To compare the validity and robustness of five methods for handling missing characteristics when using cardiovascular disease risk prediction models for individual patients in a real-world clinical ...setting.
The performance of the missing data methods was assessed using data from the Swedish National Diabetes Registry (n = 419,533) with external validation using the Scottish Care Information ˗ diabetes database (n = 226,953). Five methods for handling missing data were compared. Two methods using submodels for each combination of available data, two imputation methods: conditional imputation and median imputation, and one alternative modeling method, called the naïve approach, based on hazard ratios and populations statistics of known risk factors only. The validity was compared using calibration plots and c-statistics.
C-statistics were similar across methods in both development and validation data sets, that is, 0.82 (95% CI 0.82–0.83) in the Swedish National Diabetes Registry and 0.74 (95% CI 0.74–0.75) in Scottish Care Information-diabetes database. Differences were only observed after random introduction of missing data in the most important predictor variable (i.e., age).
Validity and robustness of median imputation was not dissimilar to more complex methods for handling missing values, provided that the most important predictor variables, such as age, are not missing.
Anti-inflammatory drugs reduce the risk of cardiovascular events in patients with coronary artery disease (CAD), but less is known about the relation between inflammation and outcomes in patients ...with cerebrovascular disease (CeVD), peripheral artery disease (PAD), and abdominal aortic aneurysm (AAA). This study assessed the association between C-reactive protein (CRP) and clinical outcomes in patients with CAD (n = 4,517), CeVD (n = 2,154), PAD (n = 1,154), and AAA (n = 424) from the prospective Utrecht Cardiovascular Cohort-Second Manifestations of ARTerial disease study. The primary outcome was recurrent cardiovascular disease (CVD), defined as myocardial infarction, ischemic stroke, or cardiovascular death. Secondary outcomes were major adverse limb events and all-cause mortality. Associations between baseline CRP and outcomes were assessed using Cox proportional hazards models adjusted for age, sex, smoking, diabetes mellitus, body mass index, systolic blood pressure, non–high-density lipoprotein cholesterol, and glomerular filtration rate. Results were stratified by CVD location. During a median follow-up of 9.5 years, 1,877 recurrent CVD events, 887 major adverse limb events, and 2,341 deaths were observed. CRP was independently associated with recurrent CVD (hazard ratio HR per 1 mg/L 1.08, 95% confidence interval CI 1.05 to 1.10), and all secondary outcomes. Compared with the first quintile of CRP, HRs for recurrent CVD were 1.60 (95% CI 1.35 to 1.89) for the last quintile ≤10 mg/L and 1.90 (95% CI 1.58 to 2.29) for the subgroup with CRP >10 mg/L. CRP was associated with recurrent CVD in patients with CAD (HR per 1 mg/L 1.08, 95% CI 1.04 to 1.11), CeVD (HR 1.05, 95% CI 1.01 to 1.10), PAD (HR 1.08, 95% CI 1.03 to 1.13), and AAA (HR 1.08, 95% CI 1.01 to 1.15). The association between CRP and all-cause mortality was stronger for patients with CAD (HR 1.13, 95% CI 1.09 to 1.16) than for patients with other CVD locations (HRs 1.06 to 1.08; p = 0.002). Associations remained consistent beyond 15 years after the CRP measurement. In conclusion, greater CRP is independently associated with an increased risk of recurrent CVD and mortality, irrespective of previous CVD location.
The predictive value of traditional risk factors for vascular events in patients with manifest vascular disease is limited, underscoring the need for novel biomarkers to improve risk stratification. ...Since hematological parameters are routinely assessed in clinical practice, they are readily available candidates.
We used data from 3,922 vascular patients, who participated in the Second Manifestations of ARTerial Disease (SMART) study. We first investigated associations between recurrent vascular events and 22 hematological parameters, obtained from the Utrecht Patient Oriented Database (UPOD), and then assessed whether parameters associated with outcome improved risk prediction.
After adjustment for all SMART risk score (SRS) variables, lymphocyte %, neutrophil count, neutrophil % and red cell distribution width (RDW) were significantly associated with vascular events. When individually added to the SRS, lymphocyte % improved prediction of recurrent vascular events with a continuous net reclassification improvement (cNRI) of 17.4% 95% CI: 2.1, 32.1% and an increase in c-statistic of 0.011 0.000, 0.022. The combination of lymphocyte % and neutrophil count resulted in a cNRI of 22.2% 3.2, 33.4% and improved c-statistic by 0.011 95% CI: 0.000, 0.022. Lymphocyte % and RDW yielded a cNRI of 18.7% 3.3, 31.9% and improved c-statistic by 0.016 0.004, 0.028. However, the addition of hematological parameters only modestly increased risk estimates for patients with an event during follow-up.
Several hematological parameters were independently associated with recurrent vascular events. Lymphocyte % alone and in combination with other parameters enhanced discrimination and reclassification. However, the incremental value for patients with a recurrent event was limited.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Suboptimal secondary prevention in patients with stroke causes a remaining cardiovascular risk desirable to reduce. We have validated a prognostic model for secondary preventive settings and ...estimated future cardiovascular risk and theoretical benefit of reaching guideline recommended risk factor targets.
