A Proposed Pediatric Clinical Cardiovascular Health Reference Standard.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Quality and Content Concordance of International Clinical Guidelines on Hypertensive Disorders of Pregnancy Using the AGREE II Instrument: An Updated Systematic Review.

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.

Dietary and Complementary Feeding Practices of US Infants, 6 to 12 Months: A Narrative Review of the Federal Nutrition Monitoring Data.

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.

Metabolites Associated with Coffee Consumption and Incident Chronic Kidney Disease.

BACKGROUND AND OBJECTIVES: Moderate coffee consumption has been associated with lower risk of CKD; however, the exact biologic mechanisms underlying this association are unknown. Metabolomic profiling may identify metabolic pathways that explain the association between coffee and CKD. The goal of this study was to identify serum metabolites associated with coffee consumption and examine the association between these coffee-associated metabolites and incident CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using multivariable linear regression, we identified coffee-associated metabolites among 372 serum metabolites available in two subsamples of the Atherosclerosis Risk in Communities study (ARIC; n=3811). Fixed effects meta-analysis was used to pool the results from the two ARIC study subsamples. Associations between coffee and metabolites were replicated in the Bogalusa Heart Study (n=1043). Metabolites with significant associations with coffee in both cohorts were then evaluated for their prospective associations with incident CKD in the ARIC study using Cox proportional hazards regression. RESULTS: In the ARIC study, mean (SD) age was 54 (6) years, 56% were daily coffee drinkers, and 32% drank >2 cups per day. In the Bogalusa Heart Study, mean (SD) age was 48 (5) years, 57% were daily coffee drinkers, and 38% drank >2 cups per day. In a meta-analysis of two subsamples of the ARIC study, 41 metabolites were associated with coffee consumption, of which 20 metabolites replicated in the Bogalusa Heart Study. Three of these 20 coffee-associated metabolites were associated with incident CKD in the ARIC study. CONCLUSIONS: We detected 20 unique serum metabolites associated with coffee consumption in both the ARIC study and the Bogalusa Heart Study, and three of these 20 candidate biomarkers of coffee consumption were associated with incident CKD. One metabolite (glycochenodeoxycholate), a lipid involved in primary bile acid metabolism, may contribute to the favorable kidney health outcomes associated with coffee consumption. Two metabolites (O-methylcatechol sulfate and 3-methyl catechol sulfate), both of which are xenobiotics involved in benzoate metabolism, may represent potential harmful aspects of coffee on kidney health.

Clinical Effectiveness of Decision Support for Prescribing Opioids for Chronic Noncancer Pain: A Prospective Cohort Study.

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.

Risk Factors for Low Pharmacy Refill Adherence Among Older Hypertensive Men and Women by Race.

BACKGROUND: Sex-race stratification may lead to identification of risk factors for low antihypertensive medication adherence that are not apparent when assessing risk factors in women and men without race stratification. We examined risk factors associated with low pharmacy refill adherence across sex-race subgroups (white women, black women, white men, black men) within the Cohort Study of Medication Adherence among Older Adults (n = 2,122). METHODS: Pharmacy refill adherence was calculated as proportion of days covered using all antihypertensive prescriptions filled in the year prior to a baseline risk factor survey. Sex- and sex-race-stratified multivariable Poisson regression models with robust standard errors were used to estimate adjusted prevalence ratios and 95% confidence intervals for associations between participant characteristics and low adherence. RESULTS: Prevalence of low adherence was 22.9% vs. 40.7% in white vs. black women (P < 0.001) and 26.3% vs. 37.2% in white vs. black men (P = 0.003). In multivariable models, reducing antihypertensive medication due to cost was associated with low adherence within each sex-race subgroup. Additional factors associated with low adherence included shorter hypertension duration and comorbidities in white women; not being married and depressive symptoms in white men; and ≥6 primary care visits/year and complementary and alternative medicine use in black men. Among men, not being married and reporting depressive symptoms were associated with low adherence for whites, but not blacks. CONCLUSIONS: Identification of sex-race-specific risk factors for low antihypertensive medication adherence may guide development and implementation of tailored interventions to increase antihypertensive medication adherence and blood pressure control among older patients.

