Plastic debris <1 mm (defined here as microplastic) is accumulating in marine habitats. Ingestion of microplastic provides a potential pathway for the transfer of pollutants, monomers, and ...plastic-additives to organisms with uncertain consequences for their health. Here, we show that microplastic contaminates the shorelines at 18 sites worldwide representing six continents from the poles to the equator, with more material in densely populated areas, but no clear relationship between the abundance of miocroplastics and the mean size-distribution of natural particulates. An important source of microplastic appears to be through sewage contaminated by fibers from washing clothes. Forensic evaluation of microplastic from sediments showed that the proportions of polyester and acrylic fibers used in clothing resembled those found in habitats that receive sewage-discharges and sewage-effluent itself. Experiments sampling wastewater from domestic washing machines demonstrated that a single garment can produce >1900 fibers per wash. This suggests that a large proportion of microplastic fibers found in the marine environment may be derived from sewage as a consequence of washing of clothes. As the human population grows and people use more synthetic textiles, contamination of habitats and animals by microplastic is likely to increase.
Elevated lipoprotein(a) is a genetic risk factor for cardiovascular disease in general population studies. However, its contribution to risk for cardiovascular events in patients with established ...cardiovascular disease or on statin therapy is uncertain.
Patient-level data from seven randomised, placebo-controlled, statin outcomes trials were collated and harmonised to calculate hazard ratios (HRs) for cardiovascular events, defined as fatal or non-fatal coronary heart disease, stroke, or revascularisation procedures. HRs for cardiovascular events were estimated within each trial across predefined lipoprotein(a) groups (15 to <30 mg/dL, 30 to <50 mg/dL, and ≥50 mg/dL, vs <15 mg/dL), before pooling estimates using multivariate random-effects meta-analysis.
Analyses included data for 29 069 patients with repeat lipoprotein(a) measurements (mean age 62 years SD 8; 8064 28% women; 5751 events during 95 576 person-years at risk). Initiation of statin therapy reduced LDL cholesterol (mean change −39% 95% CI −43 to −35) without a significant change in lipoprotein(a). Associations of baseline and on-statin treatment lipoprotein(a) with cardiovascular disease risk were approximately linear, with increased risk at lipoprotein(a) values of 30 mg/dL or greater for baseline lipoprotein(a) and 50 mg/dL or greater for on-statin lipoprotein(a). For baseline lipoprotein(a), HRs adjusted for age and sex (vs <15 mg/dL) were 1·04 (95% CI 0·91–1·18) for 15 mg/dL to less than 30 mg/dL, 1·11 (1·00–1·22) for 30 mg/dL to less than 50 mg/dL, and 1·31 (1·08–1·58) for 50 mg/dL or higher; respective HRs for on-statin lipoprotein(a) were 0·94 (0·81–1·10), 1·06 (0·94–1·21), and 1·43 (1·15–1·76). HRs were almost identical after further adjustment for previous cardiovascular disease, diabetes, smoking, systolic blood pressure, LDL cholesterol, and HDL cholesterol. The association of on-statin lipoprotein(a) with cardiovascular disease risk was stronger than for on-placebo lipoprotein(a) (interaction p=0·010) and was more pronounced at younger ages (interaction p=0·008) without effect-modification by any other patient-level or study-level characteristics.
In this individual-patient data meta-analysis of statin-treated patients, elevated baseline and on-statin lipoprotein(a) showed an independent approximately linear relation with cardiovascular disease risk. This study provides a rationale for testing the lipoprotein(a) lowering hypothesis in cardiovascular disease outcomes trials.
Novartis Pharma AG.
BACKGROUND:Clinical lipid measurements do not show the full complexity of the altered lipid metabolism associated with diabetes mellitus or cardiovascular disease. Lipidomics enables the assessment ...of hundreds of lipid species as potential markers for disease risk.
METHODS:Plasma lipid species (310) were measured by a targeted lipidomic analysis with liquid chromatography electrospray ionization–tandem mass spectrometry on a case-cohort (n=3779) subset from the ADVANCE trial (Action in Diabetes and Vascular DiseasePreterax and Diamicron-MR Controlled Evaluation). The case-cohort was 61% male with a mean age of 67 years. All participants had type 2 diabetes mellitus with ≥1 additional cardiovascular risk factors, and 35% had a history of macrovascular disease. Weighted Cox regression was used to identify lipid species associated with future cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) and cardiovascular death during a 5-year follow-up period. Multivariable models combining traditional risk factors with lipid species were optimized with the Akaike information criteria. C statistics and NRIs were calculated within a 5-fold cross-validation framework.
