Search

BACKGROUND: It is unknown whether dietary intake of polyunsaturated fatty acids (PUFA) modifies the cardiovascular disease (CVD) risk associated with a family history of CVD. We assessed interactions between biomarkers of low PUFA intake and a family history in relation to long-term CVD risk in a large consortium. METHODS: Blood and tissue PUFA data from 40 885 CVD-free adults were assessed. PUFA levels ≤25th percentile were considered to reflect low intake of linoleic, alpha-linolenic, and eicosapentaenoic/docosahexaenoic acids (EPA/DHA). Family history was defined as having ≥1 first-degree relative who experienced a CVD event. Relative risks with 95% CI of CVD were estimated using Cox regression and meta-analyzed. Interactions were assessed by analyzing product terms and calculating relative excess risk due to interaction. RESULTS: After multivariable adjustments, a significant interaction between low EPA/DHA and family history was observed (product term pooled RR, 1.09 [95% CI, 1.02-1.16]; P=0.01). The pooled relative risk of CVD associated with the combined exposure to low EPA/DHA, and family history was 1.41 (95% CI, 1.30-1.54), whereas it was 1.25 (95% CI, 1.16-1.33) for family history alone and 1.06 (95% CI, 0.98-1.14) for EPA/DHA alone, compared with those with neither exposure. The relative excess risk due to interaction results indicated no interactions. CONCLUSIONS: A significant interaction between biomarkers of low EPA/DHA intake, but not the other PUFA, and a family history was observed. This novel finding might suggest a need to emphasize the benefit of consuming oily fish for individuals with a family history of CVD.

Per‐ and polyfluoroalkyl substances (PFAS) are a group of persistent and widespread environmental pollutants that represent a high concern for human health. They have been shown to be associated with several important physiological processes such as lipid metabolism and the immune system. Consequently, PFAS are suspected to play a role in cardiometabolic disease development. However, the evidence regarding associations between PFAS and overt cardiovascular disease and type 2 diabetes remains limited and inconsistent. To address this, we conducted a review of the epidemiological evidence. A deeper understanding of potential underlying molecular mechanisms may help to explain inconsistencies in epidemiological findings. Thus, to gain more mechanistic insight, we also summarized evidence from omics and laboratory studies into an adverse outcome pathway framework. Our observations indicate the potential for associations of PFAS with multiple molecular pathways that could have opposite associations with disease risk, which could be further modified by mixture composition, lifestyle factors or genetic polymorphisms. This identifies the need for exposome studies considering mixture effects, the use of multi‐omics data to gain insight in relevant pathways and the integration of epidemiological and laboratory studies to enhance mechanistic understanding and causal inference. Improved comprehension is essential for environmental health risk assessments. [ABSTRACT FROM AUTHOR]

Background Colorectal cancer is the third most common malignancy worldwide and is strongly linked to lifestyle and environmental risk factors. Although several drinking-water disinfection by-products are confirmed rodent carcinogens, the evidence in humans for carcinogenicity associated with these by-products, including colorectal cancer, is still inconclusive. Methods We assessed the association of long-term exposure to trihalomethanes (THMs), the most prevalent disinfection by-products in chlorinated drinking water, with incidence of colorectal cancer in 58 672 men and women in 2 population-based cohorts. Exposure was assessed by combining long-term information of residential history with drinking water–monitoring data. Participants were categorized according to no exposure, low exposure (<15 µg/L), and high exposure (≥15 µg/L). Incident cases of colorectal cancer were ascertained by use of the Swedish National Cancer Register. Results During an average follow-up of 16.8 years (988 144 person-years), 1913 cases of colorectal cancer were ascertained (1176 cases in men and 746 in women, respectively). High THM concentrations in drinking water (≥15 µg/L) were associated with increased risk of colorectal cancer in men (hazard ratio = 1.26, 95% confidence interval = 1.05-1.51) compared with no exposure. When subsites were assessed, the association was statistically significant for proximal colon cancer (hazard ratio = 1.59, 95% confidence interval = 1.11 to 2.27) but not for distal colon cancer or rectal cancer. In women, we observed overall no association of THMs with colorectal cancer. Conclusion These results add further evidence that disinfection by-products in drinking water may be a possible risk factor for proximal colon cancer in men. This observation was made at THM concentrations lower than those in most previous studies. [ABSTRACT FROM AUTHOR]

