Amlodipine suppresses Ang-II-induced endothelium dysfunction by diminishing ROCK1 expression.

OBJECTIVE: To investigate the effects and mechanisms of amlodipine therapy on endothelium dysfunction induced by angiotensin-II (Ang-II) stimulation. METHODS: Human umbilical vein endothelial cells (HUVECs) were used and divided into five groups: Blank control, Ang-II (10(-6 )mol/L), levorotatory amlodipine (5 × 10(-6 )mol/L) + Ang-II (10(-6 )mol/L), dextrorotatory amlodipine (5 × 10(-6 )mol/L) + Ang-II (10(-6 )mol/L) and racemic amlodipine (5 × 10(-6 )mol/L) + Ang-II (10(-6 )mol/L) groups. Twenty-four hours later, HUVECs were collected for evaluating endothelial nitric oxide synthase (eNOS), p-eNOS, rho-associated kinase 1 (ROCK1), Bcl-2 and Bax expressions. Nitric oxide (NO) concentration within endothelium was also detected. Flow cytometry was conducted to assess HUVECs apoptosis. RESULTS: With 24 hours of Ang-II stimulation, compared to blank control group, expressions of eNOS and p-eNOS and NO production were significantly reduced in Ang-II group (p < 0.05), while adding amlodipine-protected HUVECs from dysfunction induced by Ang-II. In contrast, ROCK1 expression was promoted in Ang-II group (p < 0.05). However, the expression of ROCK1 in each enantiomer of amlodipine group was significantly decreased (p < 0.05). Compared to levorotatory amlodipine group, the magnitude of ROCK1 diminishment in dextrorotatory amlodipine group was more profound (p < 0.05). The pro-survival protein (Bcl-2) was significantly upregulated, while the pro-apoptotic protein (Bax) was significantly downregulated in three amlodipine groups compared to Ang-II group. Flow cytometry revealed that amlodipine therapy could protect HUVECs from apoptosis, and no significant difference between three amlodipine groups was observed. CONCLUSION: Amlodipine could suppress Ang-II-induced endothelial dysfunction and apoptosis through diminishing ROCK1 expression.

Atorvastatin protects endothelium by decreasing asymmetric dimethylarginine in dyslipidemia rats.

BACKGROUND: Asymmetric Dimethylarginine (ADMA) is an inhibitor of endogenous nitric oxide synthase, which is the key synthase for nitric oxide (NO) production. Whether statins could protect endothelium by reducing ADMA concentration is unclear, and whether this effect is associated with the dose of statins usage is also needed further studied. METHODS: Dyslipidemia rat model was produced by giving high-fat and high-cholesterol diet for 8 weeks. Thereafter, low-dose (5 mg/kg body weight/day) and high-dose (20 mg/kg body weight/day) atorvastatin were orally prescribed for 4 weeks. Parameters of interest including lipid profiles, inflammatory and oxidative markers, NO production and plasma levels of ADMA and ADMA concentration of myocardium were evaluated. Liver enzymes and creatinine kinase (CK) were also detected for safety concern. RESULTS: At baseline, all parameters were comparable between the sham and the dyslipidemia groups. At 8 weeks of dyslipidemia establishment, as compared to the sham group, body weight and lipid profiles were significantly elevated, and plasma levels of C-reactive protein (CRP), malondialdehyde (MDA) and ADMA were concomitantly increased in accompanying with NO reduction in the dyslipidemia groups. With 4 weeks of atorvastatin therapy, as compared to the control group, lipid disorders and NO production were improved, and plasma levels of CRP, MDA and ADMA were significantly decreased in the high-dose atorvastatin group. ADMA concentration of cardiac tissues was also significantly reduced in the high-dose atorvastatin group. Notably, there was a trend to similar effects which did not reach statistical significance in the low-dose atorvastatin group when compared to the control group. Liver enzyme and CK were comparable after 4 weeks of atorvastatin therapy between groups. CONCLUSION: In rats with dyslipidemia, atorvastatin therapy could reduce plasma level of ADMA and ADMA concentration in cardiac tissues, and these effects are associated with the dose of atorvastatin therapy.

