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Background and Aims: Identify novel metabolite associations with blood pressure (BP) salt-sensitivity and hypertension.Methods and Results: The Genetic Epidemiology Network of Salt Sensitivity (GenSalt) Replication study includes 698 Chinese participants who underwent a 3-day baseline examination followed by a 7-day low-sodium feeding and 7-day high-sodium feeding. Latent mixture models identified three trajectories of blood pressure (BP) responses to the sodium interventions. We selected 50 most highly salt-sensitive and 50 most salt-resistant participants for untargeted metabolomics profiling. Multivariable adjusted mixed logistic regression models tested the associations of baseline metabolites with BP salt-sensitivity. Multivariable adjusted mixed linear regression models tested the associations of BP salt-sensitivity with metabolite changes during the sodium interventions. Identified metabolites were tested for associations with hypertension among 1249 Bogalusa Heart Study (BHS) participants using multiple logistic regression. Fifteen salt-sensitivity metabolites were associated with hypertension in the BHS. Baseline values of serine, 2-methylbutyrylcarnitine and isoleucine directly associated with high salt-sensitivity. Among them, serine indirectly associated with hypertension while 2-methylbutyrylcarnitine and isoleucine directly associated with hypertension. Baseline salt-sensitivity status predicted changes in 14 metabolites when switching to low-sodium or high-sodium interventions. Among them, glutamate, 1-carboxyethylvaline, 2-methylbutyrylcarnitine, 3-methoxytyramine sulfate, glucose, alpha-ketoglutarate, hexanoylcarnitine, gamma-glutamylisoleucine, gamma-glutamylleucine, and gamma-glutamylphenylalanine directly associated with hypertension. Conversely, serine, histidine, threonate and 5-methyluridine indirectly associated with hypertension. Together, these metabolites explained an additional 7% of hypertension susceptibility when added to a model including traditional risk factors.Conclusions: Our findings contribute to the molecular characterization of BP response to sodium and provide novel biological insights into salt-sensitive hypertension. [ABSTRACT FROM AUTHOR]

Background and Aims: Women with prior gestational diabetes mellitus (GDM) are at elevated risk of type 2 diabetes mellitus and cardiovascular disease. We compared cardiometabolic risk factors among parous U.S. women ages 20-44 by history of GDM.Methods and Results: Using data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018, 3537 parous women were classified by self-reported GDM history. We compared anthropometric measures, glycemia, blood pressure, lipids, lifestyle factors, cardiovascular health, and cardiometabolic disease prevalence by GDM status. NHANES survey design was taken into account. Women without history of GDM were younger and, after adjusting for age, race/ethnicity, and education, had more favorable cardiometabolic risk factor profiles for measures of anthropometry, glycemia, diabetes, many lipids, physical activity, diet, and overall cardiovascular health than women with history of GDM. Many patterns persisted after further adjustment for lifestyle factors. In analyses stratified by race/ethnicity, many patterns persisted, though there were key differences. Hypertension prevalence differed by GDM history only among Hispanic women. In women of other race/ethnicity, there was no difference in healthy eating or body mass index by GDM history. In non-Hispanic Black women, there was no difference in healthy eating by GDM history.Conclusion: Among parous U.S. women ages 20-44, those with history of GDM had less favorable cardiometabolic risk factor profiles than those without history of GDM. This highlights the importance of continued efforts to develop and test multilevel interventions to improve cardiometabolic risk factors among reproductive-age women with a history of GDM. [ABSTRACT FROM AUTHOR]

The purpose of this study was to identify predictors of healthy arterial aging (long-term coronary artery calcification [CAC] of 0) among individuals with metabolic syndrome (MetS) or type 2 diabetes (T2D), which may improve primary prevention strategies. Individuals with MetS or T2D have a heterogeneously increased risk of atherosclerotic cardiovascular disease and not all have a high-intermediate risk. We included 574 participants from the MESA (Multi-Ethnic Study of Atherosclerosis) with MetS or T2D who had CAC=0 at baseline and a repeat CAC scan 10 years later. Multivariable logistic regression assessed the association of traditional and novel atherosclerotic cardiovascular disease risk factors and the MetS severity score (based on the 5 MetS criteria) with healthy arterial aging. The mean age of participants was 58.9 years, 67% were women, 422 participants had MetS, and 152 had T2D. The proportion with long-term CAC=0 was similar for MetS (42%) and T2D (44%). A younger age was the only individual low/normal traditional risk factor associated with an increased likelihood of long-term CAC=0 (odds ratio [OR]: 1.50; 95% confidence interval [CI]: 1.22 to 1.85 per 10-years younger). The strongest associations of nontraditional risk factors were observed for an absence of thoracic calcification (OR: 2.42; 95% CI: 1.24 to 4.72), absence of carotid plaque (OR: 1.81; 95% CI: 1.25 to 2.61), and among persons with a high sensitivity troponin <3 ng/ml (OR: 1.55; 95% CI: 1.01 to 2.38). In addition, persons with the lowest quartile MetS severity score had a substantially higher odds of healthy long-term CAC=0 (OR: 2.71; 95% CI: 1.27 to 5.76). More than 40% of adults with MetS or T2D and baseline CAC=0 had long-term absence of CAC, which was most strongly associated with an absence of extracoronary atherosclerosis and a low MetS score. An optimal overall cardiovascular profile appears to be more important than an ideal value of any individual risk factor to maintain healthy arterial aging. [ABSTRACT FROM AUTHOR]

