Nutritional Blood Concentration Biomarkers in the Hispanic Community Health Study/Study of Latinos: Measurement Characteristics and Power.

Measurement error is a major issue in self-reported diet that can distort diet-disease relationships. Use of blood concentration biomarkers has the potential to mitigate the subjective bias inherent in self-reporting. As part of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) baseline visit (2008-2011), self-reported information on diet was collected from all participants (n = 16,415). The HCHS/SOL also included annual telephone follow-up, as well as a second (2014-2017) and third (2020-2023) clinic visit. Blood concentration biomarkers for carotenoids, tocopherols, retinol, vitamin B12, and folate were measured in a subset of participants (n = 476) as part of the Study of Latinos: Nutrition and Physical Activity Assessment Study (SOLNAS) (2010-2012). We examined the relationships among biomarker levels, self-reported intake, Hispanic/Latino background (Central American, Cuban, Dominican, Mexican, Puerto Rican, or South American), and other participant characteristics in this diverse cohort. We built regression calibration-based prediction equations for 10 nutritional biomarkers and used a simulation to study the power of detecting a diet-disease association in a multivariable Cox model using a predicted concentration level. Good statistical power was observed for some nutrients with high prediction model R2 values, but further research is needed to understand how best to realize the potential of these dietary biomarkers. This study provides a comprehensive examination of several nutritional biomarkers within the HCHS/SOL, characterizing their associations with subject characteristics and the influence of the measurement characteristics on the power to detect associations with health outcomes.

Interlaboratory comparison of 25-hydroxyvitamin D assays: Vitamin D Standardization Program (VDSP) Intercomparison Study 2 - Part 1 liquid chromatography - tandem mass spectrometry (LC-MS/MS) assays - impact of 3-epi-25-hydroxyvitamin D3 on assay performance.

An interlaboratory comparison study was conducted by the Vitamin D Standardization Program (VDSP) to assess the performance of liquid chromatography - tandem mass spectrometry (LC-MS/MS) assays used for the determination of serum total 25-hydroxyvitamin D (25(OH)D), which is the sum of 25-hydroxyvitamin D2 (25(OH)D2) and 25-hydroxyvitamin D3 (25(OH)D3). A set of 50 single-donor samples was assigned target values for concentrations of 25(OH)D2, 25(OH)D3, 3-epi-25-hydroxyvitamin D3 (3-epi-25(OH)D3), and 24R,25-dihydroxyvitamin D3 (24R,25(OH)2D3) using isotope dilution liquid chromatography - tandem mass spectrometry (ID LC-MS/MS). VDSP Intercomparison Study 2 Part 1 includes results from 14 laboratories using 14 custom LC-MS/MS assays. Assay performance was evaluated using mean % bias compared to the assigned target values and using linear regression analysis of the test assay mean results and the target values. Only 53% of the LC-MS/MS assays met the VDSP criterion of mean % bias ≤ |±5%|. For the LC-MS/MS assays not meeting the ≤ |±5%| criterion, four assays had mean % bias of between 12 and 21%. Based on multivariable regression analysis using the concentrations of the four individual vitamin D metabolites in the 50 single-donor samples, the performance of several LC-MS/MS assays was found to be influenced by the presence of 3-epi-25(OH)D3. The results of this interlaboratory study represent the most comprehensive comparison of LC-MS/MS assay performance for serum total 25(OH)D and document the significant impact of the lack of separation of 3-epi-25(OH)D3 and 25(OH)D3 on assay performance, particularly with regard to mean % bias.

Interlaboratory comparison of 25-hydroxyvitamin D assays: Vitamin D Standardization Program (VDSP) Intercomparison Study 2 - Part 2 ligand binding assays - impact of 25-hydroxyvitamin D2 and 24R,25-dihydroxyvitamin D3 on assay performance.

