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Coagulation Unit, Department of Hematology, Karolinska University Hospital, Stockholm, SwedenDepartment of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USADepartment of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, SwedenUnit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
Corresponding author. Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Nobels väg 13, Stockholm, 17177, Sweden.
Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, SwedenUnit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
Consumption of foods with high anti-inflammatory potential was associated with a reduced risk of venous thromboembolism in smokers.
•
Consumption of French fries was associated with an increased risk of venous thromboembolism, in particular pulmonary embolism.
•
A high fruit and vegetable consumption was associated with a decreased risk of pulmonary embolism.
•
Wine consumption was associated with a decreased risk of deep vein thrombosis.
Abstract
Background and aims
Inflammation has been revealed to facilitate thrombogenesis and to increase the risk of venous thromboembolism (VTE). However, limited data are available on the association between the anti-inflammatory diet and incident VTE. We conducted a cohort analysis to examine this association and to further examine whether this association is modified by smoking status, a trigger of systemic inflammation.
Methods and results
We used data from two cohorts including 81,507 middle-aged and older Swedish adults without previous VTE at baseline. An empirically validated anti-inflammatory diet index (AIDI), based on 12 foods with anti-inflammatory potential and 5 foods with pro-inflammatory potential, was employed to estimate the anti-inflammatory potential of diet. Hazard ratios (HRs), with corresponding 95% confidence intervals (CIs), of VTE were estimated by Cox proportional hazards regression models. During a mean follow-up of 17.8-years, 5241 VTE cases were diagnosed. Compared with individuals in the lowest quartile of the AIDI (score ≤4), those in the highest quartile (score ≥8) had a 9% (95% CI, 0–17%) lower risk of VTE. The inverse association was observed in current and past smokers (HR between the two extreme quartiles, 0.80, 95% CI, 0.70–0.91) but not in never smokers (HR, 1.03, 95% CI, 0.91–1.17). French fries (HR per serving, 1.33, 95% CI, 1.06, 1.67) but no other foods included in AIDI was associated with VTE.
Conclusion
The study suggests that a consumption of foods with high anti-inflammatory potential may play a role in the prevention of VTE in smokers.
Greater fish, fruit, and vegetable intakes are related to lower incidence of venous thromboembolism: the Longitudinal Investigation of Thromboembolism Etiology.
]) with antiinflammation potentials. These associations suggest that diet with high anti-inflammatory potential might play a role in the prevention of VTE.
A recent study developed a questionnaire-based anti-inflammatory diet index (AIDI) that predicts low-grade systemic chronic inflammation [
]. However, there was no study evaluating the association between AIDI and VTE risk. Therefore, we conducted the present analyses based on two cohort studies of middle-aged and older adults to assess the association of this empirically developed AIDI [
] with risk of incident VTE and its two subtypes, pulmonary embolism and deep vein thrombosis, with the aim of confirming the role of a diet with high anti-inflammatory potential in the development of VTE. Given that smoking is a strong trigger of systemic inflammation [
], we also evaluated if the association would be modified by smoking status.
Methods
Study population
The study used data from two Swedish population-based cohorts (the Swedish Mammography Cohort (SMC) and the Cohort of Swedish Men (COSM)), which belong to the national research infrastructure SIMPLER (www.simpler4health.se). The SMC was established in 1987–1990 when all women born in 1914–1949 and residing in Västmanland and Uppsala counties were invited to participate in a mammography screening programme and to complete a food-frequency questionnaire. A second extended questionnaire that solicited information on a range of potential risk factors for cardiovascular disease was sent to all SMC participants who were still alive and living in the study area (n = 56,030) in the fall of 1997. At the same time, the COSM was created. All men who were born between 1918 and 1952 and who were living in Västmanland and Örebro counties (n = 100,303) were invited to participate in this cohort study. A total of 39,227 women (70% of those eligible from the SMC) and 48,850 men (49% of those eligible from the COSM) completed the 1997 questionnaire. Participants of the two cohorts well represented the Swedish population in 1997 regarding age distribution, educational level, prevalence of overweight and obesity, and smoking status [
]. We removed individuals with an incorrect or a missing personal identification number, previous cancer or venous thromboembolism, extreme energy intake, or who died before the start of follow-up (January 1, 1998) (Supplementary Fig. 1). The final study population included 81,507 participants. The study has been approved by the Swedish Ethical Review Authority (Dnr: 2019-03986). All participants have provided informed consent.
