Dataset Information

Lipoprotein(a) plasma levels are not associated with survival after acute coronary syndromes: An observational cohort study.

ABSTRACT: BACKGROUND:Lipoprotein(a) [Lp(a)] is associated with coronary artery disease in population studies, however studies on its predictive value in patients with cardiovascular disease, in particular after acute coronary syndromes (ACS), are conflicting. The aim of this study was to investigate whether Lp(a) is associated with survival after ACS. METHODS AND RESULTS:We analyzed Lp(a) measurement in 1,245 patients who underwent coronary angiography for ACS. The median follow-up for cardiovascular and all-cause mortality was 5.0 (IQR 3.2-8.0) years. 655 (52.6%) presented with ST-segment elevation myocardial infarction (STEMI), 424 (34.1%) with Non-ST-segment elevation myocardial infarction (NSTEMI) and 166 (13.3%) underwent coronary angiography for unstable angina. Cardiovascular mortality was 9.1% and all-cause mortality was 15.7%. Patients were stratified into four groups to their Lp(a) levels. (?15mg/dL, >15-30mg/dL, >30-60mg/dL, and >60mg/dL). Multivessel disease was significantly more common in patients with Lp(a)>60mg/dL (p<0.05). Increased levels of Lp(a) were not associated with cardiovascular mortality (HR compared with Lp(a) ?15mg/dL were 1.2, 1.2, and 1.0, respectively; p = 0.69) and not with all-cause mortality (HR compared with Lp(a) ?15mg/dL were 1.2, 1.2, and 1.2, respectively; p = 0.46). CONCLUSIONS:Lp(a) levels at time of ACS were neither associated with cardiovascular nor with all-cause mortality. Although Lp(a) has been shown to be associated with incidence of coronary artery disease, this study does not support any role of Lp(a) as a risk factor for mortality after ACS. This should be taken into account for development of outcome studies for agents targeting Lp(a) plasma levels.

SUBMITTER: Roth C

PROVIDER: S-EPMC6952077 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Lipoprotein(a) plasma levels are not associated with survival after acute coronary syndromes: An observational cohort study.

Roth Christian C Krychtiuk Konstantin A KA Gangl Clemens C Schrutka Lore L Distelmaier Klaus K Wojta Johann J Hengstenberg Christian C Berger Rudolf R Speidl Walter S WS

PloS one 20200109 1

<h4>Background</h4>Lipoprotein(a) [Lp(a)] is associated with coronary artery disease in population studies, however studies on its predictive value in patients with cardiovascular disease, in particular after acute coronary syndromes (ACS), are conflicting. The aim of this study was to investigate whether Lp(a) is associated with survival after ACS.<h4>Methods and results</h4>We analyzed Lp(a) measurement in 1,245 patients who underwent coronary angiography for ACS. The median follow-up for card ...[more]

PMID: 31917789

Similar Datasets

Project description:In acute aortic syndromes (AAS), organ malperfusion represents a key event impacting both on diagnosis and outcome. Increased levels of plasma lactate dehydrogenase (LDH), a biomarker of malperfusion, have been reported in AAS, but the performance of LDH for the diagnosis of AAS and the relation of LDH with outcome in AAS have not been evaluated so far.This was a bi-centric prospective diagnostic accuracy study and a cohort outcome study. From 2008 to 2014, patients from 2 Emergency Departments suspected of having AAS underwent LDH assay at presentation. A final diagnosis was obtained by aortic imaging. Patients diagnosed with AAS were followed-up for in-hospital mortality.One thousand five hundred seventy-eight consecutive patients were clinically eligible, and 999 patients were included in the study. The final diagnosis was AAS in 201 (20.1%) patients. Median LDH was 424 U/L (interquartile range [IQR] 367-557) in patients with AAS and 383 U/L (IQR 331-460) in patients with alternative diagnoses (P < 0.001). Using a cutoff of 450 U/L, the sensitivity of LDH for AAS was 44% (95% confidence interval [CI] 37-51) and the specificity was 73% (95% CI 69-76). Overall in-hospital mortality for AAS was 23.8%. Mortality was 32.6% in patients with LDH ≥ 450 U/L and 16.8% in patients with LDH < 450 U/L (P = 0.006). Following stratification according to LDH quartiles, in-hospital mortality was 12% in the first (lowest) quartile, 18.4% in the second quartile, 23.5% in the third quartile, and 38% in the fourth (highest) quartile (P = 0.01). LDH ≥ 450 U/L was further identified as an independent predictor of death in AAS both in univariate and in stepwise logistic regression analyses (odds ratio 2.28, 95% CI 1.11-4.66; P = 0.025), in addition to well-established risk markers such as advanced age and hypotension. Subgroup analysis showed excess mortality in association with LDH ≥ 450 U/L in elderly, hemodynamically stable and in nonsurgically treated patients.Plasma LDH constitutes a biomarker of poor outcome in patients with AAS. LDH is a rapid and universally available assay that could be used to improve risk stratification and to individualize treatment in patient groups where options are controversial.