An interlaboratory comparison study was conducted by the Vitamin D Standardization Program (VDSP) to assess the performance of ligand binding assays (Part 2) for the determination of serum total 25-hydroxyvitamin D [25(OH)D]. Fifty single-donor samples were assigned target values for concentrations of 25-hydroxyvitamin D2 [25(OH)D2], 25-hydroxyvitamin D3 [25(OH)D3], 3-epi-25-hydroxyvitamin D3 [3-epi-25(OH)D3], and 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] using isotope dilution liquid chromatography-tandem mass spectrometry (ID LC-MS/MS). VDSP Intercomparison Study 2 Part 2 includes results from 17 laboratories using 32 ligand binding assays. Assay performance was evaluated using mean % bias compared to the assigned target values and using linear regression analysis of the test assay mean results and the target values. Only 50% of the ligand binding assays achieved the VDSP criterion of mean % bias ≤ |± 5%|. For the 13 unique ligand binding assays evaluated in this study, only 4 assays were consistently within ± 5% mean bias and 4 assays were consistently outside ± 5% mean bias regardless of the laboratory performing the assay. Based on multivariable regression analysis using the concentrations of individual vitamin D metabolites in the 50 single-donor samples, most assays underestimate 25(OH)D2 and several assays (Abbott, bioMérieux, DiaSorin, IDS-EIA, and IDS-iSYS) may have cross-reactivity from 24R,25(OH)2D3. The results of this interlaboratory study represent the most comprehensive comparison of 25(OH)D ligand binding assays published to date and is the only study to assess the impact of 24R,25(OH)2D3 content using results from a reference measurement procedure.

Assessment of serum total 25-hydroxyvitamin D assays for Vitamin D External Quality Assessment Scheme (DEQAS) materials distributed at ambient and frozen conditions.

The Vitamin D External Quality Assessment Scheme (DEQAS) distributes human serum samples four times per year to over 1000 participants worldwide for the determination of total serum 25-hydroxyvitamin D [25(OH)D)]. These samples are stored at -40 °C prior to distribution and the participants are instructed to store the samples frozen at -20 °C or lower after receipt; however, the samples are shipped to participants at ambient conditions (i.e., no temperature control). To address the question of whether shipment at ambient conditions is sufficient for reliable performance of various 25(OH)D assays, the equivalence of DEQAS human serum samples shipped under frozen and ambient conditions was assessed. As part of a Vitamin D Standardization Program (VDSP) commutability study, two sets of the same nine DEQAS samples were shipped to participants at ambient temperature and frozen on dry ice. Twenty-eight laboratories participated in this study and provided 34 sets of results for the measurement of 25(OH)D using 20 ligand binding assays and 14 liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. Equivalence of the assay response for the frozen versus ambient DEQAS samples for each assay was evaluated using multi-level modeling, paired t-tests including a false discovery rate (FDR) approach, and ordinary least squares linear regression analysis of frozen versus ambient results. Using the paired t-test and confirmed by FDR testing, differences in the results for the ambient and frozen samples were found to be statistically significant at p < 0.05 for four assays (DiaSorin, DIAsource, Siemens, and SNIBE prototype). For all 14 LC-MS/MS assays, the differences in the results for the ambient- and frozen-shipped samples were not found to be significant at p < 0.05 indicating that these analytes were stable during shipment at ambient conditions. Even though assay results have been shown to vary considerably among different 25(OH)D assays in other studies, the results of this study also indicate that sample handling/transport conditions may influence 25(OH)D assay response for several assays.

Assessment of serum total 25-hydroxyvitamin D assay commutability of Standard Reference Materials and College of American Pathologists Accuracy-Based Vitamin D (ABVD) Scheme and Vitamin D External Quality Assessment Scheme (DEQAS) materials: Vitamin D Standardization Program (VDSP) Commutability Study 2.

An interlaboratory study was conducted through the Vitamin D Standardization Program (VDSP) to assess commutability of Standard Reference Materials® (SRMs) and proficiency testing/external quality assessment (PT/EQA) samples for determination of serum total 25-hydroxyvitamin D [25(OH)D] using ligand binding assays and liquid chromatography-tandem mass spectrometry (LC-MS/MS). A set of 50 single-donor serum samples were assigned target values for 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] using reference measurement procedures (RMPs). SRM and PT/EQA samples evaluated included SRM 972a (four levels), SRM 2973, six College of American Pathologists (CAP) Accuracy-Based Vitamin D (ABVD) samples, and nine Vitamin D External Quality Assessment Scheme (DEQAS) samples. Results were received from 28 different laboratories using 20 ligand binding assays and 14 LC-MS/MS methods. Using the test assay results for total serum 25(OH)D (i.e., the sum of 25(OH)D2 and 25(OH)D3) determined for the single-donor samples and the RMP target values, the linear regression and 95% prediction intervals (PIs) were calculated. Using a subset of 42 samples that had concentrations of 25(OH)D2 below 30 nmol/L, one or more of the SRM and PT/EQA samples with high concentrations of 25(OH)D2 were deemed non-commutable using 5 of 11 unique ligand binding assays. SRM 972a (level 4), which has high exogenous concentration of 3-epi-25(OH)D3, was deemed non-commutable for 50% of the LC-MS/MS assays.

Ancestry-specific recent effective population size in the Americas.

