Clinical impact of blood pressure on cardiovascular death in patients 80 years and older following acute myocardial infarction: a prospective cohort study.

Numerous trials have shown that lowering blood pressure (BP) reduces cardiovascular risk and mortality, yet data about the impact of BP on cardiovascular death risk in patients aged ≥80 years with acute myocardial infarction (AMI) are sparse. This study explored the prognostic value of BP for cardiovascular death during the first 48 h after admission following AMI among patients aged ≥80 years. A total of 1005 patients ≥80 years with AMI were enrolled. Average BP parameters, including systolic, diastolic, and pulse BP, over the first 48 h after admission were calculated. The end point was cardiovascular death. Receiver operating curve (ROC) analysis was used to identify whether BP was relevant to cardiovascular death. The relationship between BP levels and cardiovascular death was evaluated by Cox regression models. ROC analysis showed that average diastolic blood pressure (aDBP), but not systolic and pulse BP, was relevant to cardiovascular death, and the optimal cutoff was 65 mmHg. During the 2.9-year follow-up, patients who died from a cardiovascular cause had lower aDBP levels than those who did not (p = 0.002). Patients with aDBP <65 mmHg had a 1.5-fold higher incidence of cardiovascular death than those with aDBP ≥65 mmHg (35.9% vs. 24.0%; p < 0.001). In multivariable regression analysis, low aDBP remained a strong and independent predictor of cardiovascular death (adjusted hazard ratio 1.907; 95% CI 1.303-2.792). aDBP was independently associated with cardiovascular death in patients aged ≥80 years with AMI, suggesting that aDBP may be a useful index to predict worse outcome in these patients.

Differential leukocyte counts and cardiovascular mortality in very old patients with acute myocardial infarction: a Chinese cohort study.

BACKGROUND: Total leukocyte and differential Leukocyte counts are prognostic indictors in patients with coronary artery disease (CAD). However, there is no data available regarding their prognostic utility in very old patients with acute myocardial infarction (AMI). The aim of this study is to investigate the potential role of different leukocyte parameters in predicting the mortality among very old patients with AMI. METHODS: A total of 523 patients aged over 80 years with AMI were consecutively enrolled into this study. Leukocyte and its subtypes were obtained at admission in each patient. The primary study endpoint was cardiovascular mortality. Patients were followed up for an average of 2.2 years and 153 patients died. The associations of leukocyte parameters with mortality were assessed using Cox regression analyses. The concordance index was calculated to test the model efficiency. RESULTS: In multivariable regression analysis, neutrophils-plus-monocytes-to-lymphocytes ratio (NMLR) and neutrophils-to-lymphocytes ratio (NLR) were two most significant predictors of mortality among all the leukocyte parameters (HR = 3.21, 95% CI 1.75-5.35; HR = 2.79, 95% CI 1.59-4.88, respectively, all p < 0.001, adjusted for age, male gender, body mass index, family history of CAD, smoking, hypertension, diabetes mellitus, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, high sensitivity C-reactive protein, creatinine, left ventricular ejection fraction, troponin I, use of statin, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and percutaneous coronary intervention). Furthermore, adding NMLR and NLR into the Cox model increased the C-statistic by 0.038 and 0.037 respectively, which were more significant than that of other leukocyte parameters. Besides, addition of NMLR and NLR to the Canada Acute Coronary Syndrome Risk Score model also increased the C-statistic by 0.079 and 0.077 respectively. CONCLUSION: Our data firstly indicated that most leukocyte subtypes were independent markers for the mortality in very old patients with AMI, while NMLR and NLR appeared to be more effective.

Association of lipoprotein(a) levels with recurrent events in patients with coronary artery disease.

