World variation in head circumference for children from birth to 5 years and a comparison with the WHO standards.

OBJECTIVE: A recent review reported that the WHO 2006 growth standards reflect a smaller head circumference at 24 months than seen in 18 countries. Whether this happens in early infancy and to what extent populations differ is not clear. This scooping review aimed to estimate the rates of children in different populations identified as macrocephalic or microcephalic by WHO standards. METHODS: We reviewed population-representative head circumference-for-age references. For each reference, we calculated the percentages of head circumferences that would be classified as microcephalic (<3rd WHO centile) or macrocephalic (>97th WHO centile) at selected ages. RESULTS: Twelve references from 11 countries/regions (Belgium, China, Ethiopia, Germany, Hong Kong, India, Japan, Norway, Saudi Arabia, UK and USA) were included. Median head circumference was larger than that for the Multicentre Growth Reference Study populations in both sexes in all these populations except for Japanese and Chinese children aged 1 month and Indians. Overall, at 12/24 months, 8%-9% children would be classified as macrocephalic and 2% would be classified as microcephalic, compared with the expected 3%. However at 1 month, there were geographic differences in the rate of macrocephaly (6%-10% in Europe vs 1%-2% in Japan and China) and microcephaly (1%-3% vs 6%-14%, respectively). CONCLUSIONS: Except for Indians and some Asian neonates, adopting the WHO head circumference standards would overdiagnose macrocephaly and underdiagnose microcephaly. Local population-specific cut-offs or references are more appropriate for many populations. There is a need to educate healthcare professionals about the limitations of the WHO head circumference standards.

Increased leisure-time physical activity associated with lower onset of diabetes in 44 828 adults with impaired fasting glucose: a population-based prospective cohort study.

AIMS: To evaluate the effects of habitual leisure-time physical activity (LTPA) on incident type 2 diabetes in a prospective cohort of Chinese adults with impaired fasting glucose (IFG). METHODS: 44 828 Chinese adults aged 20-80 years with newly detected IFG but free from cardiovascular and cerebrovascular disease were recruited and followed up from 1996 to 2014. Incident type 2 diabetes was identified by fasting plasma glucose ≥7 mmol/L. The participants were classified into four categories based on their self-reported weekly LTPA: inactive, low, moderate, or high. Hazard ratios (HRs) and population attributable fractions (PAFs) were estimated with adjustment for established diabetic risk factor. RESULTS: After 214 148 person-years of follow-up, we observed an inverse dose-response relationship between LTPA and diabetes risk. Compared with inactive participants, diabetes risk in individuals reporting low, moderate and high volume LTPA were reduced by 12% (HR 0.88, 95% CI 0.80 to 0.99; P=0.015), 20% (HR 0.80, 95% CI 0.71 to 0.90; P<0.001), and 25% (HR 0.75, 95% CI 0.67 to 0.83; P<0.001), respectively. At least 19.2% (PAF 19.2%, 95% CI 5.9% to 30.6%) of incident diabetes cases could be avoided if the inactive participants had engaged in WHO recommendation levels of LTPA. This would correspond to a potential reduction of at least 7 million diabetic patients in the Greater China area. CONCLUSIONS: Our results show higher levels of LTPA are associated with a lower risk of diabetes in IFG subjects. These data emphasise the urgent need for promoting physical activity as a preventive strategy against diabetes to offset the impact of population ageing and the growing obesity epidemic.

Long-Term Exposure to Ambient Fine Particulate Matter and Chronic Kidney Disease: A Cohort Study.

