Anping Cai

Lipoprotein-associated phospholipase A2 (Lp-PLA(2)): a novel and promising biomarker for cardiovascular risks assessment.

Atherosclerosis and its manifestations namely cardiovascular diseases (CVD) are still the leading cause of morbidity and mortality worldwide. Although intensified interventions have been applied, the residual cardiovascular (CV) risks are still very high. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a novel and unique biomarker highly specific for vascular inflammation and atherosclerosis. Both pro-atherogenic property of Lp-PLA2 and positive correlation with CV events have already been demonstrated by a large number of scientific and clinical studies. Currently, in the Adult Treatment Panel III (ATP III) guideline, Lp-PLA2 has been recommended as an adjunct to traditional risk factors in assessing future CV risks. Encouragingly, darapladib, an orally Lp-PLA2 specific inhibitor, has been tested in basic research and preclinical trials and the outcomes are quite striking. Additionally, there are two phase III ongoing clinical trials in evaluating the efficacy and safety of darapladib on cardiovascular outcomes. With regard to the potential values of Lp-PLA2 in risk stratification, therapeutic regimen establishment and prognosis evaluation in patients with moderate or high risk, our present review is going to summarize the relevant data about the bio-chemical characteristics of Lp-PLA2, the actions of Lp-PLA2 on atherosclerosis and the results of Lp-PLA2 in scientific research and clinical studies.

Hypertension and obstructive sleep apnea

Obstructive sleep apnea (OSA) is a major modifiable risk factor of hypertension and hypertensive patients with OSA are at increased risk for cardiovascular diseases. A substantial number of studies have revealed that OSA and hypertension have synergistic effects on the cardiovascular system and, therefore, it is clinically important and relevant to increase our understanding of the pathophysiological interactions between OSA and hypertension. In our present review, after briefly reviewing the characteristics and pathophysiological effects of OSA, we focus on the current understanding of OSA-associated hypertension, the potential approaches for treatment of OSA and the effect of OSA treatment on hypertension management. We hope our present review will shed light for future studies that investigate effective therapeutic strategies to simultaneously improve the management of OSA and hypertension.

Rho‐GTPase and Atherosclerosis: Pleiotropic Effects of Statins

3‐Hydroxy‐methylglutaryl‐coenzyme A (HMG‐CoA) reductase inhibitors or statins are a class of medications with potent effects on reducing serum cholesterol level, and currently have been widely used in the primary and secondary prevention of atherosclerotic cardiovascular diseases (ASCVD).

SDF-1α upregulation by atorvastatin in rats with acute myocardial infarction via nitric oxide production confers anti-inflammatory and anti-apoptotic effects

BackgroundThe effects of atorvastatin on SDF-1α expression under acute myocardial infarction (AMI) are still unclear. Therefore, our present study is to investigate the roles and mechanisms of atorvastatin treatment on SDF-1α expression in rats with AMI.MethodsMale Sprague–Dawley rats were underwent permanent coronary artery ligation and randomly assigned into four groups as follow: blank control (B), atorvastatin (A), atorvastatin plus L-NAME (A+L-NAME), and atorvastatin plus AMD3100 (A+AMD3100). Rats underwent similar procedure but without ligation were used as group sham operated (S). Atorvastatin (10mg/Kg/d body weight) was administrated by gavage to rats in three atorvastatin treated groups, and L-NAME (40mg/Kg/d body weight) or AMD3100 (5mg/Kg/d body weight) was given to group A+L-NAME or A+AMD3100, respectively.ResultsComparing with group B, NO production, SDF-1α and CXCR4 expression were significantly up-regulated in three atorvastatin treated groups at the seventh day. However, the increments of SDF-1α and CXCR4 expression in group A+L-NAME were reduced when NO production was inhibited by L-NAME. Anti-inflammatory and anti-apoptotic effects of atorvastatin were offset either by decrease of SDF-1α and CXCR4 expression (by L-NAME) or blockage of SDF-1α coupling with CXCR4 (by AMD3100). Expression of STAT3, a cardioprotective factor mediating SDF-1α/CXCR4 axis induced cardiac protection, was up-regulated most significantly in group A. The effects of atorvastatin therapy on cardiac function were also abrogated either when SDF-1α and CXCR4 expression was diminished or the coupling of SDF-1α with CXCR4 was blocked.ConclusionSDF-1α upregulation by atorvastatin in rats with AMI was, at least partially, via the eNOS/NO dependent pathway, and SDF-1α upregulation and SDF-1α coupling with CXCR4 conferred anti-inflammatory and anti-apoptotic effects under AMI setting which we speculated that ultimately contributed to cardiac function improvement.

Associations of systolic and diastolic blood pressure night-to-day ratios with atherosclerotic cardiovascular diseases.

