Comparison of non-vitamin K antagonist oral anticoagulants and well-controlled warfarin in octogenarians with non-valvular atrial fibrillation: Real-world data from a single tertiary center.

OBJECTIVE: Atrial fibrillation (AF) is the most common arrhythmia in clinical practice, and its prevalence increases with age. Nevertheless, data about the use of oral anticoagulants (OACs) among patients with ≥80 years remains limited. This study aimed to evaluate the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in octogenarians with non-valvular AF (NVAF). METHODS: Medical records of 387 patients who were ≥80 years and diagnosed with NVAF in our hospital between January 2017 and December 2019 were evaluated retrospectively. Patients with NVAF were divided into 2 groups (NOACs and warfarin), and the incidence of stroke/systemic embolism and major bleeding were analyzed. RESULTS: A total of 322 patients were included in the study. The median follow-up duration was 10.9 months for the NOACs group and 12.1 months for the warfarin group. The primary efficacy outcome was stroke/systemic embolism, and the primary safety outcome was major bleeding. A total of 220 patients were taking NOACs, and the most preferred NOACs were apixaban (53.6%), rivaroxaban (29.5%), dabigatran (13.2%), and edoxaban (3.6%) in this order. During a mean follow-up of 302.7 patient-years, the incidence of stroke or systemic embolic events was slightly higher among patients with warfarin but the difference was not statistically significant (p=0.862). The incidence rates of major bleeding events were similar between the treatment groups (p=0.824). CONCLUSION: Our study revealed that the safety and efficacy outcomes are similar between the 2 treatment groups in octogenarians with NVAF.

Is there a relationship between resistin levels and left ventricular end-diastolic pressure?

OBJECTIVE: Resistin, a cysteine-rich peptide, is associated with atherosclerosis and diabetes. Resistin levels increase corresponding to coronary artery disease (CAD) and heart failure severity. Since resistin level tends to elevate with symptomatic heart failure, it is expected to be associated with left ventricular end-diastolic pressure (LVEDP). However, there is no relevant literature on the relationship between resistin levels and LVEDP. We aimed to evaluate the association between resistin levels and LVEDP, severity of CAD, carotid intima-media thickness (CIMT), and echocardiographic diastolic dysfunction parameters. METHODS: For this study, 128 euvolemic patients with creatinine clearance >50 mg/dL and without acute coronary syndrome, who had typical chest pain or were stress test positive, were enrolled. Resistin level was measured by Enzyme-linked immunosorbent assays (ELISA) method. Severe CAD is defined as ≥50% stenosis in one of the major coronary arteries. LVEDP was measured during left heart catheterization. RESULTS: After coronary angiography, 60 patients (46.9%) had severe CAD. The mean LVEDPs were similar for patients with and without severe CAD (p=0.480). The resistin levels did not differ between the groups (p=0.154). The resistin levels did not correlate with LVEDP (r=-0.045, p=0.627), ejection fraction (EF; r=0.110, p=0.228), the Gensini score (r=-0.091, p=0.328), and CIMT (r=0.082, p=0.457). No significant correlation was found between the echocardiographic diastolic dysfunction parameters and resistin levels. CONCLUSION: There was no significant correlation between resistin level and LVEDP, CAD severity, echocardiographic diastolic dysfunction parameters, and CIMT. Further studies are warranted to determine the efficacy of resistin in clinical use.

Plasma osteopontin concentration is elevated in patients with coronary bare metal stent restenosis.

OBJECTIVE: Osteopontin is a component of atherosclerotic lesions, secreted by monocytes, macrophages and endothelial and vascular smooth muscle cells, which together are responsible for neointimal proliferation. We examined whether elevated plasma osteopontin concentration was associated with in-stent restenosis in patients with coronary artery disease. SUBJECTS AND METHODS: We enrolled 91 patients who underwent coronary artery stenting, and 60 control patients with normal findings on coronary angiography, between June 2012 and September 2013. For patients with stents, we measured plasma osteopontin concentration at the first follow-up coronary angiogram. For controls, plasma osteopontin concentration was measured at the time of angiography. RESULTS: Of the 91 patients who had undergone coronary artery stenting, 31 (34.1%) had developed in-stent restenosis and the mean time passed to control coronary angiography was 36.7 months (±SD 35.1 months). Mean plasma osteopontin concentration in this group was 2721.4 ± 1787.8 pg/ml, significantly higher than the 60 patients (65.9%) with no in-stent restenosis (1770.4 ± 1208.2 pg/ml, p = .011) and the 60 patients with a normal coronary angiogram (1572.4 ± 904.8 pg/ml, p = .002). There was no significant difference in mean osteopontin concentration between the patients with no in-stent restenosis and the control group (p = .312). CONCLUSIONS: Elevated plasma osteopontin concentration is associated with in-stent stenosis in patients with coronary artery disease. Further studies will be needed to establish whether osteopontin can predict in-stent restenosis and guide clinical management strategies.