RESULTS:Sphingolipids, phospholipids (including lyso- and ether- species), cholesteryl esters, and glycerolipids were associated with future cardiovascular events and cardiovascular death. The addition of 7 lipid species to a base model (14 traditional risk factors and medications) to predict cardiovascular events increased the C statistic from 0.680 (95% confidence interval CI, 0.678–0.682) to 0.700 (95% CI, 0.698–0.702; P<0.0001) with a corresponding continuous NRI of 0.227 (95% CI, 0.219–0.235). The prediction of cardiovascular death was improved with the incorporation of 4 lipid species into the base model, showing an increase in the C statistic from 0.740 (95% CI, 0.738–0.742) to 0.760 (95% CI, 0.757–0.762; P<0.0001) and a continuous net reclassification index of 0.328 (95% CI, 0.317–0.339). The results were validated in a subcohort with type 2 diabetes mellitus (n=511) from the LIPID trial (Long-Term Intervention With Pravastatin in Ischemic Disease).
CONCLUSIONS:The improvement in the prediction of cardiovascular events, above traditional risk factors, demonstrates the potential of plasma lipid species as biomarkers for cardiovascular risk stratification in diabetes mellitus.
CLINICAL TRIAL REGISTRATION:URLhttps://clinicaltrials.gov. Unique identifierNCT00145925.
Abstract
Aims
Distinct ceramide lipids have been shown to predict the risk for cardiovascular disease (CVD) events, especially cardiovascular death. As phospholipids have also been linked with CVD ...risk, we investigated whether the combination of ceramides with phosphatidylcholines (PCs) would be synergistic in the prediction of CVD events in patients with atherosclerotic coronary heart disease in three independent cohort studies.
Methods and results
Ceramides and PCs were analysed using liquid chromatography–mass spectrometry (LC-MS) in three studies: WECAC (The Western Norway Coronary Angiography Cohort) (N = 3789), LIPID (Long-Term Intervention with Pravastatin in Ischaemic Disease) trial (N = 5991), and KAROLA (Langzeiterfolge der KARdiOLogischen Anschlussheilbehandlung) (N = 1023). A simple risk score, based on the ceramides and PCs showing the best prognostic features, was developed in the WECAC study and validated in the two other cohorts. This score was highly significant in predicting CVD mortality multiadjusted hazard ratios (HRs; 95% confidence interval) per standard deviation were 1.44 (1.28–1.63) in WECAC, 1.47 (1.34–1.61) in the LIPID trial, and 1.69 (1.31–2.17) in KAROLA. In addition, a combination of the risk score with high-sensitivity troponin T increased the HRs to 1.63 (1.44–1.85) and 2.04 (1.57–2.64) in WECAC and KAROLA cohorts, respectively. The C-statistics in WECAC for the risk score combined with sex and age was 0.76 for CVD death. The ceramide-phospholipid risk score showed comparable and synergistic predictive performance with previously published CVD risk models for secondary prevention.
Conclusion
A simple ceramide- and phospholipid-based risk score can efficiently predict residual CVD event risk in patients with coronary artery disease.
The role of aspirin in reducing lipoprotein(a)-mediated atherothrombotic events in primary prevention is not established.
This study sought to assess whether low-dose aspirin benefits individuals ...with elevated plasma lipoprotein(a)-associated genotypes in the setting of primary prevention.
The study analyzed 12,815 genotyped individuals ≥70 years of age of European ancestry and without prior cardiovascular disease events enrolled in the ASPREE (ASPirin in Reducing Events in the Elderly) randomized controlled trial of 100 mg/d aspirin. We defined lipoprotein(a)-associated genotypes using rs3798220-C carrier status and quintiles of a lipoprotein(a) genomic risk score (LPA-GRS). We tested for interaction between genotypes and aspirin allocation in Cox proportional hazards models for incidence of major adverse cardiovascular events (MACE) and clinically significant bleeding. We also examined associations in the aspirin and placebo arms of the trial separately.
During a median 4.7 years (IQR: 3.6-5.7 years) of follow-up, 435 MACE occurred, with an interaction observed between rs3798220-C and aspirin allocation (P = 0.049). rs3798220-C carrier status was associated with increased MACE risk in the placebo group (HR: 1.90; 95% CI: 1.11-3.24) but not in the aspirin group (HR: 0.54; 95% CI: 0.17-1.70). High LPA-GRS (vs low) was associated with increased MACE risk in the placebo group (HR: 1.70; 95% CI: 1.14-2.55), with risk attenuated in the aspirin group (HR: 1.41; 95% CI: 0.90-2.23), but the interaction was not statistically significant. In all participants, aspirin reduced MACE by 1.7 events per 1,000 person-years and increased clinically significant bleeding by 1.7 events per 1,000 person-years. However, in the rs3798220-C and high LPA-GRS subgroups, aspirin reduced MACE by 11.4 and 3.3 events per 1,000 person-years respectively, without significantly increased bleeding risk.
