Background There is growing evidence that sleep duration and quality may be associated with cardiovascular harm and mortality. Methods and Results We conducted a systematic review, meta-analysis, and ...spline analysis of prospective cohort studies that evaluate the association between sleep duration and quality and cardiovascular outcomes. We searched MEDLINE and EMBASE for these studies and extracted data from identified studies. We utilized linear and nonlinear dose-response meta-analysis models and used DerSimonian-Laird random-effects meta-analysis models of risk ratios, with inverse variance weighting, and the I
statistic to quantify heterogeneity. Seventy-four studies including 3 340 684 participants with 242 240 deaths among 2 564 029 participants who reported death events were reviewed. Findings were broadly similar across both linear and nonlinear dose-response models in 30 studies with >1 000 000 participants, and we report results from the linear model. Self-reported duration of sleep >8 hours was associated with a moderate increased risk of all-cause mortality, with risk ratio , 1.14 (1.05-1.25) for 9 hours, risk ratio, 1.30 (1.19-1.42) for 10 hours, and risk ratio, 1.47 (1.33-1.64) for 11 hours. No significant difference was identified for periods of self-reported sleep <7 hours, whereas similar patterns were observed for stroke and cardiovascular disease mortality. Subjective poor sleep quality was associated with coronary heart disease (risk ratio , 1.44; 95% confidence interval, 1.09-1.90), but no difference in mortality and other outcomes. Conclusions Divergence from the recommended 7 to 8 hours of sleep is associated with a higher risk of mortality and cardiovascular events. Longer duration of sleep may be more associated with adverse outcomes compared with shorter sleep durations.
► Putrescine accumulates in response to altered polyamine biosynthesis and stress. ► GABA accumulation in stressed plants is not correlated with putrescine levels. ► Putrescine catabolism relies on ...both gene-dependent and -independent processes. ► Putative diamine oxidases may be stress inducible and limited by O2 supply. ► 4-Aminobutyraldehyde dehydrogenase activity should be controlled by redox status.
4-Aminobutyrate (GABA) accumulates in various plant parts, including bulky fruits such as apples, in response to abiotic stress. It is generally believed that the GABA is derived from glutamate, although a contribution from polyamines is possible. Putrescine, but not spermidine and spermine, generally accumulates in response to the genetic manipulation of polyamine biosynthetic enzymes and abiotic stress. However, the GABA levels in stressed plants are influenced by processes other than putrescine availability. It is hypothesized that the catabolism of putrescine to GABA is regulated by a combination of gene-dependent and -independent processes. The expression of several putative diamine oxidase genes is weak, but highly stress-inducible in certain tissues of Arabidopsis. In contrast, candidate genes that encode 4-aminobutyraldehyde dehydrogenase are highly constitutive, but not stress inducible. Changes in O2 availability and cellular redox balance due to stress may directly influence the activities of diamine oxidase and 4-aminobutyraldehyde dehydrogenase, thereby restricting GABA formation. Apple fruit is known to accumulate GABA under controlled atmosphere storage and therefore could serve as a model system for investigating the relative contribution of putrescine and glutamate to GABA production.
IgA nephropathy (IgAN), an important cause of kidney failure, is characterized by glomerular IgA deposition and is associated with changes in
-glycosylation of the IgA1 molecule. Here, we sought to ...identify genetic factors contributing to levels of galactose-deficient IgA1 (Gd-IgA1) in white and Chinese populations. Gd-IgA1 levels were elevated in IgAN patients compared with ethnically matched healthy subjects and correlated with evidence of disease progression. White patients with IgAN exhibited significantly higher Gd-IgA1 levels than did Chinese patients. Among individuals without IgAN, Gd-IgA1 levels did not correlate with kidney function. Gd-IgA1 level heritability (h
), estimated by comparing midparental and offspring Gd-IgA1 levels, was 0.39. Genome-wide association analysis by linear regression identified alleles at a single locus spanning the
gene that strongly associated with Gd-IgA1 level (
=0.26;
=2.35×10
). This association was replicated in a genome-wide association study of separate cohorts comprising 308 patients with membranous GN from the UK (
<1.00×10
) and 622 controls with normal kidney function from the UK (
<1.00×10
), and in a candidate gene study of 704 Chinese patients with IgAN (
<1.00×10
). The same extended haplotype associated with elevated Gd-IgA1 levels in all cohorts studied.