OBJECTIVE: Whether lipoprotein(a) (Lp(a)) is a predictor for recurrent cardiovascular events (RCVEs) in patients with coronary artery disease (CAD) has not been established. This study, hence, aimed to examine the potential impact of Lp(a) on RCVEs in a real-world, large cohort of patients with the first cardiovascular event (CVE). METHODS: In this multicentre, prospective study, 7562 patients with angiography-diagnosed CAD who had experienced a first CVE were consecutively enrolled. Lp(a) concentrations of all subjects were measured at admission and the participants were categorised according to Lp(a) tertiles. All patients were followed-up for the occurrence of RCVEs including cardiovascular death, non-fatal myocardial infarction and stroke. RESULTS: During a mean follow-up of 61.45±19.57 months, 680 (9.0%) RCVEs occurred. The results showed that events group had significantly higher Lp(a) levels than non-events group (20.58 vs 14.95 mg/dL, p<0.001). Kaplan-Meier analysis indicated that Lp(a) tertile 2 (p=0.001) and tertile 3 (p<0.001) groups had significantly lower cumulative event-free survival rates compared with tertile 1 group. Moreover, multivariate Cox regression analysis further revealed that Lp(a) was independently associated with RCVEs risk (HR: 2.01, 95% CI: 1.44 to 2.80, p<0.001). Moreover, adding Lp(a) to the SMART risk score model led to a slight but significant improvement in C-statistic (∆C-statistic: 0.018 (95% CI: 0.011 to 0.034), p=0.002), net reclassification (6.8%, 95% CI: 0.5% to 10.9%, p=0.040) and integrated discrimination (0.3%, 95% CI: 0.1% to 0.7%, p<0.001). CONCLUSIONS: Circulating Lp(a) concentration was indeed a useful predictor for the risk of RCVEs in real-world treated patients with CAD, providing additional information concerning the future clinical application of Lp(a).

Lipoprotein(a) Is Associated with the Presence and Severity of New-Onset Coronary Artery Disease in Postmenopausal Women.

Background: Lipid disorder was one of the major risk factors for coronary artery disease (CAD), especially in postmenopausal women, whose lipid profile significantly changed during the transition period to menopause. The aim of the present study was to examine whether plasma lipoprotein(a) [Lp(a)] was a biomarker for predicting the presence and severity of CAD in postmenopausal women. Methods: A total of 783 postmenopausal women who had their first angina-like chest pain were enrolled and classified into two groups according to the results of coronary angiography: CAD group (n = 309) and age-matched non-CAD group (n = 309). Patients with CAD were further divided into the three groups based on Gensini score (GS). The relationships of plasma Lp(a) levels to the presence and severity of CAD were evaluated, and the predictive value of Lp(a) for CAD was also examined. Results: CAD group had higher Lp(a) levels when compared to non-CAD ones (p < 0.001). The multivariate logistic regression analysis suggested that Lp(a) was an independent predictor for the presence of CAD (p < 0.001). Plasma levels of Lp(a) were significantly related to GS (p < 0.001). In addition, plasma Lp(a) level was significantly elevated according to the tertiles of GS (p = 0.001) and was independently associated with high GS (p < 0.001). In receiver-operating characteristic analysis for predicting the presence of CAD in postmenopausal women, Lp(a) was found to have the area under the curve of 0.703, with an optimal cutoff value of 255.69 mg/L. Conclusions: Lp(a) is an independent risk factor for predicting the presence and the severity of new-onset CAD in postmenopausal women, suggesting that Lp(a) may be a lipid target for prevention and treatment in such patients.

Predictive value of non-fasting remnant cholesterol for short-term outcome of diabetics with new-onset stable coronary artery disease.

BACKGROUND: The relationship between non-fasting remnant cholesterol and cardiovascular outcome in the era of potent statin therapy remained to be elucidated. METHODS: A cohort study of three hundred and twenty eight diabetics diagnosed with new-onset stable coronary artery disease (CAD) by coronary angiography were enrolled. All cases were followed up for an average duration of twelve months. The association between baseline remnant cholesterol levels and major cardiovascular outcomes were evaluated using the receivers operating characteristic (ROC) curves and Cox proportional hazards regression analysis. RESULTS: During a period of 12-month's follow-up, 14.3% patients (47/328) underwent pre-specified adverse outcomes. The remnant cholesterol associated with high sensitivity C-reactive protein, neutrophil count and fibrinogen (R 2 = 0.20, 0.12 and 0.14; P = 0.000, 0.036 and 0.010 respectively). Area under the ROC curves (AUC) indicated discriminatory power of the remnant cholesterol to predict the adverse outcomes for this population (AUC = 0.64, P < 0.005). Kaplan-Meier curve suggested that the lower levels of remnant cholesterol showed relatively lower cardiac events for diabetic patients with stable CAD (Log rank X 2 = 8.94, P = 0.04). However, according to multivariate Cox proportional hazards regression, apart from hemoglobin A1C (Hazard ratio [H.R.] =1.38, 95% CI: 1.14-1.66, P = 0.001) and Gensini scores (H.R. = 1.00, 95% CI: 1.00-1.02; P = 0.035), remnant cholesterol did not qualify as an independent predictor of adverse prognosis in these settings (H.R. = 1.05, 95% CI: 0.46-2.37, P = 0.909). CONCLUSIONS: Non-fasting remnant cholesterol was associated with inflammatory biomarkers and high incidence of revascularization, but not qualified as an independent predictor for short-term prognosis of diabetics with new-onset stable coronary artery disease.

