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1.
Br J Nutr ; 123(2): 190-197, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31554528

RESUMO

A mixture of natural ingredients, namely, DHA, phosphatidylcholine, silymarin, choline, curcumin and d-α-tocopherol, was studied in subjects with non-alcoholic fatty liver disease (NAFLD). Primary endpoints were serum levels of hepatic enzymes, and other parameters of liver function, the metabolic syndrome and inflammation were the secondary endpoints. The coagulation-fibrinolysis balance was also thoroughly investigated, as NAFLD is associated with haemostatic alterations, which might contribute to increased cardiovascular risk of this condition. The present study involved a double-blind, randomised, multicentre controlled trial of two parallel groups. Subjects with NAFLD (18-80 years, either sex) received the active or control treatment for 3 months. All assays were performed on a total of 113 subjects before and at the end of supplementation. The hepatic enzymes aspartate aminotransferase (AST), alanine aminotransferase and γ-glutamyl transpeptidase decreased from 23·2 to 3·7 % after treatment, only the AST levels reaching statistical significance. However, no differences were found between control and active groups. Metabolic and inflammatory variables were unchanged, except for a slight (less than 10 %) increase in cholesterol and glucose levels after the active treatment. Coagulation-fibrinolytic parameters were unaffected by either treatment. In conclusion, chronic supplementation with the mixture of dietary compounds was well tolerated and apparently safe in NAFLD subjects. The trial failed to demonstrate any efficacy on relevant physiopathological markers, but its protocol and results may be useful to design future studies with natural compounds.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31791640

RESUMO

BACKGROUND AND AIMS: The diagnosis of LVH by ECG may particularly difficult in obese individuals. The aim of this study was to prospectively investigate whether the correction for body mass index (BMI) might improve the prognostic significance for cerebro and cardiovascular events of two electrocardiographic (ECG) criteria for left ventricular hypertrophy (LVH) in a large cohort of Italian adults. METHODS AND RESULTS: In 18,330 adults (54 ± 11 years, 55% women) from the Moli-sani cohort, obesity was defined using the ATPIII criteria. The Sokolow-Lyon (SL) and Cornell Voltage (CV) criteria were used for ECG-LVH. In overweight and obese subjects, as compared with normal weight, the prevalence of ECG-LVH by the SL index was lower. During follow-up (median 4.3 yrs), 503 cerebro and cardiovascular events occurred. One standard deviation (1-SD) increment in uncorrected and in BMI-corrected SL index and CV was associated with an increased risk of events (HR 1.12, 95% CI 1.02-1.22 and HR 1.16, 95% CI 1.06-1.26 and HR 1.12, 95% CI 1.03-1.23 and HR 1.17, 95% CI 1.07-1.27, respectively for SL and CV). In obese subjects, 1-SD increment in uncorrected CV and in BMI-corrected CV was not associated to a significant risk of events (HR 1.05, 95% CI 0.910-1.22 and HR 1.08, 95% CI 0.95-1.23 respectively). Uncorrected SL index showed a significant association with events, which was marginally stronger with BMI-corrected SL voltage (HR 1.18, 95% CI 1.02-1.37 and HR 1.17, 95% CI 1.04-1.33 respectively, Akaike information criterion change from 3220 to 3218). CONCLUSIONS: BMI correction of ECG LVH voltage criteria does not significantly improve the prediction of cerebro and cardiovascular events in obese patients in a large cohort at low cardiovascular risk.

3.
Lancet ; 394(10215): 2173-2183, 2019 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-31810609

RESUMO

BACKGROUND: The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment. METHODS: In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol. FINDINGS: Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7-59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0-20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men; p<0·0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1·1, 95% CI 1·0-1·3 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9, 1·6-2·2 for ≥5·7 mmol/L in women and from 1·1, 1·0-1·3 to 2·3, 2·0-2·5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced. INTERPRETATION: Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician-patient communication about primary prevention strategies. FUNDING: EU Framework Programme, UK Medical Research Council, and German Centre for Cardiovascular Research.


Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , LDL-Colesterol/sangue , Medição de Risco/métodos , Adulto , Idoso , Austrália/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estados Unidos/epidemiologia
4.
J Am Coll Cardiol ; 74(25): 3139-3149, 2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31856971

RESUMO

BACKGROUND: Chili pepper is a usual part of a traditional Mediterranean diet. Yet epidemiological data on the association between chili pepper intake and mortality risk are scarce, with a lack of studies from Mediterranean populations. OBJECTIVES: This study sought to examine the association between chili pepper consumption and risk of death in a large sample of the adult Italian general population, and to account for biological mediators of the association. METHODS: Longitudinal analysis was performed on 22,811 men and women enrolled in the Moli-sani Study cohort (2005 to 2010). Chili pepper intake was estimated by the EPIC (European Prospective Investigation Into Cancer) Food Frequency Questionnaire and categorized as none/rare consumption, up to 2 times/week, >2 to ≤4 times/week, and >4 times/week. RESULTS: Over a median follow-up of 8.2 years, a total of 1,236 deaths were ascertained. Multivariable hazard ratios (HRs) for all-cause and cardiovascular disease (CVD) mortality among participants in the regular (>4 times/week) relative to none/rare intake were 0.77 (95% confidence interval [CI]: 0.66 to 0.90) and 0.66 (95% CI: 0.50 to 0.86), respectively. Regular intake was also inversely associated with ischemic heart disease (HR: 0.56; 95% CI: 0.35 to 0.87) and cerebrovascular (HR: 0.39; 95% CI: 0.20 to 0.75) death risks. The association of chili pepper consumption with total mortality appeared to be stronger in hypertension-free individuals (p for interaction = 0.021). Among known biomarkers of CVD, only serum vitamin D marginally accounted for such associations. CONCLUSIONS: In a large adult Mediterranean population, regular consumption of chili pepper is associated with a lower risk of total and CVD death independent of CVD risk factors or adherence to a Mediterranean diet. Known biomarkers of CVD risk only marginally mediate the association of chili pepper intake with mortality.

5.
Adv Nutr ; 10(Supplement_4): S308-S319, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31728500

RESUMO

To update the European Association for the Study of Diabetes clinical practice guidelines for nutrition therapy, we conducted an umbrella review and updated systematic review and meta-analysis (SRMA) of prospective cohort studies of the association between dietary pulses with or without other legumes and cardiometabolic disease outcomes. We searched the PubMed, MEDLINE, EMBASE, and Cochrane databases through March 2019. We included the most recent SRMAs of prospective cohort studies and new prospective cohort studies published after the census dates of the included SRMAs assessing the relation between dietary pulses with or without other legumes and incidence and mortality of cardiovascular diseases (CVDs) [including coronary heart disease (CHD), myocardial infarction (MI), and stroke], diabetes, hypertension, and/or obesity. Two independent reviewers extracted data and assessed risk of bias. Risk estimates were pooled using the generic inverse variance method and expressed as risk ratios (RRs) with 95% CIs. The overall certainty of the evidence was assessed using the GRADE approach. Six SRMAs were identified and updated to include 28 unique prospective cohort studies with the following number of cases for each outcome: CVD incidence, 10,261; CVD mortality, 16,168; CHD incidence, 7786; CHD mortality, 3331; MI incidence, 2585; stroke incidence, 8570; stroke mortality, 2384; diabetes incidence, 10,457; hypertension incidence, 83,284; obesity incidence, 8125. Comparing the highest with the lowest level of intake, dietary pulses with or without other legumes were associated with significant decreases in CVD (RR: 0.92; 95% CI: 0.85, 0.99), CHD (RR: 0.90; 95% CI: 0.83, 0.99), hypertension (RR: 0.91; 95% CI: 0.86, 0.97), and obesity (RR: 0.87; 95% CI: 0.81, 0.94) incidence. There was no association with MI, stroke, and diabetes incidence or CVD, CHD, and stroke mortality. The overall certainty of the evidence was graded as "low" for CVD incidence and "very low" for all other outcomes. Current evidence shows that dietary pulses with or without other legumes are associated with reduced CVD incidence with low certainty and reduced CHD, hypertension, and obesity incidence with very low certainty. More research is needed to improve our estimates. This trial was registered at clinicaltrials.gov as NCT03555734.

