Proportion of venous thromboembolism attributed to recognized prothrombotic genotypes in men and women.

Background: Data on the proportion of venous thromboembolism (VTE) risk attributed to prothrombotic genotypes in men and women are limited. Objectives: We aimed to estimate the population attributable fraction (PAF) of VTE for recognized, common prothrombotic genotypes in men and women using a population-based case cohort. Methods: Cases with incident VTE (n = 1493) and a randomly sampled subcohort (n = 13,069) were derived from the Tromsø study (1994-2012) and the Trøndelag Health Study (1995-2008) cohorts. DNA samples were genotyped for 17 single-nucleotide polymorphisms (SNPs) previously associated with VTE. PAFs with 95% bias-corrected CIs (based on 10,000 bootstrap samples) were estimated for SNPs significantly associated with VTE, and a 6-SNP cumulative model was constructed for both sexes. Results: In women, the individual PAFs for SNPs included in the cumulative model were 16.9% for ABO (rs8176719), 17.6% for F11 (rs2036914), 15.1% for F11 (rs2289252), 8.7% for FVL (rs6025), 6.0% for FGG (rs2066865), and 0.2% for F2 (rs1799963). The cumulative PAF for this 6-SNP model was 37.8%. In men, the individual PAFs for SNPs included in the cumulative model were 21.3% for ABO, 12.2% for F11 (rs2036914), 10.4% for F11 (rs2289252), 7.5% for FVL, 7.8% for FGG, and 1.1% for F2. This resulted in a cumulative PAF in men of 51.9%. Conclusion: Our findings in a Norwegian population suggest that 52% and 38% of the VTEs can be attributed to known prothrombotic genotypes in men and women, respectively.

Complement factors B, D, C3bBbP and risk of future venous thromboembolism.

The complement system appears to be involved in the pathogenesis of venous thromboembolism (VTE). We investigated the association of complement factors (CF) B, D, and the alternative pathway convertase, C3bBbP, measured at inclusion, with the risk of future VTE in a nested case-control study; 380 VTE patients and 804 age- and sex-matched controls derived from the Tromsø study. Odds ratios (ORs) with 95% confidence intervals (95% CI) for VTE across tertiles of CF concentrations were estimated using logistic regression. There was no association between CFB or CFD and risk of future VTE. Higher levels of C3bBbP gave an increased risk of provoked VTE; subjects in Q4 had a 1.68-fold higher OR compared with Q1 in the age-, sex- and BMI-adjusted model (OR 1.68; 95% CI 1.08-2.64). There was no increased risk of future VTE in individuals with higher levels of complement factors B or D of the alternative pathway. Increased levels of the alternative pathway activation product, C3bBbP, showed an association with future risk of provoked VTE.

Autoimmune disease and risk of postpartum venous thromboembolism.

Background: The risk of pregnancy-related mortality in the United States has nearly doubled since 1990, with venous thromboembolism (VTE) accounting for approximately 10% of these deaths. Objectives: The objective of this study was to assess whether preexisting autoimmune disease is a risk factor for postpartum VTE. Methods: Using the MarketScan Commercial and Medicare Supplemental administrative databases, a retrospective cohort study analyzed whether postpartum persons with autoimmune disease had a higher risk of postpartum VTE incidence than postpartum persons without autoimmune disease. Using International Classification of Diseases codes, we identified 757,303 individuals of childbearing age who had a valid delivery date with at least 12 weeks of follow-up. Results: Individuals were, on average, 30.7 years old (SD, 5.4), and 3.7% (N = 27,997 of 757,303) of them had evidence of preexisting autoimmune disease. In covariate-adjusted models, postpartum persons with preexisting autoimmune disease had higher rates of postpartum VTE than postpartum persons without autoimmune disease (hazard ratio [HR], 1.33; 95% CI, 1.07-1.64). When analyzed by individual autoimmune disease, those with systemic lupus erythematosus (HR, 2.49; 95% CI, 1.47-4.21) and Crohn's disease (HR, 2.49; 95% CI, 1.34-4.64) were at an elevated risk of postpartum VTE compared with those without autoimmune disease. Conclusion: Autoimmune disease was associated with a higher rate of postpartum VTE, with evidence that the association was most pronounced among individuals with systemic lupus erythematosus and Crohn's disease. These findings suggest that postpartum persons of childbearing age with autoimmune disease may require more monitoring and prophylactic care after delivery to prevent potentially fatal VTE events.