Background and Aims: To examine the associations between history of gestational diabetes mellitus (GDM) and breastfeeding with branched-chain amino acids (BCAA) and their metabolites in later life.Methods and Results: 638 women (mean age 48.0 y) who had participated in the Bogalusa Heart Study and substudies of pregnancy history had untargeted, ultrahigh performance liquid chromatography-tandem mass spectroscopy conducted by Metabolon© on serum samples. Metabolites were identified that were BCAA or associated with BCAA metabolic pathways. History of GDM at any pregnancy (self-reported, confirmed with medical records when possible) as well as breastfeeding were examined as predictors of BCAA using linear models, controlling for age, race, BMI, waist circumference, and menopausal status. None of the BCAA differed statistically by history of either GDM or breastfeeding, although absolute levels of each of the BCAA were higher with GDM and lower with breastfeeding. Of the 27 metabolites on the leucine, isoleucine and valine metabolism subpathway, 1-carboxyethylleucine, 1-carboxyethyvaline, and 3-hydroxy-2-ethylpropionate were higher in women with a history of GDM, but lower in women in women with a history of breastfeeding. Similar results were found for alpha-hydroxyisocaproate, 1-carboxyethylisoleucine, and N-acetylleucine.Conclusions: GDM and breastfeeding are associated in opposite directions with several metabolites on the BCAA metabolic pathway. [ABSTRACT FROM AUTHOR]

Background and Aims: Dyslipidemia has been identified as a major risk factor for cardiovascular disease. We aimed to identify metabolites and metabolite modules showing novel association with lipids among Bogalusa Heart Study (BHS) participants using untargeted metabolomics.Methods and Results: Untargeted ultrahigh performance liquid chromatography-tandem mass spectroscopy was used to quantify serum metabolites of 1 243 BHS participants (816 whites and 427 African-Americans). The association of single metabolites with lipids was assessed using multiple linear regression models to adjust for covariables. Weighted correlation network analysis was utilized to identify modules of co-abundant metabolites and examine their covariable adjusted correlations with lipids. All analyses were conducted according to race and using Bonferroni-corrected α-thresholds to determine statistical significance. Thirteen metabolites with known biochemical identities showing novel association achieved Bonferroni-significance, p < 1.04 × 10-5, and showed consistent effect directions in both whites and African-Americans. Twelve were from lipid sub-pathways including fatty acid metabolism (arachidonoylcholine, dihomo-linolenoyl-choline, docosahexaenoylcholine, linoleoylcholine, oleoylcholine, palmitoylcholine, and stearoylcholine), monohydroxy fatty acids (2-hydroxybehenate, 2-hydroxypalmitate, and 2-hydroxystearate), and lysoplasmalogens [1-(1-enyl-oleoyl)-GPE (P-18:1) and 1-(1-enyl-stearoyl)-GPE (P-18:0)]. The gamma-glutamylglutamine, peptide from the gamma-glutamyl amino acid sub-pathway, were also identified. In addition, four metabolite modules achieved Bonferroni-significance, p < 1.39 × 10-3, in both whites and African-Americans. These four modules were largely comprised of metabolites from lipid sub-pathways, with one module comprised of metabolites which were not identified in the single metabolite analyses.Conclusion: The current study identified 13 metabolites and 4 metabolite modules showing novel association with lipids, providing new insights into the physiological mechanisms regulating lipid levels. [ABSTRACT FROM AUTHOR]

Background: Although it has become increasingly clear that pregnancy-related health predicts later-life cardiometabolic health, the relationship between reproductive history and cognitive health is less frequently studied. Although some research has identified associations between parity or hypertensive disorders of pregnancy and cognitive changes, the evidence is mixed.Objective: To examine the association between reproductive history and midlife cognition in a community-based population.Study Design: Seven hundred and thirty midlife women in the Bogalusa Heart Study completed a brief cognitive battery (memory, attention, executive function, and processing speed) and were interviewed about their reproductive history. Reproductive history (parity, age at first pregnancy, and breastfeeding) and pregnancy complications (low birthweight, preterm birth, hypertensive disorders, and miscarriage) were examined as predictors of cognitive function, with adjustment for potential confounders.Results: Nulliparous women had an overall lower cognitive score (adjusted beta -1.50, standard error [SE]: 0.41). Adolescent birth was associated with a somewhat better performance on the Trail Making Test (beta -0.31, SE: 0.15 for birth <16 years), while high parity was not strongly associated with any of the cognitive measures. History of pregnancy complications was not strongly associated with cognitive function, whereas history of miscarriage was associated with better cognitive function, as was a history of breastfeeding (beta overall score 0.90, SE: 0.29), particularly noticeable for semantic memory and in those with more total breastfeeding time (beta for overall score among those with >24 weeks lifetime breastfeeding, beta 1.21, SE: 0.44).Conclusion: Nulliparity and breastfeeding are associated with midlife cognition in women. Future studies should examine possible mechanisms by which these associations are created. [ABSTRACT FROM AUTHOR]

Background Little is known about the contribution of genetic variation to food timing, and breakfast has been determined to exhibit the most heritable meal timing. As breakfast timing and skipping are not routinely measured in large cohort studies, alternative approaches include analyses of correlated traits. Objectives The aim of this study was to elucidate breakfast skipping genetic variants through a proxy-phenotype genome-wide association study (GWAS) for breakfast cereal skipping, a commonly assessed correlated trait. Methods We leveraged the statistical power of the UK Biobank (n  = 193,860) to identify genetic variants related to breakfast cereal skipping as a proxy-phenotype for breakfast skipping and applied several in silico approaches to investigate mechanistic functions and links to traits/diseases. Next, we attempted validation of our approach in smaller breakfast skipping GWAS from the TwinUK (n  = 2,006) and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium (n  = 11,963). Results In the UK Biobank, we identified 6 independent GWAS variants, including those implicated for caffeine (ARID3B/CYP1A1), carbohydrate metabolism (FGF21), schizophrenia (ZNF804A), and encoding enzymes important for N 6-methyladenosine RNA transmethylation (METTL4, YWHAB , and YTHDF3), which regulates the pace of the circadian clock. Expression of identified genes was enriched in the cerebellum. Genome-wide correlation analyses indicated positive correlations with anthropometric traits. Through Mendelian randomization (MR), we observed causal links between genetically determined breakfast skipping and higher body mass index, more depressive symptoms, and smoking. In bidirectional MR, we demonstrated a causal link between being an evening person and skipping breakfast, but not vice versa. We observed association of our signals in an independent breakfast skipping GWAS in another British cohort (P =  0.032), TwinUK, but not in a meta-analysis of non-British cohorts from the CHARGE consortium (P  = 0.095). Conclusions Our proxy-phenotype GWAS identified 6 genetic variants for breakfast skipping, linking clock regulation with food timing and suggesting a possible beneficial role of regular breakfast intake as part of a healthy lifestyle. [ABSTRACT FROM AUTHOR]