The SMART-REACH (Secondary Manifestations of Arterial Disease-Reduction of Atherothrombosis for Continued Health) model for 10-year and lifetime risk of cardiovascular events was applied to 465 patients in the Norwegian Cognitive Impairment After Stroke (Nor-COAST) study, a multicenter observational study with two-year follow-up by linkage to national registries for cardiovascular disease and mortality. The residual risk when reaching recommended targets for blood pressure, low-density lipoprotein cholesterol, smoking cessation and antithrombotics was estimated.
In total, 11.2% had a new event. Calibration plots showed adequate agreement between estimated and observed 2-year prognosis (C-statistics 0.63, 95% confidence interval 0.55-0.71). Median estimated 10-year risk of recurrent cardiovascular events was 42% (Interquartile range (IQR) 32-54%) and could be reduced to 32% by optimal guideline-based therapy. The corresponding numbers for lifetime risk were 70% (IQR 63-76%) and 61%. We estimated an overall median gain of 1.4 (IQR 0.2-3.4) event-free life years if guideline targets were met.
Secondary prevention was suboptimal and residual risk remains elevated even after optimization according to current guidelines. Considerable interindividual variation in risk exists, with a corresponding variation in benefit from intensification of treatment. The SMART-REACH model can be used to identify patients with the largest benefit from more intensive treatment and follow-up.
Abstract
Aims
Deciding to stop or continue anticoagulation for venous thromboembolism (VTE) after initial treatment is challenging, as individual risks of recurrence and bleeding are heterogeneous. ...The present study aimed to develop and externally validate models for predicting 5-year risks of recurrence and bleeding in patients with VTE without cancer who completed at least 3 months of initial treatment, which can be used to estimate individual absolute benefits and harms of extended anticoagulation.
Methods and results
Competing risk-adjusted models were derived to predict recurrent VTE and clinically relevant bleeding (non-major and major) using 14 readily available patient characteristics. The models were derived from combined individual patient data from the Bleeding Risk Study, Hokusai-VTE, PREFER-VTE, RE-MEDY, and RE-SONATE (n = 15,141, 220 recurrences, 189 bleeding events). External validity was assessed in the Danish VTE cohort, EINSTEIN-CHOICE, GARFIELD-VTE, MEGA, and Tromsø studies (n = 59 257, 2283 recurrences, 3335 bleeding events). Absolute treatment effects were estimated by combining the models with hazard ratios from trials and meta-analyses. External validation in different settings showed agreement between predicted and observed risks up to 5 years, with C-statistics ranging from 0.48–0.71 (recurrence) and 0.61–0.68 (bleeding). In the Danish VTE cohort, 5-year risks ranged from 4% to 19% for recurrent VTE and 1% –19% for bleeding.
Conclusion
The VTE-PREDICT risk score can be applied to estimate the effect of extended anticoagulant treatment for individual patients with VTE and to support shared decision-making.
Structured Graphical Abstract
Structured Graphical Abstract
BMI, body mass index; DOAC, direct oral anticoagulant; DVT, deep venous thrombosis; Hb, haemoglobin; SBP, systolic blood pressure; VKA, vitamin K antagonist; VTE, venous thromboembolism.
To explore the presence of heterogeneity of treatment effect (HTE) of an intensive lifestyle intervention on the occurrence of major cardiovascular events (MACE) in overweight or obese patients with ...type 2 diabetes, and to identify patient characteristics associated with individual treatment effect.
In 4,901 participants from the Action for Health in Diabetes (Look AHEAD) trial, a penalized Cox regression model to predict treatment effect of intensive lifestyle intervention for the risk of MACE was derived, including all possible treatment-by-covariate interaction terms. The ability of the model to predict HTE was confirmed by calculating hazard ratios (HRs) and absolute risk change in quartiles of predicted treatment effect, and baseline patient characteristics were compared between quartiles.
In quartile 1 of predicted treatment effect, with the highest predicted risk reduction, there was a significant treatment benefit of intensive lifestyle intervention (HR 0.64 95% CI 0.49-0.83), whereas there was no effect from treatment in quartiles 2 and 3 (HR 0.81 95% CI 0.58-1.14 and 1.13 95% CI 0.80-1.60, respectively) and a detrimental effect in quartile 4 (HR 1.37 95% CI 1.09-1.73). Several patient characteristics in demographics, medical history, physical examination, and laboratory values were associated with the level of treatment effect.
This post hoc analysis of the Look AHEAD trial showed that an intensive lifestyle intervention aimed at weight loss may reduce cardiovascular events in selected patients but may have a detrimental treatment effect in others.
Abstract
Background
Bleeding risk is highly relevant for treatment decisions in cancer-associated thrombosis (CAT). Several risk scores exist, but have never been validated in patients with CAT and ...are not recommended for practice.
Objectives
To compare methods of estimating clinically relevant (major and clinically relevant nonmajor) bleeding risk in patients with CAT: (1) existing risk scores for bleeding in venous thromboembolism, (2) pragmatic classification based on cancer type, and (3) new prediction model.