Our objective was to evaluate the associations of the systolic and diastolic blood pressure night-to-day ratios (SBP-NDR and DBP-NDR) with composite atherosclerotic cardiovascular diseases (ASCVDs) comprising coronary heart disease (CHD) and ischemic stroke (IS) cases, respectively. The clinical conditions associated with SBP-NDR and DBP-NDR were also evaluated. A total of 401 patients who underwent 24-h ambulatory BP monitoring were enrolled. In general, the mean age was 59.7±14.7 years and male subjects accounted for 59.1% of the study subjects. Regarding the ASCVD risk factors, 17.0% of the study subjects smoked, 5.2% abused alcohol, 2.0% had a family history of ASCVD, 23.3% had diabetes and 96.0% had dyslipidemia. Fifty (12.5%) and 128 (31.9%) study subjects had a previous diagnosis of CHD and IS, respectively. Dipper and non-dipper pattern-specific differences in clinical characteristics between the SBP-NDR and DBP-NDR categories were observed. The multiple linear regression analysis showed that advanced age, smoking, CHD and IS were positively associated with SBP-NDR and statins were inversely associated with SBP-NDR; only IS was positively associated with DBP-NDR. The logistic regression analysis showed that after adjusting for the covariates of age, smoking, alcohol abuse, diabetes, hypertension, dyslipidemia, and SBP and DBP at admission, only DBP-NDR remained significantly associated with composite ASCVD, with an odds ratio of 1.029 (95% confidence interval 1.002–1.056, P=0.038). There were significant differences in the associations of SBP-NDR and DBP-NDR with composite ASCVD. Clinical conditions independently associated with SBP-NDR and DBP-NDR were also somewhat different. In a specific population group, DBP-NDR may be superior to SBP-NDR with respect to screening for ASCVD.

Pathophysiological effects of RhoA and Rho-associated kinase on cardiovascular system.

In past decades, growing evidence from basic and clinical researches reveal that small guanosine triphosphate binding protein ras homolog gene family, member A (RhoA) and its main effector Rho-associated kinase (ROCK) play central and complex roles in cardiovascular systems, and increasing RhoA and ROCK activity is associated with a broad range of cardiovascular diseases such as congestive heart failure, atherosclerosis, and hypertension. Favorable outcomes have been observed with ROCK inhibitors treatment. In this review, we briefly summarize the pathophysiological roles of RhoA/ROCK signaling pathway on cardiovascular system, displaying the potential benefits in the cardiovascular system with controlling RhoA/ROCK signaling pathway.

Circulating miRNA29 family expression levels in patients with essential hypertension as potential markers for left ventricular hypertrophy

ABSTRACT Objectives: The role of microRNAs (miRs,miRNAs) in the pathogenesis of cardiovascular diseases such as hypertension, as well as their diagnostic potential, has recently attracted much attention. However, target-organ damage (TOD) of hypertension remains a substantial challenge due to the lack of specific biomarkers. The present study was undertaken to identify and validate the potential of circulating miRs as novel biomarkers for TOD. Methods: We assessed the expression levels of miR-29a, miR-29b, and miR-29c in 54 patients with untreated essential hypertension and 30 healthy individuals. All patients underwent two-dimensional echocardiography, office, and ambulatory blood pressure monitoring. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to evaluate the expression of selected miRs. The expression level of miR-29a, miR-29b, and miR-29c correlations between blood pressure and echocardiography parameters were assessed using the Spearman correlation coefficient. Results: We observed higher expression levels of miR-29a (31.50 ± 3.90 vs 26.55 ± 1.74; p < 0.001), miR-29b (32.31 ± 2.85vs 27.21 ± 1.59; p < 0.001), and miR-29c (31.13 ± 3.42 vs 25.96 ± 1.88; p < 0.001) in hypertensive patients compared with healthy control individuals. In hypertension patients, 25 patients were left ventricular hypertrophy (LVH), miR-29a (32.82 ± 4.06 vs 30.07 ± 3.68; p = 0.012), miR-29b (33.27 ± 2.84 vs 30.71 ± 3.04; p = 0.02), and miR-29c (32.33 ± 3.52 vs 29.55 ± 3.46; p = 0.005) in LVH patients compared with nLVH patients. We found miR-29a, miR-29b, and miR-29c expression levels showed significant positive correlations with office SBP (p = 0.579, p < 0.001; r = 0.576, p < 0.001; r = 0.598, p < 0.001), office DBP (p = 0.243, p = 0.026; r = 0.304, p = 0.005; r = 0.287, p = 0.008), office PP(r = 0.49, p < 0.001; r = 0.442, p < 0.001; r = 0.479, p < 0.001), 24 h mean SBP(p = 0.511, p < 0.001; r = 0.6, p < 0.001; r = 0.533, p < 0.001), 24 h mean DBP (p = 0. 304, p = 0.005; r = 0.283, p = 0.009; r = 0.340, p = 0.002), and 24 h mean PP (p = 0.385, p < 0.001; r = 0. 506, p < 0.001; r = 0.386, p < 0.001), respectively. The expression levels of miR-29a, miR-29b, and miR-29c were positively related to LVMI (r = 0.65, p < 0.001; r = 0.715, p < 0.001; r = 0.654, p < 0.001), respectively. Conclusion: Circulating the miR-29 family may possibly represent potential non-invasive markers of hypertension and TOD in essential hypertensive patients.

