Association of cognitive impairment and diabetes on survival in Chinese older people with hypertension: a 10-year prospective study.

BACKGROUND: Older people with hypertension may have more complex multisystem problems and a higher risk of morbidity and mortality. We aimed to examine the association of cognitive impairment (CI) and diabetes mellitus (DM) on all-cause mortality in the aged with hypertension (HTN). METHODS: This is a prospective cohort study with a sample of 1017 older people with hypertension aged 60 years or older who completed baseline examinations in 2009-2010 and followed up for ten years in 2020. The endpoint was death from any cause. Subjects were categorized as HTN only, HTN + DM, HTN + CI, and HTN + DM + CI. Cox regression model was used to determine the association of comorbidities on all-cause mortality. RESULTS: During the 10-year follow-up period, 196 deaths occurred. After adjusted for covariates, risk of death from any cause was significantly increased in the older people with increased comorbidities (P = 0.003). Compared with the HTN only, with HTN + CI, and HTN + DM + CI, the HRs (95% confidence intervals) for all-cause mortality were 1.61(1.13-2.30) and 1.79(1.07-2.99), respectively. In stratified analyses, the relationship between comorbidities level and the risk of all-cause mortality persisted. CONCLUSION: All-cause mortality risks increased with increasing the comorbidities. This study emphasizes the importance of comprehensive management of the older people with HTN in clinical practice and public health policy.

Catheter ablation vs. drug therapy in the treatment of atrial fibrillation patients with heart failure: An update meta-analysis for randomized controlled trials.

Background: Atrial fibrillation (AF) and heart failure (HF) often coexist. The treatment of AF in patients with HF has been challenging because of the ongoing debate about the merits of catheter ablation vs. drug therapy. Methods: The Cochrane Library, PubMed, and www.clinicaltrials.gov were searched until June 14, 2022. Inclusion criteria were catheter ablation compared with drug therapy in adults with AF and HF in randomized controlled trials (RCTs). Primary outcomes consisted of all-cause mortality, re-hospitalization, change in left ventricular ejection fraction (LVEF), and AF recurrence. Secondary outcomes referred to quality of life [QoL; measured by the Minnesota Living with Heart Failure Questionnaire (MLHFQ)], six-minute walk distance (6MWD), and adverse events. The PROSPERO registration ID was CRD42022344208. Findings: In total, nine RCTs with 2,100 patients met the inclusion criteria, with 1,062 for catheter ablation and 1,038 for medication. According to the meta-analysis, catheter ablation significantly reduced all-cause mortality compared with drug therapy [9.2% vs. 14.1%, OR: 0.62, (95% CI: 0.47-0.82), P = 0.0007, I 2 = 0%], improved LVEF [MD: 5.65%, (95% CI: 3.32-7.98), P < 0.00001, I 2 = 86%], reduced AF recurrence [41.6% vs. 61.9%, OR: 0.23, (95% CI: 0.11-0.48), P < 0.0001, I 2 = 82%], decreased the MLHFQ score [MD: -6.38, (95% CI: -11.09 to -1.67), P = 0.008, I2 = 64%] and increased 6MWD [MD: 17.55, (95% CI: 15.77-19.33), P < 0.0001, I 2 = 37%]. Catheter ablation did not increase the re-hospitalization [30.4% vs. 35.5%, OR: 0.68, (95% CI: 0.42-1.10), P = 0.12, I 2 = 73%] and adverse events [31.5% vs. 30.9%, OR: 1.06, (95% CI: 0.83-1.35), P = 0.66, I 2 = 48%]. Interpretation: In AF patients with HF, catheter ablation improves exercise tolerance, QoL, and LVEF and significantly reduced all-cause mortality and AF recurrence. Although the differences were not statistically significant, the study found lower re-hospitalization and approximate adverse events with improved catheter ablation tendency. PROSPERO registration ID: CRD42022344208.

Hypertriglyceridemic waist phenotype is associated with left ventricular hypertrophy in Chinese hypertension patients.