Background Dementia and late-life cognitive decline are leading causes of death and disability in the United States. Prevention of these diseases, by maintaining brain health throughout the life course, is essential. Diet and lifestyle changes are the chief strategies aimed at primary prevention for many of the risk factors of cognitive decline. Objective The aim of this study was to examine the potential impact of dietary factors on cognitive function. Methods This prospective cohort study followed 516 young adults through midlife. The Youth/Adolescent Questionnaire was used to collect habitual nutrition data (mean age: 32.03 ± 5.96 y) at baseline. Scores from a neurocognitive battery were used to assess cognitive function (mean age: 49.03 ± 4.86 y) at follow-up and were transformed to z scores. Separate multivariable-adjusted linear regression models were fitted. The trend across quintiles for each dietary variable was assessed. Results Vitamin B-6, whole grains, processed meats, and foods fried at home all displayed significant linear trends in their relation with cognitive function. Dietary intake of vitamin B-6 and whole grains was directly associated with better cognitive function after adjustment for age, race, sex, and total calorie intake (β coefficient from linear regression and SE: 1.755 ± 0.621, P  = 0.005, and 0.001 ± 0.000, P  = 0.018, respectively). Processed meat and foods fried at home consistently displayed inverse associations with cognitive function across crude and adjusted models (linear trend P values were 0.05 and <0.0001, respectively). Conclusions Our findings suggest that dietary consumption in young adulthood may affect cognitive function in midlife. Strong associations between dietary intake and cognition were observed in our analysis, but as with all observational studies, the possibility of residual confounding cannot be excluded. [ABSTRACT FROM AUTHOR]

Highlights • Trends in use of bariatric procedure for adolescence were estimated. •Differences in weight loss by procedure at 1, 3, and 5 years were compared. •Gastric bypass and sleeve resulted in comparable BMI reduction. •AGB was markedly less effective. Abstract Background Bariatric surgery has been used for treatment of severe obesity in adolescents but most studies have been small and limited in follow-up. Objectives We hypothesized that electronic health record data could be used to compare effectiveness of bariatric procedures in adolescents. Setting Data were obtained from clinical research networks using a common data model to extract data from each site. Methods Adolescents who underwent a primary bariatric procedure from 2005 through 2015 were identified. The percent change in body mass index (BMI) at 1, 3, and 5 years was estimated using random effects linear regression for patients undergoing all operations. Propensity score adjusted estimates and 95% confidence intervals were estimated for procedures with >25 patients at each time period. Results This cohort of 544 adolescents was predominantly female (79%) and White (66%), with mean (±standard deviation) age of 17.3 (±1.6) years and mean BMI of 49.8 (± 7.8) kg/m2. Procedures included Roux-en-Y gastric bypass (RYGB; n = 177), sleeve gastrectomy (SG; n = 306), and laparoscopic adjustable gastric banding (n = 61). For those undergoing RYGB, SG, and laparoscopic adjustable gastric banding, mean (95% confidence interval) BMI changes of −31% (−30% to −33%), −28% (−27% to −29%), and −10% (−8% to −12%), were estimated at 1 year. For RYGB and SG, BMI changes of −29% (−26% to −33%) and −25% (−22% to −28%) were estimated at 3 years. Conclusions Adolescents undergoing SG and RYGB experienced greater declines in BMI at 1- and 3-year follow-up time points, while laparoscopic adjustable gastric banding was significantly less effective for BMI reduction. [ABSTRACT FROM AUTHOR]

Purpose: The influence of childhood health on later-life health outcomes is increasingly hypothesized but rarely tested. We examined the relationship between cardiometabolic indicators in childhood and risk of pregnancy-induced hypertension, preeclampsia, and gestational diabetes.Methods: Childhood measurements from 755 women in the Bogalusa Heart Study included body mass index, systolic and diastolic blood pressure (SBP and DBP), low- and high-density lipoprotein cholesterol, total cholesterol, triglycerides, insulin, and glucose. Average childhood values were estimated by area under the curve computed from longitudinal quadratic random-effects growth models to account for the unequally spaced repeated measures. Women reported pregnancy complications, and medical records were linked to interview data where possible. Log-Poisson models predicted adjusted risk associated with an interquartile range increase in cardiometabolic indicators.Results: Elevated childhood insulin was associated with 10%-15% increased risk across the three outcomes. Elevated childhood SBP was associated with preeclampsia (SBP RR = 1.50, 95% CI: 1.13, 2.01) and SBP, DBP, and body mass index predicted pregnancy-induced hypertension (SBP RR = 2.15, 95% CI: 1.65, 2.82; DBP RR = 1.83, 95% CI: 1.38, 2.43; BMI RR = 1.67, 95% CI: 1.41, 1.98). Blood pressure mediated the association between childhood body mass index and pregnancy-induced hypertension.Conclusions: Results suggest the potential long-term impact of early-life cardiometabolic profiles on complications of pregnancy. [ABSTRACT FROM AUTHOR]

The authors discuss a study by T. S-Yeh and colleagues which analyzed repeated dietary data from semi-quantitative food frequency questionnaires (SFFQs) and subjective cognitive decline (SCD), measured twice, among women that took part in the Nurses' Health Study and men from the Health professionals Follow-Up Study. Topics include mechanisms that may contribute to the reported inverse association between dietary protein intake and SCD and clinical and public health implications of the study.