Is the ratio of apoB/apoA-1 the best predictor for the severity of coronary artery lesions in Chinese diabetics with stable angina pectoris? An assessment based on Gensini scores.

BACKGROUND: There is a paucity of data about the best lipid ratio predicting the severity of coronary artery disease (CAD) in patients with diabetes mellitus. We determined the relationship between five conventional lipid ratios and the extent of coronary artery lesions in Chinese Type 2 diabetics with stable angina pectoris (SAP). METHODS: A prospective cohort study within 373 type 2 diabetic patients diagnosed with stable CAD by coronary angiography was performed. All patients were classified into three groups according to the tertiles of Gensini scores (GS, low group < 8 points n = 143; intermediate group 8-28 points, n = 109; high group > 28 points, n = 121). Association between the ratios of apolipoprotein (apo) B and apoA-1, total cholesterol and high density lipoprotein cholesterol (TC/HDL-C), triglycerides and HDL-C (TG/HDL-C), low density lipoprotein cholesterol and HDL-C (LDL-C/HDL-C), Non-HDL-C/HDL-C and GS were evaluated using the receivers operating characteristic (ROC) curves and multivariate logistic regression models. RESULTS: The ratio of apoB/apoA-1, TC/HDL-C, LDL-C/HDL-C, and Non-HDL-C/HDL-C were correlated with Gensini scores. Area under the ROC curves for predicting high Gensini scores in the ratios of apoB/apoA-1, TC/HDL-C, LDL-C/HDL-C and Non-HDL-C/HDL-C were 0.62, 0.60, 0.59 and 0.60, respectively (P < 0.005 for all). According to multivariate logistic regression analysis after adjusted with demographic characteristic and other lipid parameters, the ratio of apoB/apoA-1 is qualified as an independent discriminator for the severity of CAD. However, after further adjusting different baseline variables, such as left ventricular ejective fraction, hemoglobin A1c, leukocytes count and serum creatinine, none of the above lipid ratios remained. CONCLUSIONS: Compared with other lipid parameters, the ratio of apoB/apoA-1 appears to be more significantly correlated with the extent of coronary artery lesions in Chinese diabetics, but it was not an independent predictor in these settings.

Impact of 1, 25-(OH)2D3 on Left Ventricular Hypertrophy in Type 2 Diabetic Rats.

OBJECTIVE: To investigate the impact of 1, 25-(OH)2D3 on left ventricular hypertrophy (LVH) in type 2 diabetic rats. METHODS: Type 2 diabetic mellitus (DM) model rats were established by intraperitoneally injecting with 30 mg/kg streptozotocin. After 8 weeks, 19 male rats were identified as diabetic with left ventricular hypertrophy (LVH) by ultrasound examination, and randomly assigned into three groups: untreated (DM-LVH, n=7), treated with insulin (DM-LVH+INS, n=6), and treated with 1, 25-(OH)2D3 (DM-LVH+VD, n=6). Healthy male rats were used as the controls group (n=6). The fasting blood glucose and the insulin level were determined weekly. The left ventricular mass index, myocardial collagen content, collagen volume fraction, and 1, 25-(OH)2D3-receptor level were determined by 4 weeks later. RESULTS: In the DM-LVH model group, the insulin level was significantly decreased compared with the non-diabetic control group (P<0.05), whereas the blood glucose, left ventricular mass index, myocardial collagen content, collagen volume fraction, and 1, 25-(OH)2D3-receptor expression were significantly increased (all P<0.05). In the DM-LVH+INS and DM-LVH+VD groups, the insulin levels were significantly increased compared with the DM-LVH model group (P<0.05), whereas the other parameters were significantly decreased (all P<0.05). CONCLUSION: 1, 25-(OH)2D3 could reverse LVH in diabetic rats and that the mechanism may involve stimulating insulin secretion and reducing blood glucose via direct up-regulation of 1, 25-(OH)2D3-receptor expression.

Impact of estimated HDL particle size via the ratio of HDL-C and apoprotein A-I on short-term prognosis of diabetic patients with stable coronary artery disease.

