Real-World Data from the Use of Ranolazine in Patients with Stable Angina Pectoris: The RANGER Study.

Background: Although ranolazine has been available for years as a second-line treatment to reduce angina attacks in patients with stable angina pectoris, real-world data on the effectiveness, tolerability, and safety of ranolazine are limited. Methods: A non-interventional, prospective study was conducted to assess the effectiveness and safety of ranolazine. Patients eligible for enrolment had a baseline assessment between one and fourteen days after initiating ranolazine for the first time and a follow-up visit three months later. The primary endpoints comprised the weekly frequency of angina attacks, total adverse events, and ranolazine discontinuation rate. The secondary endpoints included the use of short-acting nitrates, changes on the Canadian Cardiovascular Society (CCS) angina classification score and quality of life scale score (QoL). Results: In total, 1101 patients were enrolled at 214 sites. Mean weekly angina attacks were reduced from 3.6 ± 2.9 to 0.4 ± 0.9 (p < 0.0001) and the mean weekly consumption of short-acting nitrates decreased by 1.7 ± 2.2 (p < 0.0001). CCS class and QoL were also improved (p < 0.0001). Adverse events were reported by 11 (1%) patients in total, while 2 of them (0.2%) were characterised as serious. Treatment was discontinued for various reasons in 23 patients (2.1%) after the follow-up period. Ranolazine treatment was equally effective in all subgroups tested, with larger benefits observed in patients with more frequent angina and CCS angina class III and IV. Up-titration of ranolazine during the study improved the outcomes. Conclusions: Ranolazine was well tolerated and effectively reduced angina attacks, with simultaneous improvement of the CCS class and QoL score in patients with stable angina.

Plasma nesfatin-1 and DDP-4 levels in patients with coronary artery disease: Kozani study.

BACKGROUND: Nesfatin-1, a novel adipokine and dipeptidyl peptidase-4 (DPP4), a mam malian serine protease, are potent factors of atherosclerosis. In the present cross-sectional study, we investigated whether the plasma nesfatin-1 and DPP4 is associated with the prevalence and severity of coronary artery disease (CAD) with and without diabetes mellitus (DM). METHODS: We consecutively enrolled a total of 240 patients with significant CAD (previous revascularization or angiographically-proven coronary artery stenosis > 50%) presented with either unstable angina (UA, N = 76) or stable chronic CAD (SCAD, N = 165). 85 patients with at least 2 classical cardiovascular risk factors but without significant CAD served as controls. The severity of CAD was assessed using coronary angiography by the Gensini score. Clinical parameters, glycemic and lipid profile, high-sensitivity CRP (hsCRP), nesfatin-1 and DPP4 levels were assayed. RESULTS: No differences were found for age, sex, hypertension and diabetes distribution between groups. Low nesfatin-1 levels were found in both CAD groups (UA & SCAD) with respect to controls. The difference between UA and SCAD groups was marginally non-significant. There was a significant increase of DPP4 along UA to SCAD and control groups. Differences between groups remained unchanged in non-diabetic participants. Nesfatin-1 significantly correlated to hsCRP (r = - 0.287, p = 0.036), HOMA-IR (r = - 0.587, p = 0.007) and hyperlipidemia (r = - 0.331, p = 0.034). DPP4 was significantly associated with hs-CRP (r = 0.353 p < 0.001) and FPG (r = 0.202, p = 0.020) in univariate analysis, but those correlations were lost in multiple regression analysis. There was a negative correlation between nesfatin-1 and the severity of CAD, quantified by the Gensini score (r = - 0.511, p < 0.001), but no association was found for DPP4. CONCLUSIONS: Serum DPP4 levels are increased in patients with CAD, while serum nesfatin-1 levels have a negative association with both the incidence and the severity of CAD. These results are independent of the presence of diabetes mellitus. In addition, both peptides have a strong association with hsCRP. Trial registration ClinicalTrials.gov Identifier: NCT00306176.

