Jennifer Weuve

Red Blood Cell Distribution Width and Mortality Risk in a Community-Based Prospective Cohort

BACKGROUNDnRed blood cell distribution width (RDW), an automated measure of red blood cell size heterogeneity (eg, anisocytosis) that is largely overlooked, is a newly recognized risk marker in patients with established cardiovascular disease (CVD). It is unknown whether RDW is associated with mortality in the general population or whether this association is specific to CVD.nnnMETHODSnWe examined the association of RDW with all-cause mortality and with CVD, cancer, and chronic lower respiratory tract disease mortality in 15 852 adult participants in the Third National Health and Nutrition Examination Survey (1988-1994), a nationally representative sample of the US population. Mortality status was obtained by matching to the National Death Index, with follow-up through December 31, 2000.nnnRESULTSnEstimated mortality rates increased 5-fold from the lowest to the highest quintile of RDW after accounting for age and 2-fold after multivariable adjustment (P(trend) < .001 for each). A 1-SD increment in RDW (0.98%) was associated with a 23% greater risk of all-cause mortality (hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.18-1.28) after multivariable adjustment. The RDW was also associated with risk of death due to CVD (HR, 1.22; 95% CI, 1.14-1.31), cancer (1.28; 1.21-1.36), and chronic lower respiratory tract disease (1.32; 1.17-1.49).nnnCONCLUSIONSnHigher RDW is associated with increased mortality risk in this large, community-based sample, an association not specific to CVD. Study of anisocytosis may, therefore, yield novel pathophysiologic insights, and measurement of RDW may contribute to risk assessment.

Use of Di(2-ethylhexyl) Phthalate-Containing Medical Products and Urinary Levels of Mono(2-ethylhexyl) Phthalate in Neonatal Intensive Care Unit Infants

Objective: Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer used in medical products made with polyvinyl chloride (PVC) plastic and may be toxic to humans. DEHP is lipophilic and binds non-covalently to PVC, allowing it to leach from these products. Medical devices containing DEHP are used extensively in neonatal intensive care units (NICUs). Among neonates in NICUs, we studied exposure to DEHP-containing medical devices in relation to urinary levels of mono(2-ethylhexyl) phthalate (MEHP), a metabolite of DEHP. Design: We used a cross-sectional design for this study. Participants: We studied 54 neonates admitted to either of two level III hospital NICUs for at least 3 days between 1 March and 30 April 2003. Measurements: A priori, we classified the infants’ exposures to DEHP based on medical products used: The low-DEHP exposure group included infants receiving primarily bottle and/or gavage feedings; the medium exposure group included infants receiving enteral feedings, intravenous hyperalimentation, and/or nasal continuous positive airway pressure; and the high exposure group included infants receiving umbilical vessel catheterization, endotracheal intubation, intravenous hyperalimentation, and indwelling gavage tube. We measured MEHP in the infants’ urine using automated solid-phase extraction/isotope dilution/high-performance liquid chromatography/ tandem mass spectrometry. Results: Urinary MEHP levels increased monotonically with DEHP exposure. For the low-, medium-, and high-DEHP exposure groups, median (interquartile range) MEHP levels were 4 (18), 28 (58), and 86 ng/mL (150), respectively (p = 0.004). After adjustment for institution and sex, urinary MEHP levels among infants in the high exposure group were 5.1 times those among infants in the low exposure group (p = 0.03). Conclusion: Intensive use of DEHP-containing medical devices in NICU infants results in higher exposure to DEHP as reflected by elevated urinary levels of MEHP.

Accounting for bias due to selective attrition: The example of smoking and cognitive decline

Background: Selective attrition may introduce bias into analyses of the determinants of cognitive decline. This is a concern especially for risk factors, such as smoking, that strongly influence mortality and dropout. Using inverse-probability-of-attrition weights, we examined the influence of selective attrition on the estimated association of current smoking (vs. never smoking) with cognitive decline. Methods: Chicago Health and Aging Project participants (n = 3713), aged 65–109 years, who were current smokers or never- smokers, underwent cognitive assessments up to 5 times at 3-year interval. We used pooled logistic regression to fit predictive models of attrition due to death or study dropout across the follow-up waves. With these models, we computed inverse-probability-of-attrition weights for each observation. We fit unweighted and weighted, multivariable-adjusted generalized-estimating-equation models, contrasting rates of change in cognitive scores in current versus never-smokers. Estimates are expressed as rates of change in z score per decade. Results: During the 12 years of follow-up, smokers had higher mortality than never-smokers (hazard ratio = 1.93 [95% confidence interval = 1.67 to 2.23]). Higher previous cognitive score was associated with increased likelihood of survival and continued participation. In unweighted analyses, current smokers cognitive scores declined 0.11 standard units per decade more rapidly than never-smokers (95% CI = −0.20 to −0.02). Weighting to account for attrition yielded estimates that were 56% to 86% larger, with smokers estimated 10-year rate of decline up to 0.20 units faster than never-smokers (95% CI = −0.36 to −0.04). Conclusions: Estimates of smokings effects on cognitive decline may be underestimated due to differential attrition. Analyses that weight for the inverse probability of attrition help compensate for this attrition.