The Life Course Implications of Ready to Use Therapeutic Food for Children in Low-Income Countries.

The development of ready-to-use therapeutic food (RUTF) for the treatment of uncomplicated cases of severe acute malnutrition in young children from 6 months to 5 years old has greatly improved survival through the ability to treat large numbers of malnourished children in the community setting rather than at health facilities during emergencies. This success has led to a surge in demand for RUTF in low income countries that are frequently food insecure due to environmental factors such as cyclical drought. Worldwide production capacity for the supply of RUTF has increased dramatically through the expansion and development of new manufacturing facilities in both low and high income countries, and new business ventures dedicated to ready-to-use foods have emerged not only for emergencies, but increasingly, for supplementing caloric intake of pregnant women and young children not experiencing acute undernutrition. Due to the lack of evidence on the long term health impact these products may have, in the midst of global nutrition transitions toward obesity and metabolic dysfunction, the increased use of manufactured, commercial products for treatment and prevention of undernutrition is of great concern. Using a framework built on the life course health development perspective, the current research presents several drawbacks and limitations of RUTF for nutrition of mothers and young children, especially in non-emergency situations. Recommendations follow for potential strategies to limit the use of these products to the treatment of acute undernutrition only, study the longer term health impacts of RUTF, prevent conflict of interests arising for social enterprises, and where possible, ensure that whole foods are supported for life-long health and nutrition, as well as environmental sustainability.

Reproducibility of blood pressure responses to dietary sodium and potassium interventions: the GenSalt study.

Blood pressure responses to dietary sodium and potassium interventions vary among individuals. We studied the long-term reproducibility of blood pressure responses to dietary sodium and potassium intake. We repeated the dietary sodium and potassium interventions among 487 Chinese adults 4.5 years after the original dietary intervention. The identical dietary intervention protocol, which included a 7-day low-sodium feeding (51.3 mmol/d), a 7-day high-sodium feeding (307.8 mmol/d), and a 7-day high-sodium feeding with oral potassium supplementation (60.0 mmol/d), was applied in both the initial and repeated studies. Three blood pressure measurements were obtained during each of the 3 days of baseline observation and on days 5, 6, and 7 of each intervention period. The results from the 24-hour urinary excretion of sodium and potassium showed excellent compliance with the study diet. Blood pressure responses to dietary intervention in the original and repeated studies were highly correlated. For example, the correlation coefficients (95% confidence interval) for systolic blood pressure levels were 0.77 (0.73-0.80) at baseline, 0.79 (0.75-0.82) during low sodium, 0.80 (0.77-0.83) during high sodium, and 0.82 (0.79-0.85) during high sodium and potassium supplementation interventions (all P<0.0001). The correlation coefficients for systolic blood pressure changes were 0.37 (0.29-0.44) from baseline to low sodium, 0.37 (0.29-0.44) from low to high sodium, and 0.28 (0.20-0.36) from high sodium to high sodium plus potassium supplementation (all P<0.0001). These data indicate that blood pressure responses to dietary sodium and potassium interventions have long-term reproducibility and stable characteristics in the general population.

Effect of coenzyme Q10 supplementation on heart failure: a meta-analysis.

BACKGROUND: Coenzyme Q10 (CoQ10; 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 CoQ10 on CHF with inconclusive results. OBJECTIVE: The objective of this meta-analysis was to evaluate the impact of CoQ10 supplementation on the ejection fraction (EF) and New York Heart Association (NYHA) functional classification in patients with CHF. 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 CHF. 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.

Meta-analysis of folic acid supplementation trials on risk of cardiovascular disease and risk interaction with baseline homocysteine levels.

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 mumol/L and 0.94 (95% CI 0.86 to 1.03) in strata with baseline homocysteine levels <12 micromol/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.

