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Background: High alcohol intake has many negative health effects, but its association with venous thromboembolism (VTE) is based on self-reported consumption and is unclear. This study aimed to investigate the association between alcohol consumption measured by the biomarker phosphatidylethanol (PEth) and risk of first-ever VTE.

Methods: We conducted a population-based nested case-referent study in northern Sweden. The study is based on the Västerbotten Intervention Programme VIP which includes health examinations and prospective blood sampling. Cases of objectively verified first-ever VTE between 1985 and 2014 were registered. Referents were matched for age, sex, health examination date, geographical area, and sample freeze-thaw cycles. In 2024, PEth concentrations were measured using a liquid chromatography tandem-mass spectrometry method with a limit of quantification of 0.01 μmol/L.

Results: The study included 1410 cases with objectively verified VTE and 1410 matched referents. The median age of cases at the health examination was 50.2 years, and 55.2 % of cases were men. We found an association between the highest PEth concentration category (>0.30 μmol/L) and risk of VTE (odds ratio 1.44 [95 % confidence interval 1.05–1.98]) compared to the lowest concentration category (PEth <0.01 μmol/L) in a model adjusted for education level, body mass index, smoking, hypertension, and cancer at inclusion.

Conclusions: A high PEth concentration was independently associated with an increased risk of first-ever VTE. Furthermore, the study highlights the benefits of PEth as a biomarker to identify individuals with high alcohol consumption that are at an increased risk of adverse medical outcomes.

Background: Previous studies on the association between n–3 (ω-3) polyunsaturated fatty acids (n–3 PUFAs) and risk of venous thromboembolism (VTE), mainly derived from self-reported dietary intake of n–3 PUFAs, have shown mixed results.

Objectives: The aim of this cohort study was to investigate the association between measured serum n–3 PUFA concentrations and risk of first-ever VTE.

Methods: The present cohort (N = 17,087) was derived from the third survey of the Trøndelag Health Study and consisted of individuals aged ≥20 y without previous VTE. Serum n–3 PUFA concentrations were measured in blood drawn at inclusion (2006–2008) using a nuclear magnetic resonance metabolomic platform (Nightingale), and participants were followed until an objectively verified first-ever VTE event, death, migration, or 31 December, 2019. Cox regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs).

Results: During a median follow-up of 12 y, 340 experienced an incident VTE event. Participants with n–3 PUFA concentrations in the highest tertile had 28% lower relative risk of VTE (HR: 0.72; 95% CI: 0.54, 0.96) than those with n–3 PUFAs in the lowest tertile in age-adjusted analysis. The inverse association was most pronounced for provoked VTE (HR: 0.62; 95% CI: 0.44, 0.87) and deep vein thrombosis (HR: 0.61; 95% CI: 0.40, 0.93). HRs remained virtually unaffected after further adjustment for sex, body mass index, and history of cardiovascular disease or cancer at baseline.

Conclusions: Our finding of an inverse association between serum n–3 PUFA concentrations and VTE suggest that a diet enriched with n–3 PUFAs might protect against future VTE.

Background: Venous thromboembolism (VTE) has a high mortality rate and can be the first manifestation of cancer. We investigated the incidence of cancer after first-ever VTE and the association between VTE and all-cause mortality.

Methods: A Swedish cohort study that included 105,997 participants without previous cancer who underwent a health examination from 1985–2014 was conducted. Manually validated first-ever VTE events, incident cancer according to the Swedish cancer registry, and mortality were registered. Participants were followed until September 5, 2014.

Results: The mean age at inclusion was 46.2 years, and 50.3% of participants were female. We identified 1303 persons in the cohort with a VTE and no previous cancer. Among these, 179 (13.7%) were diagnosed with cancer after the VTE event, resulting in a cancer incidence of 26.4 (95% CI 22.8–30.6) cases per 1000 person-years. The incidence was highest during the first 6 months after the VTE. In the study population, VTE was associated with an increased risk of cancer (HR 1.95 [95% CI 1.67–2.29] in a multivariable model). VTE was also associated with an increased risk of death (HR 6.30 [95% CI 5.82–6.81]) in a multivariable model). There was an interaction between sex and VTE in relation to both risk of cancer and mortality, with a stronger association in women.

