Impact of long-term potassium supplementation on thiazide diuretic-induced abnormalities of glucose and uric acid metabolisms.

Treatment of hypertension with thiazide diuretics may trigger hypokalemia, hyperglycemia, and hyperuricemia. Some studies suggest simultaneous potassium supplementation in hypertensive patients using thiazide diuretics. However, few clinical studies have reported the impact of long-term potassium supplementation on thiazide diuretic-induced abnormalities in blood glucose and uric acid (UA) metabolisms. One hundred hypertensive patients meeting the inclusion criteria were equally randomized to two groups: IND group receiving indapamide (1.25-2.5 mg daily) alone, and IND/KCI group receiving IND (1.25-2.5 mg daily) plus potassium chloride (40 mmol daily), both for 24 weeks. At the end of 24-week follow-up, serum K+ level in IND group decreased from 4.27 ± 0.28 to 3.98 ± 0.46 mmol/L (P < 0.001), and fasting plasma glucose (FPG) and UA increased from 5.11 ± 0.52 to 5.31 ± 0.57 mmol/L (P < 0.05), and from 0.404 ± 0.078 to 0.433 ± 0.072 mmol/L (P < 0.05), respectively. Serum K+ level in IND/KCl group decreased from 4.27 ± 0.36 to 3.89 ± 0.28 mmol/L (P < 0.001), and FPB and UA increased from 5.10 ± 0.41 to 5.35 ± 0.55 mmol/L (P < 0.01), and from 0.391 ± 0.073 to 0.457 ± 0.128 mmol/L (P < 0.001), respectively. The difference value between the serum K+ level and FPG before and after treatment was not statistically significant between the two groups. However, the difference value in UA in IND/KCl group was significantly higher than that in IND group (0.066 (95% confidence interval (CI): 0.041-0.090) mmol/L vs. 0.029 (95% CI: 0.006-0.058) mmol/L, P < 0.05). The results showed that long-term routine potassium supplementation could not prevent or attenuate thiazide diuretic-induced abnormalities of glucose metabolism in hypertensive patients; rather, it may aggravate the UA metabolic abnormality.

Immediate- and medium-term effects of simultaneous percutaneous corrections of secundum type atrial septal defect combined with pulmonary valve stenosis in local anesthesia and without transesophageal echocardiography guidance.

BACKGROUND: The feasibility and efficacy of simultaneous percutaneous treatment of secundum type atrial septal defect (ASD) combined with pulmonary valve stenosis (PS) have not been proved. OBJECTIVE: To evaluate the safety and efficacy on the clinical benefit of simultaneous percutaneous correction of these two pathologies under local anesthesia and without transesophageal echocardiography guidance. METHODS: Transpulmonary gradient, functional status, pulmonary regurgitation (PR), and tricuspid regurgitation (TR) were studied in 35 patients undergoing percutaneous balloon pulmonary valvuloplasty and ASD closure from March 2004 to July 2012. All patients were followed up until January 2013, an average of 39 months. RESULTS: According to color Doppler transthoracic echocardiography (TTE) before the intervention, the ASD defect size and transpulmonary gradient were 17±8.4 mm and 88±37.8 mmHg, respectively. Post-interventionally, the peak-to-peak transpulmonary gradient decreased from 77±37.6 mmHg to 20±16.2 mmHg (p<0.001) and the ASD occluder size was 23±10.5 mm. In all those patients, there was no residual shunt detected, and moderate and severe TR decreased from 45.7% (16/35) and 20% (7/35) to 8.6% (3/35) and 5.7% (2/35) before and after intervention detected by TTE, respectively. Eight patients had mild PR after procedure and two of them recovered at 6 months and no patient encountered severe adverse events at the latest follow-up. CONCLUSION: Simultaneous percutaneous corrections of ASD combined with PS are feasible, safe, and effective with satisfactory results.

Elevated microRNA-155 promotes foam cell formation by targeting HBP1 in atherogenesis.

