人血清25-羟基维生素D水平与心血管病危险因素的相关性研究

目的:了解北京地区人群维生素D含量情况,研究人血清25-羟基维生素D水平与多种心血管病危险因素的关系,为早期预防心血管疾病提供数据支持。方法:采用横断面调查方法,收集北京地区体检人群580例。采用同位素稀释液相色谱串联质谱法测定血清25-羟基维生素D3和25-羟基维生素D2,用以评价体内维生素D状态;同时测定传统心血管病危险因素以及胆固醇酯脂肪酸类(CEFA)、支链(BCAA)及芳香族氨基酸类(AAA)、溶血卵磷脂类(LPC)等新发现的心血管病潜在危险因素,分析血清25-羟基维生素D水平与这些指标的关系。结果:580例体检人群血清总25-羟基维生素D浓度为(21.57±7.83)μg/L,参考区间(2.5%~97.5%分位数)9.41~38.32μg/L;男性(22.68±7.60)μg/L)显著高于女性(20.18±7.90)μg/L)(P0.001)。研究对象中维生素D严重缺乏、缺乏、不足和充足所占比例分别为3.3%、42.8%、39.3%及14.6%。非参数相关分析表明校正年龄、性别后总25-羟基维生素D水平与HDL-C、apo AI、不饱和LPC、Omega-3型CEFA等心血管保护因素均呈显著正相关,同时与apo B、超敏C反应蛋白、血浆致动脉粥样硬化指数、BCAA、AAA、饱和CEFA等心血管病危险因素均呈显著负相关。结论:血清25-羟基维生素D可能是心血管保护因素,其对预防和改善心血管疾病具有潜在积极作用。     

Common variation in the WNK1 gene and blood pressure in childhood: the Avon Longitudinal Study of Parents and Children

WNK1 gene variants have been associated with adult blood pressure. We aimed to investigate relationships between WNK1 variants and blood pressure, as well as blood pressure change with age, in a longitudinal childhood study. Associations between single nucleotide polymorphisms in WNK1 and blood pressure and the rate of blood pressure change between 7 and 11 years were examined in the Avon Longitudinal Study of Parent and Children Study (n=5326 for systolic blood pressure at 11 years). We observed associations (P<0.05) with diastolic blood pressure gradient with age for 33 of 82 typed and imputed polymorphisms, including polymorphisms in exons 4, 10, and 11 (rs10774466, rs1012729, and rs9804992). The minor allele (G) of rs1012729 (frequency: 25.6%) was associated with a gender-adjusted change in a diastolic blood pressure gradient of -0.11 mm Hg/y (95% CI: -0.20 to -0.03 mm Hg/y; P=0.0054). No associations were shown with the systolic blood pressure gradient. At age 11 years, 30 polymorphisms showed association (P<0.05) with systolic blood pressure, including variants in exons 4 and 10 (rs10774466 and rs1012729). Only 3 polymorphisms were associated with diastolic blood pressure at 11 years. In exploration of polymorphism-dietary cation interactions on systolic blood pressure at 11 years, 59 reached significance (P<0.05; 12.3 expected by chance), mostly (n=33) related to dietary calcium. The findings show that common intronic and exonic WNK1 variants are associated with diastolic blood pressure gradient from 7 to 11 years and with systolic blood pressure at 11 years. Our study suggests that previously reported effects of WNK1 variants on blood pressure are mediated via effects on the gradient of blood pressure change with age.     

Associations between serum 25-hydroxyvitamin D levels and allergic sensitization in early childhood

Background and objectivesVitamin D status may be related to allergen sensitizations, but the evidence is inconsistent. The objective of this study was to assess whether serum 25-hydroxyvitamin D (25(OH)D) levels were associated with allergic sensitizations in early childhood.MethodsData were collected from 2642 children who visited the Guangdong Women and Children’s Hospital from January 2016 to May 2017 for routine health check-ups. Serum 25(OH)D levels were tested by electrochemiluminescence immunoassay. Allergic sensitizations including food and inhalant allergens were tested for specific IgE antibodies at one year (12 months 0 days through 12 months 30 days) and two years (24 months 0 days through 24 months 30 days) of age.ResultsThe mean level of serum 25(OH)D was 86.47 ± 27.55 nmol/L, with a high prevalence of vitamin D insufficiency (<75 nmol/L) in children aged 0–2 years (36.8%). Lower 25(OH)D levels with serum total IgE of more than 200 IU/mL (81.54 ± 25.53 nmol/L) compared with less than 100 IU/mL (87.92 ± 28.05 nmol/L). The common sensitization to allergens in children aged one and two years were milk (44.2%), cat epithelium (26.4%), egg (13.1%), dog epithelium (12.7%) and Dermatophagoides farinae (6.7%). After multivariate adjustment, data in 25(OH)D treated as a continuous variable or categories, no consistent associations were found between 25(OH)D levels and allergen-specific IgEs.ConclusionsSerum 25(OH)D level showed an inverse relationship with total IgE level in early childhood. However, there is lack of evidence to support associations between low 25(OH)D levels and allergic sensitization to various allergens.     