Association of all-cause and cardiovascular mortality with prehypertension: a meta-analysis.

BACKGROUND: Studies of prehypertension and mortality are controversial after adjusting for other cardiovascular risk factors. This meta-analysis sought to evaluate the association of prehypertension with all-cause and cardiovascular disease (CVD) mortality. METHODS: The PubMed, EMBASE, Cochrane Library databases, and conference proceedings were searched for studies with data on prehypertension and mortality. The relative risks (RRs) of all-cause, CVD, coronary heart disease (CHD), and stroke mortality were calculated and presented with 95% CIs. Subgroup analyses were conducted according to blood pressure, age, gender, ethnicity, follow-up duration, participant number, and study characteristics. RESULTS: Data from 1,129,098 participants were derived from 20 prospective cohort studies. Prehypertension significantly increased the risk of CVD, CHD, and stroke mortality (RR 1.28, 95% CI 1.16-1.40; RR 1.12, 95% CI 1.02-1.23; and RR 1.41, 95% CI 1.28-1.56, respectively), but did not increase the risk of all-cause mortality after multivariate adjustment (RR 1.03, 95% CI 0.97-1.10). The difference between CHD mortality and stroke mortality was significant (P < .001). Subgroup analyses showed that CVD mortality was significantly increased in high-range prehypertension (RR 1.28, 95% CI 1.16-1.41) but not in low-range prehypertension (RR 1.08, 95% CI 0.98-1.18). CONCLUSION: Prehypertension is associated with CVD mortality, especially with stroke mortality, but not with all-cause mortality. The risk for CVD mortality is largely driven by high-range prehypertension.

Prehypertension and Incidence of ESRD: a systematic review and meta-analysis.

BACKGROUND: Studies of the association of prehypertension with the incidence of end-stage renal disease (ESRD) after adjusting for other cardiovascular risk factors have shown controversial results. STUDY DESIGN: Systematic review and meta-analysis of prospective cohort studies. SETTING & POPULATION: Adults with prehypertension. SELECTION CRITERIA FOR STUDIES: Studies evaluating the association of prehypertension with the incidence of ESRD identified by searches in PubMed, EMBASE, and Cochrane Library databases and conference proceedings, without language restriction. PREDICTOR: Prehypertension. OUTCOMES: The relative risks (RRs) of ESRD were calculated and reported with 95% CIs. Subgroup analyses were conducted according to blood pressure (BP), age, sex, ethnicity, and study characteristics. RESULTS: Data from 1,003,793 participants were derived from 6 prospective cohort studies. Compared with optimal BP, prehypertension significantly increased the risk of ESRD (RR, 1.59; 95% CI, 1.39-1.91). In subgroup analyses, prehypertension significantly predicted higher ESRD risk across age, sex, ethnicity, and study characteristics. Even low-range (BP, 120-129/80-84 mm Hg) prehypertension increased the risk of ESRD compared with optimal BP (RR, 1.44; 95% CI, 1.19-1.74), and the risk increased further with high-range (BP, 130-139/85-89 mm Hg) prehypertension (RR, 2.02; 95% CI, 1.70-2.40). The RR was significantly higher in the high-range compared with the low-range prehypertensive population (P = 0.01). LIMITATIONS: No access to individual patient-level data. CONCLUSIONS: Prehypertension is associated with incident ESRD. The increased risk is driven largely by high-range prehypertension.

Baseline elevated Lp-PLA2 is associated with increased risk for re-stenosis after stent placement.