Populations change in size over time due to factors such as population growth, migration, bottleneck events, natural disasters, and disease. The historical effective size of a population affects the power and resolution of genetic association studies. For admixed populations, it is not only the overall effective population size that is of interest, but also the effective sizes of the component ancestral populations. We use identity by descent and local ancestry inferred from genome-wide genetic data to estimate overall and ancestry-specific effective population size during the past hundred generations for nine admixed American populations from the Hispanic Community Health Study/Study of Latinos, and for African-American and European-American populations from two US cities. In these populations, the estimated pre-admixture effective sizes of the ancestral populations vary by sampled population, suggesting that the ancestors of different sampled populations were drawn from different sub-populations. In addition, we estimate that overall effective population sizes dropped substantially in the generations immediately after the commencement of European and African immigration, reaching a minimum around 12 generations ago, but rebounded within a small number of generations afterwards. Of the populations that we considered, the population of individuals originating from Puerto Rico has the smallest bottleneck size of one thousand, while the Pittsburgh African-American population has the largest bottleneck size of two hundred thousand.

Statin nonadherence in Latino and noncitizen neighborhoods in New York City, Los Angeles, and Chicago, 2012-2016.

BACKGROUND: Latino adults, especially immigrants without citizenship (i.e., noncitizens), experience considerable barriers to health care, including medications. Inequitable access to medications, especially statins, may exacerbate disparities in cardiovascular disease. Despite this, little is known about medication nonadherence in Latino neighborhoods, especially those with large noncitizen populations. OBJECTIVES: To estimate nonadherence to statins in Latino neighborhoods and evaluate differences on the basis of their noncitizen population. METHODS: We conducted a retrospective cohort study among 48,161 adults who lived in predominately Latino neighborhoods in New York City, Los Angeles, and Chicago and who initiated statin therapy from January 2012 to December 2015 using IQVIA LifeLink. Statin nonadherence was defined as a proportion of days covered amounting to less than 80% over 12 months. We focused on differences between neighborhoods with high noncitizen concentrations (areas where noncitizens are at least 35% of the adult population) and other Latino neighborhoods. We examined associations using logistic regressions adjusted for individual (e.g., payment method) and neighborhood characteristics (e.g., poverty). RESULTS: Individuals living in neighborhoods with high noncitizen concentrations were more nonadherent to statins than those in Latino neighborhoods with fewer noncitizens (75.0% vs. 70.0%, adjusted odds ratio [aOR] 1.18, [95% CI 1.06-1.33]). These disparities were worse in New York City (77.7% vs. 69.1%, aOR 1.37, [95% CI 1.23-1.53]) and Chicago (76.1% vs. 68.8%, aOR 1.38, [95% CI 1.14-1.67]) than in Los Angeles (73.8% vs. 71.3%, aOR 1.10, [95% CI 1.01-1.20]). CONCLUSION: Neighborhoods with large noncitizen populations have much higher rates of statin nonadherence than Latino neighborhoods with fewer noncitizens. These disparities were least pronounced in Los Angeles, where the county provides health care to all uninsured residents, including noncitizens without documentation to reside in the United States. Efforts to improve medication access in Latino neighborhoods should be multifocal and start by implementing state and local health care options for low-income residents, regardless of citizenship status.

Alternate Healthy Eating Index is Positively Associated with Cognitive Function Among Middle-Aged and Older Hispanics/Latinos in the HCHS/SOL.

BACKGROUND: Diet quality may be an important area of focus for promoting cognitive health; however, the association between diet quality and cognitive function among Hispanics/Latinos remains largely unexamined. We hypothesized that a healthier diet quality will be associated with better cognitive function in middle-aged and older Hispanics/Latinos. OBJECTIVE: The objective of this study was to examine associations between the Alternate Healthy Eating Index (AHEI-2010), a measure of diet quality, and cognitive function in middle-aged and older Hispanics/Latinos. METHODS: Data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Visit 1 (2008-2011) were used (n = 8461; ages 45-74 y). Cognitive function was assessed with tests of verbal learning and memory, verbal fluency, and processing speed; a global cognition score was derived by summing the z scores of individual tests. Dietary intake was assessed via two 24-h recalls. Total AHEI-2010 score was categorized into quintiles (higher quintiles indicating healthier diet). Linear regression models were used to examine associations between AHEI-2010 quintiles and cognitive function adjusting for sociodemographic characteristics, daily energy intake, type 2 diabetes, smoking, and depressive symptoms. RESULTS: Compared with the lowest quintile, in the second to fourth AHEI-2010 quintiles, global cognition scores were significantly higher by 0.28, 0.52, and 0.48 units (P-trend = 0.042). In the second to fifth AHEI-2010 quintiles, verbal learning scores were significantly higher by 0.60, 0.62, 0.92, and 0.88 units, and verbal memory scores were higher by 0.33, 0.40, 0.52, and 0.46 units (P-trend = 0.020 and 0.007, respectively). No associations were observed between the AHEI-2010 and verbal fluency or processing speed (P-trend = 0.49 and 0.84, respectively). Among AHEI-2010 components, adequate consumption of vegetables, alcohol, and whole fruits were each associated with better cognitive function. CONCLUSIONS: An overall healthier diet quality was associated with better global cognition, verbal learning, and verbal memory in middle-aged and older Hispanics/Latinos.