Objective: To evaluate the impact of the 2017 American Academy of Pediatrics hypertension Clinical Practice Guideline (CPG), compared with the previous guideline ("Fourth Report"), on the frequency of hypertensive blood pressure (BP) measurements in childhood and associations with hypertension in adulthood using data from the International Childhood Cardiovascular Cohort Consortium.Study Design: Childhood BPs were categorized in normal, prehypertensive/elevated, and hypertensive (stage 1 and 2) ranges using the Fourth Report and the CPG. Participants were contacted in adulthood to assess self-reported hypertension. The associations between childhood hypertensive range BPs and self-reported adult hypertension were evaluated.Results: Data were available for 34 014 youth (10.4 ± 3.1 years, 50.6% female) with 92 751 BP assessments. Compared with the Fourth Report, the CPG increased hypertensive readings from 7.6% to 13.5% and from 1.3% to 2.5% for stage 1 and 2 hypertensive range, respectively (P < .0001). Of 12 761 adults (48.8 ± 7.9 years, 43% male), 3839 (30.1%) had self-reported hypertension. The sensitivity for predicting adult hypertension among those with hypertensive range BPs at any point in childhood, as defined by the Fourth Report and the CPG, respectively, was 13.4% and 22.4% (specificity 92.3% and 85.9%, P < .001), with no significant impact on positive and negative predictive values. Associations with self-reported adult hypertension were similar and weak (c-statistic range 0.61-0.68) for hypertensive range BPs as defined by the Fourth Report and CPG.Conclusions: The CPG significantly increased the prevalence of childhood BPs in hypertensive ranges and improved the sensitivity, without an overall strengthened association, of predicting self-reported adult hypertension. [ABSTRACT FROM AUTHOR]

Background: Coenzyme Q10 (Co Q10 also called ubiquinone) is an antioxidant that has been postulated to improve functional status in congestive heart failure (CHF). Several randomized controlled trials have examined the effects of Co Q10 on CHF with inconclusive results. Objective: The objective of this meta-analysis was to evaluate the impact of Co Q10 supplementation on the ejection fraction (EF) and New York Heart Association (NYHA) functional classification in patients with CHE Design: A systematic review of the literature was conducted by using databases including MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and manual examination of references from selected studies. Studies included were randomized controlled trials of CoQ10 supplementation that reported the EF or NYHA functional class as a primary outcome. Information on participant characteristics, trial design and duration, treatment, dose, control, EF, and NYHA classification were extracted by using a standardized protocol. Results: Supplementation with CoQ10 resulted in a pooled mean net change of 3.67% (95% CI: 1.60%, 5.74%) in the EF and -0.30 (95% CI: -0.66, 0.06) in the NYHA functional class. Subgroup analyses showed significant improvement in EF for crossover trials, trials with treatment duration ≤ 12 wk in length, studies published before 1994, and studies with a dose ≤100 mg CoQ10/d and in patients with less severe CHE These subgroup analyses should be interpreted cautiously because of the small number of studies and patients included in each subgroup. Conclusions: Pooled. analyses of available randomized controlled trials suggest that CoQ10 may improve the EF in patients with CHF. Additional well-designed studies that include more diverse populations are needed. [ABSTRACT FROM AUTHOR]

Illicit drug use has been associated with chronic kidney disease (CKD) in select populations, but it is unknown whether the same association exists in the general population. By using data from the National Health and Nutrition Examination Survey 2005–2008, we conducted a cross-sectional analysis of 5861 adults who were questioned about illicit drug use, including cocaine, methamphetamines, and heroin, during their lifetime. The primary outcome was CKD as defined by an estimated glomerular filtration rate ≤60 mL/min/1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration equation or by microalbuminuria. We also examined the association between illicit drug use and blood pressure (BP) ≥120/80, ≥130/85, and ≥140/90 mm Hg. Logistic regression was used to examine the association between illicit drug use and CKD and BP. Mean estimated glomerular filtration rate was similar between illicit drug users and nonusers (100.7 vs 101.4 mL/min/1.73 m2, P = 0.4), as was albuminuria (5.7 vs 6.0 mg/g creatinine, P = 0.5). Accordingly, illicit drug use was not significantly associated with CKD in logistic regression models (odds ratio [OR], 0.98; confidence interval [CI], 0.75–1.27) after adjusting for other important factors. However, illicit drug users had higher systolic (120 vs 118 mm Hg, P = 0.04) and diastolic BP (73 vs 71 mm Hg, P = 0.0003) compared with nonusers. Cocaine use was independently associated with BP ≥130/85 mm Hg (OR, 1.24; CI, 1.00–1.54), especially when used more during a lifetime (6–49 times; OR, 1.42; CI, 1.06–1.91). In a representative sample of the US population, illicit drug use was not associated with CKD, but cocaine users were more likely to have elevated BP. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: The mean estimated glomerular filtration rate was 43.6 (±13.0) mL/(min 1.73 m2). 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 m2) 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). Conclusions: 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. [Copyright &y& Elsevier]

