Applying inappropriate cutoffs leads to misinterpretation of folate status in the US population.

BACKGROUND: Folate cutoffs for risk of deficiency compared with possible deficiency were originally derived differently (experimental compared with epidemiologic data), and their interpretations are different. The matching of cutoffs derived from one assay with population-based data derived from another assay requires caution. OBJECTIVE: We assessed the extent of folate-status misinterpretation with the use of inappropriate cutoffs. DESIGN: In the cross-sectional NHANES, serum and red blood cell (RBC) folate were first measured with the use of a radioprotein-binding assay (RPBA) (1988-2006) and, afterwards, with the use of a microbiologic assay (2007-2010). We compared prevalence estimates for assay-matched cutoffs (e.g., with the use of an RPBA cutoff with RPBA data) and assay-mismatched cutoffs (e.g., with the use of microbiologic assay cutoff with RPBA data) for risk of deficiency on the basis of megaloblastic anemia as a hematologic indicator in persons ≥4 y of age (e.g., serum folate concentration <7 nmol/L and RBC folate concentration <305 nmol/L derived with the use of a microbiologic assay), possible deficiency on the basis of rising homocysteine as a metabolic indicator in persons ≥4 y of age (e.g., serum folate concentration <10 nmol/L and RBC folate concentration <340 nmol/L derived with the use of an RPBA), and insufficiency on the basis of elevated risk of neural tube defects in women 12-49 y old (e.g., RBC folate concentration <906 nmol/L derived with the use of a microbiologic assay). RESULTS: Pre-folic acid fortification (1988-1994), risks of deficiency for assay-matched compared with assay-mismatched cutoffs were 5.6% compared with 16% (serum folate), respectively, and 7.4% compared with 28% (RBC folate), respectively; risks declined postfortification (1999-2006) to <1% compared with <1% (serum folate), respectively, and to <1% compared with 2.5% (RBC folate), respectively. Prefortification (1988-1994), risks of possible deficiency for assay-matched compared with assay-mismatched cutoffs were 35% compared with 56% (serum folate), respectively, and 37% compared with 84% (RBC folate), respectively; risks declined postfortification (1999-2006) to 1.9% compared with 7.0% (serum folate), respectively, and to 4.8% compared with 53% (RBC folate), respectively. Postfortification (2007-2010), risks of insufficiency were 3% (assay matched) compared with 39% (assay mismatched), respectively. CONCLUSIONS: The application of assay-mismatched cutoffs leads to a misinterpretation of folate status. This confusion likely applies to clinical assays because no comparability data are available, to our knowledge.

Total, free, and complexed prostate-specific antigen levels among US men, 2007-2010.

BACKGROUND: Screening for prostate cancer using prostate-specific antigen (PSA) is common. Prostate cancer has been associated with higher total PSA (tPSA), lower free PSA (fPSA), lower percent free PSA (%fPSA), and higher complexed PSA (cPSA). METHODS: Total, free and complexed PSAs were performed on 3251 men ≥40years in the 2007-2010 National Health and Nutrition Examination Survey. Distributions of the PSA tests were examined by age, race and ethnicity, and body mass index (BMI) groups. Percentages of men at PSA thresholds were examined. RESULTS: Total PSA geometric mean was 0.96µg/l among men aged ≥40years and increased from 0.74µg/l for men 40-49years, to 1.82µg/l for men 80years and older. Non-Hispanic Whites had lower age-adjusted mean tPSA (1.03µg/l) and cPSA (0.56µg/l) than non-Hispanic Blacks (tPSA 1.25µg/l and cPSA 0.72µg/l). Obese men had lower age-adjusted mean total, free and complexed PSAs (0.94, 0.27, and 0.51µg/l, respectively) than men with normal BMI (tPSA 1.21, fPSA 0.32, and cPSA 0.68µg/l, respectively). CONCLUSION: Total, free and complexed PSAs increased with age; tPSA and cPSAs were highest in non-Hispanic Blacks; and total, free, and complexed PSAs were lowest in obese men.