BACKGROUND: Lipoprotein associated phospholipase A2 (Lp-PLA2) is a novel biomarker for cardiovascular risk prediction. Whether increased Lp-PLA2 level is associated with re-stenosis after stent-placement is unclear. METHODS: Totally 326 participants eligible for stent-placement were enrolled and divided into two groups according to baseline Lp-PLA2 levels (named normal and elevated groups). Baseline characteristics and clinical outcomes were compared between normal and elevated groups. The relationships between Lp-PLA2 and other risk factors with re-stenosis were evaluated. RESULTS: Only the between-group difference of Lp-PLA2 was significant (123.2 ± 33.6 ng/mL vs 336.8 ± 85.4 ng/mL, P < 0.001) while other demographic and clinical characteristics between these two groups were comparable. Approximately 55.1% and 58.5% of participants in normal and elevated groups presented with acute coronary syndrome, and the percentage of tri-vessels stenoses was significantly higher in elevated group (40.8% vs 32.1%, P = 0.016). Nearly 96.0% and 94.0% of participants in normal and elevated Lp-PLA2 groups were placed with drug-eluting stents, and the others were with bare-metal stents. After 1 year's follow-up, the incidence of clinical end-points was comparable (13.3% vs 15.4%, P = 0.172). Nevertheless, the incidence of re-stenosis was marginally higher in elevated Lp-PLA2 group (8.5% versus 4.6%, P = 0.047). With multivariate analysis, after adjustment for other risk factors, Lp-PLA2 remained an independent predictor for re-stenosis with a hazard ratio of 1.140. No synergistic effect between Lp-PLA2 and other risk factors for re-stenosis was found. CONCLUSION: Increased Lp-PLA2 level is associated with an increased risk of re-stenosis. Lp-PLA2 assessment may be useful in predicting subjects who are at increased risk for re-stenosis.

Prehypertension and incidence of cardiovascular disease: a meta-analysis.

BACKGROUND: Prospective cohort studies of prehypertension and the incidence of cardiovascular disease (CVD) are controversial after adjusting for other cardiovascular risk factors. This meta-analysis evaluated the association between prehypertension and CVD morbidity. METHODS: Databases (PubMed, EMBASE and the Cochrane Library) and conference proceedings were searched for prospective cohort studies with data on prehypertension and cardiovascular morbidity. Two independent reviewers assessed the reports and extracted data. The relative risks (RRs) of CVD, coronary heart disease (CHD) and stroke morbidity were calculated and reported with 95% confidence intervals (95% CIs). Subgroup analyses were conducted on blood pressure, age, gender, ethnicity, follow-up duration, number of participants and study quality. RESULTS: Pooled data included the results from 468,561 participants from 18 prospective cohort studies. Prehypertension elevated the risks of CVD (RR = 1.55; 95% CI = 1.41 to 1.71); CHD (RR = 1.50; 95% CI = 1.30 to 1.74); and stroke (RR = 1.71; 95% CI = 1.55 to 1.89). In the subgroup analyses, even for low-range prehypertension, the risk of CVD was significantly higher than for optimal BP (RR = 1.46, 95% CI = 1.32 to 1.62), and further increased with high-range prehypertension (RR = 1.80, 95% CI = 1.41 to 2.31). The relative risk was significantly higher in the high-range prehypertensive populations than in the low-range populations (χ2= 5.69, P = 0.02). There were no significant differences among the other subgroup analyses (P>0.05). CONCLUSIONS: Prehypertension, even in the low range, elevates the risk of CVD after adjusting for multiple cardiovascular risk factors.

Bone marrow stromal cell transplantation combined with angiotensin-converting enzyme inhibitor treatment in rat with acute myocardial infarction and the role of insulin-like growth factor-1.