Maternal age in pregnancy and offspring blood pressure in childhood in the Avon Longitudinal Study of Parents and Children (ALSPAC)

Associations between maternal age in pregnancy and offspring blood pressure (BP) at age 7(1/2) were investigated in 7623 singletons from the Avon Longitudinal Study of Parents and Children (ALSPAC). In models adjusted for age and sex there was an inverse relationship between maternal age and BP in children: beta = -0.06 mmHg per year of maternal age (95% CI -0.10 to -0.01, P = 0.02) for systolic BP and beta = -0.04 (95% CI -0.07 to -0.01, P = 0.02) for diastolic BP. However, this association disappeared after adjustment for confounding factors: beta = -0.02 mmHg per year of maternal age (95% CI -0.07 to 0.04, P = 0.5) for systolic BP and beta = -0.03 (95% CI -0.07 to 0.01, P = 0.2) for diastolic BP. We conclude that there is no evidence of a relationship between maternal age in pregnancy and childhood BP in this contemporary birth cohort.     

The Avon Longitudinal Study of Parents and Children (ALSPAC): a resource for genetic epidemiology

The Avon Longitudinal Study of Parents and Children (ALSPAC) has collected detailed phenotypic and environmental information from pregnancy onwards on approximately 14 000 babies born in 1991-1992. A DNA bank on over 10 000 mothers and children has been established with generic consent for (undisclosed) genetic analysis, and cell lines on both children and parents are planned. As a multigenerational population cohort unselected by disease, trait or exposure, ALSPAC is uniquely placed to explore the genetic and environmental determinants of adverse developmental responses and common disease. Added value for genetic epidemiology generally is the ability to detect distortion of the expected Mendelian 50:50 transmission of alleles to study subjects (e.g. due to differential loss of embryos of one genotype) or to test for heterosis, i.e. whether heterozygotes have a greater or lesser effect than either homozygote. Finally, phenome scans (a fixed format analysis of the associations between a genotype of interest and thousands of outcome variables from the cohort database) could be used as a screening tool to test whether certain classes of genetic variation have more impact than others on human health and development.     

The Avon Longitudinal Study of Parents and Children (ALSPAC)--a resource for the study of the environmental determinants of childhood obesity

Childhood obesity is a major public health problem because the prevalence is increasing and because childhood obesity is associated with short- and long-term adverse consequences. By contributing to our understanding of the causes of childhood obesity epidemiological studies can help to inform preventive strategies. Prospective studies with all-of-life measures of exposures, objective measures of physical activity and more accurate measures of diet and body composition will be better able to identify modifiable environmental exposures that act cumulatively or at critical time periods across the lifecourse. The Avon Longitudinal Study of Parents and Children (ALSPAC) recruited around 14 000 pregnant women with estimated dates of delivery between 1991 and 1992. The children have been followed-up in detail ever since and now constitute probably the most intensively studied cohort of children ever recruited. Recent analyses have identified important modifiable risk factors and further analyses based on more accurate measures of diet, activity and body composition should provide further insights.     

The Avon Longitudinal Study of Parents and Children (ALSPAC)--study design and collaborative opportunities

The Avon Longitudinal Study of Parents and Children (ALSPAC) is a population-based study designed to understand the ways in which the physical and social environment interact, over time, with the genotype to affect health, behaviour and development. This information about causal interactions in common diseases and disorders will provide the basis on which future preventive interventions can be tested, especially in regard to people with specific genotypes. Whilst ALSPAC builds on data and hypotheses generated by earlier general population cohorts, its design offers special advantages, the most important being: enrolment in early pregnancy; banking of DNA from the children and parents (permitting genetic transmission tests and transgenerational imprinting studies); diverse physical, psychological and environmental measures; one geographical base (permitting medical record and school linkage; environmental measures in the home, and clinics for direct examination); annual hands-on examinations of the full cohort since age 7. The 14 541 enrolled pregnancies (expected date of delivery 1 April 1991 to 31 December 1992) represented about 85% of the eligible population. The 13 971 children who were still alive at age 12 months have been followed principally by questionnaires completed by a parent. Twelve years on, questionnaires are still being sent out to 11 300 families. The average questionnaire response rate from mothers is 79%. From age 7, annual examinations of both 'physical' and 'psychological' aspects have also been conducted on the children (approximately 8000 attend each 'clinic'). The quality of the data has proved high in validation studies and is maintained by collaboration with experts in each specialist field. The high participation rate ensures a viable study well into the future.     

