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BACKGROUND: The blood pressure (BP) etiologic study is complex due to multifactorial influences, including genetic, environmental, lifestyle, and their intricate interplays. We used a metabolomics approach to capture internal pathways and external exposures and to study BP regulation mechanisms after well-controlled dietary interventions. METHODS: In the ProBP trail (Protein and Blood Pressure), a double-blinded crossover randomized controlled trial, participants underwent dietary interventions of carbohydrate, soy protein, and milk protein, receiving 40 g daily for 8 weeks, with 3-week washout periods. We measured plasma samples collected at baseline and at the end of each dietary intervention. Multivariate linear models were used to evaluate the association between metabolites and systolic/diastolic BP. Nominally significant metabolites were examined for enriching biological pathways. Significant ProBP findings were evaluated for replication among 1311 participants of the BHS (Bogalusa Heart Study), a population-based study conducted in the same area as ProBP. RESULTS: After Bonferroni correction for 77 independent metabolite clusters (α=6.49x10-4), 18 metabolites were significantly associated with BP at baseline or the end of a dietary intervention, of which 11 were replicated in BHS. Seven emerged as novel discoveries, which are as follows: 1-linoleoyl-GPE (18:2), 1-oleoyl-GPE (18:1), 1-stearoyl-2-linoleoyl-GPC (18:0/18:2), 1-palmitoyl-2-oleoyl-GPE (16:0/18:1), maltose, N-stearoyl-sphinganine (d18:0/18:0), and N6-carbamoylthreonyladenosine. Pathway enrichment analyses suggested dietary protein intervention might reduce BP through pathways related to G protein--coupled receptors, incretin function, selenium micronutrient network, and mitochondrial biogenesis. CONCLUSIONS: Seven novel metabolites were identified to be associated with BP at the end of different dietary interventions. The beneficial effects of protein interventions might be mediated through specific metabolic pathways. [ABSTRACT FROM AUTHOR]

Key Points: Question: Do children who resolve dyslipidemic non–high-density lipoprotein cholesterol (non–HDL-C) levels by adulthood have attenuated risk of developing cardiovascular disease (CVD) events? Findings: Among 5121 children pooled from 6 prospective cohort studies in the US and Finland (mean follow-up, 8.9 years after age 40 years), individuals who had dyslipidemic non–HDL-C in childhood that resolved during adulthood did not have a significantly increased risk of fatal or nonfatal CVD events (hazard ratio, 1.13) than those whose non–HDL-C levels were persistently within the guideline-recommended range in childhood and adulthood. Meaning: Children in whom dyslipidemic non–HDL-C resolves by adulthood have similar risk of CVD to those who never had dyslipidemia. Importance: Elevated non–high-density lipoprotein cholesterol (non–HDL-C; a recommended measure of lipid-related cardiovascular risk) is common in children and increases risk of adult cardiovascular disease (CVD). Whether resolution of elevated childhood non–HDL-C levels by adulthood is associated with reduced risk of clinical CVD events is unknown. Objective: To examine the associations of non–HDL-C status between childhood and adulthood with incident CVD events. Design, Setting, and Participants: Individual participant data from 6 prospective cohorts of children (mean age at baseline, 10.7 years) in the US and Finland. Recruitment took place between 1970 and 1996, with a final follow-up in 2019. Exposures: Child (age 3-19 years) and adult (age 20-40 years) non–HDL-C age- and sex-specific z scores and categories according to clinical guideline–recommended cutoffs for dyslipidemia. Main Outcomes and Measures: Incident fatal and nonfatal CVD events adjudicated by medical records. Results: Over a mean length of follow-up of 8.9 years after age 40 years, 147 CVD events occurred among 5121 participants (60% women; 15% Black). Both childhood and adult non–HDL-C levels were associated with increased risk of CVD events (hazard ratio [HR], 1.42 [95% CI, 1.18-1.70] and HR, 1.50 [95% CI, 1.26-1.78] for a 1-unit increase in z score, respectively), but the association for childhood non–HDL-C was reduced when adjusted for adult levels (HR, 1.12 [95% CI, 0.89-1.41]). A complementary analysis showed that both childhood non–HDL-C levels and the change between childhood and adulthood were independently associated with the outcome, suggesting that from a preventive perspective, both childhood non–HDL-C levels and the change into adulthood are informative. Compared with those whose non-HDL-C levels remained within the guideline-recommended range in childhood and adulthood, participants who had incident non–HDL-C dyslipidemia from childhood to adulthood and those with persistent dyslipidemia had increased risks of CVD events (HR, 2.17 [95% CI, 1.00-4.69] and HR, 5.17 [95% CI, 2.80-9.56], respectively). Individuals who had dyslipidemic non–HDL-C in childhood but whose non-HDL-C levels were within the guideline-recommended range in adulthood did not have a significantly increased risk (HR, 1.13 [95% CI, 0.50-2.56]). Conclusions and Relevance: Individuals with persistent non–HDL-C dyslipidemia from childhood to adulthood had an increased risk of CVD events, but those in whom dyslipidemic non–HDL-C levels resolve by adulthood have similar risk to individuals who were never dyslipidemic. These findings suggest that interventions to prevent and reduce elevated childhood non–HDL-C levels may help prevent premature CVD. This study of individual participant data from 6 pooled cohorts assesses whether resolution of elevated childhood non–high-density lipoprotein cholesterol (non–HDL-C) by adulthood is associated with reduced risk of clinical cardiovascular disease (CVD) events. [ABSTRACT FROM AUTHOR]

Background: The metabolic changes that ultimately lead to gestational diabetes mellitus (GDM) likely begin before pregnancy. Cannabis use might increase the risk of GDM by increasing appetite or promoting fat deposition and adipogenesis. Objectives: We aimed to assess the association between preconception cannabis use and GDM incidence. Methods: We analysed individual‐level data from eight prospective cohort studies. We identified the first, or index, pregnancy (lasting ≥20 weeks of gestation with GDM status) after cannabis use. In analyses of pooled individual‐level data, we used logistic regression to estimate study‐type‐specific odds ratios (OR) and 95% confidence intervals (CI), adjusting for potential confounders using random effect meta‐analysis to combine study‐type‐specific ORs and 95% CIs. Stratified analyses assessed potential effect modification by preconception tobacco use and pre‐pregnancy body mass index (BMI). Results: Of 17,880 participants with an index pregnancy, 1198 (6.7%) were diagnosed with GDM. Before the index pregnancy, 12.5% of participants used cannabis in the past year. Overall, there was no association between preconception cannabis use in the past year and GDM (OR 0.97, 95% CI 0.79, 1.18). Among participants who never used tobacco, however, those who used cannabis more than weekly had a higher risk of developing GDM than those who did not use cannabis in the past year (OR 2.65, 95% CI 1.15, 6.09). This association was not present among former or current tobacco users. Results were similar across all preconception BMI groups. Conclusions: In this pooled analysis of preconception cohort studies, preconception cannabis use was associated with a higher risk of developing GDM among individuals who never used tobacco but not among individuals who formerly or currently used tobacco. Future studies with more detailed measurements are needed to investigate the influence of preconception cannabis use on pregnancy complications. [ABSTRACT FROM AUTHOR]