Human biomonitoring (HBM) data in Europe are often fragmented and collected in different EU countries and sampling periods. Exposure levels for children and adult women in Europe were evaluated over time. For the period 2000–2010, literature and aggregated data were collected in a harmonized way across studies. Between 2011–2012, biobanked samples from the DEMOCOPHES project were used. For 2014–2021, HBM data were generated within the HBM4EU Aligned Studies. Time patterns on internal exposure were evaluated visually and statistically using the 50th and 90th percentiles (P50/P90) for phthalates/DINCH and organophosphorus flame retardants (OPFRs) in children (5–12 years), and cadmium, bisphenols and polycyclic aromatic hydrocarbons (PAHs) in women (24–52 years). Restricted phthalate metabolites show decreasing patterns for children. Phthalate substitute, DINCH, shows a non-significant increasing pattern. For OPFRs, no trends were statistically significant. For women, BPA shows a clear decreasing pattern, while substitutes BPF and BPS show an increasing pattern coinciding with the BPA restrictions introduced. No clear patterns are observed for PAHs or cadmium. Although the causal relations were not studied as such, exposure levels to chemicals restricted at EU level visually decreased, while the levels for some of their substitutes increased. The results support policy efficacy monitoring and the policy-supportive role played by HBM. [ABSTRACT FROM AUTHOR]

Introduction: Elevated phosphate (P) in urine may reflect a high intake of inorganic P salts from food additives. Elevated P in plasma is linked to vascular dysfunction and calcification. Objective: To explore associations between P in urine as well as in plasma and questionnaire‐estimated P intake, and incidence of cardiovascular disease (CVD). Methods: We used the Swedish Mammography Cohort‐Clinical, a population‐based cohort study. At baseline (2004–2009), P was measured in urine and plasma in 1625 women. Dietary P was estimated via a food‐frequency questionnaire. Incident CVD was ascertained via register‐linkage. Associations were assessed using Cox proportional hazards regression. Results: After a median follow‐up of 9.4 years, 164 composite CVD cases occurred (63 myocardial infarctions [MIs] and 101 strokes). Median P (percentiles 5–95) in urine and plasma were 2.4 (1.40–3.79) mmol/mmol creatinine and 1.13 (0.92–1.36) mmol/L, respectively, whereas dietary P intake was 1510 (1148–1918) mg/day. No correlations were observed between urinary and plasma P (r = −0.07) or dietary P (r = 0.10). Urinary P was associated with composite CVD and MI. The hazard ratio of CVD comparing extreme tertiles was 1.57 (95% confidence interval 1.05, 2.35; P trend 0.037)—independently of sodium excretion, the estimated glomerular filtration rate, both P and calcium in plasma, and diuretic use. Association with CVD for plasma P was 1.41 (0.96, 2.07; P trend 0.077). Conclusion: Higher level of urinary P, likely reflecting a high consumption of highly processed foods, was linked to CVD. Further investigation is needed to evaluate the potential cardiovascular toxicity associated with excessive intake of P beyond nutritional requirements. [ABSTRACT FROM AUTHOR]

Early puberty has been found to be associated with adverse health outcomes such as metabolic and cardiovascular diseases and hormone-dependent cancers. The decrease in age at menarche observed during the past decades has been linked to an increased exposure to endocrine-disrupting compounds (EDCs). Evidence for the association between PFAS and phthalate exposure and menarche onset, however, is inconsistent. We studied the association between PFAS and phthalate/DINCH exposure and age at menarche using data of 514 teenagers (12 to 18 years) from four aligned studies of the Human Biomonitoring for Europe initiative (HBM4EU): Riksmaten Adolescents 2016–2017 (Sweden), PCB cohort (follow-up; Slovakia), GerES V-sub (Germany), and FLEHS IV (Belgium). PFAS concentrations were measured in blood, and phthalate/DINCH concentrations in urine. We assessed the role of each individual pollutant within the context of the others, by using different multi-pollutant approaches, adjusting for age, age- and sex-standardized body mass index z-score and household educational level. Exposure to di(2-ethylhexyl) phthalate (DEHP), especially mono(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), was associated with an earlier age at menarche, with estimates per interquartile fold change in 5OH-MEHP ranging from −0.34 to −0.12 years in the different models. Findings from this study indicated associations between age at menarche and some specific EDCs at concentrations detected in the general European population, but due to the study design (menarche onset preceded the chemical measurements), caution is needed in the interpretation of causality. [ABSTRACT FROM AUTHOR]