Assessment of anti-inflammatory diet
Dietary data over the previous year were obtained via a validated 96-item food frequency questionnaire in 1997. Participants were asked to report the frequency of consumption of each item by choosing from eight predefined frequency categories, ranging from “never” to “≥3 times per day”. An empirically developed AIDI that has been validated in a subgroup of the SMC (3503 women) was used to assess anti-inflammatory diet potential [
]. The AIDI was based on frequency of consumption of 17 foods, including 12 foods with anti-inflammatory potential and five foods with pro-inflammatory potential. The 12 foods with anti-inflammatory potential were: fruits and vegetables (cut-off for getting 1 AIDI score ≥6 servings/day); tea (≥3 servings/day); coffee (≥2 servings/day); whole grain bread (≥2 servings/day); breakfast cereals (≥1 servings/day); low-fat cheese (≥1 servings/day); olive oil and canola oil (>0 servings/day); chocolate (≥1 servings/day); nuts (≥2 servings/week); legumes (≥2 servings/week); red wine (2–7 servings/week); and beer (2–14 servings/week). The five foods with pro-inflammatory potential were: unprocessed red meat (≤0.5 servings/day); processed red meat (≤0.5 servings/day); organ meats (0 servings/day); French fries (0 servings/day); and soft-drink beverages (0 servings/day) [
]. A weak correlation was observed among the 17 foods (Supplementary Fig. 2). We assigned 1 to consumption of each food when the cut-off criteria were met otherwise as 0. The sum of AIDI score ranges from 0 to 17. A higher AIDI score indicates an increased consumption of foods with anti-inflammatory potential and a decreased consumption of foods with inflammatory potential, therefore represents a diet with the greater anti-inflammatory potential.
Ascertainment of cases and follow-up
Diagnostic information of VTE and its two subtypes (i.e., pulmonary embolism and deep vein thrombosis) was obtained by linkage of the cohorts to the Swedish National Patient Register, which has a high coverage of hospital-based inpatient and outpatient care [
]. Incident cases of VTE and two subtypes were defined by the International Classification of Diseases 9th and 10th Revisions (Supplementary Table 1). Individuals were followed up from January 1, 1998 until the date of diagnosis, date of death, or end of follow-up (i.e., 31 December 2019), whichever came first. Death information was derived from the Swedish Death Registry.
Assessment of covariables
Data on age, sex, body mass index, highest education attainment, history of hypertension, hypercholesterolemia, and diabetes mellitus, smoking status, walking/cycling, and dietary supplement use was available in the 1997 questionnaire. Total energy intake was estimated by multiplying the frequency of consumption of each food by the energy content of age- and sex-specific serving sizes and summed up for all foods.
Statistical analysis
We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of VTE in groups defined by the quartiles of AIDI score, quartiles of each food, and per one unit increase of the AIDI score or one additional serving of each food consumed. The models treated age as the underlying time scale and sex as a strata variable. The multivariable-adjusted models were further adjusted for body mass index (≤18.5, 18.6–24.9, 25–29.9, ≥30 kg/m2), education attainment (≤9, 10 to 12, >12 years), baseline cardiovascular risk factors (hypertension, hypercholesterolemia, and diabetes mellitus), smoking status (never smoker, past smoker, and current smoker with 1–5, 6–10, 11–20 and > 20 cigarettes per day), walking/cycling (0–10, 11–30 and > 30 minutes per day), dietary supplement use (no use, irregular use and regular use) and total energy intake (kcal per day, continuous). Interaction between AIDI and smoking status was examined, and corresponding stratification analyses were performed by smoking status (never smokers, and current or past smokers). The assumption of proportionality was examined using Schoenfeld residuals and found to be satisfied. All statistical tests were two-sided, and the analyses were performed in Stata/SE (version 15.0; StataCorp, Texas, USA) and R software (version 4.0.2). A p value below 0.05 was regarded as statistically significant.