Serum 25-hydroxyvitamin D concentration, established and emerging cardiovascular risk factors and risk of myocardial infarction before the age of 60 years

ObjectiveWe examined the relationships of serum 25-hydroxyvitamin D (25(OH)D) concentration to established and emerging cardiovascular risk factors and risk of myocardial infarction (MI) in a population-based case–control study of MI before the age of 60 years.MethodsA total of 387 survivors of a first MI and 387 sex- and age-matched controls were included. Fasting blood samples drawn three months after the MI in cases and at the same time in the matched controls were used for biochemical analyses.ResultsSerum concentrations of 25(OH)D, adjusted for seasonal variation, were lower in cases than controls (55.0 (40.0–71.0) nmol/L vs 60.5 (47.0–75.0) nmol/L; median (interquartile range); standardized odds ratio (OR) for MI with 95% confidence interval in univariable analysis: 0.80 (0.69–0.93); p = 0.003). The 25(OH)D association with MI disappeared after adjustment for established and emerging risk factors (OR: 1.01 (0.82–1.25)). Current smoking and plasma levels of proinsulin and PAI-1 activity were independently associated with 25(OH)D in controls, whereas waist circumference, plasma triglycerides, proinsulin, PAI-1 activity and cystatin C, and non-Nordic ethnicity were independently associated with 25(OH)D in patients. Serial measurements of 25(OH)D (samples drawn <4 h and 3 months after the onset of MI) in 57 patients showed no systematic differences between sampling times.ConclusionVitamin D insufficiency, which is associated with a multitude of metabolic, procoagulant and inflammatory perturbations, is not independently related to premature MI. This suggests that vitamin D insufficiency either constitutes an epiphenomenon or increases the risk of MI by promoting established risk factor mechanisms that predispose to atherothrombosis.     

Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States: data from the Third National Health and Nutrition Examination Survey

BACKGROUND: Results of several epidemiologic and clinical studies have suggested that there is an excess risk of hypertension and diabetes mellitus in persons with suboptimal intake of vitamin D. METHODS: We examined the association between serum levels of 25-hydroxyvitamin D (25[OH]D) and select cardiovascular disease risk factors in US adults. A secondary analysis was performed with data from the Third National Health and Nutrition Examination Survey, a national probability survey conducted by the National Center for Health Statistics between January 1, 1988, and December 31, 1994, with oversampling of persons 60 years and older, non-Hispanic black individuals, and Mexican American individuals. RESULTS: There were 7186 male and 7902 female adults 20 years and older with available data in the Third National Health and Nutrition Examination Survey. The mean 25(OH)D level in the overall sample was 30 ng/mL (75 nmol/L). The 25(OH)D levels were lower in women, elderly persons (>or=60 years), racial/ethnic minorities, and participants with obesity, hypertension, and diabetes mellitus. The adjusted prevalence of hypertension (odds ratio [OR], 1.30), diabetes mellitus (OR, 1.98), obesity (OR, 2.29), and high serum triglyceride levels (OR, 1.47) was significantly higher in the first than in the fourth quartile of serum 25(OH)D levels (P<.001 for all). CONCLUSIONS: Serum 25(OH)D levels are associated with important cardiovascular disease risk factors in US adults. Prospective studies to assess a direct benefit of cholecalciferol (vitamin D) supplementation on cardiovascular disease risk factors are warranted.     

Positive association between circulating 25-hydroxyvitamin D levels and prostate cancer risk: new findings from an updated meta-analysis

Purpose

To investigate and clarify the relationship between circulating 25-hydroxyvitamin D level and prostate cancer risk.

Methods

We conducted the meta-analysis to better evaluate the association. Terms “25-Hydroxyvitamin D”/“vitamin D” and “prostate cancer” were used for literature search.

