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Background: Alcohol consumption at low to moderate levels has long been debated in relation to cardiovascular risk, with inconsistent findings. Multi-decade cohort data with repeated exposure assessments are rare, especially in a northern Scandinavian population. This study aims to investigate associations between alcohol consumption at age 40, 50, and 60 and markers of subclinical atherosclerosis [carotid plaque and intima-media thickness (IMT)] at age 60 in a healthy below-risk-threshold alcohol-consuming cohort in Northern Sweden.

Methods: Participants in the Visualisation of Asymptomatic Atherosclerotic Disease for Optimum Cardiovascular Prevention (VIPVIZA) trial, aged 60 and with alcohol data from the Västerbotten Intervention Programme (VIP) at 40, 50, and 60, with below-risk-threshold alcohol consumption (>0 to ≤100 g/week) (n = 1,014) were included. Alcohol intake data were collected via a food frequency questionnaire in VIP. Carotid plaque and IMT were assessed at age 60 at VIPVIZA baseline.

Results: Mean weekly alcohol consumption for the study period was 26 g (±21.4 g), higher in men (37.5 ± 23.8 g) than in women (19.2 ± 16.3 g) and increasing over time in both sexes. At age 60, 49.6% had carotid plaque, and mean IMT was 0.77 mm (±0.15). No indication of associations was found between midlife alcohol consumption and carotid plaque in the total cohort [odds ratio (OR): 1.00, 95% confidence interval (CI): 0.99–1.01], men (OR: 1.00, 95% CI: 0.99–1.01), or women (OR: 0.99, 95% CI: 0.99–1.00) per gram increase of weekly alcohol intake. No associations were observed across consumption groups (>25 to ≤50, >50 to ≤75, >75 to ≤100 vs. >0 to ≤25 g/week).

Conclusion: No association was found between self-reported midlife alcohol consumption and subclinical atherosclerosis at age 60 in the VIPVIZA baseline cohort. Results were consistent across sexes and intake levels, contributing to the evidence base used to guide primary prevention and public health recommendations.

Background: The ABO blood group system has shown an association with cardiovascular disease. The susceptibility to CVD is proposed to be partly mediated by dyslipidaemia in non-O individuals. Previous studies are scarce for the RhD blood group, but we recently showed that RhD − young individuals are associated with subclinical atherosclerosis. Hence, we sought to examine whether the ABO blood groups and RhD factor are associated with dyslipidaemia.

Methods: All participants were part of the VIPVIZA study, including 3532 individuals with available plasma lipid levels. Lipids were assessed as total, LDL, HDL, remnant, non-HDL cholesterol and triglycerides. Information about ABO and RhD was retrieved by linking VIPVIZA with the SCANDAT-3 database, where 85% of VIPVIZA participants were registered.

Results: For the ABO blood groups, no significant differences in lipid levels between non-O and O individuals were seen. In 40-year-old males, RhD − individuals compared to RhD + had higher levels of non-HDL cholesterol, LDL cholesterol, and remnant cholesterol, with ratios of geometric means of 1.21 (CI95% 1.03; 1.43), 1.20 (1.02; 1.41) and 1.38 (1.00; 1.92), respectively. No differences in lipid levels depending on the RhD blood group were seen in women or the older age groups.

Conclusion: Our study indicates that younger RhD − men have increased non-HDL, LDL, and remnant cholesterol levels. Thus, the RhD blood group, but not ABO, seems to be associated with dyslipidaemia and may act as a future possible risk marker of cardiovascular disease.

Objectives: We examined the magnitude of transcription errors in lipid variables in the VIPVIZA study and assessed whether education among the research personnel reduced the error frequency at follow-up. We also examined how the errors affected the SCORE2 risk prediction algorithm for cardiovascular disease, which includes lipid parameters, as this could lead to an incorrect treatment decision.

Methods: The VIPVIZA study includes assessment of lipid parameters, where results for total cholesterol, triglycerides, HDL cholesterol, and calculated LDL cholesterol are transcribed into the research database by research nurses. Transcription errors were identified by recalculating LDL cholesterol, and a difference>0.15 indicated a transcription error in any of the four lipid parameters. To assess the presence of risk category misclassification, we compared the individual's SCORE2 risk category based on incorrect lipid levels to the SCORE2 categories based on the correct lipid levels.

Results: The transcription error frequency was 0.55 % in the 2019 VIPVIZA research database and halved after the educational intervention to 0.25 % in 2023. Of the 39 individuals who had a transcription error in total or HDL cholesterol (with the possibility of affecting the SCORE2 risk category based on non-HDL cholesterol), six individuals (15 %) received an incorrect risk category due to the error.