BACKGROUND: Chronic kidney disease (CKD) is a serious global public health challenge, but there is limited information on the connection between air pollution and risk of CKD. OBJECTIVE: The aim of this study was to investigate the association between long-term exposure to particulate matter (PM) with an aerodynamic diameter of less than [Formula: see text] ([Formula: see text]) and the development of CKD in a large cohort. METHODS: A total of 100,629 nonCKD Taiwanese residents age 20 y or above were included in this study between 2001 and 2014. Ambient [Formula: see text] concentration was estimated at each participant's address using a satellite-based spatiotemporal model. Incident CKD cases were identified by an estimated glomerular filtration rate (eGFR) of less than [Formula: see text]. We collected information on a wide range of potential confounders/modifiers during the medical examinations. Cox proportional hazard regression was applied to calculate hazard ratios (HRs). RESULTS: During the follow-up, 4,046 incident CKD cases were identified, and the incidence rate was 6.24 per 1,000 person-years. In contrast with participants with the first quintile exposure of [Formula: see text], participants with the fourth and fifth quintiles exposure of [Formula: see text] had increased risk of CKD development, adjusting for age, sex, educational level, smoking, drinking, body mass index, systolic blood pressure, fasting glucose, total cholesterol, and self-reported heart disease or stroke, with an HR [95% confidence interval (CI)] of 1.11 (1.02, 1.22) and 1.15 (1.05, 1.26), respectively. A significant concentration-response trend was observed ([Formula: see text]). Every [Formula: see text] increment in the [Formula: see text] concentration was associated with a 6% higher risk of developing CKD (HR: 1.06, 95% CI: 1.02, 1.10). Sensitivity and stratified analyses yielded similar results. CONCLUSIONS: Long-term exposure to ambient [Formula: see text] was associated with an increased risk of CKD development. Our findings reinforce the urgency to develop global strategies of air pollution reduction to prevent CKD. https://doi.org/10.1289/EHP3304.

Sleep Quality, Sleep Duration, and the Risk of Coronary Heart Disease: A Prospective Cohort Study With 60,586 Adults.

STUDY OBJECTIVES: There is limited information on the relationship between risk of cardiovascular disease and the joint effects of sleep quality and sleep duration, especially from large, prospective, cohort studies. This study is to prospectively investigate the joint effects of sleep quality and sleep duration on the development of coronary heart disease. METHODS: This study examined 60,586 adults aged 40 years or older. A self-administered questionnaire was used to collect information on sleep quality and sleep duration as well as a wide range of potential confounders. Events of coronary heart disease were self-reported in subsequent medical examinations. Two types of Sleep Score (multiplicative and additive) were constructed to reflect the participants' sleep profiles, considering both sleep quality and sleep duration. The Cox regression model was used to estimate the hazard ratio (HR) and the 95% confidence interval (CI). RESULTS: A total of 2,740 participants (4.5%) reported new events of coronary heart disease at follow-up. For sleep duration, participants in the group of < 6 h/d was significantly associated with an increased risk of coronary heart disease (HR: 1.13, 95% CI: 1.04-1.23). However, the association in the participants with long sleep duration (> 8 h/d) did not reach statistical significance (HR: 1.11, 95% CI: 0.98-1.26). For sleep quality, both dreamy sleep (HR: 1.21, 95% CI: 1.10-1.32) and difficult to fall asleep/use of sleeping pills or drugs (HR: 1.40, 95% CI: 1.25-1.56) were associated with an increased risk of the disease. Participants in the lowest quartile of multiplicative Sleep Score (HR: 1.31, 95% CI: 1.16-1.47) and of additive sleep score (HR: 1.31, 95% CI: 1.16-1.47) were associated with increased risk of coronary heart disease compared with those in the highest quartile. CONCLUSIONS: Both short sleep duration and poor sleep quality are associated with the risk of coronary heart disease. The association for long sleep duration does not reach statistical significance. Lower Sleep Score (poorer sleep profile) increases the risk of coronary heart disease, suggesting the importance of considering sleep duration and sleep quality together when developing strategies to improve sleep for cardiovascular disease prevention.

Measuring non-polyaminated lipocalin-2 for cardiometabolic risk assessment.