6.
Europace ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31740944

RESUMO

AIMS: Limited evidence is available on the temporal relationship between atrial fibrillation (AF) and ischaemic stroke and their impact on mortality in the community. We sought to understand the temporal relationship of AF and ischaemic stroke and to determine the sequence of disease onset in relation to mortality. METHODS AND RESULTS: Across five prospective community cohorts of the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project we assessed baseline cardiovascular risk factors in 100 132 individuals, median age 46.1 (25th-75th percentile 35.8-57.5) years, 48.4% men. We followed them for incident ischaemic stroke and AF and determined the relation of subsequent disease diagnosis with overall mortality. Over a median follow-up of 16.1 years, N = 4555 individuals were diagnosed solely with AF, N = 2269 had an ischaemic stroke but no AF diagnosed, and N = 898 developed both, ischaemic stroke and AF. Temporal relationships showed a clustering of diagnosis of both diseases within the years around the diagnosis of the other disease. In multivariable-adjusted Cox regression analyses with time-dependent covariates subsequent diagnosis of AF after ischaemic stroke was associated with increased mortality [hazard ratio (HR) 4.05, 95% confidence interval (CI) 2.17-7.54; P < 0.001] which was also apparent when ischaemic stroke followed after the diagnosis of AF (HR 3.08, 95% CI 1.90-5.00; P < 0.001). CONCLUSION: The temporal relations of ischaemic stroke and AF appear to be bidirectional. Ischaemic stroke may precede detection of AF by years. The subsequent diagnosis of both diseases significantly increases mortality risk. Future research needs to investigate the common underlying systemic disease processes.

7.
JAMA Cardiol ; : 1-10, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31664431

RESUMO

Importance: Risk stratification for coronary heart disease (CHD) remains challenging because of the complex causative mechanism of the disease. Metabolomic profiling offers the potential to detect new biomarkers and improve CHD risk assessment. Objective: To evaluate the association between circulating metabolites and incident CHD in a large European cohort. Design, Setting, and Participants: This population-based study used the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) case-cohort to measure circulating metabolites using a targeted approach in serum samples from 10 741 individuals without prevalent CHD. The cohort consisted of a weighted, random subcohort of the original cohort of more than 70 000 individuals. The case-cohort design was applied to 6 European cohorts: FINRISK97 (Finland), Monitoring of Trends and Determinants in Cardiovascular Diseases/Cooperative Health Research in the Region of Augsburg (MONICA/KORA; Germany), MONICA-Brianza and Moli-Sani (Italy), DanMONICA (Denmark), and the Scottish Heart Health Extended Cohort (United Kingdom). Main Outcomes and Measures: Associations with time to CHD onset were assessed individually by applying weighted and adjusted Cox proportional hazard models. The association of metabolites with CHD onset was examined by C indices. Results: In 10 741 individuals (4157 women [38.7%]; median [interquartile range] age, 56.5 [49.2-62.2] years), 2166 incident CHD events (20.2%) occurred over a median (interquartile range) follow-up time of 9.2 (4.5-15.0) years. Among the 141 metabolites analyzed, 24 were significantly associated with incident CHD at a nominal P value of .05, including phosphatidylcholines (PCs), lysoPCs, amino acids, and sphingolipids. Five PCs remained significant after correction for multiple testing: acyl-alkyl-PC C40:6 (hazard ratio [HR], 1.13 [95% CI, 1.07-1.18]), diacyl-PC C40:6 (HR, 1.10 [95% CI, 1.04-1.15]), acyl-alkyl-PC C38:6 (HR, 1.11 [95% CI, 1.05-1.16]), diacyl-PC C38:6 (HR, 1.09 [95% CI, 1.04-1.14]) and diacyl-PC C38:5 (HR, 1.10 [95% CI, 1.05-1.16]). Lower levels of these metabolites were associated with increased risk of incident CHD. The strength of the associations competes with those of classic risk factors (C statistics: acyl-alkyl-PC C40:6, 0.756 [95% CI, 0.738-0.774], diacyl-PC C40:6, 0.754 [95% CI, 0.736-0.772], acyl-alkyl-PC C38:6, 0.755 [95% CI, 0.736-0.773], diacyl-PC C38:6, 0.754 [95% CI, 0.736-0.772]), diacyl-PC C38:5, 0.754 [95% CI, 0.736-0.772]). Adding metabolites to a base risk model including classic risk factors high-sensitivity C-reactive protein and high-sensitivity troponin I did not improve discrimination by C statistics. Conclusions and Relevance: Five PCs were significantly associated with increased risk of incident CHD and showed comparable discrimination with individual classic risk factors. Although these metabolites do not improve CHD risk assessment beyond that of classic risk factors, these findings hold promise for an improved understanding of the pathophysiology of CHD.