Cadmium exposure in association with history of stroke and heart failure.

BACKGROUNDnIt is unclear whether environmental cadmium exposure is associated with cardiovascular disease, although recent data suggest associations with myocardial infarction and peripheral arterial disease.nnnOBJECTIVEnThe objective of this study was to evaluate the association of measured cadmium exposure with stroke and heart failure (HF) in the general population.nnnMETHODSnWe analyzed data from 12,049 participants, aged 30 years and older, in the 1999-2006 National Health and Nutrition Examination Survey (NHANES) for whom information was available on body mass index, smoking status, alcohol consumption, and socio-demographic characteristics.nnnRESULTSnAt their interviews, 492 persons reported a history of stroke, and 471 a history of HF. After adjusting for demographic and cardiovascular risk factors, a 50% increase in blood cadmium corresponded to a 35% increased odds of prevalent stroke [OR: 1.35; 95% confidence interval (CI): 1.12-1.65] and a 50% increase in urinary cadmium corresponded to a 9% increase in prevalent stroke [OR: 1.09; 95% CI: 1.00-1.19]. This association was higher among women [OR: 1.38; 95% CI: 1.11-1.72] than men [OR: 1.30; 95% CI: 0.93-1.79] (p-value for interaction=0.05). A 50% increase in blood cadmium corresponded to a 48% increased odds of prevalent HF [OR: 1.48; 95% CI: 1.17-1.87] and a 50% increase in urinary cadmium corresponded to a 12% increase in prevalent HF [OR: 1.12; 95% CI: 1.03-1.20], with no difference in sex-specific associations.nnnCONCLUSIONSnEnvironmental exposure to cadmium was associated with significantly increased stroke and heart failure prevalence. Cadmium exposure may increase these important manifestations of cardiovascular disease.

Serum Total Bilirubin Level, Prevalent Stroke, and Stroke Outcomes: NHANES 1999–2004

BACKGROUNDnBilirubin inhibits experimental atherosclerosis, is inversely associated with carotid plaque burden, and confers neuroprotection in experimental stroke. Clinical data addressing the association of bilirubin with stroke are not available. We hypothesized that higher bilirubin levels would be associated with reduced stroke prevalence and improved stroke outcomes.nnnMETHODSnWe used the National Health and Nutrition Examination Survey 1999 to 2004, a nationally representative cross-sectional examination of the United States civilian population, to examine the association of bilirubin with stroke. Of 13,214 adult participants with data on stroke history, serum total bilirubin level, and stroke risk factors, 453 reported a history of stroke. Of these, 138 participants reported an adverse stroke outcome, defined as a long-term health problem or disability due to stroke. We performed multivariable logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) with adjustment for demographic characteristics and stroke risk factors.nnnRESULTSnAfter multivariable adjustment, a 1.71 micromol/L (0.1 mg/dL) increment in bilirubin level was associated with a 9% reduced odds of stroke (OR 0.91; 95% CI, 0.86-0.96) among all participants and with a 10% reduced odds of an adverse stroke outcome (OR 0.90; 95% CI, 0.80-1.00) among participants with a history of stroke.nnnCONCLUSIONSnThese results suggest that a higher serum total bilirubin level is associated with reduced stroke prevalence and improved stroke outcomes. Our findings support the hypothesis that bilirubin may protect from stroke events and from neurologic damage in stroke.

Exposure to Phthalates in Neonatal Intensive Care Unit Infants: Urinary Concentrations of Monoesters and Oxidative Metabolites

Objective We previously demonstrated that among 54 infants in neonatal intensive care units, exposure to polyvinyl chloride plastic medical devices containing the plasticizer di(2-ethylhexyl) phthalate (DEHP) is associated with urinary concentrations of mono(2-ethylhexyl) phthalate (MEHP), a DEHP metabolite. In this follow-up report, we studied the neonates’ exposure to DEHP-containing devices in relation to urinary concentrations of two other DEHP metabolites, and to urinary concentrations of metabolites of dibutyl phthalate (DBP) and benzylbutyl phthalate (BzBP), phthalates found in construction materials and personal care products. Measurements A priori, we classified the intensiveness of these 54 infants’ exposure to DEHP-containing medical products. We measured three metabolites of DEHP in infants’ urine: MEHP and two of its oxidative metabolites, mono(2-ethyl-5-hydroxylhexyl) phthalate (MEHHP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP). We also measured monobutyl phthalate (MBP), a metabolite of DBP, and monobenzyl phthalate (MBzP), a metabolite of BzBP. Results Intensiveness of DEHP-containing product use was monotonically associated with all three DEHP metabolites. Urinary concentrations of MEHHP and MEOHP among infants in the high-DEHP-intensiveness group were 13–14 times the concentrations among infants in the low-intensiveness group (p ≤ 0.007). Concentrations of MBP were somewhat higher in the medium-and high-DEHP-intensiveness group; MBzP did not vary by product use group. Incorporating all phthalate data into a structural equation model confirmed the specific monotonic association between intensiveness of product use and biologic measures of DEHP. Conclusion Inclusion of the oxidative metabolites MEHHP and MEOHP strengthened the association between intensiveness of product use and biologic indices of DEHP exposure over that observed with MEHP alone.