Report of two cases of acute cardiac adverse events in patients with colorectal carcinoma receiving oral capecitabine.

Capecitabine is an oral fluoropyrimidine chemotherapeutic agent, which, after oral administration, is metabolized to its active cytotoxic compound: 5-fluorouracil (5-FU). Cardiotoxicity is a recognized side effect of 5-FU, a closely related fluorinated pyrimidine antagonist. In the present report, we report on two patients who were admitted to our department after being treated with oral capecitabine for colorectal carcinoma and developed symptoms and signs of acute myocardial infarction that resolved after appropriate treatment and monitoring. The above two cases are discussed in the context of fluoropyrimidine, 5-FU, and capecitabine-induced cardiotoxicity; in addition, a detailed literature review of relevant cases and patient series reports is presented.

Impact of income status on prognosis of acute coronary syndrome patients during Greek financial crisis.

BACKGROUND: The effect of income status on patient outcome merits investigation during periods of financial crisis. We evaluated the impact of income status on out-of-hospital prognosis in a cohort of acute coronary syndrome (ACS) patients, included in a countrywide study during a period of financial crisis. METHODS: The study is a secondary analysis of a prospective, multicenter, observational study-the PHAETHON study-enrolling consecutive ACS patients in 37 hospitals in Greece. Patients were classified as low or high income based on the reported net annual household income using as a cut-off point the relative poverty threshold for Greece of 12,000 Euros. The outcome measure was survival free of the primary composite endpoint (cardiovascular death, myocardial infarction, stroke/transient ischemic attack, urgent revascularization and urgent hospitalization due to cardiovascular causes). RESULTS: The study population included 794 patients. The administration rate of evidence-based medications was similar in the low- (n = 455) and high-income (n = 339) groups during hospitalization and upon discharge. In a median follow-up of 189 days (interquartile range: 180-212 days), low-income patients had 92 % higher risk of the combined endpoint as compared to high-income patients [Hazard ratio (HR):1.92, 95 % CI:1.25-2.94, p = 0.003]. The effect of low-income status on the combined outcome remained significant after adjustment for age, gender and depression (HR:1.59, 95 % CI:1.02-2.49; p = 0.043). CONCLUSIONS: In a period of financial crisis, low income is a significant and independent predictor of poor out-of-hospital outcome in ACS patients. This association has profound implications and should be taken into consideration by public health policy makers.

Serum levels of novel adipokines, omentin-1 and chemerin, in patients with acute myocardial infarction: KOZANI STUDY.

OBJECTIVES: The role of the novel adipokines, omentin-1 and chemerin, in coronary artery disease is still obscure. The present study analyzed the serum levels of omentin-1 and chemerin in patients with acute myocardial infarction (AMI) as well as prospectively 6 months post-AMI. METHODS: Seventy-eight patients (63 men and 15 women) with first AMI were enrolled. Thirty-two age-matched and sex-matched individuals without overt cardiovascular disease served as healthy controls. Serum levels of omentin-1, chemerin, interleukin-18 (IL-18), high-sensitivity C-reactive protein (hsCRP), glycemic and lipid profiles, blood pressure, BMI and ejection fraction were assayed. In AMI patients, blood samples were obtained at hospital admission and after 6 months, whereas coronary angiography was performed within 7 days after admission. RESULTS: At baseline, AMI group appeared with significantly lower ejection fraction, omentin-1 and high-density lipoprotein serum levels, whereas it had higher concentrations of white blood cells count (WBC), hsCRP, IL-18 and chemerin compared with healthy controls (P < 0.05). After 6 months of follow-up, the concentrations of WBC, hsCRP and IL-18 significantly downregulated, whereas omentin-1 levels considerably increased (from 18.73 ± 3.66 ng/ml to 28.62 ± 5.61 ng/ml, P < 0.001) within AMI group. In contrast, serum chemerin did not significantly change (263.37 ± 73.32 ng/ml vs. 195.90 ± 84.32 ng/ml, P = 0.190). In standard multiple regression analyses, baseline levels and changes of hsCRP and IL-18 levels during follow-up remained independent determinants of omentin-1, respectively at baseline and after follow-up. CONCLUSION: Patients with AMI showed at admission lower omentin-1 and higher chemerin serum levels compared with healthy controls. The suppression of inflammation in the 6-month post-AMI period might have mediated the significant upregulation of omentin-1, implicating a novel target of treatment.

