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BACKGROUND: Observational studies have shown that women with an early menopause are at higher risk of stroke compared with women with a later menopause. However, associations with stroke subtypes are inconsistent, and the causality is unclear.

METHODS AND RESULTS: We analyzed data of the UK Biobank and EPIC-CVD (European Prospective Investigation Into Cancer and Nutrition-Cardiovascular Diseases) study. A total of 204 244 postmenopausal women without a history of stroke at baseline were included (7883 from EPIC-CVD [5292 from the subcohort], 196 361 from the UK Biobank). Pooled mean baseline age was 58.9 years (SD, 5.8), and pooled mean age at menopause was 47.8 years (SD, 6.2). Over a median follow-up of 12.6 years (interquartile range, 11.8–13.3), 6770 women experienced a stroke (5155 ischemic strokes, 1615 hemorrhagic strokes, 976 intracerebral hemorrhages, and 639 subarachnoid hemorrhages). In multivariable adjusted observational Cox regression analyses, the pooled hazard ratios per 5 years younger age at menopause were 1.09 (95% CI, 1.07–1.12) for stroke, 1.09 (95% CI, 1.06–1.13) for ischemic stroke, 1.10 (95% CI, 1.04–1.16) for hemorrhagic stroke, 1.14 (95% CI, 1.08–1.20) for intracerebral hemorrhage, and 1.00 (95% CI, 0.84–1.20) for subarachnoid hemorrhage. When using 2-sample Mendelian randomization analysis, we found no statistically significant association between genetically proxied age at menopause and risk of any type of stroke.

CONCLUSIONS: In our study, earlier age at menopause was related to a higher risk of stroke. We found no statistically significant association between genetically proxied age at menopause and risk of stroke, suggesting no causal relationship.

Background: Previous studies have shown an increased risk for atrial fibrillation and atrial flutter (AF) in people with type 2 diabetes and prediabetes. It is unclear whether this increase in AF risk is independent of other risk factors for AF.

Objective: To investigate the association between diabetes and different prediabetic states, as independent risk factors for the onset of AF.

Methods: We performed a population-based cohort study in Northern Sweden, including data on fasting plasma glucose, oral glucose tolerance test, major cardiovascular risk factors, medical history, and lifestyle factors. Participants were divided into six groups depending on glycemic status and followed through national registers for AF diagnosis. Cox proportional hazard model was used to assess the association between glycemic status and AF, using normoglycemia as reference.

Results: The cohort consisted of 88,889 participants who underwent a total of 139,661 health examinations. In the model adjusted for age and sex, there was a significant association between glycemic status and development of AF in all groups except the impaired glucose tolerance group, with the strongest association for the group with known diabetes (p-value <0.001). In a model adjusted for sex, age, systolic blood pressure, body mass index, antihypertensive drugs, cholesterol, alcohol, smoking, education level, marital status, and physical activity, there was no significant association between glycemic status and AF.

Conclusions/interpretation: The association between glycemic status and AF disappears upon adjustment for potential confounders. Diabetes and prediabetes do not appear to be independent risk factors for AF.

Background: Atrial fibrillation (AF) is the most common clinically significant arrythmia with a prevalence of approximately 3% in the general population. Less is known about the incidence of AF. In order to reduce the incidence of AF, it is of essence to identify modifiable risk factors for the disease.

Aims: The aims of this thesis were (1) to estimate the incidence of AF and to assess the prevalence of provoking factors and risk factors for stroke and systemic embolism at the time of AF diagnosis, (2) to study the association between alcohol consumption and risk of AF, (3) to study the association between weight, height, weight change, and risk of AF, and (4) to study the association between normal or high normal blood pressure (BP), compared to optimal BP, and risk of AF.