encodes a galactosyltransferase enzyme that is important in
-galactosylation of glycoproteins. These findings demonstrate that common variation at
influences Gd-IgA1 level in the population, which independently associates with risk of progressive IgAN, and that the pathogenic importance of changes in IgA1
-glycosylation may vary between white and Chinese patients with IgAN.
Objective To investigate dietary fibre intake and any potential dose-response association with coronary heart disease and cardiovascular disease.Design Systematic review of available literature and ...dose-response meta-analysis of cohort studies using random effects models.Data sources The Cochrane Library, Medline, Medline in-process, Embase, CAB Abstracts, ISI Web of Science, BIOSIS, and hand searching.Eligibility criteria for studies Prospective studies reporting associations between fibre intake and coronary heart disease or cardiovascular disease, with a minimum follow-up of three years and published in English between 1 January 1990 and 6 August 2013.Results 22 cohort study publications met inclusion criteria and reported total dietary fibre intake, fibre subtypes, or fibre from food sources and primary events of cardiovascular disease or coronary heart disease. Total dietary fibre intake was inversely associated with risk of cardiovascular disease (risk ratio 0.91 per 7 g/day (95% confidence intervals 0.88 to 0.94)) and coronary heart disease (0.91 (0.87 to 0.94)). There was evidence of some heterogeneity between pooled studies for cardiovascular disease (I2=45% (0% to 74%)) and coronary heart disease (I2=33% (0% to 66%)). Insoluble fibre and fibre from cereal and vegetable sources were inversely associated with risk of coronary heart disease and cardiovascular disease. Fruit fibre intake was inversely associated with risk of cardiovascular disease.Conclusions Greater dietary fibre intake is associated with a lower risk of both cardiovascular disease and coronary heart disease. Findings are aligned with general recommendations to increase fibre intake. The differing strengths of association by fibre type or source highlight the need for a better understanding of the mode of action of fibre components.
International studies report a decline in mortality following non-ST-elevation myocardial infarction (NSTEMI). Whether this is due to lower baseline risk or increased utilization of ...guideline-indicated treatments is unknown.
To determine whether changes in characteristics of patients with NSTEMI are associated with improvements in outcomes.
Data on patients with NSTEMI in 247 hospitals in England and Wales were obtained from the Myocardial Ischaemia National Audit Project between January 1, 2003, and June 30, 2013 (final follow-up, December 31, 2013).
Baseline demographics, clinical risk (GRACE risk score), and pharmacological and invasive coronary treatments.
Adjusted all-cause 180-day postdischarge mortality time trends estimated using flexible parametric survival modeling.
Among 389 057 patients with NSTEMI (median age, 72.7 years IQR, 61.7-81.2 years; 63.1% men), there were 113 586 deaths (29.2%). From 2003-2004 to 2012-2013, proportions with intermediate to high GRACE risk decreased (87.2% vs 82.0%); proportions with lowest risk increased (4.2% vs 7.6%; P= .01 for trend). The prevalence of diabetes, hypertension, cerebrovascular disease, chronic obstructive pulmonary disease, chronic renal failure, previous invasive coronary strategy, and current or ex-smoking status increased (all P < .001). Unadjusted all-cause mortality rates at 180 days decreased from 10.8% to 7.6% (unadjusted hazard ratio HR, 0.968 95% CI, 0.966-0.971; difference in absolute mortality rate per 100 patients AMR/100, -1.81 95% CI, -1.95 to -1.67). These findings were not substantially changed when adjusted additively by baseline GRACE risk score (HR, 0.975 95% CI, 0.972-0.977; AMR/100, -0.18 95% CI, -0.21 to -0.16), sex and socioeconomic status (HR, 0.975 95% CI, 0.973-0.978; difference in AMR/100, -0.24 95% CI, -0.27 to -0.21), comorbidities (HR, 0.973 95% CI, 0.970-0.976; difference in AMR/100, -0.44 95% CI, -0.49 to -0.39), and pharmacological therapies (HR, 0.972 95% CI, 0.964-0.980; difference in AMR/100, -0.53 95% CI, -0.70 to -0.36). However, the direction of association was reversed after further adjustment for use of an invasive coronary strategy (HR, 1.02 95% CI, 1.01-1.03; difference in AMR/100, 0.59 95% CI, 0.33-0.86), which was associated with a relative decrease in mortality of 46.1% (95% CI, 38.9%-52.0%).