Left ventricular hypertrophy (LVH), the most common target organ damage in patients with hypertension, is closely related to excessive visceral adipose tissue (VAT) accumulation in the body. The hypertriglyceridemic waist (HTHW) phenotype can act as a surrogate marker of excessive VAT. However, the relationship between the HTHW phenotype and LVH in patients with hypertension remains unknown. The present study aimed to investigate whether the HTHW phenotype is associated with LVH, using echocardiography in a cross-sectional study involving 4470 middle-aged and older Chinese patients with hypertension. Logistic regression analysis revealed that patients with the HTHW phenotype were 1.52-fold more likely to experience LVH than those with normal triglyceride levels and normal waist circumference. This association was independent of age, sex, and other potentially confounding factors. In the stratified analysis, a stronger correlation was found among women, people of at least 70 years of age, and people with hyperuricemia. These results suggest that distinguishing the HTHW phenotype in patients with hypertension could serve as a simple and effective screening strategy for identifying people with a higher risk of developing LVH.

Conicity-index predicts all-cause mortality in Chinese older people: a 10-year community follow-up.

BACKGROUND: Abdominal obesity (AO) has been regarded as the most dangerous type of obesity. The Conicity-index (C-index) had a high ability to discriminate underlying AO. The purpose of this study was to determine the ability of C-index to predict all-cause mortality among non-cancer Chinese older people. METHODS: The participants were residents of the Wanshou Road community in Beijing, China. Receiver operating curve (ROC) curves were used to determine the sensitivity and specificity of the best cut-off values for different anthropometric measures for predicting all-cause mortality. The area under the curve (AUC) of the ROC curves were calculated to compare the relative ability of various anthropometric measures to correctly identify older people in the community where all-cause mortality occurs. Included subjects were grouped according to C-index tertiles. The association between C-index and all-cause mortality was verified using Kaplan-Meier survival analysis and different Cox regression models. RESULTS: During a mean follow-up period of 9.87 years, 1821 subjects completed follow-up. The average age was 71.21 years, of which 59.4% were female. The ROC curve results showed that the AUC of the C-index in predicting all-cause mortality was 0.633. Kaplan-Meier survival curves showed a clear dose-response relationship between C-index and all-cause mortality. With the increase of C-index, the survival rate of the study population showed a significant downward trend (P < 0.05). Adjusted for age, gender, hip circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose (FBG), 2-h postprandial blood glucose (2hPG), glycosylated hemoglobin, high-density lipids protein (LDL), triglyceride, serum creatinine, serum uric acid, urine albumin-creatinine ratio (UACR), Mini-Mental State Examination (MMSE), smoking history, and drinking history, COX regression analysis showed that in the model adjusted for all covariates, the risk of all-cause mortality in tertile 3 was 1.505 times that in tertile 1, and the difference was statistically significant. CONCLUSIONS: The C-index is an independent risk factor for all-cause mortality in the non-cancer Chinese older people.

Effects of ankle-brachial index and brachial-ankle pulse wave velocity on all-cause mortality in a community-based elderly population.

Background: Ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) are both important indicators of arterial stiffness and vascular injury. At present, most studies on the relationship between ABI and baPWV and all-cause mortality in community-based elderly are analyzing ABI or baPWV alone, and will focus on a single special population such as diabetes and stroke. The purpose of this study was to evaluate the relationship between ABI and baPWV in a Chinese community-based elderly population, and to analyze their impact on all-cause mortality in a community-based population through a follow-up of nearly 10 years. Methods: Participants were residents of the Wanshou Road community in Beijing, China. A total of 2,162 people in the community were included, with an average age of 71.48 years. During a mean follow-up period of 9.87 years, 1,826 subjects completed follow-up. Kaplan-Meier survival analysis and different Cox regression models were used to verify the association of ABI and baPWV with all-cause mortality. The selected subjects were divided into two groups according to ABI and baPWV, and ABI was divided into two groups with 0.90 as the cut-off point (group 1: 0.9 < ABI ≤ 1.3; group 2: ABI ≤ 0.9); according to the level of baPWV, they were divided into three groups (Tertile 1: baPWV <1761.5 cm/s; Tertile 2: 1761.5 ≤ baPWV <2121.5 cm/s; Tertile 3: baPWV ≥2121.5 cm/s). Results: 1,826 people were included in the statistical analysis, and the total mortality rate was 181.3/1000. The 10-year all-cause mortality rate of the abnormal ABI group (group 2) was 44.7%, and that of the normal ABI group (group 1) was 17.0%; The 10-year all-cause mortality rates from low to high in the baPWV tertile were 10.0%, 18.7%, and 26.4%. In the Cox proportional hazards model, after adjusting for possible confounders, the effect of baPWV on all-cause mortality was significant, with the 3rd tertile having a 1.647-fold higher risk of all-cause mortality than the 1st tertile (P = 0.014 ). Conclusions: ABI and baPWV are risk factors affecting all-cause mortality in the elderly community population, and baPWV is an independent predictor of all-cause mortality in the elderly community population.

