Background-C-reactive protein (CRP) and interleukin (IL)-6 are important risk factors for atherosclerosis and coronary heart disease. In the present study, we examined serum levels of CRP and IL-6, IL-6 production by monocytes, and the effect of nasal continuous positive airway pressure (nCPAP) in patients with obstructive sleep apnea syndrome (OSAS). Methods and Results-After polysomnography, venous blood was collected at 5 AM from 30 patients with OSAS and 14 obese control subjects. Serum levels of CRP and IL-6 and spontaneous production of IL-6 by monocytes were investigated. In addition, the effects of 1 month of nCPAP were studied in patients with moderate to severe OSAS. Levels of CRP and IL-6 were significantly higher in patients with OSAS than in obese control subjects (CRP PϽ0.001, IL-6 PϽ0.05). IL-6 production by monocytes was also higher in patients with OSAS than in obese control subjects (PϽ0.01). In patients with OSAS, the primary factors influencing levels of CRP were severity of OSAS and body mass index and those influencing levels of IL-6 were body mass index and nocturnal hypoxia. nCPAP significantly decreased levels of both CRP (PϽ0.0001) and IL-6 (PϽ0.001) and spontaneous IL-6 production by monocytes (PϽ0.01). Conclusions-Levels of CRP and IL-6 and spontaneous production of IL-6 by monocytes are elevated in patients with OSAS but are decreased by nCPAP. Therefore, OSAS is associated with increased risks for cardiovascular morbidity and mortality, and nCPAP may be useful for decreasing these risks.

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OBJECTIVE -Three measures-heart rate, a global index of the influence of the autonomic nervous system on the heart; circulating concentrations of adiponectin, an adipose-specific protein; and C-reactive protein (CRP), a sensitive marker of inflammation-have been reported to be closely associated with insulin resistance. Patients with borderline hypertension are known to be more insulin resistant and dyslipidemic than those with normal blood pressure (BP). BP can be classified into three categories: optimal, normal, and high-normal. The present study examined whether those with high-normal BP have any of these three conditions as compared with those with optimal BP in young healthy men.RESEARCH DESIGN AND METHODS -Anthropometric, blood pressure, heart rate, and blood tests, including tests for adiponectin and CRP, were conducted in 198 male students, ages 18 -26 years, who had fasted overnight. Insulin resistance (IR) and insulin secretion (␤-cell levels) were calculated using the homeostasis model assessment (HOMA), and LDL size was measured by PAGE.RESULTS -Compared with the 90 men who had optimal BP, the 46 men with high-normal BP had increased heart rate, BMI, percent body fat, and serum leptin levels. In addition, they had greater serum insulin, HOMA IR, and ␤-cell levels, lower adiponectin levels, and comparable CRP levels. Furthermore, the 46 men with high-normal BP had higher serum triglyceride and apolipoprotein (apo) B levels, and smaller LDL size; however, there was no difference in LDL and HDL cholesterol and apoA-I between men with optimal and high-normal BP. After adjusting for BMI, differences were still significant in serum adiponectin, heart rate, and LDL particle size. As BP rose, there was an increase in heart rate (BMI-adjusted least square means were 63, 65, and 70 bpm in men with optimal, normal, and high-normal BP, respectively; P ϭ 0.005), whereas serum adiponectin (7.5, 6.6, and 6.4 mg/l; P ϭ 0.007) and LDL particle size (271, 269, and 269 Å; P ϭ 0.008) decreased.CONCLUSIONS -Young men with high-normal BP have a faster heart rate, lower serum adiponectin levels, and smaller LDL size than men with optimal BP, even after adjustment for BMI. These results suggest the necessity of preventing further development of cardiac and metabolic diseases in young people who have high-normal BP. Diabetes Care 25:971-976, 2002

A preponderance of small, dense (sd) LDL is strongly associated with the development of coronary heart disease, but the method for the measurement of sd LDL is too laborious for clinical use. We report a simple method for the quantification of sd LDL that is applicable to an autoanalyzer. This method consists of two steps: first, to precipitate the lipoprotein of density (d) Ͻ 1.044 g/ml using heparin-magnesium; and second, to measure LDL-cholesterol in the supernatant by the homogenous method or apolipoprotein B (apoB) by an immunoturbidometric assay. LDL particles are heterogenous with respect to size and density (d) of lipid composition. Two distinct phenotypes based on LDL particles have been recognized: pattern A, with a higher proportion of large, buoyant LDL particles, and pattern B, with a predominance of small, dense (sd) LDL particles (1, 2, 3). It has been suggested that compared with buoyant LDL, sd LDLs are highly atherogenic as a result of their higher penetration into the arterial wall, their lower binding affinity for the LDL receptor, prolonged plasma half-life, and lower resistance to oxidative stress (4, 5). Several studies have reported a 2-to 3-fold increase in coronary heart disease (CHD) risk among patients with pattern B (1, 2). We have also reported that sd LDL is highly associated with CHD events in Japanese, an ethnic group with lower LDL-cholesterol levels, compared with Western populations (6, 7). Therefore, sd LDL has been highlighted as a new potent risk marker for CHD.LDL particle size is usually measured by gradient gel electrophoresis (GGE) using nondenaturing polyacrylamide according to the method of Krauss and Burke (8). However, this procedure requires a long assay time, i.e., overnight electrophoresis, staining, and destaining. Of course, this assay does not allow quantitative determination of sd LDL. Ultracentrifugation is the standard technique for the isolation of the sd LDL fraction (9, 10) and allows quantification of sd LDL. Griffin et al. (10) reported that LDL-III (equivalent to sd LDL, with d ϭ 1.044-1.060 g/ml) concentration was significantly increased in CHD patients, and the relative CHD risk was increased 4.5-fold in individuals having LDL-III concentrations (protein plus lipid) Ͼ 100 mg/dl, compared with those with lower concentrations. Their study suggests that in addition to measurement of LDL size, quantification of sd LDL is also useful for the assessment of CHD risk. However, the ultracentrifugation technique is too laborious for general clinical use, because it requires special equipment and a long running time.It is well known that a combination of divalent cations and polyanions precipitates apolipoprotein B (apoB)-containing lipoproteins, which allows for the measurement of HDL-cholesterol. However, we found that the combination of heparin and Mg did not precipitate all of the apoBcontaining lipoproteins; the denser part of LDL remained in the supernatant. Here we report a simple precipitation method for the direct measurement of sd LDL in serum