Among patients hospitalized with NSTEMI in England and Wales, improvements in all-cause mortality were observed between 2003 and 2013. This was significantly associated with use of an invasive coronary strategy and not entirely related to a decline in baseline clinical risk or increased use of pharmacological therapies.
The aim of this study was to determine if earlier administration of oral β blocker therapy in patients with acute coronary syndromes (ACSs) is associated with an increased short-term survival rate ...and improved left ventricular (LV) function. We studied 11,581 patients enrolled in the International Survey of Acute Coronary Syndromes in Transitional Countries registry from January 2010 to June 2014. Of these patients, 6,117 were excluded as they received intravenous β blockers or remained free of any β blocker treatment during hospital stay, 23 as timing of oral β blocker administration was unknown, and 182 patients because they died before oral β blockers could be given. The final study population comprised 5,259 patients. The primary outcome was the incidence of in-hospital mortality. The secondary outcome was the incidence of severe LV dysfunction defined as an ejection fraction <40% at hospital discharge. Oral β blockers were administered soon (≤24 hours) after hospital admission in 1,377 patients and later (>24 hours) during hospital stay in the remaining 3,882 patients. Early β blocker therapy was significantly associated with reduced in-hospital mortality (odds ratio 0.41, 95% CI 0.21 to 0.80) and reduced incidence of severe LV dysfunction (odds ratio 0.57, 95% CI 0.42 to 0.78). Significant mortality benefits with early β blocker therapy disappeared when patients with Killip class III/IV were included as dummy variables. The results were confirmed by propensity score–matched analyses. In conclusion, in patients with ACSs, earlier administration of oral β blocker therapy should be a priority with a greater probability of improving LV function and in-hospital survival rate. Patients presenting with acute pulmonary edema or cardiogenic shock should be excluded from this early treatment regimen.
The ubiquitous, non-proteinaceous amino acid GABA (γ-aminobutyrate) accumulates in plants subjected to abiotic stresses such as chilling, O2 deficiency and elevated CO2. Recent evidence indicates ...that controlled atmosphere storage causes the accumulation of GABA in apple (Malus x domestica Borkh.) fruit, and now there is increasing interest in the biochemical mechanisms responsible for this phenomenon. Here, we investigated whether this phenomenon could be mediated via Ca(2+)/calmodulin (CaM) activation of glutamate decarboxylase (GAD) activity.
GAD activity in cell-free extracts of apple fruit was stimulated by Ca(2+)/CaM at physiological pH, but not at the acidic pH optimum. Based on bioinformatics analysis of the apple genome, three apple GAD genes were identified and their expression determined in various apple organs, including fruit. Like recombinant Arabidopsis GAD1, the activity and spectral properties of recombinant MdGAD1 and MdGAD2 were regulated by Ca(2+)/CaM at physiological pH and both enzymes possessed a highly conserved CaM-binding domain that was autoinhibitory. In contrast, the activity and spectral properties of recombinant MdGAD3 were not affected by Ca(2+)/CaM and they were much less sensitive to pH than MdGAD1, MdGAD2 and Arabidopsis GAD1; furthermore, the C-terminal region neither bound CaM nor functioned as an autoinhibitory domain.