Immigration Status and Disparities in the Treatment of Cardiovascular Disease Risk Factors in the Hispanic Community Health Study/Study of Latinos (Visit 2, 2014-2017).

Objectives. To estimate treatment rates of high cholesterol, hypertension, and diabetes among Hispanic/Latino immigrants by immigration status (i.e., naturalized citizens, documented immigrants, or undocumented immigrants).Methods. We performed a cross-sectional analyses of the Hispanic Community Health Study/Study of Latinos (visit 2, 2014-2017). We restricted our analysis to Hispanic/Latino immigrants with high cholesterol (n = 3974), hypertension (n = 3353), or diabetes (n = 2406); treatment was defined as use of statins, antihypertensives, and antidiabetics, respectively.Results. When compared with naturalized citizens, undocumented and documented immigrants were less likely to receive treatment for high cholesterol (38.4% vs 14.1%; prevalence ratio [PR] = 0.37 [95% confidence interval [CI] = 0.27, 0.51] and 25.7%; PR = 0.67 [95% CI = 0.58, 0.76]), hypertension (77.7% vs 57.7%; PR = 0.74 [95% CI = 0.62, 0.89] and 68.1%; PR = 0.88 [95% CI = 0.82, 0.94]), and diabetes (60.3% vs. 50.4%; PR = 0.84 [95% CI = 0.68, 1.02] and 55.8%; PR = 0.93 [95% CI = 0.83, 1.03]); the latter did not reach statistical significance. Undocumented and documented immigrants had less access to health care, including insurance coverage or a usual health care provider, than naturalized citizens. Therefore, adjusting for health care access largely explained treatment disparities across immigration status.Conclusions. Preventing cardiovascular disease among Hispanic/Latino immigrants should focus on undertreatment of high cholesterol, hypertension, and diabetes by increasing health care access, especially among undocumented immigrants.

Associations of Lipid Levels and Cognition: Findings from the Hispanic Community Health Study/Study of Latinos.

OBJECTIVE: Hispanics/Latinos in the United States are less aware of their cholesterol levels and have a higher burden of associated adverse cardiovascular and cerebrovascular outcomes than non-Latino whites. Investigations of the associations between cholesterol levels and cognition in this population have often occurred within the context of metabolic syndrome and are limited to select lipids despite the fact that triglycerides (TGs) may be more relevant to the health of Hispanics/Latinos. METHODS: Baseline data from the Hispanic Community Health Study/Study of Latinos, collected from 2008 to 2011, was used to investigate the associations of lipid levels (i.e., TG, total cholesterol, TC; low-density and high-density lipoprotein cholesterol, LDL-C and HDL-C) with cognition (i.e., learning, memory, verbal fluency, and digit symbol substitution, DSS), adjusting for relevant confounders. RESULTS: In 7413 participants ages 45 to 74 years from Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American backgrounds, separate, fully adjusted linear regression models revealed that TG levels were inversely associated with DSS performance; however, this relationship was no longer significant once additional cardiovascular disease risk factors were added to the model (p = .06). TC and LDL-C levels (separately) were positively associated with learning and verbal fluency regardless of adjustments (p-values < .05). Separate analyses investigating the effect modification by background and sex revealed a particularly robust association between TC levels and DSS performance for Puerto Ricans and Central Americans (albeit in opposite directions) and an inverse relationship between TG levels and DSS performance for women (p-values < .02). CONCLUSIONS: It is important to consider individual lipid levels and demographic characteristics when investigating associations between cholesterol levels and cognition in Hispanics/Latinos.

Associations between perceived neighborhood environment and cognitive function among middle-aged and older women and men: Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study.

