Low-dose colchicine reduces cardiovascular risk in patients with coronary artery disease (CAD), but absolute benefits may vary between individuals. This study aimed to assess the range of individual ...absolute benefits from low-dose colchicine according to patient risk profile.
The European Society of Cardiology (ESC) guideline-recommended SMART-REACH model was combined with the relative treatment effect of low-dose colchicine and applied to patients with CAD from the Low-Dose Colchicine 2 (LoDoCo2) trial and the Utrecht Cardiovascular Cohort-Second Manifestations of ARTerial disease (UCC-SMART) study (n = 10 830). Individual treatment benefits were expressed as 10-year absolute risk reductions (ARRs) for myocardial infarction, stroke, or cardiovascular death (MACE), and MACE-free life-years gained. Predictions were also performed for MACE plus coronary revascularization (MACE+), using a new lifetime model derived in the REduction of Atherothrombosis for Continued Health (REACH) registry. Colchicine was compared with other ESC guideline-recommended intensified (Step 2) prevention strategies, i.e. LDL cholesterol (LDL-c) reduction to 1.4 mmol/L and systolic blood pressure (SBP) reduction to 130 mmHg. The generalizability to other populations was assessed in patients with CAD from REACH North America and Western Europe (n = 25 812). The median 10-year ARR from low-dose colchicine was 4.6% interquartile range (IQR) 3.6-6.0% for MACE and 8.6% (IQR 7.6-9.8%) for MACE+. Lifetime benefit was 2.0 (IQR 1.6-2.5) MACE-free years, and 3.4 (IQR 2.6-4.2) MACE+-free life-years gained. For LDL-c and SBP reduction, respectively, the median 10-year ARR for MACE was 3.0% (IQR 1.5-5.1%) and 1.7% (IQR 0.0-5.7%), and the lifetime benefit was 1.2 (IQR 0.6-2.1) and 0.7 (IQR 0.0-2.3) MACE-free life-years gained. Similar results were obtained for MACE+ and in American and European patients from REACH.
The absolute benefits of low-dose colchicine vary between individual patients with chronic CAD. They may be expected to be of at least similar magnitude to those of intensified LDL-c and SBP reduction in a majority of patients already on conventional lipid-lowering and blood pressure-lowering therapy.
Gaia Data Release 2 Prusti, T.; Evans, D. W.; Eyer, L. ...
Astronomy and astrophysics (Berlin),
08/2018, Letnik:
616
Journal Article, Web Resource
Recenzirano
Odprti dostop
Context.
We present the second
Gaia
data release,
Gaia
DR2, consisting of astrometry, photometry, radial velocities, and information on astrophysical parameters and variability, for sources brighter ...than magnitude 21. In addition epoch astrometry and photometry are provided for a modest sample of minor planets in the solar system.
Aims.
A summary of the contents of
Gaia
DR2 is presented, accompanied by a discussion on the differences with respect to
Gaia
DR1 and an overview of the main limitations which are still present in the survey. Recommendations are made on the responsible use of
Gaia
DR2 results.
Methods.
The raw data collected with the
Gaia
instruments during the first 22 months of the mission have been processed by the
Gaia
Data Processing and Analysis Consortium (DPAC) and turned into this second data release, which represents a major advance with respect to
Gaia
DR1 in terms of completeness, performance, and richness of the data products.
Results. Gaia
DR2 contains celestial positions and the apparent brightness in
G
for approximately 1.7 billion sources. For 1.3 billion of those sources, parallaxes and proper motions are in addition available. The sample of sources for which variability information is provided is expanded to 0.5 million stars. This data release contains four new elements: broad-band colour information in the form of the apparent brightness in the
G
BP
(330–680 nm) and
G
RP
(630–1050 nm) bands is available for 1.4 billion sources; median radial velocities for some 7 million sources are presented; for between 77 and 161 million sources estimates are provided of the stellar effective temperature, extinction, reddening, and radius and luminosity; and for a pre-selected list of 14 000 minor planets in the solar system epoch astrometry and photometry are presented. Finally,
Gaia
DR2 also represents a new materialisation of the celestial reference frame in the optical, the
Gaia
-CRF2, which is the first optical reference frame based solely on extragalactic sources. There are notable changes in the photometric system and the catalogue source list with respect to
Gaia
DR1, and we stress the need to consider the two data releases as independent.
Conclusions. Gaia
DR2 represents a major achievement for the
Gaia
mission, delivering on the long standing promise to provide parallaxes and proper motions for over 1 billion stars, and representing a first step in the availability of complementary radial velocity and source astrophysical information for a sample of stars in the
Gaia
survey which covers a very substantial fraction of the volume of our galaxy.
Essentials
The association between chronic kidney disease and bleeding is unknown.
We followed 10 347 subjects at high cardiovascular risk for bleeding events.