Conclusions: Transcription errors persist despite digitalisation improvements. It is essential to minimise transcriptions in fields outside the laboratory environment, as we observed that critical decisions also rely on accurate information such as the SCORE2-risk algorithm, which is dependent on lab results but not necessarily reported by the laboratory.

BACKGROUND: Elevated low-density lipoprotein (LDL) cholesterol levels represent a significant modifiable risk factor for atherosclerotic cardiovascular disease. However, a residual risk persists, possibly attributed to other atherogenic lipoproteins such as non-high-density lipoprotein (non-HDL) and remnant cholesterol. Nevertheless, few studies have explored the independent associations between these lipid biomarkers and early atherosclerotic disease.

OBJECTIVE: To evaluate the relative contributions of LDL, non-HDL, and remnant cholesterol to subclinical atherosclerosis, assessed by carotid ultrasonography.

METHOD: In this cross-sectional study, we included 1929 previously healthy individuals from the pragmatic VIPVIZA trial who had available lipid levels and carotid ultrasonography results to assess subclinical disease. Non-HDL, LDL, and remnant cholesterol were calculated from a standard lipid profile. Subclinical atherosclerosis was assessed by carotid intima-media thickness (cIMT) and the presence of carotid plaques.

RESULTS: We found that all lipid variables (LDL, non-HDL, and remnant cholesterol) were associated with subclinical atherosclerosis in univariable models (P < .01 across all models for cIMT and P < .001, P < .001, P = .003 respectively for carotid plaques). In multivariable-adjusted models, increasing LDL and non-HDL cholesterol levels were still significantly associated with increased odds of having carotid plaques (P < .001 for both) and increased cIMT (P < .001 for both). However, no independent association between remnant cholesterol and subclinical atherosclerosis was observed in the model adjusted for LDL cholesterol levels (P = .073 for cIMT and = .818 for plaque).

CONCLUSION: Increasing LDL and non-HDL cholesterol levels, but not remnant cholesterol, seem to contribute to carotid subclinical atherosclerosis.

Background & Aims: Biomarkers are needed to identify individuals at elevated risk of inflammatory bowel disease. This study aimed to identify protein signatures predictive of inflammatory bowel disease. Methods: Using large population-based cohorts (n ≥180,000), blood samples were obtained from individuals who later in life were diagnosed with inflammatory bowel disease and compared with age and sex-matched controls, free from inflammatory bowel disease during follow-up. A total of 178 proteins were measured on Olink platforms. We used machine-learning methods to identify protein signatures of preclinical disease in the discovery cohort (n = 312). Their performance was validated in an external preclinical cohort (n = 222) and assessed in an inception cohort (n = 144) and a preclinical twin cohort (n = 102).

Results: In the discovery cohort, a signature of 29 proteins differentiated preclinical Crohn's disease (CD) cases from controls, with an area under the curve (AUC) of 0.85. Its performance was confirmed in the preclinical validation (AUC = 0.87) and the inception cohort (AUC = 1.0). In preclinical samples, downregulated (but not upregulated) proteins related to gut barrier integrity and macrophage functionality correlated with time to diagnosis of CD. The preclinical ulcerative colitis signature had a significant, albeit lower, predictive ability in the discovery (AUC = 0.77), validation (AUC = 0.67), and inception cohorts (AUC = 0.95). The preclinical signature for CD demonstrated an AUC of 0.89 when comparing twins with preclinical CD with matched external healthy twins, but its predictive ability was lower (AUC = 0.58; P = .04) when comparing them with their healthy twin siblings, that is, when accounting for genetic and shared environmental factors.

Conclusion: We identified protein signatures for predicting a future diagnosis of CD and ulcerative colitis, validated across independent cohorts. In the context of CD, the signature offers potential for early prediction.

Background: The ABO blood group system has previously been associated with cardiovascular disease (CVD), where non-O blood group individuals have shown an increased risk. Studies assessing early atherosclerotic disease while also including RhD are few. We aimed to determine whether the ABO and RhD blood groups are associated with subclinical atherosclerosis in a healthy population.

Methods: We included 3532 participants from the VIPVIZA trial with available carotid ultrasonography results to assess subclinical disease. Information about blood groups was obtained from the SCANDAT-3 database, where 85% of VIPVIZA participants were registered.

Results: RhD− individuals aged 40 years showed increased carotid intima–media thickness (B 1.09 CI 95% 1.03; 1.14) compared to RhD+ individuals. For ABO, there were no differences in ultrasonography results when assessing the whole study population. However, 60-year-old individuals with heredity for CVD and a non-O blood group had decreased odds for carotid plaques (OR 0.54 CI 95% 0.33; 0.88).