Methods: To determine the incidence of AF and the prevalence of provoking factors and risk factors for stroke and systemic embolism at AF diagnosis, an observational study was performed between January 1, 2011, and December 31, 2012, in the municipalities of Skellefteå and Norsjö, Västerbotten, Sweden. Diagnosis registries were searched for cases of incident AF. All AF diagnoses were verified by electrocardiogram. Data regarding provoking factors, type of AF and presence of risk factors for stroke and systemic embolism (as assessed by the CHA₂DS₂-VASc score) was obtained from medical records. Incidence was calculated by dividing the number of incident AF cases by the time at risk for the population.

The association between alcohol consumption, weight, height, weight change, normal BP, high normal BP, and risk of AF was investigated in a population-based cohort study of participants of the Västerbotten Intervention Programme (VIP). Residents of Västerbotten County aged 30, 40, 50 and 60 years who had participated in the VIP health examinations between January 1, 1988, and September 5, 2014, were included. Individuals who had been diagnosed with AF before participating in the VIP were excluded. Study participants were followed until a diagnosis of AF, death, migration from the study area, or the end of the study on September 5, 2014. Incident AF cases were identified using the Swedish National Patient Registry. The health examinations included measurements of height and weight, systolic BP, diastolic BP, fasting glucose, oral glucose tolerance, and cholesterol. 

Participants also answered a questionnaire addressing any history of diabetes and myocardial infarction, alcohol use, education level, smoking habits, medications, and physical activity. Optimal BP was defined as BP < 120/80 mm Hg. Normal BP was defined as BP 120–129/80–84 mm Hg. High normal BP was defined as BP 130–139/85–89 mm Hg. Hypertension was defined as BP ≥ 140/90 mm Hg. Cox proportional hazards regression analysis was used to assess the associations between alcohol consumption, weight, height, weight change, normal BP, high normal BP, and risk of AF. These were performed with crude, age-adjusted, and multivariable models adjusted for other cardiovascular risk factors (age, sex, body mass index, hypertension, cholesterol, previous myocardial infarction, diabetes, problem drinking, smoking, education level, and leisure-time physical activity).

Results: The incidence of AF was 4.0 cases of AF per 1000 person-years. In approximately one fifth of participants, a provoking factor was present at the first episode of AF. The CHA₂DS₂-VASc score was 2 or higher in 81% of participants. Permanent AF was the most common type of AF and was seen in about one third of the participants.

When studying the association between alcohol consumption and risk of AF, 109,230 health examination participants were included in the study cohort and were followed for 1,484,547 person-years. During the study period, 5230 participants developed incident AF. Men with alcohol consumption in the highest quartile (≥ 4.83 standard drinks weekly) had a hazard ratio (HR) of 1.21 (95% confidence interval [CI] 1.09-1.34) for AF in a multivariable model when compared to men with an alcohol consumption in the lowest quartile (< 0.90 standard drinks weekly). In men, problem drinking was also associated with an increased risk of AF (HR 1.24, 95% CI 1.10–1.39 in a multivariable model). Among women, no significant association between alcohol consumption, problem drinking, and risk of AF was identified.

In a fully adjusted model, height, weight, body mass index, and body surface area were positively associated with risk of incident AF. Among participants who underwent two health examinations 10 years apart, 1142 persons developed AF. The mean weight change from baseline was a weight gain of 4.8%. There was no significant association between either weight gain or weight loss and risk of AF.

In the study of the association between normal BP, high normal BP, and risk of AF, 109,697 persons with a total of 162,982 health examinations were included. Incident AF was diagnosed in 5260 participants. There was an increased risk of incident AF in persons with normal BP (HR 1.11, 95% CI 1.01–1.27) and in persons with high normal BP (HR 1.23, 95% CI 1.10–1.38) compared to optimal BP in a multivariable model. Systolic BP and diastolic BP were associated with risk of incident AF, with HRs of 1.11 (95% CI 1.10–1.13) and 1.13 (95% CI 1.09–1.16) per 10 mmHg, respectively, in multivariable models. A restricted cubic spline analysis indicated a gradually increasing risk of AF with increasing systolic BP and diastolic BP.