Folate status and concentrations of serum folate forms in the US population: National Health and Nutrition Examination Survey 2011-2.

Serum and erythrocyte (RBC) total folate are indicators of folate status. No nationally representative population data exist for folate forms. We measured the serum folate forms (5-methyltetrahydrofolate (5-methylTHF), unmetabolised folic acid (UMFA), non-methyl folate (sum of tetrahydrofolate (THF), 5-formyltetrahydrofolate (5-formylTHF), 5,10-methenyltetrahydrofolate (5,10-methenylTHF)) and MeFox (5-methylTHF oxidation product)) by HPLC-MS/MS and RBC total folate by microbiologic assay in US population ≥ 1 year (n approximately 7500) participating in the National Health and Nutrition Examination Survey 2011-2. Data analysis for serum total folate was conducted including and excluding MeFox. Concentrations (geometric mean; detection rate) of 5-methylTHF (37·5 nmol/l; 100 %), UMFA (1·21 nmol/l; 99·9 %), MeFox (1·53 nmol/l; 98·8 %), and THF (1·01 nmol/l; 85·2 %) were mostly detectable. 5-FormylTHF (3·6 %) and 5,10-methenylTHF (4·4 %) were rarely detected. The biggest contributor to serum total folate was 5-methylTHF (86·7 %); UMFA (4·0 %), non-methyl folate (4·7 %) and MeFox (4·5 %) contributed smaller amounts. Age was positively related to MeFox, but showed a U-shaped pattern for other folates. We generally noted sex and race/ethnic biomarker differences and weak (Spearman's r< 0·4) but significant (P< 0·05) correlations with physiological and lifestyle variables. Fasting, kidney function, smoking and alcohol intake showed negative associations. BMI and body surface area showed positive associations with MeFox but negative associations with other folates. All biomarkers showed significantly higher concentrations with recent folic acid-containing dietary supplement use. These first-time population data for serum folate forms generally show similar associations with demographic, physiological and lifestyle variables as serum total folate. Patterns observed for MeFox may suggest altered folate metabolism dependent on biological characteristics.

Total and high-density lipoprotein cholesterol in adults: National Health and Nutrition Examination Survey, 2011-2012.

High levels of total cholesterol and low levels of high-density lipoprotein (HDL) cholesterol (the "good cholesterol") are risk factors for coronary heart disease (1­5). To identify persons who may be at risk for developing coronary heart disease, adults are advised to have their cholesterol checked at least once every 5 years (i.e., to be screened for cholesterol) (6). A previous study reported declining trends in the percentage of adults with high total cholesterol during 1999­2010 (7). This report presents estimates of the percentages of adults aged 20 and over with high total cholesterol, low HDL cholesterol, and screened for cholesterol, based on data from 2011­2012, and compares them with corresponding estimates from 2009­2010. Analysis is based on measured cholesterol only and does not take into account whether lipid-lowering medications were taken.

Assessment of iron status in US pregnant women from the National Health and Nutrition Examination Survey (NHANES), 1999-2006.

BACKGROUND: Total body iron calculated from serum ferritin and soluble transferrin receptor concentrations allows for the evaluation of the full range of iron status. OBJECTIVE: We described the distribution of total body iron and the prevalence of iron deficiency (ID) on the basis of total body iron in US pregnant women. DESIGN: We examined data from the National Health and Nutrition Examination Survey (NHANES) in 1999-2006 for 1171 pregnant women. RESULTS: ID prevalence (±SE) in US pregnant women, which was defined as total body iron <0 mg/kg, was 18.0 ± 1.4%. Pregnant women in the first trimester had a higher mean total body iron than did pregnant women in the second or third trimesters. ID prevalence in pregnant women increased significantly with each trimester (6.9 ± 2.2%, 14.3 ± 2.1%, and 29.5 ± 2.7% in the first, second, and third trimesters, respectively). Pregnant women with parity ≥2 had the lowest mean total body iron and the highest prevalence of ID compared with values for pregnant women with parity of 0 or 1. The ID prevalence in non-Hispanic white pregnant women was significantly lower than in Mexican American or non-Hispanic black pregnant women. The mean total body iron and the prevalence of ID did not differ by educational level or by family income. CONCLUSIONS: To our knowledge, these are the first data on total body iron distributions for a representative sample of US pregnant women. Low total body iron is more prevalent in pregnant women in the second or third trimesters, in Mexican American pregnant women, in non-Hispanic black pregnant women, and in women with parity ≥2.