Results
A total of 5241 VTE cases were diagnosed over a mean follow-up time of 17.8 years (standard deviation of 6.0 years) and 1,453,302 person-years. The incidence rate was 3.6 per 1000 person-years, and the mean age at diagnosis was 74.6 years (standard deviation of 9.2 years). The baseline characteristics of participants by quartiles of the AIDI score are displayed in Table 1. Individuals with lower AIDI score were more likely to be men, tended to be older, had higher body mass index, lower education levels, and lower levels of walking or cycling, and were less likely to regularly use dietary supplements but more likely to have a history of diabetes and hypertension compared with individuals with a higher AIDI score.
Table 1Age-standardized baseline characteristics of participants from the Swedish Mammography Cohort and the Cohort of Swedish Men by quartiles of the anti-inflammatory diet index.
Characteristics
Venous thromboembolism
All participants
Quartiles of AIDI
Q 1
Q 2
Q 3
Q 4
AIDI, range (median), scores
0-4 (4)
5
6
7-12 (7)
0-12 (5)
Number of individuals
33,950
19,421
12,815
10,080
81,507
Male, %
61.9
54.2
49.2
42.5
55.2
Age, years, mean ± SD
61.3 ± 9.7
61.2 ± 9.6
60.4 ± 9.4
59.7 ± 8.9
60.9 ± 9.5
BMI, kg/m2, mean ± SD
25.7 ± 3.7
25.4 ± 3.6
25.2 ± 3.5
24.7 ± 3.4
25.4 ± 3.6
University education, %
11.6
16.0
22.2
31.3
17.2
Never smoker, %
41.8
43.6
44.3
46.7
43.3
Walking/cycling, %
0–10 min/day
10.0
8.0
6.7
4.8
8.3
10–30 min/day
16.0
14.8
13.4
11.4
14.6
>30 min/day
64.3
68.2
72.0
77.1
68.3
Dietary supplement use, %
Regular
14.2
17.2
21.1
27.3
17.8
Irregular
18.8
20.9
22.9
25.2
20.9
No use
59.0
53.7
49.5
42.4
53.8
Diabetes history, %
5.8
5.3
4.9
5.0
5.4
Hypertension history, %
23.0
21.6
21.2
19.7
21.9
Hypercholesterolemia history, %
11.2
11.4
12.0
12.2
11.5
Energy intake, kcal/day, mean ± SD
2296 ± 909
2181 ± 853
2207 ± 865
2282 ± 882
2247 ± 886
Servings/day
Fruits and vegetables
3.5 ± 2.4
4.0 ± 3.0
4.9 ± 3.5
6.6 ± 3.6
4.5 ± 2.8
Tea
0.6 ± 1.1
0.6 ± 1.1
0.7 ± 1.1
0.8 ± 1.3
0.6 ± 1.2
Coffee
3.0 ± 2.6
3.0 ± 2.0
3.0 ± 2.0
3.0 ± 2.0
3.1 ± 2.0
Wholegrain foods
8.3 ± 5.5
8.0 ± 5.1
8.0 ± 5.2
7.9 ± 5.1
8.8 ± 4.2
Breakfast cereals
0.1 ± 0.2
0.1 ± 0.5
0.2 ± 1.0
0.8 ± 0.9
0.4 ± 0.4
Low-fat cheese
0.1 ± 0.6
0.2 ± 0.9
0.4 ± 1.1
0.7 ± 1.4
0.3 ± 0.9
Chocolate
0.1 ± 0.1
0.1 ± 0.2
0.1 ± 0.1
0.1 ± 0.1
0.1 ± 0.2
Unprocessed red meat
0.5 ± 0.3
0.3 ± 0.3
0.3 ± 0.3
0.3 ± 0.3
0.4 ± 0.4
Processed red meat
0.6 ± 0.6
0.3 ± 0.4
0.3 ± 0.3
0.3 ± 0.3
0.5 ± 0.5
Organ meats
0.2 ± 0.3
0.2 ± 0.3
0.2 ± 0.3
0.1 ± 0.2
0.2 ± 0.3
French fries
0.1 ± 0.1
0.0 ± 0.1
0.0 ± 0.1
0.0 ± 0.1
0.1 ± 0.1
Soft drinks
0.7 ± 1.2
0.5 ± 1.0
0.4 ± 1.0
0.3 ± 0.8
0.5 ± 1.1
Servings/week
Nuts
0.0 ± 0.5
0.0 ± 0.5
0.0 ± 0.5
0.5 ± 0.5
0.2 ± 0.5
Legumes
0.5 ± 0.5
0.5 ± 0.5
0.5 ± 1.0
0.5 ± 1.0
0.5 ± 0.8
Wine
0.2 ± 0.6
0.2 ± 0.6
0.6 ± 1.4
0.6 ± 1.4
0.4 ± 1.0
Beer
0.0 ± 1.6
0.0 ± 4.1
1.0 ± 5.0
2.2 ± 5.6
0.8 ± 3.4
Use of olive/canola oil, %
17.5
41.3
61.4
79.4
39.1
AIDI, anti-inflammatory diet index; BMI, body mass index; IQR, interquartile range; SD, standard deviation. The maximum AIDI score is 17.