Conclusions: RhD blood group is associated with subclinical atherosclerosis in younger individuals, indicating a role as a mediator in the atherosclerotic process. In addition, a non-O blood group was associated with decreased subclinical atherosclerosis in individuals aged 60 and with heredity (corresponding to the group with the highest atherosclerotic burden).

Background: Nutri-score is now widely available in food packages in Europe.

Aim: To study the overall nutritional quality of the diet in relation to risks of Crohn's disease (CD) and ulcerative colitis (UC), in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Methods: We collected dietary data at baseline from validated food frequency questionnaires. We used a dietary index based on the UK Food Standards Agency modified nutrient profiling system (FSAm-NPS-DI) underlying the Nutri-Score label, to measure the nutritional quality of the diet. We estimated the association between FSAm-NPS-DI score, and CD and UC risks using Cox models stratified by centre, sex and age; and adjusted for smoking status, BMI, physical activity, energy intake, educational level and alcohol intake.

Results: We included 394,255 participants (68.1% women; mean age at recruitment 52.1 years). After a mean follow-up of 13.6 years, there were 184 incident cases of CD and 459 incident cases of UC. Risk of CD was higher in those with a lower nutritional quality, that is higher FSAm-NPS-DI Score (fourth vs. first quartile: aHR: 2.04, 95% CI: 1.24–3.36; p-trend: <0.01). Among items of the FSAm-NPS-DI Score, low intakes of dietary fibre and fruits/vegetables/legumes/nuts were associated with higher risk of CD. Nutritional quality was not associated with risk of UC (fourth vs. first quartile of the FSAm-NPS-DI Score: aHR: 0.91, 95% CI: 0.69–1.21; p-trend: 0.76).

Conclusions: A diet with low nutritional quality as measured by the FSAm-NPS-DI Score is associated with a higher risk of CD but not UC.

Introduction: Dietary intake of (poly)phenols has been linked to reduced adiposity and body weight (BW) in several epidemiological studies. However, epidemiological evidence on (poly)phenol biomarkers, particularly plasma concentrations, is scarce. We aimed to investigate the associations between plasma (poly)phenols and prospective BW change in participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Methods: This study included 761 participants with data on BW at baseline and after 5 years of follow-up. Plasma concentrations of 36 (poly)phenols were measured at baseline using liquid chromatography-tandem mass spectrometry. Associations were assessed through general linear mixed models and multinomial logistic regression models, using change in BW as a continuous or as a categorical variable (BW loss, maintenance, gain), respectively. Plasma (poly)phenols were assessed as log2-transformed continuous variables. The false discovery rate (FDR) was used to control for multiple comparisons.

Results: Doubling plasma (poly)phenol concentrations showed a borderline trend towards a positive association with BW loss. Plasma vanillic acid showed the strongest association (−0.53 kg/5 years; 95% confidence interval [CI]: −0.99, −0.07). Similar results were observed for plasma naringenin comparing BW loss versus BW maintenance (odds ratio: 1.1; 95% CI: 1.0, 1.2). These results did not remain significant after FDR correction.

Conclusion: Higher concentrations of plasma (poly)phenols suggested a tendency towards 5-year BW maintenance or loss. While certain associations seemed promising, they did not withstand FDR correction, indicating the need for caution in interpreting these results. Further studies using (poly) phenol biomarkers are needed to confirm these suggestive protective trends.

Objectives: Aortic stenosis (AS) is the most prevalent valvular heart disease among adults. The adipocyte-derived hormones, leptin and adiponectin, have profound metabolic actions. We examined whether these adipokines are independently associated with future aortic valve replacement (AVR).

Design: In this longitudinal case-control study, we identified 336 cases who had undergone AVR due to AS, and who had previously participated in population-based health surveys. Two referents were matched to each case and leptin and adiponectin concentrations were analysed from stored baseline survey samples. Uni- and multivariable logistic regression analyses were used to estimate the risk of future AVR. An additional cohort was identified for validation including 106 cases with AVR and 212 matched referents.

Results: Median age (interquartile range (IQR)) in years at survey was 59.9 (10.4) and at surgery 68.3 (12.7), and 48% were women. An elevated concentration of leptin was not associated with future AVR (odds ratio [95% confidence interval]) (1.10 [0.92–1.32]), although leptin was associated with a higher risk in patients with coronary artery disease (CAD) having more than 5 years between survey and AVR (1.41 [1.08–1.84]). Adiponectin was not associated with higher risk for future AVR (0.95 [0.82–1.11]), although after stratification for age, higher levels were associated with reduced risk for AVR in persons aged ≥60 years at surgery (0.79 [0.64–0.98]). In the validation study, leptin was associated with future AVR whereas adiponectin was not. None of the associations remained significant after adjustment for body mass index (BMI).

Conclusions: The adipokine leptin may promote the development of AS.