Treatment-associated change in apelin concentration in patients with hypertension and its relationship with left ventricular diastolic function.

OBJECTIVE: We examined the change in apelin concentration and its relationship with left ventricular diastolic function in patients treated for hypertension. METHODS: Ninety treatment-naive patients with newly diagnosed hypertension and 33 age- and sex-matched control subjects were prospectively enrolled. Patients with hypertension were randomized to treatment either with telmisartan 80 mg or amlodipine 10 mg. Apelin concentration was measured and echocardiography was performed at baseline and after 1 month of treatment. RESULTS: The data of 77 patients and 33 controls were analyzed. Mean age, gender, baseline blood pressure, apelin levels, and echocardiographic measurements were similar between the treatment groups (p>0.05 for all). Apelin concentration was significantly lower in patients with hypertension than in controls. There was a significant increase in apelin level after 1 month of treatment in both groups (0.32±0.17 vs. 0.38±0.17 ng/dL in telmisartan group, p=0.009, and 0.27±0.13 vs. 0.34±0.18 ng/dL in amlodipine group, p=0.013). Diastolic function improved significantly in both groups (p<0.05) but was not significantly associated with change in apelin concentration. CONCLUSION: Apelin concentration increased significantly after 1 month of effective treatment with telmisartan or amlodipine to a similar extent. Change in apelin concentration was not associated with improvement in diastolic function.

Cardiac autonomic nervous dysfunction detected by both heart rate variability and heart rate turbulence in prediabetic patients with isolated impaired fasting glucose.

OBJECTIVE: Cardiac autonomic nervous dysfunction (CAND), a severe complication of diabetes, has also been shown to affect prediabetic patients. The role of isolated impaired fasting plasma glucose (IFG), a subtype of prediabetes, is not clear in the pathogenesis of CAND. The aim of this study was to examine the relationship between isolated IFG and cardiac autonomic function using heart rate variability (HRV) and heart rate turbulence (HRT) indices derived from 24-h Holter electrocardiogram recordings. METHODS: This observational, prospective, cross-sectional study examined 400 consecutive subjects divided into three groups according to oral glucose tolerance test results: the control group [Group I, fasting plasma glucose (FPG) <100 mg/dL and normal glucose tolerance, n=193], the isolated IFG group (Group II, FPG ≥100 and <126 mg/dL, n=134), and the isolated impaired glucose tolerance (IGT), both IFG and IGT, or newly diagnosed diabetes' group (Group III, n=73). Patients with non-sinus rhythm, known diabetes mellitus, coronary artery disease, heart failure, severe valvular disease, or receiving medical therapy that may affect HRV and HRT indices were excluded. Time domain HRV parameters, turbulence onset (TO), turbulence slope (TS), and HRT category were examined. Chi-square, one-way analysis of variance, Kruskal-Wallis H, and Mann-Whitney U tests were used to compare variables where appropriate. The correlation between Holter data and FPG levels was analyzed using the Spearman's test. Multiple linear regression analysis was performed to identify independent predictors of the HRV and HRT parameters. RESULTS: Median (interquartile range 25-75) FPG levels in Groups I, II, and III were 89 (83/93) mg/dL, 109 (104/116) mg/dL, and 174 (150.5/197) mg/dL, respectively. There were significant differences in HRV and HRT parameters between and among all groups. While HRV parameters and TS decreased from Group I to Group III, TO and HRT category gradually increased. Additionally, FPG level was significantly correlated with SDNN, r=-0.220; SDNN index, r=-0.192; SDANN, r=-0.207; RMSSD, r=-0.228; pNN50, r=-0.226; TO, r=0.354; and TS, r=-0.331 (all p<0.001). CONCLUSION: CAND, as detected by both HRV and HRT, appear to be present in the isolated IFG subtype of prediabetes.

Which is responsible for cardiac autonomic dysfunction in non-diabetic patients with metabolic syndrome: Prediabetes or the syndrome itself?