Serum levels of fetuin-A, osteoprotegerin and osteopontin in patients with coronary artery disease: effects of statin (HMGCoA-reductase inhibitor) therapy.

BACKGROUND AND OBJECTIVES: Statins (HMGCoA-reductase inhibitors) produce numerous non-lipid related, 'pleiotropic' effects. Our aim was to investigate whether simvastatin treatment affects serum levels of vascular calcification inhibitors, such as fetuin-A, osteoprotegerin (OPG) and osteopontin (OPN), in patients with coronary artery disease (CAD). METHODS: A total of 98 statin-free patients with angiographically proven, newly diagnosed CAD were treated with simvastatin (20-40 mg daily) for 6 months to target a low-density lipoprotein (LDL) level <100 mg/dL (the statin group [SG]). Thirty-five age- and sex-matched healthy individuals without any chronic metabolic or cardiovascular disease at baseline served as a healthy control group (HCG). Clinical, anthropometrical and metabolic parameters and serum fetuin-A, OPG, OPN and high-sensitivity C-reactive protein (hsCRP) levels were assayed at baseline in all participants and after 6 months only in SG patients. RESULTS: Compared with HCG subjects at baseline, SG patients exhibited higher serum levels of OPG (7.39 ± 2.94 pmol/L vs 2.47 ± 1.15 pmol/L, p < 0.001), OPN (60.99 ± 17.52 ng/mL vs 45.45 ± 10.26 ng/mL, p = 0.005) and hsCRP (4.66 ± 1.74 mg/L vs 1.58 ± 0.56 mg/L, p < 0.001) as well as lower serum levels of fetuin-A (0.222 ± 0.036 µg/L vs 0.839 ± 0.092 µg/L, p < 0001). Apart from significantly reducing plasma total cholesterol and LDL, simvastatin also reduced serum levels of fetuin-A (by ~62.6 %), OPG (by ~47.2 %), OPN (by ~44.6 %) and hsCRP (by ~45.3 %) (p < 0.05) in SG patients. In standard multiple regression analysis, the simvastatin-induced reduction in fetuin-A was independently associated with changes in total cholesterol (ß = -0.289, p = 0.048) and LDL (ß = -0.302, p = 0.032) (R (2) = 0.305, p = 0.040). CONCLUSION: Patients with CAD showed derangements in serum levels of all vascular calcification inhibitors compared with those in healthy controls. Simvastatin treatment for 6 months significantly decreased serum fetuin-A, OPG and OPN levels, but the clinical relevance of this requires further investigation.

Arterial stiffness and novel biomarkers in patients with abdominal aortic aneurysms.