BACKGROUND AIMS: We investigated bone marrow stromal cell (BMSC) transplantation combined with angiotensin-converting enzyme inhibitor (ACEI) treatment in acute myocardial infarction (AMI) and the role of insulin-like growth factor-1 (IGF-1). METHODS: AMI models were established in Sprague-Dawley rats by ligation of the left anterior descending coronary artery and grouped into blank control (BC), ACEI treatment (ACEI), BMSC transplantation (BMSC) and BMSC transplantation plus ACEI (combined). Perindopril (2.5 mg/kg) was administered by gavage to ACEI and combined groups from the day after AMI. BMSC (2 × 10(8)) were injected into the border of the MI area a week later in the BMSC and combined groups. RESULTS: After 4 weeks, hemodynamics in the BMSC and combined groups were significantly improved (P < 0.05 versus BC), with the greatest improvement in the combined group (P < 0.05). In addition, an increased number of BMSC survived in the combined group (P < 0.05 versus BMSC). A proportion of BMSC was positive for troponin T, as detected by immunofluorescence. The number of apoptotic cardiomyocytes was decreased in the BMSC and ACEI groups, and even further in the combined group (P < 0.05). IGF-1 expression was up-regulated in the BMSC and combined groups (P < 0.05 versus BC), but not in the ACEI group. B cell lymphoma-2 (Bcl-2) expression was up-regulated in the ACEI, BMSC and combined groups, with the highest expression in the combined group (P < 0.05). CONCLUSIONS: Our results show that BMSC engrafted in AMI can survive well and secrete IGF-1 and preserve cardiac function significantly. These data suggest that BMSC transplantation inhibits apoptosis of cardiomyocytes by up-regulation of Bcl-2 expression in the myocardium, and this effect might be sensitized by ACEI.

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

BACKGROUND: The 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. METHODS: Male 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 (40 mg/Kg/d body weight) or AMD3100 (5mg/Kg/d body weight) was given to group A+L-NAME or A+AMD3100, respectively. RESULTS: Comparing 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. CONCLUSION: SDF-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.

Association of spironolactone treatment and arterial stiffness and cardiovascular disease in hypertensive patients.

Introduction: The aim of the current study was to evaluate the association of spironolactone and arterial stiffness and composite cardiovascular disease (CVD, including coronary heart disease, congestive heart failure and ischemic stroke) in hypertensive patients. Material and methods: Baseline data were collected and arterial stiffness was presented by carotid-femoral pulse wave velocity (cf-PWV) using applanation tonometry. Serum levels of fasting plasma glucose, total cholesterol, C-reactive protein and creatinine were measured using an automatic biochemistry analyzer. Plasma aldosterone concentration and plasma renin activity were determined by radioimmunoassay. The associations of spironolactone and arterial stiffness and composite CVD were evaluated. Results: Compared to patients without spironolactone (n = 274), those with spironolactone (n = 170) were older and more likely to have diabetes and chronic heart failure. No differences in antihypertensive medications used were observed except for spironolactone. Mean number of antihypertensive medications used was significantly higher in the spironolactone group (2.6 ±0.8 vs. 2.2 ±0.6). Compared to patients without spironolactone, those with spironolactone had significantly lower cf-PWV (9.4 ±1.8 vs. 10.1 ±2.2 m/s). After adjustment for covariates, spironolactone was still associated with 10% lower risk of arterial stiffness, with a 95% confidence interval (CI) of 0.85-0.97. In patients without arterial stiffness, after adjustment for covariates, no significant association of spironolactone and composite CVD was observed. However, in patients with increased arterial stiffness, after adjustment for covariates, spironolactone was still independently associated with 11% lower risk of composite CVD (95% CI: 0.83-0.97). Conclusions: Spironolactone treatment is independently associated with lower cf-PWV and lower prevalence of composite CVD in patients with increased arterial stiffness.

Effects of statins in primary and secondary prevention for venous thromboembolism events: A meta analysis.

OBJECTIVE: The associations between statins use and incidence or recurrence of venous thromboembolism (VTE) are controversial. We aimed to conduct a meta-analysis to reconcile the conflicting results. METHODS: We searched PubMed, Embase and Cochrane Library for studies published from database inception until May 31, 2021. Cohort studies and Randomized Controlled Trials that reported incidence or recurrence of VTE using statins compared with placebo or non-statins were included for meta-analysis. RESULTS: A total of 43 studies comprising over 8.6 million participants were included for analysis. The median follow-up duration was 38.1 months. Compared with no statins treatment, statins appeared to have a protective effect in primary prevention of VTE (RR 0.78, 95% CI 0.72-0.85), but significant heterogeneity was found among included studies (I2 = 81%). Statins was also associated with a 26% reduced risk of recurrent VTE (RR 0.74, 95% CI 0.70-0.78), even in patients receiving anticoagulant therapy (RR 0.77, 95% CI 0.65-0.92). In patients with a history of VTE, statins was associated with a reduced risk of bleeding and all cause mortality. The NNT of statins to prevent one case of VTE in the cancer population, and one case of recurrent VTE in patients with a history of VTE was 103.1 and 90.7 person-years respectively. CONCLUSION: In high-risk patients, statins treatment may reduce the incidence of VTE. Statins can also reduce the risk of recurrent VTE and all-cause mortality in patients with a history of VTE.

