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Prostate cancer (PCa) incidence has steadily increased in Sweden, more steeply in the mid-1990s caused by increased opportunistic prostate-specific antigen (PSA) testing. Tallness, normal weight, and non-smoking are associated with more PSA testing, which increases detection of low-risk and localised PCa. We investigated time trends of height, body mass index (BMI), and smoking with PCa risk in 171,889 men in Sweden aged 50-64 years at baseline, who were linked to nationwide cancer registers during follow-up. Cox regression determined the association of these factors assessed before 1980, 1980-1994, and 1995-2004 with PCa risk. During 15 follow-up years, 8,049 men were diagnosed with PCa. The association of height with PCa was weakly positive across all calendar periods. For obesity (BMI >= 30 kg/m2) vs. normal weight (BMI 18.5-24.9 kg/m2) and current vs. never smoking, the associations changed from null before 1980 (HR 1.03, 95% CI 0.86-1.23, and 1.11, 95% CI 0.97-1.27) to negative in 1995-2004 (HR 0.83, 95% CI 0.74-0.93, and 0.86, 95% CI 0.79-0.93; pinteraction between periods = 0.05 and 0.001). In men with clinical characteristics available, height was positively associated with both aggressive and non-aggressive PCa whilst obesity and smoking showed negative associations only with non-aggressive PCa. These findings likely reflect differences in PSA testing by BMI and smoking habits and contribute important knowledge for etiological studies of PCa.

Background

How cardiovascular diseases (CVD) predispose to a higher risk of fragility fractures is not well understood. Both contribute to significant components of disease burden and health expenditure. Poor bone quality, central obesity, sarcopenia, falls, and low grip strength are independent risk factors for hip and other fragility fractures and also for CVD and early death.

Methods

We used proteomics and a cohort design combined with Mendelian randomisation analysis to understand shared mechanisms for developing CVD and fragility fractures, two significant sources of disease burden and health expenditure. We primarily aimed to discover and replicate the association of 274 cardio-metabolic-related proteins with future rates of hip and any fracture in two separate population-based cohorts, with a total of 12,314 women and men.

Findings

The average age at baseline was 68 years in the discovery cohort of women and 74 years in the mixed-sex replication cohort. During 100,619 person-years of follow-up, 2168 had any fracture, and 538 had a hip fracture. Our analysis resulted in 24 cardiometabolic proteins associated with fracture risk: 20 with hip fracture, 9 with any fracture, and 5 with both. The associations remained even if protein concentrations were measured from specimens taken during preclinical stages of cardio-metabolic diseases, and 19 associations remained after adjustment for bone mineral density. Twenty-two of the proteins were associated with total body fat mass or lean body mass. Mendelian randomisation (MR) analysis supported causality since genetically predicted levels of SOST (Sclerostin), CCDC80 (Coiled-coil domain-containing protein 80), NT-proBNP (N-terminal prohormone brain natriuretic peptide), and BNP (Brain natriuretic peptide) were associated with risk of hip fracture. MR analysis also revealed a possible negative impact on bone mineral density (BMD) by genetically predicted higher levels of SOST, CCDC80, and TIMP4 (Metalloproteinase inhibitor 4). The MR association with BMD was positive for PTX3 (Pentraxin-related protein) and SPP1 (Osteopontin). Genetically predicted higher concentrations of SOST and lower concentrations of SPP1 also conferred a higher risk of falls and lowered grip strength. The genetically determined concentration of nine proteins influenced fat mass, and one influenced lean body mass.

Interpretation

These data reveal biological links between cardiovascular diseases and fragility fractures. The proteins should be further evaluated as shared targets for developing pharmacological interventions to prevent fractures and cardiovascular disease.

This commentary refers to 'Plasma proteome and incident myocardial infarction: sex-specific differences', by O.E. Titova et al., https://doi.org/10.1093/eurheartj/ehae658 and the discussion piece 'Gender-specific associations and circulating proteins in myocardial infarction: potential causal relationships', by Y. Xu et al., https://doi.org/10.1093/eurheartj/ehaf111

Background and aims

The relationship between uncommon phenotypes, such as metabolically healthy obesity and normal weight with metabolic syndrome (MetS), and cardiovascular disease (CVD) risk, remains unclear. We investigated how different combinations of body mass index (BMI) and MetS are associated with overall and specific CVDs and how the number of MetS components influences CVD risk in individuals with obesity.