PURPOSE: To examine cross-sectional associations between perceived neighborhood environment and cognitive function among middle-aged and older Hispanic/Latino women and men. METHODS: Data from the Hispanic Community Health Study/Study of Latinos (2008-2011) and its Sociocultural Ancillary Study (2009-2010) were used. Participants were Hispanic/Latino women (n = 1812) and men (n = 1034) aged 45-74 years. Survey-weighted linear regression models were used to examine associations between self-reported perceived neighborhood environment (i.e., neighborhood social cohesion and problems categorized as quintiles, and neighborhood safety from crime categorized as low, medium, or high) with cognitive function (i.e., global cognition, verbal learning, memory, verbal fluency, and processing speed scores) in women and men. Final model adjusted for age, Hispanic/Latino background, language, field site, household income, education, years lived in neighborhood, and depressive symptoms. RESULTS: Women in the lowest quintile of perceived neighborhood problems (vs. highest quintile) had higher global cognition (ß 0.48, 95% CI 0.03, 0.94, p trend 0.229) and memory scores (0.60, 95% CI 0.11, 1.09, p trend: 0.060). Women in the highest quintile of perceived neighborhood social cohesion (vs. lowest quintile) had lower global cognition (ß - 0.56, 95% CI - 1.02, - 0.09, p trend 0.004), verbal learning (B - 1.01, 95% CI - 2.00, - 0.03, p trend 0.015), verbal fluency (B - 2.00, 95% CI - 3.83, - 0.16, p trend 0.006), and processing speed (B - 2.11, 95% CI - 3.87, - 0.36, p trend 0.009). There was no association between perceived neighborhood safety from crime and cognition among women, or between any perceived neighborhood environment measure and cognition among men. CONCLUSIONS: Middle-aged and older Hispanic/Latina women living in neighborhoods with the lowest perceived problems had higher global cognition and memory. Women living in neighborhoods with the highest perceived social cohesion had lower global cognition, verbal learning, verbal fluency, and processing speed.

Seroprevalence of HPV serotypes 6, 11, 16 and 18 in unvaccinated children from Mexico City.

Data regarding humoral immunity against HPV infection are scarce. Most analyses focus on the identification of viruses on mucous membranes and primarily refer to women of reproductive age. The aim of this work was to estimate the seroprevalence of antibodies against HPV serotypes 6, 11, 16 and 18 among unvaccinated boys living in Mexico City. A cross-sectional study of 257 male students from 48 public primary schools in Mexico City, whose ages fluctuated between 9 and 14 years, was carried out. Immunological status was assessed by applying the competitive Luminex Immunoassay of HPV (cLIA). Among the study population, we initially found that 38.52% (n = 99) of the children tested positive against one or more of the HPV 6, 11, 16 and/or 18 serotypes. The most commonly found serotype was isolated HPV 18 or in combination with other serotypes (22% and 31%, respectively), followed by HPV 6 with frequencies of 4.7% and 11%, respectively; however, lower frequencies were estimated for HPV 16 (2%; 6%) and isolated HPV 11, 4%. If a second set of cut-off points for seropositivity is applied, the overall prevalence for any serotype is reduced to 15.2%. As it appears that a significant sector of the study population has had basal contact with an HPV serotype, we recommend considering the possibility of vaccination against HPV at earlier ages.

Multiple metal exposures and metabolic syndrome: A cross-sectional analysis of the National Health and Nutrition Examination Survey 2011-2014.

BACKGROUND: Epidemiologic studies suggest toxic metals are linked with diabetes and cardiovascular disease, while experimental studies indicate nutritionally essential metals are involved in the metabolism of macronutrients and defense against oxidative stress. OBJECTIVES: We sought to evaluate how essential and toxic metals are cross-sectionally related to metabolic syndrome, a clustering of cardiometabolic conditions. METHODS: Using data from the 2011-2014 National Health and Nutrition Examination Survey (n = 1088), we characterized metal concentrations as measured in spot urine (arsenic, cadmium, and inorganic/elemental mercury), whole blood (manganese, lead, methylmercury, and selenium), and serum (copper and zinc) samples. Principal component analysis was performed to derive patterns of exposures. Metabolic syndrome was defined according to the 2009 Joint Scientific Statement as the presence of ≥ 3 of the following conditions: high blood pressure, high triglycerides, low HDL cholesterol, high fasting glucose, and abdominal obesity. RESULTS: After adjustment for potential confounders, prevalence ratios for metabolic syndrome comparing the highest to the lowest quartiles were 1.41 (95% CI: 1.18-1.67) for the arsenic-inorganic/elemental mercury pattern, 0.95 (0.78-1.16) for the methylmercury-manganese pattern, 0.73 (0.57-0.94) for the cadmium-lead pattern, 0.91 (0.76-1.10) for the copper pattern, and 1.36 (1.13-1.63) for the selenium-zinc pattern. The positive associations observed for the arsenic-inorganic/elemental mercury pattern were due to an elevated prevalence of high blood pressure, low HDL cholesterol, and high triglycerides among those with greater exposures. Associations for the selenium-zinc pattern were driven by a positive relationship with high triglycerides. Greater lead-cadmium co-exposures were related to a lower prevalence of dyslipidemia and abdominal obesity. CONCLUSIONS: These cross-sectional findings suggest both toxic and essential metal exposures may contribute to cardiometabolic health, but need to be confirmed with prospective data.