Conclusions: AF has an incidence of 4.0 per 1000 person-years. Alcohol consumption and problem drinking were associated with higher risk of AF in men, but not in women. Weight, height, body mass index, and body surface area were associated with increased risk of incident AF. Normal BP and high normal BP, when compared to optimal BP, were associated with increased risk of incident AF.

Bakgrund: Förmaksflimmer och förmaksfladder (FF) är vanliga hjärtrytmrubbningar som finns i flera olika former. Ungefär 3% av befolkningen är diagnosticerade med FF. Kunskapen om hur många som insjuknar i FF varje år är otillräcklig. Ibland förekommer det att personer som diagnosticeras med FF har något samtidigt tillstånd som triggar FF, exempelvis infektionssjukdom eller hjärtinfarkt. FF ökar risken för stroke (slaganfall). Risken för stroke kan minskas genom behandling med blodförtunnande läkemedel, så kallade antikoagulantia.

För att om möjligt kunna förebygga FF är det viktigt att känna till bakomliggande orsaker till att människor drabbas av FF. Vi känner till att personer med hög ålder, tidigare hjärtinfarkt och uttalat förhöjt blodtryck har en ökad risk för att insjukna i FF.

Syftet med denna avhandling var att studera hur vanligt det är med nyinsjuknande i FF i befolkningen. Vi ville också undersöka hur vanligt det är att personer som diagnosticeras med FF har en utlösande faktor till tillståndet och hur vanligt det är med riskfaktorer för stroke i samband med att man diagnosticeras med FF. Dessutom ville vi studera sambandet mellan alkoholkonsumtion, vikt, längd, kroppsstorlek, viktförändring, blodtryck och risk för FF.

Metod: För att studera hur vanligt det är med nyinsjuknande i FF i befolkningen och hur vanligt det är att personer som diagnosticeras med FF har en utlösande faktor till tillståndet eller har en eller flera riskfaktorer för stroke genomförde vi en studie i Skellefteå och Norsjö kommun i Västerbottens Län med ca 75 000 invånare. Vi sökte i diagnosregister efter nya fall av FF mellan 1 januari 2011 och 31 december 2012. Alla FF-diagnoser var bekräftade med elektrokardiogram (EKG). Information om utlösande faktorer till FF, typ av FF och förekomst av riskfaktorer för stroke hämtades från medicinska journaler.

Sambandet mellan alkoholkonsumtion, vikt, längd, viktförändring, lätt förhöjt blodtryck och risk för FF undersöktes i en studie där vi utgick från deltagare i Västerbottens Hälsoundersökningar. Invånare i Västerbotten inbjuds till en hälsoundersökning vid 30, 40, 50 och 60 års ålder. I våra studier ingår personer som deltagit i Västerbottens Hälsoundersökningar från 1 januari 1988 till 5 september 2014 och som inte hade diagnosticerats med FF innan de deltog i hälsoundersökningen. Studiedeltagarna följdes från att de deltog i hälsoundersökningen tills de diagnosticerades med FF, dog, flyttade från studieområdet eller tills studien tog slut 5 september 2014. Nya fall av FF i studiegruppen identifierades genom sökning i Nationella Patientregistret. Hälsoundersökningarna omfattade mätning av vikt och längd, blodtryck, blodsocker och blodfetter. Deltagarna svarade också på en enkät som omfattade frågor om personernas alkoholintag, utbildningsnivå, rökning, läkemedelsbehandling och fysisk aktivitet samt om de hade diabetes och om de hade haft hjärtinfarkt.

Resultat: Studien visade att 4 av 1000 invånare insjuknar i FF varje år. Ungefär en femtedel av dessa har en utlösande faktor till FF i samband med sin första FF-episod. Minst fyra av fem personer med FF har i samband med diagnos en så hög risk för stroke att det motiverar behandling med antikoagulantia. Permanent FF var den vanligaste typen av FF i vår studie. 

I studierna avseende sambandet mellan alkoholkonsumtion, vikt, längd, viktförändring, blodtryck och risk för FF deltog drygt 100 000 personer. Bland dessa fick drygt 5000 personer diagnosen FF under studietiden.

