Rationale: Obstructive sleep apnea, a condition leading to chronic intermittent hypoxia (CIH), is associated with hyperlipidemia, atherosclerosis, and a high cardiovascular risk. A causal link between obstructive sleep apnea and atherosclerosis has not been established. Objectives: The objective of the present study was to examine whether CIH may induce atherosclerosis in C57BL/6J mice. Methods: Forty male C57BL/6J mice, 8 weeks of age, were fed either a high-cholesterol diet or a regular chow diet and subjected either to CIH or intermittent air (control conditions) for 12 weeks. Measurements and Main Results: Nine of 10 mice simultaneously exposed to CIH and high-cholesterol diet developed atherosclerotic lesions in the aortic origin and descending aorta. In contrast, atherosclerosis was not observed in mice exposed to intermittent air and a high-cholesterol diet or in mice exposed to CIH and a regular diet. A high-cholesterol diet resulted in significant increases in serum total and low-density lipoprotein cholesterol levels and a decrease in high-density lipoprotein cholesterol. Compared with mice exposed to intermittent air and a high-cholesterol diet, combined exposure to CIH and a high-cholesterol diet resulted in marked progression of dyslipidemia with further increases in serum total cholesterol and low-density lipoprotein cholesterol (124 ؎ 4 vs. 106 ؎ 6 mg/dl; p Ͻ 0.05), a twofold increase in serum lipid peroxidation, and up-regulation of an important hepatic enzyme of lipoprotein secretion, stearoyl-coenzyme A desaturase-1. Conclusions: CIH causes atherosclerosis in the presence of dietinduced dyslipidemia.Keywords: obstructive sleep apnea; lipids; hypoxia; mouse; stearoylcoenzyme A desaturaseObstructive sleep apnea (OSA) is characterized by recurrent collapse of the upper airway during sleep, leading to chronic intermittent hypoxia (CIH) (1). OSA has been associated with an increased risk of hypertension, type II diabetes, angina, myocardial infarction, congestive heart failure, stroke, and fatal cardiovascular events, independent of underlying obesity (2-5).Poor cardiovascular outcomes may be related to the high prevalence of atherosclerosis in patients with OSA. Studies have shown independent associations between hypoxic stress of OSA and increased carotid artery intima-media thickness (6) as well as progressive narrowing of the coronary artery lumens (7).

Abstract-Obstructive sleep apnea, a syndrome leading to recurrent intermittent hypoxia (IH), has been associated previously with hypercholesterolemia, independent of underlying obesity. We examined the effects of experimentally induced IH on serum lipid levels and pathways of lipid metabolism in the absence and presence of obesity. Lean C57BL/6J mice and leptin-deficient obese C57BL/6J-Lep ob mice were exposed to IH for five days to determine changes in serum lipid profile, liver lipid content, and expression of key hepatic genes of lipid metabolism. In lean mice, exposure to IH increased fasting serum levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, phospholipids (PLs), and triglycerides (TGs), as well as liver TG content. These changes were not observed in obese mice, which had hyperlipidemia and fatty liver at baseline. In lean mice, IH increased sterol regulatory element binding protein 1 (SREBP-1) levels in the liver, increased mRNA and protein levels of stearoyl-coenzyme A desaturase 1 (SCD-1), an important gene of TG and PL biosynthesis controlled by SREBP-1, and increased monounsaturated fatty acid content in serum, which indicated augmented SCD-1 activity. In addition, in lean mice, IH decreased protein levels of scavenger receptor B1, regulating uptake of cholesterol esters and HDL by the liver. We conclude that exposure to IH for five days increases serum cholesterol and PL levels, upregulates pathways of TG and PL biosynthesis, and inhibits pathways of cholesterol uptake in the liver in the lean state but does not exacerbate the pre-existing hyperlipidemia and metabolic disturbances in leptin-deficient obesity. Key Words: obstructive sleep apnea Ⅲ cholesterol homeostasis Ⅲ lipids Ⅲ hypoxia Ⅲ mouse Ⅲ gene expression O bstructive sleep apnea (SA) is the most common form of sleep-disordered breathing and is characterized by recurrent collapse of the upper airway during sleep, leading to periods of intermittent hypoxia (IH) and sleep fragmentation. 1 SA is present in 2% of women and 4% of men in the general US population, but it is more common in obese individuals. 2,3 SA is an independent risk factor for increased cardiovascular morbidity and mortality. 4 -7 It has been postulated that metabolic dysfunction in SA may provide an intermediate step linking IH and sleep disturbances to cardiovascular disease. Although several recent studies have focused on the effects of SA on dysregulating glucose and insulin metabolism, 2,8 -10 little information is available about the impact of SA on lipid metabolism. Abnormalities in lipid regulation that occur in response to SA may act to increase the cardiovascular risk in an already susceptible population. Although obesity is one of the risk factors for elevations in total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol levels, 11 recent clinical studies indicate that SA may also contribute to hypercholesterolemia. [12][13][14][15] Thus, obesity and IH may interact to alter lipid metabolism in SA.Key steps of lipid metaboli...