Serum vitamin C and the prevalence of vitamin C deficiency in the United States: 2003-2004 National Health and Nutrition Examination Survey (NHANES).

BACKGROUND: Vitamin C (ascorbic acid) may be the most important water-soluble antioxidant in human plasma. In the third National Health and Nutrition Examination Survey (NHANES III, 1988-1994), approximately 13% of the US population was vitamin C deficient (serum concentrations <11.4 micromol/L). OBJECTIVE: The aim was to determine the most current distribution of serum vitamin C concentrations in the United States and the prevalence of deficiency in selected subgroups. DESIGN: Serum concentrations of total vitamin C were measured in 7277 noninstitutionalized civilians aged > or =6 y during the cross-sectional, nationally representative NHANES 2003-2004. The prevalence of deficiency was compared with results from NHANES III. RESULTS: The overall age-adjusted mean from the square-root transformed (SM) concentration was 51.4 micromol/L (95% CI: 48.4, 54.6). The highest concentrations were found in children and older persons. Within each race-ethnic group, women had higher concentrations than did men (P < 0.05). Mean concentrations of adult smokers were one-third lower than those of nonsmokers (SM: 35.2 compared with 50.7 micromol/L and 38.6 compared with 58.0 micromol/L in men and women, respectively). The overall prevalence (+/-SE) of age-adjusted vitamin C deficiency was 7.1 +/- 0.9%. Mean vitamin C concentrations increased (P < 0.05) and the prevalence of vitamin C deficiency decreased (P < 0.01) with increasing socioeconomic status. Recent vitamin C supplement use or adequate dietary intake decreased the risk of vitamin C deficiency (P < 0.05). CONCLUSIONS: In NHANES 2003-2004, vitamin C status improved, and the prevalence of vitamin C deficiency was significantly lower than that during NHANES III, but smokers and low-income persons were among those at increased risk of deficiency.

Assessment of iron deficiency in US preschool children and nonpregnant females of childbearing age: National Health and Nutrition Examination Survey 2003-2006.

BACKGROUND: A new index to determine body iron promises a simpler approach to monitoring iron deficiency (ID) prevalence. OBJECTIVE: Our objective was to compare ID defined as body iron <0 mg/kg and calculated from the log ratio of transferrin receptor to ferritin (the body iron model) to ID defined as >/=2 of 3 abnormal concentrations in ferritin, transferrin saturation, or erythrocyte protoporphyrin (the ferritin model). DESIGN: We used measures of iron status and inflammation from 486 children aged 1-2 y, 848 children aged 3-5 y, and 3742 nonpregnant females aged 12-49 y from the National Health and Nutrition Examination Survey 2003-2006. RESULTS: ID prevalences (+/-SE) based on the body iron model in children (1-2 and 3-5 y) and in females (12-19 and 20-49 y) were 14.4 +/- 1.9%, 3.7 +/- 0.8%, 9.3 +/- 1.0%, and 9.2 +/- 1.6%, respectively. ID prevalences based on the ferritin model in children (3-5 y) and females (12-19 and 20-49 y) were 4.5 +/- 0.9%, 15.6 +/- 1.2%, and 15.7 +/- 0.8%, respectively. The kappa statistics for agreement between the 2 models were 0.5-0.7. Among females (12-49 y) the positive predictive values of ID based on the body iron model and the ferritin model for identifying anemia were 43 +/- 3% and 30 +/- 2%, respectively, whereas negative predictive values did not differ. C-reactive protein was elevated in 28.8 +/- 3.1% of females with ID by the ferritin model but not by the body iron model and in 0% of persons with ID by the body iron model but not by the ferritin model. CONCLUSIONS: The agreement between the 2 indexes was fair to good. Among females, the body iron model produced lower estimates of ID prevalence, better predicted anemia, and appeared to be less affected by inflammation than the ferritin model.