BACKGROUND: Revascularization and statin therapy are routinely used in the management of stable coronary artery disease. However, it is unclear whether the estimated high-density lipoprotein (HDL) particle size (eHDL-S), the ratio of HDL cholesterol (HDL-C) to apoprotein A-I (apoA-I), is associated with the clinical outcomes of diabetic patients with stable coronary artery disease (CAD). METHODS: We performed a prospective cohort study of 328 patients diagnosed with stable CAD by coronary angiography. Patients were followed up for a mean duration of 12 months. The patients were divided into three groups by the tertiles of eHDL-S: low eHDL-S (< 0.71, n = 118); intermediate eHDL-S (0.71-0.79, n = 111); and high eHDL-S (> 0.79, n = 99). The associations between the baseline eHDL-S and short-term outcomes were evaluated using the Kaplan-Meier method and Cox proportional regression. RESULTS: The low eHDL-S group had higher triglyceride, hemoglobin A1c, uric acid, and leukocyte count than the other groups. During the follow-up period, 47/328 patients experienced a pre-specified outcome. According to the Kaplan-Meier analysis, the incidence of pre-specified outcomes was lower in the high eHDL-S group (P = 0.04). However, eHDL-S was not independently associated with adverse outcomes in Cox proportional hazards regression (hazard ratio (HR): 0.23, 95% confidence interval (95% CI): 0.01-11.24, P = 0.493). CONCLUSION: Although the eHDL-S was associated with inflammatory biomarkers, it was not independently associated with the short-term prognosis of diabetic patients with stable CAD in the era of revascularization and potent statin therapy.

Glycosylated hemoglobin A1c as a marker predicting the severity of coronary artery disease and early outcome in patients with stable angina.

BACKGROUND: Glycosylated hemoglobin A1C (HbA1c) has been widely recognized as a marker for predicting the severity of diabetes mellitus (DM) and several cardiovascular diseases. However, whether HbA1c could predict the severity and clinical outcomes in patients with stable coronary artery disease (CAD) remains largely unknown. We determine relationship of HbA1c with severity and outcome in patients with stable CAD. METHODS: We enrolled 1433 patients with stable angina who underwent coronary angiography and were followed up for an average 12 months. The patients were classified into three groups by tertiles of baseline HbA1c level (low group <5.7%, n = 483; intermediate group 5.7 - 6.3%, n = 512; high group >6.3%, n = 438). The relationships between the plasma HbA1c and severity of CAD and early clinical outcomes were evaluated. RESULTS: High HbA1c was associated with three-vessel disease. Area under the receivers operating characteristic curve (AUC = 0.67, 95% CI: 0.63-0.71, P < 0.001) and multivariate logistic regression analysis suggested that HbA1C was an independent predictor of severity of CAD (OR = 1.60, 95% CI: 1.29-1.99, P < 0.001) even after adjusting for gender, age, risk factor of CAD, lipid profile and fasting blood glucose. During follow-up, 133 patients underwent pre-specified outcomes. After adjusting for multiple variables in the Cox regression model, HbA1C remained to be an independent predictor of poor prognosis (HR = 1.28, 95% CI: 1.12-1.45, P < 0.001). CONCLUSIONS: We concluded that high level of baseline HbA1c appeared to be an independent predictor for the severity of CAD and poor outcome in patients with stable CAD.

Association of fibrinogen with severity of stable coronary artery disease in patients with type 2 diabetic mellitus.

BACKGROUND: Some studies have suggested a relation of plasma fibrinogen to the severity of coronary artery disease (CAD). However, whether plasma fibrinogen can predict the presence and severity of CAD in patients with diabetes mellitus has not been determined. METHODS: A total of consecutive 373 diabetic patients with typical angina pectoris who received coronary angiography were enrolled and classified into three groups by tertiles of Gensini score (GS, low group <8; intermediate group 8~28; high group >28). The relationship between fibrinogen and GS was evaluated. RESULTS: There were correlations of fibrinogen with hemoglobin A1c, C-reactive protein, and GS (r = 0.17, r = 0.52, and r = 0.21, resp.; all P < 0.001). Area under the receivers operating characteristic curve of fibrinogen was 0.62 (95% CI 0.56-0.68, P < 0.001) for predicting a high GS. Multivariate analysis suggested that plasma fibrinogen was an independent predictor of a high GS for diabetic patients (OR = 1.40, 95% CI 1.04-1.88, and P = 0.026) after adjusting for traditional risk factors of CAD. CONCLUSIONS: The present data indicated that plasma fibrinogen, a readily measurable systematic inflammatory marker, appeared to be an independent predictor for the severity of CAD in diabetic patients.