AIMS: Lipocalin-2 is a pro-inflammatory molecule characterized by a highly diversified pattern of expression and structure-functional relationships. In vivo, this molecule exists as multiple variants due to post-translational modifications and/or protein-protein interactions. Lipocalin-2 is modified by polyamination, which enhances the clearance of this protein from the circulation and prevents its excessive accumulation in tissues. On the other hand, animal studies suggest that non-polyaminated lipocalin-2 (npLcn2) plays a causal role in the pathogenesis of obesity-associated medical complications. The present study examined the presence of npLcn2 in samples from healthy volunteers or patients with cardiac abnormalities and evaluated npLcn2 as a biomarker for cardiometabolic risk assessment. METHODS AND RESULTS: Immunoassays were developed to quantify npLcn2 in blood and urine samples collected from 100 volunteers (59 men and 41 women), or venous plasma and pericardial fluid samples obtained from 37 cardiothoracic surgery patients. In healthy volunteers, npLcn2 levels in serum are significantly higher in obese and overweight than in lean subjects. After adjustment for age, gender, smoking, and body mass index (BMI), serum npLcn2 levels are positively correlated with heart rate, circulating triglycerides, high-sensitivity C-reactive protein (hsCRP), and creatinine in plasma. The npLcn2 levels in urine are significantly increased in subjects with metabolic syndrome and positively correlated with BMI, heart rate, circulating triglycerides, and urinary aldosterone. In cardiothoracic surgery patients, the circulating concentrations of npLcn2 are higher (more than two-fold) than those of healthy volunteers and positively correlated with the accumulation of this protein in the pericardial fluid. Heart failure patients exhibit excessive expression and distribution of npLcn2 in mesothelial cells and adipocytes of the parietal pericardium, which are significantly correlated with the elevated plasma levels of npLcn2, total cholesterol, and creatinine. CONCLUSIONS: Quantitative and qualitative evaluation of npLcn2 in human biofluid samples and tissue samples can be applied for risk assessment of healthy individuals and disease management of patients with obesity-related cardiometabolic and renal complications.

Short Sleep Duration Increases Metabolic Impact in Healthy Adults: A Population-Based Cohort Study.

Objectives: The metabolic impact of inadequate sleep has not been determined in healthy individuals outside laboratories. This study aims to investigate the impact of sleep duration on five metabolic syndrome components in a healthy adult cohort. Methods: A total of 162121 adults aged 20-80 years (men 47.4%) of the MJ Health Database, who were not obese and free from major diseases, were recruited and followed up from 1996 to 2014. Sleep duration and insomnia symptoms were assessed by a self-administered questionnaire. Incident cases of five metabolic syndrome components were identified by follow-up medical examinations. Cox proportional hazard ratios (HRs) were calculated for three sleep duration categories "< 6 hours/day (short)," "6-8 hours/day (regular)," and "> 8 hours/day (long)" with adjustment for potential confounding factors. Analyses were stratified by insomnia symptoms to assess whether insomnia symptoms modified the association between sleep duration and metabolic syndrome. Results: Compared to regular sleep duration, short sleep significantly (p < .001) increased the risk for central obesity by 12% (adjusted HR 1.12 [1.07-1.17]), for elevated fasting glucose by 6% (adjusted HR 1.06 [1.03-1.09]), for high blood pressure by 8% (adjusted HR 1.08 [1.04-1.13]), for low high-density lipoprotein-cholesterol by 7% (adjusted HR 1.07 [1.03-1.11]), for hypertriglyceridemia by 9% (adjusted HR 1.09 [1.05-1.13]), and for metabolic syndrome by 9% (adjusted HR 1.09 [1.05-1.13]). Long sleep decreased the risk of hypertriglyceridemia (adjusted HR 0.89 [0.84-0.94]) and metabolic syndrome (adjusted HR 0.93 [0.88-0.99]). Insomnia symptoms did not modify the effects of sleep duration. Conclusions: Sleep duration may be a significant determinant of metabolic health.

Calorie Restriction Prevents Metabolic Aging Caused by Abnormal SIRT1 Function in Adipose Tissues.