Association of the Weight-Adjusted-Waist Index With Risk of All-Cause Mortality: A 10-Year Follow-Up Study.

Background: To explore the relationship between weight-adjusted-waist index (WWI) and the risk of all-cause mortality in one urban community-dwelling population in China. Methods: This is a prospective cohort study with a sample of 1,863 older adults aged 60 years or over in Beijing who completed baseline examinations in 2009-2010 and a 10-year follow-up in 2020. WWI was calculated as waist circumference (cm) divided by the square root of weight (kg). Cox regression analysis was performed to investigate the significance of the association of WWI with all-cause mortality. The area under the receiver operating characteristic (ROC) curves were used to compare the ability of each obesity index to predict mortality. Results: During a median follow-up of 10.8 years (1.0 to 11.3 years), 339 deaths occurred. After adjusted for covariates, the hazard ratios (HRs) for all-cause mortality progressively increased across the tertile of WWI. Compared with the lowest WWI category (tertile1 <10.68 cm/√kg), with WWI 10.68 to 11.24cm/√kg, and≥11.25 cm/√kg, the HRs (95% confidence intervals (CIs)) for all-cause mortality were 1.58 (1.12-2.22), and 2.66 (1.80-3.92), respectively. In stratified analyses, the relationship between WWI and the risk of all-cause mortality persisted. The area under ROC for WWI was higher for all-cause mortality than BMI, WHtR, and WC. Conclusion: WWI was associated with a higher risk for all-cause mortality, and the association was more robust with the highest WWI category.

The Value of Four Anthropometric Indicators for Identifying Left Ventricular Hypertrophy in Chinese Hypertensive Patients.

Left ventricular hypertrophy (LVH) has been classified separately as an independent risk factor for hypertension. However, comparisons between different body size indices and left ventricular hypertrophy (LVH) in hypertensive populations have not been reported yet. In this study, we enrolled 4,639 hypertensive patients from rural China. Anthropometric indices and cardiovascular disease risk factor variables were measured and analyzed using Spearman's correlation, logistic regression, and receiver operating characteristic (ROC) curve analyses. Patients in the highest quartile of body size indices were more likely to have left ventricular hypertrophy than those in the lowest quartile; these indices were BMI (adjusted OR: 3.55, 95% CI: 2.90; 4.35), WC (adjusted OR: 2.23, 95% CI: 1.84; 2.70), WHR (adjusted OR: 1.44, 95% CI: 1.18; 1.75), and WHtR (adjusted OR: 3.23, 95% CI: 2.62; 3.99). The areas under the ROC curves of BMI (AUC: 0.628, 95% CI: 0.612; 0.644), WHtR (AUC: 0.628, 95% CI: 0.560; 0.593), WHR (AUC: 0.530, 95% CI: 0.513; 0.547), and WC (AUC: 0.576, 95% CI: 0.513; 0.547) were all above 0.5, which indicated that the four anthropometric indicators may be associated with LVH. The four anthropometric indicators of obesity were identified as risk factors for LVH. Weight control might help reduce the risk of left ventricular hypertrophy.

The Potential Role of m6A RNA Methylation in the Aging Process and Aging-Associated Diseases.

N6-methyladenosine (m6A) is the most common and conserved internal eukaryotic mRNA modification. m6A modification is a dynamic and reversible post-transcriptional regulatory modification, initiated by methylase and removed by RNA demethylase. m6A-binding proteins recognise the m6A modification to regulate gene expression. Recent studies have shown that altered m6A levels and abnormal regulator expression are crucial in the ageing process and the occurrence of age-related diseases. In this review, we summarise some key findings in the field of m6A modification in the ageing process and age-related diseases, including cell senescence, autophagy, inflammation, oxidative stress, DNA damage, tumours, neurodegenerative diseases, diabetes, and cardiovascular diseases (CVDs). We focused on the biological function and potential molecular mechanisms of m6A RNA methylation in ageing and age-related disease progression. We believe that m6A modification may provide a new target for anti-ageing therapies.

