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Utilization of high-quality clinical practice guidelines has the potential to positively impact health outcomes. This study aimed to assess the quality and content concordance of national and international recommendations on hypertensive disorders of pregnancy (HDPs). Searches were conducted of the MEDLINE database and reference lists generated from national and international agencies. Covidence software was used for the management of the systematic review process, the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool was used to assess guidelines for quality, and three reviewers independently screened records. The research team identified and screened a total of 399 records of which 10 were deemed high quality. Guidelines were assessed and compared regarding the treatment, prevention, and categorization of disorders. The quality of guidelines varied across different domains, with significant variation in domain scores even within individual guidelines. Not all recommendations showed a high level of methodologic rigor, and the highest-rated guidelines were from the American Heart Association, the World Health Organization, and South Africa national guidelines. Classification of hypertension differed among the guidelines, particularly in defining chronic hypertension, severe hypertension, and preeclampsia. Prevention modalities varied across guidelines, with recommendations for aspirin, calcium supplementation, and against the use of certain approaches. Treatment modalities highlighted the importance of delivery as the definitive way to terminate hypertensive disorders of pregnancy, with other management strategies provided for symptom control. The variability in guidelines and consensus statements across different contexts may reflect regional differences in healthcare practices, available resources, and research evidence. There is potential to harmonize guidelines for HDP globally while considering the unique needs of individual countries. Where guidelines may be synthesized and condensed into an accessible format, doing so could improve their use in clinical decision-making.

ObjectivesHigh-quality evidence-based clinical practice guidelines can guide diagnosis and treatment to optimise outcomes. The purpose of this study was to evaluate the quality and content of national and international guidelines on hypertensive disorders of pregnancy. Data Sources: The MEDLINE database, the National Guideline Clearinghouse and several international databases were searched for appropriate guidelines from the past 10 years. Study Appraisal and Synthesis Methods: Six guidelines met inclusion and exclusion criteria and were evaluated using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument.ResultsA total of 695 records were identified and screened by two authors. Disorder definitions, classifications, preventive measures and treatment recommendations were evaluated and compared among guidelines. AGREE II results varied widely across domains and categories. Only two guidelines received consistently high ratings across domains and few demonstrated a high level of methodological rigour. Recommendations regarding classification and treatment were similar across guidelines, while assessment of preventive measures varied widely.ConclusionsClinical practice guidelines for hypertensive disorders of pregnancy vary significantly in quality and with respect to assessment of preventive measures.

In this study, childhood cardiovascular risk factors including BMI, systolic blood pressure, lipid levels, and smoking were correlated with cardiovascular events in adulthood after a mean follow-up of 35 years. Childhood risk factors and the change in risk score between childhood and adulthood were associated with midlife cardiovascular events.

Studies of adiposity and cognition’s relationship have been highly mixed, depending on points in the lifespan when adiposity and cognition were measured, primarily with low Black American representation. Therefore, we examined the association between adiposity (from early to mid-life) and mid-life cognition in an Black American (BA) and White American longitudinal cohort to address these literature gaps. The Bogalusa Heart Study has followed participants from childhood to adulthood since 1973. Adiposity was measured via body mass index (BMI) at roughly biannual visits from 1973–2016 and cognition was measured in 1295 participants between 2013- 2016. Cognition included Logical Memory I, II and II Recognition, Digit Spans Forward and Backward, Trail Making Tests A and B, and a global composite. BMI was averaged within age epochs (childhood/adolescence; early adulthood (EA); midlife (M)) with childhood/adolescence BMI as percentiles. Separate linear regression models were run for each cognitive measure (outcome), BMI within one epoch, and sex, race, and education (predictors). All analyses included the 1292 individuals who provided complete data across all epochs. Greater BMI within EA and M was associated with better global cognition (EA: Est. 0.139 S.D./BMI p = 0.000; M: Est. 0.094 S.D./BMI p = 0.022), and Logical Memory I (EA: Est. 0.036 S.D./BMI p = 0.000; M: Est. 0.022 S.D./BMI p = 0.000), II (EA: Est. 0.036 S.D./BMI p = 0.000; M: Est. 0.020 S.D./BMI p = 0.022) and II Recognition (EA: Est. 0.029 S.D./BMI p = 0.000; M: Est. 0.022 S.D./BMI p = 0.000) among men. Among BA, greater BMI within EA and M was associated with better Logical Memory I (EA: Est. 0.022 S.D./BMI p = 0.000; M: Est. 0.019 S.D./BMI p = 0.000) and II (EA: Est. 0.018 S.D./BMI p = 0.042; M: Est. 0.017 S.D./BMI p = 0.000). Greater adiposity from early adulthood to midlife was associated with better memory performance in midlife (associations strongest among men and Black Americans). More anatomically precise measurements of adiposity (e.g., subcutaneous vs. visceral fat) could help clarify the complex adiposity cognition relationship across the lifespan.