Incidence and Risk Factors of Pulmonary Hypertension After Venous Thromboembolism: An Analysis of a Large Health Care Database.

Background Pulmonary hypertension (PH) is a devastating potential complication of pulmonary embolism, a manifestation of venous thromboembolism (VTE). The incidence of and risk factors for PH in those with prior VTE are poorly characterized. Methods and Results International Classification of Diseases (ICD) codes from inpatient and outpatient medical claims from MarketScan administrative databases for years 2011 to 2018 were used to identify cases of VTE, comorbidities before the VTE event, and PH occurring subsequent to the VTE event. Cumulative incidence and hazard ratios (HR), and their 95% CI, were calculated. The 170 021 VTE cases included in the analysis were on average (±SD) 57.5±15.8 years old and 50.5% were female. A total of 5943 PH cases accrued over an average follow-up of 1.94 years. Two years after incident VTE, the cumulative incidence (95% CI) of PH was 3.5% (3.4%-3.7%) overall. It was higher among older individuals, among women (3.9% [3.8%-4.1%]) than men (3.2% [3.0%-3.3%]), and among patients presenting with pulmonary embolism (6.2% [6.0%-6.5%]) than those presenting with deep vein thrombosis only (1.1% [1.0%-1.2%]). Adjusting for age and sex, risk of PH was higher among patients with VTE with underlying comorbidities. Using the Charlson comorbidity index, there was a dose-response relationship, whereby greater scores were associated with increased PH risk (score ≥5 versus 0: HR, (2.50 [2.30-2.71])). When evaluating individual comorbidities, the strongest associations were observed with concomitant heart failure (HR, 2.17 [2.04-2.31]), chronic pulmonary disease (2.01 [1.90-2.14]), and alcohol abuse (1.66 [1.29-2.13]). Conclusions In this large, real-world population of insured people with VTE, 3.5% developed PH in the 2 years following their initial VTE event. Risk was higher among women, with increasing age, and in those with additional comorbidities at the time of the VTE event. These data provide insights into the burden of PH and risk factors for PH among patients with VTE.

The Risk of Venous Thromboembolism Attributed to Established Prothrombotic Genotypes.

BACKGROUND: The proportion of venous thromboembolism (VTE) events that can be attributed to established prothrombotic genotypes has been scarcely investigated in the general population. We aimed to estimate the proportion of VTEs in the population that could be attributed to established prothrombotic genotypes using a population-based case-cohort. METHODS: Cases with incident VTE (n = 1,493) and a randomly sampled subcohort (n = 13,069) were derived from the Tromsø Study (1994-2012) and the Nord-Trøndelag Health (HUNT) study (1995-2008). DNA samples were genotyped for 17 single-nucleotide polymorphisms (SNPs) associated with VTE. Hazard ratios with 95% confidence intervals (CIs) were estimated in Cox regression models. Population-attributable fractions (PAFs) with 95% bias-corrected CIs (based on 10,000 bootstrap samples) were estimated using a cumulative model where SNPs significantly associated with VTE were added one by one in ranked order of the individual PAFs. RESULTS: Six SNPs were significantly associated with VTE (rs1799963 [Prothrombin], rs2066865 [FGG], rs6025 [FV Leiden], rs2289252 [F11], rs2036914 [F11], and rs8176719 [ABO]). The cumulative PAF for the six-SNP model was 45.3% (95% CI: 19.7-71.6) for total VTE and 61.7% (95% CI: 19.6-89.3) for unprovoked VTE. The PAF for prothrombotic genotypes was higher for deep vein thrombosis (DVT; 52.9%) than for PE (33.8%), and higher for those aged <70 years (66.1%) than for those aged ≥70 years (24.9%). CONCLUSION: Our findings suggest that 45 to 62% of all VTE events in the population can be attributed to known prothrombotic genotypes. The PAF of established prothrombotic genotypes was higher in DVT than in PE, and higher in the young than in the elderly.

Inpatient Versus Outpatient Acute Venous Thromboembolism Management: Trends and Postacute Healthcare Utilization From 2011 to 2018.