Methods and results

We performed separate analyses and a meta-analysis of 36,233 individuals from four Swedish cohorts to assess the risk of incident CVDs across BMI/MetS combinations (normal-weight, overweight or obese/MetS yes or no). Participants were followed for CVDs and death through linkage to the Swedish National Registers.Compared to normal weight without MetS, overweight and obesity without MetS had most pronounced association with the risk of heart failure [multivariable hazard ratios, HR (95 % CI) = 1.37 (1.16–1.63) and 1.85 (1.37–2.48), respectively, p < 0.001]. In obese individuals, the risk of incident CVD (composite endpoint) increased with an increasing number of MetS components, but this relationship was not statistically significant in obese participants without additional MetS components, likely due to the small at-risk group. Normal-weight individuals with MetS had an increased risk of myocardial infarction [HR (95 % CI) 2.0 (1.51–2.64)], p < 0.001, and stroke [HR (95 % CI) 1.63 (1.17–2.28), p = 0.004].

Conclusions

Overweight and obesity without MetS showed a greater impact on the risk of heart failure, whereas normal-weight individuals with MetS had a higher risk of myocardial infarction and stroke. In obese individuals, CVD risk increased as the number of MetS components increased.

Atrial fibrillation (AF) is a common cardiac arrhythmia with strong genetic components, yet its underlying molecular mechanisms and potential therapeutic targets remain incompletely understood. We conducted a cross-population genome-wide meta-analysis of 168,007 AF cases and identified 525 loci that met genome-wide significance. Two loci of PITX2 and ZFHX3 genes were identified as shared across populations of different ancestries. Comprehensive gene prioritization approaches reinforced the role of muscle development and heart contraction while also uncovering additional pathways, including cellular response to transforming growth factor-beta. Population-specific genetic correlations uncovered common and unique circulatory comorbidities between Europeans and Africans. Mendelian randomization identified modifiable risk factors and circulating proteins, informing disease prevention and drug development. Integrating genomic data from this cross-population genome-wide meta-analysis with proteomic profiling significantly enhanced AF risk prediction. This study advances our understanding of the genetic etiology of AF while also enhancing risk prediction, prevention strategies, and therapeutic development.

BackgroundThere is evidence that some foods and dietary patterns may influence low-grade inflammation status. We aimed to develop a user-friendly empirical Anti-inflammatory Diet Index (eADI) that predicts low-grade chronic inflammation.MethodsIn this cross-sectional study of 4,432 men (aged 74 +/- 6 years) from the Cohort of Swedish Men-Clinical, inflammatory status was assessed by high-sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), tumor necrosis factor receptor 1 (TNF-R1), and tumor necrosis factor receptor 2 (TNF-R2). Dietary intake was assessed using a food frequency questionnaire. The eADI was developed in a randomly chosen Discovery group (n = 2,216) using a 10-fold feature selection with filtering (based on Lasso regression) to select food groups most correlated with inflammatory biomarkers. From the selected foods, the eADI was then constructed based on summed scores of the consumption tertiles (corresponding to 0, 0.5, and 1 point). Next, in the Replication group (n = 2,216), the association of eADI with inflammatory biomarkers was examined using multivariable-adjusted linear regression models.ResultseADI-17 included 17 food groups (11 with anti-inflammatory, 6 with pro-inflammatory potential). In the Replication group, the median of eADI-17 was 9 (range: 2-16) scores and the Spearman correlation coefficients for eADI-17 vs. hsCRP, IL-6, TNF-R1, and TNF-R2 were -0.17, -0.23, -0.28, and -0.26, respectively. Each increment by 4.5-point eADI-17 (2 SD) was associated with concentrations that were 12% lower for hsCRP, 6% lower for IL-6, 8% lower for TNF-R1, and 9% lower for TNF-R2. These results obtained for the Replication group were robust as they were essentially the same as those of the Discovery group.ConclusionsThe eADI-17 is a validated, robust and user-friendly anti-inflammatory diet index developed to predict low-grade chronic inflammation. This index has the potential to further refine future dietary guidelines and to be used in personalized nutrition. However, its predictive validity should be further evaluated in diverse populations.