Methods
In a posthoc analysis of the Hokusai VTE Cancer study, a randomized trial comparing edoxaban with dalteparin for treatment of CAT, seven bleeding risk scores were externally validated (ACCP-VTE, HAS-BLED, Hokusai, Kuijer, Martinez, RIETE, and VTE-BLEED). The predictive performance of these scores was compared with a pragmatic classification based on cancer type (gastrointestinal; genitourinary; other) and a newly derived competing risk-adjusted prediction model based on clinical predictors for clinically relevant bleeding within 6 months after CAT diagnosis with nonbleeding-related mortality as the competing event (“CAT-BLEED”).
Results
Data of 1,046 patients (149 events) were analyzed. Predictive performance of existing risk scores was poor to moderate (C-statistics: 0.50–0.57; poor calibration). Internal validation of the pragmatic classification and “CAT-BLEED” showed moderate performance (respective C-statistics: 0.61; 95% confidence interval CI: 0.56–0.66, and 0.63; 95% CI 0.58–0.68; good calibration).
Conclusion
Existing risk scores for bleeding perform poorly after CAT. Pragmatic classification based on cancer type provides marginally better estimates of clinically relevant bleeding risk. Further improvement may be achieved with “CAT-BLEED,” but this requires external validation in practice-based settings and with other DOACs and its clinical usefulness is yet to be demonstrated.
Patients with established cardiovascular disease (CVD) are at high risk of incident heart failure (HF), which may in part reflect the impact of systemic inflammation.
The goal of this study was to ...determine the association between C-reactive protein (CRP) and incident HF in patients with established CVD.
Patients from the prospective UCC-SMART (Utrecht Cardiovascular Cohort-Second Manifestations of ARTerial disease) cohort with established CVD, but without prevalent HF were included (n = 8,089). Incident HF was defined as a first hospitalization for HF. The association between baseline CRP and incident HF was assessed using Cox proportional hazards models adjusted for established risk factors (ie, age, sex, myocardial infarction, smoking, diabetes mellitus, body mass index, blood pressure, cholesterol, and kidney function).
During a median follow-up of 9.7 years (IQR 5.4-14.1 years), 810 incident HF cases were observed (incidence rate 1.01/100 person-years). Higher CRP was independently associated with an increased risk of incident HF: HR per 1 mg/L: 1.10 (95% CI: 1.07-1.13), and for last vs first CRP quartile: 2.22 (95% CI: 1.76-2.79). The association was significant for both HF with reduced (HR: 1.09; 95% CI: 1.04-1.14) and preserved ejection fraction (HR: 1.12; 95% CI: 1.07-1.18) (P for difference = 0.137). Additional adjustment for medication use and interim myocardial infarction did not attenuate the association, and the association remained consistent beyond 15 years after the CRP measurement.
In patients with established CVD, CRP is an independent risk marker of incident HF. These data support ongoing trial efforts to assess whether anti-inflammatory agents can reduce the burden of HF.
Display omitted
Patients with venous thromboembolism (VTE) are commonly classified by the presence or absence of provoking factors at the time of VTE to guide treatment decisions. This approach may not capture the ...heterogeneity of the disease and its prognosis.
To evaluate clinically important novel phenotypic clusters among patients with VTE without cancer and to explore their association with anticoagulant treatment and clinical outcomes.
Latent class analysis was performed with 18 baseline clinical variables in 3062 adult patients with VTE without active cancer participating in PREFER in VTE, a noninterventional disease registry. The derived latent classes were externally validated in a post hoc analysis of Hokusai-VTE (n = 6593), a randomized trial comparing edoxaban with warfarin. The associations between cluster membership and anticoagulant treatment, recurrent VTE, bleeding, and mortality after initial treatment were studied.
The following 5 clusters were identified: young men cluster (n = 1126, 37%), young women cluster (n = 215, 7%), older people cluster (n = 1106, 36%), comorbidity cluster (n = 447, 15%), and history of venous thromboembolism cluster (n = 168, 5%). Patient characteristics varied by age, sex, medical history, and treatment patterns. Consistent clusters were evident on external validation. In Cox proportional hazard models, recurrence risk was lower in the young women cluster (hazard ratio HR, 0.27; 95% CI, 0.12-0.61) compared with the comorbidity cluster, after adjusting for extended anticoagulation. The risk of bleeding was lower in young men, young women, and older people clusters (HR, 0.50; 95% CI, 0.38-0.66; HR, 0.23; 95% CI, 0.11-0.46; and HR, 0.55; 95% CI 0.41-0.73, respectively).
The heterogeneity of VTE cases extends beyond the distinction between provoked and unprovoked VTE.
•Classifying patients with venous thrombosis (VTE) as (un)provoked may ignore disease heterogeneity.•Latent class analysis was used to identify phenotypic clusters among patients with VTE without cancer.•Novel clusters are young men, young women, healthy elderly, comorbidity, and history of VTE clusters.•Clusters especially differed in their association with the risk of bleeding and mortality.
PDF
