The association of nativity/length of residence and cardiovascular disease risk factors in the United States.

Differences by nativity status for cardiovascular disease (CVD) risk factors have been previously reported. Recent research has focused on understanding how other acculturation factors, such as length of residence, affect health behaviors and outcomes. This study examines the association between CVD risk factors and nativity/length of US residence. Using cross-sectional data from 15,965 adults in the 2011-2016 National Health and Nutrition Examination Surveys (analyzed in 2018), prevalence ratios and predicted marginals from logistic regression models are used to estimate associations of CVD risk factors (i.e., hypertension, hypercholesterolemia, diabetes, overweight/obesity and smoking) with nativity/length of residence (<15 years, ≥15 years) in the US. In sex-, age-, education- and race and Hispanic origin- adjusted analyses, a higher percentage of US (50 states and District of Columbia) born adults (86.4%) had ≥1 CVD risk factor compared to non-US born residents in the US <15 years (80.1%) but not ≥15 years (85.1%). Compared to US born counterparts, regardless of length of residence, hypertension overall and smoking among non-Hispanic white and Hispanic adults were lower among non-US born residents. Overweight/obesity overall and diabetes among Hispanic adults were lower among non-US born residents in the US <15 years. In contrast, non-US born non-Hispanic Asian residents in the US <15 years had higher prevalence of diabetes. Non-US born adults were less likely to have most CVD risk factors compared to US born adults regardless of length of residence, although, for smoking and diabetes this pattern differed by race and Hispanic origin.

Prevalence of Obesity Among Youths by Household Income and Education Level of Head of Household - United States 2011-2014.

Obesity prevalence varies by income and education level, although patterns might differ among adults and youths (1-3). Previous analyses of national data showed that the prevalence of childhood obesity by income and education of household head varied across race/Hispanic origin groups (4). CDC analyzed 2011-2014 data from the National Health and Nutrition Examination Survey (NHANES) to obtain estimates of childhood obesity prevalence by household income (≤130%, >130% to ≤350%, and >350% of the federal poverty level [FPL]) and head of household education level (high school graduate or less, some college, and college graduate). During 2011-2014 the prevalence of obesity among U.S. youths (persons aged 2-19 years) was 17.0%, and was lower in the highest income group (10.9%) than in the other groups (19.9% and 18.9%) and also lower in the highest education group (9.6%) than in the other groups (18.3% and 21.6%). Continued progress is needed to reduce disparities, a goal of Healthy People 2020. The overall Healthy People 2020 target for childhood obesity prevalence is <14.5% (5).

Trends in active transportation and associations with cardiovascular disease risk factors among U.S. adults, 2007-2016.

Active transportation (AT), or walking or bicycling for transportation, represents one way individuals can achieve recommended physical activity (PA) levels. This study describes AT prevalence and temporal trends, and examines associations between AT levels and measured CVD risk factors (hypertension, hypercholesterolemia, low high-density [HDL] cholesterol, diabetes, and obesity) among U.S. adults. National Health and Nutrition Examination Survey (NHANES) 2007-2016 data (analyzed in 2017) were used to conduct overall trend analyses of reported AT in a typical week [none (0-9 min/week); low (10-149 min/week); or high (≥150 min/week)]. Logistic regression was used to examine associations between AT level and each CVD risk factor from NHANES 2011-2016 (n = 13,943). Covariates included age, sex, race/Hispanic origin, education, income, smoking, survey cycle, non-transportation PA, and urbanization level. U.S. adults who engaged in high AT levels increased from 13.1% in 2007-2008 to 17.9% in 2011-2012, and then decreased to 10.6% in 2015-2016 (p for quadratic trend = 0.004). Over the same period, the quadratic trend for low AT was not significant. During 2011-2016, 14.3% of adults engaged in high AT, 11.4% in low AT, and 74.4% in no AT. High AT levels were associated with decreased odds of each CVD risk factor assessed, compared to no AT. Low AT (versus no AT) was associated with decreased odds of hypertension (aOR = 0.77, 95% CI 0.64, 0.91) and diabetes (aOR = 0.68, 95% CI 0.54, 0.85). AT prevalence among adults has fluctuated from 2007 to 2016. Despite favorable associations between AT and CVD risk factors, most U.S. adults do not engage in any AT.

Prevalence of Obesity Among Adults, by Household Income and Education - United States, 2011-2014.