Background Acute outpatient management of venous thromboembolism (VTE), which includes pulmonary embolism (PE) and deep vein thrombosis (DVT), is perceived to be as safe as inpatient management in some settings. How widely this strategy is used is not well documented. Methods and Results Using MarketScan administrative claims databases for years 2011 through 2018, we identified patients with International Classification of Diseases (ICD) codes indicating incident VTE and trends in the use of acute outpatient management. We also evaluated healthcare utilization and hospitalized bleeding events in the 6 months following the incident VTE event. A total of 200 346 patients with VTE were included, of whom 50% had evidence of PE. Acute outpatient management was used for 18% of those with PE and 57% of those with DVT only, and for both DVT and PE its use increased from 2011 to 2018. Outpatient management was less prevalent among patients with cancer, higher Charlson comorbidity index scores, and whose primary treatment was warfarin as compared with a direct oral anticoagulant. Healthcare utilization in the 6 months following the incident VTE event was generally lower among patients managed acutely as outpatients, regardless of initial presentation. Acute outpatient management was associated with lower hazard ratios of incident bleeding risk for both patients who initially presented with PE (0.71 [95% CI, 0.61, 0.82]) and DVT only (0.59 [95% CI, 0.54, 0.64]). Conclusions Outpatient management of VTE is increasing. In the present analysis, it was associated with lower subsequent healthcare utilization and fewer bleeding events. However, this may be because healthier patients were managed on an outpatient basis.

Combined effects of plasma von Willebrand factor and platelet measures on the risk of incident venous thromboembolism.

Plasma von Willebrand factor (VWF) and platelet reactivity are risk factors for venous thromboembolism (VTE), and VWF can promote hemostasis by interaction with platelets. In this study, we explored the combined effects of plasma VWF and platelet measures on the risk of incident VTE. A population-based nested case-control study with 403 cases and 816 controls was derived from the Tromsø Study. VWF, platelet count and mean platelet volume (MPV) were measured in blood samples drawn at baseline. Odds ratios (ORs) with 95% confidence intervals (CIs) for VTE were estimated across VWF tertiles, within predefined MPV (<8.5, 8.5-9.5, and ≥9.5 fL) and platelet count (<230, 230-299, and ≥300 ×109/L) strata. Here, participants with VWF levels in the highest tertile and with MPV ≥9.5 fL had an OR of 1.98 (95% CI, 1.17-3.36) for VTE compared with those in the lowest VWF tertile and with MPV <8.5 fL in the age- and sex-adjusted model. In the joint exposure group, 48% (95% CI, 15-96) of VTEs were attributable to the biological interaction between VWF and MPV. Similarly, individuals with VWF in the highest tertile and platelet count ≥300 × 109/L had an OR of 2.91 (95% CI, 1.49-5.67) compared with those with VWF in the lowest tertile and platelet count <230 × 109/L, and 39% (95% CI, -2 to 97) of VTEs in the joint exposure group were explained by the interaction. Our results suggest that platelet reactivity and platelet count interact biologically with high plasma VWF, resulting in an increased risk for incident VTE.

Hemostatic factors, inflammatory markers, and risk of incident venous thromboembolism: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Several hemostatic factors and inflammatory markers are associated with the risk of incident venous thromboembolism (VTE), however, most existing data are from case-control studies in Caucasian populations. OBJECTIVES: We aimed to prospectively confirm previous findings and explore less studied biomarkers in relation to VTE risk in a multi-racial/multi-ethnic cohort. METHODS: Circulating levels of factor VIII, fibrinogen, D-dimer, plasmin-antiplasmin complex (PAP), C-reactive protein (CRP), and interleukin-6 (IL-6) were measured at baseline (2000-2002) in 6706 participants of the Multi-Ethnic Study of Atherosclerosis. Incident VTE was identified using hospitalization discharge codes from baseline to December 31, 2015. Hazard ratios (HRs) of VTE were estimated in Cox regression models. RESULTS: There were 227 events during a median of 14 years of follow-up. Compared with participants in the lowest quartile, the HRs for those above the 95th percentile and p for trend across categories were 3.50 (95% confidence interval [CI] 1.98-6.19; p < .001) for D-dimer, 1.49 (95% CI 0.84-2.63; p = .02) for factor VIII, 1.32 (95% CI 0.76-2.28; p = .99) for fibrinogen, 1.92 (95% CI 1.08-3.42; p = .15) for PAP, 1.68 (95% CI 0.81-3.48; p = .08) for CRP, and 2.55 (95% CI 1.15-5.66; p = .07) for IL-6, after adjustment for demographics and body mass index. For CRP and IL-6, follow-up was restricted to 10 years because of violations of the proportional hazards assumption. No significant interactions by age/ethnicity were observed. CONCLUSIONS: We demonstrated a fairly novel association between PAP and risk of incident VTE, and contributed further prospective confirmation regarding the associations of D-dimer, factor VIII, and IL-6 with VTE.