Prevalence and Related Factors of White Coat Hypertension and Masked Hypertension in Shunde District, Southern China.

Background: White coat hypertension (WCH) and masked hypertension (MH) can increase the risk of target organ damage. Home blood pressure monitoring is an important method for detecting WCH and MH. However, the prevalence and related factors of WCH and MH in China have been rarely reported. Objective: To explore the prevalence and related factors associated with white coat hypertension (WCH) and masked hypertension (MH) in Shunde District, Southern China. Methods: This study recruited subjects from the Physical Examination Center in Shunde Hospital, Southern Medical University. Office blood pressure and home blood pressure values were collected using the home blood pressure monitor with telemedicine device and office blood pressure monitor, and the prevalence of WCH and MH was calculated by the values. Multivariate logistic regression was used to explore the related factors for WCH and MH. Results: Four-hundred and sixty-one participants (61% male), with an average age of 49 years, were included. The prevalence of WCH and MH was 5.1 and 15.2%, respectively. Multivariate logistic regression analysis showed that smoking (OR = 4.71, 95% CI = 1.05-21.15) and family history of coronary heart disease (OR = 4.51, 95% CI = 1.08-18.93) were associated with higher odds of WCH. The associated factors for higher odds of MH were smoking (OR = 2.83, 95% CI = 1.11-7.23), family history of hypertension (OR = 2.17, 95% CI = 1.11-4.26) and family history of coronary heart disease (OR = 2.82, 95% CI = 1.07-7.45). Conclusion: WCH and MH are highly prevalent in the Physical Examination Center in Shunde Hospital, Southern Medical University. We found smoking and family history of coronary heart disease were related factors for WCH, and smoking, family history of hypertension and coronary heart disease were associated with the odds of MH. Home blood pressure monitoring with a telemedicine device should be recommended to identity abnormal BP phenotype.

AMPK activation enhances PPARα activity to inhibit cardiac hypertrophy via ERK1/2 MAPK signaling pathway.

Activation of adenosine monophosphate-activated protein kinase (AMPK) has been shown to inhibit cardiac hypertrophy through peroxisome proliferators-activated receptor-α (PPARα) signaling pathway, but the detailed mechanism remains unclear. A rat model of cardiac hypertrophy created by transaortic constriction (TAC) was used to investigate the mechanism involved in regulation of PPARα activity by AMPK. It was observed that treatment with AICAR (5-aminoimidazole 1 carboxamide ribonucleoside), an AMPK activator, significantly inhibited cardiac hypertrophy in vivo and in vitro. Phosphorylated extracellular signal regulated protein kinase (phospho-ERK1/2) and phospho-p38 mitogen-activated protein kinase (MAPK) protein levels were significantly up-regulated, while PPARα protein level was down-regulated in TAC rats. AICAR treatment reversed the changes of PPARα and phospho-ERK1/2, but increased phospho-p38 MAPK protein level in TAC rats. Similar changes of PPARα and phospho-ERK1/2 protein levels were observed in the hypertrophied cardiomyocytes induced by phenylephrine treatment. Epidermal growth factor (EGF, ERK1/2 activator), but not SB203580 (p38 inhibitor) blocked the up-regulation of PPARα protein level induced by AICAR. Luciferase assay showed that AICAR increased PPARα transcriptional activity which was abrogated by EGF, but not by SB203580. These results demonstrate that AMPK activation enhances the activity of PPARα to inhibit cardiac hypertrophy through ERK1/2, but not p38 MAPK, signaling pathway.

Efficacy of Atorvastatin combined with adipose-derived mesenchymal stem cell transplantation on cardiac function in rats with acute myocardial infarction.

Mesenchymal stem cells (MSCs) have been extensively applied for the restoration of cardiomyocytes loss after acute myocardial infarction (AMI). However, the optimal therapeutic efficacy of MSCs in ischemic heart diseases has been hampered by their poor survival and low differentiated rates. Therefore, the improvement of MSC survival and differentiated rates is warranted and critical for the efficacy of MSCs in AMI. In this paper, MSCs isolated from rat inguinal fat tissues were termed as adipose-derived mesenchymal stem cells (ASCs), and the fourth passage of ASCs was pre-specified by co-culturing with cardiomyocytes in a transwell system termed as co-ASCs. Fourteen days later, GATA-4 (a transcription factor) and cardiac troponin-I were detected by cellular immunofluorescence. Atorvastatin (Ator group) or vehicle (control group) was administrated for the first 24 h after AMI production in rats. Fourteen days later, inflammatory parameters and cardiac function were evaluated. The other surviving rats were injected with a total of 1 × 10(6) co-ASCs/100 µl phosphate-buffered saline (PBS), 1×10(6) ASCs/100 µl PBS, or 100 µl PBS. Twenty-eight days after cell injection, survival and differentiated rates of transplanted cells and cardiac function were evaluated. The percentage of GATA-4 expression in co-ASCs was 28.5% ± 5.6% and of cardiac troponin-I was 22.8% ± 3.2%. Compared with the control group, the number of infiltrating inflammatory cells, myeloperoxidase activity, inflammatory cytokines (VCAM-1, TNF-α, Hs-CRP) mRNA expression, and Bax protein expression were significantly reduced in the three Ator groups, accompanied by a significant improvement of Bcl-2 protein expression and cardiac function (P< 0.05). Compared with the Ator2 + ASCs group and Con + co-ASCs group, the number of 4-6-diamidino-2-phenylindole-stained cells and cardiac troponin-I-positive transplanted cells, concomitant with cardiac function, were improved most prominently in the Ator3 + co-ASCs group (P< 0.05). Pre-amelioration of the cardiac milieu, in conjunction with pre-specification of ASCs, was beneficial for enhancing ASCs' therapeutic efficacy on cardiac function after AMI.

Meta-Analysis Evaluating the Efficacy and Safety of Low-Intensity Warfarin for Patients >65 Years of Age With Non-Valvular Atrial Fibrillation.

Nonvalvular atrial fibrillation (NVAF) is the most common arrhythmia. It is of a high disability and death rate, and seriously affects quality of life. Although New oral anticoagulants (NOACs) are recommended for anticoagulation therapy of atrial fibrillation, they are not widely used for the high cost and limited availability. Warfarin is effective and economical. The risk of thromboembolism and anticoagulant hemorrhage is higher in patients >65 years with NVAF. So, it is of great clinical significance to explore the optimal anticoagulation intensity of warfarin in patients >65 years of China, and other ethnicities. Some studies suggested that low-intensity international normalized ratio (INR) has similar antithrombotic efficacy comparing to standard-intensity INR, whereas bleeding risk was significantly reduced. But others showed conflicting results. We pooled the efficacy and safety data of low- and standard-intensity warfarin therapy for patients over 65 years with NVAF by meta-analysis, as to evaluate optimal INR intensity of warfarin therapy in patients over 65 years. We identified 18 studies providing data of 2105 patients receiving anticoagulation therapy with warfarin. On meta-analysis (odds ratio [OR] [95% confidence interval {CI}]), low-intensity INR conferred similar efficacy to standard intensity INR on all thrombosis (1.28 [0.90 to 1.81]), stroke (1.09 [0.67 to 1.77]), other thromboembolism ([peripheral and pulmonary embolism] 2.26 [0.89 to 5.79]), and all cause death (1.38 [0.94 to 2.02]). Low-intensity INR conferred better safety profile than standard intensity INR in major bleeding (intracranial and gastrointestinal hemorrhage) (0.32 [0.19 to 0.52]), minor bleeding (gum, nasal cavity and conjunctival hemorrhage, skin ecchymosis, hematuria, hemoptysis) (0.30 [0.20 to 0.45]), and all bleeding (0.30 [0.22 to 0.40]). In conclusion, low-intensity INR (1.5 to 2.0) of warfarin therapy is as effective as standard intensity INR (2.0 to 3.0) therapy in reducing thromboembolic risk in patients>65 years with NVAF, and has a safer profile of bleeding.