The epidemiology of atrial fibrillation (AF) has been mainly investigated in patients with end-stage renal disease, with limited data on less advanced chronic kidney disease (CKD) stages. A total of 3,267 adult participants (50% non-Hispanic blacks, 46% women) with CKD from the Chronic Renal Insufficiency Cohort were included in this study. None of the study participants had been on dialysis. Those with self-identified race/ethnicity other than non-Hispanic black or white (n = 323) or those without electrocardiographic data (n = 22) were excluded. Atrial fibrillation was ascertained by a 12-lead electrocardiogram and self-report. Age-, sex-, and race/ethnicity-specific prevalence rates of AF were estimated and compared between subgroups. Cross-sectional associations and correlates with prevalent AF were examined using unadjusted and multivariable-adjusted logistic regression analysis. The mean estimated glomerular filtration rate was 43.6 (±13.0) mL/(min 1.73 m 2). Atrial fibrillation was present in 18% of the study population and in >25% of those ≥70 years old. In multivariable-adjusted models, 1-SD increase in age (11 years) (odds ratio 1.27, CI 95% 1.13-1.43, P < .0001), female sex (0.80, 0.65-0.98, P = .0303), smoking (former vs never) (1.34, 1.08-1.66, P = .0081), history of heart failure (3.28, 2.47-4.36, P < .001), and history of cardiovascular disease (1.94, 1.56-2.43, P < .0001) were significantly associated with AF. Race/ethnicity, hypertension, diabetes, body mass index, physical activity, education, high-sensitivity C-reactive protein, total cholesterol, and alcohol intake were not significantly associated with AF. An estimated glomerular filtration rate <45 mL/(min 1.73 m 2) was associated with AF in an unadjusted model (1.35, 1.13-1.62, P = .0010), but not after multivariable adjustment (1.12, 0.92-1.35, P = .2710). Nearly 1 in 5 participants in Chronic Renal Insufficiency Cohort, a national study of CKD, had evidence of AF at study entry, a prevalence similar to that reported among patients with end-stage renal disease and 2 to 3 times of that reported in the general population. Risk factors for AF in this CKD population do not mirror those reported in the general population.

BackgroundThioredoxin Interacting Protein (TXNIP) functions as a master regulator for glucose homeostasis. Hypomethylation at the 5’-cytosine-phosphate-guanine-3’ (CpG) site cg19693031 of TXNIP has been consistently related to islet dysfunction, hyperglycemia, and type 2 diabetes. DNA methylation (DNAm) may reveal the missing mechanistic link between obesity and type 2 diabetes. We hypothesize that baseline DNAm level at TXNIP in blood may be associated with glycemic traits and their changes in response to weight-loss diet interventions.MethodsWe included 639 adult participants with overweight or obesity, who participated in a 2-year randomized weight-loss diet intervention. Baseline blood DNAm levels were profiled by high-resolution methylC-capture sequencing. We defined the regional DNAm level of TXNIP as the average methylation level over CpGs within 500 bp of cg19693031. Generalized linear regression models were used for main analyses.ResultsWe found that higher regional DNAm at TXNIP was significantly correlated with lower fasting glucose, HbA1c, and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at baseline (P < 0.05 for all). Significant interactions were observed between dietary protein intake and DNAm on changes in insulin (P-interaction = 0.007) and HOMA-IR (P-interaction = 0.009) at 6 months. In participants with the highest tertile of regional DNAm at TXNIP, average protein (15%) intake was associated with a greater reduction in insulin (β: −0.14; 95% CI: −0.24, -0.03; P = 0.011) and HOMA-IR (β: −0.15; 95% CI: −0.26, −0.03; P = 0.014) than high protein (25%) intake, whereas no significant associations were found in those with the lower tertiles (P > 0.05). The interaction was attenuated to be non-significant at 2 years, presumably related to decreasing adherence to the diet intervention.ConclusionsOur data indicate that higher regional DNAm level at TXNIP was significantly associated with better fasting glucose, HbA1c, and HOMA-IR; and people with higher regional DNAm levels benefited more in insulin and HOMA-IR improvement by taking the average-protein weight-loss diet.