Studies have suggested that obesity prevalence varies by income and educational level, although patterns might differ between high-income and low-income countries (1-3). Previous analyses of U.S. data have shown that the prevalence of obesity varied by income and education, but results were not consistent by sex and race/Hispanic origin (4). Using data from the National Health and Nutrition Examination Survey (NHANES), CDC analyzed obesity prevalence among adults (aged ≥20 years) by three levels of household income, based on percentage (≤130%, >130% to ≤350%, and >350%) of the federal poverty level (FPL) and individual education level (high school graduate or less, some college, and college graduate). During 2011-2014, the age-adjusted prevalence of obesity among adults was lower in the highest income group (31.2%) than the other groups (40.8% [>130% to ≤350%] and 39.0% [≤130%]). The age-adjusted prevalence of obesity among college graduates was lower (27.8%) than among those with some college (40.6%) and those who were high school graduates or less (40.0%). The patterns were not consistent across all sex and racial/Hispanic origin subgroups. Continued progress is needed to achieve the Healthy People 2020 targets of reducing age-adjusted obesity prevalence to <30.5% and reducing disparities (5).

Multivitamin-mineral use is associated with reduced risk of cardiovascular disease mortality among women in the United States.

BACKGROUND: Multivitamin-mineral (MVM) products are the most commonly used supplements in the United States, followed by multivitamin (MV) products. Two randomized clinical trials (RCTs) did not show an effect of MVMs or MVs on cardiovascular disease (CVD) mortality; however, no clinical trial data are available for women with MVM supplement use and CVD mortality. OBJECTIVE: The objective of this research was to examine the association between MVM and MV use and CVD-specific mortality among US adults without CVD. METHODS: A nationally representative sample of adults from the restricted data NHANES III (1988-1994; n = 8678; age ≥40 y) were matched with mortality data reported by the National Death Index through 2011 to examine associations between MVM and MV use and CVD mortality by using Cox proportional hazards models, adjusting for multiple potential confounders. RESULTS: We observed no significant association between CVD mortality and users of MVMs or MVs compared with nonusers; however, when users were classified by the reported length of time products were used, a significant association was found with MVM use of >3 y compared with nonusers (HR: 0.65; 95% CI: 0.49, 0.85). This finding was largely driven by the significant association among women (HR: 0.56; 95% CI: 0.37, 0.85) but not men (HR: 0.79; 95% CI: 0.44, 1.42). No significant association was observed for MV products and CVD mortality in fully adjusted models. CONCLUSIONS: In this nationally representative data set with detailed information on supplement use and CVD mortality data ∼20 y later, we found an association between MVM use of >3 y and reduced CVD mortality risk for women when models controlled for age, race, education, body mass index, alcohol, aspirin use, serum lipids, blood pressure, and blood glucose/glycated hemoglobin. Our results are consistent with the 1 available RCT in men, indicating no relation with MVM use and CVD mortality.

Serum carbon isotope values change in adults in response to changes in sugar-sweetened beverage intake.

Serum carbon isotope values [13C-to-12C serum carbon isotope ratio (δ(13)C)], which reflect consumption of corn- and cane-based foods, differ between persons consuming high and low amounts of sugar-sweetened beverages (SSBs). In this study, we determined whether serum δ(13)C changes in response to change in SSB intake during an 18-mo behavioral intervention trial. Data were from a subset of 144 participants from the PREMIER trial, a completed behavioral intervention (Maryland, 1998-2004). SSB intake was assessed using 2 24-h dietary recall interviews. Blinded serum samples were assayed for δ(13)C by natural abundance stable isotope mass spectroscopy. Multiple linear regression models with generalized estimating equations and robust variance estimation were used. At baseline, mean SSB intake was 13.8 ± 14.2 fl oz/d, and mean δ(13)C serum value was -19.3 ± 0.6 units per mil (designated ‰). A reduction of 12 oz (355 mL)/d SSB (equivalent to 1 can of soda per day) was associated with 0.17‰ (95% CI: 0.08‰, 0.25‰ P < 0.0001) reduction in serum δ(13)C values over 18 mo (equivalent to a 1% reduction in δ(13)C from baseline). After adjusting for potential confounders, a reduction of 12 oz/d SSB (equivalent to 1 can of soda per day), over an 18-mo period, was associated with 0.12‰ (95% CI: 0.01‰, 0.22‰ P = 0.025) reduction in serum δ(13)C. These findings suggest that serum δ(13)C can be used as a measure of dietary changes in SSB intake.