OBJECTIVES: Pulse wave velocity (PWV) constitutes a valid index of arterial stiffness osteoprotegerin (OPG) and osteopontin (OPN) which are well-established vascular calcification inhibitors, highly correlated with inflammation, and cardiovascular events incidence. We investigated the association of PWV with the aforementioned novel biomarkers in patients with abdominal aortic aneurysm (AAA). METHODS: We enrolled 108 men with AAA (AAA group) candidates for endovascular repair. We excluded patients with Marfan syndrome or other collagen-related disorders. Forty-one age-matched men, with stable coronary artery disease (CAD), but without AAA, served as controls (CO group). PWV, clinical parameters and serum levels of osteoprotegerin (OPG), osteopontin (OPN), interleukin-6 (IL-6) and IL-10 were determined. RESULTS: With the exception of higher smoking rate and the lower statin's usage in the AAA group, there were non-significant differences in the rest of demographic and clinical parameters (p>0.05). We found significantly higher levels of PWV in AAA than CO group (12.99±3.75 m/s vs 10.03±1.57 m/s, p<0.001). In parallel, serum OPG, OPN, IL-6 levels were considerably increased, while IL-10 levels were downregulated (p<0.001) in AAA group. PWV positively correlated with mean blood pressure, OPG concentrations and AAA diameter in univariate and multivariate analysis (R(2)=0.498, p=0.008). Finally, age and OPG remained independent determinants of AAA presence in the whole study cohort. CONCLUSIONS: Arterial stiffness, circulating vascular calcification inhibitors and inflammatory mediators seem to be significantly upregulated in patients with AAA. An independent association of PWV with mean blood pressure, OPG and AAA diameter is of clinical importance which requires further investigation.

The effects of resistance training on ApoB/ApoA-I ratio, Lp(a) and inflammatory markers in patients with type 2 diabetes.

The purpose of this study was to investigate the effects of resistance training (RT) on novel cardiovascular risk factors in patients with type 2 diabetes mellitus (T2DM). We enrolled 52 overweight/obese, type 2 diabetic patients, with inadequate glycemic control (HbA1c > 6.5 %), but without overt diabetic vascular complications. Participants were randomly assigned into two equivalent groups (n = 26): (1) Resistance exercise group: subjects underwent a supervised RT program (3-times/week, 60 min/session, 2-3 sets of 8 machine-weight exercises, 60-80 % of one-repetition maximum). (2) Control group (CG): at study entrance, they received a structured exercise counseling to increase daily physical activity. Clinical parameters, cardiorespiratory capacity, glycemic and lipid profile, apolipoprotein A-I (ApoA-I), apolipoprotein B (ApoB), Lipoprotein(a) [Lp(a)], insulin resistance (HOMA-IR), high-sensitivity CRP (hsCRP), fibrinogen were measured before and after 3 months. RT significantly reduced glycemic indexes, insulin resistance and systolic blood pressure, compared to CG (p < 0.05). Moreover, exercise-treated patients conferred a remarkable downregulation in ApoB levels (from 135.92 ± 30.97 mg/dL to 85.9 ± 26.46 mg/dL, p < 0.001) as compared to CG (from 126.33 ± 36.59 mg/dL to 116.23 ± 27.52 mg/dL, p = 0.872) (p < 0.001). Similarly, ApoB/ApoA-I ratio was considerably decreased in REG rather than CG (-0.32 ± 0.09 vs 0.02 ± 0.01, p < 0.001). Notably, ApoA-I, Lp(a), hsCRP, fibrinogen, the rest of lipid parameters, body weight and exercise capacity remained unaltered in both groups (p > 0.05). Among variables, HOMA-IR reduction was found to be an independent predictor of changes in ApoB/ApoA-I ratio (R (2) = 0.406, p = 0.041) in REG. Long-term RT ameliorated glycemic control, insulin sensitivity and ApoB/ApoA-I ratio in individuals with T2DM. Although we did not observe significant benefits in the rest of cardiovascular risk factors, our results indicate a merely beneficial impact of RT.

Epidemiological characteristics and in-hospital management of acute coronary syndrome patients in Greece: results from the TARGET study.