8.
Clin Epigenetics ; 11(1): 151, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31665082

RESUMO

BACKGROUND: Platelet-endothelial aggregation receptor 1 (PEAR-1) is a transmembrane receptor involved in platelet activation and megakaryopoiesis whose expression is driven by DNA methylation. PEAR1 variants were associated with differential platelet response to activation and cardiovascular outcomes. We aimed at investigating the link between PEAR1 methylation and platelet and leukocyte function markers in a family-based population. RESULTS: We measured PEAR1 methylation in 605 Moli-family participants with available blood counts, plasma P-selectin and C-reactive protein, whole blood platelet P-selectin, and platelet-leukocyte mixed conjugate measurements. We performed principal component analysis (PCA) to identify groups of highly correlated CpG sites. We used linear mixed regression models (using age, gender, BMI, smoking, alcohol drinking, being a proband for family recruitment, being a member of myocardial infarction (MI) family as fixed effects, and family as a random effect) to evaluate associations between PEAR1 methylation and phenotypes. PEAR1 methylation Factor2, characterized by the previously identified megakaryocyte-specific CpG sites, was inversely associated with platelet-monocyte conjugates, P-selectin, and WBC counts, while positively associated with the platelet distribution width (PDW) and with leukocyte CD11b and L-selectin. Moreover, PEAR1 Factor2 methylation was negatively associated with INFLAscore, a low-grade inflammation score. The latter was partially mediated by the PEAR1 methylation effect on platelet variables. PEAR1 methylation association with WBC measurements and INFLAscore was confirmed in the independent cohort FLEMENGHO. CONCLUSIONS: We report a significant link between epigenetic signatures in a platelet functional gene and inflammation-dependent platelet function variability measured in two independent cohorts.

11.
Nutrients ; 11(8)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31374914

RESUMO

Opinions are conflicting about the epidemiology of vitamin D deficiency. This population-based study investigated cross-sectionally the associations of 25-hydroxyvitamin D (calcidiol) and 1,25-dihydroxyvitamin D (calcitriol) with indices of mineral homeostasis. Study cohort consisted of 979 persons of the Moli-Sani study, both sexes, ages ≥35 years. Data collection included serum calcidiol by different assays, serum calcitriol, serum parathyroid hormone, serum and urine calcium, and phosphorus. Prevalence of mild-to-moderate calcidiol deficiency (10-19 ng/mL) was 36.4% and did not associate with hypocalcemia or hyperparathyroidism. Prevalence of severe calcidiol deficiency (<10 ng/mL) was 16.8% and associated with hyperparathyroidism only (odds ratio = 8.81, 95% confidence interval = 2.4/32.9). Prevalence of calcitriol deficiency (<18 pg/mL) was 3.1% and associated with hypocalcemia (29.1, 7.4/114.5) but not hyperparathyroidism. In ANOVA along concentration strata, lower calcidiol associated with higher parathyroid hormone only (p < 0.001). Lower calcitriol associated with lower serum and urine calcium (p < 0.001) but not with parathyroid hormone. Calcidiol findings were consistent with different calcidiol assays. In the population, mild-to-moderate calcidiol deficiency did not associate with abnormal mineral homeostasis. Severe calcidiol deficiency and calcitriol deficiency associated with different disorders: lower calcidiol associated with hyperparathyroidism whereas lower calcitriol associated with hypocalcemia and low urine calcium.


Assuntos
Cálcio/sangue , Hiperparatireoidismo/sangue , Hipocalcemia/sangue , Hormônio Paratireóideo/sangue , Deficiência de Vitamina D/sangue , Vitamina D/análogos & derivados , Adulto , Idoso , Biomarcadores/sangue , Estudos Transversais , Feminino , Homeostase , Humanos , Hiperparatireoidismo/diagnóstico , Hiperparatireoidismo/epidemiologia , Hipocalcemia/diagnóstico , Hipocalcemia/epidemiologia , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Índice de Gravidade de Doença , Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico , Deficiência de Vitamina D/epidemiologia
12.
Front Med (Lausanne) ; 6: 146, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31338367