The Role of Peripheral Inflammatory Markers in Dementia and Alzheimer’s Disease: A Meta-Analysis

BACKGROUNDnStudies that have investigated the association between markers of inflammation and risk of dementia are conflicting. Therefore, the researchers conducted a systematic review and meta-analysis of observational studies with the hypothesis that an increased level of peripheral proinflammatory markers would be associated with risk of all-cause dementia or Alzheimers disease (AD).nnnMETHODSnThe researchers conducted a literature search of observational studies indexed in the PubMed and PsycInfo databases. Selected studies included those with at least one peripheral inflammatory biomarker and its association with risk of all-cause dementia or AD. Random effects models were used to generate pooled hazard ratios (HRs) comparing the top versus bottom quantile of inflammatory marker level. Heterogeneity was assessed using the I (2) statistic.nnnRESULTSnSeven studies were identified, combining for a total 5,717 participants, 746 cases of all-cause dementia and 565 cases of AD. An increased level of C-reactive protein was associated with a 45% increased risk of all-cause dementia (HR: 1.45; 95% CI: 1.10, 1.91). Similarly, a higher level of interleukin-6 was associated with a 32% increased risk (HR: 1.32; 95% CI: 1.06, 1.64) of all-cause dementia. For AD alone, the association with C-reactive protein was less pronounced (HR: 1.21; 95% CI: 1.03, 1.42) and interleukin-6 was not associated with risk of AD (HR: 1.06; 95% CI: 0.83, 1.35). No significant heterogeneity was found in any of the meta-analyses (I (2) = 0%-40%, p ≥ .16).nnnCONCLUSIONSnAn increased peripheral level of inflammatory markers is associated with a modest increase in risk of all-cause dementia. Evidence for an association with risk of AD alone is limited.

Social Ties and Cognitive Recovery after Stroke: Does Social Integration Promote Cognitive Resilience?

Background/Aims: Little is known about the possible effects of social resources on stroke survivors’ level and change in cognitive outcomes. Understanding this association may help us identify strategies to improve stroke recovery and help elucidate the etiology of dementia. Methods: We examined the relationship of social ties and social support to cognitive function and cognitive change 6 months after stroke. Participants in the Families in Recovery from Stroke Trial (FIRST) (n = 272) were interviewed approximately 17 days (baseline) and 6 months (follow-up) after stroke. Cognition was assessed with the Mini Mental State Examination (MMSE) and a summary battery of 7 neuropsychological tests. Median-based regression was used to model cognitive outcomes by level of baseline intimate, personal and organizational social ties and received emotional and instrumental support. Results: Baseline social ties and emotional sup- port independently predicted 6-month Cognitive Summary Scores. Emotional support also predicted greater improvements in Cognitive Summary Scores from baseline to the 6-month follow-up. No other social exposures predicted improvements in the MMSE or the Cognitive Summary. Conclusions: Our results suggest that emotional support may promote cognitive resilience while social ties provide cognitive reserve that protects against impaired cognition after stroke. Social ties did not predict cognitive recovery however, so reverse causation cannot be ruled out.

Deaths in the United States among persons with Alzheimer's disease (2010-2050)

Alzheimers disease (AD) profoundly affects the end‐of‐life experience. Yet, counts of deaths attributable to AD understate this burden of AD in the population. Therefore, we estimated the annual number of deaths in the United States among older adults with AD from 2010 to 2050.

Cognitive impairment 18 years before clinical diagnosis of Alzheimer disease dementia

Objective: To examine the relation of performance on brief cognitive tests to development of clinically diagnosed Alzheimer disease (AD) dementia over the following 18 years in a sample of African Americans and European Americans. Methods: A composite cognitive test score based on tests of episodic memory, executive function, and global cognition was constructed in a prospective population-based sample of 2,125 participants (55% African American and 61% female) aged 65 years and older residing in 4 Chicago neighborhoods. Time before AD dementia diagnosis was categorized into 6 groups corresponding to data collection periods: 0.1–0.9, 1.0–3.9, 4.0–6.9, 7.0–9.9, 10.0–12.9, and 13.0–17.9 years. Results: Of 2,125 participants without clinical AD dementia, 442 (21%) developed clinical AD dementia over 18 years of follow-up. Lower composite cognitive test scores were associated with the development of AD dementia over the duration of the study. The magnitude of association between composite cognitive test score and development of AD dementia increased from an odds ratio of 3.39 (95% confidence interval 1.72, 6.67; p < 0.001) at 13.0–17.9 years to 9.84 (95% confidence interval 7.41, 13.06; p < 0.001) at 0.1–0.9 years, per SD increment. These associations were consistently larger among European Americans than among African Americans. Performance on individual cognitive tests of episodic memory, executive function, and global cognition also significantly predicted the development of AD dementia, with associations exhibiting a similar trend over 18 years. Conclusions: Our findings suggest that cognitive impairment may manifest in the preclinical phase of AD dementia substantially earlier than previously established.