INTRODUCTION: Conduction of national surveys is needed to depict temporal trends in the risk profile, type of implemented treatment strategy and outcome of patients with acute coronary syndromes (ACS). The TARGET study is a multicenter, observational study that aimed to evaluate the epidemiological characteristics, management pattern and outcome of ACS patients in Greece. METHODS: A total of 418 consecutive patients with ACS (44.7% STEMI, 34.2% NSTEMI, 21.1% unstable angina) from 17 centers (52.9% with catheterization facilities) were enrolled in the study (78.0% males, 63.9 ± 12.9 years). RESULTS: Overall, 67.9% of the patients had hypertension, 27.5% were diabetics and 57.4% had dyslipidemia. Thrombolytic therapy (60.7% tenecteplase, 38.2% reteplase) was administered in 22.7% of the study population, while invasive management was performed in 40.2% of patients (27.0% PCI and 1.0% CABG) during the index hospitalization. In-hospital all-cause mortality was 1.9%, with 12.2% of patients experiencing adverse clinical events. Evidence-based medications were prescribed to the majority of enrolled patients during hospitalization and upon discharge (97% and 94% received aspirin, 93% and 84% clopidogrel, 87% and 86% beta-blockers, 96% and 93% statins, respectively). CONCLUSION: The prevalence of modifiable risk factors exhibits an increasing trend among ACS patients in Greece. The prescription pattern of evidence-based medications has improved considerably, while there remains considerable room for improvement in expanding the implementation of invasive management in realworld clinical practice.

Effects of atorvastatin on apelin, visfatin (nampt), ghrelin and early carotid atherosclerosis in patients with type 2 diabetes.

To investigate the influence of atrovastatin treatment on carotid intima-media thickness (CIMT) and serum levels of novel adipokines, like apelin, visfatin (nampt), and ghrelin, in patients with type 2 diabetes mellitus (T2DM). 87 statin-free patients (50 males) with T2DM, aged 55-70, but without carotid atherosclerotic plaques were initially enrolled. CIMT was assayed in all participants by ultrasound. Patients were then treated with atorvastatin (10-80 mg) to target LDL <100 mg/dl. Anthropometric parameters, blood pressure, glycemic and lipid profile, high-sensitivity CRP (hsCRP), insulin resistance (HOMA-IR), apelin, visfatin and ghrelin were measured at baseline and after 12 months. Atorvastatin treatment significantly improved lipid profile across with increased apelin (from 0.307 ± 0.130 pg/ml to 1.537 ± 0.427 pg/ml; P < 0.001) and suppressed visfatin (from 21.54 ± 10.14 ng/ml to 15.13 ± 7.61 ng/ml; P = 0.002) serum levels in our diabetic patients. Standard multiple regression analysis showed that the atorvastatin-induced increment in apelin was independently associated with changes in total cholesterol (ß = -0.510, P = 0.030) and LDL-cholesterol (ß = -0.590, P < 0.001) (R (2) = 0.449, P = 0.014), while the reduction of visfatin concentration was independently associated with the change in hsCRP (ß = 0.589, P < 0.001; R (2) = 0.256, P = 0.006), after adjustment for age, sex and BMI. CIMT and ghrelin did not alter significantly after 12 months of atorvastatin treatment (NS). Among participants, high-dose (80 mg) rather than low-dose (10 mg) of atorvastatin treatment yielded greater (P < 0.05) changes in apelin, visfatin and CIMT levels despite the final equivalent levels of LDL. Atorvastatin administration increased apelin and decreased visfatin serum levels significantly, without change of CIMT, in patients with T2DM. However, high-dose of atorvastatin exerted more favourable impact on adipokines and CIMT than low-dose. Our results implicate another important link between adiposity and atherosclerosis.

The pathophysiology of HIV-/HAART-related metabolic syndrome leading to cardiovascular disorders: the emerging role of adipokines.

