Fengjuan Yao

The Role of Macrolide Antibiotics in Increasing Cardiovascular Risk

BACKGROUND Large cohort studies provide conflicting evidence regarding the potential for oral macrolide antibiotics to increase the risk of serious cardiac events. OBJECTIVES This study performed a meta-analysis to examine the link between macrolides and risk of sudden cardiac death (SCD) or ventricular tachyarrhythmias (VTA), cardiovascular death, and death from any cause. METHODS We performed a search of published reports by using MEDLINE (January 1, 1966, to April 30, 2015) and EMBASE (January 1, 1980, to April 30, 2015) with no restrictions. Studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of interest were included. RESULTS Thirty-three studies involving 20,779,963 participants were identified. Patients taking macrolides, compared with those who took no macrolides, experienced an increased risk of developing SCD or VTA (RR: 2.42; 95% CI: 1.61 to 3.63), SCD (RR: 2.52; 95% CI: 1.91 to 3.31), and cardiovascular death (RR: 1.31; 95% CI: 1.06 to 1.62). No association was found between macrolides use and all-cause death or any cardiovascular events. The RRs associated with SCD or VTA were 3.40 for azithromycin, 2.16 for clarithromycin, and 3.61 for erythromycin, respectively. RRs for cardiovascular death were 1.54 for azithromycin and 1.48 for clarithromycin. No association was noted between roxithromycin and adverse cardiac outcomes. Treatment with macrolides is associated with an absolute risk increase of 118.1 additional SCDs or VTA, and 38.2 additional cardiovascular deaths per 1 million treatment courses. CONCLUSIONS Administration of macrolide antibiotics is associated with increased risk for SCD or VTA and cardiovascular death but not increased all-cause mortality.

Subclinical endothelial dysfunction and low‐grade inflammation play roles in the development of erectile dysfunction in young men with low risk of coronary heart disease

The purpose of this study is to investigate the possible underlying pathogenesis of erectile dysfunction(ED) in young men with low risk of coronary heart disease and no well-known aetiology. To conduct this study, 122 patients with ED under the age of 40 were enrolled, along with 33 age-matched normal control subjects. The patients with ED had significantly higher levels of systolic blood pressure (SBP), total cholesterol and triglyceride, high sensitivity C-reactive protein (hs-CRP), greater carotid intima-media thickness (CIMT) and Framingham risk score (FRS) than the control group, though all of these values were within the respective normal range. Further, the brachial artery flow- mediated vasodilation (FMD) values were significantly lower in ED patients and correlated positively with the severity of ED (r = 0.714, p < 0.001). When these significant factors were studied in the multivariate logistic regression model, FMD, SBP, hs-CRP and FRS remained the statistical significance. The receiver-operating characteristic (ROC) analysis demonstrated that FMD had a high ability to predict ED in young male with low FRS [area under the curve (AUC) 0.921, p < 0.001]. The cutoff value of FMD <10.25% had sensitivity of 82.8% and specificity of 100% for diagnosis of ED. FRS and hs- CRP were also proven to be predictors of ED (AUC 0.812, p < 0.001; AUC 0.645, p = 0.011, respectively). The results of this study validated that subclinical endothelial dysfunction and low-grade inflammation may be the underlying pathogenesis of ED with no well-known aetiology. Young patients complaining of ED should be screened for cardiovascular risk factors and possible subclinical atherosclerosis. Measurement of FMD, hs-CRP and FRS can improve our ability to predict and treat ED, as well as subclinical cardiovascular disease early for young male.

Weaker Masturbatory Erection May Be a Sign of Early Cardiovascular Risk Associated with Erectile Dysfunction in Young Men Without Sexual Intercourse

INTRODUCTION Although increasing evidences emphasize the importance of early cardiovascular evaluation in men with erectile dysfunction (ED) of unexplained aetiology, impaired masturbation-induced erections in young men are usually overlooked and habitually presumed to be psychological origin. AIMS To evaluate the young men presenting weaker masturbatory erection with no sexual intercourse (WME-NS) and verify if this cohort have early cardiovascular risks associated with ED. METHODS Male subjects aged 18-40 years with WME-NS were screened by analyzing detailed sexual intercourse and masturbatory history. The age-matched ED and non-ED population were identified by using International Index of Erectile Function-5 (IIEF-5). All subjects with acute and/or chronic diseases (including diagnosed hypertension and diabetes) and long-term pharmacotherapy were excluded. Nocturnal penile tumescence and rigidity (NPTR), systemic vascular parameters and biochemical indicators related to metabolism were assessed. MAIN OUTCOME MEASURES Comparison analysis and logistic regression analysis were conducted among WME-NS, ED and non-ED population. RESULTS In total, 78 WME-NS cases (mean 28.99 ± 5.92 years), 179 ED cases (mean 30.69 ± 5.21 years) and 43 non-ED cases (mean 28.65 ± 4.30 years) were screened for analysis. Compared with non-ED group, WME-NS group had higher prevalence of early ED risk factors including endothelial dysfunction, insulin resistance, high level of glycosylated serum protein and abnormal NPTR. Multivariable-adjusted logistic regression analysis showed endothelia dysfunction (odds ratio: 8.83 vs. 17.11, both P < 0.001) was the independent risk factor for both WME-NS and ED. CONCLUSIONS Weaker masturbatory erection may be a sign of early cardiovascular risk associated with ED in young men without sexual intercourse. More studies are warranted to elucidate the clinical benefits by targeting these formulated strategies.