The prevalence of the MS increased with aging, and this was associated with lower androgen levels. Lower total T and SHBG predicted a higher incidence of the MS.

sense mutation (Ile135Val), which may be functional. Moreover, rs3782287 (p = 0.023) and rs5888 (p = 0.003) were significantly associated with higher HDL-C levels in women younger than 50 years but not in women aged 50 years or older ( p for interaction between age and rs5888 = 0.045). None of the SNP effects on HDL-C were modified in the presence of diabetes, in either men or women. Conclusions: SCARB1 SNPs influence HDL-C levels in women, particularly in those less than 50 years old. Condensed Abstract: We assessed associations between SCARB1 SNPs and lipid traits in 919 Amish men and women. Two SNPs, rs3782287 and rs5888, were significantly associated with higher HDL-C levels in women younger than 50 years but not in women aged 50 years or older, supporting an interaction between common sequence variants in SCARB1 and estrogen on HDL-C. The metabolism of high-density lipoprotein (HDL) is complex, with many factors influencing its circulating plasma levels. One such factor is the scavenger receptor, class B, type I (SR-BI), first characterized by Acton et al.[1] , and subsequently shown to be a physiologically relevant receptor that exerts a major influence on HDL cho- Key WordsAtherosclerosis ؒ Autosomal SNPs ؒ SNP Abstract Objective: Variants within the scavenger receptor class B type I ( SCARB1 ) receptor gene have been previously associated with lipid levels, especially in women, with some studies reporting the association to be stronger in the presence of diabetes or post-menopausal estrogen use. Based on the reported gender-specific association and modification effect of estrogen on lipid levels according to SCARB1 variants, we explored the relationship between SCARBI single nucleotide polymorphisms (SNPs) and lipid levels in an Amish population to assess sex and age differences. Methods: Eight SCARB1 SNPs, identified from public databases, were genotyped in 919 subjects. Results: Rs5888 and rs3782287 were in high linkage disequilibrium (LD), with r 2 > 0.8. None of the SNPs were significantly associated with lipid levels in men; however in women, rs5888 (p = 0.04) and rs5891 (p ! 0.001) were significantly associated with higher HDL-C levels. Rs5891 had an allele frequency of 3% and predicts a mis-

Background. Statin therapy significantly reduces cardiovascular events. Older patients, however, are less likely to be prescribed statins than younger patients due to concern over lack of indication, lower predictive value of cholesterol levels, and increased risk of adverse events. To determine the effect of statins on all-cause mortality and on major cardiovascular events, including stroke, we performed a meta-analysis of statin trials that included older adult participants.

Background. Inpatient diabetes treatment has become more complicated recently with the introduction of new insulin formulations and a new emphasis on tight blood glucose control. Insufficient knowledge of insulin contributes to errors in its use that may cause adverse patient outcomes. Methods. Seventy-three faculty members, 113 residents, and 191 nurses from four hospitals completed a 20-item multiple-choice questionnaire that assessed knowledge of insulin nomenclature and characteristics and inpatient insulin use. Results. The percentage of knowledge-based questions answered correctly was low: 51% for faculty, 59% for house staff, and 47% for nurses. Scores on questions testing knowledge of insulin nomenclature and characteristics were similar to scores on those addressing inpatient insulin use among faculty and house staff; however, nurses scored better on the former than the latter (60 vs. 34%, P < 0.0001). Knowledge of names and characteristics of newer insulins, such as glargine, aspart, and lispro, was poor compared to knowledge of older insulin formulations among all professional categories (46 vs. 78%, P < 0.0001). House staff performed better than faculty (62 vs. 49%, P = 0.09) and nurses (62 vs. 34%, P < 0.0001) on questions regarding inpatient diabetes management, but all groups frequently missed questions involving sliding-scale insulin use and dosing insulin in patients with type 1 diabetes. Conclusion. Educational programs teaching insulin characteristics and inpatient diabetes management are needed for all categories of health care providers. Increased knowledge may help to improve patient safety in the hospital.

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Context:In mice, scavenger receptor class B, type I (SR-BI) receptor protein deficiency is associated with elevated high-density lipoprotein (HDL)-cholesterol (HDL-C) levels.Objective: Our objective was to determine the relationship between SR-BI protein and HDL-C levels in humans.Design: This was a prospective study of adults with hyperalphalipoproteinemia. Fasting blood was obtained for lipid and lipoprotein measurement, genomic DNA, and monocyte-derived macrophages. SR-BI protein levels were measured by Western blots, and SR-BI activity was measured by cholesteryl ester (CE) uptake of each donor's radiolabeled HDL with their monocyte-derived macrophages, or by degradation and specific cell association of dual-labeled HDL in vitro. Setting:The study was performed in a tertiary university teaching hospital. Results:The mean age was 57.2 Ϯ 10.9 yr (n ϭ 65). SR-BI protein levels were inversely associated with HDL-C levels (P Ͻ 0.002), HDL particle size (P Ͻ 0.05), and positively associated with CE uptake (P Ͻ 0.004); there was no association with plasma apolipoprotein levels. SR-BI protein levels (P ϭ 0.01) were independent predictors of HDL-C levels. Subjects who were carriers of the A allele for the rs4238001 (glycine to serine at position 2) polymorphism [single nucleotide polymorphism (SNP)] had lower SR-BI protein levels (P ϭ 0.01), whereas carriers of the C allele for the rs2278986 SNP also had lower SR-BI protein levels (P ϭ 0.02). Body mass index (P ϭ 0.05), rs4238001 (P ϭ 0.01), and rs2278986 (P ϭ 0.01) SNPs were independent predictors of SR-BI protein levels. In vitro studies of murine macrophages stably expressing the glycine to serine at position 2 SNP showed less degradation (P Ͻ 0.0004) and specific cell association (P Ͻ 0.0004) of [ 125 I, 3 H]-CE-labeled HDL.Conclusions: SR-BI protein has an independent effect on HDL-C levels in women with hyperalphalipoproteinemia. Two SNPs were significantly associated with lower SR-BI protein levels. (J Clin Endocrinol