Impact of admission triglyceride for early outcome in diabetic patients with stable coronary artery disease.

BACKGROUND: The role of triglyceride (TG) in predicting the outcomes in diabetic patients with coronary artery disease (CAD) has not been well investigated. METHODS: A total of 329 cases with stable angina pectoris (SAP) were prospectively enrolled and followed up for an average of 12 months. They were classified into the two groups according to the cut-off values of predicting early outcome of fasting TG level (low group <1.2 mmol/L, n = 103; High group ≥1.2 mmol/L, n = 226). The relationship between the TG levels and early outcomes were evaluated. RESULTS: High TG group showed severer lipid profile and elevated inflammatory markers. During an average of 12-month follow-up, 47 out of 329 patients suffered from pre-specified outcomes. Area under the receivers operating characteristic curve suggested that TG, similar to serum Hemoglobin A1C (HbA1C), was a significant predictor of early outcome for diabetic patients with SAP (P = 0.002). In Cox regression models, after adjusted age, gender, body mass index, other lipid parameters, fasting blood glucose, high sensitivity C-reactive protein, neutrophil count and HbA1C, TG remained as an independent predictor of adverse prognosis. CONCLUSIONS: High level of fasting TG (≥1.2 mmol/L) was an independent predictor for early outcome of diabetic patients with SAP as like as HBA1c and number of affected coronary arteries in the era of revascularization and statin therapeutics.

Significance of red cell distribution width measurement for the patients with isolated coronary artery ectasia.

BACKGROUND: Red cell distribution width (RDW) has been recognized as a novel marker for several cardiovascular diseases. The aim of this study was to evaluate the association between RDW levels and the presence of isolated coronary artery ectasia (CAE). METHODS: We studied 414 subjects including 113 patients with isolated CAE (Group A), 144 patients with coronary artery disease (CAD, group B) and 157 angiographically normal controls (group C). Baseline clinical characteristics and laboratory findings including RDW were compared among three groups. RESULTS: The levels of RDW were significantly higher in group A and B compared with that in group C (12.97 ± 1.4 and 12.88 ± 1.0 vs 12.34 ± 0.9, p = 0.020) while no difference was found between CAE and CAD (p = 0.17). Additionally, the levels of CRP were also higher in patients with CAE and CAD compared with normal controls (0.26 ± 0.14 mg/L, 0.31 ± 0.27 mg/L vs 0.20 ± 0.06 mg/L, p = 0.04). The multivariate analysis indicated that RDW and CRP were the independent variables most strongly associated with the presence of isolated CAE and CAD. There was a positive correlation between levels of RDW and CRP in patients with isolated CAE (γ=0.532, p = 0.001). CONCLUSIONS: Our data suggested that RDW may be a useful marker and independent predictor for the presence of isolated CAE.

Relation of leukocytes and its subsets counts with the severity of stable coronary artery disease in patients with diabetic mellitus.

BACKGROUND: Both coronary artery disease (CAD) and diabetes mellitus (DM) are associated with inflammation. However, whether and which leukocytes can predict the presence and extent of CAD in patients with DM has not been investigated. The aim of the present study was to examine the association of leukocyte and its subsets counts with the severity of CAD in patients with DM. METHODS AND FINDINGS: Three hundred and seventy-three diabetic patients who were scheduled for coronary angiography due to typical stable angina pectoris were enrolled in this study. They were classified into the three groups according to tertiles of Gensini score (GS, low group <8, n=143; intermediate group 8~28, n=109; high group >28, n=121). The relationship between the leukocyte and its subsets counts with the severity of CAD were evaluated. The data indicated that there were significant correlations between leukocyte and neutrophil counts with GS (r=0.154 and 0.156, respectively, all P<0.003 for Pearson's correlation). Similarly, area under the receivers operating characteristic curve of leukocyte and neutrophil counts were 0.61 and 0.60 respectively (95%CI: 0.55-0.67, all P=0.001) for predicting high GS. Multivariate logistic regression analysis demonstrated that leukocyte count was an independent predictor for high GS patients with DM (OR=1.20, 95%CI 1.03-1.39, P=0.023) after adjusting for conventional risk factors of CAD. CONCLUSIONS: Compared with its subsets, leukocyte count appeared to be an independent predictor for the severity of CAD and the optimal cut-off value for predicting high GS (>28 points) was 5.0 × 10(9) cells/L in diabetic patients.

Percutaneous coronary intervention with anomalous origin of right coronary artery: case reports and literature review.

Percutaneous coronary intervention (PCI) in an anomalous right coronary artery (RCA) can be technically difficult because selective cannulation of the vessel may not be easy. We thereby present two cases with unstable angina pectoris of anomalous originated RCA. The PCI were successfully performed in two patients with a special guiding wire manipulating skill which we called "gone with the flow" combined with balloon anchoring technology, providing excellent angiographic visualization and sound guide support for stent delivery throughout the procedure without severe cardiovascular adverse effects. Our primary data suggested that PCI for geriatric patients with an anomalous origin of RCA accompanied by severe atherosclerotic lesions might also be a safe, available, and feasible strategy.

[Erythropoietin inhibits angiotensin II induced cardiomyocyte hypertrophy in vitro via activating PI3K/Akt-eNOS pathway].

OBJECTIVE: To explore the effect of erythropoietin (EPO) on angiotensin II (AngII) induced neonatal rat cardiomyocyte hypertrophy and the association with PI3K/Akt-eNOS signaling pathway. METHODS: Cardiomyocytes were isolated from new-born Sprague-Dawley rats and stimulated by AngII in vitro. The cell surface area and mRNA expression of atrial natriuretic factor (ANF) of cardiomyocytes were determined in the presence and absence of various concentrations of EPO, phosphatidylinositol 3'-kinase (PI3K) inhibitor LY294002 and nitric oxide synthase (NOS) inhibitor L-NAME. Intracellular signal molecules, such as Akt, phosphorylated Akt, eNOS and phosphorylated eNOS protein expressions were detected by western blot. Nitric oxide (NO) level in the supernatant of cultured cardiomyocytes was assayed by NO assay kit. RESULTS: EPO (20 U/ml) significantly inhibited AngII induced cardiomyocyte hypertrophy as shown by decreased cell surface area and ANF mRNA expression (all P < 0.05). EPO also activated Akt and enhanced the expression of eNOS and its phosphorylation (all P < 0.05), increased the NO production (P < 0.01). These effects could be partially abolished by cotreatment with LY294002 or L-NAME (all P < 0.05). CONCLUSION: EPO attenuates AngII induced cardiomyocytes hypertrophy via activating PI3K-Akt-eNOS pathway and promoting NO production.

Erythropoietin attenuates hypertrophy of neonatal rat cardiac myocytes induced by angiotensin-II in vitro.

OBJECTIVE: Erythropoietin (EPO) is a haematopoietic hormone that has been confirmed as a novel cardioprotective agent. In this study, we test the hypothesis that EPO inhibits angiotensin-II (Ang-II)-induced hypertrophy in cultured neonatal rat cardiomyocytes. MATERIAL AND METHODS: Cultured neonatal rat cardiomyocytes were used to evaluate the effects of EPO on Ang-II-induced hypertrophy in vitro. The surface area and mRNA expression of atrial natriuretic (ANF) myocytes were employed to detect cardiac hypertrophy. A phosphatidylinositol 3'-kinase (PI3K) inhibitor LY294002 and an endothelial nitric oxide synthase (eNOS) inhibitor L-NAME were also employed to detect the underlying mechanism of EPO. Intracellular signal molecules, such as Akt (PKB), phosphorylated Akt, eNOS and transforming growth factor-beta1 (TGF-beta1) protein expression were determined by Western blot. Nitric oxide (NO) levels in the supernatant of cultured cardiomyocytes were assayed using an NO assay kit. RESULTS: The results indicate that EPO significantly attenuates Ang-II-induced hypertrophy shown as inhibition of increases in cell surface area and ANF mRNA levels. NO production was also increased proportionally in the EPO-treated group. EPO enhanced Akt activation and eNOS protein expression, whereas LY294002 or L-NAME partially abolished the anti-hypertrophic effect of EPO, accompanied by a decrease in Akt activation, eNOS protein expression and/or a reduction of NO production. EPO also down-regulated the protein expression of TGF-beta1. CONCLUSION: We conclude that EPO attenuates cardiac hypertrophy via activation of the PI3K-Akt-eNOS-NO pathway and the down-regulation of TGF-beta1.