A diet with a high anti-inflammatory potential was associated with a decreased risk of VTE (Table 2). Compared with individuals in the lowest quartile of AIDI, those in the highest quartile had a 12% (95% CI, 4%, 19%) and 8% (95% CI, 0%, 17%) lower risk of VTE in the age- and -sex-adjusted and multivariable-adjusted model, respectively. The risk of VTE decreased by 2% (95% CI, 0%, 4%) for one AIDI score increment in the multivariable-adjusted model. The association was broadly similar for pulmonary embolism and deep vein thrombosis (Supplementary Tables 2 and 3). Higher consumption of French fries was associated with an increased risk, while no other foods was associated with risk of VTE (Table 2). The HR of VTE was 1.33 (1.06, 1.67) per one-serving increase in consumption of French fries after the adjustment for covariates. The association for French fries was confirmed in the analysis of deep vein thrombosis (HR per serving increase, 1.39, 95% CI, 1.03, 1.88). We also observed an inverse association between fruit and vegetable consumption and pulmonary embolism (HR per serving increase, 0.98, 95% CI, 0.96, 1.00), and an inverse association between wine consumption and deep vein thrombosis (HR per serving increase, 0.96, 95% CI, 0.92, 1.00).
Table 2Associations of the anti-inflammatory diet index and food groups with incident venous thromboembolism in 81,507 participants, 1998–2019.
Adjusted for age (year, continuous), sex, education levels (primary and high school and university and above), energy intake (kcal per day, continuous), body mass index (≤18.5, 18.6–24.9, 25–29.9, ≥30 kg/m2), smoking status (never, past and current smoker 0–5, 6–10, 11–20 and > 20 cigarettes per day), walking/cycling (0–10, 11–30 and > 30 minutes per day), dietary supplement use (regular, non-regular, not use), baseline history of diabetes, hypertension or hypercholesteremia (yes and no).
Estimates for food groups were based on multivariable-adjusted model plus all studied food groups.
Fruits & vegetables
1.00
1.04 (0.96, 1.12)
0.99 (0.91, 1.07)
1.03 (0.94, 1.13)
0.99 (0.98, 1.00)
0.14
Tea
1.00
–
1.00 (0.94, 1.07)
0.97 (0.89, 1.06)
1.00 (0.97, 1.02)
0.93
Coffee
1.00
0.94 (0.87, 1.01)
0.98 (0.91, 1.07)
0.99 (0.91, 1.07)
1.00 (0.98, 1.02)
0.97
Wholegrains
1.00
1.01 (0.93, 1.09)
0.94 (0.86, 1.03)
0.97 (0.88, 1.07)
0.99 (0.98, 1.00)
0.20
Breakfast cereals
1.00
1.00 (0.92, 1.10)
1.02 (0.95, 1.09)
0.94 (0.86, 1.02)
0.97 (0.91, 1.03)
0.29
Low-fat cheese
1.00
–
–
0.93 (0.85, 1.01)
0.98 (0.95, 1.01)
0.11
Chocolate
1.00
–
1.04 (0.97, 1.11)
0.91 (0.82, 1.01)
0.92 (0.80, 1.06)
0.27
Nuts
1.00
–
1.00 (0.93, 1.06)
0.97 (0.86, 1.11)
1.03 (1.00, 1.07)
0.05
Legumes
1.00
–
1.06 (0.98, 1.15)
0.96 (0.90, 1.03)
1.00 (0.98, 1.02)
0.96
Wine
1.00
0.99 (0.91, 1.07)
0.94 (0.86, 1.02)
0.94 (0.86, 1.02)
0.99 (0.96, 1.01)
0.32
Beer
1.00
–
1.03 (0.95, 1.11)
0.99 (0.92, 1.06)
1.00 (0.99, 1.00)
0.53
Unprocessed red meat
1.00
1.03 (0.95, 1.11)
1.04 (0.96, 1.12)
0.96 (0.86, 1.07)
0.96 (0.88, 1.05)
0.40
Processed red meat
1.00
1.01 (0.93, 1.09)
0.98 (0.90, 1.07)
1.05 (0.96, 1.15)
1.03 (0.97, 1.10)
0.30
Organ meat
1.00
1.01 (0.93, 1.09)
1.01 (0.93, 1.09)