Vi fann att de män som drack mest alkohol (minst 4,8 standardglas alkoholhaltig dryck i veckan) hade 20% högre risk att drabbas av FF jämfört med de män som drack minst alkohol (under 0,9 standardglas alkohol i veckan) efter att hänsyn tagits till andra faktorer som skulle kunna påverka risken för FF. Hos kvinnor fanns det inget samband mellan alkoholintag och risk för FF.

Vi såg ett samband mellan högre vikt, längd samt kroppsstorlek mätt som body mass index och som kroppsyta och högre risk för FF. Sambandet mellan viktförändring och risk för FF undersöktes hos de studiedeltagare som deltagit i två hälsoundersökningar med tio års mellanrum. Det fanns inget samband mellan vare sig viktökning eller viktminskning och risk för FF.

Vi fann en ökad risk för FF hos personer med lätt förhöjt blodtryck (120–129/80–84 och 130–139/85–89 mm Hg) jämfört med hos personer med blodtryck under 120/80 mm Hg. Vad gäller uppmätta blodtrycksvärden fanns det samband mellan både högre övertryck, undertryck och ökad risk för FF.

Slutsatser: Fyra av 1000 invånare insjuknar i FF varje år. Alkoholkonsumtion hade samband med högre risk för FF hos män men inte hos kvinnor. Det fanns också ett samband mellan högre vikt, längd, body mass index, kroppsyta och högre risk för FF.  Vi såg också ett samband mellan högre nivåer på blodtryck och högre risk för FF.

AIMS: Atrial fibrillation (AF) is a common tachyarrhythmia. High alcohol consumption is associated with increased AF risk. It remains unclear whether lower levels of alcohol consumption are also associated with AF risk, and whether the association differs between men and women. In this study, we investigated the association between low to moderate levels of alcohol consumption and AF risk in men and women.

METHODS: We performed a population-based cohort study of 109,230 health examination participants in northern Sweden. Data regarding alcohol intake were obtained using a questionnaire administered at the health examination. Incident AF cases were identified from the Swedish National Patient Registry.

RESULTS: AF was diagnosed in 5,230 individuals during a total follow-up of 1,484,547 person-years. Among men, AF risk increased over quartiles of weekly alcohol consumption (P for trend 0.001). Men with alcohol consumption in the highest quartile (≥4.83 standard drinks [each drink containing 12 gs of ethanol] per week; SDW) had a HR of 1.21 (95% CI 1.09-1.34) for AF compared to men in the lowest quartile (<0.90 SDW). In men, problem drinking was also associated with an increased AF risk (HR: 1.24; 95% CI: 1.10-1.39). Among women, AF risk was not significantly associated with alcohol consumption (P for trend 0.09 for decreasing risk of AF over quartiles of weekly alcohol consumption) or problem drinking (HR: 1.00; 95% CI 0.70-1.42).

CONCLUSION: Self-reported alcohol consumption and problem drinking were associated with an increased risk of AF among men, but not in women.

Background: Anthropometric factors are reported to be risk factors for atrial fibrillation (AF), but it is unclear whether weight change in mid‐life is associated with AF. We aimed to study the possible associations of weight, height, and weight change with the risk of incident AF in men and women.

Methods: Our study cohort included 108 417 persons (51% women) who participated in a population‐based health examination in northern Sweden at 30, 40, 50, or 60 years of age. The health examination included weight and height measurement and collection of data regarding cardiovascular risk factors. Within this cohort, 40 275 participants underwent two health examinations with a 10‐year interval. We identified cases with a first‐ever diagnosis of AF through the Swedish National Patient Registry.

Results: During a total follow‐up of 1 469 820 person‐years, 5154 participants developed incident AF. The mean age at inclusion was 46.3 years, and mean age at AF diagnosis was 66.6 years. After adjustment for potential confounders, height, weight, body mass index (BMI), and body surface area (BSA) were positively associated with risk of incident AF in both men and women. Among participants who underwent two health examinations 10 years apart, 1142 persons developed AF. The mean weight change from baseline was a gain of 4.8%. Weight gain or weight loss was not significantly associated with risk of incident AF.