Adipose tissue is a pivotal organ determining longevity, due largely to its role in maintaining whole-body energy homeostasis and insulin sensitivity. SIRT1 is a NAD-dependent protein deacetylase possessing antiaging activities in a wide range of organisms. The current study demonstrates that mice with adipose tissue-selective overexpression of hSIRT1(H363Y), a dominant-negative mutant that disrupts endogenous SIRT1 activity, show accelerated development of metabolic aging. These mice, referred to as Adipo-H363Y, exhibit hyperglycemia, dyslipidemia, ectopic lipid deposition, insulin resistance, and glucose intolerance at a much younger age than their wild-type littermates. The metabolic defects of Adipo-H363Y are associated with abnormal epigenetic modifications and chromatin remodeling in their adipose tissues, as a result of excess accumulation of biotin, which inhibits endogenous SIRT1 activity, leading to increased inflammation, cellularity, and collagen deposition. The enzyme acetyl-CoA carboxylase 2 plays an important role in biotin accumulation within adipose tissues of Adipo-H363Y. Calorie restriction prevents biotin accumulation, abolishes abnormal histone biotinylation, and completely restores the metabolic and adipose functions of Adipo-H363Y. The effects are mimicked by short-term restriction of biotin intake, an approach potentially translatable to humans for maintaining the epigenetic and chromatin remodeling capacity of adipose tissues and preventing aging-associated metabolic disorders.

Deamidated lipocalin-2 induces endothelial dysfunction and hypertension in dietary obese mice.

BACKGROUND: Lipocalin-2 is a proinflammatory adipokine upregulated in obese humans and animals. A pathogenic role of lipocalin-2 in hypertension has been suggested. Mice lacking lipocalin-2 are protected from dietary obesity-induced cardiovascular dysfunctions. Administration of lipocalin-2 causes abnormal vasodilator responses in mice on a high-fat diet (HFD). METHODS AND RESULTS: Wild-type and lipocalin-2 knockout mice were fed with standard chow or HFD. Immunoassays were performed for evaluating the circulating and tissue contents of lipocalin-2. The relaxation and contraction of arteries were studied using a wire myograph. Blood pressure was monitored with implantable radio telemetry. Dietary obesity promoted the accumulation of lipocalin-2 protein in blood and arteries. Deficiency of this adipokine protected mice from dietary obesity-induced elevation of blood pressure. Mass spectrometry analysis revealed that human and murine lipocalin-2 were modified by polyamination. Polyaminated lipocalin-2 was rapidly cleared from the circulation. Adipose tissue was a major site for lipocalin-2 deamidation. The circulating levels and the arterial accumulation of deamidated lipocalin-2 were significantly enhanced by treatment with linoleic acid (18:2n-6), which bound to lipocalin-2 with high affinity and prevented its interactions with matrix metalloproteinase 9 (MMP9). Combined administration of linoleic acid with lipocalin-2 caused vascular inflammation and endothelial dysfunction and raised the blood pressure of mice receiving standard chow. A human lipocalin-2 mutant with cysteine 87 replaced by alanine (C87A) contained less polyamines and exhibited a reduced capacity to form heterodimeric complexes with MMP9. After treatment, C87A remained in the circulation for a prolonged period of time and evoked endothelial dysfunction in the absence of linoleic acid. CONCLUSIONS: Polyamination facilitates the clearance of lipocalin-2, whereas the accumulation of deamidated lipocalin-2 in arteries causes vascular inflammation, endothelial dysfunction, and hypertension.

A polymorphism in transforming growth factor-ß1 is associated with carotid plaques and increased carotid intima-media thickness in older Chinese men: the Guangzhou Biobank Cohort Study-Cardiovascular Disease Subcohort.

OBJECTIVE: Polymorphisms of the transforming growth factor-ß1 (TGFB1) gene have not been associated with asymptomatic atherosclerosis previously. We investigated the relationship between a single nucleotide polymorphism (SNP) rs4803455 in TGFB1 and atherosclerosis identified by the presence of carotid plaque and increased intima-media thickness (IMT) in an older Chinese population. METHODS: 1996 subjects (992 (49.7%) men aged 50-85 years) from the Guangzhou Biobank Cohort Study-Cardiovascular Subcohort (GBCS-CVD) were genotyped. Carotid plaque and IMT were assessed by B-mode ultrasonography. RESULTS: In male subjects, the C allele of TGFB1 rs4803455 was significantly associated with prevalence of carotid plaque (adjusted OR: 2.49, 95% CI: 1.16-5.36, P = 0.03). The C allele was related to increased number of common carotid artery (CCA) plaques (P=0.03) and larger carotid plaque area (P = 0.02) in men. The homozygous carriers of allele C in male subjects also had a higher risk of having carotid IMT ≥ 1 mm (adjusted OR: 1.75, 95% CI: 1.05-2.93, P = 0.03). These associations were independent of age, smoking, physical activity, body mass index, blood pressure, lipid profile, fasting glucose and high sensitivity C-reactive protein. CONCLUSION: This is the first study to show that the C allele in TGFB1 was associated with increased risk of atherosclerosis in older Chinese men. Further investigations on the linkage between the TGFB1 gene and progression of atherosclerosis in asymptomatic populations are warranted.