Correlation between blood pressure responses to dietary sodium and potassium intervention in a Chinese population.

BACKGROUND: Blood pressure (BP) responses to dietary sodium and potassium intake vary among individuals. We examined the correlation between BP responses to dietary low-sodium, high-sodium, and potassium supplementation interventions in a feeding study. METHODS: A total of 1,906 Chinese aged > or = 16 years participated in the dietary intervention that included a 7-day low-salt intervention (51.3 mmol/day), a 7-day high-salt intervention (307.8 mmol/day), and a 7-day high-salt plus potassium supplementation (60 mmol/day) intervention. BP was measured nine times during the 3-day baseline observation and during the last 3 days of each intervention phase using a random-zero sphygmomanometer. RESULTS: The correlation coefficients (95% confidence intervals (CIs)) of the BP responses to low-sodium and high-sodium interventions were -0.47 (-0.51 to -0.44), -0.47 (-0.50 to -0.43), and -0.45 (-0.49 to -0.42) for systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP), respectively (all P < 0.0001). The correlation coefficients (95% CI) of the BP responses to high-sodium intervention and potassium supplementation were -0.52 (-0.56 to -0.49), -0.48 (-0.52 to 0.45), and -0.52 (-0.55 to -0.48) for SBP, DBP, and MAP, respectively (all P < 0.0001). The kappa coefficients were moderate, varying from 0.28 to 0.34, between BP responses to low-sodium and high-sodium interventions (all P < 0.0001). CONCLUSIONS: These results indicate there is a moderate correlation between BP responses to low-sodium and to high-sodium interventions, and BP responses to high-sodium intervention and potassium supplementation. Furthermore, our study suggests that individuals who were more sensitive to high-sodium diet might benefit more from a low-sodium and/or high-potassium intervention aimed at lowering BP levels.

Folic acid supplementation and cardiovascular disease: the state of the art.

High levels of homocysteine, a non-protein-forming, sulfur-containing amino acid, have been associated with elevated cardiovascular risk in observational studies. Support for the homocysteine hypothesis comes from 2 primary lines of epidemiologic evidence, observational studies, such as case control and cohort studies, and studies of genetic variation. On the basis of unequivocally supportive epidemiologic data, a series of large randomized controlled trials of homocysteine lowering through folic acid supplementation were launched. The recently reported results of the 3 large, randomized clinical trials (SEARCH, WENBIT, WAFACS) in combination with those previously reported (CHAOS-2, VISP, NORVIT, HOPE-2) effectively rule out the possibility of large effect on risk of coronary heart disease, stroke, and all-cause mortality. Although the potential for prevention of atherosclerotic cardiovascular disease in adults through folic acid supplementation has not yet been substantiated, folic acid supplementation prenatally may reduce congenital heart defects in offspring.

Gender difference in blood pressure responses to dietary sodium intervention in the GenSalt study.

OBJECTIVE: To examine factors related to blood pressure (BP) responses to dietary sodium and potassium interventions. METHODS: We conducted a dietary feeding study that included a 7-day low-salt intervention (51.3 mmol sodium/day), a 7-day high-salt intervention (307.8 mmol sodium/day), and a 7-day high-salt and potassium-supplementation (60 mmol potassium/day) intervention among 1906 study participants in rural China. The BP was measured nine times during the 3-day baseline observation and during the last 3 days of each intervention phase using a random-zero sphygmomanometer. RESULTS: The BP responses to low-sodium intervention were significantly greater in women than in men: -8.1 [95% confidence interval (-8.6 to -7.6)] versus -7.0 (-7.5 to -6.6) mmHg for systolic and -4.5 (-4.9 to -4.1) versus -3.4 (-3.8 to -3.0) mmHg for diastolic. Likewise, BP responses to high-sodium interventions were significantly greater in women than in men: 6.4 (5.9-6.8) versus 5.2 (4.8-5.7) mmHg for systolic and 3.1 (2.7-3.5) versus 1.7 (1.4-2.1) mmHg for diastolic (all P < 0.001). In addition, systolic BP responses to sodium interventions increased with age, and both systolic and diastolic BP responses to sodium interventions increased with baseline BP levels. BP responses to potassium supplementation also increased with baseline BP levels. CONCLUSION: These results suggest that female gender, older age, and hypertension increase the sensitivity to dietary sodium intervention. Furthermore, low dietary sodium intake may be more effective in reducing BP among these subgroups.