RESUMO

In recent years, different machine learning algorithms have been developed for the estimation of Biological Age (BA), defined as the hypothetical underlying age of an organism. BA can be computed based on different circulating and non-circulating biomarkers. In this perspective, identifying biomarkers with a prominent influence on BA and developing reliable models for its estimation is of fundamental importance for monitoring healthy aging, and could provide new tools to screen health status and the risk of clinical events in the general population. Here, we briefly review the different machine learning (ML) approaches used for BA estimation, focusing on those methods with potential application to the Moli-sani study, a prospective population-based cohort study of 24,325 subjects (35-99 years). In particular, we discuss the potential of BA estimation based on blood biomarkers, which likely represents the easiest and most immediate way to compute organismal BA. Similarly, we describe ML methods for the estimation of brain age based on structural neuroimaging features. For each method, we discuss the relation with epidemiological variables (e.g., mortality), genetic and environmental factors, and common age-related diseases (e.g., Alzheimer disease), to examine the potential as aging biomarker in the general population. Finally, we hypothesize new approaches for BA estimation, both at the single organ and at the whole organism level. Overall, here we trace the road ahead in the Big Data era for our and other prospective general population cohorts, presenting ways to exploit the notable amount of data available nowadays.

13.
Appetite ; 142: 104376, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31326439

RESUMO

AIM: The neuropeptide neuromedin U (NMU) known for its role in appetite, feeding and energy balance could be involved in the control of food choice and taste sensitivity. We examined the association between NMU polymorphisms/haplotypes and taste thresholds and food preferences in a population of European children. METHODS: A total of 578 subjects from the IDEFICS study (mean age 7.5 ±â€¯0.8 SD, boys 53.6%) with NMU genotype data and food preference (salty, fatty, sweet, flavour and umami food) and taste threshold (salt, fat, sweet, umami) tests available were analysed. Three single nucleotide polymorphisms (SNPs; rs6827359, T:C; rs12500837, T:C; rs9999653, C:T) of NMU gene were analyzed and five major haplotypes were inferred. The associations between genotypes and food preferences or taste thresholds were investigated (odds ratios -OR, adjusted for age, sex and country). A p < 0.05 after false discovery rate adjustment (pFDR) was considered statistically significant. RESULTS: The association between NMU genotypes and food preference showed two NMU SNPs associated with preference for food containing sodium glutamate (umami taste; rs6827359C, OR = 1.61, 95% confidence interval (CI):1.20-2.17; rs9999653T, OR = 1.59, 95%CI:1.18-2.13). In the haplotype analysis, the CTT haplotype showed an OR of 1.70 (95%CI:1.16-2.5) for the umami food preference, while CCT haplotype showed an OR of 1.63 (95%CI:1.11-2.40), compared to the most frequent haplotype (TTC). Carriers of CCT/CCT vs subjects with no CCT haplotype showed an OR of 4.78 (95%CI:1.86-12.30). Umami food preference was associated with low values of BMI z-score, arm circumferences, skinfolds and fat mass (pFDR<0.05). No association between NMU genetic variants and taste thresholds was found. CONCLUSIONS: This study shows for the first time in children an association between preference for umami food and a NMU haplotype, previously found associated with low BMI values.

