917-100 8-Epi-Prostaglandin F2α(8-Isoprostane), a Novel Marker of Lipid Peroxidation, is Elevated and Inversely Correlated to Serum Antioxidant Vitamins in Smokers

Oxidative modification of lipoproteins is thought to be an essential event in atherosclerosis. Current methods of quantifying lipid peroxidation in vivo are technically difficult and/or nonspecific. A simple, clinically reliable test is needed to assess an individual's degree of lipid peroxidation which could be a powerful predictor of cardiovascular disease risk. 8-lsoprostane is a chemically stable prostanoid resulting from free radical catalyzed peroxidation of arachidonic acid. This molecule is produced by oxidation of low density lipoprotein and is present in both plasma and urine. To evaluate this novel marker of in vivo lipid peroxidation, we compared 24 hour urinary levels of 8-isoprostane in healthy smokers (n=15) and nonsmokers (n=9) with a competitive enzyme immunoassay. Serum was also obtained for analysis of lipid and antioxidant vitamin levels. Smokers were found to have higher levels of urinary 8-isoprostane than nonsmokers and these levels were inversely correlated with serum beta carotene (P=0.04, r=-0.44) and vitamin C (P=0.01, r=-0.52). No significant differences were detected in lipid profiles between smokers and nonsmokers.8-lsoprostaneMean ± SEMP-ValueNonsmokers1.55±0.22P=0.002Smokers2.77±0.21Values=μg/24 hoursConclusionUrinary 8-isoprostane is elevated in smokers and may provide a sensitive, specific and noninvasive method for assessment of in vivo lipid peroxidation. Further studies are indicated to determine whether elevated 8-isoprostane identifies individuals at risk for developing atherosclerosis

Testosterone and Cardiovascular Disease

Abstract Testosterone (T) is the principal male sex hormone. As men age, T levels typically fall. Symptoms of low T include decreased libido, vasomotor instability, and decreased bone mineral density. Other symptoms may include depression, fatigue, erectile dysfunction, and reduced muscle strength/mass. Epidemiology studies show that low levels of T are associated with more atherosclerosis, coronary artery disease, and cardiovascular events. However, treating hypogonadism in the aging male has resulted in discrepant results in regard to its effect on cardiovascular events. Emerging studies suggest that T may have a future role in treating heart failure, angina, and myocardial ischemia. A large, prospective, long-term study of T replacement, with a primary endpoint of a composite of adverse cardiovascular events including myocardial infarction, stroke, and/or cardiovascular death, is needed. The Food and Drug Administration recently put additional restrictions on T replacement therapy labeling and called for additional studies to determine its cardiac safety

Diabetes reduces bone marrow and circulating porcine endothelial progenitor cells, an effect ameliorated by atorvastatin and independent of cholesterol

Bone marrow derived endothelial progenitor cells (EPCs) are early precursors of mature endothelial cells which replenish aging and damaged endothelial cells. The authors studied a diabetic swine model to determine if induction of DM adversely affects either bone marrow or circulating EPCs and whether a HMG-CoA reductase inhibitor (statin) improves development and recruitment of EPCs in the absence of cholesterol lowering. Streptozotocin was administered to Yorkshire pigs to induce DM. One month after induction, diabetic pigs were treated with atorvastatin (statin, n = 10), ezetimibe (n = 10) or untreated (n = 10) and evaluated for number of bone marrow and circulating EPCs and femoral artery endothelial function. There was no effect of either medication on cholesterol level. One month after induction of DM prior to administration of drugs, the number of bone marrow and circulating EPCs significantly decreased (P < 0.0001) compared to baseline. Three months after DM induction, the mean proportion of circulating EPCs significantly increased in the atorvastatin group, but not in the control or ezetimibe groups. The control group showed progressive reduction in percentage of flow mediated vasodilatation (no dilatation at 3 months) whereas the atorvastatin group and ezetimibe exhibited vasodilatation, 6% and 4% respectively. DM results in significant impairment of bone marrow and circulating EPCs as well as endothelial function. The effect is ameliorated, in part, by atorvastatin independent of its cholesterol lowering effect. These data suggest a model wherein accelerated atherosclerosis seen with DM may, in part, result from reduction in EPCs which may be ameliorated by treatment with a statin

Peripheral arterial disease, prevalence and cumulative risk factor profile analysis.