Abstract: Background: Observational studies suggest that moderate alcohol consumption may lower risk of myocardial infarction (MI) and coronary heart disease (CHD); yet, evidence for this comes almost entirely from Western populations. Methods: We conducted a prospective cohort study in 64,597 Chinese men aged ≥40 years who were free of clinical CHD at baseline examination. Data on frequency and type of alcohol consumed were collected at the baseline examination in 1991 using a standard protocol. Follow-up evaluation was conducted in 1999–2000, with a response rate of 94%. Results: Over 494,084 person-years of follow-up, we documented 725 (361 fatal) incident MI and 976 (588 fatal) incident CHD events. After stratification by province to account for multi-stage sampling design and adjustment for age, education, physical activity, cigarette smoking, body mass index, systolic blood pressure, urbanization (urban vs. rural), geographic variation (north vs. south) and history of diabetes, relative risk (95% confidence interval) of MI was 0.93 (0.70–1.24) for participants consuming 1 to 6 drinks/week, 0.66 (0.54–0.82) for those consuming 7 to 34 drinks/week, and 0.58 (0.41–0.81) for those consuming ≥35 drinks/week (p for linear trend <0.0001) compared to non-drinkers. The corresponding relative risks for CHD events were 0.99 (0.77–1.27), 0.67 (0.56–0.81), and 0.58 (0.44–0.78), respectively (p for linear trend <0.0001). Conclusion: Alcohol consumption may be related to lower risk of MI and CHD in middle-aged and older Chinese men. However, heavy alcohol consumption may lead to increased mortality from other causes; therefore, the implications of these findings should be interpreted cautiously. [Copyright &y& Elsevier]

Background: Epidemiologic studies report inconsistent findings on the association of fruit and vegetable intake with the risk of cardiovascular disease. Objective: The objective was to examine the relation between fruit and vegetable intake and the risk of cardiovascular disease. Design: We studied 9608 adults aged 25-74 y participating in the first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study and free of cardiovascular disease at the time of their baseline examination between 1971 and 1975. Fruit and vegetable intake at baseline was measured with a food-frequency questionnaire. The incidence of and mortality from cardiovascular disease were obtained from medical records and death certificates. Results: Over an average of 19 y, 888 strokes (218 fatal), 1786 ischemic heart disease events (639 fatal), 1145 cardiovascular disease deaths, and 2530 all-cause deaths were documented. Consuming fruit and vegetables =3 times/d⩾ compared with < 1 time/d was associated with a 27% lower stroke incidence [relative risk (RR): 0.73; 95% CI: 0.57, 0.95; P for trend = 0.01), a 42% lower stroke mortality (0.58; 0.33, 1.02; P for trend = 0.05), a 24% lower ischemic heart disease mortality (0.76; 0.56, 1.03; P for trend = 0.07), a 27% lower cardiovascular disease mortality (0.73; 0.58, 0.92; P for trend = 0.008), and a 15% lower all-cause mortality (0.85; 0.72, 1.00; P for trend = 0.02) after adjustment for established cardiovascular disease risk factors. Conclusion: We showed an inverse association of fruit and vegetable intake with the risk of cardiovascular disease and all-cause mortality in the general US population. [ABSTRACT FROM AUTHOR]

Clinical cardiovascular health is a construct that includes 4 health factors—systolic and diastolic blood pressure, fasting glucose, total cholesterol, and body mass index—which together provide an evidence-based, more holistic view of cardiovascular health risk in adults than each component separately. Currently, no pediatric version of this construct exists. This study sought to develop sex-specific charts of clinical cardiovascular health for age to describe current patterns of clinical cardiovascular health throughout childhood. Data were used from children and adolescents aged 8–19 years in six pooled childhood cohorts (19,261 participants, collected between 1972 and 2010) to create reference standards for fasting glucose and total cholesterol. Using the models for glucose and cholesterol as well as previously published reference standards for body mass index and blood pressure, clinical cardiovascular health charts were developed. All models were estimated using sex-specific random-effects linear regression, and modeling was performed during 2020–2022. Models were created to generate charts with smoothed means, percentiles, and standard deviations of clinical cardiovascular health for each year of childhood. For example, a 10-year-old girl with a body mass index of 16 kg/m2 (30th percentile), blood pressure of 100/60 mm Hg (46th/50th), glucose of 80 mg/dL (31st), and total cholesterol of 160 mg/dL (46th) (lower implies better) would have a clinical cardiovascular health percentile of 62 (higher implies better). Clinical cardiovascular health charts based on pediatric data offer a standardized approach to express clinical cardiovascular health as an age- and sex-standardized percentile for clinicians to assess cardiovascular health in childhood to consider preventive approaches at early ages and proactively optimize lifetime trajectories of cardiovascular health. [ABSTRACT FROM AUTHOR]

Objective: To examine the relationship between generation 1 (grandmaternal) cardiometabolic risk factors and generation 3 (grandchild's) birthweight and gestational age.Study Design: Mother-daughter pairs in the Bogalusa Heart Study (1973-present) were linked to their children's birth certificates; women were also interviewed about their reproductive histories, creating a 3-generation linkage including 177 generation 1 (grandmothers), 210 generation 2 (mothers), and 424 generation 3 (children). Prepregnancy cardiometabolic risk factors (body mass index [BMI], lipids, glucose) or generation 1 (mean age 16.2 years) and 2 (mean age 11.1 years) were examined as predictors of generation 3 birthweight and gestational age using linear and logistic regression with adjustment for age, race, parity, and other confounders.Results: Generation 2 higher BMI was associated with higher birthweight (28 g per 1 unit, 95% CI 12-44) and gestational age (0.08 weeks, 95% CI 0.02-0.14) in generation 3, and generation 1 higher BMI was associated with higher birthweight (52 g, 95% CI 34-70) in the generation 2. Generation 1's higher glucose levels were associated with higher birthweight in generation 3 (adjusted beta 111 g, 95% CI 33-189), and triglycerides (adjusted beta -21, 95% CI -43-0) and low-density lipoprotein (adjusted beta -24, 95% CI -48-0) were associated with lower birthweight.Conclusions: These results suggest the possibility of multigenerational developmental programming of birth outcomes, although mechanisms (whether biological or environmental) are undetermined. [ABSTRACT FROM AUTHOR]