Chronic kidney disease was associated ...with a 1.5‐fold increased bleeding risk.
Especially albuminuria rather than decreased kidney function was associated with bleeding events.
Summary
Background
There are indications that patients with chronic kidney disease have an increased bleeding risk.
Objectives
To investigate the association between chronic kidney disease and bleeding in patients at high cardiovascular risk.
Methods
We included 10 347 subjects referred to the University Medical Center Utrecht (the Netherlands) from September 1996 to February 2015 for an outpatient visit with classic risk factors for arterial disease or with symptomatic arterial disease (Second Manifestation of Arterial disease SMART cohort). Patients were staged according to the KDIGO guidelines, on the basis of estimated glomerular filtration rate (eGFR) and albuminuria, and were followed for the occurrence of major hemorrhagic events until March 2015. Hazard ratios (HRs) with 95% confidence intervals (CIs) for bleeding were calculated with Cox proportional hazards analyses.
Results
The incidence rate for bleeding in subjects with chronic kidney disease was 8.0 per 1000 person‐years and that for subjects without chronic kidney disease was 3.5 per 1000 person‐years. Patients with chronic kidney disease (n = 2443) had a 1.5‐fold (95% CI 1.2–1.9) increased risk of bleeding as compared with subjects without chronic kidney disease (n = 7904) after adjustment. Subjects with an eGFR of < 45 mL min−1 1.73 m–2 with albuminuria had a 3.5‐fold (95% CI 2.3–5.3) increased bleeding risk, whereas an eGFR of < 45 mL min−1 1.73 m–2 without albuminuria was not associated with an increased bleeding risk (HR 1.3, 95% CI 0.7–2.5).
Conclusion
Chronic kidney disease is a risk factor for bleeding in patients with classic risk factors for arterial disease or with symptomatic arterial disease, especially in the presence of albuminuria.
Unhealthy dietary habits are an important risk factor for cardiovascular disease (CVD) and adopting a healthy diet is a central recommendation in CVD prevention. This study assessed the dietary ...habits of patients with established CVD, their compliance to dietary guidelines, and the relationship between guideline-compliance and recurrent cardiovascular event risk.
2656 patients with established CVD from the Utrecht Cardiovascular Cohort-Secondary Manifestations of ARTerial disease (UCC-SMART) prospective cohort study, were included between 1996 and 2022. Data on dietary intake was retrospectively collected for all participants in December 2022 using a 160-item food frequency questionnaire. Compliance with dietary guidelines was quantified using an amended version of the Dutch Healthy Diet 2015 (DHD-15) index (range: 0-135). Cox proportional hazard models were used to quantify the relationship with cardiovascular events (stroke and myocardial infarction).
Among 2656 CVD patients (77% male, mean age 59 ± 9 years), median energy intake was 1922 IQR: 1536-2351 kcal/day. The median DHD-15 index was 81.7 IQR 71.2-92.0, with high compliance scores for recommendations on legumes and fish, and low scores for recommendations on whole grains, red meat, processed meat, and dairy. A higher DHD-15 score was associated with lower stroke risk (HR 0.78, 95% CI 0.66-0.92 per 10-point increase) but not with myocardial infarction.
Compliance with dietary guidelines was suboptimal in patients with established CVD. High compliance was associated with a clinically significant reduction in stroke risk in patients with established CVD, emphasizing the importance of dietary counseling.
The long-term predictive performance of existing bleeding risk models in patients with various manifestations of cardiovascular disease (CVD) is not well known. This study aims to assess and compare ...the performance of relevant existing bleeding risk models in estimating the long-term risk of major bleeding in a cohort of patients with established CVD.
Seven existing bleeding risk models (PRECISE-DAPT, DAPT, Ducrocq et al, de Vries et al, S2TOP-BLEED, Intracranial B2LEED3S and HAS-BLED) were identified and externally validated in 7,249 patients with established CVD included in the Utrecht Cardiovascular Cohort–second manifestations of arterial disease study. Predictive performance was assessed in terms of discrimination and calibration, both at 10 years and the original prediction horizon of the models. Major bleeding was defined as Bleeding Academic Research Consortium type 3 or 5.
After a median follow-up of 8.4 years (interquartile range 4.5-12.5), a total of 233 (3.2%) major bleeding events occurred. C-statistics for discrimination at 10 years ranged from 0.53 (95%CI 0.49-0.57) to 0.64 (95%CI 0.60-0.68). Calibration plots after recalibration to 10 years showed best agreement between predicted and observed bleeding risk for De Vries et al, S2TOP-BLEED, DAPT and PRECISE-DAPT.
The performance of existing bleeding risk models to predict long-term bleeding in patients with CVD varied. Discrimination and calibration were best for the models of de Vries et al, S2TOP-BLEED, DAPT and PRECISE-DAPT. Of these, recalibrated models requiring the least predictors may be preferred for use to personalize prevention with antithrombotic therapy.