Conclusions: The incidence of cancer is high after first-ever VTE, especially close to the VTE event. VTE seems to be a stronger risk marker in women than in men for both cancer and death.

The incidence of recurrent venous thromboembolism (VTE) changes over time from the first VTE event and depends on the presence of risk factors. In this study, we aimed to determine the yearly incidence of VTE recurrence during five years of follow-up after a first-ever VTE event. For this cohort study, we identified persons who experienced a validated first-ever VTE between 2006-2014 in northern Sweden. These patients' medical records were reviewed to identify recurrent VTE events during five years of follow-up. The yearly incidence rates (IRs) of recurrent VTE per 100 person-years were calculated and stratified into three groups defined by characteristics at the first-ever VTE event: no risk factors, cancer, or other risk factors. A total of 1413 persons experienced a first-ever VTE during the study period, of whom 213 experienced a recurrent VTE. Among persons without risk factors, the IR was 4.2 during the first year of follow-up, and 4.1 during the fifth year. Among persons with cancer, the IR was 9.5 during the first year, and 5.4 during the fifth year. Among persons with other risk factors, the corresponding IRs were 6.1 and 2.3. In conclusion, after a first-ever VTE event, persons with cancer had the highest recurrence rate during the first years of follow-up. Among persons with cancer who were alive after five years, the incidence of recurrent VTE during the fifth year was similar to that in participants without risk factors.

Poor self-rated health (SRH) is associated with various adverse health outcomes, including cardiovascular disease. Little is known about SRH and health-related quality of life (HRQoL) as predictors of first-time venous thromboembolism (VTE). Our aim was to investigate the association between SRH, HRQoL, and risk of VTE in a whole cohort, as well as in women and men separately. A total of 108,025 middle-aged inhabitants (51 % women) of Västerbotten, Sweden, participated in a health examination between 1985 and 2014. Data on SRH, HRQoL, and potential confounders were collected by questionnaire. Participants were followed as a cohort and validated first-time VTE events were registered. The mean follow-up time was 13.9 years, during which 2054 participants experienced a first-time VTE. Overall, 27 % of participants reported their health as very good, 46 % as good, 20 % as average, 5 % as somewhat bad, and 1 % as bad. In a multivariable analysis, compared with participants who self-rated as having very good SRH, hazard ratios (95 % confidence intervals) for VTE were 1.17 (1.02–1.33) with good SRH, 1.27 (1.09–1.47) with average SRH, and 1.48 (1.00–2.18) with bad SRH. The risk of VTE increased with lower SRH for both men (p for trend 0.02) and women (p for trend 0.04). In a fully adjusted model, we also found significant associations between four aspects of HRQoL (general health, bodily pain, vitality, emotional well-being) and VTE risk. In conclusion, lower perceived health is associated with an increased risk of VTE in both men and women.

Introduction: Studies have indicated that men have a higher overall risk of VTE than women. In previous studies, we have noted that risk factors for VTE, such as alcohol consumption and physical activity, can differ between sexes.

The aim of the present study was to estimate the incidence of first-ever VTE and the association of traditional cardiovascular risk factors with VTE risk in men and women separately.

Materials and methods: Inhabitants of Västerbotten County in northern Sweden, who had participated in a health examination between 1985 and 2014 were included. The mean age at inclusion was 46.3 years (range 26–65 years). All first-ever VTE events experienced by the participants from the health examination to September 5, 2014 were identified and validated.

Results: A total of 1110 men and 944 women had an objectively verified first-ever VTE event. The incidence of VTE was 1.54 (95% CI 1.45–1.63) per 1000 years of follow-up for men and 1.22 (95% CI 1.14–1.30) for women. Higher age, weight and body mass index were associated with increased risk of VTE in both sexes. Men with hypertension had a lower risk of VTE, HR 0.75 (95% CI 0.65–0.87) and men with more than secondary school education had a higher risk of VTE. Taller women had an increased risk of VTE.

Conclusions: In the studied age group, we found that men had a higher incidence of first-ever VTE than women. Notably, we also found that hypertension was associated with lower risk of VTE in men but not in women.

