorbilidad , Estudios Prospectivos , China/epidemiología , Enfermedad CrónicaRESUMEN
BACKGROUND: Vitamin D supplementation may prevent acute respiratory infections (ARIs). This study aimed to identify the optimal methods of vitamin D supplementation. METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and the ClinicalTrials.gov registry were searched from database inception through July 13, 2023. Randomized-controlled trials (RCTs) were included. Data were pooled using random-effects model. The primary outcome was the proportion of participants with one or more ARIs. RESULTS: The analysis included 43 RCTs with 49320 participants. Forty RCTs were considered to be at low risk for bias. The main pairwise meta-analysis indicated there were no significant preventive effects of vitamin D supplementation against ARIs (risk ratio [RR]: 0.99, 95% confidence interval [CI]: 0.97 to 1.01, I2 = 49.6%). The subgroup dose-response meta-analysis indicated that the optimal vitamin D supplementation doses ranged between 400-1200 IU/day for both summer-sparing and winter-dominant subgroups. The subgroup pairwise meta-analysis also revealed significant preventive effects of vitamin D supplementation in subgroups of daily dosing (RR: 0.92, 95% CI: 0.85 to 0.99, I2 = 55.7%, number needed to treat [NNT]: 36), trials duration < 4 months (RR: 0.81, 95% CI: 0.67 to 0.97, I2 = 48.8%, NNT: 16), summer-sparing seasons (RR: 0.85, 95% CI: 0.74 to 0.98, I2 = 55.8%, NNT: 26), and winter-dominant seasons (RR: 0.79, 95% CI: 0.71 to 0.89, I2 = 9.7%, NNT: 10). CONCLUSION: Vitamin D supplementation may slightly prevent ARIs when taken daily at doses between 400 and 1200 IU/d during spring, autumn, or winter, which should be further examined in future clinical trials.
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Suplementos Dietéticos , Ensayos Clínicos Controlados Aleatorios como Asunto , Infecciones del Sistema Respiratorio , Vitamina D , Humanos , Vitamina D/administración & dosificación , Vitamina D/uso terapéutico , Infecciones del Sistema Respiratorio/prevención & control , Relación Dosis-Respuesta a Droga , Estaciones del Año , Enfermedad Aguda , Vitaminas/administración & dosificaciónRESUMEN
BACKGROUND: We aimed to investigate the association between serially measured HDL-C (high-density lipoprotein cholesterol) levels and stroke risk in a prospective cohort study. METHODS: We included 96 258 individuals (79.6% men, mean age 51.5 years) without a history of stroke, myocardial infarction, or cancer at baseline from the Kailuan Study, with repeated measurements of HDL-C in 2006, 2008, 2010, 2012, 2014, and 2016. Cumulatively, averaged HDL-C concentrations were calculated using all available HDL-C measurements before incidence stroke or end of follow-up (December 31, 2017). Incident stroke cases were confirmed by review of medical records and further subclassified into ischemic or hemorrhagic stroke. Cox proportional hazards regression and restricted cubic splines were used to examine these associations. RESULTS: During a median follow-up of 10.7 years, 5012 incident stroke cases occurred. Restricted cubic splines analysis suggested a U-shaped association between concentrations of cumulatively averaged HDL-C and risk of stroke (Pnonlinearity <0.001), with the nadir of risk at 1.29 mmol/L. After adjustment for cardiovascular risk factors, individuals with cumulatively averaged HDL-C ≤1.06 mmol/L or ≥2.05 mmol/L had hazard ratios for total stroke of 1.31 (95% CI, 1.15-1.49) and 1.85 (1.63-2.09) compared with those with HDL-C of 1.26 to 1.39 mmol/L. Corresponding hazard ratios were 1.29 (1.11-1.48) and 1.84 (1.60-2.11) for ischemic stroke and 1.54 (1.12-2.12) and 2.29 (1.73-3.04) for hemorrhagic stroke, respectively. CONCLUSIONS: Both low and high cumulatively averaged HDL-C were associated with an increased risk of ischemic and hemorrhagic strokes.