The relationship between urinary albumin to creatinine ratio and all-cause mortality in the elderly population in the Chinese community: a 10-year follow-up study.

BACKGROUND: In patients with diabetes and hypertension, proteinuria is independently associated with all-cause death. However, in the general population, urinary albumin to creatinine ratio (UACR) is less used to predict all-cause mortality. When the urinary albumin to creatinine ratio is within the normal range (UACR< 30 mg/g), the clinical relevance of an increased urinary albumin excretion rate is still debated. We studied the relationship between UACR and all-cause mortality in community populations, and compared UACR groups within the normal range. METHODS: The participants were the inhabitants from the Wanshoulu community in Beijing, China. The average age is 71.48 years, and the proportion of women is 60.1%. A total of 2148 people completed random urine samples to determine the urinary albumin to creatinine ratio (UACR). The subjects were divided into three groups according to UACR: Group 1 (UACR< 10 mg/g), Group 2 (10 mg/g < UACR< 30 mg/g), Group 3 (UACR> 30 mg/g). We used Kaplan-Meier survival analysis and Cox regression model to verify the relationship between UACR and all-cause mortality. RESULTS: At an average follow-up of 9.87 years (718,407.3 years), the total mortality rate were 183.4/1000. In the Cox proportional hazards model, after adjusting for possible confounders, those with normal high-value UACR (group 2) showed a higher all-cause mortality than those with normal low-value UACR (group 1) [hazard ratio (HR) 1.289, 95% confidence interval (CI) 1.002 ~ 1.659 for all-cause mortality]. Those with proteinuria (group 3) showed a higher all-cause mortality than those with normal low-value UACR (group 1) [hazard ratio (HR) 1.394, 95% confidence interval (CI) 1.020 ~ 1.905 for all-cause mortality]. CONCLUSION: Urinary albumin to creatinine ratio is an important risk factor for all-cause death in community population. Even if it is within the normal range (UACR< 30 mg/g), it occurs in people with high normal value (10 mg/g < UACR< 30 mg/g), the risk of all-cause death will also increase.

Mediation effect of obesity on the association between triglyceride-glucose index and hyperuricemia in Chinese hypertension adults.

The triglyceride glucose (TyG) index was regarded as a simple surrogate marker of insulin resistance (IR). It is confirmed that IR was significantly associated with hyperuricemia, and obesity was the risk factor for IR and hyperuricemia. However, the relationship between the TyG index and hyperuricemia and the potential role of obesity in Han Chinese hypertension are not entirely elucidated. A community-based cross-sectional study was conducted in 4551 hypertension patients aged 40-75 years with clinical and biochemical data. The TyG index was calculated as ln [fasting triglyceride (mg/dl) × fasting plasma glucose (mg/dl)/2]. Hyperuricemia was determined as serum uric acid ≥357µmol/L (6 mg/dl) for females and ≥417µmol/L (7 mg/dl) for males. Our study suggested that the TyG index was higher in patients with hyperuricemia than in those without (8.99±0.61, 8.70±0.59, p < .001). The prevalence of hyperuricemia in patients with the lowest (≤8.32), second (8.33-8.66), third (8.67-9.07) and the highest quartile (≥9.08) of the TyG index was 6.0%, 10.4%, 15.4%, 21.4%, respectively. Logistic regression analysis suggested that the higher quartile of TyG index was associated with increased hyperuricemia risk whether in crude or adjusted models (p < .05). Mediation analysis showed that all of our obesity indexes partially mediated the association between the TyG index and hyperuricemia to some extent. In Conclusions, the TyG index is significantly associated with hyperuricemia in hypertension patients among Han Chinese, obesity plays a partial mediation role in this relationship.

Cognitive function assessed by Mini-mental state examination and risk of all-cause mortality: a community-based prospective cohort study.