Implications of standardization of serum 25-hydroxyvitamin D data for the evaluation of vitamin D status in Germany, including a temporal analysis.

BACKGROUND: Comparability of 25-hydroxyvitamin D (25(OH)D) measurements is hampered by method-related differences in measurement values. International standardization of laboratory assays has been suggested to solve this problem. METHODS: As part of the European Commission-funded project 'Food-based solutions for optimal vitamin D nutrition and health through the life cycle' (ODIN), original measurements of serum 25(OH)D of three German national health surveys conducted between 1998 and 2011 have been standardized retrospectively. In these representative population-based samples including persons aged between 1 and 79 years, the original 25(OH)D values were compared with those after standardization. Mean values and prevalences of vitamin D deficiency, insufficiency, and sufficiency (25(OH)D levels < 30, 30- < 50, and > =50 nmol/l, respectively) were calculated by sex and age groups based on original and standardized 25(OH)D data. RESULTS: In comparison to the original 25(OH)D levels, the standardized levels showed higher means overall and in age- and sex-specific analyses. After standardization, the prevalence of vitamin D deficiency was lower in all surveys while the prevalence of vitamin D sufficiency was higher. Nevertheless, even after standardization ~ 15% of adults and 12.5% of children had serum 25(OH)D levels < 30 nmol/l. Thus, the proportion of deficient vitamin D levels in the German population is still considerable. CONCLUSIONS: The use of standardization of 25(OH)D levels has a substantial impact on estimates of the vitamin D status in Germany. Since clinical diagnostic, therapeutic and public health decision-making require valid and comparable data, standardization and calibration of commercial, clinical and research laboratory assays for 25(OH)D measurement should become common practice. Until then, researchers, health practitioners and policy makers should be aware of the peculiarities of the measurement methods when comparing and interpreting 25(OH)D levels.

The Reverse J-Shaped Association Between Serum Total 25-Hydroxyvitamin D Concentration and All-Cause Mortality: The Impact of Assay Standardization.

We evaluated the impact of standardizing the originally measured serum total 25-hydroxyvitamin D (25(OH)D) values from Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994) on the association between 25(OH)D and rate of all-cause mortality. Values were standardized to the gold-standard laboratory method. Follow-up from 1990-2006 consisted of 15,099 participants aged at least 20 years at baseline, among whom there were 3,784 deaths. Relative risk of death was adjusted for age, sex, race/ethnicity, and season using Poisson regression. Results were obtained for eight 25(OH)D (nmol/L) categories: <20 nmol/L, 20-29 nmol/L, 30-39 nmol/L, 40-49 nmol/L, 50-59 nmol/L, 60-74 nmol/L, 75-99 nmol/L (reference), and ≥100 nmol/L. Assay standardization dramatically shifted original 25(OH)D values toward zero. Accordingly, risk ≥120 nmol/L could not be evaluated (i.e., n = 7 and ndeaths = 2). Relative risk (95% confidence interval (CI)) <40 nmol/L remained significant (30-39 nmol/L: relative risk (RR) = 1.4 (95% CI: 1.1, 1.6); 20-29 nmol/L: RR = 1.6 (95% CI: 1.3, 1.9), and <20 nmol/L: RR = 2.1 (95% CI: 1.6, 2.7). However, adjusted relative risk estimates for 25(OH)D levels ≥40 nmol/L were no longer significant (40-49 nmol/L: RR = 1.2 (95% CI: 0.99, 1.4); 50-59 nmol/L: RR = 1.2 (95% CI: 1.04, 1.4); 60-74 nmol/L: RR = 1.1 (95% CI: 0.94, 1.2); 75-99 nmol/L: RR = 1.0 (referent), and ≥100 nmol/L: RR = 1.1 (95% CI: 0.6, 2.1). In summary, after standardization, risk of death from all causes increased with decreasing 25(OH)D <40 nmol/L, while there was no association with values in categories between 40 nmol/L and 120 nmol/L.