Background & Aims: There is controversy over whether the treatment of patients with ulcerative colitis (UC) with thiopurines increases their risk of lymphoma. We evaluated the risk of lymphoma (ongoing, residual, and per year of therapy) among thiopurine-treated patients with UC. Methods: We obtained nationwide data from the Veterans Affairs (VA) health care system from 2001 to 2011. We performed a retrospective cohort study, analyzing data on 36,891 patients from their date of diagnosis of UC in the VA health care system to a diagnosis of lymphoma or October 1, 2011 (subjects followed up for a median of 6.7 years). Thiopurine exposure was assessed using the VA pharmacy database. Patients who developed lymphoma were identified based on ICD-9 codes and confirmed by manual chart review. Results: In total, 4734 patients with UC (13%) were treated with thiopurines for a median of 1 year. Lymphoma developed in 119 patients who had not been treated with thiopurines, 18 who were treated with thiopurines, and 5 who had discontinued treatment with thiopurines. The incidence rates of lymphoma were 0.60 per 1000 person-years among patients who had not been treated with thiopurines, 2.31 among patients who were treated with thiopurines, and 0.28 among patients who had discontinued treatment with thiopurines. The incidence rates of lymphoma during the first year, second year, third year, fourth year, and >4 years of thiopurine therapy were 0.9, 1.6, 1.6, 5, and 8.9 per 1000 person-years, respectively. The age-, sex-, and race-adjusted hazard ratios of developing lymphoma were 4.2 (95% confidence interval, 2.5–6.8; P < .0001) while being treated with thiopurines and 0.5 (95% confidence interval, 0.2–1.3; P = .17) after discontinuing treatment with thiopurines compared with patients who had not been treated with thiopurines. Conclusions: Based on a retrospective, nationwide cohort study, patients with UC have a 4-fold increase in risk of lymphoma while being treated with thiopurines compared with patients who have not been treated with thiopurines. The risk increases gradually for successive years of therapy. Discontinuing thiopurine therapy reduces the risk of lymphoma. [Copyright &y& Elsevier]

Introduction: Childhood declines in cardiovascular health have been linked to the development of subclinical atherosclerosis; however, less is known about the timing and sequence of the decline of the specific cardiovascular health components. The study objective is to identify the patterns of decline and associations with adulthood subclinical atherosclerosis.Methods: Data were pooled from 5 cardiovascular cohorts. Clinical components of cardiovascular health (BMI, blood pressure, cholesterol, and blood glucose) were categorized as ideal or nonideal using American Heart Association definitions. Multitrajectory models simultaneously fitted the probability ideal for each factor. Adjusted associations between trajectory groups and carotid intima-media thickness were modeled. Data were pooled from December 1, 2015 to June 1, 2019; statistical analysis occurred between June 1, 2019 and June 1, 2020.Results: This study included 9,388 individuals (55% female, 66% White). A total of 5 distinct trajectory groups were created: 1 maintained the ideal levels of all the 4 health factors, 2 had risk onset of a single factor in childhood, 1 had risk onset of multiple factors in childhood, and 1 had risk onset in adulthood. Those with childhood multiple risk onset had 8.1% higher carotid intima-media thickness (95% CI=0.067, 0.095) than those in the ideal group, childhood cholesterol risk onset had 5.9% higher carotid intima-media thickness (95% CI=0.045, 0.072), childhood BMI risk onset had 5.5% higher carotid intima-media thickness (95% CI=0.041, 0.069), and early adulthood multiple risk onset had 2.7% higher carotid intima-media thickness (95% CI=0.013, 0.041).Conclusions: Those who lost the ideal status of cardiovascular health in childhood and early adulthood had more subclinical atherosclerosis than those who retained the ideal cardiovascular health across the life course, underscoring the importance of preserving the ideal cardiovascular health beginning in childhood and continued into adulthood. [ABSTRACT FROM AUTHOR]

Objectives: This prospective cohort study examines the clinical effectiveness of electronic medical record clinical decision support (EMR CDS) for opioid prescribing.Methods: Data analysis included primary care patients with chronic opioid therapy for noncancer pain seen within an integrated health delivery system in Louisiana between January 2017 and October 2018. EMR CDS incorporated an opioid health maintenance tool to display the status of risk mitigation, and the medication order embedded the morphine equivalent daily dose (MEDD) calculator and a hyperlink to the Louisiana pharmacy drug monitoring program. Outcome measures included change in the average MEDD and rates of opioid risk mitigation, hospitalization, and emergency department use.Results: Among 14 221 patients, 9% had prescriptions with an average MEDD ≥90 mg. There were no significant changes in MEDD after EMR CDS implementation. Increasing age, Charlson Comorbidity Index score, female sex, black non-Hispanic race, non-opioid pain medication co-prescriptions, and specialty referrals were associated with a lower odds of MEDD ≥90 (high-dose threshold). Medicare or self-pay, substance abuse history, and pain agreements were associated with increased odds of prescribing above this high-dose threshold. After incorporation of EMR CDS, patients had higher rates of urine drug screens (17% vs 7%) and naloxone prescriptions (3% vs 1%, all P < .001). In addition, specialty referrals to physical or occupational therapy, orthopedics, neurology, and psychiatry or psychology increased in the postintervention period. Although emergency department use decreased (rate ratio 0.92; 95% confidence interval 0.89-0.95), hospitalization rates did not change.Conclusions: EMR CDS improved adherence to opioid risk mitigation strategies. Further research examining which practice redesign interventions effectively reduce high-dose opioid prescribing is needed. [ABSTRACT FROM AUTHOR]