14.
N Engl J Med ; 380(26): 2529-2540, 2019 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-31242362

RESUMO

BACKGROUND: Data regarding high-sensitivity troponin concentrations in patients presenting to the emergency department with symptoms suggestive of myocardial infarction may be useful in determining the probability of myocardial infarction and subsequent 30-day outcomes. METHODS: In 15 international cohorts of patients presenting to the emergency department with symptoms suggestive of myocardial infarction, we determined the concentrations of high-sensitivity troponin I or high-sensitivity troponin T at presentation and after early or late serial sampling. The diagnostic and prognostic performance of multiple high-sensitivity troponin cutoff combinations was assessed with the use of a derivation-validation design. A risk-assessment tool that was based on these data was developed to estimate the risk of index myocardial infarction and of subsequent myocardial infarction or death at 30 days. RESULTS: Among 22,651 patients (9604 in the derivation data set and 13,047 in the validation data set), the prevalence of myocardial infarction was 15.3%. Lower high-sensitivity troponin concentrations at presentation and smaller absolute changes during serial sampling were associated with a lower likelihood of myocardial infarction and a lower short-term risk of cardiovascular events. For example, high-sensitivity troponin I concentrations of less than 6 ng per liter and an absolute change of less than 4 ng per liter after 45 to 120 minutes (early serial sampling) resulted in a negative predictive value of 99.5% for myocardial infarction, with an associated 30-day risk of subsequent myocardial infarction or death of 0.2%; a total of 56.5% of the patients would be classified as being at low risk. These findings were confirmed in an external validation data set. CONCLUSIONS: A risk-assessment tool, which we developed to integrate the high-sensitivity troponin I or troponin T concentration at emergency department presentation, its dynamic change during serial sampling, and the time between the obtaining of samples, was used to estimate the probability of myocardial infarction on emergency department presentation and 30-day outcomes. (Funded by the German Center for Cardiovascular Research [DZHK]; ClinicalTrials.gov numbers, NCT00470587, NCT02355457, NCT01852123, NCT01994577, and NCT03227159; and Australian New Zealand Clinical Trials Registry numbers, ACTRN12611001069943, ACTRN12610000766011, ACTRN12613000745741, and ACTRN12611000206921.).


Assuntos
Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Medição de Risco/métodos , Troponina/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos de Coortes , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Sensibilidade e Especificidade , Troponina I/sangue
15.
Clin Epigenetics ; 11(1): 74, 2019 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-31077224

RESUMO

BACKGROUND: Zinc finger and BTB domain-containing protein 12 (ZBTB12) is a predicted transcription factor with potential role in hematopoietic development. Recent evidence linked low methylation level of ZBTB12 exon1 to myocardial infarction (MI) risk. However, the role of ZBTB12 in the pathogenesis of MI and cardiovascular disease in general is not yet clarified. We investigated the relation between ZBTB12 methylation and several blood parameters related to cardio-cerebrovascular risk in an Italian family-based cohort. RESULTS: ZBTB12 methylation was analyzed on white blood cells from the Moli-family cohort using the Sequenom EpiTYPER MassARRAY (Agena). A total of 13 CpG Sequenom units were analyzed in the small CpG island located in the only translated ZBTB12 exon. Principal component analysis (PCA) was performed to identify groups of CpG units with similar methylation estimates. Linear mixed effect regressions showed a positive association between methylation of ZBTB12 Factor 2 (including CpG units 8, 9-10, 16, 21) and TNF-ɑ stimulated procoagulant activity, a measure of procoagulant and inflammatory potential of blood cells. In addition, we also found a negative association between methylation of ZBTB12 Factor 1 (mainly characterized by CpG units 1, 3-4, 5, 11, and 26) and white blood cell and granulocyte counts. An in silico prediction analysis identified granulopoiesis- and hematopoiesis-specific transcription factors to potentially bind DNA sequences encompassing CpG1, CpG3-4, and CpG11. CONCLUSIONS: ZBTB12 hypomethylation is linked to shorter TNF-ɑ stimulated whole blood coagulation time and increased WBC and granulocyte counts, further elucidating the possible link between ZBTB12 methylation and cardiovascular disease risk.

16.
J Epidemiol Community Health ; 73(6): 516-528, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30898851

RESUMO

BACKGROUND: A life course approach has been suggested as the most appropriate to establish the total impact of socioeconomic status (SES) on adult health outcomes; however, such an approach has been poorly used within Mediterranean populations. We aimed to examine the SES trajectories from childhood to adulthood associated with mortality risk in a large general population-based cohort and to test potential pathways (eg, inflammation) underlying such associations. METHODS: Longitudinal analyses on 22 194 subjects recruited in the Moli-sani Study, Italy (2005-2010). Low and high SES in childhood, educational attainment (low/high) and SES during adulthood (measured by a score including material resources and dichotomised as low/high) were used to define overall trajectories. RESULTS: Over 8.3 years of follow-up, 1155 deaths occurred. In the group with poor childhood SES, an upward trajectory in both educational and material circumstances was associated with lower risk of all-cause death (HR=0.64; 95% CI 0.47 to 0.87), as opposed to subjects who remained stably low (low education and adulthood SES). Subjects with high childhood SES, but not educational achievement, were at increased risk of total and cardiovascular disease (CVD) death, although reporting higher material SES in adult life, as compared with the stably high SES group (HR=1.44; 1.02 to 2.02 and HR=1.90; 1.10 to 3.28, respectively). Inflammatory markers marginally accounted for such associations. CONCLUSION: For individuals with low SES in early life, an educational and material upward trajectory over the life course was associated with lower mortality risk. In the high SES childhood group, lack of a higher educational attainment appeared to be unfavourably associated with survival.