BACKGROUND: The relationship between alcohol intake and risk of venous thromboembolism (VTE) is unclear. Men and women differ in their drinking habits, which may affect a possible association.

OBJECTIVE: This article investigates the association between alcohol consumption, alcohol dependence and VTE in the total population as well as in men and women separately.

METHODS: We performed a prospective, population-based cohort study in northern Sweden. Study participants were 108,025 (51% women) persons aged 30 to 60 years who underwent a health examination between 1985 and 2014. We assessed alcohol consumption and defined alcohol dependence using a questionnaire. The outcome was a validated first-time VTE.

RESULTS: The mean follow-up time was 13.9 years, and 2,054 participants had a first-time VTE. The mean alcohol consumption was 3.5 standard drinks weekly in men and 1.5 in women. Alcohol dependence was found in 10% of men and 3% of women. There was an association between alcohol consumption (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.00-1.03 per standard drink weekly) as well as alcohol dependence (HR, 1.27; 95% CI, 1.06-1.52) and VTE after adjustments. In men, the risk of VTE increased over quartiles of weekly alcohol consumption (p for trend 0.02), with a HR of 1.22 (95% CI, 1.01-1.47) for the highest quartile. Alcohol dependence was associated with VTE in men (HR, 1.30; 95% CI, 1.07-1.59). In women, there were no significant associations.

CONCLUSION: High alcohol consumption and alcohol dependence were associated with increased risk of first-time VTE in men, but not in women.

Background: Venous thromboembolism (VTE) is a vascular disease with an incidence of approximately 140 cases per 100,000 person-years in adults. The incidence of VTE has increased over the last decades, and more than 20% of affected individuals die in the first year after diagnosis. To reduce the incidence of VTE, it is important to identify modifiable risk factors for the condition.

Aims: The aims of this thesis were a) To study the incidence of first-time VTE and the prevalence of risk markers for VTE at the time of VTE diagnosis, b) To determine the validity of diagnoses of deep vein thrombosis and pulmonary embolism in administrative registries, and c) To study the association between glucose levels, diabetes, alcohol consumption, physical activity and risk of first-time VTE.

Methods: To determine the incidence of first-time VTE and the prevalence of risk markers for VTE at the time of VTE diagnosis, a retrospective, population-based cohort study was conducted. The study included all adult residents of Västerbotten County during the year 2006. All other aims were addressed in the prospective, population-based Venous thromboEmbolism In Northern Sweden (VEINS) cohort study. The VEINS cohort included 108,025 residents of Västerbotten County aged 30 to 60 years without previous VTE events. They were included from 1985 onwards and were followed until a VTE event, death, emigration, or the study end on September 5, 2014. All underwent a health examination within the Västerbotten Intervention Programme where weight, height, blood pressure and glucose levels were measured, and answered a questionnaire regarding smoking, education level, medication use, history of diabetes, alcohol intake and physical activity. VTE diagnoses were validated by review of medical records and radiology reports. To study the validity of diagnoses of deep vein thrombosis and pulmonary embolism in administrative registries, a registry search for International Classification of Diseases diagnosis codes indicating pulmonary embolism and/or deep vein thrombosis events was made in the Swedish National Patient Registry and the Cause of Death Registry. An additional search using an extended set of International Classification of Diseases diagnosis codes was performed in order to identify misclassified events.

Results: The incidence of first-time VTE was 137 (95% confidence interval [CI] 122–154) per 100,000 adults per year. The most common risk markers for VTE were recent hospitalization and concurrent malignancy. The positive predictive value for a diagnosis of pulmonary embolism was 80.7% (95% CI 78.4–82.9), and that of deep vein thrombosis 59.2% (95% CI 56.7–61.7). Misclassification occurred in 1.1% (95% CI 0.4–1.7) of pulmonary embolism events and in 16.4% (95% CI 14.2–18.7) of deep vein thrombosis events. In the VEINS cohort, a total of 2,054 participants experienced an objectively verified first-time VTE event during approximately 1.5 million person-years of follow-up. In univariable analysis, there were associations between fasting plasma glucose, oral glucose tolerance test two-hour post-load plasma glucose, diabetes and increased risk of first-time VTE. These associations were attenuated after adjustment for potential confounders, and were no longer significant. There was an association between alcohol consumption and risk of first-time VTE in men (P for trend 0.02 after adjustments for increased risk of first-time VTE over quartiles of weekly alcohol consumption). Alcohol dependence was associated with risk of first-time VTE in men (hazard ratio [HR] 1.30; 95% CI 1.07–1.59 after adjustments). In women, there were no significant associations between alcohol consumption and risk of first-time VTE. Women who performed leisure time physical activity at least once a week had a lower risk of first-time VTE (HR 0.83; 95% CI 0.71–0.98 after adjustments) compared to women with less or no physical activity. Women with high occupational physical activity also had a lower risk of first-time VTE (HR 0.85; 95% CI 0.74–0.98 after adjustments). In men, there were no consistent association between either measure of physical activity and risk of first-time VTE. 

