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Background: Although physical activity is associated with cardiovascular health benefits and reduced all-cause mortality, vigorous exertion is also recognized as a trigger for sudden cardiac death (SCD). This study investigated vigorous exertion as a trigger for SCD resulting from myocardial infarction (MI) and the potential modifying effect of habitual vigorous exercise training among Swedish men who subsequently experienced SCD due to MI.

Methods: This prospective nested case-crossover study was performed within the Västerbotten Intervention Programme cohort from 1985 to 2006 and included male participants who later experienced SCD caused by MI. The risk of SCD during and within 30 min of vigorous exertion was compared with the risk during periods of non-exertion. Participants were categorized into three groups according to baseline frequency of habitual vigorous exercise training to assess effect modification.

Results: We included 192 men with SCD caused by MI, with a mean time from screening to event of 6.5 years. A majority of cases reported physical inactivity, with 161 cases reporting no exercise or <1 exercise event per week. 24 men suffered SCD in relation to vigorous exertion, yielding a relative risk of 43.6 (95% CI: 27.1-70.3) compared to non-exertion. The highest relative risk (107.7 [95% CI: 63.4-182.9]) was found among physically inactive men and was mitigated by a higher frequency of habitual exercise training at baseline.

Conclusion: Among Swedish men who experienced SCD caused by MI, vigorous exertion was associated with a transiently increased risk, which was mitigated by higher levels of habitual vigorous exercise training.

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.

Aims: Plasminogen activator inhibitor-1 (PAI-1) is the main inhibitor of the fibrinolytic system and is mainly secreted from adipose tissue. It is associated with cardiovascular disease and has also been considered a possible early risk marker for type 2 diabetes. Here, we present the results of a large prospective study investigating PAI-1 levels in relation to incident type 2 diabetes mellitus.

Methods: We conducted a prospective incident case-referent study within the Västerbotten Intervention Programme (VIP). Data on cardiovascular risk factors, fasting plasma glucose (FPG) and 2-hour plasma glucose (2-hPG) were collected at baseline health examination 1990–2005. Blood samples were collected and stored for future analyses. Participants were followed and 484 cases developed type 2 diabetes. Referents without type 2 diabetes were matched for sex, age, and year of participation, n = 484. Baseline plasma samples were analysed for PAI-1. Subgroup analysis was performed for 201 cases and 201 matched referents with normal baseline glucose levels (FPG < 6.1 and 2hPG < 8.9 mmol/L).

Results: Elevated baseline levels of PAI-1 were associated with incident type 2 diabetes after adjustments for BMI, family history of diabetes, smoking status, hypertension, FPG and 2hPG (PAI-1; OR = 1.87, 95% CI: 1.06–3.29). A similar result was shown in the subgroup analysis with 201 participants who had normal glucose levels at time of the health examination (PAI-1; OR = 2.68, 95% CI: 1.03–6.95).

Conclusions: Elevated PAI-1 levels in non-diabetic persons precede the manifestation of type 2 diabetes and can be detected before an elevation of FPG or 2-hPG is observed.

Background and Aims: This study aimed to investigate the association between normal BP, (blood pressure [BP] 120–129/80–84 mmHg), and high normal BP, (BP 130–139/85–89 mmHg), compared to optimal BP, and risk of atrial fibrillation (AF).

Methods: A population-based cohort study was performed including inhabitants of Västerbotten County, Sweden, aged 30–60 years without AF at inclusion who participated in health examinations in 1988–2014. Approximately 40% of participants had ≥ 2 health examinations. The health examination included a questionnaire and measurement of BP, weight, height, and glucose. Cox regression with time-updated covariates was used to estimate the association between BP and AF risk. Restricted cubic spline analyses were performed.

Results: The cohort included 109,697 persons with 162,982 observations and a mean follow-up of 13.6 years. Incident AF was diagnosed in 5260 participants. We found an increased risk of incident AF associated with normal BP (hazard ratio [HR] 1.13, 95% confidence interval [CI] 1.01–1.27) and high normal BP (HR 1.23, 95% CI 1.10–1.38) compared to optimal BP after multivariable adjustment. Systolic BP and diastolic BP in 10 mmHg increments 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), respectively, in multivariable models. A restricted cubic spline analysis indicated that the AF risk increased gradually with increasing systolic and diastolic BP.

Conclusion: Individuals with both normal BP and high normal BP have an increased risk of developing incident AF. The risk of AF increased gradually with increasing systolic and diastolic BP.

Introduction: Fine-needle aspiration cytology (FNAC) is an effective tool in the diagnostic work-up of patients with thyroid nodules. The aim of our study was to assess the diagnostic sensitivity of FNAC in thyroid cancer (TC) in Sweden by correlating the findings of preoperative FNAC with those obtained through final histology of the surgical specimen.

Methods: A Swedish nationwide cohort of patients having surgery for TC (n = 2519) from the Scandinavian Quality Register for Thyroid, Parathyroid and Adrenal surgery between 2004 and 2013 was obtained. Data was validated through scrutinizing patient FNAC and histology reports.

