Joint effect of ischemic stroke and obesity on the risk of venous thromboembolism: the Tromsø Study.

Background: Patients with ischemic stroke have increased risk of venous thromboembolism (VTE). Obesity is prevalent in stroke patients and a well-established risk factor for VTE. Whether obesity further increases the VTE risk in patients with stroke remains unclear. Objectives: We investigated the joint effect of ischemic stroke and obesity on the risk of incident VTE in a population-based cohort. Methods: Participants (n = 29,920) were recruited from the fourth to sixth surveys of the Tromsø Study (1994-1995, 2001, and 2007-2008) and followed through 2014. Incident events of ischemic stroke and VTE during follow-up were recorded. Hazard ratios (HRs) of VTE with 95% CIs were estimated according to combined categories of ischemic stroke and obesity (body mass index ≥ 30 kg/m2), with exposure to neither risk factors as reference. Results: During a median follow-up of 19.6 years, 1388 participants experienced ischemic stroke and 807 participants developed VTE. Among those with stroke, 51 developed VTE, yielding an incidence rate of VTE after stroke of 7.2 per 1000 person-years (95% CI, 5.5-9.5). In subjects without stroke, obesity was associated with a 1.8-fold higher VTE risk (HR, 1.76; 95% CI, 1.47-2.11). In nonobese subjects, stroke was associated with a 1.8-fold higher VTE risk (HR, 1.77; 95% CI, 1.27-2.46). Obese subjects with stroke had a 2-fold increased VTE risk (HR, 2.44; 95% CI, 1.37-4.36). Conclusion: The combination of obesity and ischemic stroke did not yield an excess risk of VTE. Our findings suggest that obese subjects with ischemic stroke do not have a more than additive risk of VTE.

Joint effect of myocardial infarction and obesity on the risk of venous thromboembolism: The Tromsø Study.

BACKGROUND: Myocardial infarction (MI) is associated with an increased risk of venous thromboembolism (VTE). Obesity is a recognized risk factor for both MI and VTE. Whether obesity further increases the risk of VTE in MI patients is scarcely investigated. AIM: To study the joint effect of MI and obesity on the risk of VTE. METHODS: Study participants (n = 29 410) were recruited from three surveys of the Tromsø Study (conducted in 1994-1995, 2001, and 2007-2008) and followed up through 2014. All incident MI and VTE cases during follow-up were recorded. Cox regression models with MI as a time-dependent variable were used to estimate hazard ratios (HRs) of VTE (adjusted for age and sex) by combinations of MI exposure and obesity status. Joint effects were assessed by calculating relative excess risk and attributable proportion (AP) due to interaction. RESULTS: During a median of 19.6 years of follow-up, 2090 study participants experienced an MI and 784 experienced a VTE. Among those with MI, 55 developed a subsequent VTE, yielding an overall incidence rate (IR) of VTE of 5.3 per 1000 person-years (95% confidence interval [CI]: 4.1-6.9). In the combined exposure group (MI+/Obesity+), the IR was 11.3 per 1000 person-years, and the adjusted HR indicated a 3-fold increased risk of VTE (HR 3.16, 95% CI: 1.99-4.99) compared to the reference group (MI-/Obesity-). The corresponding AP was 0.46 (95% CI: 0.17-0.74). CONCLUSIONS: The combination of MI and obesity yielded a supra-additive effect on VTE risk of which 46% of the VTE events were attributed to the interaction.

Myocardial infarction, prothrombotic genotypes, and venous thrombosis risk: The Tromsø Study.