Although it is widely thought that childhood levels of cardiovascular (CV) risk factors are related to adult CV disease, longitudinal data directly linking the two are lacking. This paper describes the design and organization of the International Childhood Cardiovascular Cohort Consortium Outcomes Study (i3C Outcomes), the first longitudinal cohort study designed to locate adults with detailed, repeated, childhood biological, physical, and socioeconomic measurements and a harmonized database. I3C Outcomes uses a Heart Health Survey (HHS) to obtain information on adult CV endpoints, using mail, email, telephone, and clinic visits in the United States (U.S.) and Australia and a national health database in Finland. Microsoft Access, REsearch Data Capture (REDCap) (U.S.), LimeSurvey (Australia), and Medidata™ Rave data systems are used to collect, transfer and organize data. Self-reported CV events are adjudicated via hospital and doctor-released medical records. After the first two study years, participants ( N  = 10,968) were more likely to be female (56% vs. 48%), non-Hispanic white (90% vs. 80%), and older (10.4 ± 3.8 years vs. 9.4 ± 3.3 years) at their initial childhood study visit than the currently non-recruited cohort members. Over 48% of cohort members seen during both adulthood and childhood have been found and recruited, to date, vs. 5% of those not seen since childhood. Self-reported prevalences were 0.7% Type 1 Diabetes, 7.5% Type 2 Diabetes, 33% hypertension, and 12.8% CV event. 32% of CV events were judged to be true. I3C Outcomes is uniquely able to establish evidence-based guidelines for child health care and to clarify relations to adult CV disease. [ABSTRACT FROM AUTHOR]

Objective: To examine the relationship between reproductive history, pregnancy complications, and later physical function.Study Design: The Bogalusa Heart Study is a long-running study of cardiovascular health in a semirural community. 761 women were interviewed about their pregnancy history and complications, and underwent tests of physical function. Logistic models for dichotomous outcomes and linear models for continuous outcomes were used, adjusted for covariates.Main Outcome Measures: Overall scores on the Short Physical Performance Battery (SPPB), which combines scores for balance, gait speed, and chair stands. Additional tests were a 6-min walk, knee extension strength, grip strength, and a pegboard challenge.Results: Nulliparity was associated with lower scores on the walking and balance portions of the SPPB, less distance covered in the 6-min walk, less knee and grip strength, and higher pegboard time, especially among pre-menopausal women. A history of gestational diabetes was associated with more problems on the walk portion of the SPPB (aOR 2.44, 1.06-5.65), higher chair stand time, and lower knee strength. Young age at first birth (<16 or 18 years) was associated with a shorter chair stand time and a better pegboard score.Conclusions: Nulliparity was associated with worse physical functioning, while high parity and early pregnancy were not, suggesting that fertility is associated with better health later in life. Pregnancy complications were associated with worse physical functioning, even after controlling for body mass index. Future studies should attempt to establish the pathways by which reproductive health relates to overall physical functioning. [ABSTRACT FROM AUTHOR]

Aims: To evaluate several adult diabetes risk calculation tools for predicting the development of incident diabetes and pre-diabetes in a bi-racial, young adult population.Methods: Surveys beginning in young adulthood (baseline age ≥18) and continuing across multiple decades for 2122 participants of the Bogalusa Heart Study were used to test the associations of five well-known adult diabetes risk scores with incident diabetes and pre-diabetes using separate Cox models for each risk score. Racial differences were tested within each model. Predictive utility and discrimination were determined for each risk score using the Net Reclassification Index (NRI) and Harrell's c-statistic.Results: All risk scores were strongly associated (p<.0001) with incident diabetes and pre-diabetes. The Wilson model indicated greater risk of diabetes for blacks versus whites with equivalent risk scores (HR=1.59; 95% CI 1.11-2.28; p=.01). C-statistics for the diabetes risk models ranged from 0.79 to 0.83. Non-event NRIs indicated high specificity (non-event NRIs: 76%-88%), but poor sensitivity (event NRIs: -23% to -3%).Conclusions: Five diabetes risk scores established in middle-aged, racially homogenous adult populations are generally applicable to younger adults with good specificity but poor sensitivity. The addition of race to these models did not result in greater predictive capabilities. A more sensitive risk score to predict diabetes in younger adults is needed. [ABSTRACT FROM AUTHOR]

Complementary foods and beverages (CFBs) are key components of an infant's diet in the second 6 months of life. This article summarizes nutrition and feeding practices examined by the 2020 Dietary Guidelines Advisory Committees during the CFB life stage. Breastfeeding initiation is high (84%), but exclusive breastfeeding at 6 months (26%) is below the Healthy People 2030 goal (42%). Most infants (51%) are introduced to CFBs sometime before 6 months. The primary mode of feeding (ie, human milk fed [HMF]; infant formula or mixed formula and human milk fed [FMF]) at the initiation of CFBs is associated with the timing of introduction and types of CFBs reported. FMF infants (42%) are more likely to be introduced to CFBs before 4 months compared with HMF infants (19%). Different dietary patterns, such as higher prevalence of consumption and mean amounts, were observed, including fruit, grains, dairy, proteins, and solid fats. Compared with HMF infants of the same age, FMF infants consume more total energy (845 vs 631 kcal) and protein (22 vs 12 g) from all sources, and more energy (345 vs 204 kcal) and protein (11 vs 6 g) from CFBs alone. HMF infants have a higher prevalence of risk of inadequate intakes of iron (77% vs 7%), zinc (54% vs <3%), and protein (27% vs <3%). FMF infants are more likely to have an early introduction (<12 months) to fruit juice (45% vs 20%) and cow's milk (36% vs 24%). Registered dietitian nutritionists and nutritional professionals should consider tailoring their advice to caregivers on dietary and complementary feeding practices, taking into account the primary mode of milk feeding during this life stage to support infants' nutrient adequacy. National studies that address the limitations of this analysis, including small sample sizes and imputed breast milk volume, could refine findings from this analysis. [ABSTRACT FROM AUTHOR]