Results: Among the 2519 cases operated with a final diagnosis of TC, the diagnosis was substantiated and validated through the histology report in 2332 cases (92.6%), included in the present study. Among these, 1679 patients (72%) were female and the median age at TC diagnosis was 52.3 years (range 18-94.6). In 353 cases (15.1%) FNAC was not performed at all; whereas in the remaining 1965 cases, the diagnostic sensitivity of FNAC was 81.6%. In lesions > 1 cm, FNAC diagnostic sensitivity reached 86.5%, whereas in lesions < 1 cm, FNAC yielded a sensitivity of 61.5%. Approximately 85% of FNACs (n = 1981/2332) were performed using ultra-sonographic (US) guidance. In TC lesions > 1 cm, the diagnostic sensitivity of US-guided FNAC (n = 1504) was 86.9% as compared to 76.9% in clinically applied FNAC without US utilization (n = 118).

Conclusions: FNAC is performed in most patients operated for TC in Sweden (85%) and retains its value as a tool in TC diagnostic work-up with an overall sensitivity of 82%, reaching 87% in lesions > 1 cm, that harbor clinically relevant TC.

Objectives: Electrocardiogram (ECG) and measurement of plasma brain natriuretic peptides (BNP) are established markers of right ventricular dysfunction (RVD) in the setting of acute pulmonary embolism (PE) but their value at long-term follow-up is largely unknown. The purpose of this prospective study was to determine the prevalence of ECG abnormalities, describe levels of N-terminal proBNP (NT-proBNP), and establish their association with dyspnea at long-term follow-up after PE.

Design: All Swedish patients diagnosed with acute PE in 2005 (n = 5793) were identified through the Swedish National Patient Registry. Surviving patients in 2007 (n = 3510) were invited to participate. Of these, 2105 subjects responded to a questionnaire about dyspnea and comorbidities. Subjects with dyspnea or risk factors for development of chronic thromboembolic pulmonary hypertension were included in the study in a secondary step, which involved collection of blood samples and ECG registration.

Results: Altogether 49.3% had a completely normal ECG. The remaining participants had a variety of abnormalities, 7.2% had atrial fibrillation/flutter (AF). ECG with any sign of RVD was found in 7.2% of subjects. Right bundle branch block was the most common RVD sign with a prevalence of 6.4%. An abnormal ECG was associated with dyspnea. AF was associated with dyspnea, whereas ECG signs of RVD were not. 61.2% of subjects had NT-proBNP levels above clinical cut-off (>125 ng/L). The degree of dyspnea did not associate independently with NT-proBNP levels.

Conclusions: We conclude that the value of ECG and NT-proBNP in long term follow-up after PE lies mostly in differential diagnostics.

Purpose: To assess the impact of fine-needle aspiration cytology (FNAC) in the extent of surgery in patients with thyroid cancer (TC) and the associated surgical morbidity in primary and completion setting.

Methods: A Swedish nationwide cohort of patients having surgery for TC (n = 2519) from the Scandinavian Quality Register for Thyroid, Parathyroid and Adrenal surgery between 2004 and 2013 was obtained. Data was validated through scrutinizing FNAC and histology reports.

Results: Among the 2519 cases operated for TC, the diagnosis was substantiated and validated through the histology report in 2332 cases (92.6%). Among these, 1679 patients (72%) were female, and the median age at TC diagnosis was 52.3 years (range 18–94.6). Less than total thyroidectomy (LTT) was undertaken in 944 whereas total thyroidectomy (TT) in 1388 cases. The intermediate FNAC categories of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/ FLUS), as well as suspicion for follicular neoplasm (SFN) lesions were more often encountered in LTT (n = 314, 33.3%) than TT (n = 63, 4.6%), whereas FNACs suspicion for malignancy and/or malignancy were overrepresented in TT (n = 963, 69.4%). Completion thyroidectomies were undertaken in 553 patients out of 944 that initially had LTT. In 201 cases with cancer lesions > 1 cm, other than FTC (Follicular TC)/ HTC (Hürthle cell TC) subjected to primary LTT, inadequate procedures were undertaken in 81 due to absent, Bethesda I or II FNAC categories, preoperatively. Complications at completion of surgery in this particular setting were 0.5% for RLN palsy (n = 1) and 1% (n = 2) for hypoparathyroidism 6 months postoperatively. The overall postoperative complication rate was higher in primary TT vs. LTT for RLN palsy (4.8% [n = 67] vs. 2.4% [n = 23]; p = 0.003) and permanent hypoparathyroidism (6.8% [n = 95] vs. 0.8% [n = 8]; p < 0.0001).

Conclusions: FNAC results appear to affect surgical planning in TC as intermediate FNAC categories lead more often to LTT. Overall, inadequate procedures necessitating completion surgery are encountered in up to 15% of TC patients subjected to LTT due to absent, inconclusive, or misleading FNAC, preoperatively. However, completion of thyroidectomy in this setting did not yield significant surgical morbidity. Primary LTT is a safer primary approach compared to TT in respect of RLN palsy and permanent hypoparathyroidism complication rates; therefore, primary TT should probably be reserved for lesions > 1 cm or even larger with suspicion for malignancy or malignant FNAC.

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.

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.

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.