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Accidente Cerebrovascular Hemorrágico , Accidente Cerebrovascular , HDL-Colesterol , Estudios de Cohortes , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Accidente Cerebrovascular/epidemiologíaRESUMEN
BACKGROUND: Recent studies have suggested that triglyceride-glucose (TyG) index is an independent predictor of cardiovascular disease (CVD). However, the impact of long-term visit-to-visit variability in TyG index on the risk of CVD is not known. We aimed to investigate the longitudinal association between baseline and mean TyG index as well as TyG index variability and incident CVD in a Chinese population. METHODS: We included 49,579 participants without previous history of CVD in the Kailuan study who underwent three health examinations (2006, 2008, and 2010) and were followed up for clinical events until 2019. TyG index was calculated as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. We measured TyG index variability as the SD of the residuals obtained from a linear regression on the three TyG index measurements for each individual. Multivariate-adjusted Cox models were used to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) with incident CVD. RESULTS: During a median follow-up time of 9.0 years, 2404 developed CVD. The highest tertile (T3) of baseline and mean TyG index were each associated with higher CVD incidence as compared with the lowest tertile (T1): aHR, 1.25; 95% CI 1.11-1.42; and aHR 1.40; 95% CI 1.24-1.58, respectively. Tertile 3 of TyG index variability was associated with increased CVD incidence compared to T1 group (aHR, 1.12; 95% CI 1.01-1.24). Similar findings were observed in a series of sensitivity analyses. CONCLUSION: Higher TyG index level and greater TyGindex variability were each independently associated with a higher incidence of CVD.
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Enfermedades Cardiovasculares , Biomarcadores , Glucemia/análisis , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Glucosa , Humanos , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , TriglicéridosRESUMEN
BACKGROUND: We aimed to investigate the association of serum pentadecanoic acid (15:0), a biomarker of dairy fat intake, with incident cardiovascular disease (CVD) and all-cause mortality in a Swedish cohort study. We also systematically reviewed studies of the association of dairy fat biomarkers (circulating or adipose tissue levels of 15:0, heptadecanoic acid [17:0], and trans-palmitoleic acid [t16:1n-7]) with CVD outcomes or all-cause mortality. METHODS AND FINDINGS: We measured 15:0 in serum cholesterol esters at baseline in 4,150 Swedish adults (51% female, median age 60.5 years). During a median follow-up of 16.6 years, 578 incident CVD events and 676 deaths were identified using Swedish registers. In multivariable-adjusted models, higher 15:0 was associated with lower incident CVD risk in a linear dose-response manner (hazard ratio 0.75 per interquintile range; 95% confidence interval 0.61, 0.93, P = 0.009) and nonlinearly with all-cause mortality (P for nonlinearity = 0.03), with a nadir of mortality risk around median 15:0. In meta-analyses including our Swedish cohort and 17 cohort, case-cohort, or nested case-control studies, higher 15:0 and 17:0 but not t16:1n-7 were inversely associated with total CVD, with the relative risk of highest versus lowest tertile being 0.88 (0.78, 0.99), 0.86 (0.79, 0.93), and 1.01 (0.91, 1.12), respectively. Dairy fat biomarkers were not associated with all-cause mortality in meta-analyses, although there were ≤3 studies for each biomarker. Study limitations include the inability of the biomarkers to distinguish different types of dairy foods and that most studies in the meta-analyses (including our novel cohort study) only assessed biomarkers at baseline, which may increase the risk of misclassification of exposure levels. CONCLUSIONS: In a meta-analysis of 18 observational studies including our new cohort study, higher levels of 15:0 and 17:0 were associated with lower CVD risk. Our findings support the need for clinical and experimental studies to elucidate the causality of these relationships and relevant biological mechanisms.