Conclusions: VTE is a common vascular disease. Registry data on diagnoses of pulmonary embolism, but not deep vein thrombosis, is of acceptable quality and can be considered for use in registry-based studies. Glucose levels and diabetes are not associated with risk of first-time VTE. Alcohol intake and alcohol dependence are associated with an increased risk of first-time VTE in men, whereas high leisure time physical activity and occupational physical activity are associated with a decreased risk of first-time VTE in women.

Bakgrund: Venös trombos är en vanlig och allvarlig kärlsjukdom. De vanligaste formerna av venös trombos är djup ventrombos och lungemboli. Förekomsten av venös trombos har ökat under de senaste decennierna. Mer än en av fem personer som drabbas av venös trombos dör under det första året efter diagnos. Hos ungefär en tredjedel av dem som insjuknar i venös trombos hittar man ingen uppenbar förklaring till att de får sjukdomen. För att minska insjuknandet i venös trombos är det viktigt att identifiera påverkbara riskfaktorer för tillståndet.

Syfte: Syftet med denna avhandling var att studera frekvensen av nyinsjuknande i venös trombos i befolkningen och förekomsten av bidragande faktorer till venös trombos vid insjuknandet. Vi ville också undersöka i vilken utsträckning personer med en diagnoskod för venös trombos i sjukvårdsregister faktiskt haft en venös trombos. Slutligen ville vi studera om det finns ett samband mellan blodsockernivåer, diabetes, alkoholintag, fysisk aktivitet och risken för att senare i livet få en första venös trombos.

Metod: För att undersöka antalet personer som nyinsjuknar i venös trombos och förekomsten av riskmarkörer för venös trombos vid insjuknandet genomförde vi en retrospektiv (tillbakablickande) befolkningsbaserad studie. Vi registrerade alla vuxna i Västerbottens Län som fick venös trombos under år 2006 och vilka bidragande faktorer till venös trombos de hade vid insjuknandet. För att studera i vilken utsträckning diagnoser för venös trombos i sjukvårdsregister var korrekta gjorde vi en sökning för att hitta diagnoskoder för lungemboli och djup ventrombos i Nationella Patientregistret och Dödsorsaksregistret. Vi gjorde ytterligare en sökning, efter ännu fler diagnoskoder, för att hitta insjuknanden i venös trombos som felklassificerats som andra sjukdomar. Sambandet mellan blodsockernivåer, diabetes, alkoholintag, fysisk aktivitet och risken för att senare i livet få en första venös trombos undersökte vi i en prospektiv (framåtblickande), befolkningsbaserad studie som vi kallat Venous thromboEmbolism In Northern Sweden (VEINS)-studien. I VEINS-studien deltog de 108 025 invånare i Västerbottens Län som inte haft någon tidigare venös trombos och som genomgått en hälsoundersökning inom ramen för Västerbottens Hälsoundersökningar under åren 1985 till 2014. I hälsoundersökningen ingick kontroll av vikt, längd, blodtryck och blodsockernivåer. Deltagarna svarade på en enkät om rökning, utbildningsnivå, medicinering, förekomst av diabetes, alkoholintag och fysisk aktivitet. Deltagarna var 30 till 60 år gamla vid studien start. Studiedeltagarna följdes inom ramen för studien från hälsoundersökningen tills de insjuknade i venös trombos, dog, flyttade från området eller fram tills studiens slut 5:e september 2014. Personer i studiegruppen som fått en venös trombos identifierades genom sökning efter diagnoskoder för venös trombos i diagnosregister. Riktigheten i diagnoserna kontrollerades genom granskning av svar på röntgenundersökningar och medicinska journaler.