Demographic Diversity of Clinical Trials for Therapeutic Drug Products: A Systematic Review of Recently Published Articles, 2017-2022.

The US Food and Drug Administration (FDA) encourages the use of enrollment practices that will lead to clinical trials that reflect the population most likely to use the therapeutic product (drug or biologic), if approved. In doing so, the benefit-risk profile of the product may be assessed more completely and offer patients and their health care providers a better understanding of the drug profile and greater confidence in clinical trial results. The objective of this systematic review was to assess recent literature on the demographic diversity of clinical trial participants, describe the methods used in defining clinical trial diversity, and address knowledge gaps to enhance clinical trial diversity. Our literature search initially yielded 246 articles. After applying our eligibility criteria, we conducted a full-text review and analyzed the contents of the 28 remaining articles in our systematic review. Eleven (39%) of the 28 articles used a reference standard to compare the participation of populations in clinical trials to assess diversity. The majority of the 28 articles reported on adult participants; only 5 included pediatric populations. Most articles found that women and minority populations were underrepresented in clinical trials. Some articles proposed solutions to improve clinical trial diversity; however, several did not comment on clinical trial diversity. Despite a growing emphasis on demographic diversity in research, certain populations continue to be underrepresented in clinical trials. There is a need to standardize the definition of diversity in clinical trials. Future research into effective enrollment approaches and appropriate reference standards could improve demographic diversity.

Current Status and Future Directions: The Application of Artificial Intelligence/Machine Learning for Precision Medicine.

Technological innovations, such as artificial intelligence (AI) and machine learning (ML), have the potential to expedite the goal of precision medicine, especially when combined with increased capacity for voluminous data from multiple sources and expanded therapeutic modalities; however, they also present several challenges. In this communication, we first discuss the goals of precision medicine, and contextualize the use of AI in precision medicine by showcasing innovative applications (e.g., prediction of tumor growth and overall survival, biomarker identification using biomedical images, and identification of patient population for clinical practice) which were presented during the February 2023 virtual public workshop entitled "Application of Artificial Intelligence and Machine Learning for Precision Medicine," hosted by the US Food and Drug Administration (FDA) and University of Maryland Center of Excellence in Regulatory Science and Innovation (M-CERSI). Next, we put forward challenges brought about by the multidisciplinary nature of AI, particularly highlighting the need for AI to be trustworthy. To address such challenges, we subsequently note practical approaches, viz., differential privacy, synthetic data generation, and federated learning. The proposed strategies - some of which are highlighted presentations from the workshop - are for the protection of personal information and intellectual property. In addition, methods such as the risk-based management approach and the need for an agile regulatory ecosystem are discussed. Finally, we lay out a call for action that includes sharing of data and algorithms, development of regulatory guidance documents, and pooling of expertise from a broad-spectrum of stakeholders to enhance the application of AI in precision medicine.

Dynamic chromatin organization during foregut development mediated by the organ selector gene PHA-4/FoxA.

Central regulators of cell fate, or selector genes, establish the identity of cells by direct regulation of large cohorts of genes. In Caenorhabditis elegans, foregut (or pharynx) identity relies on the FoxA transcription factor PHA-4, which activates different sets of target genes at various times and in diverse cellular environments. An outstanding question is how PHA-4 distinguishes between target genes for appropriate transcriptional control. We have used the Nuclear Spot Assay and GFP reporters to examine PHA-4 interactions with target promoters in living embryos and with single cell resolution. While PHA-4 was found throughout the digestive tract, binding and activation of pharyngeally expressed promoters was restricted to a subset of pharyngeal cells and excluded from the intestine. An RNAi screen of candidate nuclear factors identified emerin (emr-1) as a negative regulator of PHA-4 binding within the pharynx, but emr-1 did not modulate PHA-4 binding in the intestine. Upon promoter association, PHA-4 induced large-scale chromatin de-compaction, which, we hypothesize, may facilitate promoter access and productive transcription. Our results reveal two tiers of PHA-4 regulation. PHA-4 binding is prohibited in intestinal cells, preventing target gene expression in that organ. PHA-4 binding within the pharynx is limited by the nuclear lamina component EMR-1/emerin. The data suggest that association of PHA-4 with its targets is a regulated step that contributes to promoter selectivity during organ formation. We speculate that global re-organization of chromatin architecture upon PHA-4 binding promotes competence of pharyngeal gene transcription and, by extension, foregut development.