Conclusions: Height, weight, BMI, and BSA showed positive associations with risk of incident AF in both men and women. Midlife weight change was not significantly associated with AF risk.

Purpose: The aims of this study were to estimate the incidence of atrial fibrillation and atrial flutter (AF), to assess the presence of provoking factors and risk factors for stroke and systemic embolism, and to determine the type of AF in patients with first-diagnosed AF. Patients and methods: This cohort study was performed in northern Sweden between January 1, 2011 and December 31, 2012. Diagnosis registries were searched for the International Classification of Diseases-10 code for AF (I48) to identify cases of incident AF. All AF diagnoses were electrocardiogram-verified. Data pertaining to provoking factors, type of AF and presence of risk factors for stroke and systemic embolism according to the CHA(2)DS(2)-VASc score were obtained from medical records. Results: The incidence of AF in the entire population was 4.0 per 1,000 person-years. The incidence was 27.5 per 1,000 person-years in patients aged >= 80 years. A total of 21% of all patients had a provoking factor in association with the first-diagnosed episode of AF. The CHA(2)DS(2)-VASc score was 2 or higher in 81% of the patients. Permanent AF was the most common type of AF (29%). Conclusion: There was a considerable increase in the incidence of AF with age, and a provoking factor was found in one-fifth. The most common type of AF was permanent AF. Four in five patients had a CHA(2)DS(2)-VASc score of 2 or more.

Objective: An underuse of oral anticoagulants (OAC) in patients with atrial fibrillation (AF) has been suggested, as only 50% of all patients with AF receive OAC treatment. Whether this is due to contraindications, lack of an indication to treat, or an expression of underuse is sparsely investigated. This study therefore aimed to characterize individuals without OAC treatment in a real-life population of patients with AF. Design: Retrospective cross-sectional study. The medical records were scrutinized in order to identify the type of AF, risk factors for embolism and bleeding, and other factors of importance for OAC treatment. Setting: The municipalities of Skellefteå and Norsjö, northern Sweden. Subjects: A total of 2274 living residents with at least one verified episode of AF on or before December 31, 2010. Main outcome measures: Prevalence of treatment with OAC and documented reasons to withhold OAC treatment. Results: Among all 2274 patients with AF, 1187 (52%) were not treated with OAC. Of the untreated patients, 19% had no indication or had declined or had experienced adverse effects other than bleeding on warfarin treatment. The most common reason to withhold OAC was presence of risk factors for bleeding, found in 38% of all untreated patients. Furthermore, a documented reason could be identified to withhold OAC in 75%. Conclusions: Among patients with AF without OAC treatment a reason could be identifi ed to withhold OAC in 75%. The underuse of OAC is estimated to be 25%.

Objective: Our primary objective was to determine the proportion of patients with atrial fibrillation (AF) eligible for enrollment in a randomized controlled trial for a novel oral anticoagulant, the ARISTOTLE trial. A secondary objective was to describe the reasons for trial ineligibility.

Methods: We performed a cross-sectional study of an unselected population including 2274 patients in Skelleftea, Sweden with at least one verified episode of AF on or before December 31, 2010. Patients were classified as suitable or unsuitable for anticoagulant treatment according to current guidelines. The enrollment criteria from the ARISTOTLE trial were extracted from the original publication and applied to the population.

Results: Among all patients with AF, 1579 were classified as suitable for anticoagulant treatment. Of these, only 658 patients (42%) were eligible for participation in the ARISTOTLE trial. Among the 921 patients ineligible for participation, 498 did not meet the ECG criteria, 272 had psychosocial problems, and in addition, 78 patients were excluded due to both of these criteria.

Conclusion: Our study shows that a majority of the patients in an unselected population with AF suitable for anticoagulant treatment were ineligible for participation in the ARISTOTLE trial. The applicability of the ARISTOTLE trial is therefore unknown for a considerable proportion of patients with AF in real life.