Results

We identified 21 relevant publications from databases of PubMed and MEDLINE and included 11,941 cases and 13,870 controls in the meta-analysis. Overall studies revealed a significant 17 % elevated risk of prostate cancer for individuals with higher level of 25-hydroxyvitamin D (OR = 1.17, 95 % CI = 1.05–1.30, P  = 0.004), and no publication bias was found in the calculations (P  = 0.629). Subgroup analysis confirmed the association from nested case–control study group, studies from USA group and studies using serum samples group (nested case–control studies: OR = 1.17, 95 % CI = 1.08–1.27, P < 0.001; USA: OR = 1.15, 95 % CI = 1.03–1.29, P = 0.017; serum: OR = 1.20, 95 % CI = 1.01–1.42, P = 0.042); moreover, sensitivity tests also indicated significant results in studies from Europe and studies conducting with plasma samples after exclusion of some influential single study from the analysis, respectively (Europe: OR = 1.21, 95 % CI = 1.04–1.40, P = 0.014; plasma: OR = 1.13, 95 % CI = 1.00–1.27, P = 0.05).

Conclusions

Our meta-analysis, for the first time, suggested significant positive relationship between high level of 25-hydroxyvitamin D and increased risk of prostate cancer, reminding us that more concern should be taken into account during assessing the effect of 25-hydroxyvitamin D.     

Associations between serum 25-hydroxyvitamin D3 concentrations and liver histology in patients with non-alcoholic fatty liver disease

Background and aimTo explore associations between serum 25-hydroxyvitamin D₃ [25(OH)D] concentrations and liver histology in patients with non-alcoholic fatty liver disease (NAFLD).Methods and resultsWe studied 60 consecutive patients with biopsy-proven NAFLD, and 60 healthy controls of comparable age, sex and body mass index (BMI).NAFLD patients had a marked decrease in winter serum 25(OH)D concentrations (51.0 ± 22 vs. 74.5 ± 15 nmol/L, P < 0.001) compared with controls. Metabolic syndrome (MetS; as defined by the Adult Treatment Panel III criteria) and its individual components occurred more frequently among NAFLD patients. The marked differences in 25(OH)D concentrations observed between the groups were little affected by adjustment for age, sex, BMI, creatinine, calcium, homeostasis model assessment (HOMA)-insulin resistance, and the presence of the MetS. Interestingly, among NAFLD patients, decreased 25(OH)D concentrations were closely associated with the histological severity of hepatic steatosis, necroinflammation and fibrosis (P < 0.001 for all) independent of age, sex, BMI, creatinine, calcium, HOMA-insulin resistance, and presence of the MetS.ConclusionsCompared with controls, NAFLD patients have a marked decrease in serum 25(OH)D concentrations, which is closely associated with histopathological features of NAFLD. Further investigation into whether vitamin D₃ may play a role in the development and progression of NAFLD appears to be warranted.     

Neck circumference is associated with non-traditional cardiovascular risk factors in individuals at low-to-moderate cardiovascular risk: cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

Background

Neck circumference (NC) is associated with traditional cardiovascular risk factors (CVRF), but its usefulness to identify earlier atherogenic risk has been scarcely examined. Associations of NC with non-traditional CVRF were investigated in participants at low-to-moderate risk from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

Methods

807 individuals (35–54 years) without obesity, diabetes or cardiovascular disease was stratified into quartiles of NC (cut-off for men: 36.5; 37.9 and 39.5 cm; women: 31.4; 32.5 and 34 cm) and traditional and non-traditional risk factors (lipoprotein subfractions by Vertical Auto Profile, adiponectin, leptin, E-selectin) were compared across groups. In linear regression models, associations of NC with non-traditional risk factors were tested for the entire sample and for low-risk group (≤?2 CVRF).

Results

In both sexes, BMI, waist circumference, systolic and diastolic blood pressure, fasting and 2-h plasma glucose, HOMA-IR, triglycerides, leptin, E-selectin, small dense LDL-cholesterol, IDL-cholesterol, VLDL₃-cholesterol and TG/HDL ratio increased significantly, while HDL₂-cholesterol and HDL₃-cholesterol decreased across NC quartiles. In linear regression models, a direct association [β(95% CI)] of NC with leptin [(0.155 (0.068–0.242); 0.147 (0.075–0.220)], E-selectin [(0.105 (0.032–0.177); 0.073 (0.006 to 0.140)] and small-dense LDL [(1.866 (0.641–3.091); 2.372 (1.391–3.353)] and an inverse association with HDL₂-cholesterol [(??0.519 (??0.773 to ??0.266); ??0.815 (??1.115 to 0.515)] adjusted for age were detected for men and women, respectively.

Conclusion

Our findings indicate that measurement of NC may be useful for an earlier identification of unfavorable atherogenic metabolic profile in middle-aged individuals at lower cardiovascular risk level.