Methylglyoxal (MGO) is a reactive dicarbonyl compound and a potential key player in diabetic cardiovascular disease (CVD). Whether plasma MGO levels are associated with CVD in type 2 diabetes is ...unknown.
We included 1,003 individuals (mean ± SD age 59.1 ± 10.5 years, 69.3% male, and 61.6% with prior CVD) with type 2 diabetes from the Second Manifestations of ARTerial disease cohort (SMART). We measured plasma MGO levels and two other dicarbonyls (glyoxal GO and 3-deoxyglucosone 3-DG) at baseline with mass spectrometry. Median follow-up of CVD events was 8.6 years. Data were analyzed with Cox regression with adjustment for sex, age, smoking, systolic blood pressure, total cholesterol, HbA
, BMI, prior CVD, and medication use. Hazard ratios are expressed per SD Ln-transformed dicarbonyl.
A total of 287 individuals suffered from at least one CVD event (
= 194 fatal events,
= 146 myocardial infarctions, and
= 72 strokes); 346 individuals died, and 60 individuals underwent an amputation. Higher MGO levels were associated with total (hazard ratio 1.26 95% CI 1.11-1.42) and fatal (1.49 1.30-1.71) CVD and with all-cause mortality (1.25 1.11-1.40), myocardial infarction (1.22 1.02-1.45), and amputations (1.36 1.05-1.76). MGO levels were not apparently associated with stroke (1.03 0.79-1.35). Higher GO levels were significantly associated with fatal CVD (1.17 1.00-1.37) but not with other outcomes. 3-DG was not significantly associated with any of the outcomes.
Plasma MGO and GO levels are associated with cardiovascular mortality in individuals with type 2 diabetes. Influencing dicaronyl levels may therefore be a target to reduce CVD in type 2 diabetes.
Objective To identify determinants associated with insulin resistance and to assess the association between insulin resistance and cardiovascular events, vascular interventions and mortality in ...people with type 1 diabetes at high risk of cardiovascular disease. Design Prospective cohort study. Methods One hundred and ninety-five people with type 1 diabetes from the Secondary Manifestations of ARTerial disease (SMART) cohort were included. Insulin resistance was quantified by the estimated glucose disposal rate (eGDR) with higher eGDR levels indicating higher insulin sensitivity (i.e. lower eGDR levels indicating higher insulin resistance). Linear regression models were used to evaluate determinants associated with eGDR. The effect of eGDR on cardiovascular events, cardiovascular events or vascular interventions (combined endpoint) and on all-cause mortality was analysed using Cox proportional hazards models adjusted for confounders. Results In 195 individuals (median follow-up 12.9 years, IQR 6.7–17.0), a total of 25 cardiovascular events, 26 vascular interventions and 27 deaths were observed. High eGDR as a marker for preserved insulin sensitivity was independently associated with a lower risk of cardiovascular events (HR: 0.75; 95% CI: 0.61–0.91), a lower risk of cardiovascular events and vascular interventions (HR: 0.74; 95% CI: 0.63–0.87) and a lower risk of all-cause mortality (HR: 0.81; 95% CI: 0.67–0.98). Conclusions Insulin resistance as measured by eGDR is an additional risk factor for cardiovascular disease in individuals with type 1 diabetes. Modification of insulin resistance by lifestyle interventions or pharmacological treatment could be a viable therapeutic target to lower the risk of cardiovascular disease.
To enable risk stratification of patients with various types of arterial disease by the development and validation of models for prediction of recurrent vascular event risk based on vascular risk ...factors, imaging or both.
Prospective cohort study.
University Medical Centre.
5788 patients referred with various clinical manifestations of arterial disease between January 1996 and February 2010.
788 recurrent vascular events (ie, myocardial infarction, stroke or vascular death) that were observed during 4.7 (IQR 2.3 to 7.7) years' follow-up.
Three Cox proportional hazards models for prediction of 10-year recurrent vascular event risk were developed based on age and sex in addition to clinical parameters (model A), carotid ultrasound findings (model B) or both (model C). Clinical parameters were medical history, current smoking, systolic blood pressure and laboratory biomarkers. In a separate part of the dataset, the concordance statistic of model A was 0.68 (95% CI 0.64 to 0.71), compared to 0.64 (0.61 to 0.68) for model B and 0.68 (0.65 to 0.72) for model C. Goodness-of-fit and calibration of model A were adequate, also in separate subgroups of patients having coronary, cerebrovascular, peripheral artery or aneurysmal disease. Model A predicted < 20% risk in 59% of patients, 20-30% risk in 19% and > 30% risk in 23%.
Patients at high risk for recurrent vascular events can be identified based on readily available clinical characteristics.
PDF