BACKGROUND: The risk of venous thromboembolism (VTE) is increased after a myocardial infarction (MI). Some prothrombotic genotypes associated with VTE have also been associated with risk of MI. Whether prothrombotic single-nucleotide polymorphisms (SNPs) further increase the risk of VTE in MI patients is scarcely investigated. AIM: To study the combined effect of MI and prothrombotic SNPs on the risk of VTE. METHODS: Cases with incident VTE (n = 641) and a randomly sampled subcohort weighted for age (n = 1761) were identified from the 4 to 6 surveys of the Tromsø Study (1994-2012). DNA was genotyped for rs8176719 (ABO), rs6025 (F5), rs1799963 (F2), rs2066865 (FGG), and rs2036914 (F11). Hazard ratios (HRs) for VTE with 95% confidence intervals (CIs) were estimated by categories of risk alleles and MI status. RESULTS: Patients with MI had a 1.4-fold increased risk of VTE, and adjustments for the 5 SNPs, either alone or in combination, did not affect this relationship (adjusted HR, 1.52; 95% CI, 1.12-2.07). In subjects without MI, an increased risk of VTE was observed for each of the individual SNPs (≥1 vs. 0 risk alleles), and the risk increased linearly with increasing number of risk alleles in the 5-SNP score. The combination of MI and prothrombotic genotypes, either as individual SNPs or in the 5-SNP score, did not result in an excess risk of VTE. CONCLUSION: The relationship between MI and VTE was not explained by these 5 prothrombotic genotypes. Prothrombotic genotypes did not yield an excess risk of VTE in patients with MI.

Myocardial Infarction as a Transient Risk Factor for Incident Venous Thromboembolism: Results from a Population-Based Case-Crossover Study.

Patients with myocardial infarction (MI) are at increased short-term risk of venous thromboembolism (VTE). The mechanisms behind this association are unclear. We aimed to investigate the impact of acute MI as a transient risk factor for incident VTE while taking other concomitant VTE risk factors into account. We conducted a case-crossover study of VTE patients (n = 707) recruited from the fourth survey of the Tromsø Study. VTE risk factors and hospitalizations were registered during the 90-day period preceding the VTE diagnosis (hazard period) and in four 90-day control periods. Conditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for VTE according to acute MI and after adjustment for other risk factors. Additionally, we applied a mediation analysis to quantify how much the known transient risk factors account for the observed effect of MI on VTE risk. MI was recorded in 13 (1.8%) of the hazard periods and in 6 (0.2%) of the control periods, which yielded a crude OR of 11.9 (95% CI: 3.9-36.7). Adjustment for immobilization and infection yielded an OR of 2.7 (95% CI: 0.6-11.2). The OR was attenuated to 2.6 (95% CI: 0.6-11.9) after further adjustment for major surgery, trauma, red blood cell transfusion, and central venous catheterization. Approximately 60% of the association between MI and VTE was mediated through infection and immobilization. In conclusion, our findings suggest that the increased VTE risk after MI may to a large extent be explained by concomitant conditions related to MI, particularly infections and immobilization.

The Role of Stroke as a Trigger for Incident Venous Thromboembolism: Results from a Population-based Case-Crossover Study.

Stroke is associated with a short-term increased risk of subsequent venous thromboembolism (VTE). It is unclear to what extent this association is mediated by stroke-related complications that are potential triggers for VTE, such as immobilization and infection. We aimed to investigate the role of acute stroke as a trigger for incident VTE while taking other concomitant VTE triggers into account. We conducted a population-based case-crossover study with 707 VTE patients. Triggers were registered during the 90 days before a VTE event (hazard period) and in four preceding 90-day control periods. Conditional logistic regression was used to estimate odds ratios with 95% confidence intervals (CIs) for VTE according to triggers. Stroke was registered in 30 of the 707 (4.2%) hazard periods and in 6 of the 2,828 (0.2%) control periods, resulting in a high risk of VTE, with odds ratios of 20.0 (95% CI: 8.3-48.1). After adjustments for immobilization and infection, odds ratios for VTE conferred by stroke were attenuated to 6.0 (95% CI: 1.6-22.1), and further to 4.0 (95% CI: 1.1-14.2) when other triggers (major surgery, red blood cell transfusion, trauma, and central venous catheter) were added to the regression model. A mediation analysis revealed that 67.8% of the total effect of stroke on VTE risk could be mediated through immobilization and infection. Analyses restricted to ischemic stroke yielded similar results. In conclusion, acute stroke was a trigger for VTE, and the association between stroke and VTE risk appeared to be largely mediated by immobilization and infection.