AIMS: Cardiac autonomic dysfunction (CAD) is associated with both prediabetes and metabolic syndrome (MS). Heart rate variability (HRV) and heart rate turbulence (HRT) are reliable 24-h Holter-ECG findings of cardiac autonomic function. This study aimed to investigate the relation between MS and its components and CAD using HRV and HRT. MATERIALS AND METHODS: The study included 80 non-diabetic patients with MS and 70 control subjects. All study population and the patients with MS were further analyzed for each diagnostic component of MS to investigate which criteria impaired HRV and HRT. RESULTS: HRV and HRT parameters were disturbed in patients in the MS group. While impairment in HRV and HRT was significantly related to the presence of the fasting plasma glucose (FPG) criterion, there were no differences between groups in terms of the other 4 MS criteria. Moreover, FPG level was significantly correlated with SDNN (r=-0.352, p<0.001), SDNN index (r=-0.423, p<0.001), SDANN (r=-0.301, p<0.001), RMSSD (r=-0.237, p<0.001), pNN50 (r=-0.237, p<0.001), turbulence onset (TO) (r=0.365, p<0.001) and turbulence slope (TS) (r=-0.365, p<0.001). Among the MS diagnostic criteria, only FPG level was an independent determinant of all HRV and HRT parameters. CONCLUSIONS: This study confirms the relation between MS and CAD. Increased FPG alone appears to be responsible for the mentioned findings among the 5 diagnostic criteria. Accordingly, CAD may be the result of prediabetes, not MS in patients with MS.

Comparison of Carvedilol and Metoprolol for Preventing Contrast-Induced Nephropathy after Coronary Angiography.

AIMS: Contrast-induced nephropathy (CIN) is one of the most common causes of hospital-acquired acute renal failure. Oxidative stress and vasoconstriction might play key roles in its pathogenesis. In a few experimental models, antioxidant properties of carvedilol have been documented. The aim of this study was to analyze and compare the effects of carvedilol and metoprolol on the development of CIN in patients undergoing coronary angiography. METHODS: One hundred patients currently taking metoprolol and 100 patients currently taking carvedilol were enrolled into the study. Venous blood samples were obtained before and 48 h after contrast administration. Cystatin C and malondialdehyde values were examined and compared. CIN was defined as a creatinine increase of at least 25% or 0.5 mg/dl from the baseline value. RESULTS: Seven patients in the carvedilol group (7%) and 22 patients in the metoprolol group (22%) developed CIN (p = 0.003). In the metoprolol group, the median cystatin C concentration increased significantly from 978 to 1,086 ng/ml (p = 0.001) 48 h after radiocontrast administration. In the carvedilol group, the median cystatin C concentration did not change significantly (1,143 vs. 1,068 ng/ml; p = 0.94). In the metoprolol group, the mean malondialdehyde concentration increased significantly from 7.09 ± 1.48 to 8.38 ± 2.6 nmol/l (p < 0.001). In the carvedilol group, the mean serum malondialdehyde concentration did not change significantly (7.44 ± 1.21 vs. 7.56 ± 1.11 nmol/l; p = 0.59). CONCLUSION: When compared to metoprolol, carvedilol might decrease oxidative stress and subsequent development of CIN.

Arrhythmogenic evidence for epicardial adipose tissue: heart rate variability and turbulence are influenced by epicardial fat thickness.

BACKGROUND: Epicardial adipose tissue (EAT) is a local source of various hormones, cytokines, and vasoactive substances affecting the myocardium. EAT contains abundant ganglionic plexi that interact with the autonomic nervous system. Evidence of the association between EAT and arrhythmia is limited, with the exception of atrial fibrillation. This study aimed to investigate the relation between EAT and cardiac autonomic function using heart rate variability (HRV) and heart rate turbulence (HRT) parameters. METHODS: All subjects underwent a 24-hour Holter recording to assess HRV and HRT parameters and a transthoracic echocardiography to measure EAT thickness. Patients were divided into two groups according to the median EAT thickness (3.9 mm). The higher EAT group consisted of 111 patients with a >3.9-mm thickness and the lower EAT group 113 patients with a ≤ 3.9-mm EAT thickness. RESULTS: HRV and HRT parameters were significantly influenced in the higher EAT group. Moreover, we observed significant correlations between EAT thickness and Holter findings (standard deviation of all NN intervals [SDNN]: r = -0.462, P < 0.001; SDNN index: r = -0.349, P < 0.001; standard deviation of the average NN intervals: r = -0.465, P < 0.001; root mean square of successive differences: r = -0.251, P < 0.001; pNN50: r = -0.354, P < 0.001; turbulence onset: r = 0.172, P = 0.010; turbulence slope: r = -0.279, P < 0.001, HRT category: r = 0.169, P = 0.011). In multivariate regression analysis, EAT thickness was independently associated with all measures of HRV and HRT, with the exception of turbulence onset. CONCLUSIONS: Sympathovagal imbalance, detected by HRV and HRT parameters, is related to EAT thickness. As sympathovagal imbalance is a predictor of arrhythmic events, EAT may play an important arrhythmogenic role not limited to atrial fibrillation.

The effect of raloxifene on left ventricular hypertrophy in postmenopausal women: A prospective, randomized, and controlled study.