1.05 (0.96, 1.14)
1.06 (0.96, 1.16)
0.23
French fries
1.00
–
1.05 (0.98, 1.12)
1.10 (0.98, 1.24)
1.33 (1.06, 1.67)
0.01
Soft drinks
1.00
–
1.03 (0.96, 1.11)
1.02 (0.95, 1.10)
1.00 (0.98, 1.03)
0.80
Use of olive/canola oil
1.00
–
–
1.00 (0.94, 1.06)
0.99 (0.94, 1.05)
0.85
AIDI, anti-inflammatory diet index; CI, confidence interval; HR, hazard ratio. The blank (−) indicates that no individuals were classified into that quartile.
a Adjusted for age (year, continuous), sex, education levels (primary and high school and university and above), energy intake (kcal per day, continuous), body mass index (≤18.5, 18.6–24.9, 25–29.9, ≥30 kg/m2), smoking status (never, past and current smoker 0–5, 6–10, 11–20 and > 20 cigarettes per day), walking/cycling (0–10, 11–30 and > 30 minutes per day), dietary supplement use (regular, non-regular, not use), baseline history of diabetes, hypertension or hypercholesteremia (yes and no).
b Estimates for food groups were based on multivariable-adjusted model plus all studied food groups.
c Trend was examined per 1-score increase for AIDI and per 1-serving increase for each food group.
We found a statistically significant interaction between AIDI and smoking status in relation to VTE risk (p for interaction = 0.004). The association between higher anti-inflammatory potential of diet and lower risk of VTE was observed in ever smokers, but not when considering current smokers alone (Fig. 1). The HR of VTE between two extreme quartiles of AIDI was 0.80 (95% CI, 0.70, 0.91) in current and past smokers and 1.03 (95% CI, 0.91, 1.17) in never smokers. In current and past smokers, the risk of VTE was 4% (95% CI, 2%, 7%) lower for each 1-score increment in the AIDI. Likewise, smoking status modified the associations of AIDI with pulmonary embolism and deep vein thrombosis and the inverse association of a higher AIDI score with these outcomes was merely observed in current and past smokers (Fig. 1).
Figure 1Multivariable-adjusted associations of the anti-inflammatory diet index with incident venous thromboembolism and its two subtypes by smoking status, 1998–2019. CI, confidence interval; HR, hazard ratio. Hazard ratios adjusted for age, sex, education, smoking status, body mass index, walking/cycling, dietary supplement use, history of diabetes, hypertension or hypercholesterolemia, and energy intake.
In the analysis of two population-based cohorts, a high consumption of foods with high anti-inflammatory potential was associated with a reduced risk of VTE in current and past smokers. The association was similar for pulmonary embolism and deep vein thrombosis. These findings may suggest that a diet with high anti-inflammatory potential partially offsets the cardiovascular risk introduced by smoking. Among foods included in the AIDI, consumption of French fries was associated with an increased risk of VTE, in particular pulmonary embolism. An inverse association was observed between fruit and vegetable consumption and pulmonary embolism, and between wine consumption and deep vein thrombosis. There were no associations between the other studied food groups and risk of VTE or either of its subtypes.