Project description:BackgroundPolymorphisms in microRNAs (miRNAs) play an important role in acute coronary syndromes (ACS). The purpose of this study was to assess the association of miR-146a rs2910164 and miR-34b rs4938723 polymorphisms with the development and prognosis of ACS and to explore the underlying mechanisms.MethodsA case-control study of 1171 subjects was included to determine the association of miR-146a rs2910164 and miR-34b rs4938723 polymorphisms with ACS risk. An additional 612 patients with different miR-146a rs2910164 genotypes, who underwent percutaneous coronary intervention (PCI) were included in the validation cohort and followed for 14 to 60 months. The endpoint was major adverse cardiovascular events (MACE). A luciferase reporter gene assay was used to validate the interaction of oxi-miR-146a(G) with the IKBA 3'UTR. Potential mechanisms were validated using immunoblotting and immunostaining.ResultsThe miR-146a rs2910164 polymorphism was significantly associated with the risk of ACS (Dominant model: CG + GG vs. CC, OR = 1.270, 95% CI (1.000-1.613), P = 0.049; Recessive model: GG vs. CC + CG, OR = 1.402, 95% CI (1.017-1.934), P = 0.039). Serum inflammatory factor levels were higher in patients with the miR-146a rs2910164 G allele than in those with the C allele. MiR-146a rs2910164 polymorphism in dominant model was associated with the incidence of MACE in post-PCI patients (CG + GG vs. CC, HR = 1.405, 95% CI (1.018-1.939), P = 0.038). However, the miR-34b rs4938723 polymorphism was not associated with the prevalence and prognosis of ACS. The G allele of miR-146a rs2910164 tends to be oxidized in ACS patients. The miRNA fractions purified from monocytes isolated from ACS patients were recognized by the 8OHG antibody. Mispairing of Oxi-miR-146a(G) with the 3'UTR of IKBA results in decreased IκBα protein expression and activation of the NF-κB inflammatory pathway. P65 expression was higher in atherosclerotic plaques from patients carrying the miR-146a rs2910164 G allele.ConclusionThe variant of miR-146a rs2910164 is closely associated with the risk of ACS in Chinese Han population. Patients carrying miR-146a rs2910164 G allele may have worse pathological change and poorer post-PCI prognosis, partly due to the oxidatively modified miR-146a mispairing with 3'UTR of IKBA and activating NF-κB inflammatory pathways.

Project description:Red blood cell transfusions remain one of the cornerstones in supportive care of lower-risk patients with myelodysplastic syndromes. We hypothesized that patients develop oxidant-mediated tissue injury through the formation of toxic iron species, caused either by red blood cell transfusions or by ineffective erythropoiesis. We analyzed serum samples from 100 lower-risk patients with myelodysplastic syndromes at six-month intervals for transferrin saturation, hepcidin-25, growth differentiation factor 15, soluble transferrin receptor, non-transferrin bound iron and labile plasma iron in order to evaluate temporal changes in iron metabolism and the presence of potentially toxic iron species and their impact on survival. Hepcidin levels were low in 34 patients with ringed sideroblasts compared to 66 patients without. Increases of hepcidin and non-transferrin bound iron levels were visible early in follow-up of all transfusion-dependent patient groups. Hepcidin levels significantly decreased over time in transfusion-independent patients with ringed sideroblasts. Increased soluble transferrin receptor levels in transfusion-independent patients with ringed sideroblasts confirmed the presence of ineffective erythropoiesis and suppression of hepcidin production in these patients. Detectable labile plasma iron levels in combination with high transferrin saturation levels occurred almost exclusively in patients with ringed sideroblasts and all transfusion-dependent patient groups. Detectable labile plasma iron levels in transfusion-dependent patients without ringed sideroblasts were associated with decreased survival. In conclusion, toxic iron species occurred in all transfusion-dependent patients and in transfusion-independent patients with ringed sideroblasts. Labile plasma iron appeared to be a clinically relevant measure for potential iron toxicity and a prognostic factor for survival in transfusion-dependent patients. clinicaltrials.gov Identifier: 00600860.