Apolipoproteins and liver parameters optimize cardiovascular disease risk-stratification in nonalcoholic fatty liver disease.

BACKGROUND: Advanced Non-alcoholic fatty liver disease (NAFLD) is associated with increased risk of cardiovascular disease (CVD). AIM: We determine whether combinations of ultrasound graphic steatosis grades, fibrosis scores and apolipoprotein levels add value to CVD risk prediction in NAFLD patients. METHODS: The retrospective cohort study enrolled 10,453 individuals (3519 NAFLD; 6934 non NAFLD) from 2004 to 2018. Hepatic ultrasound measurements, lipid and apolipoprotein profiles, Fibrosis-4 and the NAFLD fibrosis scores (NFS) were assessed. The primary outcome included both clinical and subclinical CVD. RESULTS: During 116-month follow-up period, there were 957 clinical and 752 subclinical CVD events. NAFLD patients had a higher incidence of CVD than non NAFLD patients as the steatosis degree, NFS, and FIB4 scores increased (25.1% vs 11.9%, Log Rank: p < 0.001). For the lipid and apolipoprotein profiles excluding triglyceride or ApoE, subjects with varied steatosis severity in the upper two tertiles had different risk of CVD (p for interaction < 0.001). A nomogram model combination of Framingham Risk Score (FRS), NFS and apolipoprotein profiles presented a higher AUC than FRS in a time-dependent ROC curve (0.816 vs 0.752, p < 0.001). CONCLUSION: The novel risk score considering ultrasonography-defined steatosis grades, non-invasive liver fibrosis scores and apolipoprotein profiles accurately predicted the 10-year risk of CVD.

Clinical applications for out-of-office blood pressure monitoring.

Hypertension is one of the most common chronic diseases as well as the leading risk factor for cardiovascular disease (CVD). Efficient screening and accurate blood pressure (BP) monitoring are the basic methods of detection and management. However, with developments in electronic technology, BP measurement and monitoring are no longer limited to the physician's office. Epidemiological and clinical studies have documented strong evidence for the efficacy of out-of-office BP monitoring in multiple fields for managing hypertension and CVD. This review discusses applications for out-of-office BP monitoring, including home blood pressure monitoring (HBPM) and ambulatory blood pressure monitoring (ABPM), based on recent epidemiological data and clinical studies regarding the following factors: the detection of abnormal BP phenotypes, namely, white coat hypertension and masked hypertension; stronger ability to determine the prognosis for target organ damage and mortality; better BP control; screening for hypotension; and unique approaches to identifying circadian BP patterns and BP variability.

Multiple Roles of sFRP2 in Cardiac Development and Cardiovascular Disease.

The Wnt signaling pathway plays important roles in organ development and disease processes. Secreted frizzled-related protein 2 (sFRP2), a vital molecule of Wnt signaling, can regulate cardiac development and cardiovascular disease. Recent studies have suggested that sFRP2 is not only an antagonist of the canonical Wnt signaling pathway, but also has a more complex relationship in myocardial fibrosis, angiogenesis, cardiac hypertrophy and cardiac regeneration. Here, we review the role of sFRP2 and Wnt signaling in cardiac development and cardiovascular disease.

Prognosis of unrecognised myocardial infarction determined by electrocardiography or cardiac magnetic resonance imaging: systematic review and meta-analysis.

OBJECTIVE: To evaluate the prognosis of unrecognised myocardial infarction determined by electrocardiography (UMI-ECG) or cardiac magnetic resonance imaging (UMI-CMR). DESIGN: Systematic review and meta-analysis of prospective studies. DATA SOURCES: Electronic databases, including PubMed, Embase, and Google Scholar. STUDY SELECTION: Prospective cohort studies were included if they reported adjusted relative risks, odds ratios, or hazard ratios and 95% confidence intervals for all cause mortality or cardiovascular outcomes in participants with unrecognised myocardial infarction compared with those without myocardial infarction. DATA EXTRACTION AND SYNTHESIS: The primary outcomes were composite major adverse cardiac events, all cause mortality, and cardiovascular mortality associated with UMI-ECG and UMI-CMR. The secondary outcomes were the risks of recurrent coronary heart disease or myocardial infarction, stroke, heart failure, and atrial fibrillation. Pooled hazard ratios and 95% confidence intervals were reported. The heterogeneity of outcomes was compared in clinically recognised and unrecognised myocardial infarction. RESULTS: The meta-analysis included 30 studies with 253 425 participants and 1 621 920 person years of follow-up. UMI-ECG was associated with increased risks of all cause mortality (hazard ratio 1.50, 95% confidence interval 1.30 to 1.73), cardiovascular mortality (2.33, 1.66 to 3.27), and major adverse cardiac events (1.61, 1.38 to 1.89) compared with the absence of myocardial infarction. UMI-CMR was also associated with increased risks of all cause mortality (3.21, 1.43 to 7.23), cardiovascular mortality (10.79, 4.09 to 28.42), and major adverse cardiac events (3.23, 2.10 to 4.95). No major heterogeneity was observed for any primary outcomes between recognised myocardial infarction and UMI-ECG or UMI-CMR. The absolute risk differences were 7.50 (95% confidence interval 4.50 to 10.95) per 1000 person years for all cause mortality, 11.04 (5.48 to 18.84) for cardiovascular mortality, and 27.45 (17.1 to 40.05) for major adverse cardiac events in participants with UMI-ECG compared with those without myocardial infarction. The corresponding data for UMI-CMR were 32.49 (6.32 to 91.58), 37.2 (11.7 to 104.20), and 51.96 (25.63 to 92.04), respectively. CONCLUSIONS: UMI-ECG or UMI-CMR is associated with an adverse long term prognosis similar to that of recognised myocardial infarction. Screening for unrecognised myocardial infarction could be useful for risk stratification among patients with a high risk of cardiovascular disease.

A prospective cohort study of home blood pressure monitoring based on an intelligent cloud platform (the HBPM-iCloud study): rationale and design.

BACKGROUND: Hypertension, as a predominant risk factor for cardiovascular disease, is a severe public health burden in China. Home blood pressure monitoring (HBPM) is an important tool in the detection and management of hypertension. However, there is a lack of HBPM data from prospective cohorts in China. Hence, we designed this study to investigate the impact of HBPM on major health outcomes in Chinese population participating in regular health check-ups. METHODS: Leveraging telemedicine technology, the open prospective, multicenter, HBPM-iCloud (Home Blood Pressure Monitoring Based on an Intelligent Cloud Platform) cohort study will recruit participants from three participating health check-up centers in southern China to participate in cloud-based HBPM for 1 week. The prevalence of sustained hypertension, white coat hypertension (WCH), masked hypertension (MH), white coat uncontrolled hypertension (WUCH), and masked uncontrolled hypertension (MUCH) will be defined by a combination of average readings of home-based and office-based blood pressure (BP). Cardiovascular risk factors and subclinical target organ damage will be recorded. Participants will be followed-up for 5 years to examine the incidence and associated risk factors of composite major adverse cardiovascular and cerebrovascular event. CONCLUSION: The study will help to determine the best way to implement telemedicine technology in BP control for better prevention and treatment of hypertension. Results will provide data for a Chinese population to aid in the construction of screening, risk stratification, and intervention strategies for abnormal BP phenotypes, including WCH, MH, WUCH, and MUCH.