Plasma levels of von Willebrand factor and future risk of incident venous thromboembolism.

Several case-control studies have reported elevated plasma von Willebrand factor (VWF) levels in patients with venous thromboembolism (VTE) compared with controls. However, because few studies have investigated the association in a prospective design, it is unclear whether elevated plasma VWF is a risk factor or a consequence of the VTE event. Therefore, we aimed to investigate the prospective association between plasma VWF levels and risk of VTE, as well as to perform subgroup analyses of deep vein thrombosis (DVT) and pulmonary embolism. We established a population-based nested case-control study of 414 VTE cases and 843 age- and sex-matched controls based on the Tromsø study cohort (1994-2007). Blood samples were collected at cohort baseline (1994-1995). Odds ratios (ORs) with 95% confidence intervals (CIs) for VTE were estimated across quartiles of VWF levels. We found that the risk of VTE increased linearly across quartiles of VWF levels (P for trend = .023). Participants with VWF in the highest quartile had an OR of 1.45 (95% CI, 1.03-2.03) for VTE compared with those in the lowest quartile. The association was strongest for unprovoked VTE (OR, 2.74; 95% CI, 1.66-4.54) and unprovoked DVT in particular (OR, 6.73; 95% CI, 3.07-14.76). Further adjustment for body mass index, C-reactive protein, hypertension, estrogen use, and smoking had a modest effect on the risk estimates. To conclude, we found a dose-dependent relationship between plasma VWF levels and future risk of incident VTE, and unprovoked events in particular. Our findings suggest that VWF may represent a promising biomarker for future risk of incident VTE.

Impact of respiratory symptoms and oxygen saturation on the risk of incident venous thromboembolism-the Tromsø study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with risk of venous thromboembolism (VTE). It remains unknown whether individual respiratory symptoms and lowered oxygen saturation (SpO2), individually and in combination with COPD, affect the risk of VTE. OBJECTIVES: To investigate whether measures of respiratory impairments including respiratory symptoms and SpO2, individually and combined with COPD, were associated with an increased risk of VTE. METHODS: Spirometry, SpO2, and self-reported respiratory symptoms were collected in 8686 participants from the fifth (2001-2002) and sixth (2007-2008) surveys of the Tromsø Study. Incident VTE events were registered from the date of inclusion to December 31, 2016. Cox regression models with exposures and confounders as time-varying covariates (for repeated measurements) were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for VTE. RESULTS: During a median follow-up of 9.1 years, 330 participants developed incident VTE. Subjects with SpO2 ≤ 96% (lowest 20th percentile) had a 1.5-fold higher risk of VTE (adjusted HR, 1.48; 95% CI, 1.13-1.93) compared with those with SpO2 ≥ 98%. Severe respiratory symptoms (dyspnea, cough, and phlegm) were associated with a 1.4- to 2.0-fold higher risk of VTE compared with no such symptoms. COPD, combined with respiratory symptoms or lowered SpO2, had an additive effect on the VTE risk. CONCLUSIONS: Lowered SpO2 and severe respiratory symptoms were associated with increased VTE risk. COPD combined with respiratory impairments had an additive effect on VTE risk, and may suggest particular attention on VTE preventive strategies in COPD patients with respiratory impairments.

Chronic Obstructive Pulmonary Disease and Risk of Mortality in Patients with Venous Thromboembolism-The Tromsø Study.