Individuals infected with human immunodeficiency virus (HIV) frequently demonstrate metabolic syndrome (MS) associated with increased incidence of cardiovascular disorders. Characteristics of HIV infection, such as immunodeficiency, viral load, and duration of the disease, in addition to the highly active antiretroviral therapy (HAART) have been suggested to induce MS in these patients. It is well documented that MS involves a number of traditional cardiovascular risk factors, like glucose, lipids, and arterial blood pressure abnormalities, leading to extensive atherogenic arterial wall changes. Nevertheless, the above traditional cardiovascular risk factors merely explain the exacerbated cardiovascular risk in MS. Nowadays, the adipose-tissue derivatives, known as adipokines, have been suggested to contribute to chronic inflammation and the MS-related cardiovascular disease. In view of a novel understanding on how adipokines affect the pathogenesis of HIV/HAART-related MS and cardiovascular complications, this paper focuses on the interaction of the metabolic pathways and the potential cardiovascular consequences. Based on the current literature, we suggest adipokines to have a role in the pathogenesis of the HIV/HAART-related MS. It is crucial to understand the pathophysiology of the HIV/HAART-related MS and apply therapeutic strategies in order to reduce cardiovascular risk in HIV patients.

Impact of atorvastatin on serum vaspin levels in hypercholesterolemic patients with moderate cardiovascular risk.

AIM: Vaspin and visfatin have emerged as novel adipokines, involved in atherosclerosis progression. The aim of the present study was to investigate the effects of atorvastatin and lifestyle modification on the above adipokines in hypercholesterolemic patients. METHODS: One hundred four statin-free subjects with moderate cardiovascular risk (Framingham risk score of 10-20%) were randomly assigned to receive either atorvastatin 20mg per day (AT group, n=52) or lifestyle modification (LM, group, n=52). For comparison, age and gender-matched blood donors, without any chronic cardiovascular or metabolic disease served as healthy controls (HC group, n=40). Clinical and anthropometrical parameters, lipids, fasting glucose, serum vaspin, visfatin and insulin levels were obtained at the beginning and after 12 weeks. RESULTS: At the end of the study, intra-group and inter-group comparison revealed that atorvastatin administration considerably ameliorated most lipid parameters and downregulated hsCRP levels (p=0.002, p=0.041, respectively). Moreover, we observed a significant increase of vaspin concentrations after 12-week atorvastatin treatment (from 1.37±0.6ng/ml to 2.13±0.61ng/ml), as compared to baseline (p=0.007) and LM group (p=0.030). In standard multiple regression analysis, the atorvastatin-induced decrease of vaspin was independently associated with hsCRP reduction (p=0.015). On the other hand, within and between groups comparison revealed a non-significant (p>0.05) reduction of visfatin serum levels. In our study, lifestyle modification had totally modest influence on clinical and biochemical variables (p>0.05). CONCLUSION: In hypercholesterolemic patients with moderate estimated cardiovascular risk, atorvastatin administration reduced hsCRP and increased serum vaspin levels compared to lifestyle modification. The relation of those pleiotropic, non-lipid-lowering effects of statins with their clinical outcomes remains to be proved.

The impact of hypertension on systolic and diastolic left ventricular function. A tissue Doppler echocardiographic study.

BACKGROUND: The purpose of this study is to assess the impact of hypertension on systolic function and diastolic function using 2-dimensional echocardiography, conventional Doppler imaging of the transmitral inflow, and tissue Doppler imaging (TDI) of the mitral annulus. METHODS: From an outpatient clinic population, 414 consecutive patients underwent 2-dimensional echocardiography, conventional Doppler imaging of the transmitral inflow, and TDI of the septal, lateral, inferior, and posterior walls near the mitral annulus. Parameters of systolic left ventricular (LV) function and diastolic LV function were assessed. Patients were divided according to the presence or absence of systemic hypertension (blood pressure > or = 140/90 mm Hg on > or = 3 measurements or treatment with antihypertensive medication). RESULTS: A complete echocardiographic evaluation was obtained in 397 patients. Among these, 269 (68%) had hypertension. There was no difference with respect to age between patients with and without hypertension. Patients with hypertension had higher LV mass index and relative wall thickness and lower TDI peak systolic velocity (V(S)) when compared with patients without hypertension. In addition, indices of diastolic LV function were significantly impaired in hypertensive patients. CONCLUSIONS: Quantitative echocardiography using TDI reveals that hypertensive patients with preserved global LV systolic function often have combined impairment of systolic function and diastolic function.