High serum total cholesterol--an indicator for monitoring cholesterol lowering efforts: U.S. adults, 2005-2006.

Elevated serum total cholesterol is a major and modifiable risk factor for heart disease, the lead-ing cause of death in the United States (1,2). Reducing mean total serum cholesterol levels among adults to less than 200 mg/dL and reducing the proportion who have levels of 240 mg/dL or higher to less than 17% are national Healthy People 2010 objectives (3). Age-adjusted mean serum cholesterol levels among adults aged 20-74 years declined from 222 mg/dL in 1960-1962 to 203 mg/dL in 1999-2002 (4). Among adults aged 20 years and older, the percent of the population with high serum total cholesterol levels (240 mg/dL or higher) declined from 20% during 1988-1994 to 17% during 1999-2002 (4). In individual patients, a high serum total cholesterol level indicates a potential increased risk for heart disease, but further evaluation of other risk factors and the specific components of cholesterol provide the basis for determining the need for initiating therapeutic lifestyle changes or treatment with medication (5). Low-density-lipoprotein (LDL) is the cholesterol component associated with arterial blockage, and it is the primary clinical target for cholesterol management. High-density-lipoprotein (HDL) may help to protect individuals from developing heart disease. In populations, comparisons of total cholesterol levels over time can show if population groups are experiencing improvement in cholesterol levels, and knowledge of trends in levels of total cholesterol can help identify subgroups where additional prevention efforts may be needed.

Total, free, and percent free prostate-specific antigen levels among U.S. men, 2001-04.

OBJECTIVE: Screening for prostate cancer using prostate-specific antigen (PSA) tests is common but remains controversial. Total PSA using thresholds of 4.0 and 2.5 ng/mL has been used for screening men. In addition, the percent free PSA (free PSA/total PSA x 100%) using thresholds of less than 25% and 15% have been proposed for use in screening for prostate cancer in conjunction with the total PSA. The distributions of total PSA, free PSA, and percent free PSA, which vary with age and race-ethnicity among American men, would help determine the burden of screening using different thresholds of PSA tests. METHODS: PSA tests were performed on serum samples from men age 40 years and older (n = 2,546) who participated in the 2001-04 National Health and Nutrition Examination Survey (NHANES). Total, free and percent free PSA were estimated for Mexican American, non-Hispanic white, and non-Hispanic black men. RESULTS: About 6.2%, (95% confidence interval, 95% CI: 5.2-7.2%), corresponding to an estimated 3.6 million (95% CI: 3.0-4.2 million) men 40 years of age and older, had a total PSA of greater than or equal to 4.0 ng/mL. Approximately 3.6% (95% CI: 1.8-6.2%) of Mexican American men, 6.2% (95% CI: 5.1-7.6%) of non-Hispanic white men, and 7.8% (95% CI: 5.2-11.1 ) of non-Hispanic black men had total PSA of 4.0 ng/mL or more. Approximately 13.1 (95% CI: 11.7-14.5%) of men 40 years of age and older had total PSA greater than or equal to 2.5 ng/mL. For men with total PSA less than 2.5 ng/mL, 23.1% (95% CI: 21.0-25.3%) had a percent free PSA between 15% and 25%, and 5.0% had free PSA (95% CI: 3.9-6.4%) less than or equal to 15%. CONCLUSIONS: The effect of lowering the total PSA thresholds increases the number of U.S. men who would be referred for screening for prostate cancer. Total and free PSA increased with age in Mexican American, non-Hispanic white, and non-Hispanic black men. Information about the distribution of total, free, and percent free PSA will help guide public health policy in screening for prostate cancer.