BACKGROUND: Previous studies have shown increased mortality in venous thromboembolism (VTE) patients with chronic obstructive pulmonary disease (COPD), but it is unknown to what extent the association is influenced by the severity of COPD and physical inactivity. OBJECTIVES: This article investigates whether COPD, and stages of COPD, influenced the risk of mortality after a first episode of VTE when physical inactivity was taken into account. METHODS: Patients with a first lifetime VTE (n = 256) were recruited among individuals who participated and performed spirometry in the fifth (2001-2002) and sixth (2007-2008) surveys of the Tromsø Study (n = 9577). All-cause mortality was registered up to December 31, 2015. RESULTS: There were 123 deaths during a median of 2.9 years of follow-up. The overall mortality rate was 11.9 (95% confidence interval [CI] 10.0-14.2) per 100 person-years. The risk of death was twofold higher in COPD patients compared with those with normal airflow (hazard ratio [HR] 2.00, 95% CI 1.30-3.08) after multivariable adjustment. The risk of death increased with the severity of COPD. VTE patients with COPD stage III/IV had a fivefold increased risk of death (HR 5.20, 95% CI 2.65-10.2) compared with those without COPD, and 50% of these patients died within 3.5 months after the incident VTE event. Adjustment for physical inactivity had minor effect on the risk estimates. CONCLUSION: VTE patients with COPD had increased risk of death, particularly patients with severe COPD. The detrimental effect of COPD on mortality in VTE patients was apparently explained by factors other than physical inactivity among patients with COPD.

Dietary Intake of Marine Polyunsaturated n-3 Fatty Acids and Risk of Recurrent Venous Thromboembolism.

BACKGROUND: Limited knowledge exists on the association between intake of long-chained n-3 polyunsaturated fatty acids (n-3 PUFAs) and risk of recurrence and all-cause mortality in patients with venous thromboembolism (VTE). OBJECTIVES: This article investigates whether intake of marine n-3 PUFAs was associated with risk of recurrence and mortality in patients with incident VTE. METHODS: A total of 595 patients with incident VTE and available data on n-3 PUFA intake were derived from the Tromsø Study surveys 4 (1994-1995) and 6 (2007-2008). Weekly intake of n-3 PUFAs was categorized as low, medium, and high based on tertiles. Recurrent VTEs and all-cause mortality were registered up to December 31, 2016. Hazard ratios (HRs) were calculated using Cox regression models with the low intake category as reference. RESULTS: There were 98 recurrent VTEs and 227 deaths during follow-up. Overall, we found no association between intake of n-3 PUFAs and risk of recurrent VTE. However, inverse associations were found for high intakes in patients with unprovoked VTE (HR 0.45, 95% confidence interval [CI]: 0.20-1.01), cancer-free patients (HR 0.51, 95% CI: 0.27-0.95), and deep vein thrombosis (DVT) patients (HR 0.49, 95% CI: 0.24-0.97). The inverse associations were more evident when follow-up was restricted to the time after discontinuation of anticoagulant therapy. No association was observed between intake of n-3 PUFAs and mortality after incident VTE. CONCLUSION: A high dietary intake of marine n-3 PUFAs was associated with lower risk of recurrent VTE after unprovoked index events, DVT, and in cancer-free patients.

Cardiorespiratory fitness and future risk of venous thromboembolism.

BACKGROUND: Cardiorespiratory fitness (CRF) is a strong predictor of future arterial cardiovascular disease and premature mortality. However, there are limited data on the association between CRF and the risk of incident venous thromboembolism (VTE). OBJECTIVES: To investigate whether estimated CRF (eCRF) was associated with the risk of incident VTE in a cohort recruited from the general population. METHODS: Participants (n = 10 393) from the sixth survey of the Tromsø Study (2007-08) were included, and incident VTEs were recorded up to 31 December 2016. CRF was estimated in sex-specific algorithms based on age, waist circumference, resting heart rate, and self-reported physical activity. Hazard ratios (HRs) with 95% confidence intervals (CIs) of VTE according to categories of eCRF were estimated in Cox regression models adjusted for sex with age as timescale. The impact of weight status was evaluated in analyses stratified by weight category. RESULTS: There were 176 incident VTEs during follow-up. Compared with individuals with eCRF < 85% of age-predicted, those with eCRF of 85% to 100% and >100% of age-predicted had 46% (HR 0.54; 95% CI 0.39-0.77) and 67% (HR 0.33; 95% CI 0.20-0.54) lower VTE risk, respectively. Compared with overweight/obese individuals with eCRF < 85% of age-predicted, overweight/obese individuals with eCRF ≥ 85% had 50% (HR 0.50, 95% CI 0.35-0.74) lower risk, and normal weight individuals with eCRF ≥ 85% had 55% (HR 0.45, 95% CI 0.30-0.68) lower risk. CONCLUSIONS: Higher eCRF was associated with lower risk of incident VTE. The association was independent of weight categories, suggesting that higher eCRF may modify the association between obesity and VTE.