Aspirin may benefit older individuals with elevated lipoprotein(a) genotypes in primary prevention.
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Millions of people can potentially be exposed to smoke from forest fires, making this an important public health problem in many countries.
In this study we aimed to measure the association between ...out-of-hospital cardiac arrest (OHCA) and forest fire smoke exposures in a large city during a severe forest fire season, and estimate the number of excess OHCAs due to the fire smoke.
We investigated the association between particulate matter (PM) and other air pollutants and OHCA using a case-crossover study of adults (≥ 35 years of age) in Melbourne, Australia. Conditional logistic regression models were used to derive estimates of the percent change in the rate of OHCA associated with an interquartile range (IQR) increase in exposure. From July 2006 through June 2007, OHCA data were collected from the Victorian Ambulance Cardiac Arrest Registry. Hourly air pollution concentrations and meteorological data were obtained from a central monitoring site.
There were 2,046 OHCAs with presumed cardiac etiology during our study period. Among men during the fire season, greater increases in OHCA were observed with IQR increases in the 48-hr lagged PM with diameter ≤ 2.5 μm (PM2.5) (8.05%; 95% CI: 2.30, 14.13%; IQR = 6.1 μg/m(3)) or ≤ 10 μm (PM10) (11.1%; 95% CI: 1.55, 21.48%; IQR = 13.7 μg/m(3)) and carbon monoxide (35.7%; 95% CI: 8.98, 68.92%; IQR = 0.3 ppm). There was no significant association between the rate of OHCA and air pollutants among women. One hundred seventy-four "fire-hours" (i.e., hours in which Melbourne's air quality was affected by forest fire smoke) were identified during 12 days of the 2006/2007 fire season, and 23.9 (95% CI: 3.1, 40.2) excess OHCAs were estimated to occur due to elevations in PM2.5 during these fire-hours.
This study found an association between exposure to forest fire smoke and an increase in the rate of OHCA. These findings have implications for public health messages to raise community awareness and for planning of emergency services during forest fire seasons.
BACKGROUND:D-dimer, a degradation product of cross-linked fibrin, is a marker for hypercoagulability and thrombotic events. Moderately elevated levels of D-dimer are associated with the risk of ...venous and arterial events in patients with vascular disease. We assessed the role of D-dimer levels in predicting long-term vascular outcomes, cause-specific mortality, and new cancers in the LIPID trial (Long-Term Intervention with Pravastatin in Ischaemic Disease) in the context of other risk factors.
METHODS:LIPID randomized patients to placebo or pravastatin 40 mg/d 5 to 38 months after myocardial infarction or unstable angina. D-dimer levels were measured at baseline and at 1 year. Median follow-up was 6.0 years during the trial and 16 years in total.
RESULTS:Baseline D-dimer levels for 7863 patients were grouped by quartile (≤112, 112–173, 173–273, >273 ng/mL). Higher levels were associated with older age, female sex, history of hypertension, poor renal function, and elevated levels of B-natriuretic peptide, high-sensitivity C-reactive protein, and sensitive troponin I (each P<0.001). During the first 6 years, after adjustment for up to 30 additional risk factors, higher D-dimer was associated with a significantly increased risk of a major coronary event (quartile 4 versus 1hazard ratio HR, 1.45; 95% confidence interval, 1.21–1.74), major cardiovascular disease (CVD) event (HR, 1.45; 95% confidence interval, 1.23–1.71) and venous thromboembolism (HR, 4.03; 95% confidence interval, 2.31–7.03; each P<0.001). During the 16 years overall, higher D-dimer was an independent predictor of all-cause mortality (HR, 1.59), CVD mortality (HR, 1.61), cancer mortality (HR, 1.54), and non-CVD noncancer mortality (HR, 1.57; each P<0.001), remaining significant for deaths resulting from each cause occurring beyond 10 years of follow-up (each P≤0.01). Higher D-dimer also independently predicted an increase in cancer incidence (HR, 1.16; P=0.02).The D-dimer level increased the net reclassification index for all-cause mortality by 4.0 and venous thromboembolism by 13.6.