Development of an Improved Standard Reference Material for Vitamin D Metabolites in Human Serum.

The National Institute of Standards and Technology (NIST) has developed Standard Reference Material (SRM) 972a Vitamin D Metabolites in Frozen Human Serum as a replacement for SRM 972, which is no longer available. SRM 972a was developed in collaboration with the National Institutes of Health's Office of Dietary Supplements. In contrast to the previous reference material, three of the four levels of SRM 972a are composed of unmodified human serum. This SRM has certified and reference values for the following 25-hydroxyvitamin D [25(OH)D] species: 25(OH)D2, 25(OH)D3, and 3-epi-25(OH)D3. The value assignment and certification process included three isotope-dilution mass spectrometry approaches, with measurements performed at NIST and at the Centers for Disease Control and Prevention (CDC). The value assignment methods employed have been modified from those utilized for the previous SRM, and all three approaches now incorporate chromatographic resolution of the stereoisomers, 25(OH)D3 and 3-epi-25(OH)D3.

Cardiovascular risk status of Afro-origin populations across the spectrum of economic development: findings from the Modeling the Epidemiologic Transition Study.

BACKGROUND: Cardiovascular risk factors are increasing in most developing countries. To date, however, very little standardized data has been collected on the primary risk factors across the spectrum of economic development. Data are particularly sparse from Africa. METHODS: In the Modeling the Epidemiologic Transition Study (METS) we examined population-based samples of men and women, ages 25-45 of African ancestry in metropolitan Chicago, Kingston, Jamaica, rural Ghana, Cape Town, South Africa, and the Seychelles. Key measures of cardiovascular disease risk are described. RESULTS: The risk factor profile varied widely in both total summary estimates of cardiovascular risk and in the magnitude of component factors. Hypertension ranged from 7% in women from Ghana to 35% in US men. Total cholesterol was well under 200 mg/dl for all groups, with a mean of 155 mg/dl among men in Ghana, South Africa and Jamaica. Among women total cholesterol values varied relatively little by country, following between 160 and 178 mg/dl for all 5 groups. Levels of HDL-C were virtually identical in men and women from all study sites. Obesity ranged from 64% among women in the US to 2% among Ghanaian men, with a roughly corresponding trend in diabetes. Based on the Framingham risk score a clear trend toward higher total risk in association with socioeconomic development was observed among men, while among women there was considerable overlap, with the US participants having only a modestly higher risk score. CONCLUSIONS: These data provide a comprehensive estimate of cardiovascular risk across a range of countries at differing stages of social and economic development and demonstrate the heterogeneity in the character and degree of emerging cardiovascular risk. Severe hypercholesterolemia, as characteristic in the US and much of Western Europe at the onset of the coronary epidemic, is unlikely to be a feature of the cardiovascular risk profile in these countries in the foreseeable future, suggesting that stroke may remain the dominant cardiovascular event.

National Estimates of Serum Total 25-Hydroxyvitamin D and Metabolite Concentrations Measured by Liquid Chromatography-Tandem Mass Spectrometry in the US Population during 2007-2010.

BACKGROUND: The 2007-2010 NHANES provides the first US nationally representative serum 25-hydroxyvitamin D [25(OH)D] concentrations measured by standardized liquid chromatography-tandem mass spectrometry. OBJECTIVE: We describe patterns for total 25(OH)D and individual metabolites in persons aged ≥1 y stratified by race-ethnicity and grouped by demographic, intake, physiologic, and lifestyle variables. METHODS: We measured 25-hydroxycholecalciferol [25(OH)D3], 25-hydroxyergocalciferol [25(OH)D2], and C3-epimer of 25(OH)D3 [C3-epi-25(OH)D3] in serum samples (n = 15,652) from the 2007-2010 cross-sectional NHANES [total 25(OH)D = 25(OH)D3 + 25(OH)D2]. RESULTS: Concentrations (median, detection rate) of 25(OH)D3 (63.6 nmol/L, 100%) and C3-epi-25(OH)D3 (3.40 nmol/L, 86%) were generally detectable; 25(OH)D2 was detectable in 19% of the population. Total 25(OH)D, 25(OH)D3, and C3-epi-25(OH)D3 displayed similar demographic patterns and were strongly correlated (Spearman's r > 0.70). Concentrations of 25(OH)D2 (90th percentile) were much higher in persons aged ≥60 y (17.3 nmol/L) than in younger age groups (≤4.88 nmol/L). We noted significant race-ethnicity differences in mean total 25(OH)D [non-Hispanic blacks (NHBs), Hispanics, and non-Hispanic whites (NHWs): 46.6, 57.2, and 75.2 nmol/L, respectively] and in the prevalence of total 25(OH)D <30 nmol/L overall (24% of NHBs, 6.4% of Hispanics, and 2.3% of NHWs) as well as stratified by season (winter months: 30% of NHBs, 7.5% of Hispanics, and 3.8% of NHWs; summer months: 17% of NHBs, 4.4% of Hispanics, and 1.6% of NHWs). Persons with higher vitamin D intakes (diet, supplements, or both) and those examined during May-October had significantly higher total 25(OH)D. Significant race-ethnicity interactions in a multiple linear regression model confirmed the necessity of providing race-ethnicity-specific estimates of total 25(OH)D. CONCLUSIONS: Race-ethnicity differences in the prevalence of low total 25(OH)D remained strong even after adjustment for season to account for the NHANES design imbalance between season, latitude, and race-ethnicity. The strong correlation between C3-epi-25(OH)D3 and 25(OH)D3 may be because the epimer is a metabolite of 25(OH)D3. The presence of 25(OH)D2 mainly in older persons is likely a result of high-dose prescription vitamin D2.

