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Nutr Metab (Lond) ; 17: 39, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32489394


Background: Accumulating evidence shows that circulating levels of trimethylamine N-oxide, which is generated from the metabolism of dietary choline, may predict cardiovascular disease among Caucasians. Acute coronary syndrome (ACS), one common presentation of cardiovascular disease, is a spectrum of signs and symptoms due to acute decreased blood flow in the coronary arteries. The relationship between the metabolites from choline pathway and ACS remains unclear. We aimed to assess the associations of circulating metabolites from the choline pathway with ACS among a Chinese population, who consume a different dietary pattern than their Western counterparts. Methods: We recruited 501 participants who were admitted to the Department of Cardiology, Zhongshan Hospital,Shanghai China between March 2017 and June 2018, including 254 ACS cases and 247 controls. Liquid chromatography-tandem mass spectrometry was used to measure circulating concentrations of metabolites in the choline pathway, including betaine, choline, trimethylamine, and trimethylamine N-oxide. A composite metabolite score using a weighted sum of these four metabolites, and the betaine/choline ratio were calculated. Multivariable logistic regressions were applied to estimate the association of metabolites with ACS, with adjustment of age, sex, body mass index, smoking index, history of diseases, and kidney function. Results: After adjusting for traditional risk factors, per 1-standard deviation (SD) increment in choline was positively associated with the odds of ACS [odds ratio (OR), 95% confidence interval (CI), 1.77(1.44-2.18)], and the other metabolites were not associated with ACS at a statistical significance level. Compared with participants in the lowest quartile of the metabolite score, those in the highest quartile had higher odds of ACS [OR (95% CI), 3.18(1.85-5.54), p < 0.001 for trend]. Per 1-SD increment in metabolite score was positively associated with higher odds of ACS [OR (95% CI), 1.80 (1.37-2.40)], and per 1-SD increment in the betaine/choline ratio was inversely associated with the odds of ACS [OR (95% CI), 0.49 (0.39-0.60)]. Conclusions: Among our Chinese participants, trimethylamine N-oxide was not associated with ACS, while a composite metabolite score of metabolites from the choline pathway was associated with increased odds of ACS. The choline pathway metabolites may be related to the pathophysiology of ACS among Chinese.

Eur J Epidemiol ; 35(7): 685-697, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32383070


Epidemiology studies suggested that low birthweight was associated with a higher risk of hypertension in later life. However, little is known about the causality of such associations. In our study, we evaluated the causal association of low birthweight with adulthood hypertension following a standard analytic protocol using the study-level data of 183,433 participants from 60 studies (CHARGE-BIG consortium), as well as that with blood pressure using publicly available summary-level genome-wide association data from EGG consortium of 153,781 participants, ICBP consortium and UK Biobank cohort together of 757,601 participants. We used seven SNPs as the instrumental variable in the study-level analysis and 47 SNPs in the summary-level analysis. In the study-level analyses, decreased birthweight was associated with a higher risk of hypertension in adults (the odds ratio per 1 standard deviation (SD) lower birthweight, 1.22; 95% CI 1.16 to 1.28), while no association was found between genetically instrumented birthweight and hypertension risk (instrumental odds ratio for causal effect per 1 SD lower birthweight, 0.97; 95% CI 0.68 to 1.41). Such results were consistent with that from the summary-level analyses, where the genetically determined low birthweight was not associated with blood pressure measurements either. One SD lower genetically determined birthweight was not associated with systolic blood pressure (ß = - 0.76, 95% CI - 2.45 to 1.08 mmHg), 0.06 mmHg lower diastolic blood pressure (ß = - 0.06, 95% CI - 0.93 to 0.87 mmHg), or pulse pressure (ß = - 0.65, 95% CI - 1.38 to 0.69 mmHg, all p > 0.05). Our findings suggest that the inverse association of birthweight with hypertension risk from observational studies was not supported by large Mendelian randomization analyses.