The utility of HbA1c for screening gestational diabetes mellitus and its relationship with adverse pregnancy outcomes.

AIMS To evaluate the utility of glycated hemoglobin A1c (HbA1c) for screening gestational diabetes mellitus (GDM) and analyze its association with adverse pregnancy outcomes in a cohort of pregnant women. METHODS Women with singleton pregnancies, who completed a 2h oral glucose tolerance test (OGTT) and HbA1c test at gestational week 24-28 were enrolled in this retrospective study. Clinical information was obtained and statistical analyses were performed to assess the diagnostic value of HbA1c for GDM and the association of HbA1c with adverse pregnancy outcomes. RESULTS Of the 1959 pregnant women enrolled in the study, 413 were diagnosed with GDM. A HbA1c cutoff value <4.8% (29mmol/mol) showed adequate sensitivity to exclude GDM (85.0%) but low specificity (31.8%). While HbA1c cutoff value ≥5.5% (37mmol/mol) presented adequate specificity (95.7%) but low sensitivity (14.8%) in diagnosing GDM. Adoption of HbA1c as a screening test for GDM could eliminate the need for an OGTT in 34.7% women in our study, however, with 6.5% being wrongly diagnosed. HbA1c level was significantly associated with the risk of preterm delivery, neonatal hyperbilirubinemia, and neonatal asphyxia. CONCLUSIONS Whether adoption of HbA1c as a screening test for GDM would benefit pregnant women remains to be determined. However, HbA1c might be a useful tool to predict patients at increased risk of several adverse pregnancy outcomes.

Sex Differences Between Vascular Endothelial Function and Carotid Intima-Media Thickness by Framingham Risk Score

To investigate sex differences associated with changes in brachial artery flow‐mediated dilatation and carotid intima‐media thickness by Framingham Risk Score.

Erectile dysfunction is associated with subclinical carotid vascular disease in young men lacking widely-known risk factors

This study aimed to gain insight into the underlying pathogenesis of erectile dysfunction in young men under the age of 40 years without widely-known risk factors. Compared with normal controls, patients with erectile dysfunction had increased carotid intima–media thickness, fasting levels of blood glucose and insulin, and homeostatic model assessment index, as well as lower flow-mediated vasodilation and testosterone levels (P < 0.05), though all of these values were within their respective normal range. Multivariate logistic regression analysis identified carotid intima–media thickness, flow-mediated vasodilation, insulin level, and homeostatic model assessment index as significant predictors of erectile dysfunction. Young men with flow-mediated vasodilation <10.65% were 11.645 times more likely to have erectile dysfunction, young men with carotid intima–media thickness >0.623 mm had a 4.16-fold, and young men with homeostatic model assessment index >1.614 had a 5.993-fold greater risk of having erectile dysfunction. In conclusions, in young men with normal results from general clinical screening, an increased carotid intima–media thickness and homeostatic model assessment index and reduced flow-mediated vasodilation were associated with a higher incidence of erectile dysfunction. Erectile dysfunction may appear before the detection of traditional cardiovascular risk factors and may be the earliest clinical sign of subclinical cardiovascular disease.

High Serum Phosphorus Level Is Associated with Left Ventricular Diastolic Dysfunction in Peritoneal Dialysis Patients

Objectives We initiated this study to explore the relationships of serum phosphorus level with left ventricular ultrasound features and diastolic function in peritoneal dialysis (PD) patients. Methods 174 patients with end-stage renal disease (ESRD) receiving PD were enrolled in this retrospective observational study. Conventional echocardiography examination and tissue Doppler imaging (TDI) were performed in each patient. Clinical information and laboratory data were also collected. Analyses of echocardiographic features were performed according to phosphorus quartiles groups. And multivariate regression models were used to determine the association between serum phosphorus and Left ventricular diastolic dysfunction (LVDD). Results With the increase of serum phosphorus levels, patients on PD showed an increased tissue Doppler-derived E/e’ ratio of lateral wall (P < 0.001), indicating a deterioration of left ventricular diastolic function. Steady growths of left atrium and left ventricular diameters as well as increase of left ventricular muscle mass were also observed across the increasing quartiles of phosphorus, while left ventricular ejection fraction remained normal. In a multivariate analysis, the regression coefficient for E/e’ ratio in the highest phosphorus quartile was almost threefold higher relative to those in the lowest quartile group. And compared with patients in the lowest phosphorus quartile (<1.34 mmol/L) those in the highest phosphorus quartile (>1.95 mmol/L) had a more than fivefold increased odds of E/e’ ratio >15. Conclusions Our study showed an early impairment of left ventricular diastolic function in peritoneal dialysis patients. High serum phosphorus level was independently associated with greater risk of LVDD in these patients. Whether serum phosphorus will be a useful target for prevention or improvement of LVDD remains to be proved by further studies.