BACKGROUND: A peroneus longus to brevis tendon transfer is recommended for a severely torn peroneus tendon, but there is little research on the outcome. We conducted a prospective cohort study to examine patient-reported outcomes after this procedure.

METHODS: Thirty-two patients underwent a peroneus longus to brevis tendon transfer and lateral ankle ligament reconstruction, 11 had an additional calcaneal osteotomy. The Foot and Ankle Outcome Score (FAOS) and Short Form-36 (SF-36) were assessed preoperatively, six and 12 months after surgery.

RESULTS: Preoperative mean FAOS was 51.7 (SD 17.8) compared with 72.7 (SD 21.2) at 12 months, an improvement of 21 (95 % CI 12.7-28.0) (p < 0.0001). SF-36 improved significantly in the three domains involving physical function and bodily pain (p < 0.007).

CONCLUSION: Patient-reported outcomes improved significantly through peroneus longus to brevis tendon transfer. This procedure is worth considering for patients with a severely damaged peroneus tendon.

LEVEL OF EVIDENCE: Level II: Prospective cohort study.

OBJECTIVE: Meat intake is suggested to affect gut microbiome composition and the risk of chronic diseases. We aimed to identify meat-associated gut microbiome features and their association with host factors.

DESIGN: Gut microbiota species were profiled by deep shotgun metagenomics sequencing in 9669 individuals. Intake of white meat, unprocessed red meat, and processed red meat was assessed using a food frequency questionnaire. The associations of meat intake with alpha-diversity and relative abundance of gut microbiota species were tested using linear regression models with adjustment for dietary fiber intake, body mass index, and other potential confounders. Meat-associated species were further assessed for association with enrichment of microbial gene function, meat-associated plasma metabolites, and clinical biomarkers.

RESULTS: Higher intake of processed red meat was associated with reduced alpha microbial diversity. White meat, unprocessed, and processed red meat intakes were associated with 36, 14, and 322 microbiota species, respectively. Species associated with processed red meat were enriched for bacterial pathways like amino acid degradation, while those negatively linked were enriched for pathways like homoacetogenesis. Furthermore, species positively associated with processed red meat were to a large extent associated with reduced trimethylamine N-oxide and glutamine levels but increased creatine and carnitine metabolites, fasting insulin and glucose, C-reactive protein, apolipoprotein A1, and triglyceride levels and higher blood pressure.

CONCLUSION: This largest to date population-based study on meat and gut microbiota suggests that meat intake, particularly processed red meat, may modify the gut microbiota composition, functional capacity, and health-related biomarkers.

Sleep problems and inadequate physical activity (PA) are associated with numerous adverse health outcomes. Most studies explored the influence of PA on sleep, but how sleep affects engagement in PA across adulthood remains less well investigated. This study examined the association between sleep traits and PA reported the following year in 51,247 Swedish women and men (55–93 years), who completed questionnaires regarding their sleep, PA, and other characteristics. Health status was assessed with data from the Swedish National Patient Registry. Odds ratios and 95% confidence intervals were estimated by binary logistic regression. In multivariable analysis, long sleep duration (≥ 9 h/night), sleep disturbance, and symptoms of sleep-disordered breathing (SDB) were associated with lower odds of engaging in walking or cycling, and exercising the following year. In addition, short sleep duration (< 7 h/night), sleep disturbance, and symptoms of SDB were linked to sedentary behavior (time spent on reading or watching TV). Several sex- and age-specific associations were observed. In addition to previous evidence of a positive effect of PA on sleep, our findings indicate that poor sleep may contribute to lower engagement in PA and a higher level of sedentary behavior, highlighting the bidirectional nature of the relationship between PA and sleep.