Project description:BACKGROUND:Development of collateral circulation in coronary artery disease is cardio-protective. A key process in forming new blood vessels is attraction to occluded arteries of monocytes with their subsequent activation as macrophages. In patients from a prospectively recruited post-acute coronary syndromes cohort we investigated the prognostic performance of three products of activated macrophages, soluble vascular endothelial growth factor (VEGF) receptors (sFlt-1 and sKDR) and pterins, alongside genetic variants in VEGF receptor genes, VEGFR-1 and VEGFR-2. METHODS:Baseline levels of sFlt-1 (VEGFR1), sKDR (VEGFR2) and pterins were measured in plasma samples from subgroups (n =?513; 211; 144, respectively) of the Coronary Disease Cohort Study (CDCS, n =?2067). DNA samples from the cohort were genotyped for polymorphisms from the VEGFR-1 gene SNPs (rs748252 n =?2027, rs9513070 n =?2048) and VEGFR-2 gene SNPs (rs2071559 n =?2050, rs2305948 n =?2066, rs1870377 n =?2042). RESULTS:At baseline, levels of sFlt-1 were significantly correlated with age, alcohol consumption, NTproBNP, BNP and other covariates relevant to cardiovascular pathophysiology. Total neopterin levels were associated with alcohol consumption at baseline. 7,8 dihydroneopterin was associated with BMI. The A allele of VEGFR-2 variant rs1870377 was associated with higher plasma sFlt-1 and lower levels of sKDR at baseline. Baseline plasma sFlt-1 was univariately associated with all cause mortality with (p <?0.001) and in a Cox's proportional hazards regression model sFlt-1 and pterins were both associated with mortality independent of established predictors (p <?0.027). CONCLUSIONS:sFlt-1 and pterins may have potential as prognostic biomarkers in acute coronary syndromes patients. Genetic markers from VEGF system genes warrant further investigation as markers of levels of VEGF system components in these patients. TRIAL REGISTRATION:Australian New Zealand Clinical Trials Registry. ACTRN12605000431628 . 16 September 2005, Retrospectively registered.

Project description:AimHigh-density lipoproteins (HDLs) have several potentially protective vascular effects. Most clinical studies of therapies targeting HDL have failed to show benefits vs. placebo.ObjectiveTo investigate the effects of an HDL-mimetic agent on atherosclerosis by intravascular ultrasonography (IVUS) and quantitative coronary angiography (QCA).Design and settingA prospective, double-blinded, randomized trial was conducted at 51 centres in the USA, the Netherlands, Canada, and France. Intravascular ultrasonography and QCA were performed to assess coronary atherosclerosis at baseline and 3 (2-5) weeks after the last study infusion.PatientsFive hundred and seven patients were randomized; 417 and 461 had paired IVUS and QCA measurements, respectively.InterventionPatients were randomized to receive 6 weekly infusions of placebo, 3 mg/kg, 6 mg/kg, or 12 mg/kg CER-001.Main outcome measuresThe primary efficacy parameter was the nominal change in the total atheroma volume. Nominal changes in per cent atheroma volume on IVUS and coronary scores on QCA were also pre-specified endpoints.ResultsThe nominal change in the total atheroma volume (adjusted means) was -2.71, -3.13, -1.50, and -3.05 mm(3) with placebo, CER-001 3 mg/kg, 6 mg/kg, and 12 mg/kg, respectively (primary analysis of 12 mg/kg vs. placebo: P = 0.81). There was also no difference among groups for the nominal change in per cent atheroma volume (0.02, -0.02, 0.01, and 0.19%; nominal P = 0.53 for 12 mg/kg vs. placebo). Change in the coronary artery score was -0.022, -0.036, -0.022, and -0.015 mm (nominal P = 0.25, 0.99, 0.55), and change in the cumulative coronary stenosis score was -0.51, 2.65, 0.71, and -0.77% (compared with placebo, nominal P = 0.85 for 12 mg/kg and nominal P = 0.01 for 3 mg/kg). The number of patients with major cardiovascular events was 10 (8.3%), 16 (13.3%), 17 (13.7%), and 12 (9.8%) in the four groups.ConclusionCER-001 infusions did not reduce coronary atherosclerosis on IVUS and QCA when compared with placebo. Whether CER-001 administered in other regimens or to other populations could favourably affect atherosclerosis must await further study. Name of the trial registry: Clinicaltrials.gov; Registry's URL: http://clinicaltrials.gov/ct2/show/NCT01201837?term=cer-001&rank=2;Trial registration numberNCT01201837.

Dataset Information

Lipoprotein(a) plasma levels are not associated with survival after acute coronary syndromes: An observational cohort study.

Publications

Lipoprotein(a) plasma levels are not associated with survival after acute coronary syndromes: An observational cohort study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets