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Background The red cell distribution width (RDW), an automated measure of red blood cell size heterogeneity (e.g. 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. Methods We examined the association of RDW with all-cause mortality, as well as cardiovascular, cancer, and chronic lower respiratory disease mortality among 15,852 adult participants in The Third National Health and Nutrition Examination Survey (1988–1994), a nationally representative sample of the United States population. Mortality status was obtained by matching to the National Death Index, with follow-up through December 31, 2000. Results Estimated mortality rates increased 5-fold from the lowest to highest quintile of RDW after accounting for age, and 2-fold after multivariable adjustment (each Ptrend < 0.001). A 1- standard deviation 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. RDW was also associated with risk of death due to cardiovascular disease (HR 1.22, 95% CI 1.14–1.31), cancer (HR 1.28, 95% CI 1.21–1.36), and chronic lower respiratory disease (HR 1.32, 95% CI 1.17–1.49). Conclusions Higher RDW was associated with increased mortality risk in this large, community-based sample, an association not specific to CVD. Study of anisocytosis may therefore yield novel pathophysiological insights, and measurement of RDW may contribute to risk assessment.

Mass spectrometry with stable isotope labels has been seminal in discovering the dynamic state of living matter1,2 but is limited to bulk tissues or cells. We developed multi-isotope imaging mass spectrometry (MIMS) that allowed us to view and measure stable isotope incorporation with sub-micron resolution3,4. Here we apply MIMS to diverse organisms, including Drosophila, mice, and humans. We test the “immortal strand hypothesis,” which predicts that during asymmetric stem cell division chromosomes containing older template DNA are segregated to the daughter destined to remain a stem cell, thus insuring lifetime genetic stability. After labeling mice with 15N-thymidine from gestation through post-natal week 8, we find no 15N label retention by dividing small intestinal crypt cells after 4wk chase. In adult mice administered 15N-thymidine pulse-chase, we find that proliferating crypt cells dilute label consistent with random strand segregation. We demonstrate the broad utility of MIMS with proof-of-principle studies of lipid turnover in Drosophila and translation to the human hematopoietic system. These studies show that MIMS provides high-resolution quantitation of stable isotope labels that cannot be obtained using other techniques and that is broadly applicable to biological and medical research.

Background-Bilirubin, with recently recognized antioxidant and antiinflammatory activity, has emerged as a candidate for atheroprotection. We hypothesized that higher levels of bilirubin would reduce susceptibility to peripheral arterial disease (PAD

Urinary aldosterone excretion and AngII-stimulated aldosterone are increased in overweight, compared with lean, normotensive adults. The correlation of these measures of aldosterone production with insulin resistance suggests a potential role for aldosterone in the pathophysiology of obesity-mediated insulin resistance.

Background It is unclear whether environmental cadmium exposure is associated with cardiovascular disease, although recent data suggest associations with myocardial infarction and peripheral arterial disease. Objective The objective of this study was to evaluate the association of measured cadmium exposure with stroke and heart failure (HF) in the general population. Methods We 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, blood cotinine level, alcohol consumption, and socio-demographic characteristics. Results At 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. Conclusions Environmental exposure to cadmium was associated with significantly increased stroke and heart failure prevalence. Cadmium exposure may increase these important manifestations of cardiovascular disease.

Background Whether individuals with peripheral artery disease (PAD) identified by screening ankle-brachial index (ABI) benefit from preventative therapies to reduce cardiovascular risk is unknown. We aimed to determine the number of US adults with PAD not receiving preventative therapies and whether treatment is associated with reduced mortality in PAD subjects without known cardiovascular disease (CVD). Methods and Results We analyzed data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004 with mortality follow-up through December 31, 2006. PAD was defined as ABI ≤ 0.90. Of 7458 eligible participants ≥ 40 years, weighted PAD prevalence was 5.9% ± SE 0.3%, corresponding to approximately 7.1 million US adults with PAD. Statin use was reported in only 30.5% ± 2.5%, angiotensin converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) use in 24.9% ± 1.9%, and aspirin use in 35.8% ± 2.9%, corresponding to 5.0 million adults with PAD not taking statins, 5.4 million not taking ACEI/ARBs, and 4.5 million not receiving aspirin. Adjusting for age, gender, and race/ethnicity, PAD was associated with all-cause mortality (HR 2.4 [1.9-2.9], p<0.0001). Even after excluding individuals with known CVD, subjects with PAD had higher mortality rates (16.1% ± 2.1%) than subjects without PAD or CVD (4.1% ± 0.3%) with adjusted HR 1.9 [1.3-2.8], p=0.001. Among PAD subjects without CVD, use of multiple preventative therapies was associated with 65% lower all-cause mortality (HR 0.35 [0.20-0.86], p=0.02). Conclusions Millions of US adults with PAD are not receiving secondary prevention therapies. Treatment with multiple therapies is associated with reduced all-cause mortality.

The presence of resistant hypertension identifies a subgroup of patients with hypertension and atherothrombosis who are at heightened risk for adverse long-term outcomes.