Assessing consent for and response to health survey components in an era of falling response rates: National Health and Nutrition Examination Survey, 2011-2018.

Response rates for national population-based surveys have declined, including the National Health and Nutrition Examination Survey (NHANES). Declining response to the initial NHANES interview may impact consent and participation in downstream survey components such as record linkage, physical exams, storage of biological samples and phlebotomy. Interview response rates dropped from 68% in 2011-2012 to 53% in 2017-2018 for adults age 18 and older. Response was higher for children (1-17 years) but with a similar downward trend (2011-2012, 81%; 2017-2018, 65%). Despite declining interview response rates, changes in consent and response rates for downstream components over time have been mixed. Among those interviewed, the examination response rate was over 93%, consent for record linkage was over 90%, and consent for storage of specimens for future research was over 99%. The availability of a blood sample for storage ranged between 60%-65% for children and 78%-85% for adults.

National Health and Nutrition Examination Survey, 2015-2018: Sample Design and Estimation Procedures.

Background The purpose of the National Health and Nutrition Examination Survey (NHANES) is to produce national estimates representative of the total noninstitutionalized civilian U.S. population. The sample for NHANES is selected using a complex, four-stage sample design. NHANES sample weights are used by analysts to produce estimates of the health-related statistics that would have been obtained if the entire sampling frame (i.e., the noninstitutionalized civilian U.S. population) had been surveyed. Sampling errors should be calculated for all survey estimates to aid in determining their statistical reliability. For complex sample surveys, exact mathematical formulas for variance estimates that fully incorporate the sample design are usually not available. Variance approximation procedures are required to provide reasonable, approximately unbiased, and design-consistent estimates of variance. Objective This report describes the NHANES 2015-2018 sample design and the methods used to create sample weights and variance units for the public-use data files, including sample weights for selected subsamples, such as the fasting subsample. The impacts of sample design changes on estimation for NHANES 2015-2018 are described. Approaches that data users can use to modify sample weights when combining survey cycles or when combining subsamples are also included.

An Investigation of Nonresponse Bias and Survey Location Variability in the 2017-2018 National Health and Nutrition Examination Survey.

Over the past two decades, a steady decline in response rates on national face-to-face surveys has been documented, with steeper declines observed in recent years. The impact of nonresponse on survey estimates is inconsistent and depends on the correlation between response propensity and the survey estimates. To better understand the impact of declining response rates on the 2017-2018 National Health and Nutrition Examination Survey (NHANES), potential nonresponse bias (NRB) was investigated. NRB was assessed using three approaches: (a) studying variation within the respondent set; (b) benchmarking and comparisons to external data; and (c) comparing alternative weighting adjustments. Because NHANES only samples 30 counties in every 2-year cycle, the sample of counties in any given cycle may be an outlier on some characteristics. Such sampling variability may compound the effects of NRB. For this reason, the representativeness of the 2017-2018 NHANES counties was examined by comparing: (a) the characteristics of the 2017-2018 sampled counties with those from prior cycles; (b) each sampled county with the average of all the counties in the sampling stratum from which that county was selected; and (c) the 2017-2018 counties with 5,000 other samples that could have been drawn under the same sample design using a simulation study. The NRB analyses showed that the 2017-2018 NHANES sample had a lower proportion of college graduates and higher-income individuals compared with prior cycles. Additionally, the 2017-2018 NHANES counties had lower proportions of college graduates and lower mean incomes compared with counties from prior cycles and counties not selected in 2017-2018, which exacerbated the effects of NRB. Weighting adjustments used in prior cycles were not sufficient to address the bias in the 2017-2018 NHANES. Instead, enhanced weighting adjustments for education and income reduced the bias resulting from nonresponse and location sampling variability.

Prescription Medication Use Among Older Adults in the US.

This survey study describes changes in the use of prescription medications in individuals aged 65 years or older from 1999 through March 2020.

Prevalence and Correlates of Receiving Medical Advice to Increase Physical Activity in U.S. Adults: National Health and Nutrition Examination Survey 2013-2016.