The social patterning of risk factors for noncommunicable diseases in five countries: evidence from the modeling the epidemiologic transition study (METS).

BACKGROUND: Associations between socioeconomic status (SES) and risk factors for noncommunicable diseases (NCD-RFs) may differ in populations at different stages of the epidemiological transition. We assessed the social patterning of NCD-RFs in a study including populations with different levels of socioeconomic development. METHODS: Data on SES, smoking, physical activity, body mass index, blood pressure, cholesterol and glucose were available from the Modeling the Epidemiologic Transition Study (METS), with about 500 participants aged 25-45 in each of five sites (Ghana, South Africa, Jamaica, Seychelles, United States). RESULTS: The prevalence of NCD-RFs differed between these populations from five countries (e.g., lower prevalence of smoking, obesity and hypertension in rural Ghana) and by sex (e.g., higher prevalence of smoking and physical activity in men and of obesity in women in most populations). Smoking and physical activity were associated with low SES in most populations. The associations of SES with obesity, hypertension, cholesterol and elevated blood glucose differed by population, sex, and SES indicator. For example, the prevalence of elevated blood glucose tended to be associated with low education, but not with wealth, in Seychelles and USA. The association of SES with obesity and cholesterol was direct in some populations but inverse in others. CONCLUSIONS: In conclusion, the distribution of NCD-RFs was socially patterned in these populations at different stages of the epidemiological transition, but associations between SES and NCD-RFs differed substantially according to risk factor, population, sex, and SES indicator. These findings emphasize the need to assess and integrate the social patterning of NCD-RFs in NCD prevention and control programs in LMICs.

Significance of serum 24,25-dihydroxyvitamin D in the assessment of vitamin D status: a double-edged sword?

BACKGROUND: 24,25-Dihydroxyvitamin D [24,25(OH)2D] in serum may be both a nuisance and nutritionally valuable. METHODS: We investigated the impact of 24,25(OH)2D3 on the performance of commercially available immunoassays for serum total 25-hydroxyvitamin D [25(OH)D] using (a) serum from a nationally representative sample of adults, (b) serum from a spiking experiment, and (c) data from the UK Vitamin D External Quality Assurance Scheme (DEQAS). We also investigated the utility of the serum ratio of 24,25(OH)2D3 to 25(OH)D as an index of inactivation and of response to vitamin D supplementation using randomized controlled trial (RCT) data. Measurement of 24,25(OH)2D in sera by a LC-MS/MS method allowed for an investigation of its impact on immunoassay-derived serum 25(OH)D values as well as its clinical utility. We report data from a nationally representative sample of adults, a recent vitamin D RCT in older adults, and DEQAS. RESULTS: 24,25(OH)2D3 contributed to the positive bias observed in some immunoassays relative to LC-MS/MS-derived estimates for total 25(OH)D. A spiking experiment showed that the degree of cross-reactivity with 24,25(OH)2D was high and may underpin this positive bias. Adjustment for 24,25(OH)2D3 concentration brought estimates closer to true values. Data from the vitamin D RCT showed that the ratio of 24,25(OH)2D3 to 25(OH)D was associated with serum 25(OH)D3 and with response of serum 25(OH)D to vitamin D supplementation. CONCLUSIONS: Our findings highlight that the effect of 24,25(OH)2D3 in serum is a double-edged sword-an interferent for some immunoassays, yet potentially informative of nutritional status.