AIM: MicroRNAs (miRNAs) play key roles in inflammatory responses of macrophages. However, the function of miRNAs in macrophage-derived foam cell formation is unclear. Here, we investigated the role of miRNAs in macrophage-derived foam cell formation and atherosclerotic development. METHODS AND RESULTS: Using quantitative reverse transcription-PCR (qRT-PCR), we found that the level of miR-155 expression was increased significantly in both plasma and macrophages from atherosclerosis (ApoE(-/-)) mice. We identified that oxidized low density lipoprotein (oxLDL) induced the expression and release of miR-155 in macrophages, and that miR-155 was required to mediate oxLDL-induced lipid uptake and reactive oxygen species (ROS) production of macrophages. Furthermore, ectopic overexpression and knockdown experiments identified that HMG box-transcription protein1 (HBP1) is a novel target of miR-155. Knockdown of HBP1 enhanced lipid uptake and ROS production in oxLDL-stimulated macrophages, and overexpression of HBP1 repressed these effects. Furthermore, bioinformatics analysis identified three YY1 binding sites in the promoter region of pri-miR-155 and verified YY1 binding directly to its promoter region. Detailed analysis showed that the YY1/HDAC2/4 complex negatively regulated the expression of miR-155 to suppress oxLDL-induced foam cell formation. Importantly, inhibition of miR-155 by a systemically delivered antagomiR-155 decreased clearly lipid-loading in macrophages and reduced atherosclerotic plaques in ApoE(-/-) mice. Moreover, we observed that the level of miR-155 expression was up-regulated in CD14(+) monocytes from patients with coronary heart disease. CONCLUSION: Our findings reveal a new regulatory pathway of YY1/HDACs/miR-155/HBP1 in macrophage-derived foam cell formation during early atherogenesis and suggest that miR-155 is a potential therapeutic target for atherosclerosis.

Effect of metformin on weight gain during antihypertensive treatment with a beta-blocker in Chinese patients.

BACKGROUND: Overweight and obesity are associated with cardiovascular disease (CVD). This study was designed to investigate whether combined use of nitrendipine and atenolol has any effect on body weight (BW) and whether metformin can prevent antihypertensive medication-induced weight gain and has any effect on blood glucose (BG). METHODS: Included in the present study were 94 hypertensive patients with a body mass index (BMI) > or =25 kg/m(2), of whom 45 patients were treated with nitrendipine plus atenolol (N/A group), and the remaining 49 patients were treated with nitrendipine, atenolol, and metformin (N/A/M group). The mean follow-up duration was 14 months. BW and glucose tolerance were measured. RESULTS: In N/A group, BW and fasting BG significantly increased from 73.5 +/- 9.6 kg to 74.2 +/- 9.7 kg (P < 0.05) and from 94.2 +/- 10.5 mg/dl to 97.9 +/- 11.3 mg/dl (P < 0.01), respectively, whereas postprandial BG did not change significantly. In N/A/M group, BW slightly decreased from 72.7 +/- 10.1 kg to 72.3 +/- 10.2 kg (P = 0.30), and fasting BG did not change significantly (93.5 +/- 10.4 mg/dl vs. 92.7 +/- 10.2 mg/dl, P = 0.59), whereas 2-h postprandial BG significantly decreased from 133.7 +/- 30.5 mg/dl to 124.0 +/- 29.6 mg/dl (P < 0.05). Furthermore, a significant difference was observed in difference value of BW before and after treatment between the two groups (0.7 (95% confidence interval, 0.1-1.3) kg in N/A group vs. -0.4 (95% confidence interval, -1.3 to 0.4) kg in N/A/M group, P < 0.05). CONCLUSIONS: Combination therapy of nitrendipine and atenolol may significantly increase BW and fasting BG in overweight or obese patients with hypertension. Metformin may prevent BW gain and improve BG levels in hypertensive patients who received combination therapy of nitrendipine and atenolol.