Impact of prothrombotic genotypes on the association between family history of myocardial infarction and venous thromboembolism.

BACKGROUND: Family history of myocardial infarction (FHMI) is known to increase the risk of venous thromboembolism (VTE). OBJECTIVES: To investigate the effect of prothrombotic genotypes on the association between FHMI and VTE in a case-cohort recruited from a general population. METHODS: Cases with a first VTE (n = 1493) and a subcohort (n = 13 072) were sampled from the Tromsø study (1994-2012) and the Nord-Trøndelag health (HUNT) study (1995-2008). The DNA samples were genotyped for rs8176719 (ABO), rs6025 (F5), rs1799963 (F2), rs2066865 (FGG), and rs2036914 (F11). Participants with missing information on risk alleles (n = 175), FHMI (n = 2769), and BMI (n = 52) were excluded. Cox regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for VTE. To explore the role of prothrombotic genotypes for the association between FHMI and VTE, we (a) included the genotypes in the multivariable-adjusted models and (b) assessed the joint effects between FHMI and genotypes on VTE risk. RESULTS: The FHMI was associated with a 1.3-fold increased risk of VTE (HR 1.32, 95% CI 1.16-1.50) and 1.5-fold increased risk of unprovoked VTE (HR 1.47, 95% CI 1.22-1.78). The risk of VTE by FHMI did not alter after adjustment for the five genotypes. The combination of FHMI and the different prothrombotic genotypes did not result in an excess VTE risk (i.e. no biological interaction). CONCLUSIONS: Our findings suggest that the risk of VTE by FHMI is not explained by rs8176719 (ABO), rs6025 (F5), rs1799963 (F2), rs2066865 (FGG), and rs2036914 (F11). The combination of FHMI with prothrombotic genotypes had an additive effect on VTE risk.

Physical activity and risk of recurrence and mortality after incident venous thromboembolism.

BACKGROUND: Limited data exist on the relationship between physical activity and major complications after incident venous thromboembolism (VTE). OBJECTIVES: To investigate whether physical activity was associated with risk of recurrence and mortality in patients with VTE recruited from the general population. METHODS: Patients with incident VTE (n = 786) derived from the Tromsø Study surveys 4-6 (1994-1995, 2001-2002, and 2007-2008) were included, and data on physical activity were dichotomized according to the activity level reported in the survey preceding the incident VTE (inactive: <1 hour per week, active: ≥1 hour per week). Recurrent VTE and all-cause mortality were registered up to December 31, 2015. Hazard ratios (HRs) for recurrence and all-cause mortality were calculated using Cox regression models with the inactive group as reference. RESULTS: There were 139 recurrences and 395 deaths during follow-up. Physical activity was not associated with the risk of recurrence in men (HR model 2: 1.48, 95% confidence interval [CI] 0.83-2.65) or in women (HR model 2: 0.95, 95% CI 0.52-1.74). In contrast, physical activity was associated with a 28% lower risk of mortality during 10 years of follow up (HR model 3: 0.72, 95% CI 0.57-0.91). The inverse association was stronger in patients with a first deep vein thrombosis ( HR model 2: 0.59, 95% CI 0.44-0.79) than a pulmonary embolism (HR model 3: 0.87, 95% CI 0.61-1.26). CONCLUSION: Our results suggest that habitual physical activity prior to incident VTE does not influence the risk of recurrence. In contrast, active individuals were at lower risk of mortality, particularly following deep vein thrombosis.

Dietary intake of marine n-3 polyunsaturated fatty acids and future risk of venous thromboembolism.