Antioxidant plasma concentration and supplementation in carotid intima media thickness.

Cerebrovascular diseases represent a major problem in Western countries. Oxidative stress, an important condition of increased amounts of reactive oxygen species, is now recognized to be a prominent feature of many acute and chronic diseases, and even of the normal aging process. Carotid intima media thickness is an important marker of atherosclerosis that correlates with established coronary heart disease. Changes in carotid intima media thickness, measured by B-mode high-resolution carotid ultrasonography, represent an important and early step in carotid plaque formation and progression and are the most common currently used marker to evaluate the progression of atherosclerotic processes. Several therapeutic strategies have been adopted to slow the early atherosclerotic process in asymptomatic subjects in order to reduce the risk of cardiovascular events. An additional step to slow the atherosclerotic process may include interventions to decrease newly emerging coronary risk factors, such as oxidative stress and inflammation. Consuming a diet rich in fruits and vegetables will provide antioxidant vitamins, and carotenoids, which are believed to inhibit tissue damage derived from oxidative processes and may slow the progression of early atherosclerosis, modify the increase in carotid intima media thickness and, consequently, reduce cardiovascular events. This review synthesizes the published literature regarding antioxidant vitamins plasma concentration and supplementation and carotid intima media thickness.

Effect of folic acid supplementation on risk of cardiovascular diseases: a meta-analysis of randomized controlled trials.

CONTEXT: Epidemiologic studies have suggested that folate intake decreases risk of cardiovascular diseases. However, the results of randomized controlled trials on dietary supplementation with folic acid to date have been inconsistent. OBJECTIVE: To evaluate the effects of folic acid supplementation on risk of cardiovascular diseases and all-cause mortality in randomized controlled trials among persons with preexisting cardiovascular or renal disease. DATA SOURCES: Studies were retrieved by searching MEDLINE (January 1966-July 2006) using the Medical Subject Headings cardiovascular disease, coronary disease, coronary thrombosis, myocardial ischemia, coronary stenosis, coronary restenosis, cerebrovascular accident, randomized controlled trial, clinical trials, homofolic acid, and folic acid, and the text words folic acid and folate. Bibliographies of all retrieved articles were also searched, and experts in the field were contacted. STUDY SELECTION: From 165 relevant retrieved reports, 12 randomized controlled trials compared folic acid supplementation with either placebo or usual care for a minimum duration of 6 months and with clinical cardiovascular disease events reported as an end point. DATA EXTRACTION: Data on study design, characteristics of participants, changes in homocysteine levels, and cardiovascular disease outcomes were independently abstracted by 2 investigators using a standardized protocol. DATA SYNTHESIS: Studies including data from 16 958 participants with preexisting vascular disease were analyzed using a random-effects model. The overall relative risks (95% confidence intervals) of outcomes for patients treated with folic acid supplementation compared with controls were 0.95 (0.88-1.03) for cardiovascular diseases, 1.04 (0.92-1.17) for coronary heart disease, 0.86 (0.71-1.04) for stroke, and 0.96 (0.88-1.04) for all-cause mortality. The relative risk was consistent among participants with preexisting cardiovascular or renal disease. CONCLUSIONS: Folic acid supplementation has not been shown to reduce risk of cardiovascular diseases or all-cause mortality among participants with prior history of vascular disease. Several ongoing trials with large sample sizes might provide a definitive answer to this important clinical and public health question.