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Enfermedades Cardiovasculares/epidemiología , Productos Lácteos , Grasas de la Dieta/administración & dosificación , Ácidos Grasos/sangre , Biomarcadores/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/prevención & control , Causas de Muerte , Productos Lácteos/efectos adversos , Grasas de la Dieta/efectos adversos , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Observacionales como Asunto , Prevalencia , Factores Protectores , Medición de Riesgo , Factores de Riesgo , Suecia/epidemiología , Factores de TiempoRESUMEN
OBJECTIVES: Existing studies evaluating the accuracy of heparin-binding protein for the diagnosis of sepsis have been inconsistent. We conducted a systematic review and meta-analysis to assess the totality of current evidence regarding the utility of heparin-binding protein to diagnose sepsis in patients with presumed systemic infection. DATA SOURCE: PubMed, Embase, the China National Knowledge infrastructure, and WangFang electronic database were searched from inception to December of 2019. STUDY SELECTION: Two independent reviewers identified eligible studies. Cohort and case-control studies, which measured serum levels of heparin-binding protein among adult patients with suspected sepsis, were eligible for inclusion. DATA EXTRACTION: Two reviewers independently extracted data elements from the selected studies. A bivariate random-effects meta-analysis model was used to synthesize the prognostic accuracy measures. Risk of bias of studies was assessed with Quality Assessment of Diagnostic Accuracy Studies 2 tool. DATA SYNTHESIS: We identified 26 studies with 3,868 patients in the meta-analysis. Heparin-binding protein had a pooled sensitivity of 0.85 (95% CI, 0.79-0.90) and a pooled specificity of 0.91 (95% CI, 0.82-0.96) for the diagnosis of sepsis. There was low heterogeneity between the studies (I2 = 12%), and no evidence of publication bias was detected. Heparin-binding protein had a higher sensitivity and specificity when compared with procalcitonin (0.75 [95% CI, 0.62-0.85] and 0.85 [95% CI, 0.73-0.92]) as well as C-reactive protein (0.75 [95% CI, 0.65-0.84] and 0.71 [95% CI, 0.63-0.77]). Serial measurements of heparin-binding protein also showed that heparin-binding protein levels rose significantly at least 24 hours before a diagnosis of sepsis. CONCLUSIONS: The diagnostic ability of heparin-binding protein is favorable, demonstrating both high sensitivity and specificity in predicting progression to sepsis in critically ill patients. Future studies could assess the incremental value that heparin-binding protein may add to a multimodal sepsis identification and prognostication algorithm for critically ill patients.
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Péptidos Catiónicos Antimicrobianos/sangre , Sepsis/diagnóstico , Algoritmos , Proteínas Sanguíneas , Humanos , Reproducibilidad de los Resultados , Sepsis/sangreRESUMEN
BACKGROUND: The optimal antibiotic regimen for the medical management of acute appendicitis remains unknown due to a lack of head-to-head comparisons between different antibiotic regimens. METHODS: We systematically searched the PubMed, EMBASE, Scopus and Cochrane Central Register of Controlled Trials databases from their inception through to August 2020. We selected randomized controlled trials (RCTs) or observational studies comparing antibiotic therapy and appendectomy as the initial treatment for adult or paediatric patients with acute appendicitis. We performed a Bayesian network meta-analysis (NMA) to obtain the indirect comparison results between different antibiotic regimens by employing the group managed by surgery as a common comparator. Antibiotic regimens were classified into three categories: those including a carbapenem; those including a cephalosporin; and those including a ß-lactam/ß-lactamase inhibitor combination. RESULTS: A total of 9 RCTs (adults, nâ=â8; paediatrics, nâ=â1) and 12 observational studies (adults, nâ=â3; paediatrics, nâ=â9) were included in the NMA, with a total of 4551 patients. The most commonly administered regimen was a ß-lactam/ß-lactamase inhibitor combination (9/21; 43%), followed by a cephalosporin (7/21; 33%) or a carbapenem (5/21; 24%). The NMA indicated that surgery significantly increased 1 year treatment success, compared with cephalosporins [OR: 16.79; 95% credible interval: 3.8-127.64] or ß-lactam/ß-lactamase inhibitor combinations (OR: 19.99; 95% credible interval: 4.87-187.57), but not carbapenems (OR: 3.50, 95% credible interval: 0.55-38.63). In contrast, carbapenems were associated with fewer treatment-related complications compared with surgery (OR: 0.12; 95% credible interval: 0.01-0.85). CONCLUSIONS: Carbapenems might be recommended as the initial antibiotic regimen for the non-operative management of adult patients with acute appendicitis. Nevertheless, due to the imprecise estimates in our NMA, additional RCTs are needed to corroborate these findings, especially for paediatric patients.