17.
J Clin Hypertens (Greenwich) ; 21(5): 572-578, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30892825

RESUMO

The present study aims to examine the cross-sectional and longitudinal association between self-reported nocturnal sleep duration, blood pressure, and hypertension in European children, aged 2-9.9 years, participating in the IDEFICS project. Blood pressure (BP) and the main anthropometric indices were measured according to standardized procedures. Childhood elevated BP and hypertension were defined according to the European Society of Hypertension Guidelines for children and adolescents. Parents reported lifestyle and socio-demographic data. Nocturnal sleep duration was assessed as part of a parental 24-h recall and categorized as follows: (a) ≤9 hours/night; (b) >9 hours to ≤10 hours/night; (c) >10 hours to ≤11 hours/night; and (d) >11 hours/night. A complete set of variables included in the present analysis was provided by 7974 participants (boys/girls = 4049/3925) at the baseline survey (T0). Of them, 5656 were re-examined 2 years later at follow-up (T1). Children reporting shorter sleep duration at T0 had significantly higher BP values (P for trend < 0.001) compared to those who slept more. Prospective analyses showed that shorter sleep duration at baseline predicted, over the 2-year follow-up, higher increases in systolic blood pressure and diastolic blood pressure, after adjustment for age, sex, country of origin, BMI z-score, parental education, physical activity, screen time, and T0 value of the examined outcome variables (P for trend < 0.001). Our findings reveal that shorter sleep duration is associated with higher BP in childhood, suggesting that sleep may be a potential risk factor for hypertension later in life.

18.
JACC Heart Fail ; 7(3): 204-213, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30819375

RESUMO

OBJECTIVES: This study investigates differences between women and men in heart failure (HF) risk and mortality. BACKGROUND: Sex differences in HF epidemiology are insufficiently understood. METHODS: In 78,657 individuals (median 49.5 years of age; age range 24.1 to 98.7 years; 51.7% women) from community-based European studies (FINRISK, DanMONICA, Moli-sani, Northern Sweden) of the BiomarCaRE (Biomarker for Cardiovascular Risk Assessment in Europe) consortium, the association between incident HF and mortality, the relationship of cardiovascular risk factors, prevalent cardiovascular diseases, biomarkers (C-reactive protein [CRP]; N-terminal pro-B-type natriuretic peptide [NT-proBNP]) with incident HF, and their attributable risks were tested in women vs. men. RESULTS: Over a median follow-up of 12.7 years, fewer HF cases were observed in women (n = 2,399 [5.9%]) than in men (n = 2,771 [7.3%]). HF incidence increased markedly after 60 years of age, initially with a more rapid increase in men, whereas incidence in women exceeded that of men after 85 years of age. HF onset substantially increased mortality risk in both sexes. Multivariable-adjusted Cox models showed the following sex differences for the association with incident HF: systolic blood pressure hazard ratio (HR) according to SD in women of 1.09 (95% confidence interval [CI]: 1.05 to 1.14) versus HR of 1.19 (95% CI: 1.14 to 1.24) in men; heart rate HR of 0.98 (95% CI: 0.93 to 1.03) in women versus HR of 1.09 (95% CI: 1.04 to 1.13) in men; CRP HR of 1.10 (95% CI: 1.00 to 1.20) in women versus HR of 1.32 (95% CI: 1.24 to 1.41) in men; and NT-proBNP HR of 1.54 (95% CI: 1.37 to 1.74) in women versus HR of 1.89 (95% CI: 1.75 to 2.05) in men. Population-attributable risk of all risk factors combined was 59.0% in women and 62.9% in men. CONCLUSIONS: Women had a lower risk for HF than men. Sex differences were seen for systolic blood pressure, heart rate, CRP, and NT-proBNP, with a lower HF risk in women.