CONCLUSIONS:D-dimer levels predict long-term risk of arterial and venous events, CVD mortality, and non-CVD noncancer mortality independent of other risk factors. D-dimer is also a significant predictor of cancer incidence and mortality. These results support an association of D-dimer with fatal events across multiple diseases and demonstrate that this link extends beyond 10 years’ follow-up.
For patients in whom statins are not tolerated or effective as monotherapy, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) represent a new class of lipid lowering therapies that ...may reduce low-density lipoprotein cholesterol (LDL-C) levels by up to 50% and lower cardiovascular events. While an important treatment option, the cost-effectiveness of PCSK9i in Australia remains unknown. This study aimed to determine the cost-effectiveness of PCSK9i compared to placebo in the prevention of atherosclerotic cardiovascular disease (CVD).
A Markov cohort state-transition model was developed in Microsoft Excel. A hypothetical sample of 1000 individuals based on subjects in the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) trial populated the model. With each five-year cycle, model subjects could have non-fatal CVD events (myocardial infarction and/or stroke), or die from CVD or other causes. Follow-up was simulated for 25 years. CVD risk reduction, cost and utility data were gathered from published sources. At current acquisition prices (AU$8174 per person per year), the incremental cost effectiveness ratio (ICER) was AU$308,558 per quality-adjusted life year (QALY) saved. Acquisition prices would need to be reduced to approximately AU$1500 per person per annum for PCSK9i to reach the arbitrary cost-effectiveness threshold of AU$50,000 per QALY saved.
PCSK9i are an effective alternative for those with existing CVD or at high risk of CVD in whom statin therapy alone is ineffective, but are not cost-effective to the Australian healthcare system based on current prices.
•PCSK9 inhibitors are an efficacious alternative for those with statin intolerance.•This is the first cost-effectiveness analysis of PCSK9 inhibitors in Australia.•The analysis was from the Australian healthcare perspective.•The model comprised a secondary prevention population based on the FOURIER study.•At current prices, PCSK9 inhibitors would not be considered cost-effective.
Stroke Outcomes in the COMPASS Trial Sharma, Mukul; Hart, Robert G; Connolly, Stuart J ...
Circulation (New York, N.Y.),
2019-February-26, 2019-02-26, 20190226, Letnik:
139, Številka:
9
Journal Article
Recenzirano
Odprti dostop
BACKGROUND:Strokes were significantly reduced by the combination of rivaroxaban plus aspirin in comparison with aspirin in the COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation ...Strategies). We present detailed analyses of stroke by type, predictors, and antithrombotic effects in key subgroups.
METHODS:Participants had stable coronary artery or peripheral artery disease and were randomly assigned to receive aspirin 100 mg once daily (n=9126), rivaroxaban 5 mg twice daily (n=9117), or rivaroxaban 2.5 mg twice daily plus aspirin (n=9152). Patients who required anticoagulation or had a stroke within 1 month, previous lacunar stroke, or intracerebral hemorrhage were excluded.
RESULTS:During a mean follow-up of 23 months, fewer patients had strokes in the rivaroxaban plus aspirin group than in the aspirin group (83 0.9% per year versus 142 1.6% per year; hazard ratio HR, 0.58; 95% CI, 0.44–0.76; P<0.0001). Ischemic/uncertain strokes were reduced by nearly half (68 0.7% per year versus 132 1.4% per year; HR, 0.51; 95% CI, 0.38–0.68; P<0.0001) by the combination in comparison with aspirin. No significant difference was noted in the occurrence of stroke in the rivaroxaban alone group in comparison with aspirinannualized rate of 0.7% (HR, 0.82; 95% CI, 0.65–1.05). The occurrence of fatal and disabling stroke (modified Rankin Scale, 3–6) was decreased by the combination (32 0.3% per year versus 55 0.6% per year; HR, 0.58; 95% CI, 0.37–0.89; P=0.01). Independent predictors of stroke were prior stroke, hypertension, systolic blood pressure at baseline, age, diabetes mellitus, and Asian ethnicity. Prior stroke was the strongest predictor of incident stroke (HR, 3.63; 95% CI, 2.65–4.97; P<0.0001) and was associated with a 3.4% per year rate of stroke recurrence on aspirin. The effect of the combination in comparison with aspirin was consistent across subgroups with high stroke risk, including those with prior stroke.
CONCLUSIONS:Low-dose rivaroxaban plus aspirin is an important new antithrombotic option for primary and secondary stroke prevention in patients with clinical atherosclerosis.
CLINICAL TRIAL REGISTRATION:URLhttps://www.clinicaltrials.gov. Unique identifierNCT01776424.
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