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Antibacterianos , Apendicitis , Adulto , Antibacterianos/uso terapéutico , Apendicitis/tratamiento farmacológico , Apendicitis/cirugía , Carbapenémicos/uso terapéutico , Cefalosporinas , Niño , Humanos , Metaanálisis en RedRESUMEN
BACKGROUND: Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown. METHODS: We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models. RESULTS: Observed height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95% confidence interval [CI]: 0.94-1.23). Height-GS showed similar results (HR = 1.02, 95% CI: 0.85-1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95% CI: 1.06-1.48) and HR = 1.59 (95% CI: 1.08-2.33) per 5-kg/m2 increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (Pinteraction < 0.05). CONCLUSION: Our observation of a positive association between BMI and ovarian cancer risk in premenopausal BRCA1/2 mutation carriers is consistent with findings in the general population.
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Estatura , Índice de Masa Corporal , Genes BRCA1 , Genes BRCA2 , Heterocigoto , Análisis de la Aleatorización Mendeliana , Mutación , Neoplasias Ováricas/etiología , Adulto , Anciano , Femenino , Humanos , Menopausia , Persona de Mediana Edad , Neoplasias Ováricas/genética , Modelos de Riesgos ProporcionalesRESUMEN
Multiple breast cancer loci have been identified in previous genome-wide association studies, but they were mainly conducted in populations of European ancestry. Women of African ancestry are more likely to have young-onset and oestrogen receptor (ER) negative breast cancer for reasons that are unknown and understudied. To identify genetic risk factors for breast cancer in women of African descent, we conducted a meta-analysis of two genome-wide association studies of breast cancer; one study consists of 1,657 cases and 2,029 controls genotyped with Illumina's HumanOmni2.5 BeadChip and the other study included 3,016 cases and 2,745 controls genotyped using Illumina Human1M-Duo BeadChip. The top 18,376 single nucleotide polymorphisms (SNP) from the meta-analysis were replicated in the third study that consists of 1,984 African Americans cases and 2,939 controls. We found that SNP rs13074711, 26.5 Kb upstream of TNFSF10 at 3q26.21, was significantly associated with risk of oestrogen receptor (ER)-negative breast cancer (odds ratio [OR]=1.29, 95% CI: 1.18-1.40; P = 1.8 × 10 − 8). Functional annotations suggest that the TNFSF10 gene may be involved in breast cancer aetiology, but further functional experiments are needed. In addition, we confirmed SNP rs10069690 was the best indicator for ER-negative breast cancer at 5p15.33 (OR = 1.30; P = 2.4 × 10 − 10) and identified rs12998806 as the best indicator for ER-positive breast cancer at 2q35 (OR = 1.34; P = 2.2 × 10 − 8) for women of African ancestry. These findings demonstrated additional susceptibility alleles for breast cancer can be revealed in diverse populations and have important public health implications in building race/ethnicity-specific risk prediction model for breast cancer.
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Neoplasias de la Mama/genética , Cromosomas Humanos Par 3/genética , Negro o Afroamericano/genética , Alelos , Población Negra/genética , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes/genética , Sitios Genéticos , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo/métodos , Humanos , Polimorfismo de Nucleótido Simple/genética , Receptores de Estrógenos/genética , Factores de Riesgo , Ligando Inductor de Apoptosis Relacionado con TNF/genética , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismoRESUMEN
BACKGROUND: Few studies have evaluated the performance of existing breast cancer risk prediction models among women of African ancestry. In replication studies of genetic variants, a change in direction of the risk association is a common phenomenon. Termed flip-flop, it means that a variant is risk factor in one population but protective in another, affecting the performance of risk prediction models. METHODS: We used data from the genome-wide association study (GWAS) of breast cancer in the African diaspora (The Root consortium), which included 3686 participants of African ancestry from Nigeria, USA, and Barbados. Polygenic risk scores (PRSs) were constructed from the published odds ratios (ORs) of four sets of susceptibility loci for breast cancer. Discrimination capacity was measured using the area under the receiver operating characteristic curve (AUC). RESULTS: Flip-flop phenomenon was observed among 30~40% of variants across studies. Using the 34 variants with consistent directionality among previous studies, we constructed a PRS with AUC of 0.531 (95% confidence interval [CI]: 0.512-0.550), which is similar to the PRS using 93 variants and ORs from European ancestry populations (AUC = 0.525, 95% CI: 0.506-0.544). Additionally, we found the 34-variant PRS has good discriminative accuracy in women with family history of breast cancer (AUC = 0.586, 95% CI: 0.532-0.640). CONCLUSIONS: We found that PRS based on variants identified from prior GWASs conducted in women of European and Asian ancestries did not provide a comparable degree of risk stratification for women of African ancestry. Further large-scale fine-mapping studies in African ancestry populations are desirable to discover population-specific genetic risk variants.
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Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Predisposición Genética a la Enfermedad , Pronóstico , Adulto , Anciano , Pueblo Asiatico , Población Negra/genética , Neoplasias de la Mama/patología , Femenino , Variación Genética , Estudio de Asociación del Genoma Completo , Humanos , Persona de Mediana Edad , Nigeria/epidemiología , Polimorfismo de Nucleótido Simple , Factores de RiesgoRESUMEN
MicroRNAs (miRNA) regulate breast biology by binding to specific RNA sequences, leading to RNA degradation and inhibition of translation of their target genes. While germline genetic variations may disrupt some of these interactions between miRNAs and their targets, studies assessing the relationship between genetic variations in the miRNA network and breast cancer risk are still limited, particularly among women of African ancestry. We systematically put together a list of 822 and 10,468 genetic variants among primary miRNA sequences and 38 genes in the miRNA biogenesis pathway, respectively; and examined their association with breast cancer risk in the ROOT consortium which includes women of African ancestry. Findings were replicated in an independent consortium. Logistic regression was used to estimate the odds ratio (OR) and 95 % confidence intervals (CI). For overall breast cancer risk, three single-nucleotide polymorphisms (SNPs) in miRNA biogenesis genes DROSHA rs78393591 (OR = 0.69, 95 % CI: 0.55-0.88, P = 0.003), ESR1 rs523736 (OR = 0.88, 95 % CI: 0.82-0.95, P = 3.99 × 10(-4)), and ZCCHC11 rs114101502 (OR = 1.33, 95 % CI: 1.11-1.59, P = 0.002), and one SNP in primary miRNA sequence (rs116159732 in miR-6826, OR = 0.74, 95 % CI: 0.63-0.89, P = 0.001) were found to have significant associations in both discovery and validation phases. In a subgroup analysis, two SNPs were associated with risk of estrogen receptor (ER)-negative breast cancer, and three SNPs were associated with risk of ER-positive breast cancer. Several variants in miRNA and miRNA biogenesis pathway genes were associated with breast cancer risk. Risk associations varied by ER status, suggesting potential new mechanisms in etiology.
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Neoplasias de la Mama/genética , Proteínas de Unión al ADN/genética , Receptor alfa de Estrógeno/genética , MicroARNs/genética , Ribonucleasa III/genética , Adulto , Anciano , Anciano de 80 o más Años , Población Negra , Neoplasias de la Mama/patología , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , MicroARNs/biosíntesis , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Factores de RiesgoRESUMEN
OBJECTIVE: To estimate the prevalence of elevated blood pressure (EBP) in Chinese children and identify individual and family factors associated with EBP. METHODS: A nationwide cross-sectional study was conducted in 2010 using stratified cluster sampling. Participants' blood pressure was measured, and their parents completed a questionnaire on personal and family characteristics. Prevalence and correlates of EBP were assessed. RESULTS: Among a total of 24,333 participants, 20.2% of boys and 16.3% of girls had EBP. The prevalence of EBP increased with the ascending trend of waist circumference, Waist-to-height ratio, and body mass index. The adjusted prevalence ratios (aPRs) for obese boys and girls were 2.50 and 2.97, respectively. Fewer urban boys (16.2%) had EBP than rural boys (21.7%). Boys with a family history of hypertension were 12% more likely to have EBP. Children whose mothers received a college education tended to have lower likelihood of EBP; with an aPR was 0.85 among boys and 0.78 among girls. CONCLUSION: EBP is common among obese students and those who have a family history of hypertension. A negative association between mothers' education levels and EBP risk in children was found.
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Presión Sanguínea , Instituciones Académicas/estadística & datos numéricos , Encuestas y Cuestionarios , Adolescente , Índice de Masa Corporal , Niño , China/epidemiología , Análisis por Conglomerados , Estudios Transversales , Femenino , Humanos , Hipertensión/epidemiología , Masculino , Linaje , Prevalencia , Circunferencia de la Cintura , Relación Cintura-EstaturaRESUMEN
Numerous observational studies have demonstrated a significant inverse association between vitamin D status and the risk of major chronic disease, including type 2 diabetes (T2D), cardiovascular disease (CVD), and cancer. However, findings from Mendelian randomization (MR) studies and randomized controlled trials (RCTs) suggest minimal or no benefit of increased vitamin D levels. We provide an overview of recent literature linking vitamin D to major chronic diseases. Because emerging evidence indicates a potential threshold effect of vitamin D, future well-designed studies focused on diverse populations with vitamin D deficiency or insufficiency are warranted for a more comprehensive understanding of the effect of maintaining sufficient vitamin D status on the prevention of major chronic diseases.
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BACKGROUND: Optimal blood pressure (BP) levels to reduce the long-term risk of cognitive decline remains controversial. We aimed to investigate the association between BP and anti-hypertensive treatment status with cognitive decline in older adults. METHODS: This study used data from the China Health and Retirement Longitudinal Study. Cognitive function was assessed at year 2011, 2013, 2015, and 2018. Global cognitive Z-score was calculated as the average score of episodic memory and mental intactness. BP were measured at the first and second wave. Pulse pressure (PP) was calculated as systolic BP (SBP) minus diastolic BP. Cumulative BP was calculated as the area under the curve using BP measurements from 2011 to 2013. Linear mixed models were used to assess the longitudinal association between BP-related measurements and cognitive decline. RESULTS: We included 11,671 participants (47.3% men and mean age 58.6 years). Individual with BP > 140/90 mm Hg or taking anti-hypertensive medication were independently associated with accelerated cognitive decline (ß=-0.014, 95% CI: -0.020 to -0.007). Individuals with anti-hypertensive medication use, but with controlled SBP to less than 120 mm Hg did not have a significantly increased risk of cognitive decline compared with normotension (ß=-0.003, 95% CI: -0.021 to 0.014). Individuals on anti-hypertensive treatment with PP of more than 70 mm Hg had a significantly higher risk of cognitive decline (ß=-0.033, 95% CI: -0.045 to -0.020). Regardless of anti-hypertensive treatment status, both elevated baseline and cumulative SBP and PP were found to be independently associated with accelerated cognitive decline. CONCLUSIONS: Cumulatively elevated SBP, PP and uncontrolled BP were associated with subsequent cognitive decline. Effectively controlling BP with anti-hypertensive treatment may be able to preserve cognitive decline in older adults.