NRC publication: Yes

Background and objectivesAdult class II/III obesity (BMI ≥ 35 kg/m2) has significant adverse health outcomes. Early prevention and treatment are critical, but prospective childhood risk estimates are lacking. This study aimed to define the prospective risk of adult class II/III obesity, using childhood BMI.MethodsChildren ages 3–19 years enrolled in cohorts of the International Childhood Cardiovascular Cohort (i3C) consortium with measured BMI assessments in childhood and adulthood were included. Prospective risk of adult class II/III obesity was modeled based on childhood age, sex, race, and BMI.ResultsA total of 12,142 individuals (44% male, 85% white) were assessed at median age 14 [Interquartile range, IQR: 11, 16] and 33 [28, 39] years. Class II/III adult obesity developed in 6% of children with normal weight; 29% of children with overweight; 56% of children with obesity; and 80% of children with severe obesity. However, 38% of the 1440 adults with class II/III obesity (553/1440) were normal weight as children. Prospective risk of adult class II/III obesity varied by age, sex, and race within childhood weight status classifications, and is notably higher for girls, black participants, and those in the United States. The risk of class II/III obesity increased with older adult age.ConclusionsChildren with obesity or severe obesity have a substantial risk of adult class II/III obesity, and observed prospective risk estimates are now presented by age, sex, race, and childhood BMI. Clinical monitoring of children’s BMI for adult class II/III obesity risk may be especially important for females and black Americans.

The 2020 Dietary Guidelines Advisory Committee conducted a systematic review of existing research on diet and health to inform the current Dietary Guidelines for Americans. The committee answered this public health question: what is the association between dietary patterns consumed and all-cause mortality (ACM)? To ascertain the association between dietary patterns consumed and ACM. Guided by an analytical framework and predefined inclusion and exclusion criteria developed by the committee, the US Department of Agriculture's Nutrition Evidence Systematic Review (NESR) team searched PubMed, the Cochrane Central Register of Controlled Trials, and Embase and dual-screened the results to identify articles that were published between January 1, 2000, and October 4, 2019. These studies evaluated dietary patterns and ACM in participants aged 2 years and older. The NESR team extracted data from and assessed risk of bias in included studies. Committee members synthesized the evidence, developed conclusion statements, and graded the strength of the evidence supporting the conclusion statements. A total of 1 randomized clinical trial and 152 observational studies were included in the review. Studies enrolled adults and older adults (aged 17-84 years at baseline) from 28 countries with high or very high Human Development Index; 53 studies originated from the US. Most studies were well designed, used rigorous methods, and had low or moderate risks of bias. Precision, directness, and generalizability were demonstrated across the body of evidence. Results across studies were highly consistent. Evidence suggested that dietary patterns in adults and older adults that involved higher consumption of vegetables, fruits, legumes, nuts, whole grains, unsaturated vegetable oils, fish, and lean meat or poultry (when meat was included) were associated with a decreased risk of ACM. These healthy patterns were also relatively low in red and processed meat, high-fat dairy, and refined carbohydrates or sweets. Some of these dietary patterns also included intake of alcoholic beverages in moderation. Results based on additional analyses with confounding factors generally confirmed the robustness of main findings. In this systematic review, consuming a nutrient-dense dietary pattern was associated with reduced risk of death from all causes.

Epigenetic clocks have emerged as promising biomarkers of aging, but their responsiveness to lifestyle interventions and relevance for short‐term changes in cardiometabolic health remain uncertain. In this study, we examined the associations between three epigenetic aging measures (DunedinPACE, PCPhenoAge acceleration, and PCGrimAge acceleration) and a broad panel of cardiometabolic biomarkers in 144 obese participants from the MACRO trial, a 12‐month weight‐loss dietary intervention comparing low‐carbohydrate and low‐fat diets. At pre‐intervention baseline, DunedinPACE was significantly associated with several cardiometabolic biomarkers (FDR [false discovery rate] < 0.05), including insulin, homeostatic model assessment for insulin resistance (HOMA‐IR), total cholesterol, high‐density lipoprotein cholesterol, C‐reactive protein, adiponectin, and ghrelin. These associations were substantially attenuated following the intervention, with only CRP and adiponectin remaining significant. Changes in epigenetic aging measures were not significantly associated with changes in biomarkers, nor did they mediate the effects of weight loss. Our findings highlight DunedinPACE as a sensitive biomarker of cardiometabolic health in adults with obesity but raise questions about the utility of epigenetic clocks as causal targets in short‐term lifestyle interventions. While caloric restriction may attenuate some phenotypic manifestations of biological aging, short‐term changes in epigenetic aging measures may not fully reflect underlying cardiometabolic changes. These results underscore the need for caution in interpreting epigenetic aging as a modifiable intervention target. In a 12‐month weight‐loss trial, DunedinPACE was associated with cardiometabolic biomarkers at baseline, but not over time. No evidence supported epigenetic clocks as mediators of intervention effects, raising caution about their causal mechanisms as short‐term intervention targets for healthy aging.