BACKGROUND: The Mini-Mental State Examination (MMSE) is the most widely used instrument to test cognitive functioning. The present study prospectively investigated the association between MMSE scores, MMSE domains, and all-cause mortality. METHODS: A total of 2134 participants aged 60 years or over, selected from one urban community-dwelling population in China, were enrolled in the study. The cognitive test was performed by use of the MMSE at baseline, and covariates were recorded simultaneously. Cox regression models were used for examining the cognitive function, expressed by different MMSE transformations, and all-cause mortality. After followed up for a median of 10.8 years (ranging from 1.0 to 11.3 years), loss to follow-up was 13.1% and 1854 individuals were finally included in the analyses. RESULTS: The subjects had the mean (SD) age of 71.01 (7.00) years, and 754 (40.67%) of them were women. Per point increase on MMSE scores was associated a 4% decreased risk of all-cause mortality [hazard ratio (HR): 0.96; 95%confidence interval (CI): 0.93-0.98]; compared to MMSE scores of ≥24, MMSE scores of < 24 was associated with a 43% increased risk of all-cause mortality (HR: 1.43; 95% CI: 1.05-1.95); compared to MMSE scores of 30, MMSE scores of 27-29 (HR: 1.27; 95% CI: 0.89-1.82), 24-26 (HR: 1.30; 95% CI: 0.86-1.99), and < 24 (HR: 1.79; 95% CI: 1.15-2.77) had a graded increase in risk of all-cause mortality (p for trend =0.003). Of MMSE domains, orientation to time (HR: 2.00; 95% CI: 1.29-3.11), attention and calculation (HR: 1.49; 95% CI: 1.16-1.92), recall (HR: 2.59; 95% CI: 1.22-5.47), and language (HR: 1.68; 95% CI: 1.25-2.26) were significantly associated with all-cause mortality in the unadjusted model; for one increase in the number of impaired MMSE domains, the unadjusted HR (95% CI) of mortality is 1.51 (1.38, 1.65), and the HR (95% CI) of mortality is 1.12 (1.01, 1.25) with full adjustment; compared to 0 and 1 impaired MMSE domains, the HRs of all-cause mortality associated with 2, 3, 4, and ≥ 5 impaired MMSE domains were 1.14 (95% CI: 0.84-1.54), 1.50 (95% CI: 0.98-2.28), 2.14 (95% CI: 1.12-4.09) and 2.29 (95% CI: 1.24-5.04), respectively, and a dose-dependent relationship was significant (p for trend =0.003). CONCLUSION: Cognitive impairment is associated with the increased risk of all-cause mortality in the Chinese elderly. Similarly, reduced MMSE scores, as well as impaired MMSE domains, are also associated with the increasing risk of all-cause mortality.

Triglyceride Glucose Index Associated With Arterial Stiffness in Chinese Community-Dwelling Elderly.

Background: The population of older adults is growing rapidly with the increasing pace of aging worldwide. The triglyceride glucose (TyG) index has been a convenient and reliable surrogate marker of insulin resistance (IR). This study aimed to determine the association between the TyG index and arterial stiffness assessed by brachial-ankle pulse wave velocity (baPWV) in Chinese older adults. Methods: A total of 2,035 participants aged 60 years or above were enrolled. Demographic, anthropometric, and cardiovascular risk factors were collected. TyG index was calculated using ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). Arterial stiffness was measured using baPWV. Results: The participants, with the mean [standard deviation (SD)] age of 71.32 (6.75) years, the female proportion of 39.65%, the mean (SD) baPWV of 1,998 (437) cm/s, and the mean (SD) TyG index of 8.86 (0.54), were divided into four groups according to TyG index quartiles. Age-adjusted baPWV presented an increasing trend according to TyG index quartiles. In the fully adjusted linear regression model, the baPWV increased 49 cm/s, with the 95% confidence interval (CI) from 24 to 75 cm/s, per-SD increase in the TyG index. In the fully-adjusted logistic regression model, the odds ratio (95% CI) of high baPWV (>75th percentile) was 1.32 (1.09, 1.60) for each SD increase in the TyG index. The generalized additive model analysis also confirmed the significant association of the TyG index with baPWV and high baPWV. Conclusion: The TyG index is significantly associated with arterial stiffness assessed by baPWV in Chinese older adults.

The high normal ankle brachial index is associated with left ventricular hypertrophy in hypertension patients among the Han Chinese.