Peso ao Nascer , Pressão Sanguínea/genética , Hipertensão/epidemiologia , Hipertensão/genética , Análise da Randomização Mendeliana/métodos , Adulto , Peso ao Nascer/genética , Peso ao Nascer/fisiologia , Pressão Sanguínea/fisiologia , Índice de Massa Corporal , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Masculino , Polimorfismo de Nucleotídeo Único/genética
BMC Cardiovasc Disord ; 20(1): 178, 2020 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-32299366


BACKGROUND: Heart failure is associated with ventricular dyssynchrony and energetic inefficiency, which can be alleviated by cardiac resynchronization therapy (CRT) with approximately one-third of non-response rate. Thus far, there is no specific biomarker to predict the response to CRT in patients with heart failure. In this study, we assessed the role of the blood metabolomic profile in predicting the response to CRT. METHODS: A total of 105 dilated cardiomyopathy patients with severe heart failure who received CRT were included in our two-stage study. Baseline blood samples were collected prior to CRT implantation. The response to CRT was defined according to echocardiographic criteria. Metabolomic profiling of serum samples was carried out using ultrahigh performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry. RESULTS: Seventeen metabolites showed significant differences in their levels between responders and non-responders, and these metabolites were primarily involved in six pathways, including linoleic acid metabolism, Valine, leucine and isoleucine biosynthesis, phenylalanine metabolism, citrate cycle, tryptophan metabolism, and sphingolipid metabolism. A combination of isoleucine, tryptophan, and linoleic acid was identified as an ideal metabolite panel to distinguish responders from non-responders in the discovery set (n = 51 with an AUC of 0.981), and it was confirmed in the validation set (n = 54 with an AUC of 0.929). CONCLUSIONS: Mass spectrometry based serum metabolomics approach provided larger coverage of metabolome which can help distinguish CRT responders from non-responders. A combination of isoleucine, tryptophan, and linoleic acid may associate with significant prognostic values for CRT.

Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/terapia , Isoleucina/sangue , Ácido Linoleico/sangue , Metabolômica , Triptofano/sangue , Idoso , Biomarcadores/sangue , Terapia de Ressincronização Cardíaca/efeitos adversos , Cromatografia Líquida de Alta Pressão , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Recuperação de Função Fisiológica , Índice de Gravidade de Doença , Resultado do Tratamento
Hum Reprod ; 34(12): 2330-2339, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31858122


STUDY QUESTION: Is physical activity or sedentary time associated with semen quality parameters? SUMMARY ANSWER: Among healthy men screened as potential sperm donors, higher self-reported physical activity was associated with increased progressive and total sperm motility. WHAT IS KNOWN ALREADY: Despite the claimed beneficial effect of moderate physical activity on semen quality, results from epidemiological studies have been inconclusive. Previous studies were mostly conducted among endurance athletes or male partners of couples who sought infertility treatment. STUDY DESIGN, SIZE, DURATION: Healthy men screened as potential sperm donors were recruited at the Hubei Province Human Sperm Bank of China. Between April 2017 and July 2018; 746 men completed the long-form International Physical Activity Questionnaire (IPAQ) and provided repeated semen samples (n = 5252) during an approximately 6-month period. PARTICIPANTS/MATERIALS, SETTING, METHODS: Total metabolic equivalents (METs), moderate-to-vigorous METs and sedentary time were abstracted from the IPAQ. Sperm concentration, total sperm count, progressive motility and total motility in repeated specimens were determined by trained clinical technicians. Mixed-effect models were applied to investigate the relationships between physical activity and sedentary time and repeated measures of semen quality parameters. MAIN RESULTS AND THE ROLE OF CHANCE: After adjusting for multiple confounders, total METs and moderate-to-vigorous METs were both positively associated with progressive and total sperm motility. Compared with men in the lowest quartiles, those in the highest quartiles of total and moderate-to-vigorous METs had increased progressive motility of 16.1% (95% CI: 6.4, 26.8%) and 17.3% (95% CI: 7.5, 27.9%), respectively, and had increased total motility of 15.2% (95% CI: 6.2, 24.9%) and 16.4% (95% CI: 7.4, 26.1%), respectively. Sedentary time was not associated with semen quality parameters. LIMITATIONS, REASONS FOR CAUTION: The IPAQ was reported only once from study participants; measurement errors were inevitable and may have biased our results. Furthermore, although we have adjusted for various potential confounders, the possibility of unmeasured confounding cannot be fully ruled out. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that maintaining regular exercise may improve semen quality parameters among healthy, non-infertile men. Specifically, we found that higher self-reported total and moderate-to-vigorous METs were associated with improved sperm motility, which reinforces the existing evidence that physical activity may improve male reproductive health. STUDY FUNDING/COMPETING INTEREST(S): Y.-X.W was supported by the Initiative Postdocs Supporting Program (No. BX201700087). A.P. was supported by the National Key Research and Development Program of China (2017YFC0907504). C.-L.X. was supported by the National Key Research and Development Program of China (2016YFC1000206). The authors report no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Exercício Físico , Comportamento Sedentário , Contagem de Espermatozoides/estatística & dados numéricos , Motilidade Espermática , Adulto , Voluntários Saudáveis , Humanos , Masculino , Adulto Jovem