Associations of high HDL cholesterol level with all-cause mortality in patients with heart failure complicating coronary heart disease

Abstract The aim of the present study was to evaluate the association between HDL cholesterol level and all-cause mortality in patients with ejection fraction reduced heart failure (EFrHF) complicating coronary heart disease (CHD). A total of 323 patients were retrospectively recruited. Patients were divided into low and high HDL cholesterol groups. Between-group differences and associations between HDL cholesterol level and all-cause mortality were assessed. Patients in the high HDL cholesterol group had higher HDL cholesterol level and other lipid components (P <0.05 for all comparison). Lower levels of alanine aminotransferase (ALT), high-sensitivity C-reactive protein (Hs-CRP), and higher albumin (ALB) level were observed in the high HDL cholesterol group (P <0.05 for all comparison). Although left ventricular ejection fraction (LVEF) were comparable (28.8 ± 4.5% vs 28.4 ± 4.6%, P = 0.358), mean mortality rate in the high HDL cholesterol group was significantly lower (43.5% vs 59.1%, P = 0.007). HDL cholesterol level was positively correlated with ALB level, while inversely correlated with ALT, Hs-CRP, and NYHA classification. Logistic regression analysis revealed that after extensively adjusted for confounding variates, HDL cholesterol level remained significantly associated with all-cause mortality although the magnitude of association was gradually attenuated with odds ratio of 0.007 (95% confidence interval 0.001–0.327, P = 0.012). Higher HDL cholesterol level is associated with better survival in patients with EFrHF complicating CHD, and future studies are necessary to demonstrate whether increasing HDL cholesterol level will confer survival benefit in these populations of patients.

Increased serum level of Lp-PLA2 is independently associated with the severity of coronary artery diseases: a cross-sectional study of Chinese population

BackgroundLipoprotein-associated phospholipase A2 (Lp-PLA2) plays complex and adverse roles on atherosclerosis. Current study was to investigate whether increased plasma Lp-PLA2 level is independently associated with the severity of coronary artery diseases (CAD).MethodsTotally 781 participants were enrolled and performed coronary angiography (CAG) to figure out the number of coronary artery stenosis. According to clinical presentation, electrocardiography, cardiac biomarker, and CAG result, participants were divided into control (excluded CAD), stable angina (SA), unstable angina (UA) and acute myocardial infarction (AMI) groups. Baseline characteristics were recorded. Statistical analyses were performed to evaluate the relationship between Lp-PLA2 level and CAD severity.ResultsPlasma levels of Lp-PLA2 in control, SA, UA and AMI groups were 7.38(3.33-9.26) μg/L, 5.94(2.89-8.55) μg/L, 8.56(5.34-11.95) μg/L and 8.68(5.56-13.27) μg/L respectively (P < 0.001). After adjusted for age, gender, smoking, diabetes mellitus, hypertension, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), apoprotein A (apoA) and statins, Lp-PLA2 level was still independently associated with CAD severity, with odd ratio (OR) of 1.055 (AMI group versus control group, 95% confidence interval (CI) 1.021-1.090, P < 0.05). Additionally, the relationship between Lp-PLA2 level and the number of stenosis coronary artery was also assessed. Lp-PLA2 levels in control, single-vessel, and multiple-vessels stenosis groups were 7.38(3.33-9.26) μg/L, 7.80 (4.05-10.76) μg/L and 8.29(5.18-11.76) μg/L respectively (P for trend < 0.001). After adjusted for age, gender, smoking, diabetes mellitus, hypertension, LDL-C and HDL-C, apoA and statins, Lp-PLA2 level remained independently associated with the number of coronary artery stenosis, with OR of 1.053 (multiple-vessels stenosis group versus control group, 95% CI 1.025-1.069, P < 0.05).ConclusionIncreased Lp-PLA2 level is independently associated with CAD severity, and Lp-PLA2 level may be used to discriminate those who are at increased risk of cardiovascular events.

Benign metastasizing leiomyoma

Benign metastasizing leiomyoma (BML) is a rare clinical condition predominantly occurring in reproductive women with a history of uterine leiomyoma resection or hysterectomy. Oftentimes, it is easy to be misdiagnosed as a malignant tumor when nodules are found in multiple tissues. In order to raise clinicians’ awareness of BML, we present a short review of the literature in combination with an unusual case.ZusammenfassungEin benignes metastasierendes Leiomyom (BML) ist eine seltene Erkrankung, die bei Frauen im fortpflanzungsfähigen Alter mit Resektion eines Leiomyoms der Gebärmutter oder Hysterektomie in der Anamnese vorkommt. In vielen Fällen ist es leicht als maligner Tumor fehlzudiagnostizieren, wenn sich Knötchen in mehreren Geweben finden. Um das Bewusstsein der klinisch tätigen Ärzte für ein BML zu erhöhen, werden Erkenntnisse zum BML in der vorliegenden Literatur zusammen mit einem ungewöhnlichen Fall dargestellt.