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Introduction: To test whether genetic variants of osteoprotegerin gene (TNFRSF11B) affect metabolic traits (body mass index [BMI], glucose, triglyceride, total cholesterol) and bone mass traits.We conducted a population based association study to investigate associations of eight tagging single nucleotide polymorphisms (tSNPs) of the TNFRSF11B gene with the aforementioned traits in a Chinese Han population and an ethnic group admixed with Caucasians and Asians - Uyghur. The associations between the tSNPs and bone mass density (BMD) were also tested in Han population.We found that SNP rs3102727, located in the first intron of the TNFRSF11B gene, was significantly associated with triglyceride levels in Uyghur population and Han population simultaneously. T allele of the rs3102727 variant was associated with a 0.10 mmol/L and 0.09 mmol/L lower level of triglyceride than C allele in Uyghur (p = 0.019) and Han subjects (p = 0.037), respectively. In addition, the T allele is also associated with a lower level of hip BMD (p = 0.025) and total BMD (p = 0.048). Further, we found significant associations between SNP rs11573869 and BMI in Uyghur subjects and SNP rs3134062 with hip BMD in Han sbujects. Rs11573869-T allele was associated with a 0.81 kg/m(2) lower level of BMI than C allele (p = 0.002) and the hip BMD decreases with the copy of rs3134062-T allele increases (p = 0.002).We detected novel associations between TNFRSF11B polymorphisms and metabolic traits in Uyghur and Han populations. In addition, we found associations between TNFRSF11B polymorphisms and bone mass traits in Han population.

HMG-CoA reductase inhibitors (statins) inhibit cholesterol biosynthesis, and also decrease the formation of isoprenoid intermediates required for the activation of Rho kinase (ROCK) pathway. ROCK pathway plays pivotal roles in cardiovascular diseases including arteriosclerosis. It has been implicated that inhibition of ROCK can reverse vascular dysfunction in humans with atherosclerosis. However, it is not clear whether statins, at doses used to lower cholesterol levels, inhibit ROCK activity in humans with atherosclerosis.We treated 40 subjects with stable atherosclerosis with rosuvastatin 10 mg/day, or rosuvastatin 40 mg/day for 28 days in a randomized, double-blinded study. We assessed the change in the lipid levels, C-reactive protein (CRP), ROCK activity, and flow-mediated dilation (FMD) of the brachial artery before and after statins therapy.Treatment with rosuvastatin 10 mg and 40 mg significantly reduced LDL cholesterol by 43.2% to 55.9% and increased FMD by 29.3% to 42.5% (p0.05 for both compared with baselines). Both doses inhibited ROCK activity (p0.05), and the extent of inhibition was greater with rosuvastatin 40 mg compared with 10 mg (p0.05). Only rosuvastatin 40 mg significantly reduced hsCRP (p0.05).There was no correlation between changes in ROCK activity and changes in low-density lipoprotein cholesterol (r=0.37, p0.05 vs. r=0.41, p0.05) among patients randomized to rosuvastatin 10 mg group or 40 mg group. There was a correlation between ROCK inhibition and change in FMD among patients with rosuvastatin 10 mg therapy (r=0.43, p0.05), and 40 mg therapy (r=0.54, p0.05). Correlation was found between changes in ROCK inhibition and changes in CRP in rosuvastatin 40 mg/day group (r=0.47, p0.05).These results demonstrate that high dose rosuvastatin exerts greater effects on LDL-C, ROCK activity, and CRP than low dose rosuvastatin. These findings provide clinical evidence that statins are effective in improving endothelium dysfunction by a cholesterol-independent mechanism in patients with atherosclerosis.

To assess the diagnostic value of adrenal venous sampling (AVS) in the subtype diagnosis of primary aldosteronism (PA).The diagnosis of PA was made in 36 patients based on an elevated ratio of plasma aldosterone (ALD) to plasma rennin activity (PRA) (ARR) and confirmed tests (saline infusion or captopril challenge) in recent 3 years. All PA patients underwent adrenal computed tomographic scan (CT) and AVS. The diagnostic accuracy of CT and AVS in the subtype differentiation of PA were evaluated by comparing the differences of CT findings, AVS results and clinical outcomes.Fifteen of 36 patients (42%) had a final diagnosis of aldosterone-producing adenoma (APA) and another 21 patients (58%) with bilateral adrenal hyperplasia (BAH). The level of ALD was significantly higher in APA group than that in BAH group (298.9 ± 91.0 vs 226.3 ± 59 ng/L, P0.05). PRA (ng×ml(-1)×h(-1)) in APA patients were markedly lower than that in BAH counterparts (0.18 ± 0.14 vs 0.28 ± 0.29 ng×ml(-1)×h(-1), P0.01). Consequently, ARR in APA group was evidently higher than that in BAH group (2444.7 ± 1405.2 vs 1550.0 ± 1059.8, P0.05). Plasma potassium in APA patients was lower than that in those with BAH (2.71 ± 0.57 vs 3.17 ± 0.40 mmol/L). But there was no statistic significance (P0.05). The CT findings were discordant with the AVS results in 27.8% of patients (10/36). The accuracy of adrenal CT scan was only 72.2% in the subtype diagnosis of PA, provided AVS was the gold standard for distinguishing between APA and BAH. Reliance on CT findings could lead to inappropriate management in 25% of PA patients. Conversely, the AVS results were concordant with the clinical outcomes in 94.4% of all patients.CT scan is not a reliable method of differentiating primary aldosteronism. Compared with CT, AVS is more accurate in establishing a correct diagnosis of primary aldosteronism. AVS should be performed routinely before operation in PA patients opting for adrenalectomy.