Left ventricular hypertrophy (LVH) is the most common target organs damage in the hypertension patients. Abnormal low (≤0.9) or high (≥1.40) ankle brachial index (ABI) are associated with an increased risk of cardiovascular events. However, the relationships between a high ABI in the normal range (0.9-1.4) and LVH in Han Chinese hypertension are not entirely elucidated. This study included 3953 hypertension patients aged 40-75 years among Han Chinese. Hypertension was defined as systolic blood pressure≥140 mm Hg, diastolic blood pressure≥90 mm Hg, or history of antihypertensive drug use. Left ventricular mass (LVM) was measured by transthoracic echocardiography. LVH was diagnosed by using the criteria of LVM ≥49.2 g/m2.7 for men and 46.7 g/m2.7 for women. Our study suggested that the ABI was higher in patients with LVH than in those without (1.13±0.11, 1.11±0.11, p < 0.001). The prevalence of LVH in patients with the lowest (0.9 < ABI≤1.03), second (1.04≤ABI≤1.11), the third (1.12≤ABI≤1.20), and the highest quartile (1.21≤ABI < 1.40) of ABI was 37.2%, 38.2%, 45.5%, 45.7%, respectively. Logistic regression analysis suggested that the highest and third quartile of ABI were significantly associated with increased LVH risk (multivariate-adjusted OR of highest group:1.83; third group:1.61). The association of ABI at second quartile with LVH was nonsignificant. Similar results were observed in less than 60 years and without coronary heart disease or diabetes group. Our observations in Chinese patients with hypertension indicated high ABI may be an important risk factor for LVH in hypertension patients among Han Chinese, even in the normal range.

The effects of pigment epithelium-derived factor on atherosclerosis: putative mechanisms of the process.

Cardiovascular disease (CVD) is a leading cause of death worldwide. Atherosclerosis is believed to be the major cause of CVD, characterized by atherosclerotic lesion formation and plaque disruption. Although remarkable advances in understanding the mechanisms of atherosclerosis have been made, the application of these theories is still limited in the prevention and treatment of atherosclerosis. Therefore, novel and effective strategies to treat high-risk patients with atherosclerosis require further development. Pigment epithelium-derived factor (PEDF), a glycoprotein with anti-inflammatory, anti-oxidant, anti-angiogenic, anti-thrombotic and anti-tumorigenic properties, is of considerable interest in the prevention of atherosclerosis. Accumulating research has suggested that PEDF exerts beneficial effects on atherosclerotic lesions and CVD patients. Our group, along with colleagues, has demonstrated that PEDF may be associated with acute coronary syndrome (ACS), and that the polymorphisms of rs8075977 of PEDF are correlated with coronary artery disease (CAD). Moreover, we have explored the anti-atherosclerosis mechanisms of PEDF, showing that oxidized-low density lipoprotein (ox-LDL) reduced PEDF concentrations through the upregulation of reactive oxygen species (ROS), and that D-4F can protect endothelial cells against ox-LDL-induced injury by preventing the downregulation of PEDF. Additionally, PEDF might alleviate endothelial injury by inhibiting the Wnt/ß-catenin pathway. These data suggest that PEDF may be a novel therapeutic target for the treatment of atherosclerosis. In this review, we will summarize the role of PEDF in the development of atherosclerosis, focusing on endothelial dysfunction, inflammation, oxidative stress, angiogenesis and cell proliferation. We will also discuss its promising therapeutic implications for atherosclerosis.

Correlation Between Pigment Epithelium-Derived Factor (PEDF) level and Degree of Coronary Angiography and Severity of Coronary Artery Disease in a Chinese Population.

BACKGROUND The role of pigment epithelium-derived factor (PEDF) in protection of coronary artery disease (CAD) remains controversial. The aim of this study was to reassess the value of PEDF in predicting the severity and prognosis of newly diagnosed stable CAD in a Chinese population. MATERIAL AND METHODS Plasma PEDF levels were measured in 259 stable CAD patients undergoing coronary angiography and 116 age- and sex-matched healthy controls. The severity of coronary atherosclerosis was assessed using Gensini score. RESULTS PEDF levels were significantly lower in CAD patients than in healthy subjects (5.856±0.790 vs. 6.658±1.070 µg/ml, respectively, p<0.01). Stepwise regression analysis showed a negative correlation between PEDF levels and severity of CAD as quantified by Gensini score value (ß=-0.626, p<0.01). CONCLUSIONS Our study showed that plasma PEDF levels were significantly lower in CAD patients than in controls, and the plasma PEDF levels may be used as a potential predicator for coronary severity.