BACKGROUND: Studies on the association between long-chained n-3 polyunsaturated fatty acids (n-3 PUFAs) and risk of venous thromboembolism (VTE) are conflicting, potentially due to challenges related to assessment of n-3 PUFA intake and changes in diet during follow-up. OBJECTIVES: To investigate whether dietary intake of marine n-3 PUFAs was associated with risk of incident VTE in a population-based cohort with repeated assessments of n-3 PUFA intake. METHODS: We recruited 21 970 participants (after excluding 7570 with incomplete data) from the fourth (1994-1995) and sixth (2007-2008) surveys of the Tromsø Study, and recorded incident VTEs up to 2016. Intake of n-3 PUFAs was computed from self-reported consumption of fat and lean fish, fish spread, and supplements. Cox proportional hazards regression models with n-3 PUFA intake as a time-varying variable were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for VTE across quartiles (Q) of n-3 PUFA intake. RESULTS: There were 541 incident VTEs during follow-up. Compared to Q1, subjects in Q2-4 had 22%-26% lower risk of VTE (HR Q2 0.74, 95% CI 0.57-0.96; HR Q3 0.77, 95% CI 0.59-0.99; HR Q4 0.78, 95% CI 0.61-1.00). The association was most pronounced for provoked VTE, particularly provoked pulmonary embolism (PE), with risk estimates of 0.42 (95% CI 0.25-0.72), 0.40 (95% CI 0.23-0.68), and 0.61 (95% CI 0.38-0.96) for Q2-4, respectively. CONCLUSIONS: Dietary intake of marine n-3 PUFAs was associated with a lower risk of VTE, particularly provoked PE. The association displayed a threshold pattern and suggested a protective effect of an n-3 PUFA intake ≥4.7 g/week.

Regular Physical Activity and Risk of Venous Thromboembolism.

Venous thromboembolism (VTE) is a complex multifactorial disease that represents a growing public health concern. Identification of modifiable risk factors at the population level may provide a measure to reduce the burden of VTE. In this review, we summarize current knowledge of the role of physical activity on the risk of VTE and VTE-related complications. We also discuss methodological challenges related to research on physical activity, and put forward plausible mechanisms for an association between physical activity and VTE. Up to now, published studies have reported diverging results on the relationship between physical activity and VTE, and a complex picture has emerged. However, the available evidence appears to be balanced toward a small beneficial effect of physical activity on the risk of incident VTE, but not in a dose-dependent manner. Still, the lack of an operational definition and standardized assessment method for physical activity, as well as several sources of bias, impairs the interpretation of the available literature. Additional work is necessary to understand the role and how to apply physical activity in the VTE setting. Future research should utilize objective assessment strategies of physical activity and physical fitness, account for the fluctuating nature in habitual activity levels, and explore the role of physical activity in the areas of secondary prevention and VTE-related complications.

Cross-sectional and longitudinal associations between different exercise types and food cravings in free-living healthy young adults.

INTRODUCTION: An increase in energy intake due to alterations in hedonic appetite sensations may, at least in part, contribute to lower-than-expected weight loss in exercise interventions. The aim of this study was to examine cross-sectional and longitudinal associations between habitual exercise participation and food cravings in free-living young adults. METHODS: A total of 417 adults (49% male, 28 ± 4 years) reported frequency and duration of walking, aerobic exercise, resistance exercise and other exercise at baseline and every 3 months over a 12-month period. Food cravings were assessed via the Control of Eating Questionnaire at baseline and 12-month follow-up. RESULTS: Cross-sectional analyses revealed more frequent cravings for chocolate and a greater difficulty to resist food cravings in women compared to men (p < 0.01). Only with resistance exercise significant sex by exercise interaction effects were observed with favorable responses in men but not in women. Significant main effects were shown for walking and aerobic exercise with exercisers reporting more frequent food cravings for chocolate and fruits and greater difficulty to resist eating compared to non-exercisers (p < 0.05). Longitudinal analyses revealed significant interaction effects for other exercise (p < 0.05) with favorable results in men but not women. Furthermore, significant main effects were observed for aerobic exercise, resistance exercise and total exercise with an increase in exercise being associated with a reduced difficulty to resist food cravings (p < 0.05). DISCUSSION: The association between exercise participation and hedonic appetite sensations varies by exercise type and sex. Even though exercise was associated with more frequent and greater difficulty to food cravings in the cross-sectional analyses, which may be attributed to greater energy demands, longitudinal results indicate beneficial effects of increased exercise on appetite control, particularly in men.