Resultat: I Västerbottens Län fick varje år 137 av 100 000 vuxna venös trombos för första gången. De vanligaste bidragande faktorerna till att personer fick venös trombos var att de nyligen legat på sjukhus eller hade en cancersjukdom. Av alla personer med en diagnoskod för lungemboli i ett sjukvårdsregister var diagnosen korrekt hos 81%. För djup ventrombos var motsvarande siffra 59%. En av hundra personer med lungemboli hade inte en diagnoskod för lungemboli i ett sjukvårdsregister. För djup ventrombos var motsvarande siffra sexton av hundra. I VEINS-studien insjuknade 2054 studiedeltagare i venös trombos för första gången. Totalt följdes studiedeltagarna i 1,5 miljoner personår. Deltagare med högre fasteblodsocker, högre blodsockervärde taget två timmar efter intag av en sockerlösning och deltagare med diabetes hade högre risk för venös trombos än andra deltagare. Efter att dessa analyser korrigerats för andra faktorer som har samband med blodsockervärden och diabetes och som kan ge ökad risk för venös trombos (störfaktorer), till exempel ålder och övervikt, fanns det inte längre något samband mellan blodsockervärden, diabetes och risk att drabbas av venös trombos. Det fanns ett samband mellan alkoholintag, mätt som antal standardglas alkohol en studiedeltagare drack per vecka, och ökad risk för venös trombos hos män. Det fanns också ett samband mellan alkoholberoende och ökad risk för venös trombos hos män. Dessa fynd kvarstod efter korrigering för möjliga störfaktorer. Vi såg inget samband mellan alkoholintag eller alkoholberoende och ökad risk för venös trombos hos kvinnor. Kvinnor som idrottade på fritiden minst en gång i veckan hade en lägre risk för att få en venös trombos jämfört med kvinnor som mer sällan eller inte alls idrottade på fritiden. Kvinnor med ett fysiskt aktivt arbete hade också lägre risk för venös trombos jämfört med kvinnor med ett mer stillasittande arbete. Hos män såg vi inget tydligt samband mellan fysisk aktivitet på fritiden eller i arbetet och risk för venös trombos.

Slutsatser: Venös trombos är en vanlig kärlsjukdom som drabbar kring 280 vuxna i Västerbotten varje år. Lungembolidiagnoser i sjukvårdsregister håller acceptabel kvalitet och skulle kunna användas i registerstudier. Diagnoser avseende djup ventrombos i sjukvårdsregister håller lägre kvalitet. Det finns inget samband mellan blodsockernivåer, diabetes och risk för venös trombos. Män med högt alkoholintag eller alkoholberoende har högre risk för venös trombos. Kvinnor med hög fysisk aktivitet på fritiden eller i arbetet har lägre risk för venös trombos.

Background: Physical activity may have a protective effect against venous thromboembolism (VTE). The aim of this study was to investigate the association between leisure time physical activity, occupational physical activity, and the risk of VTE in men and women separately.

Methods: The population-based, prospective Venous thromboEmbolism In Northern Sweden (VEINS) cohort study included 108,025 participants of health examinations between 1985 and 2014. Physical activity data were collected by questionnaire. Participants were followed from health examination to first-time VTE event, death, emigration or the end of the study. All VTE events were validated by reviewing medical records and radiology reports.

Results: During 1,496,669 person-years, 2054 participants experienced VTE. Women who performed leisure time physical activity at least once a week had a lower risk of first-time VTE (hazard ratio (HR) 0.83; 95% confidence interval (CI) 0.71–0.98 after adjustments) compared with women with less or no physical activity. Furthermore, women with high occupational physical activity also had a lower risk of VTE (HR 0.85; 95% CI 0.74–0.98). In men, there was no consistent association between either measure of physical activity and the risk of VTE.

Conclusion: We found an association between increased physical activity and a lower risk of first-time VTE in women.