INTRODUCTION: National objectives recommend healthcare professionals provide physical activity advice. This study examined health and demographic characteristics associated with receipt of medical advice to increase physical activity among U.S. health care-utilizing adults and differences in associations by age group. METHODS: Analyses included 8,410 health care-utilizing adults aged ≥20 years from the 2013-2016 National Health and Nutrition Examination Surveys (analyzed in 2018). Logistic regression was used to examine associations between receipt of medical advice to increase physical activity in the past year and measured health conditions, reported health behaviors, and demographic characteristics. Models were stratified by age group (20-39, 40-59, and ≥60 years). RESULTS: Physical activity medical advice was received by 42.9% (95% CI=40.8, 44.9) of adults overall. By age group, 32.7% of younger adults, 46.7% of middle-aged adults, and 48.9% of older adults received advice. Among all adults and across all age groups, receipt of advice was higher among adults with chronic health conditions: obesity (63.0%, 95% CI=60.3, 65.7), hypertension (56.5%, 95%=CI 53.8, 59.2), diabetes (69.8%, 95% CI=66.5, 72.8), hypercholesterolemia (55.6%, 95% CI=52.3, 59.0), and low high-density lipoprotein cholesterol (53.8%, 95% CI=50.1, 57.4). Among all adults, those with obesity, hypertension, and diabetes had significantly greater odds of receipt of advice after adjustment. Stronger associations between diabetes and hypercholesterolemia and receiving physical activity advice were observed among younger adults. CONCLUSIONS: Receipt of physical activity medical advice was highest among adults with specific chronic health conditions, and this pattern was stronger among younger adults with diabetes and hypercholesterolemia. However, most health care-utilizing adults did not receive physical activity medical advice.

Prevalence of Low High-density Lipoprotein Cholesterol Among Adults, by Physical Activity: United States, 2011-2014.

KEY FINDINGS: Data from the National Health and Nutrition Examination Survey •The prevalence of low high-density lipoprotein (HDL) cholesterol was significantly higher among adults who did not meet recommended physical activity guidelines (21.0%) than adults who met the guidelines (17.7%). •Low HDL cholesterol prevalence differed significantly for both men and women by adherence to physical activity guidelines. •Prevalence of low HDL cholesterol declined as age increased for both those who did and did not meet the physical activity guidelines. •Non-Hispanic white and non-Hispanic black adults who did not meet the physical activity guidelines had a higher prevalence than those who met the guidelines. •Low HDL cholesterol prevalence declined with increasing education level regardless of adherence to physical activity guidelines. Regular physical activity can improve cholesterol levels among adults, including increasing high-density lipoprotein (HDL) cholesterol (1). HDL cholesterol is known as "good" cholesterol because high levels can reduce cardiovascular disease risk (2). The 2008 Physical Activity Guidelines for Americans recommend that adults engage in 150 minutes or more of moderate-intensity aerobic activity per week, 75 minutes of vigorous-intensity aerobic activity per week, or an equivalent combination (3). Adherence to these guidelines is expected to decrease the prevalence of low HDL cholesterol levels (4-8). This report presents national data for 2011-2014 on low HDL cholesterol prevalence among U.S. adults aged 20 and over, by whether they met these guidelines.

Implementation of a Computerized Tablet-Survey in an Adolescent Large-Scale, School-Based Study.

BACKGROUND: Computerized surveys present many advantages over paper surveys. However, school-based adolescent research questionnaires still mainly rely on paper-and-pencil surveys as access to computers in schools is often not practical. Tablet-assisted self-interviews (TASI) present a possible solution, but their use is largely untested. This paper presents a method for and our experiences with implementing a TASI in a school setting. METHODS: A TASI was administered to 3907 middle and high school students from 79 schools. The survey assessed use of tobacco products and exposure to tobacco marketing. To assess in-depth tobacco use behaviors, the TASI employed extensive skip patterns to reduce the number of not-applicable questions that nontobacco users received. Pictures were added to help respondents identify the tobacco products they were being queried about. RESULTS: Students were receptive to the tablets and required no instructions in their use. None were lost, stolen, or broken. Item nonresponse, unanswered questions, was a pre-administration concern; however, 92% of participants answered 96% or more of the questions. CONCLUSIONS: This method was feasible and successful among a diverse population of students and schools. It generated a unique dataset of in-depth tobacco use behaviors that would not have been possible through a paper-and-pencil survey.

Trends in Anthropometric Measures Among US Children 6 to 23 Months, 1976-2014.