BACKGROUND: The primary aim of the present study was to determine the cumulative effect of a set of peripheral artery disease (PAD) risk factors among age, gender and race/ethnicity groups in the United States. METHODS: We examined data from a nationally representative sample of the US population (National Health and Nutrition Examination Survey [NHANES], 1999-2004). A total of 7058 subjects 40 years or older that completed the interview, medical examination and had ankle-brachial index (ABI) measurements were included in this study. RESULTS: The age- and sex-standardized prevalence of PAD was 4.6 % (standard error [SE] 0.3%).The highest prevalence of PAD was observed among elderly, non-Hispanic Blacks and women. In a multivariable age-, gender- and race/ethnicity-adjusted model hypertension, diabetes, chronic kidney disease, and smoking were retained as PAD risk factors (p ≤ 0.05 for each). The odds of PAD increased with each additional risk factor present from a non-significant 1.5-fold increase (O.R 1.5, 95% confidence interval [CI] 0.9-2.6) in the presence of one risk factor, to more than ten-fold (OR 10.2, 95% CI 6.4-16.3) in the presence of three or more risk factors. In stratified analysis, non-Hispanic Blacks (OR 14.7, 95% CI 2.1-104.1) and women (OR 18.6, 95% CI 7.1-48.7) were particularly sensitive to this cumulative effect. CONCLUSION: In a large nationally representative sample, an aggregate set of risk factors that included diabetes mellitus, chronic kidney disease, hypertension and smoking significantly increase the likelihood of prevalent PAD. A cumulative risk factor analysis highlights important susceptibility differences among different population groups and provides additional evidence to redefine screening strategies in PAD

Ankle Brachial Index and Subsequent Cardiovascular Disease Risk in Patients With Chronic Kidney Disease

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139089/1/jah31554.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139089/2/jah31554_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139089/3/jah31554-sup-0001-TableS1.pd

Genetic association analysis highlights new loci that modulate hematological trait variation in Caucasians and African Americans

Red blood cell, white blood cell, and platelet measures, including their count, sub-type and volume, are important diagnostic and prognostic clinical parameters for several human diseases. To identify novel loci associated with hematological traits, and compare the architecture of these phenotypes between ethnic groups, the CARe Project genotyped 49,094 single nucleotide polymorphisms (SNPs) that capture variation in ~2,100 candidate genes in DNA of 23,439 Caucasians and 7,112 African Americans from five population-based cohorts. We found strong novel associations between erythrocyte phenotypes and the glucose-6 phosphate dehydrogenase (G6PD) A-allele in African Americans (rs1050828, P < 2.0 × 10−13, T-allele associated with lower red blood cell count, hemoglobin, and hematocrit, and higher mean corpuscular volume), and between platelet count and a SNP at the tropomyosin-4 (TPM4) locus (rs8109288, P = 3.0 × 10−7 in Caucasians; P = 3.0 × 10−7 in African Americans, T-allele associated with lower platelet count). We strongly replicated many genetic associations to blood cell phenotypes previously established in Caucasians. A common variant of the α-globin (HBA2-HBA1) locus was associated with red blood cell traits in African Americans, but not in Caucasians (rs1211375, P < 7 × 10−8, A-allele associated with lower hemoglobin, mean corpuscular hemoglobin, and mean corpuscular volume). Our results show similarities but also differences in the genetic regulation of hematological traits in European- and African-derived populations, and highlight the role of natural selection in shaping these differences