To investigate the relationship of reversal of hypertensive left ventricular hypertrophy (LVH) with heart rate variability (HRV) and smoothness index (SI).A total of 127 patients with untreated essential hypertension associated with LVH were enrolled to receive a 20-week treatment. The drugs included losartan potassiumhydrochlorothiazide (1 tablet/day) and metoprolol (12.5 mg - 50 mg twice daily). The sitting systolic and diastolic blood pressures (SBPDBP), M-mode and pulsed Doppler echocardiography, 24-hour ambulatory blood pressure monitoring (ABPM) and 24-hour ambulatory ECG (Holter) were performed at pre- and post-treatment. The changes in various parameters such as echocardiography left ventricular end-systolic dimension (LVDs), left ventricular end-diastolic dimension (LVDd) and the thickness of interventricular septum (IVST) and posterior wall (PWT) were measured. And left ventricular mass index (LVMI) and smoothness index (SI) were also examined. The evaluated parameters of ABPM were average 24-hour, daytime and nighttime SBPDBP. As to 24-hour ambulatory ECG (Holter), the parameters were standard deviation of normal to normal intervals (SDNN), rate mean square of the differences of successive RR intervals (RMSSD), percentage of RR intervals differing50 ms (PNN50), high frequency (HF) and low frequency (LF).After a 20-week treatment, the levels of sitting blood pressure (SBP 158.72 ± 12.11 mm Hg vs 132.21 ± 14.03 mm Hg; DBP 97.20 ± 7.71 vs 86.36 ± 6.48 mm Hg, P0.001), parameters of 24-hour ABPM (24-hour mean SBP 146.20 ± 10.11 mm Hg vs 129.68 ± 6.12 mm Hg, P0.001; 24-hour mean DBP 93.45 ± 5.46 mm Hg vs 81.77 ± 6.71 mm Hg, P0.01; daytime mean SBP 149.53 ± 8.67 mm Hg vs 133.60 ± 6.27 mm Hg, P0.001; daytime mean DBP 94.68 ± 4.96 mm Hg vs 83.55 ± 7.03 mm Hg, P0.001; nighttime mean SBP 137.21 ± 8.73 mm Hg vs 122.74 ± 7.58 mm Hg, P0.001; nighttime mean DBP 86.75 ± 6.22 mm Hg vs 72.81 ± 5.47 mm Hg, P0.001) and LVMI significantly decreased (128.90 ± 32.35 g/m(2) vs 118.39 ± 31.10 g/m(2), P0.01) while the indicators of HRV changes such as SDNN, RMSSD, PNN50 and HF significantly increased (SDNN 97.28 ± 16.67 ms vs 152.27 ± 34.23 ms, P0.01; RMSSD 21.32 ± 8.70 ms vs 41.91 ± 10.38 ms, P0.001; PNN50 3.17 ± 1.23 vs 5.89 ± 2.18, P0.01; HF 239.82 ± 98.26 ms(2)/Hz vs 367.32 ± 188.37 ms(2)/Hz, P0.01)accompanied by the decreases in LF and LF/HF (LF 485.22 ± 217.34 ms(2)/Hz vs 287.94 ± 128.61 ms(2)/Hz, P0.01; LF/HF 2.03 ± 0.56 vs 0.79 ± 0.38, P0.001). The post-treatment SIs of SBP and DBP were 1.35 and 1.2 respectively.The combination treatment of angiotensin II receptor blocker (ARB), diuretics and β1-receptor blockers can lower the blood pressures stably, improve heart rate variability and lead to a reversal of hypertensive LVH.

The purpose of this study was to investigate the relation between the Arg389Gly polymorphism of the beta(1)-AR gene and chronic heart failure (CHF) and to evaluate the effect of this polymorphism on clinical response to beta-adrenoceptor blockade (bisoprolol) in patients with CHF.One hundred and ten patients with stable CHF receiving basic therapy for heart failure were included. Before initiation and 3 months after the maximal tolerated dose of bisoprolol was reached, all indices (including BP, HR, LAD, LVEDD, LVESD, LVEF, BNP level, 6 min walk distance) were measured and compared with the Arg389Gly genotypes, which identified by PCR-restriction fragment length polymorphism analysis. We also determined the Arg389Gly genotypes in 100 healthy control subjects, and compared the distribution of Arg389Gly genotypes with that in CHF.No difference was observed between the two groups in any of the three genotypes (CC, CG and GG). The prevalences of the three genotypes in normal subjects and patients with CHF were Arg389Arg 0.53 vs. 0.51, Arg389Gly 0.40 vs. 0.40, Gly38Gly 0.07 vs. 0.09, respectively. After 3 months of bisoprolol usage, a significant improvement in LVEF was observed in CC group, which increased from (36.7 +/- 8.63)% to (44.1 +/- 9.53)%, CG group, from (35.76 +/- 8.39)% to (42.90 +/- 9.41)%, but not GG group, from (36.00 +/- 5.66)% to (37.33 +/- 5.64)%. The improvement in BNP was also observed in CC [from (502.93 +/- 160.80) ng/L to (325.26 +/- 135.63) ng/L], CG [from (525.76 +/- 157.66) ng/L to (331.79 +/- 133.97) ng/L], but not GG [from (505.33 +/- 125.07) ng/L to (429.67 +/- 182.39) ng/L]. Arg389-homozygous patients showed a substantially greater improvement in LVEF and BNP, compared with Gly389-homozygous patients (all P0.01).There was no difference in the prevalence of the three genotypes between healthy and CHF subjects. The Gly389 polymorphism of the beta(1)-AR gene was not associated with an increased risk of CHF. The Arg389 variant of the beta(1)-AR gene was associated with a greater response to bisoprolol than that of the Gly389 variant in patients with CHF.