To cite this article: Horvei LD, Grimnes G, Hindberg K, Mathiesen EB, Njølstad I, Wilsgaard T, Brox J, Braekkan SK, Hansen JB. C-reactive protein, obesity, and the risk of arterial and venous thrombosisJ Thromb Haemost 2016; 14:1561-71. Essentials• We performed repeated measurements of C-reactive protein (CRP) and obesity in a cohort study.• CRP was associated with risk of myocardial infarction and venous thromboembolism.• CRP was a mediator for risk of myocardial infarction in obese men and women.• CRP was a partial mediator for risk of venous thromboembolism in obese women, but not in men.Summary. Background: Low-grade inflammation in obesity may be a shared pathway for the risk of venous thromboembolism (VTE) and myocardial infarction (MI). Objectives: To investigate the associations between repeated measurements of C-reactive protein (CRP) and the risks of MI and VTE, and to explore whether CRP mediated these risks in obese subjects. Methods: CRP and obesity measures were collected from 15 134 subjects who participated in one or more surveys of the Tromsø study in 1994-1995, 2001-2002, or 2007-2008. Incident VTEs and MIs were registered until 1 January 2011. Time-varying Cox regression models were used to calculate hazard ratios of MI and VTE according to categories of CRP and obesity measures. Results: There were 291 VTEs and 920 MIs during follow-up. High levels of CRP (≥ 3 mg L À1 versus < 1 mg L À1 ) were associated with increased risks of MI (hazard ratio [HR] 1.73; 95% confidence interval [CI] 1.32-2.26) and VTE (HR 1.84; 95% CI 1.22-2.78) in women, but only with MI in men (HR 1.93; 95% CI 1.53-2.44). All obesity measures showed stronger associations with CRP in women than in men. In obese women (body mass index [BMI] of ≥ 30 kg m À2 versus < 25 kg m À2 ), adjustment for CRP attenuated the risk estimate for VTE by 22%, whereas the incidence rates of VTE increased with combined categories of higher BMI and CRP. No association was found in men. Conclusions: Our findings suggest that low-grade inflammation, assessed by measurement of CRP, is associated with the risks of MI and VTE, and may be a shared pathway for MI and VTE in obesity.

Background Previous reports on recurrence and mortality rates after a first episode of venous thromboembolism (VTE) vary considerably. Advances in the management and treatment of VTE during the last 15 years may have influenced the rates of clinical outcomes. Aim To estimate the rates of recurrence and mortality after a first VTE in patients recruited from a large population-based cohort. Method From the Tromsø study, patients (n = 710) with a first, symptomatic, objectively confirmed VTE were included and followed in the period 1994-2012. Recurrent episodes of VTE were identified from multiple sources and carefully validated by review of medical records. Incidence rates and cumulative incidence rates with 95% confidence intervals (CIs) of VTE recurrence and mortality were calculated. Results The mean age of the patients was 68 years (range 28-102 years), and 166 (23.4%) had cancer at the time of first VTE. There were 114 VTE recurrences and 333 deaths during a median study period of 7.7 years (range 0.04-18.2 years). The risk of recurrence was highest during the first year. The overall 1-year recurrence rate was 7.8 (95% CI 5.8-10.6) per 100 person-years (PY), whereas the recurrence rate in the remaining follow-up period (1-18 years) was 3.0 (95% CI 2.4-3.8) per 100 PY. The overall 1-year all-cause mortality rate was 29.9 (95% CI 25.7-34.8) per 100 PY, and in those without cancer the corresponding rate was 23.6 (95% CI 17.8-31.3) per 100 PY. Conclusion Despite advances in VTE management, the rates of adverse events remained fairly high, particularly in the first year following a first VTE.

Machine-learning statistical model from EHR data can be useful to predict surgical complications. The combination of EHR extracted free text, blood samples values, and patient vital signs, improves the model performance. These results can be used as a framework for preoperative clinical decision support.

Background: Venous thromboembolism (VTE) is a life-threatening vascular event with environmental and genetic determinants. Recent VTE genome-wide association studies (GWAS) meta-analyses involved nearly 30 000 VTE cases and identified up to 40 genetic loci associated with VTE risk, including loci not previously suspected to play a role in hemostasis. The aim of our research was to expand discovery of new genetic loci associated with VTE by using cross-ancestry genomic resources. Methods: We present new cross-ancestry meta-analyzed GWAS results involving up to 81 669 VTE cases from 30 studies, with replication of novel loci in independent populations and loci characterization through in silico genomic interrogations. Results: In our genetic discovery effort that included 55 330 participants with VTE (47 822 European, 6320 African, and 1188 Hispanic ancestry), we identified 48 novel associations, of which 34 were replicated after correction for multiple testing. In our combined discovery-replication analysis (81 669 VTE participants) and ancestry-stratified meta-analyses (European, African, and Hispanic), we identified another 44 novel associations, which are new candidate VTE-associated loci requiring replication. In total, across all GWAS meta-analyses, we identified 135 independent genomic loci significantly associated with VTE risk. A genetic risk score of the significantly associated loci in Europeans identified a 6-fold increase in risk for those in the top 1% of scores compared with those with average scores. We also identified 31 novel transcript associations in transcriptome-wide association studies and 8 novel candidate genes with protein quantitative-trait locus Mendelian randomization analyses. In silico interrogations of hemostasis and hematology traits and a large phenome-wide association analysis of the 135 GWAS loci provided insights to biological pathways contributing to VTE, with some loci contributing to VTE through well-characterized coagulation pathways and others providing new data on the role of hematology traits, particularly platelet function. Many of the replicated loci are outside of known or currently hypothesized pathways to thrombosis. Conclusions: Our cross-ancestry GWAS meta-analyses identified new loci associated with VTE. These findings highlight new pathways to thrombosis and provide novel molecules that may be useful in the development of improved antithrombosis treatments.

The free text in electronic health records (EHRs) conveys a huge amount of clinical information about health state and patient history. Despite a rapidly growing literature on the use of machine learning techniques for extracting this information, little effort has been invested toward feature selection and the features' corresponding medical interpretation. In this study, we focus on the task of early detection of anastomosis leakage (AL), a severe complication after elective surgery for colorectal cancer (CRC) surgery, using free text extracted from EHRs. We use a bag-of-words model to investigate the potential for feature selection strategies. The purpose is earlier detection of AL and prediction of AL with data generated in the EHR before the actual complication occur. Due to the high dimensionality of the data, we derive feature selection strategies using the robust support vector machine linear maximum margin classifier, by investigating: 1) a simple statistical criterion (leave-one-out-based test); 2) an intensive-computation statistical criterion (Bootstrap resampling); and 3) an advanced statistical criterion (kernel entropy). Results reveal a discriminatory power for early detection of complications after CRC (sensitivity 100%; specificity 72%). These results can be used to develop prediction models, based on EHR data, that can support surgeons and patients in the preoperative decision making phase.