The Role of the Rho/ROCK Pathway in Ang II and TGF-β1-Induced Atrial Remodeling.

Objectives To study the role of the Rho/ROCK pathway in Ang II and TGF-β1-induced atrial remodeling. Methods and Results A canine atrial fibrillation (AF) model was established by rapid atrial pacing (RAP) of the left atrium. The roles of TGF-β1, the RhoA/ROCK signaling pathway and connective tissue growth factor (CTGF) in atrial remodeling were studied via both in vitro and in vivo experiments. Each of the dogs that received RAP developed persistent AF within 4 weeks. The mRNA expression levels of TGF-β1 (1.32±0.38), Collagen-I(1.33±0.91), CTGF(5.83±3.71), RhoA(1.23±0.57) and ROCK-1 (1.02±0.27) in the left atrium were significantly increased following 4 weeks of RAP. Angiotensin II (Ang II) induced the proliferation of atrial fibroblasts and up-regulated the expression of both CTGF and ROCK-1 in a dose-dependent manner. Simvastatin and Y27632 reversed Ang II-induced CFs proliferation, as well as ROCK-1(0.89±0.05 and 1.27±0.03, respectively) and CTGF (0.87±0.04 and 0.91±0.02, respectively) expression. The expression mRNA of ROCK-1(1.74±0.13) and CTGF (2.28±0.11) can upregulated by TGF-β1, and down-regulated by Simvastatin (1.22±0.03 vs 2.27±0.11), Y27632 (1.01±0.04 vs 1.64±0.03), Los (1.04±0.11 vs 1.26±0.05), respectively. Losartan and Simvastatin attenuated the effects of TGF-β1, inhibited RhoA activity as opposed to RhoA protein expression. Y27632 had no effect on either the expression or the activity of RhoA. Conclusions The increased expression of profibrotic factors (CTGF, ROCK1 and Smad2/3) played an important role in our RAP-induced AF model. Increased atrial profibrotic factors involve the activation of either the TGF-β1/RhoA/ROCK-1 or the TGF-β1/Smad2/3 signaling pathway.

EECP IMPROVE VASCULAR FUNCTION AND STATUS IN HYPERCHOLESTEROLEMIC SUBJECTS WITH SUBCLINICAL ATHEROSCLEROSIS

Enhanced external counterpulsation (EECP) is a circulation assist device that may improve endothelial dysfunction by increasing blood flow shear stress. We aim to explore the effect of EECP on non- invasive vascular makers in hypercholesterolemic subjects with subclinical atherosclerosis. 49

GW24-e1282 A noninvasive sizing method to choose fitted atrial septal defect occluder by transthoracic echocardiography in adults with secundum atrial septal defects

Objectives In our clinical practice, we try to find a feasible method to size the hole of ASD by only 2D transthoracic echocardiography (2D-TTE). It should be more practical, less expensive and without pain. Methods Sixty-seven consecutive adult patients (26 males, 41 females, mean age 38.4 ± 8.5 years) were scheduled to have ASD device closure. Before that, we calculated the size of ASD by 2D transthoracic echocardiography (2D-TTE) through parasternal four chambers view, parasternal short axes view, apical four chambers view, subcostal four chambers view and subcostal two chambers view. The biggest size from the views would be chosen for ASD device closure. Meanwhile, we paid attention to the ASD margins, and we divided them to floppy margin group (n = 24) and firm margin group (n = 43). For the floppy margin patients, we would add 2 or 4 mm more than the 2D-TTE size for preparing ASD device size. And for the firm margin patient, we chose the same 2D-TTE size for ASD device size. Results The total successful ASD device closure rate was 94.0% (63/67). The average total trans-catheter ASD closure time was 42.3 ± 12.5 minutes. ASD device closure succeeded at the first time was: 40/43 (93.0%) in the firm margin group; 16/24 (66.7%) in the floppy margin group. For the rest patient whose ASD couldn’t be closed at the first time, we reduced the size 2–5 mm in the firm margin group, the rest 3 all got successful ASD device closed. As in the floppy margin group, there were 4 patients needed adding 4–6 mm to the 2D-TTE size and then their ASD device closed successfully. There were only 4 patients (6%) in floppy margin group couldn’t be ASD device closed. For average 1.4 years follow up, only 6 patients (9.5%) had some chest pain complain, but all the devices were stable. Conclusions With our experience, the sizing based on 2D-TTE could be used for ASD device selection. The multiple views of TTE should be used to calculate the biggest size of ASD. And the margins of the ASD hole also need to be considered.