OBJECTIVE: In healthy women, there is a progressive age-related increase in myocardial mass that is not seen in their male counterparts and occurs primarily in postmenopausal women. Raloxifene is a selective estrogen receptor modulator that has estrogenic actions on bone and the cardiovascular system. The aim of this study was to investigate the effect of raloxifene on myocardial hypertrophy in postmenopausal patients. METHODS: A total of 22 postmenopausal osteoporotic women were included in this open-label, randomized, prospective, controlled study. Patients were randomized into two groups: 11 of the patients (group 1) were treated with raloxifene 60 mg/day, and the other 11 patients(group 2) were defined as the control group. Quantitative 2-dimensional and M-mode echocardiographic examination was performed in all patients at the beginning and repeated at the end of the 6-month follow-up period. Left ventricle mass (LVM) and left ventricle mass index (LVMI) were calculated for all patients. RESULTS: The mean age of the patients was 57.2±3.9 years, and baseline clinical characteristics and echocardiographic parameters were similar between the two groups. After 6 months of raloxifene treatment, there was no difference in echocardiographic parameters of LVM and LVMI compared with the control group (201.2±25.9 gr vs. 169.7±46.2 gr, p=0.14 and 120.4±25.9 gr/m2 vs. 105.5±26.3 gr/m2, p=0.195, respectively). There was also no significant difference in LVM and LVMI in the within-group analysis of both groups. CONCLUSION: Raloxifene therapy does not affect myocardial hypertrophy in postmenopausal women after 6 months of treatment.

Could plasma asymmetric dimethylarginine level be a novel predictor beyond the classic predictors of stent restenosis?

OBJECTIVE: The aim of this study was to investigate the factors associated with coronary stent restenosis and if there is an association between plasma asymmetric dimethylarginine (ADMA) levels and stent restenosis. METHODS: Ninety-one patients, who had a history of coronary bare metal stent implantation due to any cause in the last one year period, were admitted to this observational cross-sectional study. Coronary angiography was performed to all patients and quantitative angiography was used to determine the presence of stent restenosis. Laboratory parameters and angiographic features that contribute to stent restenosis were evaluated. Plasma ADMA levels were measured by using high performance liquid chromatography. Logistic regression analysis was used to determine the independent factors of stent restenosis. RESULTS: Angiographic restenosis was found in 35 patients (38.5%). Stent diameter (p=0.038) and left ventricular ejection fraction (p=0.023) were lower and stent implantation history due to acute coronary syndrome (p=0.029), plasma ADMA level (5.0±1.8x10-4 mmol/L vs. 3.9±1.0x10-4 mmol/L, p=0.001), C-reactive protein concentration (p=0.016), white blood cell count (p=0.044) and stent length (p=0.005) were higher in patients with restenosis. Plasma ADMA level (ß=0.536; OR: 1.710; CI: 1.022-2.861; p=0.041), C-reactive protein concentration (ß=0.062; OR: 1.064; CI: 1.003-1.129; p=0.041), stent diameter (ß=-3.047; OR: 0.048; CI: 0.007-0.313; p=0.002) and length (ß=0.165; OR: 1.179; CI: 1.036-1.343; p=0.013) were found to be the independent predictors of stent restenosis in logistic regression analysis. CONCLUSION: We conclude that plasma ADMA levels may be used as a novel marker for stent restenosis beyond the classic stent restenosis markers.

Epicardial adipose tissue thickness and plasma homocysteine in patients with metabolic syndrome and normal coronary arteries.

BACKGROUND: Increased epicardial adipose tissue thickness and plasma homocysteine levels are associated with Metabolic Syndrome (MS) and coronary artery disease. The majority of patients with MS have subclinical or manifest coronary artery disease. The aim of this study was to evaluate the relationship between MS and plasma homocysteine levels and epicardial adipose tissue thickness in subjects without epicardial coronary artery disease. METHODS: Patients who underwent coronary angiography due to angina or equivocal symptoms and/or abnormal stress test results and were found to have normal coronary arteries were evaluated for the presence of MS. The study group comprised 75 patients with normal coronary arteries and MS, and the control group included 75 age-gender matched subjects without coronary artery disease or MS. RESULTS: Epicardial adipose tissue thickness (5.8 ± 1.9 mm vs. 4.3 ± 1.6 mm, p <0.001) and plasma homocysteine levels (21.6 ± 6.1 µmol/L vs. 15.1 ± 5.8 µmol/L, p <0.001) were significantly higher in the MS group. Body mass index, triglyceride level, weight, age and waist circumference were positively and HDL cholesterol level were negatively correlated with both epicardial adipose tissue thickness and plasma homocysteine level. Epicardial adipose tissue thickness had the strongest correlation with plasma homocysteine level (r = 0.584, p < 0.001). For each 1 mm increase in epicardial adipose tissue thickness, an increase of 3.51 µmol/L (95% CI: 2.24-4.79) in plasma homocysteine level was expected. CONCLUSIONS: We observed a close relationship between MS and epicardial adipose tissue thickness and plasma homocysteine levels, even in the absence of overt coronary artery disease.