The T Allele of rs8075977 in the 5'-Flanking Region of the PEDF Gene Is Associated with Reduced Risk of Coronary Artery Disease in Elderly Chinese Men.

Coronary artery disease (CAD) is a multifactorial disease with a genetic component. Pigment epithelium-derived factor (PEDF) exerts anti-inflammatory, anti-oxidant, anti-thrombotic, and anti-angiogenic effects and thus has received increasing attention as a sensitive biomarker of atherosclerosis and CAD. To explore the potential association between PEDF single nucleotide polymorphisms (SNPs) and CAD, we performed this case-control study of consecutive elderly Chinese Han male patients (n = 416) and age-matched male controls (n = 528) without a history of CAD or electrocardiographic signs of CAD. The enrolled CAD patients (age ≥ 60 years) are not biologically related. A tag approach was used to examine 100% of common variations in the PEDF gene (r2 ≥ 0.8, minor allele frequency > 0.1). PEDF tag SNPs (tSNPs) were selected using the HapMap Data-CHB which describes the common patterns of human DNA sequence variation and Tagger program. SNPs were genotyped using ligase detection reaction (LDR). Seven tSNPs (rs8075977, rs11658342, rs1136287, rs12603825, rs12453107, rs6828 and rs11078634) were selected. Among them, only one SNP, rs8075977 (C/T) located in the 5'-flanking region, showed the significant effect on the susceptibility to CAD. The frequency of its T allele was significantly higher in the controls (52.7%) than that in the CAD group (46.2%) (adjusted OR = 0.88, 95% CI: 0.80-0.96; P = 0.005). In conclusion, the T allele of rs8075977 in the 5'-flanking region of the PEDF gene may be protective for CAD. Conversely, the C allele at this variation site is associated with CAD in elderly Chinese Han men.

Pigment epithelium-derived factor alleviates endothelial injury by inhibiting Wnt/ß-catenin pathway.

BACKGROUND: Oxidized low-density lipoprotein (ox-LDL) can induce endothelial injury and plays a vital role in the procession and development of atherosclerosis. Little is known regarding whether Wnt/ß-catenin pathway is involved in ox-LDL-induced endothelial injury or whether it further promotes atherosclerosis via increased oxidative stress. This study aimed to investigate the role of Wnt/ß-catenin pathway in ox-LDL-induced vascular endothelial injury and determine whether pigment epithelium-derived factor (PEDF) could alleviate ox-LDL-induced endothelial injury by inhibiting Wnt/ß-catenin pathway. METHODS: Injury of human umbilical vein endothelial cells (HUVECs) was evaluated with an MTT assay, by monitoring lactate dehydrogenase (LDH) release and determining the apoptotic ratio. The expression of ß-catenin (non-phosphorylated-ß-catenin), disheveled-1 (Dvl-1) and Cyclin D1 was analyzed with western blotting and quantitative real-time PCR. Oxidative stress status was assessed by measuring the levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO). RESULTS: Exposure of HUVECs to ox-LDL led to a decrease in cell viability and an increase in LDH release and apoptosis with concomitant enhancement of oxidative stress, as assessed by increased ROS and MDA generation, as well as decreased SOD activity and NO levels. Similar to lithium chloride (LiCl, a Wnt/ß-catenin pathway activator), ox-LDL up-regulated the expression of ß-catenin, Dvl-1 and Cyclin D1, markers of Wnt/ß-catenin pathway activation. However, ox-LDL-induced activation of Wnt/ß-catenin pathway, as well as ox-LDL-induced cell injury and oxidative stress, were synergistically promoted by LiCl and mitigated by Dickkopf 1 (DKK-1), an inhibitor of Wnt/ß-catenin pathway. Additionally, ox-LDL-induced HUVEC injury and apoptosis, oxidative stress and activation of Wnt/ß-catenin pathway were suppressed by PEDF, while they were further strengthened by a small interfering RNA of PEDF. CONCLUSION: Wnt/ß-catenin pathway may mediate ox-LDL-induced endothelial injury via oxidative stress, and PEDF ameliorates endothelial injury by suppressing Wnt/ß-catenin pathway and subsequently reducing oxidative stress.