Linkage of angiotensinogen gene polymorphisms with hypertension in a sibling study of Hong Kong Chinese.

OBJECTIVE: The angiotensinogen gene has been linked with human essential hypertension in whites but the relationship in Asian populations has been less consistent. This study aimed to examine genetic associations between hypertension and the M235T, T174M, and G-217A polymorphisms of the angiotensinogen gene in Chinese siblings. METHODS: We studied members of 126 families with a hypertensive proband, including 434 siblings, of which 178 were hypertensive. Parental history of hypertension was recorded. The M235T, T174M, and G-217A polymorphisms were examined using a microarray method, validated by sequencing. The transmission disequilibrium test was applied to identify whether the genetic polymorphism loci were related to hypertension. Haplotype analysis of the combined polymorphisms was applied using the TRANSMIT program. Linkage study was conducted by applying the affected pedigree member method. RESULTS: A significant overtransmission was observed for the T235 allele at the M235T polymorphism and hypertension (chi2 = 4.41, P = 0.036) but not for the T174M and G-217A polymorphisms. The haplotype analysis showed a significant association with the haplotypes of paired markers (T174 and T235) with chi2 value of 8.131 (P = 0.004; global test chi2 = 9.131, P = 0.028). Linkage between M235T and hypertension was detected (T = -2.25, P = 0.019), and a tendency for linkage with central obesity-related hypertension was found for the M235T and T174M polymorphisms (P = 0.0087 and P = 0.01). CONCLUSION: The M235T and T174M variants, especially the T235 allele, contribute to an increased risk of hypertension in these Chinese patients.

Reliability and validity of the IPAQ-Chinese: the Guangzhou Biobank Cohort study.

INTRODUCTION: Valid measurements of self-reported physical activity are very limited in Chinese populations, especially the elderly. Therefore, we examined the validity and reliability of the Chinese version of the International Physical Activity Questionnaire (IPAQ-C) in older Chinese people. METHODS: Two hundred twenty-four older adults (66.1% women, 33.9% men, mean age 65.2 +/- 5.7 yr) were randomly selected from the Guangzhou Biobank Cohort Study, a prospective cohort of older Chinese in Southern China. To examine the test-retest reliability, the participants completed the IPAQ-C twice during a 7-d interval. The criterion validity of the IPAQ-C was tested with pedometry. RESULTS: Good reliability was observed between the repeated IPAQ-C, with intraclass correlation coefficients (ICC) ranging from 0.81 to 0.89. Total activity measured by IPAQ-C correlated moderately with the pedometer-measured steps (partial r = 0.33 adjusted for sex, age, and education; P < 0.001). The walking domain of IPAQ-C was strongly associated with the number of steps (partial r = 0.58, P < 0.001), but there were no significant associations between other activity domains of the IPAQ-C and the pedometer data. CONCLUSION: This is the first reported validation study of an international standardized questionnaire (IPAQ-C) in older Chinese adults. Our study shows that the IPAQ-C is adequately valid and reliable for assessing total physical activity and that it may be a useful instrument for generating internationally comparable data on physical activity in this population.

Overview of dietary influences on atherosclerotic vascular disease: epidemiology and prevention.

Most dietary recommendations are based on studies of limited power and do not adequately reflect the current knowledge base, particularly with regard to effects of diet on clinical outcomes, the most important endpoint from the patients' perspective. In this review we discusses the current state of dietary research, and present a summary of the evidence upon which to base dietary recommendations and guidelines for atherosclerotic vascular disease prevention. We also highlight the complexity and limitations of interpreting current diet-based epidemiological studies in isolation.