Background Cardiovascular disease is a major cause of death, and its mortality is increasing in Latin America. However, population-based data on cardiovascular disease risk factors are sparse in these countries. Methods A total of 7524 men and women, aged 35 to 74 years old, were recruited between February 2010 and December 2011 from randomly selected samples in 4 cities (Bariloche and Marcos Paz, Argentina; Temuco, Chile; and Pando-Barros Blancos, Uruguay) in the Southern Cone of Latin America. Cardiovascular risk factors were measured using standard methods by trained and certified observers. Results Approximately 85.5% of adults ate less than five servings of fruit or vegetables per day, 35.2% engaged in low physical activity, and 29.7% currently smoked cigarettes. The prevalences of obesity, central obesity, hypertension, chronic kidney disease, dyslipidemia, diabetes, and metabolic syndrome were 35.7%, 52.9%, 40.8%, 2.0%, 58.4%, 12.4%, and 37.4%, respectively. The proportion of individuals with ⩾3 cardiovascular risk factors, including low intake of fruit and vegetables, low physical activity, current cigarette smoking, obesity or central obesity, hypertension, chronic kidney disease, dyslipidemia, and diabetes, was 68.3%, and the proportion of individuals with ⩾3 cardiometabolic risk factors, including obesity or central obesity, hypertension, chronic kidney disease, dyslipidemia, and diabetes, was 22.9%. Conclusions Cardiovascular disease risk factors are highly prevalent in the general population in the Southern Cone of Latin America. These data suggest that national efforts on the prevention, treatment, and control of cardiovascular risk factors should be a public health priority in the Southern Cone of Latin America. [ABSTRACT FROM AUTHOR]

Abstract: Background: Recent studies suggest that central obesity is an important predictor of cardiovascular disease (CVD) in addition to overall obesity. Both inflammation and endothelial dysfunction are associated with increased risk of CVD. We examined the association between body mass index (BMI) and waist circumference (WC) with plasma concentrations of biomarkers of inflammation and endothelial dysfunction. Methods: We conducted a cross-sectional study of 2589 lean, moderately active participants aged 20years and older in Inner Mongolia, China. Overnight fasting blood samples were obtained to measure the biomarkers including C-reactive protein (CRP), soluble inter-cellular adhesion molecule-1 (sICAM-1), soluble E-selectin (sE-selectin), and angiotensin II. Height, body weight, and WC were measured by trained staff and BMI was calculated (kg/m2). Results: In univariate analysis, CRP, sICAM-1, and sE-selectin were all significantly higher among individuals with a higher BMI and WC. In multivariate analysis, each standard deviation (SD) increase in WC (9.6cm) was associated with about 46% higher risk (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.21–1.76) of elevated CRP but a 1 SD increase in BMI (3.5kg/m2) was not associated with the risk of elevated CRP (OR 0.96, 95% CI 0.80–1.16). However, each SD increase in BMI was associated with about 30% higher risk of having elevated E-selectin (OR 1.30, 95% CI 1.08–1.55). Conclusions: WC is a stronger predictor of inflammation while BMI is a stronger predictor for endothelial dysfunction. These results suggest measuring both BMI and WC will help to assess the risk of CVD in the Chinese population. [Copyright &y& Elsevier]

Experimental models and observational studies suggest that homocysteine-lowering therapy with folic acid (FA) may prevent cardiovascular disease (CVD). However, FA also stimulates cell proliferation and might promote progression of atherosclerosis. Our objectives were to perform a meta-analysis of FA supplementation trials on CVD events and to explore a potential interaction between FA supplementation and baseline homocysteine levels on CVD events. We searched MEDLINE for randomized controlled trials of FA supplementation to prevent CVD events (January 1966 to July 2009) and performed meta-analyses using random effects models. For trials that reported responses to FA supplementation stratified by baseline levels of homocysteine, we pooled within-trial estimates of differences in log-relative risks by baseline homocysteine levels using a random effects model. Overall, FA supplementation did not affect primary cardiovascular clinical end points (relative risk 1.02, 95% confidence interval [CI] 0.93 to 1.13, p = 0.66) or stroke (relative risk 0.95, 95% CI 0.84 to 1.08, p = 0.43). However, in trials that reported analyses stratified by baseline homocysteine, effect of FA supplementation differed by strata of baseline homocysteine (p for interaction = 0.030). Specifically, risks of primary clinical CVD events comparing FA supplementation to control were 1.06 (95% CI 1.00 to 1.13) in strata with mean baseline homocysteine levels >12 μmol/L and 0.94 (95% CI 0.86 to 1.03) in strata with baseline homocysteine levels <12 μmol/L. In conclusion, FA had no effect on CVD or stroke. However, analysis of within-trial results stratified by baseline homocysteine suggests potential harm in those with high homocysteine at baseline. This interaction may have important implications for recommendations of FA supplement use. In the meantime, FA supplementation should not be recommended as a means to prevent or treat CVD or stroke. [ABSTRACT FROM AUTHOR]

Life-course models have been infrequently applied to physical function. We sought to examine the effects of the cumulative burden of cardiovascular risk factors (CVRFs) from childhood on physical function in midlife. This longitudinal study consisted of 718 participants (aged 37 to 56 years at follow-up) who were examined for CVRFs at least four times during childhood and at least twice in adulthood, with 39 years of follow-up. We assessed physical function in 2013–2016 with the Short Physical Performance Battery (SPPB), 6-minute walking test (6MWT), and handgrip strength. The area under the growth curve (AUC) was used as a measure of cumulative exposure to CVRFs during childhood. AUC of HDL-cholesterol levels in childhood were positively associated with SPPB score. AUC levels of body mass index (BMI) and triglycerides (TG) were inversely associated with 6MWT. Higher AUC levels of systolic/diastolic blood pressure (BP) predicted poorer hand grip strength. The number of childhood CVRFs in the top quartile, including AUC levels of BMI and TG, were inversely associated with 6MWT and remained significant after adjustment for the adulthood CVRFs. Cumulative burden of CVRFs from childhood were associated with worse physical function in midlife independent of adulthood CVRFs. • Childhood BMI and TG were inversely associated with 6MWT. • The composite childhood CVRF score were inversely associated with midlife 6MWT • The relation between the composite childhood CVRF score and midlife 6MWT remained significant after adjustment for the adulthood CVRFs. [ABSTRACT FROM AUTHOR]