BACKGROUND AND OBJECTIVES: The surveillance of children's growth reflects a population's nutritional status and risk for adverse outcomes. This study aimed to describe trends in length-for-age, weight-for-age, weight-for-length, and early childhood weight gain among US children aged 6 to 23 months. METHODS: We analyzed NHANES data from 1976-1980, 1988-1994, 1999-2002, 2003-2006, 2007-2010, and 2011-2014. We estimated z scores < -2 (low) and ≥+2 (high) in comparison with World Health Organization growth standards for each indicator. Weight gain (relative to sex-age-specific medians) from birth until survey participation was estimated. Trends were assessed by low birth weight status and race/Hispanic origin. Race/Hispanic origin trends were assessed from 1988-1994 to 2011-2014. RESULTS: In 2011-2014, the prevalence of low and high length-for-age was 3.3% (SE, 0.8) and 3.7% (SE, 0.8); weight-for-age was 0.6% (SE, 0.3) and 7.0% (SE, 1.1); and weight-for-length was 1.0% (SE, 0.4) and 7.7% (SE, 1.2). The only significant trend was a decrease in high length-for-age (5.5% in 1976-1980 vs 3.7% in 2011-2014; P = .04). Relative weight gain between birth and survey participation did not differ over time, although trends differed by race/Hispanic origin. Non-Hispanic black children gained more weight between birth and survey participation in 2011-2014 versus 1988-1994, versus no change among other groups. CONCLUSIONS: Between 1976-1980 and 2011-2014, there were no significant trends in low or high weight-for-age and weight-for-length among 6- to 23-month-old children whereas the percent with high length-for-age decreased. A significant trend in relative weight gain between birth and survey participation was observed among non-Hispanic black children.

Contribution of weight status to asthma prevalence racial disparities, 2-19 year olds, 1988-2014.

PURPOSE: Racial disparities in childhood asthma prevalence increased after the 1990s. Obesity, which also varies by race/ethnicity, is an asthma risk factor but its contribution to asthma prevalence disparities is unknown. METHODS: We analyzed nationally representative National Health Examination and Nutrition Survey data for 2-19 year olds with logistic regression and decomposition analyses to assess the contributions of weight status to racial disparities in asthma prevalence, controlling for sex, age, and income status. RESULTS: From 1988-1994 to 2011-2014, asthma prevalence increased more among non-Hispanic black (NHB) (8.4% to 18.0%) than non-Hispanic white (NHW) youth (7.2% to 10.3%). Logistic regression showed that obesity was an asthma risk factor for all groups but that a three-way "weight status-race/ethnicity-time" interaction was not significant. That is, weight status did not modify the race/ethnicity association with asthma over time. In decomposition analyses, weight status had a small contribution to NHB/NHW asthma prevalence disparities but most of the disparity remained unexplained by weight status or other asthma risk factors (sex, age and income status). CONCLUSIONS: NHB youth had a greater asthma prevalence increase from 1988-1994 to 2011-2014 than NHW youth. Most of the racial disparity in asthma prevalence remained unexplained after considering weight status and other characteristics.

Blood Lead and Other Metal Biomarkers as Risk Factors for Cardiovascular Disease Mortality.

Analyses of the Third National Health and Nutrition Examination Survey (NHANES III) in 1988 to 1994 found an association of increasing blood lead levels < 10 µg/dL with a higher risk of cardiovascular disease (CVD) mortality. The potential need to correct blood lead for hematocrit/hemoglobin and adjust for biomarkers for other metals, for example, cadmium and iron, had not been addressed in the previous NHANES III-based studies on blood lead-CVD mortality association. We analyzed 1999 to 2010 NHANES data for 18,602 participants who had a blood lead measurement, were ≥ 40 years of age at the baseline examination and were followed for mortality through 2011. We calculated the relative risk for CVD mortality as a function of hemoglobin- or hematocrit-corrected log-transformed blood lead through Cox proportional hazard regression analysis with adjustment for serum iron, blood cadmium, serum C-reactive protein, serum calcium, smoking, alcohol intake, race/Hispanic origin, and sex. The adjusted relative risk for CVD mortality was 1.44 (95% confidence interval = 1.05, 1.98) per 10-fold increase in hematocrit-corrected blood lead with little evidence of nonlinearity. Similar results were obtained with hemoglobin-corrected blood lead. Not correcting blood lead for hematocrit/hemoglobin resulted in underestimation of the lead-CVD mortality association while not adjusting for iron status and blood cadmium resulted in overestimation of the lead-CVD mortality association. In a nationally representative sample of U.S. adults, log-transformed blood lead was linearly associated with increased CVD mortality. Correcting blood lead for hematocrit/hemoglobin and adjustments for some biomarkers affected the association.