Previous studies have reported inverse associations of several dietary patterns, including the Mediterranean diet [
], with VTE risk. The food groups included in these healthy dietary patterns somewhat overlap with those included in the empirically developed anti-inflammatory diet used in the present study. A recent cohort study found that a high adherence to a modified Dietary Approaches to Stop Hypertension diet composed by 7 food groups was associated with a lower risk of VTE in 30,137 women and 36,193 men followed up for 17.3 years [
]. Another recent cohort study revealed that a high adherence to prudent dietary pattern was associated with a reduced risk of VTE in 14,818 middled-aged adults followed up for approximately 22 years [
] was not replicated in the present study, whereas we observed an inverse between fruit and vegetable consumption and risk of pulmonary embolism. Findings on the association between alcohol consumption and VTE risk were inconsistent. Moderate alcohol consumption was related to a lower risk of VTE in a previous follow-up study [
], which is in line with our finding for wine consumption and deep vein thrombosis. Consumption of French fries was linked to an increased risk of VTE, in particular pulmonary embolism, an association that warrants confirmation. Data on the associations of the other studied food groups with VTE risk are limited [
Underlying mechanisms have been proposed to explain the inverse associations of AIDI with risk of VTE. The diet of high anti-inflammatory potentials was associated with systemic inflammation and lower concentrations of high sensitivity C-recreative in the group with higher AIDI score were associated with an inactivated coagulation process [
]. In addition, other inflammatory biomarkers modified by intake of anti-inflammatory foods may be associated with coagulation cascade and thrombosis process [
] and therefore VTE risk. Resveratrol in red wine and vitamin K in berries and kiwifruit have been associated with an antithrombotic profile and a high consumption of these nutrients and foods may lower the risk of VTE [
There are several strengths of the present study, including a large number of VTE cases, the cohort design and complete follow-up information by linkage of participants to the Swedish National Patient Register. The questionnaire-based AIDI has high validity across all levels of high sensitivity C-recreative protein, age, and potential inflammatory risk factors [
]. An additional strength of the study is the adjustment for important confounders although residual confounding might exist. Dietary information was obtained from a self-administrated questionnaire. Thus, these data might suffer from problems with recalling the past diet but likely non-differential. We have no data on inflammatory and coagulation biomarkers, which thereby limiting the exploration of underlying mechanisms. In addition, lifestyle and dietary habits are time-dependent and may have changed during the follow-up, which may lead to misclassification and a corresponding underestimation of the associations.
Our findings on one side implied the importance of a healthy diet, in particular a diet of high anti-inflammation potential, in development of VTE, which may facilitate the completeness of the primary prevention strategies for this disease, especially in smokers. On the other hand, our results might strengthen the evidence that the inflammation acts as one pathological basis for thrombosis, which hints the worth of future clinical research on anti-inflammation treatments, such as aspirin, for VTE prevention [
]. Our study also highlighted the link between certain foods, such as fruit and vegetables, wine, and French fries, and VTE risk, which could guide nutrition behaviors in general populations and clinical nutrition practice.
In conclusion, this study suggests that a high adherence to a diet with high anti-inflammatory potential may lower the risk VTE in current and past smokers. Promoting a diet with high anti-inflammatory potentials may be a prevention strategy for VTE in current and past smokers.
Sources of funding
Funding for this study came from the Karolinska Institutet’s Research Foundation Grants (Grant number 2020-01842), the Swedish Research Council (Vetenskapsrådet; Grant Number 2019-00977), the Swedish Research Council for Health, Working Life and Welfare (Forte; 2018-00123) and the Swedish Heart-Lung Foundation (Hjärt-Lungfonden; Grant number 20190247). M.B. is funded by Stockholm County Council (grant no. K2892-2016). S.M.D. is supported by IK2-CX001780. This publication does not represent the views of the Department of Veterans Affairs or the United States Government.
Author contributions
S.Y. and S.C.L. conceived and designed the study. S.Y. undertook the statistical analyses and wrote the first draft of the manuscript. S.Y., M.B., S.M.D., N.H., A.W., A.Å. and S.C.L. provided important comments to the manuscript.
All authors declare no conflict of interest with the exception for SMD who receives research support from RenalytixAI and personal consulting fees from Calico Labs, outside the scope of the current research.
Acknowledgement
We want to acknowledge the participants and investigators of SIMPLER for provisioning of facilities and experimental support. SIMPLER receives funding through the Swedish Research Council under grant number 2017-00644. The computations were performed on resources provided by SNIC through Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX) under Project simpl2020002.
Appendix A. Supplementary data
The following is the Supplementary data to this article:
Greater fish, fruit, and vegetable intakes are related to lower incidence of venous thromboembolism: the Longitudinal Investigation of Thromboembolism Etiology.
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