Plant GADs typically differ from microbial and animal GAD enzymes in possessing a C-terminal 30-50 amino acid residue CaM-binding domain. To date, rice GAD2 is the only exception to this generalization; notably, the C-terminal region of this enzyme still functions as an autoinhibitory domain. In the present study, apple fruit were found to contain two CaM-dependent GADs, as well as a novel CaM-independent GAD that does not possess a C-terminal autoinhibitory domain.
To determine the effect of different types of dietary fibre on SBP and DBP.
A systematic review of the literature and a meta-analysis of randomized controlled trials using random-effects models. ...Eligibility criteria for studies included randomized controlled trials of at least 6 weeks duration, testing a fibre isolate or fibre-rich diet against a control or placebo published between 1 January 1990 and 1 December 2013.
Twenty-eight trials met the inclusion criteria and reported fibre intake and SBP and/or DBP. Eighteen trials were included in a meta-analysis. Studies were categorized into 1 of 12 fibre-type categories. The pooled estimates for all fibre types were -0.9 mmHg 95% confidence interval (CI) -2.5 to 0.6 mmHg and -0.7 mmHg (95% CI -1.9 to 0.5 mmHg) for SBP and DBP, respectively. The median difference in total fibre was 6 g. Analyses of specific fibre types concluded that diets rich in beta-glucans reduce SBP by 2.9 mmHg (95% CI 0.9 to 4.9 mmHg) and DBP by 1.5 mmHg (95% CI 0.2 to 2.7 mmHg) for a median difference in beta-glucans of 4 g. Heterogeneity for individual fibre types was generally low.
Higher consumption of beta-glucan fibre is associated with lower SBP and DBP. The results of this review are consistent with recommendations to increase consumption of foods rich in dietary fibre, but some additional emphasis on sources of beta-glucans, such as oats and barley, may be warranted.
ESC Core Curriculum for the Cardiologist Tanner, Felix C; Brooks, Nicolas; Fox, Kevin F ...
European heart journal,
10/2020, Letnik:
41, Številka:
38
Journal Article
Delayed onset of action of oral P2Y
inhibitors in ST-elevation myocardial infarction (STEMI) patients may increase the risk of acute stent thrombosis. Available parenteral anti-thrombotic strategies, ...to deal with this issue, are limited by added cost and increased risk of bleeding. We investigated the pharmacodynamic effects of a novel regimen of enoxaparin in STEMI patients undergoing primary percutaneous coronary intervention (PPCI). Twenty patients were recruited to receive 0.75 mg/kg bolus of enoxaparin (pre-PPCI) followed by infusion of enoxaparin 0.75 mg/kg/6 h. At four time points (pre-anti-coagulation, end of PPCI, 2-3 hours into infusion and at the end of infusion), anti-Xa levels were determined using chromogenic assays, fibrin clots were assessed by turbidimetric analysis and platelet P2Y
inhibition was determined by VerifyNow P2Y12 assay. Clinical outcomes were determined 14 hours after enoxaparin initiation. Nineteen of 20 patients completed the enoxaparin regimen; one patient, who developed no-reflow phenomenon, was switched to tirofiban after the enoxaparin bolus. All received ticagrelor 180 mg before angiography. Mean (± standard error of the mean) anti-Xa levels were sustained during enoxaparin infusion (1.17 ± 0.06 IU/mL at the end of PPCI and 1.003 ± 0.06 IU/mL at 6 hours), resulting in prolonged fibrin clot lag time and increased lysis potential. Onset of platelet P2Y
inhibition was delayed in opiate-treated patients. No patients had thrombotic or bleeding complications. In conclusion, enoxaparin 0.75 mg/kg bolus followed by 0.75 mg/kg/6 h provides sustained anti-Xa levels in PPCI patients. This may protect from acute stent thrombosis in opiate-treated PPCI patients who frequently have delayed onset of oral P2Y
inhibition.
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