19.
Eur J Epidemiol ; 34(4): 337-349, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30826941

RESUMO

Several meta-analyses including a small number of cohorts showed inverse associations between the Mediterranean Diet (MedDiet) and risk of stroke. However, it remains unclear whether such a relation varies by region of the study population or by major subtypes of stroke. We searched PubMed and EMBASE databases for relevant studies and we further included unpublished results from the Singapore Chinese Health Study (N = 57,078) and the Seguimiento Universidad de Navarra (SUN) study (N = 12,670). We used a random-effects model to calculate summary relative risk (RR) with 95% confidence intervals (CI) of stroke for each 4-point increment of the MedDiet score, roughly corresponding to the difference between extreme quintiles of the MedDiet score among participants of the included studies. The final analyses included 20 prospective cohort studies involving 682,149 participants and 16,739 stroke cases. The summary RRs for each 4-point increment of the MedDiet score were 0.84 (95% CI 0.81-0.88; I2 = 11.5%) for all combined, 0.76 (95% CI 0.65-0.89) for studies in Mediterranean populations and 0.86 (95% CI 0.83-0.89) for those in non-Mediterranean populations. Lower risk of stroke associated with higher MedDiet score also was observed in the analyses stratified by study population and methodological characteristics including study risk of bias, version of the MedDiet index, and definition of moderate alcohol consumption. The MedDiet was similarly associated with lower risk of ischemic stroke (RR 0.86, 95% CI 0.81-0.91; nine studies) and hemorrhagic stroke (RR 0.83, 95% CI 0.74-0.93; eight studies). Our meta-analysis suggests that adhering to the Mediterranean diet was associated with lower risk of stroke in both Mediterranean and non-Mediterranean populations, and for both ischemic stroke and hemorrhagic stroke risk.


Assuntos
Isquemia Encefálica/epidemiologia , Dieta Mediterrânea/estatística & dados numéricos , Hemorragias Intracranianas/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Humanos , Medição de Risco
20.
Stroke ; 50(3): 610-617, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30786848

RESUMO

Background and Purpose- NT-proBNP (N-terminal pro-B-type natriuretic peptide) is a risk factor for atrial fibrillation and a marker of cardiac function used in the detection of heart failure. Given the link between cardiac dysfunction and stroke, NT-proBNP is a candidate marker of stroke risk. Our aim was to evaluate the association of NT-proBNP with stroke and to determine the predictive value beyond a panel of established risk factors. Methods- Based on the Biomarkers for Cardiovascular Risk Assessment in Europe-Consortium, we analyzed data of 58 173 participants (50% men; mean age 52 y) free of stroke from 6 community-based cohorts. NT-proBNP measurements were performed in the central Biomarkers for Cardiovascular Risk Assessment in Europe laboratory. The outcomes considered were total stroke and subtypes of stroke (ischemic/hemorrhagic). Results- During a median follow-up time of 7.9 years, we observed 1550 stroke events (1176 ischemic). Increasing quarters of the NT-proBNP distribution were associated with increasing risk of stroke ( P for trend <0.0001; multivariable Cox regression analysis adjusted for risk factors and cardiac diseases). Individuals in the highest NT-proBNP quarter (NT-proBNP >82.2 pg/mL) had 2-fold (95% CI, 75%-151%) greater risk of stroke than individuals in the lowest quarter (NT-proBNP <20.4 pg/mL). The association remained unchanged when adjusted for interim coronary events during follow-up, and though it was somewhat heterogeneous across cohorts, it was highly homogenous according to cardiovascular risk profile or subtypes of stroke. The addition of NT-proBNP to a reference model increased the C-index discrimination measure by 0.006 ( P=0.0005), yielded a categorical net reclassification improvement of 2.0% in events and 1.4% in nonevents and an integrated discrimination improvement of 0.007. Conclusions- In European individuals free of stroke, levels of NT-proBNP are positively associated with risk of ischemic and hemorrhagic stroke, independently from several other risk factors and conditions. The addition of NT-proBNP to variables of established risk scores improves prediction of stroke, with a medium effect size.


Assuntos
Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/epidemiologia , Adulto , Fibrilação Atrial/complicações , Fibrilação Atrial/epidemiologia , Biomarcadores , Isquemia Encefálica/sangue , Isquemia Encefálica/epidemiologia , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Humanos , Hemorragias Intracranianas/sangue , Hemorragias Intracranianas/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Fatores Sexuais , Resultado do Tratamento
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