Summary: We conducted cohort and Mendelian randomisation (MR) analyses to examine the associations of circulating proteins with risk of venous thromboembolism (VTE) to provide evidence basis for disease prevention and drug development. Cohort analysis was performed in 11 803 participants without baseline VTE. Cox regression was used to estimate the associations between 257 proteins and VTE risk. A machine‐learning model was constructed to compare the importance of identified proteins and traditional risk factors. Genetic association data on VTE were obtained from a genome‐wide meta‐analysis (26 066 cases and 624 053 controls) and FinnGen (14 454 cases and 294 700 controls). The cohort analysis, including 353 incident VTE cases diagnosed during a 6.6‐year follow‐up, identified 21 proteins associated with VTE risk after false discovery rate correction. The machine‐learning model indicated that body mass index and von Willebrand factor (vWF) made the same as well as most of the contributions to the overall model prediction. MR analysis found that genetically predicted levels of vWF, SERPINE1 (plasminogen activator inhibitor 1, known as PAI‐1), EPHB4 (ephrin type‐B receptor 4), TYRO3 (tyrosine‐protein kinase receptor TYRO3), TNFRSF11A (tumour necrosis factor receptor superfamily member 11A), and BOC (brother of CDO) were causally associated with VTE risk. [ABSTRACT FROM AUTHOR]

The aim was to collect and appraise scientific evidence that could be used to derive an upper intake level for folic acid/folate. Five systematic reviews of the literature were conducted to identify evidence to i) characterize the dose‐response curve between plasma/serum (P/S) folate and dietary folate intake expressed as dietary folate equivalents (DFE) in adults, and to assess the relationship between 'high' folate (intake/biomarkers) in humans with low B12 status and the ii) development of neuropathy and iii) cognitive impairment or dementia, and risk of iv) colorectal adenomas and colorectal cancer (CRC) and v) and prostate cancer. Narrative reviews were also performed. The linear meta‐regression model P/S folate (nmol/L) = 6.0 + 0.034*DFE/d (95% confidence interval, CI; 0.027‐0.040), R2 = 0.68, based on 22 studies and 60 data points could be used to predict mean P/S folate (and 95% CI) based on DFE intake. In view of the paucity of data, no comprehensive uncertainty analysis and evidence integration were performed for effects of 'high' folate intake on neuropathy, cognitive function/dementia. Comprehensive uncertainty analyses and evidence integration for a detrimental effect at high folate intake/status were performed for folic acid interventions and development of colorectal adenomas, for P/S folate from observational studies in relation to CRC incidence, and for total folate intake from observational studies in relation to prostate cancer incidence. The folic acid interventions were few (n = 4) and revealed both beneficial and detrimental effects on adenoma recurrence. For CRC the meta‐analyses on P/S folate indicated no association, but the risk estimates in the highest folate exposure groups were compared to levels indicating folate inadequacy or deficiency, thus, the research question could not be adequately addressed. For prostate cancer incidence too few studies with mixed results prevented any clear conclusion on total folate intake and risk of prostate cancer. [ABSTRACT FROM AUTHOR]

Aims: We conducted observational and Mendelian randomization (MR) analyses to explore the associations between blood proteins and risk of peripheral artery disease (PAD). Methods and results: The observational cohort analyses included data on 257 proteins estimated in fasting blood samples from 12 136 Swedish adults aged 55–94 years who were followed up for incident PAD via the Swedish Patient Register. Mendelian randomization analyses were undertaken using cis-genetic variants strongly associated with the proteins as instrumental variables and genetic association summary statistic data for PAD from the FinnGen study (11 924 cases and 288 638 controls) and the Million Veteran Program (31 307 cases and 211 753 controls). The observational analysis, including 86 individuals diagnosed with incident PAD during a median follow-up of 6.6-year, identified 13 proteins [trefoil factor two, matrix metalloproteinase-12 (MMP-12), growth differentiation factor 15, V-set and immunoglobulin domain-containing protein two, N-terminal prohormone brain natriuretic peptide, renin, natriuretic peptides B, phosphoprotein associated with glycosphingolipid-enriched microdomains one, C-C motif chemokine 15, P-selectin, urokinase plasminogen activator surface receptor, angiopoietin-2, and C-type lectin domain family five member A] associated with the risk of PAD after multiple testing correction. Mendelian randomization analysis found associations of T-cell surface glycoprotein CD4, MMP-12, secretoglobin family 3A member 2, and ADM with PAD risk. The observational and MR associations for T-cell surface glycoprotein CD4 and MMP-12 were in opposite directions. Conclusion: This study identified many circulating proteins in relation to the development of incident PAD. Future studies are needed to verify our findings and assess the predictive and therapeutic values of these proteins in PAD. Graphical abstract [ABSTRACT FROM AUTHOR]